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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: Ni-kshay Poshan Yojana (NPY) is a direct benefit transfer scheme of the Government of India introduced in 2018 to support the additional nutritional requirements of persons with TB (PwTB). Our recent nationwide evaluation of implementation and utilization of NPY using programmatic data of PwTB from nine randomly selected Indian states, reported a 70% coverage and high median delay in benefit credit. We undertook a qualitative study between January and July 2023, to understand the detailed implementation process of NPY and explore the enablers and barriers to effective implementation and utilization of the NPY scheme. Methods: We followed a grounded theory approach to inductively develop theoretical explanations for social phenomena through data generated from multiple sources. We conducted 36 in-depth interviews of national, district and field-level staff of the National Tuberculosis Elimination Programme (NTEP) and NPY beneficiaries from 30 districts across nine states of India, selected using theoretical sampling. An analytical framework developed through inductive coding of a set of six interviews, guided the coding of the subsequent interviews. Categories and themes emerged through constant comparison and the data collection continued until theoretical saturation. Results: Stakeholders perceived NPY as a beneficial initiative. Strong political commitment from the state administration, mainstreaming of NTEP work with the district public healthcare delivery system, availability of good geographic and internet connectivity and state-specific grievance redressal mechanisms and innovations were identified as enablers of implementation. However, the complex, multi-level benefit approval process, difficulties in accessing banking services, perceived inadequacy of benefits and overworked human resources in the NTEP were identified as barriers to implementation and utilization. Conclusion: The optimal utilization of NPY is enabled by strong political commitment and challenged by its lengthy implementation process and delayed disbursal of benefits. We recommend greater operational simplicity in NPY implementation, integrating NTEP activities with the public health system to reduce the burden on the program staff, and revising the benefit amount more equitably. [ABSTRACT FROM AUTHOR]

Background: Patients with TB have additional nutritional requirements and thus additional costs to the household. Ni-kshay Poshan Yojana(NPY) is a Direct Benefit Transfer (DBT) scheme under the National Tuberculosis Elimination Programme(NTEP) in India which offers INR 500 monthly to all notified patients with TB for nutritional support during the period of anti-TB treatment. Five years after its implementation, we conducted the first nationwide evaluation of NPY. Methods: In our retrospective cohort study using programmatic data of patients notified with TB in nine randomly selected Indian states between 2018 and 2022, we estimated the proportion of patients who received at least one NPY instalment and the median time to receive the first instalment. We determined the factors associated (i) with non-receipt of NPY using a generalised linear model with Poisson family and log link and (ii) with time taken to receive first NPY benefit in 2022 using quantile regression at 50th percentile. Results: Overall, 3,712,551 patients were notified between 2018 and 2022. During this period, the proportion who received at least one NPY instalment had increased from 56.9% to 76.1%. Non-receipt was significantly higher among patients notified by private sector (aRR 2.10;2.08,2.12), reactive for HIV (aRR 1.69;1.64,1.74) and with missing/undetermined diabetic status (aRR 2.02;1.98,2.05). The median(IQR) time to receive the first instalment had reduced from 200(109,331) days in 2018 to 91(51,149) days in 2022. Patients from private sector(106.9;106.3,107.4days), those with HIV-reactive (103.7;101.8,105.7days), DRTB(104.6;102.6,106.7days) and missing/undetermined diabetic status (115.3;114,116.6days) experienced longer delays. Conclusions: The coverage of NPY among patients with TB had increased and the time to receipt of benefit had halved in the past five years. Three-fourths of the patients received at least one NPY instalment, more than half of whom had waited over three months to receive the first instalment. NTEP has to focus on timely transfer of benefits to enable patients to meet their additional nutritional demands, experience treatment success and avoid catastrophic expenditure. [ABSTRACT FROM AUTHOR]

India has been implementing active case-finding (ACF) for TB among marginalised and vulnerable (high-risk) populations since 2017. The effectiveness of ACF cycle(s) is dependent on the use of appropriate screening and diagnostic tools and meeting quality indicators. To determine the number of ACF cycles implemented in 2021 at national, state (n = 36) and district (n = 768) level and quality indicators for the first ACF cycle. In this descriptive study, aggregate TB program data for each ACF activity that was extracted was further aggregated against each ACF cycle at the district level in 2021. One ACF cycle was the period identified to cover all the high-risk populations in the district. Three TB ACF quality indicators were calculated: percentage population screened (≥10%), percentage tested among screened (≥4.8%) and percentage diagnosed among tested (≥5%). We also calculated the number needed to screen (NNS) for diagnosing one person with TB (≤1538). Of 768 TB districts, ACF data for 111 were not available. Of the remaining 657 districts, 642 (98%) implemented one, and 15 implemented two to three ACF cycles. None of the districts or states met all three TB ACF quality indicators' cut-offs. At the national level, for the first ACF cycle, 9.3% of the population were screened, 1% of the screened were tested and 3.7% of the tested were diagnosed. The NNS was 2824: acceptable (≤1538) in institutional facilities and poor for population-based groups. Data were not consistently available to calculate the percentage of i) high-risk population covered, ii) presumptive TB among screened and iii) tested among presumptive. In 2021, India implemented one ACF cycle with sub-optimal ACF quality indicators. Reducing the losses between screening and testing, improving data quality and sensitising stakeholders regarding the importance of meeting all ACF quality indicators are recommended. [ABSTRACT FROM AUTHOR]

Due to the workload and lack of a critical mass of trained operational researchers within their ranks, health systems and programmes may not be able to dedicate sufficient time to conducting operational research (OR). Hence, they may need the technical support of operational researchers from research/academic organisations. Additionally, there is a knowledge gap regarding implementing differentiated tuberculosis (TB) care in programme settings. In this 'how we did it' paper, we share our experience of implementing a differentiated TB care model along with an inbuilt OR component in Tamil Nadu, a southern state in India. This was a health system initiative through a collaboration of the State TB cell with the Indian Council of Medical Research institutes and the World Health Organisation country office in India. The learnings are in the form of eleven tips: four broad principles (OR on priority areas and make it a health system initiative, implement simple and holistic ideas, embed OR within routine programme settings, aim for long-term engagement), four related to strategic planning (big team of investigators, joint leadership, decentralised decision-making, working in advance) and three about implementation planning (conducting pilots, smart use of e-tools and operational research publications at frequent intervals). These may act as a guide for other Indian states, high TB burden countries that want to implement differentiated care, and for operational researchers in providing technical assistance for strengthening implementation and conducting OR in health systems and programmes (TB or other health programmes). Following these tips may increase the chances of i) an enriching engagement, ii) policy/practice change, and iii) sustainable implementation. [ABSTRACT FROM AUTHOR]

Background National tuberculosis (TB) programmes in high-burden countries do not systematically assess severity at diagnosis followed by referral for inpatient care. Due to limited capacity, comprehensive assessment of all TB patients is not practical. In three districts of Gujarat (West India) in June 2021, we determined the feasibility of screening for severe illness by paramedical staff of public facilities and the burden of 'high risk for severe illness' at notification among adults (≥15 y of age) with TB. Methods In this cross-sectional study, the screening criteria for high risk for severe illness was the presence of any one of the following: body mass index (BMI) ≤14.0 kg/m2, BMI ≤16.0 kg/m2 with bilateral leg swelling, respiratory rate >24/min, oxygen saturation <94% or inability to stand without support. We summarized the feasibility indicators and burden using proportion (95% confidence interval [CI]) and median, as applicable. Results Of 626 notified adults, 87% were screened. The median time interval for screening was 3 d from notification and all indicators were collected in 97% of patients. The burden of high risk for severe illness was high, at 41.6% (95% CI 37.5 to 45.8). Conclusions High burden and feasibility (high coverage, acceptable time interval and minimal missing data) makes a strong case for routine screening of severe illness. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of knowledge regarding challenges faced by the coronavirus disease 2019 (COVID-19) vaccinators in resource constraint settings like district Shahdol, Central India. Hence, the present study was planned to explore the perceived challenges of vaccinators regarding COVID-19 vaccination. Methods: In October 2021, district health authorities conducted a one-day workshop with the auxiliary nurse midwives, staff nurses, and lady health visitors who work as vaccinators. It had three distinct but mutually connected phases. In the first phase, a free listing exercise was performed to list out their perceived challenges that are prominent and representative of their cultural domain. In the second phase, the pile-sorting exercise with the challenges mentioned in the above step was performed to produce similar data in the form of a matrix, based on a perceived similarity between them by multi-dimensional scaling analysis. In the final phase, the transcripts generated during the discussion on the free listing and pile sorting exercises was used for the thematic analysis to find plausible explanations for the findings. Result: A total of 15 vaccinators took part in the workshop. In the free listing exercise, a total of 14 items were identified as perceived challenges for COVID-19 vaccinators. The three items with the highest Smith's S value were overtime duty, no holidays, and lack of monetary incentive. The analysis of pile-sorting suggested that participants clustered their 14 perceived challenges into five groups; 1) beneficiaries related, 2) vaccination schedule related, 3) lack of facilities at vaccination site, 4) lack of monetary incentive, and 5) issues related to digital data handling. Thematic analysis suggested that their main challenges were overtime duty, no monetary incentive, and lack of toilet, food, and transport facility at the session site. Conclusion: Vaccinators perceive overtime duty and lack of holidays as their top two challenges and expect monetary incentives for this. The study recommends better basic amenities like toilet facility, sustained and effective community engagement, a monetary incentive, and a better ecosystem for digital data handling for the vaccinators. [ABSTRACT FROM AUTHOR]

Background India implements universal drug susceptibility testing (UDST) using rapid genotypic tests (cartridge-based nucleic acid amplification test CBNAAT - and line probe assay - LPA). to bridge the gap of diagnosis of multidrug/rifampicin-resistant TB. There is limited evidence assessing the implementation of UDST in India. We assessed the implementation among people with pulmonary TB notified from public facilities in October 2019 from Raichur (Karnataka), India. Methods A cohort study involving secondary data in routine programme settings was conducted. All people with TB underwent a rapid genotypic DST for rifampicin resistance followed by first line-LPA (FL-LPA) if sensitive and second line-LPA (SL-LPA) if resistant. Results Of 217 people, 15.7% (n=34) did not undergo rapid genotypic DST. Of 135 who were rifampicin-sensitive detected on CBNAAT, 68.1% (n=92) underwent FL-LPA, and out of the six rifampicin-resistant cases, 66.7% (n=4) underwent SL-LPA. Overall, 65.4% (142/217) completed the UDST algorithm. Children (aged <15 y) and people with bacteriological non-confirmation on microscopy were less likely to undergo rapid genotypic DST. Of 183 patients who underwent both rapid genotypic DST and sputum smear microscopy, 150 were bacteriologically confirmed and, of them, 9 (6%) were 'rapid DST-negative'. Conclusion We found gaps at various steps. There were a significant number of 'rapid DST-negative, smear-positive' patients. [ABSTRACT FROM AUTHOR]

Background: In India, under-five children with Severe Acute Malnutrition (SAM) are referred to Nutritional Rehabilitation Centers (NRCs). NRCs screen the causes of SAM including tuberculosis (TB). The national TB programme recommends upfront testing with a rapid molecular test if TB is suspected in children. Objective: We estimated the yield of and adherence to the TB diagnostic guidelines (clinical assessment and assessment for microbiological confirmation) among under-five children with SAM admitted at NRCs (six in district Sagar and four in district Sheopur) of Madhya Pradesh, India in 2017. We also explored the challenges in screening from the health care providers' perspective. Methods: It was an explanatory mixed method study. The NRC records were reviewed This was followed by three key informant interviews and three focus group discussions among staff of NRC and TB programme. Manual descriptive thematic analysis was performed. Results: Of 3230, a total of 2665(83%) children underwent Mantoux test, 2438(75%) underwent physical examination, 2277(70%) were asked about the symptoms suggestive of TB, 1220(38%) underwent chest radiograph and 485(15%) were asked for recent contact with TB. A total of 547(17%) underwent assessment for microbiological confirmation. Of 547, a total of 229 gastric aspirate specimens underwent rapid molecular test (24% positive) and 318 underwent sputum microscopy (44% positive). A total of 223 were diagnosed as TB (195 microbiologically and 28 clinically confirmed) and 209 were initiated on anti-TB treatment. The treatment outcome was favourable (cure or treatment completed) for 70(31%) and not recorded for 121(54%). The main perceived challenges in screening for TB were poor team skills, lack of diagnostic facilities and poor understanding of the guidelines due to inadequate training. Conclusion: Though NRCs provided a unique window of opportunity for the screening and management of TB among under-five children with SAM, the utilization of this opportunity remained suboptimal. [ABSTRACT FROM AUTHOR]

What is known and objective: High interindividual response variability was reported with capecitabine and oxaliplatin (CAPOX) regimen in colorectal cancer (CRC). The single nucleotide polymorphisms (SNPs) of the genes related to drug efflux transport (ABCB1) and DNA repair (ERCC) could result in altered tumour response. Hence, this study was designed to assess the influence of ABCB1, ERCC‐1 and ERCC‐2 gene polymorphisms on tumour response to CAPOX treatment in CRC patients of South Indian origin. Patients and Methods: A total of 145 newly diagnosed CRC patients were included in the final analysis. Response to CAPOX treatment in the adjuvant setting was assessed in terms of disease‐free survival rate (DFSR) and overall survival rate (OSR) at 3 years, whereas in the palliative setting, the response was assessed as progression‐free survival rate (PFSR) and OSR at 3 years. Five millilitres of the venous blood sample was collected from each patient for genomic DNA extraction by the manual phenol‐chloroform method. Genotyping and allelic discrimination analysis were done using real‐time PCR (RT‐PCR). Results and discussion: With ABCB1 gene polymorphism rs1045642 (A > G), patients with AG/GG genotype showed better DFSR [P value =.02, OR = 2 (CI: 1.5‐3)] and PFSR [P value =.02, OR = 1.6 (CI: 1.1‐2.5)] when compared to AA genotype in the adjuvant and palliative settings, respectively. Similarly with rs1128503 (A > G) polymorphism, patients with AG/GG genotype were found to have better DFSR [P value =.02, OR = 1.9 (CI: 1.3‐3)] and PFSR [P value =.01, OR = 2 (CI: 1.1‐3.7)] when compared to AA genotype. However, we did not find any association between CAPOX response and ABCB1 gene polymorphisms in a binary logistic regression when non‐genetic predictors were considered for analysis. We did not find any association with ERCC1 (rs11615 A > G) and ERCC2 (rs13181 T > G) gene polymorphisms with respect to CAPOX response in either of the treatment settings. What is new and conclusion: The response to CAPOX treatment was found to be influenced by the ABCB1 gene variants (rs1128503 and rs1045642), thereby strengthening their predictive role. No association was found between ERCC1 (rs11615 A > G), ERCC2 (rs13181 T > G) gene polymorphisms and tumour response to CAPOX treatment in CRC patients of South Indian origin. [ABSTRACT FROM AUTHOR]

Context: Since the implementation of Weekly Iron and Folic acid Supplementation (WIFS) program in India in 2013, little effort has been made to comprehensively evaluate the program. Aims: This study was carried out to assess the coverage of WIFS among adolescent girls, explore implementation barriers, and suggest solutions to improve WIFS through public schools in Rishikesh, India (2018–19). Methods and Materials: This was a sequential explanatory mixed-methods study. Quantitative component was a community-based cross-sectional survey to determine the prevalence of anemia and coverage of WIFS. Qualitative component added an explanation to understand WIFS implementation through document review and nonparticipant observation of WIFS session. We invited stakeholders for nominal group discussion on barriers and solutions. Statistical Analysis Used: Variables were described as proportion and mean. Group discussion transcript was analyzed using content analysis. Results: Of 400 adolescent girls, 16% (95% CI: 12.4, 19.6) received weekly and 45% ever received iron tablets over the last 3 months and 79% were anemic. From ten schools, one school never implemented WIFS. There was iron-folic acid (IFA) stock out for 10 months last year. Major barriers identified were nonavailability of IFA, and irregularity in submitting IFA consumption report. Suggested solutions were ensuring IFA stock, strengthening supervision, ownership, training, and regular meetings of stakeholders. Conclusions: To conclude, in a setting with high anemia prevalence, WIFS was poorly implemented. Ownership and strengthening supervision is essential for the success of the program. [ABSTRACT FROM AUTHOR]

In India, cervical cancer screening is conducted at various levels; however, after screening, the adherence to the cancer care continuum is barely understood. This study evaluated a community-based cancer screening program conducted in a rural setting (Tirunelveli and Tuticorin districts) in South India and reviewed the completion of care continuum. In this longitudinal descriptive study involving secondary data collection, data from the case records of 2192 women who were consecutively screened between March 2015 and May 2016 were included. All women underwent conventional cytology-based screening (Pap smear) and Visual Inspection with Acetic Acid (VIA). Those for whom either test was positive were referred for histopathological confirmation. Patients with confirmed precancerous conditions and unsatisfactory Pap smears were referred for further management. In total, 2192 women were screened [age range, 17–69 years; mean (standard deviation), 39.2 (8.5)]. Common symptom and sign were white discharge per vaginum (34.9%) and cervical erosion (34.4%), respectively. The VIA was positive for 24% (523/2178; 14 women did not cooperate for VIA) and 113 (5.1%) had epithelial cell abnormality in the Pap smear test. Per histopathology findings, one woman had non-keratinizing squamous cell carcinoma. Seven, three, and four had cervical intraepithelial neoplasia I, II and III, respectively. Of 2192, 807 were eligible for referral (597 had positive results on either Pap or VIA). Among the 807 women referred, only 74 (9.2%) women visited the referral center. The follow-up rate was very poor accounting to fragmentation of care continuum. The success of the screening program depends on the completion of the care continuum. [ABSTRACT FROM AUTHOR]

Background: Pre-diagnosis attrition needs to be addressed urgently if we are to make progress in improving MDR-TB case detection and achieve universal access to MDR-TB care. We report the pre-diagnosis attrition, along with factors associated, and turnaround times related to the diagnostic pathway among patient with presumptive MDR-TB in Bhopal district, central India (2014).Methods: Study was conducted under the Revised National Tuberculosis Control Programme setting. It was a retrospective cohort study involving record review of all registered TB cases in Bhopal district that met the presumptive MDR-TB criteria (eligible for DST) in 2014. In quarter 1, Line Probe Assay (LPA) was used if sample was smear/culture positive. Quarter 2 onwards, LPA and Cartridge-based Nucleic Acid Amplification Test (CbNAAT) was used for smear positive and smear negative samples respectively. Pre-diagnosis attrition was defined as failure to undergo DST among patients with presumptive MDR-TB (as defined by the programme).Results: Of 770 patients eligible for DST, 311 underwent DST and 20 patients were diagnosed as having MDR-TB. Pre-diagnosis attrition was 60% (459/770). Among those with pre-diagnosis attrition, 91% (417/459) were not identified as 'presumptive MDR-TB' by the programme. TAT [median (IQR)] to undergo DST after eligibility was 4 (0, 10) days. Attrition was more than 40% across all subgroups. Age more than 64 years; those from a medical college; those eligible in quarter 1; patients with presumptive criteria 'previously treated - recurrent TB', 'treatment after loss-to-follow-up' and 'previously treated-others'; and patients with extra-pulmonary TB were independent risk factors for not undergoing DST.Conclusion: High pre-diagnosis attrition was contributed by failure to identify and refer patients. Attrition reduced modestly with time and one factor that might have contributed to this was introduction of CbNAAT in quarter 2 of 2014. General health system strengthening which includes improvement in identification/referral and patient tracking with focus on those with higher risk for not undergoing DST is urgently required. [ABSTRACT FROM AUTHOR]

PURPOSE: Escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) improves overall survival (OS) in patients with Hodgkin lymphoma (HL) relative to ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) therapy. However, the associated higher cost and toxicity discourage clinicians from prescribing it. Identifying high-risk patients and administering escalated BEACOPP remains an effective strategy. We assessed the significance of interim positron emission tomography (iPET) scan after 2 cycles (iPET2) in identifying this high-risk subset. PATIENTS AND METHODS: This cohort study used secondary data from 12 tertiary care centers in South India gathered over 10 years (2008-2018). OS, event-free survival (EFS), determinants of EFS, and complete response (CR) in iPET2 were assessed. RESULTS: The study included 409 patients with HL (mean age, 34.5 years; male/female ratio, 1.4:1). The median duration of follow-up was 2.8 years. Of 409 patients, 63% underwent PET-based staging and 37% underwent computerized tomography (CT) staging. Stage IV (28.9%) and bone involvement (9.2%) were seen more often with PET than with CT staging (9.2% and 2%, respectively). Among 171 patients with iPET2 results, 24% did not achieve CR, and no factors were significantly associated. The 5-year EFS and OS rates of the entire cohort were 78% and 97%, respectively. The 5-year EFS and OS rates of patients with CR on iPET2 were 90% and 99%, respectively, whereas these were 65% and 100%, respectively, for patients not achieving CR. On univariable analysis, sex, stage, and iPET2 response significantly predicted inferior EFS. On multivariate analysis, only iPET2 response significantly predicted EFS (P <.000). CONCLUSION: Our study supports the use of PET for staging and iPET2 for response assessment. Nonachievement of CR on iPET2 indicates unfavorable outcome, and such patients may benefit from more intensive treatment. [ABSTRACT FROM AUTHOR]

Community-level benefits of screening for active tuberculosis (TB) disease remain uncertain. Project Axshya (meaning free of TB) conducted advocacy, communication, social mobilization, and active case finding among vulnerable/marginalized populations of India. Among 15 districts of Jharkhand state, the project was initiated in 36 subdistrict level administrative units — tuberculosis units (TUs) in a staggered manner between April 2013 and September 2014, and continued till the end of 2015. Seven TUs did not implement the project. We assessed the relative change in the quarterly TB case finding indicators (n = 4) after inclusion of a TU within the project. By fitting four multilevel models (mixed-effects maximum likelihood regression using random intercept), we adjusted for secular (over previous five quarters) and seasonal trends, baseline differences within Axshya and non-Axshya TUs, and population size and clustering within districts and within TUs. After inclusion of a TU within the project, we found a significant increase [95% confidence interval (CI)] in TU-level presumptive TB sputum examination rate, new sputum-positive TB Case Notification Rate (CNR), sputum-positive TB CNR, and all forms TB CNR by 12 (5.5, 18.5), 1.1 (0.5, 1.7), 1.3 (0.6, 2.0), and 1.2 (0.1, 2.2) per 100,000 population per quarter, respectively. Overall, the project resulted in an increase (95% CI) in sputum examination and detection of new sputum-positive TB, sputum-positive TB and all forms of TB patients by 22,410 (10,203, 34,077), 2066 (923, 3210), 2380 (1162, 3616), and 2122 (203, 4059), respectively. This provides evidence for implementing project Axshya over and above the existing passive case finding. [ABSTRACT FROM AUTHOR]

Summary: What is known and objective: Variable response to docetaxel‐based neo‐adjuvant chemotherapy (NACT) in breast cancer patients had been reported. Genetic polymorphisms in the ABCB1 gene coding for the efflux transporter MDR1 (P‐glycoprotein, P‐gp) could result in altered tumour response. Hence, this study was proposed to assess the effect of single nucleotide polymorphisms (SNPs) of ABCB1 gene on tumour response in locally advanced breast cancer patients (LABC) of South India who have a distinct genetic makeup. Methods: Out of 162 LABC patients recruited, 129 patients were included for the final analysis. DNA was extracted by "phenol‐chloroform extraction method" from the WBCs, and genotyping for SNPs rs1045642 (C3435T) and rs1128503 (C1236T) in ABCB1 gene was performed with real‐time PCR system using validated TaqMan®SNP genotyping assay method. Tumour response was assessed by RECIST criteria based on the MRIs taken before and after completion of four cycles of docetaxel therapy. Results and discussion: A total of 102 (79.1%) patients were found to be responders and 27 (20.9%) patients were found to be non‐responders to docetaxel therapy. Patients with "CT/TT" genotypes (response rate: 83.3%) of ABCB1 (C1236T) gene showed better tumour response than those with "CC" genotype (response rate: 16.6%) [OR = 2.94 (CI: 1.15‐7.52); P = 0.03]. However, on performing binary logistic regression, neither the studied SNPs nor the non‐genetic factors like age, BMI, postmenopausal status, laterality of the tumour, ER status, PR status and Her‐2/neu status were found to be associated with tumour response to docetaxel (P > 0.05). What is new and conclusion: The tumour response to docetaxel was significantly influenced by the SNP C1236T of ABCB1 gene coding for the P‐gp. However, when adjusted for other non‐genetic factors, neither of the ABCB1 variants were found to be associated with tumour response to docetaxel‐based NACT in LABC patients of South India. The tumour response to docetaxel was significantly associated with the SNP C1236T (rs1128503) of ABCB1 gene coding for the MDR1 transporter or P‐glycoprotein. Patients with the "CT/TT" genotype displayed comparatively better tumour response than those with the "CC" genotype. However, when adjusted for other factors like age, BMI, postmenopausal status, laterality, ER status, PR status and Her‐2/neu status neither of the ABCB1 variants were found to be associated with tumour response to docetaxel in LABC patients of South India. [ABSTRACT FROM AUTHOR]

Introduction: Xpert MTB/RIF was implemented in 2016 as the initial diagnostic test for extrapulmonary, pediatric, and human immunodeficiency virus–associated tuberculosis (TB) and as an add-on test for sputum microscopy–negative patients under Revised National TB Control Programme, Puducherry, India. We intended to study the change in TB case notification rates (CNRs) after 2015 and explore the enablers and barriers for implementation of Xpert. Materials and Methods: Sequential mixed-methods study, quantitative phase followed by a descriptive qualitative phase (key informant interviews with healthcare providers in the program). Results: The TB (all forms) CNR increased in 2016 followed by a drop to 2015 levels in 2017. There was a reduction in patients notified as sputum-negative pulmonary TB and pediatric TB during 2016–2017. Healthcare providers used a negative Xpert result in ruling out TB among patients who would previously get diagnosed clinically. Perceived benefits of Xpert were efficiency, rapid results, and detecting resistance. Barriers included poor awareness among medical colleges and the private sector, difficulty in motivating sputum microscopy–negative patients for Xpert, and incompletely filled referral forms. Conclusion: Xpert-negative results should be interpreted cautiously after clinical assessment. Identified barriers should be addressed to ensure that all eligible undergo testing. [ABSTRACT FROM AUTHOR]

Background Axshya SAMVAD is an active tuberculosis (TB) case finding (ACF) strategy under project Axshya (Axshya meaning ‘free of TB’ and SAMVAD meaning ‘conversation’) among marginalized and vulnerable populations in 285 districts of India. Objectives To compare patient characteristics, health seeking, delays in diagnosis and treatment initiation among new sputum smear positive TB patients detected through ACF and passive case finding (PCF) under the national TB programme in marginalized and vulnerable populations between March 2016 and February 2017. Methods This observational analytic study was conducted in 18 randomly sampled Axshya districts. We enrolled all TB patients detected through ACF and an equal number of randomly selected patients detected through PCF in the same settings. Data on patient characteristics, health seeking and delays were collected through record review and patient interviews (at their residence). Delays included patient level delay (from eligibility for sputum examination to first contact with any health care provider (HCP)), health system level diagnosis delay (from contact with first HCP to TB diagnosis) and treatment initiation delays (from diagnosis to treatment initiation). Total delay was the sum of patient level, health system level diagnosis delay and treatment initiation delays. Results We included 234 ACF-diagnosed and 231 PCF-diagnosed patients. When compared to PCF, ACF patients were relatively older (≥65 years, 14% versus 8%, p = 0.041), had no formal education (57% versus 36%, p<0.001), had lower monthly income per capita (median 13.1 versus 15.7 USD, p = 0.014), were more likely from rural areas (92% versus 81%, p<0.002) and residing far away from the sputum microscopy centres (more than 15 km, 24% versus 18%, p = 0.126). Fewer patients had history of significant loss of weight (68% versus 78%, p = 0.011) and sputum grade of 3+ (15% versus 21%, p = 0.060). Compared to PCF, HCP visits among ACF patients was significantly lower (median one versus two HCPs, p<0.001). ACF patients had significantly lower health system level diagnosis delay (median five versus 19 days, p = 0.008) and the association remained significant after adjusting for potential confounders. Patient level and total delays were not significantly different. Conclusion Axshya SAMVAD linked the most impoverished communities to TB care and resulted in reduction of health system level diagnosis delay. [ABSTRACT FROM AUTHOR]

Background: Community-based active case finding (ACF) for tuberculosis (TB) implemented among marginalised and vulnerable populations in 285 districts of India resulted in reduction of diagnosis delay and prevalence of catastrophic costs due to TB diagnosis. We were interested to know whether this translated into improved treatment outcomes. Globally, there is limited published literature from marginalised and vulnerable populations on the independent effect of community-based ACF on treatment outcomes when compared to passive case finding (PCF). Objectives: To determine the relative differences in unfavourable treatment outcomes (death, loss-to-follow-up, failure, not evaluated) of ACF and PCF-diagnosed people. Methods: Cohort study involving record reviews and interviews in 18 randomly selected districts. We enrolled all ACF-diagnosed people with new smear-positive pulmonary TB, registered under the national TB programme between March 2016 and February 2017, and an equal number of randomly selected PCF-diagnosed people in the same settings. We used log binomial models to adjust for confounders. Results: Of 572 enrolled, 275 belonged to the ACF and 297 to the PCF group. The proportion of unfavourable outcomes were 10.2% (95% CI: 7.1%, 14.3%) in the ACF and 12.5% (95% CI: 9.2%, 16.7%) in the PCF group (p = 0.468). The association between ACF and unfavourable outcomes remained non-significant after adjusting for confounders available from records [aRR: 0.83 (95% CI: 0.56, 1.21)]. Due to patient non-availability at their residence, interviews were conducted for 465 (81.3%). In the 465 cohort too, there was no association after adjusting for confounders from records and interviews [aRR: 1.05 (95% CI: 0.62, 1.77)]. Conclusion: We did not find significant differences in the treatment outcomes. Due to the wide CIs, studies with larger sample sizes are urgently required. Studies are required to understand how to translate the benefits of ACF to improved treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: In a study conducted in Bhopal district (a setting with facility for molecular drug susceptibility testing (DST)) located in central India in 2014–15, we found high levels of pre-diagnosis attrition among patients with presumptive multi drug-resistant tuberculosis (MDR-TB)–meaning TB patients who were eligible for DST, were not being tested. Objectives: In this study, we explored the health care provider perspectives into barriers and suggested solutions for improving DST. Methods: This was a descriptive qualitative study. One to one interviews (n = 10) and focus group discussions (n = 2) with experienced key informants involved in programmatic management of DR-TB were conducted in April 2017. Manual descriptive thematic analysis was performed. Results: The key barriers reported were a) lack of or delay in identification of patients eligible for DST because of using treatment register as the source for identifying patients b) lack of assured specimen transport after patient identification and c) lack of tracking. Extra pulmonary TB patients were not getting identified as eligible for DST. Solutions suggested by the health care providers were i) generation of unique identifier at identification in designated microscopy center (DMC), immediate intimation of unique identifier to district and regular monitoring by senior TB laboratory and senior treatment supervisors of patients eligible for DST that were missed; ii) documentation of unique identifier at each step of cascade; iii) use of human carriers/couriers to transport specimen from DMCs especially in rural areas; and iv) routine entry of all presumptive extra-pulmonary TB specimen, as far as possible, in DMC laboratory register. Conclusion: Lack of assured specimen transport and lack of accountability for tracking patient after identification and referral were the key barriers. The identification of patients eligible for DST among microbiologically confirmed TB at the time of diagnosis and among clinically confirmed TB at the time of treatment initiation is the key. Use of unique identifier at identification and its use to ensure cohort wise tracking has to be complemented with specimen transport support and prompt feedback to the DMC. The study has implications to improve detection of MDR-TB among diagnosed/notified TB patients. [ABSTRACT FROM AUTHOR]

Objective:To estimate the prevalence of prescribing errors before and after implementing electronic discharge prescription system in the wards of General Surgery in a tertiary care hospital in India. Methodology: Patients discharged from General Surgery wards with a prescription containing atleast one drug were selected. Discharge prescriptions were collected before and after implementing the electronic prescribing system. Patients' demographic details like age, gender, diagnosis and number days of hospital stay were recorded in the specially designed case record form. Discharge orders were scanned to evaluate the prescribing errors in these orders. Results: A total of 1045 handwritten and 1152 electronic discharge summaries were collected, of which 76.7% and 76.2% were of <60 years aged patients, 64.3% and 63.5% of male gender respectively in both the groups. Average number of drugs prescribed per prescription was 3.5 and 4.1 before and after intervention; error rate was 33% and 8.4% of drugs prescribed respectively, 46.3% of prescriptions were of illegible handwriting. The intervention of an electronic prescribing system has reduced 75% of prescribing errors. Handwritten prescriptions had 5.5 higher odds of having prescribing errors (OR 5.5, 95% CI 4.6-6.1). Conclusion: The electronic prescribing system has a high impact in reducing prescribing errors in discharge prescriptions. Handwritten prescriptions had 5.5-times odds of higher risk for prescribing errors. Increase in age, number of drugs prescribed and length of hospital stay were major predictors of prescribing errors. [ABSTRACT FROM AUTHOR]

Background: In Gujarat, India, a state led public private partnership scheme to promote facility birth named Chiranjeevi Yojana (CY) was implemented in 2005. Institutional birth is provided free of cost at accredited private health facilities to women from socially disadvantaged groups (eligible women). CY has contributed in increasing facility birth and providing substantially subsidized (but not totally free) birth care; however, the retention of mothers in this scheme in subsequent child birth is unknown. Therefore, we conducted a study aimed to determine the effect of previous utilization of the scheme and previous out of pocket expenditure on subsequent child birth among multiparous eligible women in Gujarat.Methods: This was a retrospective cohort study of multiparous eligible women (after excluding abortions and births at public facility). A structured questionnaire was administered by trained research assistant to those with recent delivery between Jan and Jul 2013. Outcome of interest was CY utilization in subsequent child birth (Jan-Jul 2013). Explanatory variables included socio-demographic characteristics (including category of eligibility), pregnancy related characteristics in previous child birth, before Jan 2013, (including CY utilization, out of pocket expenditure) and type of child birth in subsequent birth. A poisson regression model was used to assess the association of factors with CY utilization in subsequent child birth.Results: Of 997 multiparous eligible women, 289 (29%) utilized and 708 (71%) did not utilize CY in their previous child birth. Of those who utilized CY (n = 289), 182 (63%) subsequently utilized CY and 33 (11%) gave birth at home; whereas those who did not utilize CY (n = 708) had four times higher risk (40% vs. 11%) of subsequent child birth at home. In multivariable models, previous utilization of the scheme was significantly associated with subsequent utilization (adjusted Relative Risk (aRR): 2.7; 95% CI: 2.2-3.3), however previous out of pocket expenditure was not found to be associated with retention in the CY scheme.Conclusion: Women with previous CY utilization were largely retained; therefore, steps to increase uptake of CY are expected to increase retention of mothers within CY in their subsequent child birth. To understand the reasons for subsequent child birth at home despite previous CY utilization and previous zero/minimal out of pocket expenditure, future research in the form of systematic qualitative enquiry is recommended. [ABSTRACT FROM AUTHOR]

Nearly half of the smear negative pulmonary TB in National TB Programme remain undetected in Haryana (north Indian state), probably due to poor access to chest radiography. A corporate hospital stepped into fill this infrastructure gap in Rewari district of Haryana by sending a mobile van with digital x-ray facilities and paramedic staff. The staff of the public health facility coordinated with the eligible patients and ensured that they visited on the designated day. The District TB Officer interpreted the x-ray and made decisions about diagnosis and treatment. The support was provided between May and Dec 2014 in seven public health centres (primary/secondary level) of the district. A total of 355 patie-nts were examined, of whom 122 (34.4%) were diagnosed as smear negative pulmonary TB and started on treatment according to programme guidelines. This public-private partnership needs to be scaled-up and better designed studies are required to assess community-level impact and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Background: Worldwide, leprosy is one of the major causes of preventable disability. India contributes to 60% of global leprosy burden. With increasing numbers of leprosy with grade 2 disability (visible disability) at diagnosis, we aimed to determine risk factors associated with grade 2 disability among new cases and explore patients and providers’ perspectives into reasons for late presentation. Methodology/Principal Findings: This was an explanatory mixed-methods study where the quantitative component, a matched case-control design, was followed by a qualitative component. A total of 70 cases (grade 2 disability) and 140 controls (grade 0) matched for age and sex were randomly sampled from new patients registered between January 2013-January 2015 in three districts of Maharashtra (Mumbai, Thane and Amaravati) and interviewed using a structured close ended questionnaire. Eight public health care providers involved in leprosy care and 7 leprosy patients were purposively selected (maximum variation sampling) and interviewed using a structured open-ended interview schedule. Among cases, overall median (IQR) diagnosis delay in months was 17.9(7–30); patient and health system delay was 7(4–16.5) and 5.5(0.9–12.5) respectively; this was significantly higher than the delay in controls. Reasons for delayed presentation identified by the quantitative and qualitative data were: poor awareness of leprosy symptoms, first health care provider visited being private practitioners who were not aware about provision of free leprosy treatment at public health care facilities, reduced engagement and capacity of the general health care system in leprosy control. Conclusions: Raising awareness in communities and health care providers regarding early leprosy symptoms, engagement of private health care provider in early leprosy diagnosis and increasing capacity of general health system staff, especially targeting high endemic areas that are hotspots for leprosy transmission may help in reducing diagnosis delays. [ABSTRACT FROM AUTHOR]

Purpose: Up to 30-40 % of the major depressive disorder patients do not respond sufficiently to antidepressant treatment. Genetic variations in the serotonin transporter gene have been implicated in modulating treatment response to selective serotonin reuptake inhibitors, and this association is influenced by ethnicity. We investigated the influence of serotonin transporter gene variants 5-HTTLPR and rs25531 in Indian population on fluoxetine response. Methods: One hundred and two major depressive disorder patients were started on fluoxetine treatment and after 6 weeks, classified as responders ( n = 56) and non-responders ( n = 46) using Hamilton depression rating scale and genotyped. Fisher's exact test was used to compare genotype frequencies between responders and non-responders. One-way analysis of variance and student t test were used to compare the percentage reduction (week 0-6) in Hamilton depression rating scores between genotype and haplotype groups. Results: We observed a significant association between LL genotype of 5-HTTLPR and fluoxetine treatment response ( p = 0.0066, OR (95 %) = 4.0 (1.45-11.03)) but not with the functional groups of 5-HTTLPR -rs25531. However, there was a significant difference in percentage reduction in HAM-D scores (week 0-6) between 5-HTTLPR genotypes (LL vs. LS + SS, p = 0.0036; LL vs. LS, p = 0.0109) as well as the functionally grouped haplotypes of 5-HTTLPR -rs25531 (LL carriers vs. non-carriers of LL, p = 0.0118; LL vs. LS+ LL, p = 0.0419). Conclusion: The LL genotype and LL haplotype of SLC6A4 are associated with favorable treatment response to fluoxetine in south Indian major depression patients. [ABSTRACT FROM AUTHOR]

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Background: "Chiranjeevi Yojana (CY)", a state-led large-scale demand-side financing scheme (DSF) under public-private partnership to increase institutional delivery, has been implemented across Gujarat state, India since 2005. The scheme aims to provide free institutional childbirth services in accredited private health facilities to women from socially disadvantaged groups (eligible women). These services are paid for by the state to the private facility with the intention of service being free to the user. This community-based study estimates CY uptake among eligible women and explores factors associated with non-utilization of the CY program.Methods: This was a community-based cross sectional survey of eligible women who gave birth between January and July 2013 in 142 selected villages of three districts in Gujarat. A structured questionnaire was administered by trained research assistant to collect information on socio-demographic details, pregnancy details, details of childbirth and out-of-pocket (OOP) expenses incurred. A multivariable inferential analysis was done to explore the factors associated with non-utilization of the CY program.Results: Out of 2,143 eligible women, 559 (26 %) gave birth under the CY program. A further 436(20 %) delivered at free public facilities, 713(33 %) at private facilities (OOP payment) and 435(20 %) at home. Eligible women who belonged to either scheduled tribe or poor [aOR = 3.1, 95 % CI:2.4 - 3.8] or having no formal education [aOR = 1.6, 95 % CI:1.1, 2.2] and who delivered by C-section [aOR = 2.1,95 % CI: 1.2, 3.8] had higher odds of not utilizing CY program. Of births at CY accredited facilities (n = 924), non-utilization was 40 % (n = 365) mostly because of lack of required official documentation that proved eligibility (72 % of eligible non-users). Women who utilized the CY program overall paid more than women who delivered in the free public facilities.Conclusion: Uptake of the CY among eligible women was low after almost a decade of implementation. Community level awareness programs are needed to increase participation among eligible women. OOP expense was incurred among who utilized CY program; this may be a factor associated with non-utilization in next pregnancy which needs to be studied. There is also a need to ensure financial protection of women who have C-section. [ABSTRACT FROM AUTHOR]

In 2011, Save the Children India launched a project for the disadvantaged population of Rajasthan, Bihar and Odisha. As a baseline activity, neonatal deaths during January-December 2012 were investigated using modified verbal autopsy tool in six sub-district-level administrative units (blocks) adopting 30-cluster sample survey approach. Our study reported a total of 189 neonatal deaths of which 50% occurred at home and 39% happened on Day 1. About half of the deaths occurred in blocks from Bihar. High number of neonatal deaths belonged to households that were below poverty line (64%) and other disadvantaged classes (46%); among mothers who were illiterate (65%), <20 years of age (54%) and during their first-order births (36%). Birth asphyxia was a major cause of neonatal deaths across all blocks. These findings indicate need for easy and early access to transport services, specialized neonatal care and advocacy targeted towards increasing community awareness. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to determine the influence of CYP2C9, VKORC1, CYP4F2, and GGCX genetic polymorphisms on mean daily dose of acenocoumarol in South Indian patients and to develop a new pharmacogenetic algorithm based on clinical and genetic factors. Methods: Patients receiving acenocoumarol maintenance therapy ( n = 230) were included in the study. Single nucleotide polymorphisms (SNP) of CYP2C9, VKORC1, CYP4F2, and GGCX were genotyped by real-time polymerase chain reaction (RT-PCR) method. Results: The mean daily acenocoumarol maintenance dose was found to be 3.7 ± 2.3 (SD) mg/day. The CYP2C9 *1*2, CYP2C9 *1*3, and CYP2C9 *2*3 variant genotypes significantly reduced the dose by 56.7 % (2.0 mg), 67.6 % (1.6 mg), and 70.3 % (1.5 mg) than wild-type carriers 4.1 mg, p < 0.0001. The genetic variants of CYP2C9 and GGCX (rs11676382) were found to be associated with lower acenocoumarol dose, whereas CYP4F2 (rs2108622) was associated with higher doses. Age, body mass index (BMI), variation of CYP2C9, VKORC1, CYP4F2, and GGCX were the major determinants of acenocoumarol maintenance dose, accounting for 61.8 % of its variability (adjusted r = 0.615, p < 0.0001). Among the VKORC1 variants, rs9923231 alone contributed up to 28.6 % of the acenocoumarol dose variation. Conclusion: VKORC1 rs9923231 polymorphism had the highest impact on acenocoumarol daily dose. A new pharmacogenetic algorithm was established to determine the acenocoumarol dose in South Indian population. [ABSTRACT FROM AUTHOR]

Objective: To determine the influence of genetic polymorphisms on warfarin maintenance dose and to explicate an algorithm using the pharmacogenetic and clinical factors to determine the maintenance and/or starting dose of warfarin in South Indian patients receiving warfarin therapy. Methods: Patients receiving stabilized warfarin therapy ( n = 257) were included in the study. Single nucleotide polymorphisms (SNPs) of CYP2C9 (rs1799853 and rs1057910), VKORC1 (rs9923231, rs7196161, rs2884737, rs9934438, rs8050894, rs2359612 and rs7294), CYP4F2 (rs2108622) and GGCX (rs11676382) were genotyped by the quantitative real time-PCR method. Results: The mean daily maintenance dose of warfarin was found to be 4.7 ± 2.1 mg/day. Patients with the CYP2C9*1/*2, *1/*3 and *2/*3 variant genotypes required a 51.0 (2.8 mg), 60.9 (2.3 mg) and 62.2 % (2.2 mg) lower daily maintenance dose of warfarin, respectively, than those patients with the CYP2C9*1/*1 wild-type genotype (5.2 mg) ( p < 0.0001). The genetic variants of CYP2C9, VKORC1 and GGCX were associated with decreased warfarin dose, except for rs7196161, rs7294 and rs2108622 which were associated with an increased warfarin dose. Genetic variations of CYP2C9 ( *2 and *3), VKORC1 (rs9923231, rs7294, rs9934438 and rs2359612), CYP4F2, GGCX and non-genetic factors such as age, body weight, clinical status (post mechanical valve replacement) could explain up to 62.1 % of the overall variation (adjusted r 60.2 %, p < 0.0001) in warfarin maintenance dose. Conclusion: Genetic polymorphisms of CYP2C9, VKORC1, CYP4F2 and GGCX are important predictive factors of warfarin maintenance dose, and the developed algorithm will be useful to predict the required maintenance and/or starting warfarin dose in South Indian populations. [ABSTRACT FROM AUTHOR]

Community medicine broadly comprises of family medicine and public health; and community physicians are those trained in both. The primary professional role of a community physician is to manage a health center. Provision of primary healthcare: Curative, preventive, and promotive are an integral part of community medicine practice. Despite being a clinical specialty, community physicians in India are not performing this role and Rural and Urban Health Training Centers have become ornamental exhibits. Most departments of community medicine have restricted themselves to teaching undergraduates and postgraduate training has taken a back seat. Instead of pondering upon why this cadre of social/community physicians was prepared, we are hastily opening up other public health courses. Clinical subspecialties of community medicine should be given equal importance at par with academics and research. Community physicians should fulfi ll their primary role which would enable them to advocate public health policy with authority. [ABSTRACT FROM AUTHOR]

A randomized controlled trial was conducted in Chandigarh, India (2011), to determine the effectiveness of indigenous ready-to-use therapeutic food (RUTF) in community-based management of uncomplicated severe acute malnutrition (SAM). Intervention was through outpatient therapeutic program site (OTP). Study and control group children (6 months–5 years) were followed up weekly for 12 weeks, in OTP and at home. All children received supplementary nutrition through anganwadis under integrated child development scheme. Study children, in addition, received therapeutic dose of RUTF in OTP. Primary outcome, 115% of baseline weight, was attained in 6 of 13 (46.2%) and 1 of 13 (7.7%) children among study and control group, respectively [odds ratio: 10.28, 95% confidence interval (CI): 1.02–103.95]. Compared with control group, addition of RUTF in study group resulted in average additional increase in weight by 13 g/kg of baseline weight/week/child (95% CI: 2–23). Indigenous RUTF was effective in community-based management of uncomplicated SAM. [ABSTRACT FROM PUBLISHER]

Background: The antiplatelet activity of clopidogrel is variable among patients suffering from ischemic heart disease. Variation in the cytochrome P450 2C19 ( CYP2C19) gene coding for the CYP2C19 enzyme is one of the major determinants of this variable response to clopidogrel. The activity of the CYP2C19 enzyme, which plays a role in the conversion of the prodrug clopidogrel to its active metabolite, is genetically influenced by polymorphisms in its gene. The aim of our study was to evaluate the association of CYP2C19 polymorphisms and the antiplatelet effect of clopidogrel in the South Indian Tamilian population. Materials and methods: Genotyping and platelet aggregation results of 149 ischemic heart disease patients on clopidogrel maintenance therapy (75 mg daily dose) were analyzed in this study. CYP2C19 polymorphisms were genotyped by the PCR-restriction fragment length polymorphism method. We measured residual platelet activities in these patients on clopidogrel therapy in terms of impedance (expressed as ohms). The study subjects were divided into two metabolizer phenotype groups [group 1: poor/intermediate metabolizers (PM/IM); group 2: extensive/ultra-rapid metabolizers (EM/URM)] based on CYP2C19 genotype, and the residual platelet activities were compared. Higher values of impedance denote increased residual platelet activity. Results: Poor/intermediate metabolizers had significantly higher impedance values than EM/URM [(median; range) 4.0; 0-13 vs. 2.0; 0-11, respectively; p = 0.04]. These higher impedance values denote higher residual platelet activities among the carriers of loss-of-function alleles ( CYP2C19*2,*3) than among non-carriers. However, residual platelet activities were lower among the carriers of the gain-of-function allele ( CYP2C19*17) than among non-carriers, although this difference was not significant. Conclusion: Patients with CYP2C19 ( *2 or *3) genetic polymorphisms had higher residual platelet activities and were associated with a reduced antiplatelet response to clopidogrel. As the South Indian Tamilian population is characterized with higher frequencies of these genetic polymorphisms, our findings mandate further studies aimed at initiating genome-based personalized antiplatelet therapy. [ABSTRACT FROM AUTHOR]

What is known and Objective: CYP2C19*17 allele increases the metabolic activity of CYP2C19 resulting in decreased therapeutic levels of CYP2C19 substrates. There exist inter-ethnic differences in the distribution of this allele. The present study was aimed at establishing the allele and genotype frequencies of CYP2C19*17 in a South Indian Tamilian population. Furthermore, we describe the haplotype structure of the three common variant alleles of CYP2C19 in the Tamilian population. Methods: Two hundred and six subjects of South Indian Tamilian origin were genotyped for CYP2C19*17 allele by nested polymerase chain reaction and restriction fragment length polymorphism. A subset of 87 subjects were also genotyped for CYP2C19*2 and CYP2C19*3 alleles. After ascertaining linkage disequilibrium (LD), haplotypes were constructed. Allele and genotype frequencies, LD pattern and haplotype frequency were compared with those of the HapMap populations. Results and Discussion: The CYP2C19*17 allele frequency in the Tamilian population ( n = 206) was found to be 19·2% (95% CI: 15·4 - 20·3). The CYP2C19*2 allele frequency ( n = 87) was found to be 40·2% (95% CI: 32·9 - 47·5), whereas the CYP2C19*3 allele was not detected in the study subjects ( n = 97). The high frequency of the CYP2C19*17 allele in the study population has resulted in a revision of frequencies for CYP2C19*1/*2 (31·0%) and CYP2C19*1/*1 (16·1%) genotypes in the Tamilian population. We also observed significant differences in haplotype structure and frequencies of these variant alleles in the HapMap population compared to Tamilian population. What is new and conclusion: CYP2C19*17 allele is present at high frequency in the Tamilian population. This study also demonstrates the need for reassessment of wild-type allele frequencies in view of CYP2C19*17 allele. The estimated high frequency of CYP2C19*17 allele will aid in genotype-phenotype association studies in the Tamilian population. Further genotype-phenotype association studies are required to evaluate the clinical utility of this allele in South Indians. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence on whether active case finding (ACF) among marginalised and vulnerable populations mitigates the financial burden during tuberculosis (TB) diagnosis. Objectives: To determine the effect of ACF among marginalised and vulnerable populations on prevalence and inequity of catastrophic costs due to TB diagnosis among TB-affected households when compared with passive case finding (PCF). Methods: In 18 randomly sampled ACF districts in India, during March 2016 to February 2017, we enrolled all new sputum-smear-positive TB patients detected through ACF and an equal number of randomly selected patients detected through PCF. Direct (medical and non-medical) and indirect costs due to TB diagnosis were collected through patient interviews at their residence. We defined costs due to TB diagnosis as 'catastrophic' if the total costs (direct and indirect) due to TB diagnosis exceeded 20% of annual pre-TB household income. We used concentration curves and indices to assess the extent of inequity. Results: When compared with patients detected through PCF (n = 231), ACF patients (n = 234) incurred lower median total costs (US$ 4.6 and 20.4, p < 0.001). The prevalence of catastrophic costs in ACF and PCF was 10.3 and 11.5% respectively. Adjusted analysis showed that patients detected through ACF had a 32% lower prevalence of catastrophic costs relative to PCF [adjusted prevalence ratio (95% CI): 0.68 (0.69, 0.97)]. The concentration indices (95% CI) for total costs in both ACF [−0.15 (−0.32, 0.11)] and PCF [−0.06 (−0.20, 0.08)] were not significantly different from the line of equality and each other. The concentration indices (95% CI) for catastrophic costs in both ACF [−0.60 (−0.81, -0.39)] and PCF [−0.58 (−0.78, -0.38)] were not significantly different from each other: however, both the curves had a significant distribution among the poorest quintiles. Conclusion: ACF among marginalised and vulnerable populations reduced total costs and prevalence of catastrophic costs due to TB diagnosis, but could not address inequity. [ABSTRACT FROM AUTHOR]

Non-communicable Diseases (NCDs) are emerging as a major cause of morbidity and mortality. Control of risk factors and early diagnosis and treatment are cost-effective modalities for prevention. To attain this, Preventive Medicine Clinics must become a regular feature in the government hospitals of India. Community Medicine and/ or Family Medicine specialists of medical colleges can establish these clinics. In addition to screening patients for NCDs and their risk factors, these clinics can screen patients who require primary health care and manage them appropriately. [ABSTRACT FROM AUTHOR]

Background: A large state-wide tobacco survey was conducted using modified version of pretested, globally validated Global Adult Tobacco Survey (GATS) questionnaire in 2015–22016 in Tamil Nadu, India. Due to resource constrains, data collection was carrid out using paper-based questionnaires (unlike the GATS-India, 2009–2010, which used hand-held computer devices) while data entry was done using open access tools. The objective of this paper is to describe the process of data entry and assess its quality assurance and efficiency. Methods: In EpiData language, a variable is referred to as ‘field’ and a questionnaire (set of fields) as ‘record’. EpiData software was used for double data entry with adequate checks followed by validation. Teamviewer was used for remote training and trouble shooting. The EpiData databases (one each for each district and each zone in Chennai city) were housed in shared Dropbox folders, which enabled secure sharing of files and automatic back-up. Each database for a district/zone had separate file for data entry of household level and individual level questionnaire. Results: Of 32,945 households, there were 111,363 individuals aged ≥15 years. The average proportion of records with data entry errors for a district/zone in household level and individual level file was 4% and 24%, respectively. These are the errors that would have gone unnoticed if single entry was used.The median (inter-quartile range) time taken for double data entry for a single household level and individual level questionnaire was 30 (24, 40) s and 86 (64, 126) s, respectively. Conclusion: Efficient and quality-assured near-real-time data entry in a large sub-national tobacco survey was performed using innovative, resource-efficient use of open access tools. [ABSTRACT FROM PUBLISHER]

Objective. To identify the challenges encountered by private health care providers (PHCP) to notify tuberculosis cases through a programme developed web-based portal mechanism called “NIKSHAY.” Study Design. It is a descriptive qualitative study conducted at two revised national tuberculosis control programme (RNTCP) districts of New Delhi. The study included in-depth interviews of PHCP registered with “NIKSHAY” and RNTCP programme personnel. Grounded theory was used to conceptualise the latent social patterns in implementation of tuberculosis case notification process and promptly identifying their challenges. Results. The analysis resulted in identification of three broad themes: (a) system implementation by RNTCP: it emphasizes the TB notification process by the RNTCP programme personnel; (b) challenges faced by PHCP for TB notification with five different subthemes; and (c) perceived gaps and suggestions: to improvise the TB notification process for the private health sector. The challenges encountered by PHCP were mainly related to unsystematic planning and suboptimal implementation by programme personnel at the state and district level. The PHCP lacked clarity on the need for TB notification. Conclusion. Implementation of TB notification among private health care providers requires systematic planning by the programme personnel. The process should be user-friendly with additional benefits to the patients. [ABSTRACT FROM AUTHOR]

Background: Variants in the candidate genes eNOS, CYP11B2 and ACE have been implicated as liable biomarkers that can predict complications like hypertension and preeclampsia. Studies on the impact and distribution of these variants on healthy pregnancy have not been done so far in south Indian or in any of the native Indian population. Examining these variants could lay a strong basis in understanding the genetic aspects of preeclampsia and further offer effective means in early risk assessment in a preeclampsia. Methods: Genotyping for 303 unrelated healthy women of Tamilian origin who underwent uncomplicated term pregnancies was executed by PCR-RFLP for eNOS, CYP11B2 and ACE variants. Haplotype assessment and pairwise linkage disequilibrium (LD) investigation were performed by Haploview software. Results: The prevalence of eNOS variants (-786T>C, Glu298Asp and intron 4 VNTR) was 12%, 21.6% and 21.1%, respectively. The incidence of CYP11B2 (-344 C>T) and ACE (287 bp Alu I/D) variants was found to be 43.8% and 42.7%. The observed frequencies of the studied polymorphisms did not diverge from the HWE (p>0.05). Significant LD was observed between 3 eNOS gene polymorphisms. Six different haplotype structures with a frequency of >1% were generated from three eNOS variants. Among the haplotypes generated, the haplotype T-4b-G was the most common with the frequency of 64.4%. There was a statistically significant inconsistency in the study population in comparison to other global races. Conclusion: The outcome of this study could be used for investigating future therapeutic value of the variants in a preeclamptic set-up which could pose a credible diagnostic potential for primary risk assessment of women susceptible to preeclamp-sia/other pregnancy related complications. [ABSTRACT FROM AUTHOR]

Background & objectives: Several studies reported the polymorphisms of β1-adrenergic receptor gene in healthy volunteers and its influence on cardiovascular disorders. We investigated the genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism in healthy volunteers of South Indian Tamilian population vis-à-vis other major ethnic groups. Methods: The genetic variants were determined by using Taqman 5′ nuclease assay- real time PCR analysis in 533 normal healthy volunteers (18-60 yr; M=290; F=243). The allelic discrimination analysis was done by 7700 SDS software. Results: The estimated genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism were compared with other major populations. The frequencies of the variant alleles Gly49 and Gly389 were 15.1 and 25.8 per cent respectively. Interpretation & conclusions: Our study shows that interethnic variation exists in the polymorphisms of β1-adrenergic receptor gene and the results generated in this study might serve as a genetic marker for further studies in Tamilian (South India) population. [ABSTRACT FROM AUTHOR]