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Abstract Background Tuberculosis (TB) poses a significant social and economic burden to households of persons with TB (PwTB). Despite free diagnosis and care under the National TB Elimination Programme (NTEP), individuals often experience significant out-of-pocket expenditure and lost productivity, causing financial catastrophe. We estimated the costs incurred by the PwTB during TB care and identified the factors associated with the costs. Methods In our cross-sectional study, we used multi-stage sampling to select PwTB notified under the NTEP, whose treatment outcome was declared between May 2022 and February 2023. Total patient costs were measured through direct medical, non-medical and indirect costs. Catastrophic costs were defined as expenditure on TB care > 20% of the annual household income. We determined the factors influencing the total cost of TB care using median regression. We plotted concentration curves to depict the equity in distribution of catastrophic costs across income quintiles. We used a cluster-adjusted, generalized model to determine the factors associated with catastrophic costs. Results The mean (SD) age of the 1407 PwTB interviewed was 40.8 (16.8) years. Among them, 865 (61.5%) were male, and 786 (55.9%) were economically active. Thirty-four (2.4%) had Drug Resistant TB (DRTB), and 258 (18.3%) had been hospitalized for TB. The median (Interquartile range [IQR] and 95% confidence interval [CI]) of total costs of TB care was US$386.1 (130.8, 876.9). Direct costs accounted for 34% of the total costs, with a median of US$78.4 (43.3, 153.6), while indirect costs had a median of US$279.8 (18.9,699.4). PwTB

Abstract 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.

To reduce TB deaths, Tamil Nadu, a southern Indian state, implemented the first state-wide differentiated TB care strategy starting April 2022. Triage-positive severely ill patients are prioritised for comprehensive assessment and inpatient care. Routine program data during October–December 2022 revealed that documentation of total score after comprehensive assessment was available in only 39%, possibly indicating poor quality of comprehensive assessment. We confirmed this using operational research. The case record form to record comprehensive assessment was used only in 26% and among these, the completeness and correctness in filling out the form were sub-optimal. There is a clear need to enhance the quality of comprehensive assessments.

Abstract 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.

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., Author(s): Tulip A. Jhaveri 1,2, Disha Jhaveri 3,4, Amith Galivanche 3, Maya Lubeck-Schricker 3, Dominic Voehler 3, Mei Chung 3,5, Pruthu Thekkur 6,7, Vineet Chadha 8, Ruvandhi Nathavitharana 9, Ajay [...]

Genetic variations in the receptor, metabolizing enzymes and transporters may explain a part of the variation in anti-emetic response to ondansetron among cancer patients. This study assesses the role of ABCB1 genetic polymorphisms in the anti-emetic efficacy of ondansetron-based medication for cisplatin-based chemotherapy in South Indian cancer patients.

BackgroundIn 2022, India's national tuberculosis (TB) elimination program (NTEP) commissioned a national level evaluation of active case finding (ACF) for TB to guide evidence-based strategic planning. As part of this evaluation, based on secondary data analysis we observed that the quality of ACF was suboptimal in 2021. Hence, this study aimed to understand the enablers, barriers, and suggested solutions to improve ACF for TB in India from NTEP staff (provider) perspective.MethodsThis was a descriptive qualitative study involving key informant interviews from six districts and eight states, conducted between February and August 2023. We purposively selected key state- district- and sub-district-level program managers and implementers who were experienced and vocal. The interviews were audio recorded and transcribed verbatim by research interns and investigators. Two investigators independently did manual descriptive thematic analysis, and a third investigator resolved inconsistencies. The themes and categories emerged by collating together the results of the coding process.ResultsA total of 34 key informant interviews were conducted and of these, four were repeat interviews. Adequate budgets for ACF including incentives, performance review mechanism, engagement of all stakeholders, adopting a community friendly approach, use of rapid diagnostic tests and digitalization were the perceived enablers. In some states ACF was implemented in general population (not restricted to high-risk population) following directives at state level. There were limited mechanisms to ensure ACF quality indicators were met before disbursing incentives and cross-verification of the aggregate ACF care cascade numbers that were reported in Ni-kshay (electronic TB information management system under NTEP). In addition to the state and district level implementers having limited understanding of concepts around ACF (quality indicators, number needed to screen and yield), we also inferred the presence of a 'know-do' gap for many activities under ACF. The suggested solutions were around capacity building and quality improvement strategies.ConclusionThe existing national ACF guidance should be revised to emphasize capacity building, need to carry out ACF in high-risk (not general) population, quality control-linked incentives, and regular implementation monitoring of the activities. This should contribute towards better coverage and improved quality translating into better ACF outcomes.

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.

Background 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. Objectives 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. Methods 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). Results 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. Conclusion 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.

Mosunetuzumab is a novel bispecific antibody targeting epitopes on CD3 on T cells and CD20 on B cells with the goal of inducing T-cell mediated elimination of malignant B cells. A recent pivotal phase I/II clinical trial (GO29781) demonstrated that mosunetuzumab induced an overall response rate of 80%, complete response rate of 60%, and a median progression-free survival of 17.9 months in patients with relapsed/refractory (r/r) follicular lymphoma (FL) following at least two prior lines of systemic therapy, including alkylator and anti-CD20 antibody-based therapy. Historical data from cohorts receiving therapy for r/r FL can provide some context for interpretation of single-arm trials. We compared the results from the mosunetuzumab trial to outcomes from a cohort of patients with r/r FL from the LEO Consortium for Real World Evidence (LEO CReWE). We applied clinical trial eligibility criteria to the LEO CReWE cohort and utilized matching-adjusted indirect comparison weighting to balance the clinical characteristics of the LEO CReWE cohort with those from the mosunetuzumab trial. Overall response rates (73%, 95% CI:65-80%) and complete response rates (53%, 95% CI:45-61%) observed in the weighted LEO CReWE cohort were lower than those reported on the mosunetuzumab trial (ORR=80%, 95% CI:70-88%; CR=60%, 95% CI:49-70% respectively). Progression-free survival at 12 months was similar in the weighted LEO CReWE (60%, 95% CI:51-69%) and the mosunetuzumab trial (PFS 58%, 95% CI:47-68%). Sensitivity analyses examining the impact of matching variables, selection of line of therapy, and application of eligibility criteria, provide context for best practices in this setting.

Objective. To assess changes in antibiotic resistance of eight of the World Health Organization priority bug-drug combinations and consumption of six antibiotics (ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin, vancomycin) before (March 2018 to July 2019) and during (March 2020 to July 2021) the COVID-19 pandemic in 31 hospitals in Valle del Cauca, Colombia. Methods. This was a before/after study using routinely collected data. For antibiotic consumption, daily defined doses (DDD) per 100 bed-days were compared. Results. There were 23 405 priority bacterial isolates with data on antibiotic resistance. The total number of isolates increased from 9 774 to 13 631 in the periods before and during the pandemic, respectively. While resistance significantly decreased for four selected bug-drug combinations (Klebsiella pneumoniae, extended spectrum beta lactamase [ESBL]-producing, 32% to 24%; K. pneumoniae, carbapenem-resistant, 4% to 2%; Pseudomonas aeruginosa, carbapenem-resistant, 12% to 8%; Acinetobacter baumannii, carbapenem-resistant, 23% to 9%), the level of resistance for Enterococcus faecium to vancomycin significantly increased (42% to 57%). There was no change in resistance for the remaining three combinations (Staphylococcus aureus, methicillin-resistant; Escherichia coli, ESBL-producing; E. coli, carbapenem-resistant). Consumption of all antibiotics increased. However, meropenem consumption decreased in intensive care unit settings (8.2 to 7.1 DDD per 100 bed-days). Conclusions. While the consumption of antibiotics increased, a decrease in antibiotic resistance of four bug-drug combinations was observed during the pandemic. This was possibly due to an increase in community-acquired infections. Increasing resistance of E. faecium to vancomycin must be monitored. The findings of this study are essential to inform stewardship programs in hospital settings of Colombia and similar contexts elsewhere.

Objectives. To determine the level of adherence to clinical guidelines in prescribing amoxicillin to children younger than 5 years with pneumonia in outpatient settings in Colombia from 2017 to 2019, and assess the factors associated with adherence Methods. This was a cross-sectional study of secondary data from the Colombian Integrated Social Protection Information System database. Adherence was defined as prescription of oral amoxicillin for bacterial and unspecified pneumonia and non-prescription for viral pneumonia. Variables examined included: age (< 1 year, 1–4 years) of child; sex; cause of pneumonia (bacterial, viral, unspecified); region (Andean, Amazonian, Pacific, Caribbean, Insular, Orinoquian); and payment mechanism (without prior authorization, capitation, direct payment, pay per case, pay for event). Results. Of 215 925 cases of community-acquired pneumonia reported during 2017–2019, 64.8% were from the Andean region, 73.9% were bacterial pneumonia and 1.8% were viral pneumonia. Adherence to guidelines was observed in 5.8% of cases: this was highest for children diagnosed with viral (86.0%) compared with bacterial (2.0%) pneumonia. For children diagnosed with bacterial pneumonia, 9.4% were prescribed any antibiotic. A greater proportion of children covered by capitated payments (22.3%) were given treatment consistent with the guidelines compared with payment for event (1.3%). Conclusion. In this first study from Colombia, adherence to guidelines for outpatient treatment of children with bacterial pneumonia was low and was better for viral pneumonia. Further qualitative studies are needed to explore the reasons for this lack of adherence and why bacterial pneumonia was the most commonly reported etiology.

Background: IgA nephropathy (IgAN) is one of the most common glomerular diseases worldwide. Approximately 25 percent of IgAN patients reach the kidney failure stage within twenty years of diagnosis. The histopathological examination of kidney biopsy is needed to confirm the diagnosis of IgAN. microRNA (miRNA) is a small RNA that plays an important role at the post-transcriptional level by downregulating mRNAs (messenger RNA). We tried to establish a miRNA-based biomarker for IgAN. Methods: We recruited 30 IgAN patients and 15 healthy controls as study participants after taking their informed written consent. A real-time PCR-based method was used for the absolute quantification of miRNAs. A logistic regression method and receiver operating characteristic analysis were performed to find the diagnostic and prognostic accuracy of miR-148b and let-7b for IgAN in histopathological MEST-C scores. Results: miR-148b and let-7b levels were higher in IgAN patients compared to the healthy controls. miR-148b was positively correlated with glomerular filtration rate (GFR) and negatively correlated with segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis (T), and blood pressure (BP). The sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic (ROC) for miR-148b against T were 0.87, 0.77, and 0.85, respectively. The threshold value of the miR-148b copy number was 8479 to differentiate the severe condition of IgAN. Conclusion: miR-148b can be used as a potential biomarker for IgAN.

BackgroundWe aimed to determine the effectiveness and safety of the Levofloxacin-containing regimen that the World Health Organization is currently recommending for the treatment of Isoniazid mono-resistant pulmonary Tuberculosis.MethodsOur eligible criteria for the studies to be included were; randomized controlled trials or cohort studies that focused on adults with Isoniazid mono-resistant tuberculosis (HrTB) and treated with a Levofloxacin-containing regimen along with first-line anti-tubercular drugs; they should have had a control group treated with first-line without Levofloxacin; should have reported treatment success rate, mortality, recurrence, progression to multidrug-resistant Tuberculosis. We performed the search in MEDLINE, EMBASE, Epistemonikos, Google Scholar, and Clinical trials registry. Two authors independently screened the titles/abstracts and full texts that were retained after the initial screening, and a third author resolved disagreements.ResultsOur search found 4,813 records after excluding duplicates. We excluded 4,768 records after screening the titles and abstracts, retaining 44 records. Subsequently, 36 articles were excluded after the full-text screening, and eight appeared to have partially fulfilled the inclusion criteria. We contacted the respective authors, and none responded positively. Hence, no articles were included in the meta-analysis.ConclusionWe found no “quality” evidence currently on the effectiveness and safety of Levofloxacin in treating HrTB.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022290333, identifier: CRD42022290333.

Background: In 2022, India's national tuberculosis (TB) elimination program (NTEP) commissioned a national level evaluation of active case finding (ACF) for TB to guide evidence-based strategic planning. As part of this evaluation, based on secondary data analysis we observed that the quality of ACF was suboptimal in 2021. Hence, this study aimed to understand the enablers, barriers, and suggested solutions to improve ACF for TB in India from NTEP staff (provider) perspective. Methods: This was a descriptive qualitative study involving key informant interviews from six districts and eight states, conducted between February and August 2023. We purposively selected key state- district- and sub-district-level program managers and implementers who were experienced and vocal. The interviews were audio recorded and transcribed verbatim by research interns and investigators. Two investigators independently did manual descriptive thematic analysis, and a third investigator resolved inconsistencies. The themes and categories emerged by collating together the results of the coding process. Results: A total of 34 key informant interviews were conducted and of these, four were repeat interviews. Adequate budgets for ACF including incentives, performance review mechanism, engagement of all stakeholders, adopting a community friendly approach, use of rapid diagnostic tests and digitalization were the perceived enablers. In some states ACF was implemented in general population (not restricted to high-risk population) following directives at state level. There were limited mechanisms to ensure ACF quality indicators were met before disbursing incentives and cross-verification of the aggregate ACF care cascade numbers that were reported in Ni-kshay (electronic TB information management system under NTEP). In addition to the state and district level implementers having limited understanding of concepts around ACF (quality indicators, number needed to screen and yield), we also inferred the presence of a 'know-do' gap for many activities under ACF. The suggested solutions were around capacity building and quality improvement strategies. Conclusion: The existing national ACF guidance should be revised to emphasize capacity building, need to carry out ACF in high-risk (not general) population, quality control-linked incentives, and regular implementation monitoring of the activities. This should contribute towards better coverage and improved quality translating into better ACF outcomes. [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.

Hand hygiene is the most important intervention for preventing healthcare-associated infections and can reduce preventable morbidity and mortality. We described the changes in hand hygiene practices and promotion in 13 public hospitals (six secondary and seven tertiary) in the Western Area of Sierra Leone following the implementation of recommendations from an operational research study. This was a “before and after” observational study involving two routine cross-sectional assessments using the WHO hand hygiene self-assessment framework (HHSAF) tool. The overall mean HHSAF score changed from 273 in May 2021 to 278 in April 2023; it decreased from 278 to 250 for secondary hospitals but increased from 263 to 303 for tertiary hospitals. The overall mean HHSAF score and that of the tertiary hospitals remained at the “intermediate” level, while secondary hospitals declined from “intermediate” to “basic” level. The mean score increased for the “system change” and “institutional safety climate” domains, decreased for “training and education” and “reminders in the workplace” domains, and remained the same for the “evaluation and feedback” domain. Limited resources for hand hygiene promotion, lack of budgetary support, and formalized patient engagement programs are the persistent gaps that should be addressed to improve hand hygiene practices and promotion.

In 2021, an operational research study in two tertiary hospitals in Freetown showed poor hand hygiene compliance. Recommended actions were taken to improve the situation. Between February–April 2023, a cross-sectional study was conducted in the same two hospitals using the World Health Organization hand hygiene tool to assess and compare hand hygiene compliance with that observed between June–August 2021. In Connaught hospital, overall hand hygiene compliance improved from 51% to 60% (p < 0.001), and this applied to both handwash actions with soap and water and alcohol-based hand rub. Significant improvements were found in all hospital departments and amongst all healthcare worker cadres. In 34 Military Hospital (34MH), overall hand hygiene compliance decreased from 40% to 32% (p < 0.001), with significant decreases observed in all departments and amongst nurses and nursing students. The improvements in Connaught Hospital were probably because of more hand hygiene reminders, better handwash infrastructure and more frequent supervision assessments, compared with 34MH where interventions were less well applied, possibly due to the extensive hospital reconstruction at the time. In conclusion, recommendations from operational research in 2021 contributed towards the improved distribution of hand hygiene reminders, better handwash infrastructure and frequent supervision assessments, which possibly led to improved hand hygiene compliance in one of the two hospitals. These actions need to be strengthened, scaled-up and guided by ongoing operational research to promote good hand hygiene practices elsewhere in the country.

Background: The National Tuberculosis Control Program (NTP) in Pakistan developed, with the Pakistan Paediatric Association, a pediatric scoring chart to aid diagnosis of childhood tuberculosis (TB). Our study compared the diagnostic practice of private healthcare providers in Pakistan with the NTP guidelines. Methods: A cross-sectional study comparing diagnosis of TB in children

Corticosteroids are so vital for organ maturation that reduced corticosteroid signaling during postembryonic development causes death in terrestrial vertebrates. Indeed, death occurs at metamorphosis in frogs lacking proopiomelanocortin (pomc) or the glucocorticoid receptor (GR; nr3c1). Some residual corticosteroids exist in pomc mutants to activate the wild-type (WT) GR and mineralocorticoid receptor (MR), and the elevated corticosteroids in GR mutants may activate MR. Thus, we expected a more severe developmental phenotype in tadpoles with inactivation of 21-hydroxylase, which should eliminate all interrenal corticosteroid biosynthesis. Using CRISPR/Cas9 in Xenopus tropicalis , we produced an 11-base pair deletion in cyp21a2 , the gene encoding 21-hydroxylase. Growth and development were delayed in cyp21a2 mutant tadpoles, but unlike the other frog models, they survived metamorphosis. Consistent with an absence of 21-hydroxylase, mutant tadpoles had a 95% reduction of aldosterone in tail tissue, but they retained some corticosterone (∼40% of WT siblings), an amount, however, too low for survival in pomc mutants. Decreased corticosteroid signaling was evidenced by reduced expression of corticosteroid-response gene, klf9 , and by impaired negative feedback in the hypothalamus-pituitary-interrenal axis with higher messenger RNA expression levels of crh , pomc , star , and cyp11b2 and an approximately 30-fold increase in tail content of progesterone. In vitro tail-tip culture showed that progesterone can transactivate the frog GR. The inadequate activation of GR by corticosterone in cyp21a2 mutants was likely compensated for by sufficient corticosteroid signaling from other GR ligands to allow survival through the developmental transition from aquatic to terrestrial life. [ABSTRACT FROM AUTHOR]

Background: Pakistan implemented initiatives to detect tuberculosis (TB) patients through extended contact screening (ECS); it improved case detection but treatment outcomes need assessment. Objectives: To compare treatment outcomes of pulmonary TB (PTB) patients detected by ECS with those detected by routine passive case finding (PCF). Methods: A cohort study using secondary program data conducted in Lahore, Faisalabad and Rawalpindi districts and Islamabad in 2013–15. We used log binomial regression models to assess if ECS was associated with unfavorable treatment outcomes (death, loss-to-follow-up, failure, not evaluated) after adjusting for potential confounders. Results: We included 79,431 people with PTB; 4604 (5.8%) were detected by ECS with 4052 (88%) bacteriologically confirmed. In all PTB patients the proportion with unfavorable outcomes was not significantly different in ECS group (9.6%) compared to PCF (9.9%), however, among bacteriologically confirmed patients unfavorable outcomes were significantly lower in ECS (9.9%) than PCF group (11.6%, P = 0.001). ECS was associated with a lower risk of unfavorable outcomes (adjusted relative risk (aRR) 0.90; 95% CI 0.82–0.99) among ‘all PTB’ patients and bacteriologically confirmed PTB patients (aRR 0.91; 95% CI 0.82–1.00). Conclusion: In PTB patients detected by ECS the treatment outcomes were not inferior to those detected by PCF.

Abstract Background In China, an indigenously developed electronic medication monitor (EMM) was designed and used in 138 counties from three provinces. Previous studies showed positive results on accuracy, effectiveness, acceptability, and feasibility, but also found some ineffective implementations. In this paper, we assessed the effect of implementation of EMMs on treatment outcomes. Methods The longitudinal ecological method was used at the county level with aggregate secondary programmatic data. All the notified TB cases in 138 counties were involved in this study from April 2017 to June 2019, and rifampicin-resistant cases were excluded. We fitted a multilevel model to assess the relative change in the quarterly treatment success rate with increasing quarterly EMM coverage rate, in which a mixed effects maximum likelihood regression using random intercept model was applied, by adjusting for seasonal trends, population size, sociodemographic and clinical characteristics, and clustering within counties. Results Among all 69 678 notified TB cases, the treatment success rate was slightly increased from 93.5% [95% confidence interval (CI): 93.0–94.0] in second quarter of 2018 to 94.9% (95% CI: 94.4–95.4) in second quarter of 2019 after implementing EMMs. There was a statistically significant effect between quarterly EMM coverage and treatment success rate after adjusting for potential confounders (P = 0.0036), increasing 10% of EMM coverage rate will lead to 0.2% treatment success rate augment. Besides, an increase of 10% of elderly or bacteriologically confirmed TB will lead to a decrease of 0.4% and 0.9% of the treatment success rate. Conclusions Under programmatic settings, we found a statistically significant effect between increasing coverage of EMM and treatment success rate at the county level. More prospective studies are needed to confirm the effect of using EMM on TB treatment outcomes. We suggest performing operational research on EMMs that provides real-time data under programmatic conditions in the future.