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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.

BackgroundIndia has the highest burden of tuberculosis (TB), accounting for more than one-quarter of people with active TB and nearly one-third of TB deaths globally. Most people contracting active TB in India do not successfully navigate all stages of the care cascade to receive treatment and achieve TB recurrence-free survival. Understanding reasons for losses across the care cascade is critical to improve outcomes. In this paper, guided by a PECO (population/exposure/comparison/outcome) framework, we describe quantitative findings of a systematic review aimed at identifying factors contributing to unfavorable outcomes experienced by people with TB at each care cascade gap in India.Methods and findingsWe defined care cascade gaps as comprising people with confirmed or presumptive TB who did not: start the TB diagnostic workup (Gap 1), complete the diagnostic workup (Gap 2), start treatment (Gap 3), achieve treatment success (Gap 4), or achieve TB recurrence-free survival (Gap 5). Three systematic searches were conducted to identify 147 unique articles published from 2000 to 2021 that evaluated factors associated with unfavorable outcomes for each gap (reported as odds, relative risk, or hazard ratios) and, among people experiencing unfavorable outcomes, reasons reported for these outcomes (reported as proportions). Findings were organized into patient-, family-, society-, or health system-related factors, using a social-ecological framework.Some factors were common and associated with unfavorable outcomes across multiple care cascade stages. These included male sex, older age (variably defined across studies), a broad array of poverty-related factors, lower symptom severity or duration, undernutrition, alcohol use, smoking, and distrust of (or dissatisfaction with) local government health services. People who had been previously treated for TB were more likely to seek care and engage in the TB diagnostic workup (Gaps 1 and 2) but were also more likely to suffer pretreatment loss to follow-up (Gap 3) and unfavorable outcomes during TB treatment (Gap 4), especially those who had been lost to follow-up during their prior treatment episode.For individual care cascade gaps, multiple studies highlighted the importance of lack of TB knowledge and structural barriers to care (e.g., transport or financial challenges in reaching clinics) in contributing to lack of care-seeking for TB symptoms (Gap 1, 15 studies or analyses); lack of access to diagnostics (e.g., chest X-ray), non-identification of eligible patients for testing, and failure of providers to communicate concern for TB to patients in contributing to non-completion of the diagnostic workup (Gap 2, 20 studies or analyses); TB stigma, poor recording of patient contact information by providers, and early death due to diagnostic delays in contributing to pretreatment loss to follow-up (Gap 3, 25 studies); and medication adverse effects, TB stigma, and lack of TB knowledge in contributing to unfavorable treatment outcomes (Gap 4, 104 studies). Medication nonadherence contributed to unfavorable treatment outcomes (Gap 4) and post-treatment TB recurrence (Gap 5, 15 studies).ConclusionsThis extensive systematic review illuminates common patterns of risk that shape outcomes for people with TB in India, while also highlighting gaps in knowledge, particularly with regard to TB care for children or in the private sector, that can help to guide future research. These findings may help inform targeting of additional support services to people with TB who are at higher risk of poor outcomes and inform development of multi-component interventions to close gaps in India’s TB care cascade.Author SummaryWhy was this study done?India has the highest burden of tuberculosis (TB), accounting for more than one-quarter of people with active TB and nearly one-third of TB deaths globally.Of the nearly 3 million people contracting active TB every year in India, most do not successfully traverse all stages of the care needed to receive TB treatment and achieve an optimal long-term outcome, and serial losses of people with TB across these stages is often referred to as the “cascade of care.”Understanding risk factors among people with active or presumptive TB that contribute to losses from care, and why these losses occur, is crucial to inform the development of targeted interventions to prevent them from experiencing unfavorable outcomes.What did the researchers do and find?To understand reasons why people with TB are lost from care in India, we conducted three systematic searches of the medical literature to identify 147 unique and relevant articles published from 2000 to 2021.We extracted information from these studies on risk factors for unfavorable outcomes at each care cascade gap, as well as reasons reported by people with TB who experienced unfavorable outcomes and were surveyed by researchers.Some barriers to care or characteristics of people with TB contributed to losses at multiple stages of the care cascade, including male sex, older age, poverty-related factors, history of previous TB treatment, lower symptom severity or duration, undernutrition, alcohol use, smoking, and distrust of (or dissatisfaction with) local government health services.Other barriers contributed more substantially to individual care cascade gaps: lack of TB knowledge and structural barriers to care (e.g., transport barriers to clinics) contributed to lack of care-seeking for TB symptoms (Gap 1); poor accessibility of diagnostic testing, non-identification of eligible patients for testing, and failure of providers to communicate concern for TB to patients contributed to non-completion of the TB diagnostic workup (Gap 2); early death due to delays in diagnosis, TB stigma, and poor recording of patient contact information by healthcare providers contributed to losses of diagnosed patients before they started treatment (Gap 3); medication adverse effects, TB stigma, and lack of TB knowledge contributed to unfavorable TB treatment outcomes (Gap 4); and medication nonadherence contributed to unfavorable treatment outcomes and post-treatment TB recurrence (Gaps 4 and 5).What do these findings mean?The reasons for losses of people with TB across the care cascade are complex, vary by care cascade gap, and involve a mix of patient- and health system-related barriers.Given the complexity of the barriers contributing to unfavorable outcomes in India’s TB care cascade, future implementation interventions should consider involving multiple components that target different challenges faced by patients and the health system.In addition, India’s TB program and those in other high incidence settings should target additional services to people with TB who are at higher risk of experiencing poor outcomes.

Background: The choice of efficient antipsychotic therapy for schizophrenia relies on a time-consuming trial-and-error approach, whereas the social and economic burdens of the disease call for faster alternatives. Material \& methods: In a search for predictive biomarkers of antipsychotic response, blood methylomes of 28 patients were analyzed before and 4 weeks into risperidone therapy. Results: Several CpGs exhibiting response-specific temporal dynamics were identified in otherwise temporally stable methylomes and noticeable global response-related differences were observed between good and bad responders. These were associated with genes involved in immunity, neurotransmission and neuronal development. Polymorphisms in many of these genes were previously linked with schizophrenia etiology and antipsychotic response. Conclusion: Antipsychotic response seems to be shaped by both stable and medication-induced methylation differences., Epigenomics, 2023

Setting Five select districts of Karnataka, India, providing anti-tubercular and antiretroviral therapy (ATT and ART) to people with Human Immunodeficiency Virus (HIV) - associated Tuberculosis (TB) through a single window care approach at the ART centres (seven ART centres and 16 link ART centres). Objectives To determine the factors associated with non-adherence to concurrent therapy. Design We conducted a case–control study involving primary and secondary data collection. Starting January 2019, we consecutively enrolled people on at least three months of ATT until we enrolled 125 cases (non-adherent to concurrent therapy) and 375 controls (adherent to concurrent therapy). Adherence was defined as taking >95% ART doses and >90% ATT doses, every month over the last three months. We performed multivariable logistic regression to identify factors associated with non-adherence. Results The mean age of the cases and control was similar: 39.8 (standard deviation: 8.8) years. The risk factors for non-adherence were status non-disclosure (aOR = 2.06), zidovudine-based ART (aOR = 4.87), >3 side effects (aOR = 6.45), not receiving counselling before ATT initiation (aOR = 5.25) and non-receipt of co-trimoxazole prophylaxis (aOR = 9.90). Conclusion Major determinants for non-adherence were clinical and treatment related factors.

Dhulikhel Hospital, Kathmandu University Hospital, Kathmandu, Nepal.1) To report the incidence of health-care-associated infections (HAIs), 2) to compare demographic, clinical characteristics and hospital outcomes in those with and without HAIs; and 3) to verify bacterial types in HAI and community-acquired infections (CAIs) among inpatients with invasive devices and/or surgical procedures.This was a cohort study using secondary data (December 2017 to April 2018).Of 1,310 inpatients, 908 (69.3%) had surgical procedures, 125 (9.5%) had invasive devices and 277 (21.1%) both. Sixty-six developed HAIs (incidence = 5/100 patient admissions, 95% CI 3.9-6.3). Individuals with HAIs had a 5.5-fold higher risk of longer hospital stays (⩾7 days) and a 6.9-fold risk of being in intensive care compared to the surgical ward. Unfavourable hospital exit outcomes were higher in those with HAIs (4.5%) than in those without (0.9%,We found relatively low incidence of HAIs, which reflects good infection prevention and control standards. This study serves as a baseline for future monitoring and action.Hôpital de Dhulikhel, Hôpital Universitaire de Katmandu, Katmandu, Népal.1) Rapporter l’incidence des infections associées aux soins (HAI), 2) comparer les caractéristiques démographiques et cliniques et les résultats hospitaliers chez les patients atteints et non atteints de HAI ; et 3) vérifier les types bactériens des HAI et des infections communautaires (CAI) parmi les patients hospitalisés avec dispositifs invasifs et/ou ayant subi une intervention chirurgicale.Étude de cohorte réalisée en utilisant des données secondaires (décembre 2017 à avril 2018).Sur 1 310 patients hospitalisés, 908 (69,3%) ont subi une intervention chirurgicale, 125 (9,5%) avaient des dispositifs invasifs et 277 (21,1%) avaient à la fois un dispositif invasif et subi une intervention chirurgicale. Au total, 66 ont contracté une HAI (incidence = 5/100 admissions de patients, IC 95% 3,9-6,3). Les patients atteints de HAI avaient un risque 5,5 fois plus élevé de séjour prolongé à l’hôpital (⩾7 jours) et un risque 6,9 fois plus élevé d’être admis en soins intensifs qu’en service de chirurgie. Les résultats défavorables à une sortie d’hôpital étaient plus fréquents chez ceux atteints de HAI (4,5%) que chez ceux non atteints de HAI (0,9%,Nous avons observé une incidence relativement faible de HAI, ce qui reflète de bons standards de contrôle et de prévention des infections. Cette étude sert de référence à de futures actions et stratégies de suivi.

SETTING: Biratnagar Eye Hospital, Biratnagar, Nepal, which offers ear surgery for chronic suppurative otitis media (CSOM).OBJECTIVE: In patients with CSOM awaiting surgery, to determine the 1) sociodemographic characteristics 2) bacterial isolates and their antibiotic resistance patterns and 3) characteristics of those refused surgery, including antibiotic resistance.DESIGN: A cohort study using hospital data, January 2018–January 2020.RESULTS: Of 117 patients with CSOM and awaiting surgery, 64% were in the 18–35 years age group, and 79% were cross-border from India. Of 118 bacterial isolates, 80% had Pseudomonas aeruginosa and 16% had Staphylococcus aureus. All isolates showed multidrug resistance to nine of the 12 antibiotics tested. The lowest antibiotic resistance in P. aeruginosa was for vancomycin (29%) and moxifloxacin (36%), and for S. aureus, this was vancomycin (9%) and amikacin (17%). Fourteen (12%) patients underwent surgery: myringoplasty (n = 7, 50%), cortical mastoidectomy with tympanostomy (n = 4, 29%) and modified radical mastoidectomy (n = 3, 21%). Those infected with P. aeruginosa and with resistance to over six antibiotics were significantly more likely to be refused for surgery.CONCLUSION: Patients awaiting ear surgery were predominantly infected with multidrug-resistant P. aeruginosa and were consequently refused surgery. This study can help inform efforts for improving surgical uptake and introducing cross-border antimicrobial resistance surveillance.

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.

Insects use diverse arrays of small molecules such as metabolites of the large class of terpenes for intra-and inter -specific communication and defense. These molecules are synthesized by specialized metabolic pathways; however, the origin of enzymes involved in terpene biosynthesis and their evolution in insect genomes is still poorly understood. We addressed this question by investigating the evolution of isoprenyl diphosphate synthase (IDS)-like genes with terpene synthase (TPS) function in the family of stink bugs (Pentatomidae) within the large order of piercing-sucking Hemipteran insects. Stink bugs include species of global pest status, many of which emit structurally related 15-carbon sesquiterpenes as sex or aggregation pheromones. We provide evidence for the emergence of IDS-type TPS enzymes at the onset of pentatomid evolution over 100 million years ago, coinciding with the evolution of flowering plants. Stink bugs of different geographical origin maintain small IDS -type families with genes of conserved TPS function, which stands in contrast to the diversification of TPS genes in plants. Expanded gene mining and phylogenetic analysis in other hemipteran insects further provides evidence for an ancient emergence of IDS-like genes under presumed selection for terpene-mediated chemical interactions, and this process occurred independently from a similar evolution of IDS-type TPS genes in beetles. Our findings further suggest differences in TPS diversification in insects and plants in conjunction with different modes of gene functionalization in chemical interactions. National Science Foundation; US Department of Agriculture National Institute of Food and Agriculture; [MCB1920914]; [MCB1920922]; [MCB1920925]; [2016-67013-24759] Published version Acknowledgements This work was supported by the National Science Foundation (MCB1920914, MCB1920922, MCB1920925) to AVM, P.O., and D.T., respectively, and the US Department of Agriculture National Institute of Food and Agriculture (2016-67013-24759) to DT, AK, DEG-R, and DCW. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture. The USDA is an equal opportunity provider and employer.

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.

Introduction: Qualitative studies are often inadequately reported, making it difficult to judge their appropriateness for decision making in public health. We assessed the publication characteristics and quality of reporting of qualitative and mixed-method studies from the Structured Operational Research and Training Initiative (SORT IT), a global partnership for operational research capacity building. Methods: A cross-sectional analysis of publications to assess the qualitative component using an adapted version of the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Results: In 67 publications involving 18 countries, 32 journals and 13 public health themes, 55 were mixed-methods studies and 12 were qualitative studies. First authorship from low-and-middle-income (LMIC) countries was present in 64 (96%), LMIC last authorship in 55 (82%), and female first authorship in 30 (45%). The mean LMIC institutions represented per publication was five (range 1–11). Sixty-three (94%) publications were open access. Reporting quality was graded as ‘good’ to ‘excellent’ in 60 (89%) publications, ‘fair’ in five (8%) and ‘poor’ in two (3%). Conclusion: Most SORT IT publications adhered to COREQ standards, while supporting gender equity in authorship and the promotion of LMIC research leadership. SORT IT plays an important role in ensuring quality of evidence for decision making to improve public health.

In this study, we described the bacterial profile, antibiotic resistance pattern, and laboratory result turnaround time (TAT) in neonates with suspected sepsis from a tertiary-level, military hospital in Accra, Ghana (2017–2020). This was a cross-sectional study using secondary data from electronic medical records. Of 471 neonates clinically diagnosed with suspected sepsis in whom blood samples were collected, the median TAT from culture request to report was three days for neonates who were culture-positive and five days for neonates who were culture-negative. There were 241 (51%) neonates discharged before the receipt of culture reports, and of them, 37 (15%) were culture-positive. Of 471 neonates, twenty-nine percent (n = 139) were bacteriologically confirmed, of whom 61% (n = 85) had late-onset sepsis. Gram-positive bacterial infection (89%, n = 124) was the most common cause of culture-positive neonatal sepsis. The most frequent Gram-positive pathogen was coagulase-negative Staphylococcus (55%, n = 68) followed by Staphylococcus aureus (36%, n = 45), of which one in two were multidrug resistant. The reasons for large numbers being discharged before the receipt of culture reports need to be further explored. There is a need for improved infection prevention and control, along with ongoing local antimicrobial resistance surveillance and antibiotic stewardship to guide future empirical treatment.

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

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 Conclusion We found gaps at various steps. There were a significant number of ‘rapid DST-negative, smear-positive’ patients.

SETTING: Adolescents (age: 15–19 years) from the National Family Health Survey-4 (2015–2016), India.OBJECTIVE: To examine the sociodemographic and nutritional characteristics of adolescents with reported TB and those with a reported household TB exposure.METHODS: This was a cross-sectional study using secondary data. We assessed the factors associated with TB (reported in adolescents, or in a household member) using log binomial regression. We used height-for-age and body mass index for age Z-scores for stunting and thinness, respectively.RESULTS: Of the total 277 059 adolescents, 377 (136/100 000, 95%CI 123–151) were reported with TB and this was similar in both sexes. Another 4528 adolescents (1.6%, 95%CI 1.6–1.7) reported household TB exposure. Poverty and urban residence were associated with higher prevalence of TB and household TB exposure. The proportion of stunting was 40.7% (95%CI 33.5–48.0) in adolescents with reported TB and 38.2% (95%CI 36.2–40.2) (P = 0.248) in those with household TB exposure.CONCLUSION: Prevalence of reported adolescent TB was lower than adult TB. Poverty and urban residence were risk factors for both TB and household TB exposure. Chronic undernutrition was highly prevalent among those reported to have TB and in those at risk of TB by virtue of having household TB exposure.

Despite considerable progress over the years, tuberculosis (TB) still remains the top cause of death among the infectious diseases and has devastating socio-economic consequences for people in low- and middle-income countries. To add to this, the emergence of the COVID-19 pandemic has worsened delivery of TB care across the globe. As a global community, we have committed to end the TB epidemic by 2030. The World Health Organization has framed a strategy to achieve this goal which consists of three pillars namely i) integrated patient-centred care and prevention, ii) bold policies and systems and iii) intensified research and innovation. An analysis of the performance of national tuberculosis programmes (NTPs) across the globe against the ten priority indicators recommended for monitoring the end TB strategy show that there are huge gaps at every step in the cascade of care of TB patients. In our view, these gaps reflect suboptimal implementation of existing strategies known to be efficacious and operational research (OR) is one of the best available tools to plug the gaps. In this paper, we define what operational research is and how it differs from other kinds of research. We also share our views and experiences about how operational research can be used by NTPs to identify implementation gaps and their reasons, and develop and test possible solutions - which are then integrated to make changes to policy and practice and eventually improve programme outcomes. OR can be defined as research into interventions, strategies and tools which produces practical useable knowledge that can be used to enhance the quality, coverage, effectiveness and efficiency of disease control programmes, health services or health systems in which the research is conducted. The key steps in integrating operational research in the NTPs include: i) securing political commitment reflected by inclusion of OR in the national strategic plans of NTPs and earmarked funding, ii) having a critical mass of dedicated and trained human resources in OR within the NTP, iii) setting research priorities and steering the direction of research in the country, iv) using output-oriented models of capacity building such as the Structured Operational Research Training Initiative (SORT IT) model and building communities of practice, v) harnessing existing capacity in the country by forging partnerships with academia, vi) NTP-led nationwide, multicentre OR studies, vii) providing access to anonymized patient and programme surveillance data, vii) creating a forum for evidence dissemination and fostering policy change and ix) monitoring and accountability. In conclusion, ending the TB epidemic will not be possible without new tools (diagnostics, drugs, vaccines) and a multi-sectoral response involving stakeholders beyond the health ministry, including private providers, patients and communities. However, timely conduct of operational research to fine-tune programme implementation and ensuring proper deployment of new tools will be equally crucial to maximize the effectiveness and efficiency of interventions and ultimately contribute towards ending TB.

SETTING: China National Tuberculosis Programme, 2010–2017.OBJECTIVE: To describe the epidemiology of childhood (age < 15 years) TB, including treatment outcomes and risk factors for unfavourable outcomes and death.DESIGN: We used a cross-sectional design for the descriptive component and a cohort design for treatment outcomes and their risk factors (assessed using log binomial regression).RESULTS: Of 40 561 children, 77.7% (n = 31 529) were aged 10–14 years and 19.6% (n = 7931) were bacteriologically confirmed. Around 14% (n = 5827) belonged to migrant families (internal migration) and 4.0% (n = 1,642) were actively detected. Over 8 years, annual notification was consistently very low (CONCLUSION: China needs to address the issue of under-detection of childhood TB, especially in younger age groups. The risk factors identified require attention if China is to attain zero child TB deaths.

Genetic factors could be attributed to the variability in docetaxel plasma levels and its subsequent therapeutic response. The objectives of this study were to assess the effect of ABCB1 gene polymorphisms [SNPs rs1045642 (C3435T) and rs1128503 (C1236T)] on docetaxel plasma levels and also to analyze the influence of docetaxel plasma levels on tumour response in the ethnically distinct South Indian population. 104 locally advanced breast cancer (LABC) patients on docetaxel-based neo‐adjuvant chemotherapy (NACT) were included. The plasma docetaxel levels were estimated using the validated reverse phase liquid chromatography with mass spectrometry (LC–MS/MS). DNA was extracted (phenol‐chloroform extraction method) and the real‐time PCR system using validated TaqMan® SNP genotyping assay method was used for genotyping. Tumour response was assessed by RECIST criteria based on the MRI images. Patients with “CT/TT” genotype of the SNP C1236T had a C0/Ct ratio of 1.6 times higher than those with “CC” genotype (13.5 ± 6.5 vs 8.3 ± 3.1, p = 0.002). Though not significant, patients with “CT/TT” genotype had greater initial plasma concentration (C0) and area under the plasma concentration–time curve (AUC0−t). Conversely, the SNP C3435T was not associated with the plasma docetaxel levels. Furthermore, the C0 and normalized C0 were found to be higher in tumour responders compared to non-responders (p

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.

Background The World Health Organization recommends the Xpert MTB/RIF Ultra assay for diagnosing pulmonary tuberculosis (PTB) in children. Though stool is a potential alternative to respiratory specimens among children, the diagnostic performance of Xpert Ultra on stool is unknown. Thus, we assessed the diagnostic performance of Xpert Ultra on stool to diagnose PTB in children. Methods We conducted a cross-sectional study among consecutively recruited children (, Xpert Ultra may be used on stool, an easy-to-obtain specimen, for childhood pulmonary tuberculosis diagnosis. Future studies with follow-up and clinical evolution are needed to provide insight on management of children with trace call.

Background/objectives: miR-21 has been linked to renal fibrosis and miR-155 too has shown different expression in IgAN whose pathogenesis is partially understood. In this study, we explored the utility of miR-21 and miR-155 in IgA nephropathy. Methods: We recruited 40 IgA nephropathy (IgAN) patients and 15 healthy controls (HC). 2 ml blood sample was collected from each study participant. Mean expressed value normalization and absolute and relative quantification methods were used for quantitative polymerase chain reaction (PCR) experiment for miRNA expression. Logistic regression analysis was performed for diagnostic and prognostic value of miR-21. Findings: Mean expressed value normalization reduced the variation in groups and between groups without changing the mean value. miR-155 showed similar expression in IgAN and healthy controls. There was three-fold increases in miR-21 in IgAN than the HC. miR-21 was able to differentiate the mesangial hypercellularity and tubular atrophy/interstitial fibrosis stages with sensitivity 84 and 70 percent, respectively. Applications: miR-155 can be used as a reference control gene for IgAN on quantitative PCR-based experiments. miR-21 can be used as a diagnostic and prognostic marker for IgAN. Keywords: miR-21, miR-155, IgAN, Tubular Atrophy, Interstitial Fibrosis.

Background: Citrate is filtered by the glomeruli and reabsorbed in tubular cells in kidney. Through this study, we have tried to explore citrate as a diagnostic tool for IgA nephropathy. Methods: We recruited 35 IgA nephropathy (IgAN) patients and 15 healthy controls (HC). 30 ml urine sample collected from each study participant. Solid phase extraction method used for urine purification. Liquid chromatography attached with mass spectrometry (LC–MS/MS) used for the citrate concentration determination. Logistic regression method used for diagnostic model prediction. Findings: Urinary citrate level was higher in IgAN patients by more than two and half times in comparison to HC. We made logistic regression model with citrate, urine protein, estimated glomerular filtration rate (eGFR), urine pH, systolic and diastolic blood pressure as variables. Citrate with urine protein was found to be the best fit statistical model with area under curve 0.77 and sensitivity and specificity more than 0.70 and 0.80, respectively. Applications: Urinary citrate with urine protein can be used for the early prediction of IgAN. Keywords: IgAN, Citrate, Urine Protein, Kidney Stone.

BACKGROUND: The study was conducted in BRAC-administered areas of the Bangladesh National Tuberculosis (TB) Programme (42 of 64 districts). According to the 2013–2017 financial support scheme, direct costs due to TB diagnosis were reimbursed among economically disadvantaged people with presumptive smear-negative pulmonary (PTB) and extrapulmonary TB (EPTB).OBJECTIVE: To describe the implementation of the scheme and associated changes in case notification.DESIGN: This was a descriptive study involving programme data.RESULTS: Between 2013 and 2017, persons reimbursed reduced from 125 680 to 88 763, and the case detection ratio increased from 18% to 24%. The number of patients with presumptive EPTB who were reimbursed decreased from 5024 to 3484. More than 95% were reimbursed for chest radiograph, fine-needle aspiration cytology and biopsy. However, large numbers of ancillary investigations were also reimbursed. During 2013–2017, the observed national quarterly new smear-negative PTB case notification rates (CNRs) were significantly higher than the forecasted CNRs (based on CNR trends during 2008–2012). New EPTB and all form TB CNRs increased but not significantly.CONCLUSION: Implementation of the financial support scheme was accompanied by a significant improvement in new, smear-negative PTB notification. The absence of a comparison arm was a key limitation, but comparison was not possible as the scheme was implemented in all districts.

Hand hygiene actions are essential to reduce healthcare-associated infections and the development of antimicrobial resistance. In this cross-sectional study at two tertiary hospitals, Freetown, Sierra Leone, we observed hand hygiene compliance (defined as using handwash with soap and water or alcohol-based hand rub (ABHR) amongst healthcare workers between June and August 2021. Using the WHO Hand Hygiene tool, observations were made in relation to the type of opportunity, different wards and types of healthcare worker. Overall, 10,461 opportunities for hand hygiene were observed, of which 5086 (49%) resulted in hand hygiene actions. ABHR was used more often than handwash (26% versus 23%, p < 0.001). Overall, compliance was significantly better: after being with a patient/doing a procedure than before (78% after body fluid exposure risk compared with 24% before touching a patient—p < 0.001); in Paediatric (61%) compared with Medical wards (46%)—p < 0.001; and amongst nurses (52%) compared with doctors (44%)—p < 0.001. Similar patterns of compliance were observed within each hospital. In summary, hand hygiene compliance was sub-optimal, especially before being with a patient or before clean/aseptic procedures. Improvement is needed through locally adapted training, hand hygiene reminders in wards and outpatient departments, uninterrupted provision of ABHR and innovative ways to change behaviour.

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.

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.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.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.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.

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 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.

Novel therapies for relapsed or refractory follicular lymphoma are commonly evaluated in single-arm studies without formal comparison with other treatments or historical controls. Consequently, rigorously defined treatment outcomes informing expectations for novel therapeutic strategies in this population are sparse. To inform outcome expectations, we aimed to describe treatment patterns, survival outcomes, and duration of response in patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy.In this multicentre cohort study, we developed a database of patients with relapsed or refractory follicular lymphoma from eight academic centres in the USA using data collected in the LEO Cohort study (NCT02736357) and the LEO Consortium. For this analysis, eligible patients were aged at least 18 years, had non-transformed grade 1-3a follicular lymphoma, and were receiving systemic therapy in the third line or later after previous therapy with an anti-CD20 antibody and an alkylating agent. Clinical data and patient outcomes were abstracted from medical records by use of a standard protocol. The index therapy for the primary analysis was defined as the first line of systemic therapy after the patient had received at least two previous systemic therapies that included an alkylating agent and an anti-CD20 therapy. The main endpoints of interest were overall response rate, progression-free survival, and overall survival. Outcomes were also evaluated in subsets of clinical interest (index therapy characteristics, patient and disease characteristics, treatment history, and best response assessment).We screened 933 patients with follicular lymphoma, of whom 441 were included and diagnosed between March 6, 2002, and July 20, 2018. Index therapies included immunochemotherapy (n=133), anti-CD20 antibody monotherapy (n=53), lenalidomide with or without anti-CD20 (n=37), and phosphoinositide 3-kinase inhibitors with or without anti-CD20 (n=25). 57 (13%) of 441 patients received haematopoietic stem-cell transplantation and 98 (23%) of 421 patients with complete data received therapy on clinical trials. After a median follow-up of 71 months (IQR 64-79) from index therapy, 5-year overall survival was 75% (95% CI 70-79), median progression-free survival was 17 months (15-19), and the overall response rate was 70% (65-74; 280 of 400 patients evaluable for response). Patients who were refractory to therapy with an alkylating agent had a lower overall response rate (170 [68%] of 251 patients vs 107 [77%] of 139 patients) and a significantly lower 5-year overall survival (72%, 95% CI 66-78 vs 81%, 73-89; hazard ratio 1·60, 95% CI 1·04-2·46) than patients who were not refractory to therapy with an alkylating agent.Patients with relapsed or refractory follicular lymphoma receive heterogeneous treatments in the third-line setting or later. We observed high response rates to contemporary therapies that were of short duration. These data identify unmet needs among patients with follicular lymphoma, especially those who are refractory to alkylating agents, and might provide evidence by which clinical trials evaluating novel treatments could be assessed.Genentech and the National Cancer Institute.

In India, the “low mortality” narrative based on the reported COVID-19 deaths may be causing more harm than benefit. The extent to which COVID-19 deaths get reported depends on the coverage of routine death surveillance [death registration along with medical certification of cause of death (MCCD)] and the errors in MCCD. In India, the coverage of routine death surveillance is 18.1%. This is compounded by the fact that COVID-19 death reporting is focused among reported cases and the case detection ratio is low. To adjust for the coverage of routine death surveillance and errors in MCCD, we calculated a correction (multiplication) factor at national and state level to produce an estimated number of COVID-19 deaths. As on July 31, 2020, we calculated the infection fatality ratio (IFR) for India (0.58:100–1.16:100) using these estimated COVID-19 deaths; this is comparable with the IFR range in countries with near perfect routine death surveillance. We recommend the release of excess deaths data during COVID-19 (at least in states with high death registration) and post-mortem COVID-19 testing as a surveillance activity for a better understanding of under-reporting. In its absence, we should adjust reported COVID-19 deaths for the coverage of routine death surveillance and errors in MCCD. This way we will have a clear idea of the true burden of deaths and our public health response will never be inadequate. We recommend that “reported” or “estimated” is added before the COVID-19 death data and related indicators for better clarity and interpretation.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is a significant source of cancer morbidity and mortality. More than half of all newly diagnosed patients are older than 65 years, among whom the 5-year relative survival rate is 54% (SEER 2020). Prior research has shown that not all elderly patients (≥80 years old) receive R-CHOP or mini-R-CHOP regimens as the first line of therapy (LoT); those who do not may have suboptimal outcomes (Williams, et al. Cancer 2015; Hamlin, et al. Oncologist 2014; Juul, et al. Eur J Cancer 2018). This study leverages two real-world data (RWD) sources, Flatiron Health (FH) electronic health record-derived de-identified database and SEER-Medicare (SEER-M) to characterize elderly patients with DLBCL (including observed treatment patterns), summarize overall survival (OS) outcomes, and identify unmet medical needs in this population. Methods: RWD from FH included patients with a DLBCL diagnosis on or after January 1, 2011, with follow-up until May 31, 2020. The SEER-M database is a linkage of two population-based RWD sources: the SEER Cancer Registry and Medicare claims database. RWD from SEER-M for this study included patients with a DLBCL diagnosis between January 1, 2011 and December 31, 2015, with follow-up until December 31, 2016. All fee-for-service Medicare enrollees in SEER-M had to have complete claims. RWD for basic demographics, treatments and outcomes were analyzed from both datasets; FH's database included data on certain clinical characteristics including granularity for dosing data when available, in comparison to SEER-M. This descriptive analysis included patients who were aged ≥80 years at diagnosis. Among patients in the FH database who received R-CHOP as first LoT and had available dosing data, those who received Results: The study included 725 patients from the FH database and 2613 patients from the SEER-M database; patient characteristics and outcomes were generally consistent between the two datasets. In total, 16% and 35% of the elderly patients had no record of systemic treatment in FH and SEER-M respectively (Table). More than half of the treated patients received R-CHOP in the first LoT (63% and 53% in FH and SEER-M, respectively); other patients received attenuated regimens, including rituximab plus bendamustine (R-Benda), rituximab plus cyclophosphamide, vincristine and prednisolone (R-CVP), and rituximab (R) monotherapy. Patients who received R-CHOP in the first LoT had numerically longer median OS (Flatiron: 55.0 months [95% CI: 41.8-NA]; SEER-M: 50.7 months [95% CI: 45.9-62.9]) compared with those who received other regimens (Figure A, B). Untreated patients had a median survival of 3.1 months (95% CI: 2.3-5.2) in the Flatiron dataset and 2.0 months (95% CI: 1.8-2.2) in the SEER-M dataset. Among those who received R-CHOP and with available dosing data, 51% received reduced-dose R-CHOP in the first LoT and OS appeared shorter than for patients who received full-dose R-CHOP (Figure C). Conclusions: Despite differences between the databases, RWD in FH and SEER-M both demonstrate considerable variation in the regimens received by elderly DLBCL patients, with 16-35% receiving no treatment and >50% receiving attenuated regimens including reduced-dose R-CHOP. Patients receiving regimens other than R-CHOP had a numerically lower survival probability compared with the standard of care (SoC) R-CHOP/reduced-dose R-CHOP. These data show a high unmet medical need among elderly patients with DLBCL who may not be able to tolerate immunochemotherapy regimens that have been evaluated in trials for a carefully selected patient population. Further research will aim to assess prognostic factors at the time of treatment initiation, as well as gather information on comorbidities and other factors that may prevent elderly patients from receiving SoC R-CHOP; these patients may be candidates for better-tolerated novel approaches. Disclosures Shewade: Genentech, Inc.: Current Employment. Olszewski:TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding; Genentech, Inc.: Research Funding; Spectrum Pharmaceuticals: Research Funding. Pace:Genentech, Inc.: Current Employment; Exponent: Ended employment in the past 24 months; Prior employer was a consulting firm. No expert testimony given. No relevant consulting work done.: Consultancy. Surinach:Seattle Genetics: Research Funding. Sellam:F. Hoffmann-La Roche: Current Employment. Mueller:Genentech, Inc.: Current Employment, Ended employment in the past 24 months; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. O'Hear:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company.

Background: In India, systematic cervical cancer screening under the national programme is yet to cover the entire population and therefore opportunistic or camp based approach is commonly practiced screening mode currently. This study presents the proportion of screen-positive women [positive visual inspection of the cervix with acetic acid (VIA) and/or Papanicolaou (Pap) smear results] and its associated factors from a rural community-based cervical cancer screening conducted in a service setting. Methods: In this cross-sectional study involving record review, data was drawn from free screening camps conducted by a non-governmental organization in two rural districts of Tamil Nadu, India between March 2015 and March 2017. The associations were assessed using adjusted prevalence ratio with 95% confidence interval. Results: A total of 5,207 women were screened from 307 camps. The mean age was 39.5 years (SD: 8.6). At least one symptom was observed among 2,245 women (43.1%). Of 5,207 women, 19.4% (n=1,009, 95% CI: 18.3%, 20.5%) were screen-positive. Screen positivity in women

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.

Low back pain (LBP) is the major cause of disability worldwide. The existing treatments are expensive and associated with complications. The present study aimed to determine the proportion of patients completing therapy and rehabilitation phases and describe the changes in self-reported symptoms and functional disability among LBP patients enrolled in a private sports medicine institute.This is a cohort study involving review of case records. We studied 2 phases out of 3 of non-invasive treatment of LBP: therapy of around 10 days (myofascial trigger point release therapy, cryotherapy, aqua therapy and acupuncture) and rehabilitation of around 3 weeks (muscle strengthening exercises).A total of 443 patients were enrolled; their mean (SD) age was 46 (15) years, 46% were male, and 193 (44%) presented with chronic (6 months) pain. The numbers of patients who completed the therapy and rehabilitation phases were 327 (74%) and 115 (26%), respectively. The median (IQR) visual analogue scale pain scores were 7 (6-9) at entry, 2 (1-3) at completion of therapy and 1 (0-2) at completion of rehabilitation (p0.001). The median (IQR) functional disability scores were 32 (22-53) at entry, 15 (6-26) at completion of therapy and 4 (0-14) at completion of rehabilitation (p0.001).Low completion rates were observed. Patients who completed therapy reported reduction in pain and improved functionalities.Hintergrund/Zielsetzung: Schmerzen im unteren Rücken (“Kreuzschmerzen”) sind weltweit die häufigste Ursache für körperliche Beeinträchtigung. Die verfügbaren Therapieoptionen sind mit hohen Kosten und vielen Komplikationen verbunden. Ziel dieser Studie war es, den Anteil der Kreuzschmerzpatienten zu ermitteln, die an einem privaten sportmedizinischen Institut ihre jeweiligen The­rapie- und Rehabilitationsphasen vollständig absolvierten, und die Veränderungen bei Symptomen und funk­tioneller Beeinträchtigung laut Selbstauskunft der Patienten zu beschreiben. Methoden: Es handelt sich um eine Kohortenstudie mit Sichtung von Patientenakten. Wir untersuchten zwei von drei Phasen nicht-invasiver Kreuzschmerztherapie von etwa 10 Tagen Dauer (Therapie zur Auflösung von myofaszialen Triggerpunkten, Kryotherapie, Wassergymnastik und Akupunktur) bzw. Rehabilitationsmaßnahmen von etwa drei Wochen (Muskelaufbautraining). Ergebnisse: Das mittlere Alter der 443 einbezogenen Patienten betrug (mit Standardabweichung) 46 (15) Jahre; 46% waren männlich, und 193 (44%) hatten chronische Schmerzen (6 Monate). Der Anteil der Patienten, die ihre Therapie- bzw. Rehabilitationsphasen vollständig abschlossen, betrug 327 (74%) bzw. 115 (26%). Der Schmerzscore auf der visuellen Analogskala betrug im Median (mit Quartilsabstand) bei Untersuchungsbeginn 7 (6–9), bei Abschluss der Therapie 2 (1–3) und bei Abschluss der Rehabilitation 1 (0–2) (p0,001). Der Score für den Grad der Funktionseinschränkung betrug im Median (mit Quartilsabstand) zu Beginn 32 (22–53), bei Abschluss der Therapie 15 (6–26) und bei Abschluss der Rehabilitation 4 (0–14) (p0,001). Schlussfolgerung: Die verzeichneten Abschlussraten waren niedrig. Diejenigen Patienten, die ihre Behandlung abschlossen, berichteten von Schmerzreduktion und funktioneller Verbesserung.

Aim: CAPOX treatment in CRC patients was reported to cause several dose-limiting toxicities, and are found responsible for treatment interruption or even discontinuation. Therefore there is a critical need for identifying the predictive biomarkers for such toxicities to prevent them. The aim of our present study is to find the influence of DPYD*9A, DPYD*6 and GSTP1 ile105val gene polymorphisms on CAPOX treatment-associated toxicities in south Indian patients with CRC. Patients and Methods: We have recruited 145 newly diagnosed and treatment naive CRC patients in the study. Each Patient received a standard treatment schedule of oxaliplatin 130 mg/m2 infusion over 2 hours on day 1 and oral capecitabine 1000mg/m2 in divided doses twice daily for the next 14 days of a 21-day cycle. 5 ml of the venous blood was collected from each patient and genomic DNA extraction and genotyping. The genotyping analysis of the selected genetic polymorphisms was carried out by real-time PCR using TaqMan SNP genotyping assays obtained from applied biosystems. Results: The major dose-limiting toxicities observed with CAPOX treatment were thrombocytopenia, HFS and PN. DPYD*9A carries were found to be at higher risk for HFS, diarrhoea and thrombocytopenia when compared to patients with wild allele. No significant association was found between DPYD*6, GSTP1 ile105val polymorphisms and CAPOX related toxicities except for thrombocytopenia. Conclusion: A significant association was observed between DPYD*9A polymorphism and CAPOX induced dose-limiting toxicities strengthening its role as a predictive biomarker.

The new child-friendly fixed dose combinations (FDCs) were introduced at Port Moresby General Hospital, Papua New Guinea, in 2016 for the first-line treatment of children (aged15 years) with tuberculosis (TB) who weighed25 kg.To describe the characteristics and outcomes for children treated with the new FDCs, and to identify risk factors for unfavourable treatment outcomes.This was a retrospective cohort study of all children treated for TB with the FDCs from August 2016 to August 2017.Of 713 children included, 488 (68%) were diagnosed with pulmonary TB. Only 6 (0.8%) TB cases were bacteriologically confirmed and human immunodeficiency virus (HIV) status was known in 50%. Treatment outcomes were favourable in 425 (60%) children. Of 288 children with unfavourable outcomes, there were 242 (84%) with loss to follow-up (LTFU) and 25 (8.4%) were known to have died. Children who were severely underweight (weight-for-age Z score-3) on presentation were at greater risk of LTFU compared to children of normal weight on multivariable analysis (aRR 1.3, 95%CI 1.0-1.6,Alternative models of care to decrease LTFU during treatment are needed, including integration with nutritional support. Improving diagnosis through microbiological confirmation of TB and HIV are major challenges to be addressed.La nouvelle combinaison à dose fixe adaptée aux enfants (FDC) a été introduite à l'hôpital général de Port Moresby, Papouasie Nouvelle Guinée, en 2016 pour le traitement de première ligne des enfants (agés15 ans) atteints de tuberculose (TB) et pesant25 kilos.Décrire les caractéristiques et les résultats des enfants traités par les nouvelles FDC et identifier les facteurs de risque de résultat défavorable du traitement.Une étude rérospective de cohorte de tous les enfants traités pour TB avec ces FDC entre août 2016 et août 2017.De 713 enfants inclus, 488 (68%) ont eu un diagnostic de TB pulmonaire. Seulement 6 (0,8%) cas de TB ont été confirmés par bactériologie et la statut du virus de l'immunodéficience humaine (VIH) n'a été connu que pour 50% d'entre eux. Les résultats du traitement ont été favorables chez 425 (60%) enfants. Sur 288 enfants ayant eu un résultat défavorable, 242 (84%) ont été perdus de vue et 25 (8,4%) sont décédés. Les enfants atteints de malnutrition grave (score Z poids/âge−3) à leur arrivée ont eu le risque le plus élevé de perte de vue comparés aux enfants de poids normal en analyse multivariables (RRa 1,3, IC95% 1,0–1,6 ;Des modèles de prise en charge alternative visant à réduire les pertes de vue pendant le traitement doivent être envisagés, comme par exemple une intégration avec un soutien nutritionnel. L'amélioration du diagnostic grâce à une confirmation microbiologique de la TB et du VIH sont des défis majeurs à affronter.Las nuevas asociaciones en dosis fijas adaptadas al uso pediátrico se introdujeron en el Hospital General de Port Moresby, en Papúa Nueva Guinea, en el 2016 para el tratamiento de primera línea de los niños (15 años) con tuberculosis (TB) con un peso25 kg.Describir las características y los desenlaces de los niños tratados con las nuevas asociaciones en dosis fijas y determinar los factores de riesgo de alcanzar desenlaces desfavorables.Un estudio de cohortes retrospectivo de todos los niños tratados por TB con asociaciones de dosis fijas de agosto del 2016 a agosto del 2017.Se incluyeron en el estudio 713 niños y se diagnosticó TB pulmonar en 488 de ellos (68%). Solo seis casos de TB contaban con confirmación bacteriológica (0,8%) y se conocía la situación frente al virus de la inmunodeficiencia humana en el 50% de los casos. Cuatrocientos veinticinco niños alcanzaron desenlaces terapéuticos favorables (60%). De los 288 niños con desenlace desfavorable, 242 fueron pérdidas durante el seguimiento (84%) y se supo que 25 niños habían fallecido (8,4%). Según el análisis multivariante, los niños con insuficiencia ponderal grave (escala Z del peso para la edad−3) en la primera consulta corrían un mayor riesgo de pérdida durante el seguimiento que los niños con peso normal (riesgo relativo ajustado: 1,3, IC95% 1,0–1,6 ;Es necesario considerar la posibilidad de utilizar otros modelos de atención que contribuyan a disminuir el riesgo de pérdida durante el seguimiento, incluida la integración con el apoyo nutricional. Los principales desafíos que deben abordarse son mejorar el diagnóstico de la tuberculosis con la confirmación bacteriológica y de la infección por el VIH.

Objectives: Routine screening for distress is a guideline prescribed by the National Comprehensive Cancer Network (NCCN) to adequately assess distress in a cancer setting. Our centre conducted routine screening but failed to utilize psycho-oncology services. Our aim was to assess the extent of self-reported distress, referrals to psycho-oncology services and healthcare provider perspectives about the existing distress management system and psycho-oncology services. Materials and Methods: We conducted a record review of adult patients (n=372) who reported to the Out-patient department of the tertiary cancer centre. Semi-structured interviews were conducted with fourteen healthcare providers. We used a concurrent mixed methods study design. Adult patients were screened for distress using NCCN-Distress Thermometer and problem checklist. Healthcare providers from different oncology specialties were interviewed and the data was analysed using descriptive thematic analysis. Results: Patients screened for distress were found to report moderate to extreme levels of distress (53.5%). The total referrals to psycho-oncology support services were low (8.6%). Interviews with healthcare providers revealed three major themes: Enablers, barriers and solutions for utilization of distress management system and psycho-oncology services. Conclusions: Moderate to extreme distress was found among patients routinely screened for distress, although there was poor utilization of distress management system and psycho-oncology support services due to time constraints, patient’s negative attitudes towards mental health referrals, generic screening tools and use of own clinical judgement to make referrals by healthcare providers. Future research warrants implementation of strategies to integrate psycho-oncology services into routine cancer care by focusing on improving visibility of services.

Background: Warfarin is primarily metabolized by cytochrome P450 2C9 (CYP2C9) enzyme, which is encoded by the CYP2C9 gene. CYP2C9*2 and CYP2C9*3 variants significantly influence warfarin metabolism and subsequently the required dose of warfarin. Objective: The current retrospective study was aimed to determine the influence of CYP2C9 variants on warfarin metabolic ratio (MR, warfarin/7-hydroxy warfarin) and warfarin maintenance therapy in 210 patients (mean age 44.6±11.6 (SD) years; male to female ratio 81:129). Method: High-performance liquid chromatography (HPLC) with UV detector was used to measure plasma concentrations of warfarin and 7-hydroxy warfarin. Plasma samples were collected 12 h after the previous dose of warfarin was administered. CYP2C9 variants (rs1799853 and rs1057910) were identified using real-time polymerase chain reaction allele-discrimination method. Results: The mean daily maintenance dose of warfarin was 4.6±1.8 (SD) mg. The mean plasma warfarin and 7-hydroxy warfarin concentrations were 3.7±1.6 (SD) μg/mL and 1.1±0.54 (SD) μg/mL, respectively. Patients carrying other CYP2C9 variants required 39% lower warfarin maintenance dose (3.3±1.2 mg) than CYP2C9*1*1 carrier (4.9±1.8 mg), (p Conclusion : The present study results provide, insights on the effect of CYP2C9 genetic polymorphisms on inter-individual variability in warfarin metabolism and emphasizes utility of phenotyping in a setting of genotype-guided dosing of warfarin in South Indian population.

Due to limited availability of diagnostics and capacity, people with tuberculosis do not always undergo systematic assessment for severe illness (requiring inpatient care). In Karnataka (south India), para-medical programme staff used a screening tool to identify people at ‘high risk of severe illness’, defined using indicators of very severe undernutrition, abnormal vital signs and poor performance status (any one): (i) body mass index (BMI) ≤ 14.0 kg/m2 (ii) BMI ≤ 16.0 kg/m2 with bilateral leg swelling (iii) respiratory rate > 24/min (iv) oxygen saturation < 94% (v) inability to stand without support. Of 3020 adults notified from public facilities (15 October to 30 November 2020) in 16 districts, 1531 (51%) were screened (district-wise range: 13–90%) and of them, 538 (35%) were classified as ‘high risk of severe illness’. Short median delays in screening from notification (five days), and all five indicators being collected for 88% of patients, suggests the feasibility of using this tool in programme settings. However, districts with poor screening coverage require further attention. To end tuberculosis deaths, screening should be followed by referral to higher facilities for comprehensive clinical evaluation, to assess the need for inpatient care. Future studies should assess the validity (especially sensitivity in picking severely ill patients) of this screening tool.

When COVID-19 was declared a pandemic, there was concern that TB and HIV services in Zimbabwe would be severely affected. We set up real-time monthly surveillance of TB and HIV activities in 10 health facilities in Harare to capture trends in TB case detection, TB treatment outcomes and HIV testing and use these data to facilitate corrective action. Aggregate data were collected monthly during the COVID-19 period (March 2020–February 2021) using EpiCollect5 and compared with monthly data extracted for the pre-COVID-19 period (March 2019–February 2020). Monthly reports were sent to program directors. During the COVID-19 period, there was a decrease in persons with presumptive pulmonary TB (40.6%), in patients registered for TB treatment (33.7%) and in individuals tested for HIV (62.8%). The HIV testing decline improved in the second 6 months of the COVID-19 period. However, TB case finding deteriorated further, associated with expiry of diagnostic reagents. During the COVID-19 period, TB treatment success decreased from 80.9 to 69.3%, and referral of HIV-positive persons to antiretroviral therapy decreased from 95.7 to 91.7%. Declining trends in TB and HIV case detection and TB treatment outcomes were not fully redressed despite real-time monthly surveillance. More support is needed to transform this useful information into action.

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.

Inappropriate antibiotic use in food-producing animals is associated with the emergence and spread of antibiotic resistance. In industrial broiler poultry farms in three districts of Kathmandu valley, Nepal, we assessed antibiotic use prevalence, and their classes, types, and quantities. A cross-sectional questionnaire study involving field visits to large poultry farms (flock size ≥ 3000) of the Kathmandu, Bhaktapur, and Lalitpur districts was conducted. Of 30 farms (total flock size 104,200, range 3000–6000), prevalence of antibiotic use was 90% (95% CI: 73–98%). Six (22%) farms used antibiotics as prophylaxis, while 21 (78%) used it for therapeutics. Seven antibiotics from six classes (including quinolones, macrolides, and polymyxins) were used. The most commonly used antibiotics were tylosin (47%), colistin (47%), and dual therapies with neomycin and doxycycline (33%). A total of 50,000 grams of antibiotics (total weight including active and inactive ingredients) were used (0.5 grams/chicken/45 days of flock life) with eight (26%) farms using more than two antibiotics. No farms had records on clinical indications for prophylaxis or treatment. No post-mortem records of sick birds were available. Prevalence of antibiotic use in broiler farms of Kathmandu valley is high and includes “highest priority critically important antibiotics” for human use, with direct implications on public health.

Additional file 4. The stepwise scaling up of EMMs among the 138 counties in China.