Novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation.

Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness globally, shows disparity in prevalence and manifestations across ancestries. We perform meta-analysis across 15 biobanks (of the Global Biobank Meta-analysis Initiative) (n = 1,487,441: cases = 26,848) and merge with previous multi-ancestry studies, with the combined dataset representing the largest and most diverse POAG study to date (n = 1,478,037: cases = 46,325) and identify 17 novel significant loci, 5 of which were ancestry specific. Gene-enrichment and transcriptome-wide association analyses implicate vascular and cancer genes, a fifth of which are primary ciliary related. We perform an extensive statistical analysis of SIX6 and CDKN2B-AS1 loci in human GTEx data and across large electronic health records showing interaction between SIX6 gene and causal variants in the chr9p21.3 locus, with expression effect on CDKN2A/B. Our results suggest that some POAG risk variants may be ancestry specific, sex specific, or both, and support the contribution of genes involved in programmed cell death in POAG pathogenesis.

Stakeholders' Initial Experience With Telemedicine Services Introduced at 13 Government Medical Colleges in Uttar Pradesh, India During the COVID-19 Lockdown: A Qualitative Study.

BACKGROUND: India went into a stringent lockdown in response to the coronavirus disease 2019 (COVID-19) pandemic in March 2020, and routine outpatient and elective health services were suspended. Thus, access to healthcare services got significantly disrupted. To mitigate the impact, 21 state-owned medical colleges in Uttar Pradesh, the most populous and among the most resource-constrained states in India, had to hastily launch telemedicine (TM) services. This created an opportunity to understand how stakeholders would react to such services and what initial challenges could be faced during service delivery. Through this study, we explored the experiences of stakeholders from 13 such "new-adopter" TM centres with the main objective to identify the perceived benefits and gaps related to TM services, and what "people-centric" TM services could look like going forward. METHODS: We used an exploratory-descriptive qualitative design with a constructivist paradigm. Using interview schedules with open-ended questions and unstructured probes, we interviewed 13 nodal officers, 20 doctors, and 20 patients (i.e., one nodal officer and one to two doctors and patients from each of the 13 new-adopter centres) and stopped thereafter since we reached saturation of information. We analysed the data on NVivo (QSR International, Burlington, MA) and reported the findings using the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. RESULTS: The perceived benefits that were reported included non-dependency on physical contact, economic benefit, better management of patient load, and ease of access to healthcare services. The common gaps identified in the TM services were lack of physical clinical examination, impeded communication due to lack of face-to-face interaction, technological challenges (e.g., inconsistent internet connectivity and unavailability of smartphones), lack of human resources and resources to manage the TM centres, cumbersome compliance requirements coupled with unclarity on medico-legal implications, and limited awareness of services among clients. Need for adequate promotion of TM services through information-education-communication efforts and frontline workers, strengthening of logistics for long-term sustainability, setting up a dedicated TM department at the hospitals, capacity building of the existing staff, reducing gaps in communication between doctors and patients for better consultation, and improved access to the prescribed medicines were some of the suggestions from different stakeholders. CONCLUSION: The stakeholders clearly appreciated the benefits of TM services offered through the new-adopter centres amidst the pandemic disruptions. However, there were certain gaps and unmet expectations, which, if addressed, could improve the TM centres' performance with further people-centricity and enhance healthcare access and the popularity of system-based services. Avenues for sustaining the TM services and their efficient scale-up should be explored.

Implementing recommended breastfeeding practices in healthcare facilities in India during the COVID-19 pandemic: a scoping review of health system bottlenecks and potential solutions.

Background: Breastfeeding practices in institutional settings got disrupted during the COVID-19 pandemic. We reviewed the challenges faced and the "work-around" solutions identified for implementing recommended breastfeeding practices in institutionalized mother-newborn dyads in resource constrained settings during the pandemic with the aim to identify learnings that could be potentially adapted to the Indian and relatable contexts, for building resilient health systems. Methods: We conducted a scoping review of literature using the PRISMA ScR Extension guidelines. We searched the Medline via PubMed and Web of Science databases for literature published between 1st December 2019 and 15th April 2022. We included original research, reviews, and policy recommendations published in English language and on India while others were excluded. Further, we searched for relevant gray literature on Google (free word search), websites of government and major professional bodies in India. Three reviewers independently conducted screening and data extraction and the results were displayed in tabular form. Challenges and potential solutions for breastfeeding were identified and were categorized under one or more suitable headings based on the WHO building blocks for health systems. Results: We extracted data from 28 papers that were deemed eligible. Challenges were identified across all the six building blocks. Lack of standard guidelines for crisis management, separation of the newborn from the mother immediately after birth, inadequate logistics and resources for infection prevention and control, limited health workforce, extensive use of formula and alternative foods, inconsistent quality of care and breastfeeding support, poor awareness among beneficiaries about breastfeeding practices (and especially, about its safety during the pandemic) were some of the challenges identified. The solutions primarily focused on the development of standard guidelines and operating procedures, restricted use of formula, use of telemedicine services for counseling and awareness and improving resource availability for risk mitigation through strategic mobilization. Conclusion: The COVID-19 pandemic has provided rich learning opportunities for health system strengthening in India. Countries must strengthen learning mechanisms to identify and adapt best practices from within their health systems and from other relatable settings.

An appraisal of peer-reviewed published literature on Influenza, 2000-2021 from countries in South-East Asia Region.

Background: Influenza poses a major public health challenge in South-East Asia Region (SEAR). To address the challenge, there is a need to generate contextual evidence that could inform policy makers and program managers for response preparedness and impact mitigation. The World Health Organization has identified priority areas across five streams for research evidence generation at a global level (WHO Public Health Research Agenda). Stream 1 focuses on research for reducing the risk of emergence, Stream 2 on limiting the spread, Stream 3 on minimizing the impact, Stream 4 on optimizing the treatment and Stream 5 on promoting public health tools and technologies for Influenza. However, evidence generation from SEAR has been arguably low and needs a relook for alignment with priorities. This study aimed to undertake a bibliometric analysis of medical literature on Influenza over the past 21 years to identify gaps in research evidence and for identifying major areas for focusing with a view to provide recommendations to member states and SEAR office for prioritizing avenues for future research. Methods: We searched Scopus, PubMed, Embase, and Cochrane databases in August 2021. We identified studies on influenza published from the 11 countries in WHO SEAR in the date range of 1 January 2000-31 December 2021. Data was retrieved, tagged and analyzed based on the WHO priority streams for Influenza, member states, study design and type of research. Bibliometric analysis was done on Vosviewer. Findings: We included a total of 1,641 articles (Stream 1: n = 307; Stream 2: n = 516; Stream 3: n = 470; Stream 4: n = 309; Stream 5: n = 227). Maximum number of publications were seen in Stream 2, i.e., limiting the spread of pandemic, zoonotic, and seasonal epidemic influenza which majorly included transmission, spread of virus at global and local levels and public health measures to limit the transmission. The highest number of publications was from India (n = 524) followed by Thailand (n = 407), Indonesia (n = 214) and Bangladesh (n = 158). Bhutan (n = 10), Maldives (n = 1), Democratic People's Republic of Korea (n = 1), and Timor-Leste (n = 3) had the least contribution in Influenza research. The top-most journal was PloS One which had the maximum number of influenza articles (n = 94) published from SEAR countries. Research that generated actionable evidence, i.e., implementation and intervention related topics were less common. Similarly, research on pharmaceutical interventions and on innovations was low. SEAR member states had inconsistent output across the five priority research streams, and there was a much higher scope and need for collaborative research. Basic science research showed declining trends and needed reprioritization. Interpretation: While a priority research agenda has been set for influenza at the global level through the WHO Global Influenza Program since 2009, and subsequently revisited in 2011 and again in 2016-2017, a structured contextualized approach to guide actionable evidence generation activities in SEAR has been lacking. In the backset of the Global Influenza Strategy 2019-2030 and the COVID-19 pandemic, attuning research endeavors in SEAR could help in improved pandemic influenza preparedness planning. There is a need to prioritize contextually relevant research themes within priority streams. Member states must inculcate a culture of within and inter-country collaboration to produce evidence that has regional as well as global value.

Analysis of genetically determined gene expression suggests role of inflammatory processes in exfoliation syndrome.

BACKGROUND: Exfoliation syndrome (XFS) is an age-related systemic disorder characterized by excessive production and progressive accumulation of abnormal extracellular material, with pathognomonic ocular manifestations. It is the most common cause of secondary glaucoma, resulting in widespread global blindness. The largest global meta-analysis of XFS in 123,457 multi-ethnic individuals from 24 countries identified seven loci with the strongest association signal in chr15q22-25 region near LOXL1. Expression analysis have so far correlated coding and a few non-coding variants in the region with LOXL1 expression levels, but functional effects of these variants is unclear. We hypothesize that analysis of the contribution of the genetically determined component of gene expression to XFS risk can provide a powerful method to elucidate potential roles of additional genes and clarify biology that underlie XFS. RESULTS: Transcriptomic Wide Association Studies (TWAS) using PrediXcan models trained in 48 GTEx tissues leveraging on results from the multi-ethnic and European ancestry GWAS were performed. To eliminate the possibility of false-positive results due to Linkage Disequilibrium (LD) contamination, we i) performed PrediXcan analysis in reduced models removing variants in LD with LOXL1 missense variants associated with XFS, and variants in LOXL1 models in both multiethnic and European ancestry individuals, ii) conducted conditional analysis of the significant signals in European ancestry individuals, and iii) filtered signals based on correlated gene expression, LD and shared eQTLs, iv) conducted expression validation analysis in human iris tissues. We observed twenty-eight genes in chr15q22-25 region that showed statistically significant associations, which were whittled down to ten genes after statistical validations. In experimental analysis, mRNA transcript levels for ARID3B, CD276, LOXL1, NEO1, SCAMP2, and UBL7 were significantly decreased in iris tissues from XFS patients compared to control samples. TWAS genes for XFS were significantly enriched for genes associated with inflammatory conditions. We also observed a higher incidence of XFS comorbidity with inflammatory and connective tissue diseases. CONCLUSION: Our results implicate a role for connective tissues and inflammation pathways in the etiology of XFS. Targeting the inflammatory pathway may be a potential therapeutic option to reduce progression in XFS.

Barriers and enablers of breastfeeding in mother-newborn dyads in institutional settings during the COVID-19 pandemic: A qualitative study across seven government hospitals of Delhi, India.

Introduction: The COVID-19 pandemic disrupted newborn care and breastfeeding practices across most healthcare facilities. We undertook this study to explore the barriers and enablers for newborn care and breastfeeding practices in hospitals in Delhi, India for recently delivered mother (RDM)-newborn dyads during the first wave of the COVID-19 pandemic (2020) and inductively design a "pathway of impaction" for informing mitigatory initiatives during the current and future pandemics, at least in the initial months. Materials and methods: We used an exploratory descriptive design (qualitative research method) and collected information from seven leading public health facilities in Delhi, India. We conducted separate interviews with the head and senior faculty from the Departments of Pediatrics/Neonatology (n = 12) and Obstetrics (n = 7), resident doctors (n = 14), nurses (labor room/maternity ward; n = 13), and RDMs (n = 45) across three profiles: (a) COVID-19-negative RDM with healthy newborn (n = 18), (b) COVID-19-positive RDM with healthy newborn (n = 19), and (c) COVID-19 positive RDM with sick newborn needing intensive care (n = 8) along with their care-giving family members (n = 39). We analyzed the data using grounded theory as the method and phenomenology as the philosophy of our research. Results: Anxiety among clients and providers, evolving evidence and advisories, separation of the COVID-positive RDM from her newborn at birth, providers' tendency to minimize contact duration and frequency with COVID-positive mothers, compromised counseling on breastfeeding, logistic difficulties in expression and transportation of COVID-positive mother's milk to her baby in the nursery, COVID restrictions, staff shortage and unavailable family support in wards and nursery, and inadequate infrastructure were identified as major barriers. Keeping the RDM-newborn together, harmonization of standard operating procedures between professional associations and within and between departments, strategic mobilization of resources, optimization of human resources, strengthening client-provider interaction, risk triaging, leveraging technology, and leadership-in-crisis-situations were notable enablers. Conclusion: The separation of the RDM and newborn led to a cascade of disruptions to newborn care and breastfeeding practices in the study institutions. Separating the newborn from the mother should be avoided during public health emergencies unless there is robust evidence favoring the same; routine institutional practices should be family centered.

Psychosocial Challenges in Palliative Care: Bridging the Gaps Using Digital Health.

Psychosocial health is a major palliative care concern globally. Patients and caregivers engaged in palliative care may experience deteriorated mental and social health conditions. Global evidence informs a high burden of depression, anxiety, psychological distress and other mental health problems among the palliative care populations. Those challenges aggravate the preexisting palliative care issues, such as lack of access and suboptimal quality of care. Palliative caregiving, both in the institutional and community settings, should be strengthened, incorporating psychosocial support for the patients and their caregivers. The recent advancements in digital health technologies have shown promising impacts in facilitating health communication, decision-making and delivering psychosocial interventions using digital devices and platforms. Adopting evidence-based interventions can help the users to access mental health resources and communicate with each other to promote shared decision-making and management of health problems. Health-care organisations and systems may explore opportunities to advance psychosocial care using digital technologies. Leveraging advanced technologies in palliative caregiving may require multifaceted research exploring potential barriers and opportunities at the user, institutional and systems levels. Nonetheless, palliative care policies and health systems measures should be strengthened to develop and implement digital support systems that may improve psychosocial health and overall palliative care outcome.

Safety and bioactivity studies of Jasad Bhasma and its in-process intermediate in Swiss mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Bhasma, Ayurvedic medicinal preparations, are prepared using herbs and minerals on following long iterative procedures. However, industrially mercury and sulphur are more commonly used to prepare bhasma from its raw material. The end point of this iterative procedure is mainly judged by the traditional tests specifying physical appearance of the powders. They fail to give better idea about chemical nature of the material. Moreover, the differences in biological activity of final product verses intermediate are not addressed. AIM OF THE STUDY: To compare the physicochemical as well as biological properties of the Jasad bhasma and its in-process intermediate using modern science methods. MATERIALS AND METHODS: The Jasad bhasma and its in-process intermediate are characterized for their physicochemical properties using electron microscopy, x-ray diffraction and CHNS(O) analysis. The biological effects of both the preparations are then studied. The bioaccumulation of zinc, effect on liver antioxidant status, liver and kidney function (by conventional tests as well as SPECT: Single Photon Emission Computed Tomography), effect on blood cells and effect on immune system are studied in mice model, Swiss albino. Since bhasma is given with an accompaniment (anupan), all the bioactivity studies were carried out by administering the preparation with and without Amala powder (Phyllanthus emblica L., fruit, dry powder) as anupan. RESULTS: The XRD results accompanied with Rietveld analysis indicate that the final bhasma is mainly oxide of zinc, whereas the intermediate is mainly sulphide of zinc. The animal studies show that the bhasma as well as its intermediate do not lead to any bioaccumulation of zinc in major organs, when administered with and without anupan. Both, bhasma and intermediate do not cause any deleterious effects on kidney and liver as indicated by blood biochemistry and SPECT studies. However, the intermediate perturbs antioxidant status more and affects the platelet turnover, in comparison with bhasma. On 28day treatment, the bhasma treated animals show prominence of TH1 mediated immune response whereas, intermediate treated animals show prominence of TH2 mediated immune response. CONCLUSION: A set of simple modern microscopy and diffraction techniques can affirmatively identify in-process intermediate from the final preparation. These can be used to decide the end point of long and iterative preparation methods in accordance with modern science practices. The differences in physicochemical properties of particles from the two preparations reflect in their different biological effects. Moreover, the bhasma affects several components of biological systems which again in-turn interact with each other, which emphasizes the need of multifaceted studies in this field.