Addressing gaps in AMR awareness in the public: an evidence-based policy brief to guide school curriculum review in Uganda.

The government of Uganda, through its Ministry of Health, previously adopted curriculum review as a mechanism to respond to public health threats such as HIV/AIDS and include content in primary and secondary schools. This approach contributes to raising public awareness, a key strategy recommended by the World Health Organization to support the global response to the threat of antimicrobial resistance (AMR). This policy brief, developed for policymakers related to school curricula, aims to advocate for and support integration of AMR content in Uganda's primary and secondary level school curricula. The policy brief supports efforts by the multisectoral National AMR Subcommittee to create awareness on this issue as part of its role in facilitating the operationalization of Uganda's National Action Plan on AMR.

Optimizing prophylactic antibiotic use among surgery patients in Ethiopian hospitals.

BACKGROUND: Since 2018, the Ethiopian Ministry of Health (MOH) has been working to institutionalize antimicrobial stewardship (AMS) programs across the country. The US Agency for International Development Medicines, Technologies, and Pharmaceutical Services Program supported Ethiopia's multipronged One Health approach to combat AMR. The objective of this paper was to evaluate the effect of a quality improvement intervention to optimize the use of antimicrobials for surgical prophylaxis. METHODS: Basic AMS interventions were introduced in five hospitals from January to May 2023. The AMS committees and multidisciplinary teams working at the surgical wards were trained and provided on-site support to implement surgical antibiotic prophylaxis (SAP) interventions. A before-after comparison was made for 206 medical records at baseline and 213 during the intervention phase. Qualitative data were gathered through discussions during experience-sharing workshops to supplement the quantitative results. RESULT: There were improvements in the presurgery dose of the prophylactic antibiotic and its timing: the doses within the recommended range increased from 11.2 % to 61.0 % (p < 0.001) and the optimal timing increased from 68 % to 82.6 % (p < 0.001). The hospitals also demonstrated some nonsignificant improvement in the duration of prophylactic antibiotic use (from 35 % to 44.6 % [p = 0.106]), with change in practice hampered by practitioners' resistance to early discontinuation for fear of infection due to perceived weaknesses in infection prevention and control practices. Nonavailability of the recommended antibiotic of choice for surgical prophylaxis was another major challenge in addressing all the elements of SAP. The intervention demonstrated a significant antibiotic-related average cost saving, 51.8 Ethiopian birr (∼1 US dollar) per patient (p = 0.028). CONCLUSION: Short-term investments with basic AMS interventions can help to improve SAP use in surgical wards. However, comprehensive success requires complementing AMS interventions with concurrent attention to proper supply chain and infection prevention and control.

Antimicrobial consumption surveillance in Uganda: Results from an analysis of national import data for the human health sector, 2018-2021.

BACKGROUND: The surveillance of antimicrobial consumption (AMC) is critical to developing appropriate antimicrobial stewardship interventions. It is a key component of World Health Organization's (WHO) Global Action Plan on Antimicrobial Resistance and the Uganda Antimicrobial Resistance National Action Plan 2018-2023. Our study's objective was to determine the national consumption of all antimicrobials. METHODS: Data on all imported antimicrobials were retrieved from paper-based records and entered in the web-based National Drug Authority (NDA) management information system from 2021. The import data for the year is a proxy for nationwide consumption because they account for 95% of all medical products. The NDA authorizes all imports to the country regardless of final distribution in the supply chain. The data were analyzed in accordance with WHO Anatomical Therapeutic Chemical codes and defined daily dose (DDD) methodology. We also retrieved consumption data for 2018, 2019, and 2020 that were previously submitted by Uganda to WHO's Global Antimicrobial Resistance and Use Surveillance System. RESULTS: In 2021, the average DDD per 1000 inhabitants was 29.02 for all antimicrobials; 80.7% of antimicrobials consumed were oral. Penicillins (27.6%) were the most consumed antimicrobial class, followed by sulfonamides and trimethoprim (15.5%). Based on WHO's Access, Watch, and Reserve (AWaRe) antibiotic classification, 62.91% of AMC was from the access class, with watch class averaging 14.51% in the period 2018-2021. Watch class AMC spiked in 2021 (34.2%) during COVID-19 pandemic compared to 2020 (24.29%). Azithromycin and ciprofloxacin were the most consumed watch class antimicrobials in 2021. CONCLUSIONS: The relatively high consumption of injectable antimicrobials and year over year increase in watch class AMC requires urgent stewardship interventions. Further work is needed to establish a system for longitudinal AMC surveillance that is well resourced and funded to overcome the challenges of estimation and provide more accurate data on consumption and use patterns.

Exposure to High Dosage of Gold Nanoparticles Accelerates Growth Rate by Modulating Ribosomal Protein Expression.

Gold nanoparticles (AuNPs) have been utilized in various biomedical applications including diagnostics and drug delivery. However, the cellular and metabolic responses of cells to these particles remain poorly characterized. In this study, we used bacteria (Escherichia coli and Bacillus subtilis) and a fungus (Saccharomyces cerevisiae) as model organisms to investigate the cellular and metabolic effects of exposure to different concentrations of citrate-capped spherical AuNPs with diameters of 5 and 10 nm. In different growth media, the synthesized AuNPs displayed stability and microorganisms exhibited uniform levels of uptake. Exposure to a high concentration of AuNPs (1012 particles) resulted in a reduced cell division time and a 2-fold increase in cell density in both bacteria and fungus. The exposed cells exhibited a decrease in average cell size and an increase in the expression of FtsZ protein (cell division marker), further supporting an accelerated growth rate. Notably, exposure to such a high concentration of AuNPs did not induce DNA damage, envelope stress, or a general stress response in bacteria. Differential whole proteome analysis revealed modulation of ribosomal protein expression upon exposure to AuNPs in both E. coli and S. cerevisiae. Interestingly, the accelerated growth observed upon exposure to AuNPs was sensitive to sub-minimum inhibitory concentration (sub-MIC) concentration of drugs that specifically target ribosome assembly and recycling. Based upon these findings, we hypothesize that exposure to high concentrations of AuNPs induces stress on the translation machinery. This leads to an increase in the protein synthesis rate by modulating ribosome assembly, which results in the rapid proliferation of cells.

What is the appropriate antimicrobial use surveillance tool at the health facility level for Uganda and other low- and middle-income countries?

BACKGROUND: An appropriate antimicrobial use (AMU) surveillance system provides critical data and evidence on which antimicrobial stewardship interventions are based. However, Uganda and most other low- and middle-income countries (LMICs) lack efficient systems for monitoring AMU due to unique health system challenges. METHODS: We reviewed the key tools available for AMU surveillance in health facilities. Based on our implementation experience, we present arguments on the need for country authorities to adapt a customized and standardized tool for national uses. RESULTS: Despite ongoing efforts to set up AMU surveillance programs in Uganda, AMU data remain sparse, with most of the available data collected through antimicrobial stewardship related continuous quality improvement efforts implemented by global AMR control programs. There is variability in the interpretation of available AMU surveillance tools and a need to identify the most appropriate AMU surveillance methodologies and tools for Uganda and other LMICs. Data fields for sex and gender are incorrectly categorized and there is no tool that records pregnancy variable. Based on the past four years of practical implementation experience since the launch of the World Health Organization's Point Prevalence Survey methodology in 2018 for inpatient settings, we believe that the tool should be modified in cognizance of existing capacity and priorities in resource-constrained settings. CONCLUSIONS: The World Health Organization, regional experts, ministry of health authorities, and other stakeholders should urgently review available tools with a view to adopting a customized and standardized facility AMU surveillance methodology suitable for national-level rollout in LMICs.

Development and evaluation of a continuous quality improvement programme for antimicrobial stewardship in six hospitals in Uganda.

BACKGROUND: Appropriate antimicrobial use is essential for antimicrobial stewardship (AMS). Ugandan hospitals are making efforts to improve antibiotic use, but improvements have not been sufficiently documented and evaluated. METHODS: Six Ugandan hospitals implemented AMS interventions between June 2019 and July 2022. We used the WHO AMS toolkit to set-up hospital AMS programmes and implemented interventions using continuous quality improvement (CQI) techniques and targeting conditions commonly associated with antibiotic misuse, that is, urinary tract infections (UTIs), upper respiratory tract infections (URTIs) and surgical antibiotic prophylaxis (SAP). The interventions included training, mentorship and provision of clinical guidelines to support clinical decision-making. Quarterly antibiotic use surveys were conducted. RESULTS: Data were collected for 7037 patients diagnosed with UTIs. There was an increase in the proportion of patients receiving one antibiotic for the treatment of UTI from 48% during the pre-intervention to 73.2%, p<0.01. There was a 19.2% reduction in the number of antimicrobials per patient treated for UTI p<0.01. There was an increase in use of nitrofurantoin, the first-line drug for the management of UTI. There was an increase in the use of Access antibiotics for managing UTIs from 50.4% to 53.8%. The proportion of patients receiving no antimicrobials for URTI increased from 26.3% at pre-intervention compared with 53.4% at intervention phase, p<0.01. There was a 20.7% reduction in the mean number of antimicrobials per patient for URTI from the pre-intervention to the intervention phase, from 0.8 to 0.6, respectively, p<0.001 and reduction in the number of treatment days, p=0.0163. Among patients undergoing surgery, 49.5% (2212) received SAP during the pre-intervention versus 50.5% (2169) during the intervention. CONCLUSIONS: Using CQI approaches to focus on specific causes of inappropriate antibiotic use led to desirable overall reductions in antibiotic use for URTI and UTI.

Moving from assessments to implementation: promising practices for strengthening multisectoral antimicrobial resistance containment capacity.

BACKGROUND: Antimicrobial resistance (AMR) poses a global threat to human, animal, and environmental health. AMR is a technical area in the Global Health Security Agenda initiative which uses the Joint External Evaluation tool to evaluate national AMR containment capacity. This paper describes four promising practices for strengthening national antimicrobial resistance containment capacity based on the experiences of the US Agency for International Development's Medicines, Technologies, and Pharmaceutical Services Program work with 13 countries to implement their national action plans on AMR in the areas of multisectoral coordination, infection prevention and control, and antimicrobial stewardship. METHODS: We use the World Health Organization (WHO) Benchmarks on International Health Regulations Capacities (2019) to guide national, subnational, and facility actions that advance Joint External Evaluation capacity levels from 1 (no capacity) to 5 (sustainable capacity). Our technical approach is based on scoping visits, baseline Joint External Evaluation scores, benchmarks tool guidance, and country resources and priorities. RESULTS: We gleaned four promising practices to achieve AMR containment objectives: (1) implement appropriate actions using the WHO benchmarks tool, which prioritizes actions, making it easier for countries to incrementally increase their Joint External Evaluation capacity from level 1 to 5; (2) integrate AMR into national and global agendas. Ongoing agendas and programs at international, regional, and national levels provide opportunities to mainstream and interlink AMR containment efforts; (3) improve governance through multisectoral coordination on AMR. Strengthening multisectoral bodies' and their technical working groups' governance improved functioning, which led to better engagement with animal/agricultural sectors and a more coordinated COVID-19 pandemic response; and (4) mobilize and diversify funding for AMR containment. Long-term funding from diversified funding streams is vital for advancing and sustaining countries' Joint External Evaluation capacities. CONCLUSIONS: The Global Health Security Agenda work has provided practical support to countries to frame and conduct AMR containment actions in terms of pandemic preparedness and health security. The WHO benchmarks tool that Global Health Security Agenda uses serves as a standardized organizing framework to prioritize capacity-appropriate AMR containment actions and transfer skills to help operationalize national action plans on AMR.

Identifying and addressing challenges to antimicrobial use surveillance in the human health sector in low- and middle-income countries: experiences and lessons learned from Tanzania and Uganda.

BACKGROUND: Antimicrobial resistance (AMR) is a global health security threat and is associated with increased morbidity and mortality. One of the key drivers of AMR is the inappropriate use of antibiotics. A key component of improving antibiotic use is conducting antimicrobial use (AMU) surveillance. METHODS: USAID Medicines Technologies and Pharmaceutical Services Program has supported the implementation of antimicrobial stewardship activities, including setting up systems for AMU surveillance in Tanzania and Uganda. Results from both countries have been previously published. However, additional implementation experience and lessons learned from addressing challenges to AMU surveillance have not been previously published and are the subject of this narrative article. RESULTS: The team identified challenges including poor quality data, low digitalization of tools, and inadequate resources including both financial and human resources. To address these gaps, the Program has supported the use of continuous quality improvement approaches addressing gaps in skills, providing tools, and developing guidelines to fill policy gaps in AMU surveillance. Recommendations to fill these gaps, based on the Potter and Brough systematic capacity building model have been proposed. CONCLUSIONS: Strengthening AMU surveillance through using a capacity-building approach will fill gaps and strengthen efforts for AMR control in both countries.

NSP4 and ORF9b of SARS-CoV-2 Induce Pro-Inflammatory Mitochondrial DNA Release in Inner Membrane-Derived Vesicles.

Circulating cell-free mitochondrial DNA (cf-mtDNA) has been found in the plasma of severely ill COVID-19 patients and is now known as a strong predictor of mortality. However, the underlying mechanism of mtDNA release is unexplored. Here, we show a novel mechanism of SARS-CoV-2-mediated pro-inflammatory/pro-apoptotic mtDNA release and a rational therapeutic stem cell-based approach to mitigate these effects. We systematically screened the effects of 29 SARS-CoV-2 proteins on mitochondrial damage and cell death and found that NSP4 and ORF9b caused extensive mitochondrial structural changes, outer membrane macropore formation, and the release of inner membrane vesicles loaded with mtDNA. The macropore-forming ability of NSP4 was mediated through its interaction with BCL2 antagonist/killer (BAK), whereas ORF9b was found to inhibit the anti-apoptotic member of the BCL2 family protein myeloid cell leukemia-1 (MCL1) and induce inner membrane vesicle formation containing mtDNA. Knockdown of BAK and/or overexpression of MCL1 significantly reversed SARS-CoV-2-mediated mitochondrial damage. Therapeutically, we engineered human mesenchymal stem cells (MSCs) with a simultaneous knockdown of BAK and overexpression of MCL1 (MSCshBAK+MCL1) and named these cells IMAT-MSCs (intercellular mitochondrial transfer-assisted therapeutic MSCs). Upon co-culture with SARS-CoV-2-infected or NSP4/ORF9b-transduced airway epithelial cells, IMAT-MSCs displayed functional intercellular mitochondrial transfer (IMT) via tunneling nanotubes (TNTs). The mitochondrial donation by IMAT-MSCs attenuated the pro-inflammatory and pro-apoptotic mtDNA release from co-cultured epithelial cells. Our findings thus provide a new mechanistic basis for SARS-CoV-2-induced cell death and a novel therapeutic approach to engineering MSCs for the treatment of COVID-19.

Phase 1 clinical trial for intravenous administration of mesenchymal stem cells derived from umbilical cord and placenta in patients with moderate COVID-19 virus pneumonia: results of stage 1 of the study.

OBJECTIVE: Mesenchymal stem cells can serve as a therapeutic option for COVID-19. Their immunomodulatory and anti-inflammatory properties can regulate the exaggerated inflammatory response and promote recovery of lung damage. METHOD: Phase-1, single-centre open-label, prospective clinical trial was conducted to evaluate the safety and efficacy of intravenous administration of mesenchymal stem cells derived from umbilical cord and placenta in moderate COVID-19. The study was done in 2 stages with total 20 patients. Herein, the results of stage 1 including first 10 patients receiving 100 million cells on day 1 and 4 with a follow up of 6 months have been discussed. RESULTS: No adverse events were recorded immediately after the administration of MSCs or on follow up. There was no deterioration observed in clinical, laboratory and radiological parameters. All symptoms of the study group resolved within 10 days. Levels of inflammatory biomarkers such as NLR, CRP, IL6, ferritin and D-dimer improved in all patients after intervention along with improved oxygenation demonstrated by improvement in the SpO2/FiO2 ratio and PaO2/FiO2 ratio. None of the patients progressed to severe stage. 9 out of 10 patients were discharged within 9 days of their admission. Improvements were noted in chest x-ray and chest CT scan scores at day 7 in most patients. No post-covid fibrosis was observed on chest CT 28 days after intervention and Chest X ray after 6 months of the intervention. CONCLUSION: Administration of 100 million mesenchymal stem cells in combination with standard treatment was found to be safe and resulted in prevention of the cytokine storm, halting of the disease progression and acceleration of recovery in moderate COVID-19. This clinical trial has been registered with the Clinical Trial Registry- India (CTRI) as CTRI/2020/08/027043. http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=43175.

Point Prevalence Survey of Antibiotic Use across 13 Hospitals in Uganda.

Standardized monitoring of antibiotic use underpins the effective implementation of antimicrobial stewardship interventions in combatting antimicrobial resistance (AMR). To date, few studies have assessed antibiotic use in hospitals in Uganda to identify gaps that require intervention. This study applied the World Health Organization's standardized point prevalence survey methodology to assess antibiotic use in 13 public and private not-for-profit hospitals across the country. Data for 1077 patients and 1387 prescriptions were collected between December 2020 and April 2021 and analyzed to understand the characteristics of antibiotic use and the prevalence of the types of antibiotics to assess compliance with Uganda Clinical Guidelines; and classify antibiotics according to the WHO Access, Watch, and Reserve classification. This study found that 74% of patients were on one or more antibiotics. Compliance with Uganda Clinical Guidelines was low (30%); Watch-classified antibiotics were used to a high degree (44% of prescriptions), mainly driven by the wide use of ceftriaxone, which was the most frequently used antibiotic (37% of prescriptions). The results of this study identify key areas for the improvement of antimicrobial stewardship in Uganda and are important benchmarks for future evaluations.

Clinical course and outcome of patients with COVID-19 in Mumbai City: an observational study.

OBJECTIVE: To understand the outcome of hospitalised patients from Mumbai City, which had the highest number of COVID-19 cases in India. DESIGN: Observational study with follow-up. SETTING: Data extraction from medical records of patients with COVID-19 admitted to Nair Hospital & TN Medical College, Mumbai, India. PARTICIPANTS: 689 patients with COVID-19 were admitted in the hospital from 26 March 2020 to 11 May 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: In-hospital mortality; joint effect of comorbidity and age on the risk of dying. RESULTS: A total of 689 patients (median age 44 years) admitted with RT-PCR-confirmed COVID-19 were included in the study. Of these, 77.36% of patients were discharged alive while 22.64% died. 11.61% required some kind of oxygen support while 2.8% of patients required intensive care unit admissions. Older age (HR 2.88, 95% CI 2.09 to 3.98), presence of comorbidities (HR 2.56, 95% CI 1.84 to 3.55), history of hypertension (HR 3.19, 95% CI 1.67 to 6.08), and presence of symptoms at the time of admission (HR 3.21, 95% CI 1.41 to 7.26) were associated with increased risk of in-hospital mortality. Treatment with a combination of azithromycin with hydroxychloroquine, antiviral or steroid compared with no treatment did not alter the disease course and in-hospital mortality. The combined effect of old age and presence of comorbid conditions was more pronounced in women than men. CONCLUSIONS: In-hospital patients were younger, less symptomatic with lesser need of ventilators and oxygen support as compared with many western countries. TRIAL REGISTRATION: Not applicable (observational study, not a clinical trial).

A Saliva-Based RNA Extraction-Free Workflow Integrated With Cas13a for SARS-CoV-2 Detection.

A major bottleneck in scaling-up COVID-19 testing is the need for sophisticated instruments and well-trained healthcare professionals, which are already overwhelmed due to the pandemic. Moreover, the high-sensitive SARS-CoV-2 diagnostics are contingent on an RNA extraction step, which, in turn, is restricted by constraints in the supply chain. Here, we present CASSPIT (Cas13 Assisted Saliva-based & Smartphone Integrated Testing), which will allow direct use of saliva samples without the need for an extra RNA extraction step for SARS-CoV-2 detection. CASSPIT utilizes CRISPR-Cas13a based SARS-CoV-2 RNA detection, and lateral-flow assay (LFA) readout of the test results. The sample preparation workflow includes an optimized chemical treatment and heat inactivation method, which, when applied to COVID-19 clinical samples, showed a 97% positive agreement with the RNA extraction method. With CASSPIT, LFA based visual limit of detection (LoD) for a given SARS-CoV-2 RNA spiked into the saliva samples was ~200 copies; image analysis-based quantification further improved the analytical sensitivity to ~100 copies. Upon validation of clinical sensitivity on RNA extraction-free saliva samples (n = 76), a 98% agreement between the lateral-flow readout and RT-qPCR data was found (Ct<35). To enable user-friendly test results with provision for data storage and online consultation, we subsequently integrated lateral-flow strips with a smartphone application. We believe CASSPIT will eliminate our reliance on RT-qPCR by providing comparable sensitivity and will be a step toward establishing nucleic acid-based point-of-care (POC) testing for COVID-19.

Changes in Mode of Oxygen Delivery and Physiological Parameters with Physiotherapy in COVID-19 Patients: A Retrospective Study.

Background: Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2, clinically presenting with common symptoms of fever, dry cough, and breathlessness within 14 days of exposure. Its severity ranges from mild to severe, latter manifesting into severe acute respiratory syndrome. As a part of multidisciplinary team, physiotherapy along with medical management was administered to patients with COVID-19 in an acute care setup. This retrospective study aims to explore various patient characteristics and will aid in identifying the impairments associated with the disease, giving a direction to the physiotherapy community in planning future management strategy to improve quality of life. Patients and methods: The present study is a unicentric study wherein prospective analysis of retrospective data of patients referred for physiotherapy from May 13 to July 31, 2020, was performed. (i) Characteristics of patients, (ii) associated comorbidities, (iii) hospital course since the time of admission to discharge, (iv) mode of oxygen delivery, (v) pre- and post-physiotherapy treatment values of oxygen saturation and heart rate, and (vi) physiotherapy treatment were recorded. The archived data were analyzed using the commercially available SPSS software version 24. Wilcoxon's matched pair test was used to compare pre- and post-treatment oxygen saturation and heart rate, and McNemar's test was used to compare mode of oxygen delivery and pre- and post-physiotherapy treatment. Results: Descriptive analysis of data showed a better outcome in terms of grade of dyspnea and rate of discharge on day 14 of physiotherapy treatment. Hence, a comparative analysis of day 1 and day 14 was performed for mode of oxygen delivery, oxygen saturation, and heart rate. A statistically significant improvement was observed in the heart rate (p = 0.001) and oxygen delivery (p = 0.000). However, no significant difference in the level of oxygen saturation was found (p = 0.6433). Conclusion: Physiotherapy treatment in conjunction with medical treatment can be effectively administered in patients with COVID-19 in acute care setup taking into consideration the health status and the hemodynamic stability of the patients. It emphasizes the role of physiotherapy in the alleviation of symptoms, facilitating early weaning and recovery enabling early discharge from the hospital. How to cite this article: Verma CV, Arora RD, Mistry HM, Kubal SV, Kolwankar NS, Patil PC, et al. Changes in Mode of Oxygen Delivery and Physiological Parameters with Physiotherapy in COVID-19 Patients: A Retrospective Study. Indian J Crit Care Med 2021;25(3):317-321.

Strengthening multisectoral coordination on antimicrobial resistance: a landscape analysis of efforts in 11 countries.

BACKGROUND: Increasingly, there has been recognition that siloed approaches focusing mainly on human health are ineffective for global antimicrobial resistance (AMR) containment efforts. The inherent complexities of AMR containment warrant a coordinated multisectoral approach. However, how to institutionalize a country's multisectoral coordination across sectors and between departments used to working in silos is an ongoing challenge. This paper describes the technical approach used by a donor-funded program to strengthen multisectoral coordination on AMR in 11 countries as part of their efforts to advance the objectives of the Global Health Security Agenda and discusses some of the challenges and lessons learned. METHODS: The program conducted a rapid situational analysis of the Global Health Security Agenda and AMR landscape in each country and worked with the governments to identify the gaps, priorities, and potential activities in multisectoral coordination on AMR. Using the World Health Organization (WHO) Joint External Evaluation tool and the WHO Benchmarks for International Health Regulations (2005) Capacities as principal guidance, we worked with countries to achieve key milestones in enhancing effective multisectoral coordination on AMR. RESULTS: The program's interventions led to the achievement of key benchmarks recommended actions, including the finalization of national action plans on AMR and tools to guide their implementation; strengthening the leadership, governance, and oversight capabilities of multisectoral governance structures; establishing and improving the functions of technical working groups on infection prevention and control and antimicrobial stewardship; and coordinating AMR activities within and across sectors. CONCLUSION: A lot of learning still needs to be done to identify best practices for building mutual trust and adequately balancing the priorities of individual ministries with cross-cutting issues. Nevertheless, this paper provides some practical ideas for countries and implementing partners seeking to improve multisectoral coordination on AMR. It also demonstrates that the WHO benchmark actions, although not intended as an exhaustive list of recommendations, provide adequate guidance for increasing countries' capacity for effective multisectoral coordination on AMR in a standardized manner.

COVID-19: The Emerging Immunopathological Determinants for Recovery or Death.

Hyperactivation of the host immune system during infection by SARS-CoV-2 is the leading cause of death in COVID-19 patients. It is also evident that patients who develop mild/moderate symptoms and successfully recover display functional and well-regulated immune response. Whereas a delayed initial interferon response is associated with severe disease outcome and can be the tipping point towards immunopathological deterioration, often preceding death in COVID-19 patients. Further, adaptive immune response during COVID-19 is heterogeneous and poorly understood. At the same time, some studies suggest activated T and B cell response in severe and critically ill patients and the presence of SARS-CoV2-specific antibodies. Thus, understanding this problem and the underlying molecular pathways implicated in host immune function/dysfunction is imperative to devise effective therapeutic interventions. In this comprehensive review, we discuss the emerging immunopathological determinants and the mechanism of virus evasion by the host cell immune system. Using the knowledge gained from previous respiratory viruses and the emerging clinical and molecular findings on SARS-CoV-2, we have tried to provide a holistic understanding of the host innate and adaptive immune response that may determine disease outcome. Considering the critical role of the adaptive immune system during the viral clearance, we have presented the molecular insights of the plausible mechanisms involved in impaired T cell function/dysfunction during various stages of COVID-19.

Appraisal of Critically Ill COVID-19 Patients at a Dedicated COVID Hospital.

PURPOSE: To study the pattern of severe COVID-19 to reduce morbidity and mortality. METHODS: It was an observational cohort study for comprehensive clinical analysis of critically ill COVID-19 patients at a dedicated COVID public hospital. RESULTS: Total 373(13.6%) patients were critically ill with 254(68.1%) males and 119(31.9%) females (including 25 pregnant) and death occurred in 69(18.5%) patients. Mean of parameters associated with critical COVID illness and having significant difference among dead and recovered were; age (47.08,p= 5.67E- 09), SpO2 (86.08), blood sugar(168.47,p= 1.86E-08), IL-6(210.5,p=0.0058) D-dimer(0.753,p= 0.00178). All the patients were given oxygen by non invasive technique, in 46(12.3%) intubation and invasive ventilation required. Use of hydroxychloroquin in 284(76.1%) (p=0.041,OR0.555,95%CI 0.314-0.981), lopinavir/ ritonavir in 283(75.9%) (p=4.222E-009,OR0.198, 95%CI0.114-0.345), tocilizumab in 124(33.2%) patients, (p=3.27E006, OR0.150, 95%CI0.063-0.358) were associated with recovery. Factors that influenced mortality were presence of co-morbidities (p=0.088,OR1.784,95%CI0.911-3.492), hypertension(p=0.0031,OR2.432,95% CI1.370 -4.318), low SpO2 (p=3.91E-010,OR0.017,95%CI0.002-0.137), high blood sugar(p=7.75E-009,OR8.514,95%CI 3.776-19.201), high LDH(p=0.00064,OR2.7 22,95%CI1.545-4.798) high ferritin(p=0.00014,OR4.606,95%CI 2.035-10.422), high D-dimer(p=2.85E-007,OR4.090,95%CI 2.371-7.056), low PFR(p=4.84E-008), and endotracheal intubation(p=3.14E-043,OR165.936,95%CI48.160-571.731). Using binary logistic regression, elevated IL-6(0.02441), low PFR(0.00082), and endotracheal intubation(2.04E-10) were statistically significant predictors of death. CONCLUSION: "Happy Hypoxia", hyperglycemia, high inflammatory markers (IL-6, ferritin), and ARDS were hallmark of critical COVID-19, early detection of factors associated with severity and mortality and starting the multipronged management with oxygen in prone position, hydroxychloroquin, antiviral, methylprednisolone, anticoagulants, tocilizumab early may help in halting the worsening of COVID and reduce morbidity and mortality.

Preparedness, administrative challenges for establishing obstetric services, and experience of delivering over 400 women at a tertiary care COVID-19 hospital in India.

OBJECTIVE: To provide a descriptive account of the challenges and administrative preparedness for establishing and sustaining safe obstetric services during the COVID-19 pandemic at Topiwala National Medical College & BYL Nair Charitable Hospital (NH), Mumbai, India. METHODS: The management of pregnant women with COVID-19 was implemented as per international (WHO, RCOG, ACOG) and national (Indian Council of Medical Research) recommendations and guidelines at an academic, tertiary care, COVID-19 hospital in India. RESULTS: Using a multidisciplinary approach and active engagement of a multispecialty team, obstetric services were provided to over 400 women with laboratory-confirmed COVID-19. A sustainable model is established for providing services to pregnant women with COVID-19 in Mumbai Metropolitan Region, India. CONCLUSION: With limited resources, it is possible to set up dedicated maternity services, aligned to international guidelines, for safe pregnancy outcomes in COVID-19 settings. This COVID-19 hospital addressed the challenges and implemented several known and novel methods to establish and sustain obstetric services for women with COVID-19. The model established in the present study can be replicated in other low- and middle-income countries.

Potential suitable habitat of Eleusine coracana (L) gaertn (Finger millet) under the climate change scenarios in Nepal.

BACKGROUND: Finger millet is the fourth major crop in Nepal and is cultivated in a traditional integrated subsistence system. Timely rain and appropriate temperature predominately affects crop distribution and yield. Climate change is evident in Nepal and it is imperative to understand how it affects habitat suitability of finger millet. Main objective of this study was to map the current suitable habitat and predicting the potential changes in the future under different climate scenarios in Nepal. Habitat mapping is important for maximizing production and minimizing the loss of local landraces. RESULTS: Maxent model was used in this study to quantify the current suitable habitat and changes in the future habitat suitability of finger millet, based on representative concentration pathways (RCP) (RCP 2.6, 4.5, 6.0 and 8.5) in two different time periods (2050 and 2070AD) using climatic predictive variables and species localities. The model shows that 39.7% (58512.71 km2) area of Nepal is highly suitable for finger millet, with cultivation mostly between 96 and 2300 m above sea level. Eastern and central parts of Nepal have more suitable areas than western parts. Our research clearly shows that the future climatic suitable area of finger millet would shrink by 4.3 to 8.9% in 2050 and 8.9-10.5% under different RCPs by 2070. CONCLUSION: Finger millet is mostly cultivated in mid-hill terraces. The substantial increase in temperature due to climate change may be one reason for decrease in habitat suitability of finger millet. This situation would further threat loss of local landraces of finger millet in the future. The findings can help in planning and policy framing for climate resilient smart agriculture practice.