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ObjectiveTo identify perceptions and awareness of changes in IPC and AMS practices among healthcare workers (HCWs) during the COVID-19 pandemic in India and South Africa (SA).MethodA self-administered online survey which included participant demographics, knowledge and sources of COVID-19 infection, perceived risks and barriers, and self-efficacy. Data were analysed using descriptive statistics.Results321 responses (response rate: 89.2%); 131/321 (40.8%) from India and 190/321 (59.2%) from SA; male to female response rate was 3:2, with majority of respondents aged 40-49 (89/321, 27.7%) and 30-39 (87/321, 27.1%) years. Doctors comprised 47.9% (57/119) of respondents in India and 74.6% (135/181) in SA. Majority of respondents in India (93/119, 78.2%) and SA (132/181, 72.9%) were from the private and public sectors, respectively with more respondents in SA (123/174, 70.7%) than in India (38/104, 36.5%) were involved in antimicrobial prescribing. Respondents reported increased IPC practices since the pandemic and noted need for more training on case management, antibiotic and personal protective equipment (PPE) use. While they noted increased antibiotic prescribing since the pandemic; they did not generally associate their practice with such increase. A willingness to be vaccinated, when vaccination becomes available, was expressed by 203/258 (78.7%) respondents.ConclusionsHCWs reported improved IPC practices and changes in antibiotic prescribing during the COVID-19 pandemic. Targeted education on correct use of PPE was an identified gap. Although HCWs expressed concerns about antimicrobial resistance, their self-perceived antibiotic prescribing practices seemed unchanged. Additional studies in other settings could explore how our findings fit other contexts.KeywordsCOVID-19infection preventioninfection prevention and control (IPC) antimicrobial stewardshiphealthcare workerchange

Background India has a high burden of invasive fungal infections. Although invasive aspergillosis was also reported during the COVID-19 pandemic, the real world data on the risk factors and outcome of CAPA are limited. Our aim is to determine risk factors and clinical outcomes of CAPA and develop a prediction model for patient stratification. Methods A retrospective, case-control study was conducted at a 1300-bedded South Indian tertiary care academic centre from June 1st, 2020 to May 31st, 2021. CAPA cases were defined by 2020 ECMM/ISHAM consensus criteria as possible, probable, and proven infection. Age and admission period matched control group with COVID-19 but without aspergillosis was selected in a 1:1 ratio. A risk scoring stratification for CAPA was developed based on the significant CAPA risk factors using logistic regression model. Figure 1:Receiving operating characteristic curve of CAPA incidence score for predicting CAPA in the study cohort Results 95 CAPA cases, of which 75(79%) were probable and 20(21%) possible, were diagnosed during the study period. 84(88.4%) patients had moderate to severe COVID-19, and 75(78.9%) were treated with steroids, most commonly dexamethasone (Table 1). The time from COVID-19 diagnosis to CAPA was 13 days (IQR 12). 40(42.1%) of patients were on mechanical ventilation at CAPA diagnosis. Outcome measures (MV, NIV and hospital/ICU stay) were significantly higher in CAPA patients compared to controls(Table 2). Neutropenia, use of steroids, broad spectrum antibiotic use, fluconazole prophylaxis and absence of co-infecting pathogen were found to be significant factors associated with CAPA(p< 0.05) (Table 3). An optimal risk score of ≥10.00 predicted CAPA with a sensitivity of 84.2% and a specificity of 59% with an area under the curve of 0.77 (PPV=67.23%, NPV=78.87%)(Fig 1). 75(78.9%) patients had positive serum aspergillus galactomannan with an average value of 1.89±1.65. 28-day (41.1% vs 33.7%, p=0.13) and 6-week all cause-mortality (48.4% vs 37.9%, p=0.07) were higher, but not statistically significant, for CAPA. Table 1:Baseline characteristics and risk factorsTable 2:Primary and secondary outcomesTable 3:CAPA incidence scoring table Significant univariate variables were included in the multivariate logistic regression model and predicted probabilities based on the beta co-efficients of the significant variables in the model were transformed to generate CAPA incidence score for patients. Conclusion Risk factors of CAPA in Indian were similar to those reported previously in other countries. CAPA can be seen in severe COVID-19 patients who are not mechanically ventilated. A CAPA risk scoring system, that needs external validation, is a simple and feasible tool that could be useful in stratification of patients suspected of CAPA. Disclosures All Authors: No reported disclosures.

Background Surgical site infections (SSIs) warrants exploring context-based interventions to minimise their occurrence especially in resource limited settings. Pre-operative interventions are highlighted as important in reducing infections along the surgical pathways. The aim of this study is to investigate whether these interventions can reduce SSIs to inform policy making. Methods A patient centred operational perspective of the entire surgical patients’ pathways including infection management was developed by employing the System Dynamics methodology using the STELLA software. The development process was based on the principles of Group Model building involving healthcare staff, and included: pre-surgery, surgery, post surgery, emergency, re-admission, clinical management, and infection management phases. The model represented (i) categories of patients entering the pathways, (ii) states of patients on the pathways and their evolution over their states, (iii) mix of resources involved in activities, (iv) rules and processes to manage patients, and (v) patients’ exit and discharge routes from the pathways. Literature and policy documents informed also the model building process and the model was validated with the participation of clinical staff involved in the pathways. Results The model was run over a period of 1 year and results regarding the total number of SSIs (TSSIs) and the total number of deaths (TND) following treatment from infections (includes deaths from both SSIs and non-surgical clinical management infections). Three World Health Organization recommended interventions scenarios namely (i) Decolonization of nasal and extranasal sites on hospital admission, (ii) administration of prophylaxis antibiotic 45 minutes before incision, and (iii) skin preparation using Chlorhexidine based alcohol were simulated. TSSIs are reduced from 48 to 33, 36, and 16 under scenarios 1, 2, and 3 respectively (Figure 1) whereas TND are reduced from 35 to 31, 32, and 31 under the same scenarios. Conclusion Pre-operative interventions can be effective in reducing SSIs. Some of these interventions can be successfully implemented in resources limited settings such as the hospital described in this study. Disclosures All Authors: No reported disclosures.

Background Baricitinib is a Janus kinase inhibitor with known anti-inflammatory effects and has been explored for beneficial outcomes in COVID-19 therapeutic management however with paucity of data on its effects on secondary infections and thrombosis. We aimed to assess the efficacy and all-cause mortality among moderate to severe COVID − 19 on a retrospective cohort of patients who received adjunct baricitinib as compared to a matched cohort who received standard of care for moderate to severe Covid 19. Methods The retrospective case control study conducted at 1300-bedded South Indian tertiary care centre from April to October 2021 recruited moderate to severe Covid patients receiving baricitinib therapy for at-least 72 hours into case group. Age and severity matched Covid patients who received standard of care without baricitinib were enrolled as control arm in 1:1 ratio. Data of the study groups on baseline characteristics, medications including antivirals, steroids, antibiotics and outcome measures were obtained. Study outcomes included all-cause mortality, daily clinical improvement assessed by ≥ 1-point improvement in WHO Ordinal Scale scores, multi-organ dysfunction syndrome, incidence of thrombotic events and secondary infections. Results Among the 527 moderate to severe COVID 19 patients in the study period, 75 patients each were recruited into case and control groups respectively. Mean age of case and control groups were 60.82 ± 13.03 and 61 ± 13.48 years respectively. 28-day mortality rate was 33.3%(n = 25) in the case group and 48%(n = 36) in the control group (p = 0.24, RR = 0.79, CI 95%). An absolute risk reduction of 16.75% was observed (NNT = 6) between the groups. All-cause mortality was 42.7%(n = 64) with 27(n = 36%) and 37(n = 49.3%) deaths in the case and control groups respectively(p = 0.09). Kaplan-Meier survival analysis revealed survival distributions to be significantly different between case and control groups (Log rank: p = 0.048). Clinical improvement assessed by decrease in WOS ≥ 1 was demonstrated to be higher in cases (n = 35,47%) than controls (n = 28,37.7%)(p = 0.32). Conclusion Our retrospective case control study revealed lower mortality and higher proportion of patients attaining clinical improvement as measured by at least one-point improvement of WHO ordinal scale in patients admitted with moderate to severe Covid 19, which did not attain statistical significance.

A cross-sectional survey was performed among the adult population of participating countries, India and South Africa. The purpose of this study was to explore perceptions and awareness of SARS-CoV-2-related risks in the relevant countries. The main outcome measures were the proportion of participants aware of SARS-CoV-2, and their perception of infection risks.Self-administered questionnaires were used to collect data via a web- and paper-based survey over three months. For data capturing, Microsoft Excel was employed, and descriptive statistics used for presenting data. Pearson’s Chi-squared test was used to assess relationships between variables, and a p-value less than 0.05 was considered significant.There were 844 respondents (India: n=660, South Africa: n=184; response rate 87.6%), with a 61.1% vs 38.3% female to male ratio. Post-high-school or university education was the lowest qualification reported by most respondents in India (77.3%) and South Africa (79.3%). Sources of information about the pandemic were usually media and journal publications (73.2%), social media (64.6%), family and friends (47.7%) and government websites (46.2%). Most respondents correctly identified infection prevention measures (such as physical distancing, mask use), with 90.0% reporting improved hand hygiene practices since the pandemic. Hesitancy or refusal to accept the SARS-CoV-2 vaccine was reported among 17.9% and 50.9% of respondents in India and South Africa, respectively. Reasons cited included rushed vaccine development and the futility of vaccines for what respondents considered a self-limiting flu-like illness.Respondents identified public health promotion measures for SARS-CoV-2. Reported hesitancy to the up-take of SARS-CoV-2 vaccines was much higher in South Africa. Vaccination campaigns should consider robust public engagement and contextually fit communication strategies with multimodal, participatory online and offline initiatives to address public concerns, specifically towards vaccines developed for this pandemic and general vaccine hesitancy.

Background The global concern over antimicrobial resistance (AMR) is gathering pace. Low- and middle-income countries (LMICs) are at the epicentre of this growing public health threat and governmental and healthcare organizations are at different stages of implementing action plans to tackle AMR. The South Indian state of Kerala was one of the first in India to implement strategies and prioritize activities to address this public health threat. Strategies Through a committed and collaborative effort from all healthcare related disciplines and its professional societies from both public and private sector, the Kerala Public Private Partnership (PPP) has been able to deliver a state-wide strategy to tackle AMR A multilevel strategic leadership model and a multilevel implementation approach that included developing state-wide antibiotic clinical guidelines, a revision of post-graduate and undergraduate medical curriculum, and a training program covering all general practitioners within the state the PPP proved to be a successful model for ensuring state-wide implementation of an AMR action plan. Collaborative work of multi-professional groups ensured co-design and development of disease based clinical treatment guidelines and state-wide infection prevention policy. Knowledge exchange though international and national platforms in the form of workshops for sharing of best practices is critical to success. Capacity building at both public and private institutions included addressing practical and local solutions to the barriers e.g. good antibiotic prescription practices from primary to tertiary care facility and infection prevention at all levels. Conclusion Through 7 years of stakeholder engagement, lobbying with government, and driving change through co-development and implementation, the PPP successfully delivered an antimicrobial stewardship plan across the state. The roadmap for the implementation of the Kerala PPP strategic AMR plan can provide learning for other states and countries aiming to implement action plans for AMR.

BACKGROUND Long COVID, or post-COVID-19 syndrome, is the persistence of signs and symptoms that develop during or after COVID-19 infection for more than 12 weeks and are not explained by an alternative diagnosis. In spite of health care recouping to prepandemic states, the post-COVID-19 state tends to be less recognized from low- and middle-income country settings and holistic therapeutic protocols do not exist. Owing to the syndemic nature of COVID-19, it is important to characterize post-COVID-19 syndrome. OBJECTIVE We aimed to determine the incidence of post-COVID-19 symptoms in a cohort of inpatients who recovered from COVID-19 from February to July 2021 at a tertiary-care center in South India. In addition, we aimed at comparing the prevalence of post-COVID-19 manifestations in intensive care unit (ICU) and non-ICU patients, assessing the persistence, severity, and characteristics of post-COVID-19 manifestations, and elucidating the risk factors associated with the presence of post-COVID-19 manifestations. METHODS A total of 120 adult patients admitted with COVID-19 in the specified time frame were recruited into the study after providing informed written consent. The cohort included 50 patients requiring intensive care and 70 patients without intensive care. The follow-up was conducted on the second and sixth weeks after discharge with a structured questionnaire. The questionnaire was filled in by the patient/family member of the patient during their visit to the hospital for follow-up at 2 weeks and through telephone follow-up at 6 weeks. RESULTS The mean age of the cohort was 55 years and 55% were men. Only 5% of the cohort had taken the first dose of COVID-19 vaccination. Among the 120 patients, 58.3% had mild COVID-19 and 41.7% had moderate to severe COVID-19 infection. In addition, 60.8% (n=73) of patients had at least one persistent symptom at the sixth week of discharge and 50 (41.7%) patients required intensive care during their inpatient stay. The presence of persistent symptoms at 6 weeks was not associated with severity of illness, age, or requirement for intensive care. Fatigue was the most common reported persistent symptom with a prevalence of 55.8%, followed by dyspnea (20%) and weight loss (16.7%). Female sex (odds ratio [OR] 2.4, 95% CI 1.03-5.58; P=.04) and steroid administration during hospital stay (OR 4.43, 95% CI 1.9-10.28; P=.001) were found to be significant risk factors for the presence of post-COVID-19 symptoms at 6 weeks as revealed by logistic regression analysis. CONCLUSIONS Overall, 60.8% of inpatients treated for COVID-19 had post-COVID-19 symptoms at 6 weeks postdischarge from the hospital. The incidence of post-COVID-19 syndrome in the cohort did not significantly differ across the mild, moderate, and severe COVID-19 severity categories. Female sex and steroid administration during the hospital stay were identified as predictors of the persistence of post-COVID-19 symptoms at 6 weeks.

Background: Safe and effective use of colistin requires robust pharmacokinetic (PK) and pharmacodynamic (PD) data to guide dosing. Aim: To evaluate the pharmacokinetics of colistimethate sodium and colistin in critically ill patients and correlate with clinical efficacy and renal function. Materials and Methods: Twenty critically ill adult patients with colistin-susceptible multidrug-resistant (MDR) infections and normal renal function treated with intravenous colistimethate sodium – at a 9 million units (270 mg CBA) loading dose followed by maintenance (MD) of 3 million units t.i.d, 24 hours later – were evaluated for clinical cure (CC) at the end of therapy. Patient characteristics and plasma colistin levels at 0, 0.5, 1, 2, 4, 8 and 12 hours after the loading dose and at 1, 2 and 8 hours after the eighth and ninth infusion of MD were evaluated. Colistimethate sodium and colistin levels were measured by high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). Results: Among the 20 patients who were evaluated, 60% had pneumonia. Predominant pathogens were Klebsiella pneumoniae and Acinetobacter spp. Clinical cure was 50% (10/20). Mean peak loading dose concentrations were 3 ± 1.1 mg/L (1.75–5.14) and 2.37 ± 1.2 mg/L (1.52–5.54) for ‘cure’ and ‘failure’ groups, respectively (p = 0.13), while mean steady-state (Cssavg) concentrations were 2.25 ± 1.3 mg/L and 1.78 ± 1.1 mg/L in ‘cure’ and ‘failure’ groups, respectively (p = 0.19). Nephrotoxicity was 5% on day 7 of therapy. However, bacteriological cure could not be correlated with PK/PD. Conclusions: Subtherapeutic Cssavg with clinical failure and lower efficacy without significant nephrotoxicity highlights the need for therapeutic drug monitoring to guide colistin dosing.

Background: The post-Covid symptoms among patients hospitalised with covid has to be determined for elucidating the spectrum of illness which persists even after the apparent recovery. The understanding of the post-Covid symptoms will help us to better manage aftermath of the pandemic.Aim: To determine the incidence of post-Covid symptoms in a cohort of inpatients who recovered from COVID-19 from a tertiary care centre in South India.Method: 120 survivors from patients admitted with COVID 19 were prospectively followed up for 6 weeks after their discharge from the hospital. The cohort included 50 patients requiring Intensive care unit (ICU) care and 70 ward patients. The follow-up was conducted on the second and sixth week after discharge with a structured questionnaire. The questionnaire was filled by the patient/bystanders during their visit to the hospital for follow-up at 2 weeks and through telephone follow up at 6 weeks.Results: Mean age of the cohort was 55 years and 55% were males. 58.3% had mild covid and 41.7% had moderate to severe covid infection. 60.8% (n=73) of patients had at least one persistent symptom at sixth week of discharge. 50 (41.7%) patients required intensive care during their inpatient stay. Presence of persistent symptoms at 6 weeks was not associated with severity of illness, age or requirement for intensive care. Fatigue was the most common reported persistent symptom with a prevalence of 55.8% followed by weight loss (22.5%) and dyspnoea (20%). Female sex (OR 2.4, 95% CI: 1.03–5.58, p = 0.041) and steroid administration during hospital stay (OR: 4.43; 95% CI: 1.9–10.28, p = 0.001), were found to be significant risk factors for the presence of post-Covid symptoms at 6 weeks as revealed by logistic regression analysis.Conclusion: 60.8% of inpatients treated for covid had post-Covid symptoms at 6 weeks post- discharge from hospital. Female sex and steroid administration during hospital stay were identified as predictors of persistence of post-Covid symptoms at 6weeks.

Background Sepsis remains a leading cause of death worldwide despite advances in management strategies. Preclinical and observational studies have found mortality benefit with high-dose vitamin C in sepsis. Our study aims to prospectively evaluate the effect of intravenous hydrocortisone, vitamin C [ascorbic acid (AA)], and thiamine (HAT) administration in reducing inpatient all-cause mortality among patients with septic shock. Materials and methods Our single-center, prospective, open-label, randomized controlled trial recruited patients with admitting diagnosis of septic shock and assigned eligible patients (1:1) into either intervention (HAT) or control group (routine). The HAT group received intravenous combination of vitamin C (1.5 g every 6 hours), thiamine (200 mg every 12 hours), and hydrocortisone (50 mg every 6 hours) within 6 hours of onset of septic shock admission. The treatment was continued for at least 4 days, in addition to the routine standard of care provided to the control group. Thiamine and hydrocortisone use in control arm was not restricted. Vitamin C levels were estimated at baseline and at the end of the 4 days of treatment for both groups. The primary outcome evaluated was mortality during inpatient stay. Results Among 90 patients enrolled, 88 patients completed the study protocol. The baseline characteristics between the HAT (n = 45) and the routine (n = 43) groups were comparable. The all-cause mortality in the HAT cohort was 57% (26/45) compared to 53% (23/43) in the routine care group (p = 0.4, OR 1.19, 95% CI 0.51-2.76). The time to reversal of septic shock was significantly lower in the HAT (34.58 ± 22.63 hours) in comparison to the routine care (45.42 ± 24.4 hours) (p = 0.03, mean difference -10.84, 95% CI -20.8 to -0.87). No significant difference was observed between the HAT and the routine care with respect to changes in sequential organ failure assessment (SOFA) scores at 72 hours (2.23 ± 2.4 vs 1.38 ± 3.1), the use of mechanical ventilation (48% vs 46%), and mean Vasoactive Inotropic Score (7.77 ± 12.12 vs 8.86 ± 12.5). Conclusion Intravenous administration of vitamin C, thiamine, and hydrocortisone did not significantly improve the inpatient all-cause mortality among patients with septic shock. Clinical significance HAT protocol does not reduce hospital mortality but decreases time to shock reversal in septic shock. How to cite this article Mohamed ZU, Prasannan P, Moni M, Edathadathil F, Prasanna P, Menon A, et al. Vitamin C Therapy for Routine Care in Septic Shock (ViCTOR) Trial: Effect of Intravenous Vitamin C, Thiamine, and Hydrocortisone Administration on Inpatient Mortality among Patients with Septic Shock. Indian J Crit Care Med 2020;24(8):653-661.

Management of candidemia in developing countries like India encounters laxity in appropriate clinical management and challenges in terms of healthcare capacity, despite its association with high morbidity and mortality. Our study aims to evaluate the impact of a comprehensive candidemia care bundle implementation on appropriateness of therapy and major clinical outcomes.The single-center, quasi-experimental study conducted at a south Indian tertiary care center included adult patients diagnosed with candidemia. Following a retrospective review of candidemia patients of the pre-implementation period (January 2013-December 2015), the hospital antifungal stewardship team instituted a clinical pharmacist driven comprehensive candidemia care bundle for candidemia patients during the post-implementation period (October 2017-2019) and its impact on appropriateness of antifungal prescriptions and inpatient mortality was evaluated.The study included 175 patients with candidemia, comprising of 103 patients in the pre-implementation period and 72 patients in the post-implementation period. Appropriateness of antifungal prescriptions rose to 65% during post-implementation period from 30% observed in pre-implementation phase (P = .0005). The inhospital mortality rate reduced from 40% in the pre-implementation phase to 36% in the post-implementation phase, recording a 10% reduction over 2 years post-implementation (P = .26). No significant difference was observed in terms length of stay (P = .17).Our study demonstrates the successful implementation of an antifungal stewardship led comprehensive care bundle in a low middle income countries setting. The results of our study will have profound implications in improving the appropriateness of management of candidemia and feasibility of scaling up to wider settings could be explored.

BackgroundThe high exposure risk to COVID among frontline heathcare workers was a major challenge to healthcare systems across the globe that warranted close monitoring through risk assessment and contact tracing strategies. The objective of our study was to characterize exposure risk factors for transmission and subsequent COVID positivity among the frontlinehealthcare workers in our institution during the pandemic period.MethodsThe retrospective observational study conducted over a period of 6 months from June 2020 to November 2020 at a 1300-bedded South Indian tertiary care centre included frontline healthcare workers who were assessed for their identified encounter with COVID positive individual using a modified WHO COVID risk assessment tool. Additional risk attributes of exposure characterized among COVID positive healthcare workers comprised of shared space, cluster related transmissions and multiple instances of exposure to COVID.ResultsAmong a total of 4744 contacts with COVID positive individuals assessed for risk stratification during the study period, 942 (19.8%) were high risk and 3802 (80.2%) were low risk exposures respectively. 106 (2.2%) turned COVID positive during the surveillance period of 14 days. Frontline workers working in COVID areas had significant low COVID rates as compared to other areas (N=1, 0.9%). The average monthly COVID positivity rates being 1.66%, the attack rates among high risk and low risk contacts among the total HCWs screened were 5% (46/942) and 1.57% (60/3802) respectively. Shared space (70%) and IPC breaches (66%) were found to be highly prevalent in the COVID positive cohort, along with maskless encounters (43%) and multiple exposure (39%). The attack rate among the 6 identified COVID cluster groups (5.5%) were found to be higher than the attack rate (2.2%) noted among the total contacts screened and no significant association was observed between risk categories in the clusters.DiscussionOur study highlights higher risk of COVID positivity among high risk contacts as compared to low risk contacts. However, the high COVID positivity rate in low risk group among cluster transmissions and its lack of association with risk assessment highlight the suboptimal utility of the risk assessment strategy among cluster groups.

Polymyxins being last resort drugs to treat infections triggered by multidrug-resistant pathogens necessitates the implementation of antimicrobial stewardship program (ASP) initiatives to support its rational prescription across healthcare settings. Our study aims to describe the change in the epidemiology of polymyxins and patient outcomes following the implementation of ASP at our institution. The antimicrobial stewardship program initiated in February 2016 at our 1300 bed tertiary care center involved post-prescriptive audits tracking polymyxin consumption and evaluating prescription appropriateness in terms of the right indication, right frequency, right drug, right duration of therapy and administration of the right loading dose (LD) and maintenance dose (MD). Among the 2442 polymyxin prescriptions tracked over the entire study period ranging from February 2016 to January 2020, the number of prescriptions dropped from 772 prescriptions in the pre-implementation period to an average of 417 per year during the post-implementation period, recording a 45% reduction. The quarterly patient survival rates had a significant positive correlation with the quarterly prescription appropriateness rates (r = 0.4774, p = 0.02), right loading dose (r = 0.5228, p = 0.015) and right duration (r = 0.4361, p = 0.04). Our study on the epidemiology of polymyxin use demonstrated favorable effects on the appropriateness of prescriptions and mortality benefits after successful implementation of antimicrobial stewardship in a real-world setting.

Background: India currently has the second largest burden of infections due to COVID-19. Health Care Worker (HCW) shortages are endemic to Indian healthcare. It should therefore be a huge priority to protect this precious resource as a critical component of the systemic response to this pandemic. Advisories from the Indian Council of Medical Research (ICMR) have focused on using hydroxychloroquine prophylaxis against COVID-19 in at risk HCW. This prophylaxis strategy has no evidence. In further jeopardy there appear to insubstantial attempts to build this evidence as well. In this connection, we commissioned a survey within our Institution to estimate the penetration of hydroxychloroquine (HCQ) use and use this to statistically model the impact of current ongoing studies in India. We also briefly review the literature on HCQ prophylaxis for COVID-19. Design and methods: A structured survey designed using RedCAP application was disseminated among healthcare professionals employed at an academic referral tertiary care centre via online social media platforms. The survey was kept open for the entire month of June 2020. The survey was additionally used to statistically model the size of studies required to comprehensively address the efficacy of HCQ in this setting. Results: 522 responses were received, of which 4 were incomplete. The ICMR strategy of 4 or more doses of HCQ was complete only in 15% of HCW in our survey. The majority of respondents were doctors (238, 46%). Amongst all category of responders, only 12% (n=63) received the full course. A majority of those who initiated the chemoprophylaxis with HCQ turned out to be medical professionals (59/63) with neither nurse nor other categories of healthcare workers accessing the medication. The respondents of our institutional survey did not report any life-threatening side effects. Presuming efficacy as per ICMR modelling for new registry trial on the lines of the published case control study, equal allocation between cases and controls and assuming a RR of 1.3.6, the power of such a study would be very low for n=2000 for event rates from 2.5-12.5%. Conclusion: We report the low penetration of HCQ chemoprophylaxis among the healthcare workers of our institution. We highlight the inherent drawbacks in the study design of current national COVID related trial based on the statistical modelling of our survey results and published literature, and thereby emphasis the need of evidence-based strategies contributing to research policy at national level. Significance for public health In the context of the mounting COVID pandemic in India crippling the public health system and curtailing healthcare workers of the country, we would like to report the low hydroxychloroquine chemoprophylaxis rate from our institutional survey among healthcare workers that highlights the poor penetration of a national hydroxychloroquine prophylaxis advisory. The brief review on hydroxychloroquine (HCQ) chemoprophylaxis strategy for COVID-19 that draws on from existing literature and countrywide COVID trials reveals tenuous research designs which would be consequently informing public health policies of the nation. We emphasize on the need for continued emphasis on evidence based protective measures and rigorous efforts to build this evidence when lacking.

Background: The global impact of COVID pandemic has been unprecedented and had expedited the urgent need of mass vaccination especially in a densely populated country like India. Sustained efforts in strategies for increase the vaccination campaigns are essential at the community level to address the acceptance of vaccines. The perception of public understanding on COVID vaccinations would help healthcare professionals advise the public on vaccination and guide policy decisions. The aim of the study was to discover knowledge gaps related to various aspects of COVID vaccination among the general population and enhance awareness that improves the vaccination practice.Methods: A semi structured questionnaire was administered exploring the knowledge and awareness of public was conducted in a tertiary care centre located in southern part of India. The study participants were contacted during the time of vaccination. The key domains we collected from our survey included general perception on vaccines, knowledge on vaccine practice, vaccination practices on special population, vaccine specific knowledge and vaccine related socio-cultural factors on vaccinations.Results: Valid and complete responses were obtained from 4471 participants, among this majority were female participants (61.04%) with the median age of 36 years. Majority of the participants had a belief that vaccines are effective 3415 (81.8%) for preventing COVID-19.Conclusions: Vaccination campaigns must consider strong public participation and contextually relevant communication tactics for the better acceptability. Furthermore, we need a targeted capacity building initiative with more emphasis towards vulnerable populations to be implemented on vaccination.

Quality problem or issue To assess impact of medical emergency team (MET) in reducing "out-of-ICU" cardiopulmonary arrests and identify barriers to its optimal utilization. Initial assessment Frequently observed critical clinical signs and laboratory values of "out-of-ICU" crashes were used to develop Amrita Early Warning Criteria. Choice of solution A physician-led MET was established to respond to code MET, activated by a primary nurse. Implementation Rates of "out-of-ICU" cardiopulmonary arrests per 1000 admissions were compared in pre-MET (2013-2014) and post-MET periods (2014-2016) along with disposition following MET and mortality. Descriptive statistics and logistic regression were used for comparative analysis. Evaluation For continued quality improvement, a Likert agreement scale questionnaire collated the nurse's feedback on MET. 386 Code MET were recorded with an activation rate of 18.8 per 1000 inpatients for 2014-2016. Common MET triggers were desaturation (53%), seizure (10%), and syncope (9%). Seventy-one percent of activations were attended within 5 minutes, with 45% reported during nurse's night shift hours. Medical emergency team interventions resulted in 59% being shifted to ICU. In the "post-MET" period, "Cold Blue" dose reduced from 6.9 in 2013-2014 to 2.6 (P = .0002) in 2014-2015 and 3.2 (P = .01) in 2015-2016. Ninety-three percent of the Code Blues with prior MET calls were "delayed MET" and 28% of the Code Blues without prior MET activation were "missed MET." Nurse's feedback revealed that 46% lacked knowledge of correct MET activation process while 31% expressed a fear of reprisal for inappropriate activation. Lessons learned Although MET intervention was successful in significantly reducing "out-of-ICU" Code Blues, focused training of nurses is required for continued quality improvement.

Severe thrombocytopenia in dengue often prompts platelet transfusion primarily to reduce bleeding risk. In India, about 11-43% of dengue patients report receiving platelet transfusions which is considered scarce and expensive especially in resource limited settings. Herein, we evaluated the efficacy and safety of Carica papaya leaf extract (CPLE) in the management of severe thrombocytopenia (≤30,000/μL) in dengue infection. 51 laboratory confirmed adult dengue patients with platelet counts ≤30,000/μL were randomly assigned to either treatment (n = 26) or placebo (n = 24) group. By day 3, CPLE treated patients reported significantly (p = 0.007) increased platelet counts (482%± 284) compared to placebo (331%±370) group. In the treatment group, fewer patients received platelet transfusions (1/26 v/s 2/24) and their median time for platelets to recover to ≥ 50,000/μL was 2 days (IQR 2-3) compared to 3 days (IQR 2-4) in placebo. Overall, CPLE was safe and well tolerated with no significant decrease in mean hospitalization days. Plasma cytokine profiling revealed that by day 3, mean percent increase in TNFα and IFNγ levels in treatment group was less compared to that observed in placebos; (TNFα: 58.6% v/s 127.5%; p = 0.25 and IFNγ: 1.93% v/s 62.6% for; p = 0.12). While a mean percent increase in IL-6 levels occurred in placebos (15.92%±29.93%) by day 3, a decrease was noted in CPLE group (12.95%±21.75%; p = 0.0232). Inversely, CPLE treated patients reported a mean percent increase compared to placebo by day 3 (143% ±115.7% v/s 12.03%± 48.4%; p = 0.006). Further, by day 3, a faster clearance kinetics of viral NS1 antigenemia occurred-mean NS1 titers in treatment group decreased to 97.3% compared to 88% in placebos (p = 0.023). This study demonstrates safety and efficacy of CPLE in increasing platelet counts in severe thrombocytopenia in dengue infections. A possible immunomodulatory and antiviral activity may be attributed to CPLE treatment. These findings merit validation in larger prospective studies. Trial registration Name of the registry: Clinical Trials Registry-India (CTRI) Registration No.: CTRI-REF/2017/02/013314.

Kerala recorded the initial cases of COVID/SARS-CoV-2 in India and managed to successfully contain it initially through its public health system. As the number of cases increased, the private sector also needed to be prepared. Here, we describe the preparedness and response of a tertiary care system in the nonpublic sector. The Health system response and preparedness consisted of establishment of leadership and infrastructural modification; screening-fever clinic, inpatient admission pathway, dynamic screening strategy training; developing protocols for emergencies and review visits of patients requiring dialysis and chemotherapy. Other priorities included maintaining supply chain of PPE, other essentials such as antivirals and establishing tele consultation. A strong leadership spearheaded infrastructural developments, meetings and troubleshooting every day to adapt to the changing epidemiological and clinical scenario. The Fever clinic was the designated area for consultation of patients with positive symptoms complex and epidemiological risk factors. In early March the screening strategy focused on the presence of a combination of epidemiological and clinical risk factors. As the number of contact cases rose, the focus shifted to identifying any of the defined epidemiological risk factors among persons reaching the hospital. The challenges included redesigning a patient movement pathway, deployment of human resources from their regular work to the screening activities, training of the repurposed human resource, procurement of good quality PPE, coordinating among the specialties, ensuring psychological support etc. The implementation of a timely COVID screening strategy aided our tertiary care centre to provide health care to all patients during the pandemic seamlessly.

Background Antimicrobial resistance is a major public health threat internationally but, particularly in India. A primary contributing factor to this rise in resistance includes unregulated access to antimicrobials. Implementing antimicrobial stewardship programs (ASPs) in the acute hospital setting will help curb inappropriate antibiotic use in India. Currently, ASPs are rare in India but are gaining momentum. This study describes ASP implementation in a large, academic, private, tertiary care center in India. Methods An ASP was established in February 2016 consisting of an administrative champion, hospitalist, microbiologist, intensivist, and pharmacists. Antimicrobial stewardship program interventions included postprescriptive audit and establishment of institutional guidelines. The ASP tracked appropriate drug selection including loading dose, maintenance dose, frequency, route, duration of therapy, de-escalation, and compliance with ASP recommendations. Defined daily dose (DDD) of drugs and cost of antimicrobials were compared between the pre-implementation phase (February 2015–January 2016) and post-implementation phase (February 2016–January 2017). Results Of 48 555 patients admitted during the post-implementation phase, 1020 received 1326 prescriptions for restricted antibiotics. Antibiotic therapy was appropriate in 56% (742) of the total patient prescriptions. A total of 2776 instances of “inappropriate” antimicrobial prescriptions were intervened upon by the ASP. Duration (806, 29%) was the most common reason for inappropriate therapy. Compliance with ASP recommendations was 54% (318). For all major restricted drugs, the DDD/1000 patient days declined, and there was a significant reduction in mean monthly cost by 14.4% in the post-implementation phase. Conclusions Implementation of a multidisciplinary antibiotic stewardship program in this academic, large, Indian hospital demonstrated feasibility and economic benefits.

Qualitative 2D gel-electrophoresis (2DE) protein profiling for osteoarthritis (OA) and rheumatoid arthritis (RA) is challenging because of selective protein loss due to discrepancies in protein precipitation methodologies. Thus, we aimed at developing qualitative protein representation from OA/RA articular cartilage without protein precipitation towards identification of clinically relevant proteins. Chondroitinase digested human articular cartilages from RA patients were subjected to protein extraction using guanidinium hydrochloride (GuHCl) or 8 M urea with 10 or 2% ASB-14-4 or 0.45 M urea with 2% ASB-14-4 with cetylpyridinium chloride (CPC). The GuHCl extract is further protein precipitated with acetone or ammonium acetate-methanol or centricon-fractionated using 100 kDa cut filters and protein precipitated using ethanol. Processed extracts were subjected to 2DE to identify protein profiles. Poor proteins representations were observed in 2D gels with protein precipitated samples compared to qualitative protein representations seen in 2D gels of 0.45 M urea and 2%ASB-14-4 extraction procedure reproducibly. The strategy circumventing protein precipitation generated qualitative 2D gels. RA vs OA gel comparison showed elevated prolargin levels in RA with biglycan levels remaining unaltered. Up regulation of prolargin in RA suggests the likelihood of an adaptive mechanism to control the increased osteoclastogenesis in RA and may have therapeutic value in controlling the disease.

Supplemental Digital Content is available in the text, Asymptomatic myocardial injury following noncardiac surgery (MINS) is an independent predictor of 30-day mortality and may go unrecognized based on standard diagnostic definition for myocardial infarction (MI). Given lack of published research on MINS in India, our study aims to determine incidence of MINS in patients undergoing noncardiac surgery at our tertiary care hospital, and evaluate the clinical characteristics including 30-day outcome. The prospective observational study included patients >65 years or >45 years with either hypertension (HTN), diabetes mellitus (DM), coronary artery disease (CAD), cerebrovascular accident (CVA), or peripheral arterial disease undergoing noncardiac surgery. MINS was peak troponin level of ≥0.03 ng/dL at 12-hour or 24-hour postoperative. All patients were followed for 30 days postoperatively. Predictors of MINS and mortality were analyzed using multivariate logistic regression. Patients categorized based on peak troponin cut-off values determined by receiver operating characteristic curve were analyzed by Kaplan–Meir test to compare the survival of patients between the groups. Among 1075 patients screened during 34-month period, the incidence of MINS was 17.5% (188/1075). Patients with DM, CAD, or who underwent peripheral nerve block anaesthesia were 1.5 (P 1 ng/mL (P = .01) were significantly associated with mortality. A peak troponin cut-off of >0.152 ng/mL predicted mortality among MINS patients at 72% sensitivity and 58% specificity. Lack of antithrombotic therapy following MINS was independent predictor of mortality (P

Cardiovascular diseases (CVDs) are the leading cause of death and disability in India. Early and sustained exposure to behavioral risk factors leads to development of CVDs.The aim of this study was to determine the baseline risk of a "hard CVD event" in subjects attending comprehensive health clinic and assess behavioral characteristics in "at risk" population.Using WHO STEPwise approach to Surveillance modified questionnaire, prevalence of noncommunicable diseases (NCDs) and risk factors was estimated in this cross-sectional study of 4507 subjects. Baseline cardiovascular risk was determined using Framingham risk score (FRS) and American College of Cardiology (ACC)/American Heart Association (AHA) atherosclerotic cardiovascular disease (ASCVD) algorithms. Modifiable behavior associated with high CVD risk was assessed. Among 40 to 59-year olds, ASCVD risk tool derived both a 10-year and lifetime risk score, which were used to stratify the cohort into 3 risk groups, namely, a high 10-year and high lifetime, a low 10-year and high lifetime, and a low 10-year and low lifetime risks.Dyslipidemia (30.6%), hypertension (25.5%), diabetes mellitus (20%), and obstructive airway disorders (17.6%) were most prevalent NCDs in our cohort. The ASCVD score stratified 26.1% subjects into high 10-yr and 59.5% into high lifetime risk while FRS classified 17.2% into high 10-year risk. Compared with FRS, the ASCVD risk estimator identified a larger proportion of subjects "at risk" of developing CVD. A high prevalence of alcohol use (38.4%), decreased intake of fruits and vegetables (96.2%) and low physical activity (58%) were observed in "at risk" population. Logistic regression analysis showed that in 40 to 59-year group, regular and occasional drinkers were 8.5- and 3.1-fold more likely to be in high 10-year and high lifetime ASCVD risk category than in low 10-year and low lifetime risk group. Similarly, regular drinkers and occasional drinkers were 2.1 and 1.3 times more likely to be in low 10-year and high lifetime risk than in low 10-year and low lifetime risk category. Subjects with inadequate intake of fruits and vegetables were 1.59 times more likely to be in low 10-year and high lifetime risk than the lower 10-year and lifetime risk group. Obese participants were 2.3-fold more likely to be in low 10-year and high lifetime risk.Identification of "at risk" subjects from seemingly healthy population will allow sustainable primary prevention strategies to reduce CVD.