Long-term survival following medical management of Aspergillus endocarditis with dissemination as a consequence of steroid therapy in severe COVID-19 pneumonia.

A male in his 40's with no known comorbidities developed severe COVID-19 pneumonia and received a four-week course of methylprednisolone. The patient subsequently developed disseminated Aspergillus endocarditis, manifesting as multiple organ involvement including the heart, eyes, and brain. Despite the poor prognosis generally associated with fungal endocarditis, the patient survived following aggressive medical management with a combination of liposomal amphotericin b and voriconazole therapy and is now doing well for over two years and is off antifungal therapy for a year.

Characterization and predictive risk scoring of long COVID in a south indian cohort after breakthrough COVID infection; a prospective single centre study.

BACKGROUND: With the World Health Organization (WHO) declaring an end to the COVID-19 pandemic, the focus has shifted to understanding and managing long-term post-infectious complications. "Long COVID," characterized by persistent or new onset symptoms extending beyond the initial phase of infection, is one such complication. This study aims to describe the incidence, clinical features and risk profile of long COVID among individuals in a South Indian cohort who experienced post-ChAdOx1 n-Cov-2 vaccine breakthrough infections. METHODS: A single-centre hospital-based prospective observational study was conducted from October to December 2021. The study population comprised adult patients (> 18 years) with a confirmed COVID-19 diagnosis who had received at least a single dose of vaccination. Data was collected using a specially tailored questionnaire at week 2, week 6, and week 12 post-negative COVID-19 test. A propensity score based predictive scoring system was developed to assess the risk of long COVID. RESULTS: Among the 414 patients followed up in the study, 164 (39.6%) reported long COVID symptoms persisting beyond 6 week's post-infection. The presence of long COVID was significantly higher among patients above 65 years of age, and those with comorbidities such as Type II Diabetes Mellitus, hypertension, dyslipidemia, coronary artery disease, asthma, and cancer. Using backwards selection, a reduced model was developed, identifying age (OR 1.053, 95% CI 0.097-1.07, p < 0.001), hypertension (OR 2.59, 95% CI 1.46-4.59, p = 0.001), and bronchial asthma (OR 3.7176, 95% CI 1.24-11.12, p = 0.018) as significant predictors of long COVID incidence. A significant positive correlation was observed between the symptomatic burden and the number of individual comorbidities. CONCLUSIONS: The significant presence of long COVID at 12 weeks among non-hospitalised patients underscores the importance of post-recovery follow-up to assess for the presence of long COVID. The predictive risk score proposed in this study may help identify individuals at risk of developing long COVID. Further research is needed to understand the impact of long COVID on patients' quality of life and the potential role of tailored rehabilitation programs in improving patient outcomes.

Penicilliosis in a Non-HIV Patient: A Case Report.

A 68-year-old female, with a known case of mantle cell lymphoma, came with complaints of persistent cough with expectoration for three months, not responding to multiple courses of antibiotics. Bronchoscopy was done and bronchoalveolar lavage (BAL) culture revealed Penicillium species. She was started on IV liposomal amphotericin B for 14 days and then switched to oral itraconazole which showed a response to treatment. Early diagnosis of penicilliosis and prompt treatment are important as it is rare and associated with a high mortality rate.

Incidence and Characterization of Post-COVID-19 Symptoms in Hospitalized COVID-19 Survivors to Recognize Syndemic Connotations in India: Single-Center Prospective Observational Cohort Study.

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.

Safety and immunogenicity of SII-NVX-CoV2373 (COVID-19 vaccine) in adults in a phase 2/3, observer-blind, randomised, controlled study.

Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with ∼90% efficacy. The same vaccine is manufactured in India after technology transfer (called as SII-NVX-CoV2373), was evaluated in this phase 2/3 immuno-bridging study. Methods: This was an observer-blind, randomised, phase 2/3 study in 1600 adults. In phase 2, 200 participants were randomized 3:1 to SII-NVX-CoV2373 or placebo. In phase 3, 1400 participants were randomized 3:1 to SII-NVX-CoV2373 or NVX-CoV2373 (940 safety cohort and 460 immunogenicity cohort). Two doses of study products (SII-NVX-CoV2373, NVX-CoV2373 or placebo) were given 3 weeks apart. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 to NVX-CoV2373 in terms of geometric mean ELISA units (GMEU) ratio of anti-S IgG antibodies 14 days after the second dose (day 36) and to determine the incidence of causally related serious adverse events (SAEs) through 180 days after the first dose. Anti-S IgG response was assessed using an Enzyme-Linked Immunosorbent Assay (ELISA) and neutralizing antibodies (nAb) were assessed by a microneutralization assay using wild type SARS CoV-2 in participants from the immunogenicity cohort at baseline, day 22, day 36 and day 180. Cell mediated immune (CMI) response was assessed in a subset of 28 participants from immunogenicity cohort by ELISpot assay at baseline, day 36 and day 180. The total follow-up was for 6 months. Trial registration: CTRI/2021/02/031554. Findings: Total 1596 participants (200 in Phase 2 and 1396 in Phase 3) received the first dose. SII-NVX-CoV2373 was found non-inferior to NVX-CoV2373 (anti-S IgG antibodies GMEU ratio 0.91; 95% CI: 0.79, 1.06). At day 36, there was more than 58-fold rise in anti-S IgG and nAb titers compared to baseline in both the groups. On day 180 visit, these antibody titers declined to levels slightly lower than those after the first dose (13-22 fold-rise above baseline). Incidence of unsolicited and solicited AEs was similar between the SII-NVX-CoV2373 and NVX-CoV2373 groups. No adverse event of special interest (AESI) was reported. No causally related SAE was reported. Interpretation: SII-NVX-CoV2373 induced a non-inferior immune response compared to NVX-CoV2373 and has acceptable safety profile. Funding: SIIPL, Indian Council of Medical Research, Novavax.

Colistin (Polymyxin E) Use in Abdominal Solid Organ Transplant Recipients.

Background: Patients undergoing solid organ transplantation are at a higher risk of multi-drug resistant (MDR) bacterial infections especially during the immediate post operative period. Objective: To audit the usage, dosage appropriateness and safety of colistin use in abdominal solid organ transplant recipients to treat immediate post-transplant bacterial infections. Methods: After completion of 1000 abdominal solid organ transplants at our institute, data of the transplant recipients who received colistin between October 2010 and December 2019 was extracted from the hospital health information system. Data of all microbiological culture isolates, the minimum inhibitory concentration (MIC) of colistin, appropriateness of colistin dosing and nephrotoxicity associated with colistin use was assessed. Results: Of the 1170 (732 liver and 438 renal) solid organ transplant recipients, 82 (66 liver and 16 renal) received colistin to treat posttransplant MDR bacterial infections. Nearly 60% received colistin as definitive therapy and 87.81% received colistin as combination. Mean duration of colistin therapy was found to be higher in renal than liver transplant recipients. Out of the total 89 bacterial isolates, there were 2 colistin resistant Klebsiella strains. Colistin in combination with meropenem (36.4%) was the most commonly used dual therapy. Out of the total 89 bacterial isolates, there were 2 colistin resistant Klebsiella strains. Overall in-hospital mortality of patients who received colistin was 43.9%. Renal impairment occurred in 28.8% of liver transplant recipients. Conclusion: Infection necessitating colistin use increases mortality by three folds in liver transplant recipients and by five percentage points in renal transplant recipients.

Epidemiology of Community-Acquired Sepsis: Data from an E-Sepsis Registry of a Tertiary Care Center in South India.

The study aims to characterize community-acquired sepsis patients admitted to our 1300-bedded tertiary care hospital in South India from the Surviving Sepsis Campaign (SSC) guideline-compliant e-sepsis registry stratified by focus of infection. The prospective observational study recruited 1009 adult sepsis patients presenting to the emergency department at the center based on Sepsis-2 criteria for a period of three years. Of the patients, 41% were between 61 and 80 years with a mean age of 57.37 ± 13.5%. A total of 13.5% (136) was under septic shock and in-hospital mortality for the study cohort was 25%. The 3 h and 6 h bundle compliance rates observed were 37% and 49%, respectively, without significant survival benefits. Predictors of mortality among patients with bloodstream infections were septic shock (p = 0.01, OR 2.4, 95% CI 1.23-4.79) and neutrophil-to-lymphocyte ratio (p = 0.008, OR 1.01, 95% CI 1.009-1.066). The presence of Acinetobacter (p = 0.005, OR 4.07, 95% CI 1.37-12.09), Candida non-albicans (p = 0.001, OR16.02, 95% CI 3.0-84.2) and septic shock (p = 0.071, OR 2.5, 95% CI 0.97-6.6) were significant predictors of mortality in patients with community-acquired pneumonia. The registry has proven to be a key data source detailing regional microbial etiology and clinical outcomes of adult sepsis patients, enabling comprehensive evaluation of regional community-acquired sepsis to tailor institutional sepsis treatment protocols.

Adverse events associated with Covishield vaccination among healthcare workers in a tertiary hospital in South India.

Background: Vaccination is the most important prophylactic measure taken to curb COVID-19 pandemics. This study was undertaken to throw light on the safety of Covishield vaccine among health care workers (HCWs) and to assess the co-variates associated with incidence of adverse events. Methods: This prospective observational study was conducted in a tertiary care center in South India as part of the HCW vaccination drive. All consenting HCWs who received the first dose of Covishield vaccine and developed ADRs were included in this study. After vaccination, all beneficiaries were monitored for AEFI for a period of half an hour and later followed up through telephone and google survey forms on day 2 and day 7 of vaccination. The data was subsequently collated into spreadsheet format and analyzed. Results: The study included 1264 consenting healthcare workers who were predominantly youth, aged 15-24 years (n = 583, 46 %) and with a female preponderance of 76 % (n = 960). Past history of COVID-19 infections was reported among 4.6 % (58) of the study population. Postvaccination symptoms were majorly reported during the first (40 %) and second day (44 %) after vaccination with a high prevalence of both local (n = 1083, 85 %) and systemic symptoms (n = 1065, 84 %). The mean duration of symptoms was observed to be 1.4 ± 0.81 days post vaccination. Symptoms were observed significantly high among females (76.7 %, p = 0.013). The prevalence of systemic (88 % vs 80 %) (p < 0.001) and allergic symptoms (7 % vs 3 %; p = 0.03) were observed to be significantly high among respondents with <25 years of age. The systemic and allergic symptoms following vaccination were reported to be low among healthcare workers who had a previous history of COVID-19 infection. Conclusion: COVID vaccination has been observed to be safe and well tolerated with more systemic symptoms reported among younger age group and females.

A quality improvement initiative to improve the appropriateness of candidemia management by the implementation of a comprehensive candidemia care bundle at a tertiary care hospital in South India: Results of a quasi-experimental study.

ABSTRACT: 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.

A comparison of clinical outcomes between vaccinated and vaccine-naive patients of COVID-19, in four tertiary care hospitals of Kerala, South India.

THE PROBLEM CONSIDERED: This multi-centric study analyzed data of COVID-19 patients and compared differences in symptomatology, management, and outcomes between vaccinated and vaccine-naive patients. METHODS: All COVID-19 positive individuals treated as an in-or out-patient from the 1stMarch to 15th May 2021 in four selected study sites were considered for the study. Treatment details, symptoms, and clinical course were obtained from hospital records. Chi-square was used to test the association of socio-demographic and treatment variables with the vaccination status and binary logistic regression were used to obtain the odds ratio with a 95% confidence interval. RESULTS: The analysis was of 1446 patients after exclusion of 156 with missing data of which males were 57.3% and females 42.7%. 346 were vaccinated; 189 received one dose and 157 both doses. Hospitalization was more in vaccinated (38.2% vs 27.4%); ICU admissions were less in vaccinated (3.5% vs 7.1%). More vaccinated were symptomatic (OR = 1.5); half less likely to be on non-invasive ventilation (OR = 0.5) while vaccine naive patients had 4.21 times the risk of death. CONCLUSION: Severe infection, duration of hospital stays, need for ventilation and death were significantly less among vaccinated when compared with vaccine naive patients.

Validation of MuLBSTA score to derive modified MuLB score as mortality risk prediction in COVID-19 infection.

COVID-19pandemic was started in December 2019. It has variable presentation from mild sore throat to severe respiratory distress. It is important to identify individuals who are likely to worsen. The Research question is how to identify patients with COVID-19 who are at high risk and to predict patient outcome based on a risk stratification model? We evaluated 251 patients with COVID-19 in this prospective inception study. We used a multi-variable Cox proportional hazards model to identify the independent prognostic risk factors and created a risk score model on the basis of available MuLBSTA score. The model was validated in an independent group of patients from October2020 to December 2021. We developed a combined risk score, the MuLBA score that included the following values and scores: Multi lobar infiltrates (negative0.254, 2), lymphopenia (lymphocytes of <0.8x109 /L, negative0.18,2), bacterial co- infection (negative, 0.306,3). In our MuLB scoring system, score of >8 was associated with high risk of mortality and <5 was at mild risk of mortality (P < 0.001). The interpretation was that The MuLB risk score model could help to predict survival in patients with severe COVID-19 infection and to guide further clinical research on risk-based treatment.

Universal screening for SARS-CoV-2 in pregnant women using a combination of antigen and RT-PCR testing.

Not available.

Evaluating the measures taken to contain a Candida auris outbreak in a tertiary care hospital in South India: an outbreak investigational study.

BACKGROUND: Candida auris infections are an emerging global threat with poor clinical outcome, high mortality rate, high transmission rate and outbreak potential. The objective of this work is to describe a multidisciplinary approach towards the investigation and containment of a Candida auris outbreak and the preventive measures adopted in a resource limited setting. METHODS: This outbreak investigational study was conducted at a 1300-bedded tertiary care academic hospital in South India. The study included 15 adult inpatients with laboratory confirmed Candida auris isolates. The outbreak cluster was identified in adult patients admitted from September 2017 to 2019. The system response consisted of a critical alert system for laboratory confirmed Candida auris infection and multidisciplinary 'Candida auris care team' for patient management. The team implemented stringent Infection Prevention and Control (IPC) measures including patient cohorting, standardized therapy and decolonization, staff training, prospective surveillance and introduction of Candida auris specific care bundle. RESULTS: Two outbreak clusters were identified; first cluster occurring between October and November 2017 and the second cluster in May 2018. The cohorts consisted of 7 and 8 Candida auris positive patients in the first and second waves of the outbreak respectively with a total survival rate of 93% (14/15). Deployment of containment measures led to gradual decline in the incidence of adult Candida auris positive cases and prevented further cluster formation. CONCLUSIONS: The sustained implementation of guideline and evidence-based IPC measures and training of healthcare workers for improving awareness on systematically following standardized protocols of Candida auris related IPC practices successfully contained Candida auris outbreaks at our hospital. This demonstrates the feasibility of establishing a multidisciplinary model and bundling of practices for preventing Candida auris outbreaks in a Low- and Middle-income country.

Antimicrobial Stewardship and Its Impact on the Changing Epidemiology of Polymyxin Use in a South Indian Healthcare Setting.

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.

Role of endoscopic ultrasound guided fine needle aspiration/biopsy in the evaluation of intra-abdominal lymphadenopathy due to tuberculosis.

BACKGROUND: Intra-abdominal lymphadenopathy due to tuberculosis (TB) poses a diagnostic challenge due to difficulty in tissue acquisition. Although endoscopic ultrasound guided fine needle aspiration/biopsy (EUS-FNA/B) has shown promise in the evaluation of mediastinal lymph nodes, its role in the evaluation of intra-abdominal lymphadenopathy is not clear. AIM: To assess the role of EUS-FNA/B in the evaluation of intra-abdominal lymphadenopathy due to TB. METHODS: This was a retrospective study where patients with intra-abdominal lymphadenopathy who underwent evaluation with EUS-FNA/B were included. TB was diagnosed if the patient had any one of the following: (1) Positive acid fast bacilli (AFB) stain/TB GeneXpert/TB-polymerase chain reaction/AFB culture of tissue sample; and (2) Positive Mantoux test and response to anti-tubercular therapy. EUS-FNA reports, clinical reports and imaging characteristics of patients were recorded for a detailed analysis of patients with TB. RESULTS: A total of 149 patients underwent an EUS-FNA/B from lymph nodes (mean age 51 ± 17 years, M:F = 1.2). Benign inflammatory reactive changes were seen in 45 patients (30.2%), while 54 patients (36.2%) showed granulomatous inflammation with/without caseation. Among these, 51 patients (94.4%) were confirmed to have TB as per pre-defined criteria. Patients with TB were more likely to have hypoechoic and matted nodes [40 patients (67.7%)]. EUS-FNA/B was found to have a sensitivity and specificity of 86% and 93% respectively, with a diagnostic accuracy of 88% in the evaluation of intra-abdominal lymphadenopathy due to TB. CONCLUSION: EUS-FNA/B has a high diagnostic yield with a good sensitivity and specificity in the evaluation of intra-abdominal lymphadenopathy due to TB. However, the validity of these findings in populations with low prevalence of TB needs further evaluation.

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.

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.

Efficacy & safety of Carica papaya leaf extract (CPLE) in severe thrombocytopenia (≤30,000/µl) in adult dengue - Results of a pilot study.

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.

Waiting for Godot: A cross sectional survey based analysis of the hydroxychloroquine prophylaxis strategy against COVID-19 in India.

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.

Myocardial injury after noncardiac surgery-incidence and predictors from a prospective observational cohort study at an Indian tertiary care centre.

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 < .01), 2 (P < .001), and 12 (P < .001) times, respectively, more likely to develop MINS than others. Patients with heart rates ≥96 bpm before induction of anesthesia were significantly associated with MINS (P = .005) and mortality (P = .02). The 30-day mortality in MINS cohort was 11.7% (22/188, 95% CI 7.5%-17.2%) vs 2.5% (23/887, 95% CI 1.7%-3.9%) in patients without MINS (P < .001). ECG changes (P = .002), peak troponin values >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 < .001), with decreased mortality in patients who took post-op ASA (Aspirin) or Clopidogrel. Mortality among MINS patients with post-op ASA intake is 6.7% vs 12.1% among MINS patients without post-op ASA intake. Mortality among MINS patients with post-op Clopidogrel intake is 10.5% vs 11.8% among MINS patients without post-op Clopidogrel intake.A higher (17.5%, 95% CI 15-19%) incidence of MINS was observed in our patient cohort with significant association with 30-day mortality. Serial postoperative monitoring of troponin following noncardiac surgery as standard of care, would identify "at risk" patients translating to improved outcomes.

A Quality Improvement Initiative to Reduce "Out-of-ICU" Cardiopulmonary Arrests in a Tertiary Care Hospital in India: A 2-Year Learning Experience.

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.