Intravenous BCAA infusion does not lead to a sustained recovery from overt HE in ACLF – An open label randomized clinical trial

Background –Hepatic encephalopathy(HE) in acute-on-chronic liver failure(ACLF) is associated with significant morbidity and mortality. We conducted a prospective, randomized controlled clinical trial to study efficacy of intravenous branched chain amino acids(IV-BCAA) with lactulose versus lactulose alone for improvement in HE at 24h, day 3 & day 7. Primary outcome was improvement in encephalopathy by ≥ 1 grade at 72 hours. Patients and Methods –EASL defined ACLF patients with overt HE were assessed and randomized into experimental arm (IV-BCAA - 500mL/day for 3 days + Lactulose;n=39) and comparator arm (Lactulose alone;n=37). Six patients developed COVID-19 after randomization & were excluded (4-experimental arm & 2-comparator arm). Results –Of 222 screened patients, 70 (35 in each arm) were included in analysis. Baseline characteristics including HE grade (2.9 ± 0.7 vs 2.8 ± 0.7;P = 0.86) and CLIF-C ACLF score (54.2 ± 5.6 vs 54.8 ± 5.7;P = 0.65) were similar. Overall survival was 40% at 28 days (48.5% vs 31.4%;P=0.14). Improvement in HESA by ≥1 grade at 24h occurred in 14 patients (40%) in BCAA arm and 6 patients (17.1%) in control group (P=0.03) which translated to shorter ICU stay. Median change in HESA at 24h was more in BCAA arm than control arm(P=0.006) which was not sustained at day 3 or 7. Ammonia levels did not correlate with grade of HE (Spearman's correlation coefficient(ρ) = - 0.0843;P=0.29). Conclusion Intravenous BCAA does not lead to a sustained improvement in HE grade in ACLF. Trial registration no NCT04238416 (clinicaltrials.gov)

Reporting adverse events of ChAdOx1 nCoV-19 coronavirus vaccine (Recombinant) among the vaccinated healthcare professionals: A cross-sectional survey.

Background & objectives: The safety of the ChAdOx1 nCoV-19 vaccine is a cause of concern for many who have been vaccinated. The people have multiple concerns and fear regarding the adverse events of the vaccine. Thus, this study was undertaken to establish the safety profile of ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant) among the healthcare professionals. Methods: This was a descriptive cross-sectional survey. After taking clearance from the institutional ethics committee 1500 healthcare professionals, who had their vaccination in the past two weeks were selected. They were provided with an online survey proforma regarding adverse events following immunization (AEFIs) of COVID-19 vaccine developed using google forms with an informed consent form affixed to it. Results: A total of 1036 individuals participated in the study. The mean and median (inter quartile range) age of the participants was 37.7 ±11.25 and 35 (29-46) yr, respectively. Of these, 52.1 per cent were female, 29.3 per cent were doctors, 33.4 per cent were nurses and 9.5 per cent were paramedical staff. Forty six per cent participants experienced one or more minor AEFIs such as pain, tenderness, redness, etc. at the injection site. Fatigue (31.75%), generalized feeling of unwell (28.57%), muscle pain (23.16%) and fever (21.71%) were the most commonly reported systemic AEFIs followed by headache (20.07%), dizziness (10.03%) and joint pains (15.25%). Most of them experienced these AEFIs within 24 h of the first dose of administration. About 42 per cent of the participants took oral antipyretics/analgesics for managing the AEFIs. Interpretation & conclusions: ChAdOx1 nCoV-19 Corona Virus Vaccine was found to be associated with mild local and systemic AEFIs that were more common after the first dose as compared to the second dose. There adverse events could be dealt with oral over-the-counter medications, with no requirement of hospitalization.

Incidence & outcomes of clinically significant bleeding events in critically ill COVID-19 patients receiving Therapeutic dose AntiCoagulanTs: A retrospective cohort study (INTerACT study).

Background & objectives: The high mortality associated with the thrombotic events in hospitalized COVID-19 patients resulted in the usage of anticoagulants in varying doses. Whether high-dose anticoagulants have led to better outcomes or higher incidence of clinically significant bleeding events is debatable. Thus, this study was conducted to find the incidence of clinically significant bleeding events in moderate-to-severe COVID-19 ARDS (acute respiratory distress syndrome) patients on therapeutic anticoagulation and their outcomes. Methods: In this retrospective, single-centre study of 155 critically ill COVID-19 patients, the incidence of clinically significant bleeding was observed. Multivariate regression models were used to evaluate the association between anticoagulant regimen, coagulation and inflammatory markers with the incidence of bleeding and thrombotic events. Results: The incidence of clinically relevant non-major bleeding was 33.54 per cent (26.17-41.46%) and major bleeding was 9.03 per cent (5.02-14.69%). The anticoagulation intensity at baseline had a high odds of major bleeding when enoxaparin and dual antiplatelet therapy were used together [adjusted odds ratio OR of 434.09 (3.81-49502.95), P<0.05]. At admission, bleeders had a poorer PaO2/FiO2 ratio with more patients on invasive ventilation. At the time of bleeding, the bleeders had a higher D-dimer, ferritin, C-reactive protein and procalcitonin compared to non-bleeders. The subhazard ratio for death in bleeders was 3.35 (95% confidence interval, 1.97-5.65; P<0.001). Interpretation & conclusions: The incidence of bleeding in critically ill COVID-19 patients on therapeutic anticoagulation may increase with the severity of the disease as well as with concurrent use of dual antiplatelets. Major bleeding may also contribute to higher mortality.

Evaluation of utility and usefulness of webinars on COVID-19 management: a questionnaire-based survey

BackgroundThe COVID-19 pandemic and its consequent “social distancing” has fueled the use of social media platforms for educational purposes. Since the start of the pandemic, a plethora of experts and self-proclaimed experts have been keenly delivering webinars on COVID. This begs the question “Do webinars on COVID-19 really help in the improvement of knowledge base or management skills?”. The questionnaire was designed to assess information regarding COVID-webinars and their usefulness from the end-user standpoint. The response to the questions was measured using a 4- or 5-point Likert scale. The survey was open for a 4-week period with the extension of 1 week.ResultsThe response rate was 54% as 270 out of 500 participants responded to the questionnaire. The majority of the respondents were anesthesiologists in-training, post-graduates, fellows, and seniors belonging to tertiary care settings with fewer percentages belonging to physicians and others. Most of the doctors had attended an average of 2 webinars per week. The tests of model effects showed a significant negative correlation of webinar quality ratings for district hospital healthcare setting of the attendees (of p value of 0.013) and for the number of COVID-related webinars attended per week (p value of 0.009).ConclusionsMost respondents had favorable perceptions of webinars happening during the pandemic. However, there is a need for improvisation in the volume of webinars, target-audience-based delivery, and participant interaction to add value to this new dimension of teaching-learning.

Combined Analysis of Anti SARS-CoV-2 IgG and IgM Responses in COVID19 Patients in India.

Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a global health problem, India being the second most affected country. The kinetics of antibody response to SARS-CoV-2 in Indian population is not studied yet. To understand serological response in relation to age, gender, time period and severity of disease, Roche Elecsys anti-SARS-CoV-2 test was used which analysed both IgM and IgG. One hundred and three COVID-19 patients were enrolled. Seropositivity was seen in 64% of patients, with 33% at ≤ 7 days, 62% between 8 and 15 days and 81% at ≥ 16 days from the time of admission. Men (65%) showed higher antibody response than women (59%), whereas no difference was observed in seropositivity with respect to age of the patients. Dynamics of antibody responses revealed individual variations. Patients in ICU had higher antibody reactivity with 67% positivity as compared to 60% positivity in non-ICU patients. Kinetics of antibody response during COVID-19 disease varied in relation to gender, age, time period and severity and these factors might play an important role in treatment and control of COVID-19.

Preparing Intensive Care Unit in Resource-Constraint Setting Amid COVID-19 Pandemic: Our Experience and Review.

COVID-19 pandemic is an emerging, rapidly evolving public health emergency where a nation's health-care system can face a marked surge in demand for intensive care unit (ICU) beds and organ support. In regions with insufficient medical resources, it may further aggravate the existing shortage, limiting an ICU's ability to provide the normal standard of care. It can present ethically or legally demanding questions about how to prioritize the allocation of life-saving medical resources. In developing countries like India, still many hospitals are challenged by competing priorities and remain underprepared. In the wake of COVID-19 pandemic, to guide the intensive care disaster planners in regions with low resources and to ensure ICU readiness, this review shares our experience and strategies for preparing ICU with existing and alternative resources, focusing on space, equipment, and health-care workers' safety and training.

Impaired anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with diabetes mellitus: A preliminary report.

BACKGROUND AND AIMS: Patients with diabetes mellitus (DM) often demonstrate impaired antibody response to influenza/hepatitis B vaccines. Hence, we compared anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with and without type 2 diabetes mellitus (T2DM). METHODS: Records of non-severe COVID-19 patients admitted at our institution between April 10, 2020 and May 20, 2020 were retrieved. Qualitative detection of total (IgG + IgM) anti-SARS-CoV-2 antibody was performed using electrochemiluminescence immunoassay in plasma samples collected at least 14 days post-polymerase chain reaction (PCR) confirmation of diagnosis. RESULTS: Thirty-one non-severe COVID-19 patients were included. Nine patients (29%) had T2DM with mean HbA1c at admission of 8.3 ± 1.0%. Anti-SARS-CoV-2 antibody was estimated at a median of 16 (14-17) days post-PCR confirmation of COVID-19 diagnosis. Only three patients (10%) were seronegative, and all had T2DM. Patients with T2DM were more likely to have non-detectable anti-SARS-CoV-2 antibodies than those without DM (p = 0.019). CONCLUSIONS: COVID-19 patients with T2DM may not undergo seroconversion even after two weeks of diagnosis. Impaired seroconversion could theoretically increase the risk of reinfections in patients with DM. However, the finding requires validation in large-scale studies involving serial estimations of anti-SARS-CoV-2 antibodies in patients with and without DM.

Demographic & clinical profile of patients with COVID-19 at a tertiary care hospital in north India.

BACKGROUND & OBJECTIVES: The COVID-19 pandemic emerged as a major public health emergency affecting the healthcare services all over the world. It is essential to analyze the epidemiological and clinical characteristics of patients with COVID-19 in different parts of our country. This study highlights clinical experience in managing patients with COVID-19 at a tertiary care centre in northern India. METHODS: Clinical characteristics and outcomes of consecutive adults patients admitted to a tertiary care hospital at Chandigarh, India, from April 1 to May 25, 2020 were studied. The diagnosis of SARS-CoV-2 infection was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) on throat and/or nasopharyngeal swabs. All patients were managed according to the institute's consensus protocol and in accordance with Indian Council of Medical Research guidelines. RESULTS: During the study period, 114 patients with SARS-CoV-2 infection were admitted. The history of contact with COVID-19-affected individuals was available in 75 (65.8%) patients. The median age of the patients was 33.5 yr (13-79 yr), and there were 66 (58%) males. Of the total enrolled patients, 48 (42%) were symptomatic. The common presenting complaints were fever (37, 77%), cough (26, 54%) and shortness of breath (10, 20.8%). Nineteen (17%) patients had hypoxia (SpO2<94%) at presentation and 36 (31%) had tachypnoea (RR >24). Thirty four (29.8%) patients had an accompanying comorbid illness. Age more than 60 yr and presence of diabetes and hypertension were significantly associated with severe COVID-19 disease. Admission to the intensive care unit (ICU) was needed in 18 patients (52%), with three (2.6%) patients requiring assisted ventilation. Mortality of 2.6 per cent (3 patients) was observed. INTERPRETATION & CONCLUSIONS: Majority of the patients with COVID-19 infection presenting to our hospital were young and asymptomatic. Fever was noted only in three-fourth of the patients and respiratory symptoms in half of them. Patients with comorbidities were more vulnerable to complications. Triaged classification of patients and protocol-based treatment resulted in good outcomes and low case fatality.

COVID-19 associated variations in liver function parameters: a retrospective study.

BACKGROUND: Characteristics of laboratory findings of COVID-19 patients are of great significance for diagnosis and treatment. Studies that have analysed the variations in hepatic profile in correlation with the inflammatory markers in SARS-CoV-2 are limited. METHODS: We retrospectively analysed liver function tests and inflammatory markers of 170 admitted patients with confirmed COVID-19 in the tertiary care centre, Post Graduate Institute of Medical Education and Research (PGIMER), India, using Roche Cobas Autoanalyzer. RESULTS: Number of patients with normal liver enzyme levels were 63 (41.5%), while with raised levels of any of the liver enzymes were 89 (58.5%), out of which 43 (48.31%) had liver injury which manifested as increased severity in terms of intensive care unit (ICU) requirement (p=0.0005). Significantly raised levels of liver enzymes and liver injury were observed with age (p<0.0001) and in males (p=0.004). Significantly decreased levels of albumin and total proteins and increased levels of total bilirubin (p<0.0001) were seen in patients with abnormal liver enzyme levels and liver injury as compared to patients with normal levels. Significant increase in the levels of alanine transaminase and gamma-glutamyl transferase was seen on the 7th day, CRP and ferritin (p<0.0001) peaks were observed on 2nd and 3rd day respectively. A significant positive correlation was found between the levels of these inflammatory markers and liver function parameters. CONCLUSIONS: More than half of patients admitted to the hospital with SARS-CoV-2 infection had an abnormal liver function which was found to be associated with raised levels of inflammatory markers. Significantly higher proportions of patients with abnormal liver function were elderly and males and were at higher risk of progressing to severe disease.