Favipiravir for treating COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the health workforce and societies worldwide. Favipiravir was suggested by some experts to be effective and safe to use in COVID-19. Although this drug has been evaluated in randomized controlled trials (RCTs), it is still unclear if it has a definite role in the treatment of COVID-19. OBJECTIVES: To assess the effects of favipiravir compared to no treatment, supportive treatment, or other experimental antiviral treatment in people with acute COVID-19. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, MEDLINE, Embase, the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease, and three other databases, up to 18 July 2023. SELECTION CRITERIA: We searched for RCTs evaluating the efficacy of favipiravir in treating people with COVID-19. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures for data collection and analysis. We used the GRADE approach to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 25 trials that randomized 5750 adults (most under 60 years of age). The trials were conducted in Bahrain, Brazil, China, India, Iran, Kuwait, Malaysia, Mexico, Russia, Saudi Arabia, Thailand, the UK, and the USA. Most participants were hospitalized with mild to moderate disease (89%). Twenty-two of the 25 trials investigated the role of favipiravir compared to placebo or standard of care, whilst lopinavir/ritonavir was the comparator in two trials, and umifenovir in one trial. Most trials (24 of 25) initiated favipiravir at 1600 mg or 1800 mg twice daily for the first day, followed by 600 mg to 800 mg twice a day. The duration of treatment varied from five to 14 days. We do not know whether favipiravir reduces all-cause mortality at 28 to 30 days, or in-hospital (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.49 to 1.46; 11 trials, 3459 participants; very low-certainty evidence). We do not know if favipiravir reduces the progression to invasive mechanical ventilation (RR 0.86, 95% CI 0.68 to 1.09; 8 trials, 1383 participants; very low-certainty evidence). Favipiravir may make little to no difference in the need for admission to hospital (if ambulatory) (RR 1.04, 95% CI 0.44 to 2.46; 4 trials, 670 participants; low-certainty evidence). We do not know if favipiravir reduces the time to clinical improvement (defined as time to a 2-point reduction in patients' admission status on the WHO's ordinal scale) (hazard ratio (HR) 1.13, 95% CI 0.69 to 1.83; 4 trials, 721 participants; very low-certainty evidence). Favipiravir may make little to no difference to the progression to oxygen therapy (RR 1.20, 95% CI 0.83 to 1.75; 2 trials, 543 participants; low-certainty evidence). Favipiravir may lead to an overall increased incidence of adverse events (RR 1.27, 95% CI 1.05 to 1.54; 18 trials, 4699 participants; low-certainty evidence), but may result in little to no difference inserious adverse eventsattributable to the drug (RR 1.04, 95% CI 0.76 to 1.42; 12 trials, 3317 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: The low- to very low-certainty evidence means that we do not know whether favipiravir is efficacious in people with COVID-19 illness, irrespective of severity or admission status. Treatment with favipiravir may result in an overall increase in the incidence of adverse events but may not result in serious adverse events.

Patient Characteristics and Outcomes in Necrotizing Soft-tissue Infections: Results from a Prospective Cohort Study in a Tertiary Care Center Intensive Care Unit in South India.

Background: Necrotizing soft tissue infections (NSTIs) are life-threatening infections characterized by progressive destruction of muscle, fascia, and overlying subcutaneous tissue. Prospective studies in the field are few, and data from the Indian subcontinent are bleak. Prompt diagnosis and timely treatment are critical for optimal outcomes. The aims of this study are to provide detailed information on the clinical profile of patients with NSTIs and to identify predictors of mortality in order to pick up reversible factors that may improve outcomes. Materials and methods: This study was a prospective cohort study of adult patients with NSTIs in a tertiary center in South India. All patients who were admitted to the surgical intensive care unit (ICU) of the institute with a diagnosis of NSTI were screened and enrolled. All patients were managed according to the local protocol for treatment of NSTIs and intensive care support. Results: In our cohort of patients, simple and multiple logistic regression analysis showed that four factors, namely, AKIN stage 3, shock, need for mechanical ventilation for more than 3 days, and low serum albumin values were found to be significantly associated with higher mortality. Conclusion: The successful management of these patients calls for early diagnosis, resuscitation, surgical debridement, appropriate and timely antibiotics, and early ventilatory weaning before multi-organ failure associated with shock and AKI occurs. How to cite this article: Kurian GP, Korula PJ, Jacob JM, Desha AMK, Karuppusami R, Kandasamy S. Patient Characteristics and Outcomes in Necrotizing Soft-tissue Infections: Results from a Prospective Cohort Study in a Tertiary Care Center Intensive Care Unit in South India. Indian J Crit Care Med 2022;26(4):452-456.

Perioperative factors impacting intensive care outcomes following Whipple procedure: A retrospective study.

BACKGROUND AND AIMS: Whipple procedure is associated with perhaps the most perioperative morbidity and mortality amongst surgical procedures. Current data regarding their ICU profile and outcomes are lacking. Thus, in the present study, we aimed to determine perioperative factors affecting patient-centred outcomes following the Whipple procedure. METHODS: In a cohort of patients undergoing pylorus-sparing pancreaticoduodenectomies, we strove to determine perioperative variables that may impact outcomes. Unfavourable outcomes (composite of mortality, prolonged ICU stay of more than 14 days or ICU readmission) of patients who underwent the procedure were recorded and logistic regressions analysis of significant variables conducted. RESULTS: Around 68 patients recruited over a 20-month period which included 57 males (83.8%); mean age was 53.4(±11.2) with mean acute physiology and chronic health evaluation (APACHE) II score12.5 (±6.1). Nineteen patients remained intubated at the end of procedures (27.9%). Median ICU stay was 2 days (IQR 2-3). Unfavourable ICU outcomes were 14 in number (20.6%) and 2 (2.9%) hospital deaths occurred. Pulmonary complications occurred in 12 patients (17.7%) and non-pulmonary complications occurred in 41 patients (60.3%). In a multiple logistic regression analysis, the APACHE score 1.34 (1.09-1.64) and pulmonary complications 17.3 (2.1-145) were variables that were identified as predictors of unfavourable outcomes. CONCLUSION: The APACHE II score may reliably predict adverse outcomes following Whipple procedure. Although non-pulmonary complications are common, pulmonary complications in these patients adversely impact patient outcomes.

An observational study on the practice of noninvasive ventilation at a tertiary level Australian intensive care unit.

BACKGROUND: Failure of Non-Invasive Ventilation (NIV) is associated with increased morbidity and mortality among critically ill patients. Although there is evidence of association between disease related factors and NIV failure, it is unclear whether factors related to NIV application contribute to NIV failure. OBJECTIVES: To evaluate NIV failure rate and factors associated with NIV failure. DESIGN, SETTINGS AND OUTCOMES: Prospective, observational, pilot study conducted in a 23-bed, tertiary care Intensive Care Unit (ICU). NIV failure was defined as application of NIV resulting in intubation or death in ICU. RESULTS: Amongst 238 patients admitted with respiratory failure, NIV was administered to 60 patients (34 males, 26 females) for a total of 70 application episodes. The etiology of respiratory failure included acute pulmonary edema (28.6%), acute lung injury (22.9%) and pneumonia (15.7%). The mean (SD) age was 62 (17.6) years, BMI 32.0 (8.5) kg/m2 and median APACHE-II score 17.5 (14.0-23.8). NIV failure occurred in 22 out of 70 applications (31.4% [95%CI 20.0-43.0]). NIV failure assessed by simple logistic regression analysis, was associated with admission diagnosis (OR 6.0, 95%CI: 1.3-28.7, p = 0.03), use of bi-level NIV-PS (OR 5.00, 95%CI: 1.04-24.1, p = 0.04), presence of nasogastric tube (OR 6.20, 95%CI: 1.9-19.8, p < 0.01) and with short NIV breaks in the 2nd 24-hours (OR 0.96, 95%CI: 0.91-0.99, p = 0.04). CONCLUSION: NIV failure was observed in 31.4%. Factors associated with NIV failure were etiology of respiratory illness, type of NIV support and short NIV breaks, presumably reflecting illness severity or progress of disease. The presence of a nasogastric tube during application of NIV may adversely impact NIV application.

Will ceftazidime/avibactam plus aztreonam be effective for NDM and OXA-48-Like producing organisms: Lessons learnt from In vitro study.

Introduction: Carbapenem resistance (CR) in Klebsiella pneumoniae is mainly mediated by bla NDM and bla OXA-48 carbapenemases. Newer Food and Drug Administration-approved antimicrobial ceftazidime/avibactam (C/A) has a potent activity against bla OXA-48-like producers. However, its activity is limited in organisms co-producing bla NDM and bla OXA-48-like. Addition of aztreonam (ATM) to C/A potentially expands the spectrum of coverage for carbapenemase co-producers. With this, we aimed to determine the synergistic activity of combination of C/A plus ATM against bla NDM, bla OXA-48-like and co-producers of bla NDM + bla OXA-48-like producing CR Klebsiella pneumoniae (CRKp). Materials and Methods: A total of 12 isolates of CRKp-harbouring genes encoding bla NDM and bla OXA-48-like were tested. Minimum inhibitory concentrations (MICs) were determined for several antimicrobial agents, including C/A (0.5-8 µg/ml) by broth microdilution method. Checkerboard assay was performed for the combination of C/A plus ATM at varying concentrations. Fold differences in the MIC of C/A with and without addition of ATM were determined to infer synergistic effects. Results: MIC of C/A and ATM ranged from 0.5 to >8 µg/ml and 64 to 2048 µg/ml, respectively. Two isolates were susceptible to C/A with MIC of 0.5 and 1 µg/ml, while others were resistant with MIC of >8 µg/ml. Synergistic effects of >8-fold MIC difference in C/A MIC were noted with addition of ATM at 4 µg/ml. This was observed for all CRKp with profiles of bla NDM, bla OXA-48-like and co-producers of bla NDM + bla OXA-48-like genes, which was a promising effect. Notably, all five of the colistin-resistant CRKp were inhibited with >8-fold MIC difference in the combination of C/A plus ATM at 4 µg/ml. Conclusion: With the increasing burden of CRKp, the use of C/A with ATM combination seems to be very promising, especially for bla NDM, bla OXA-48-like and co-producers of bla NDM + bla OXA-48like carbapenemases.

Feasibility and Accuracy of a Nonmedical Research Person in Assimilation and Calculation of Acute Physiologic Assessment and Chronic Health Evaluation Scores in an Indian Intensive Care Unit.

BACKGROUND: The Physiologic Assessment and Chronic Health Evaluation (APACHE) score assimilation and calculation, as well as other demographic data collection, is inherent to research and nonresearch related needs of intensive care. There may be a role for well-trained nonmedical personnel to collect this vital material to enhance research and the standard of care in the Intensive Care Units (ICUs) in countries that are poorly funded and resourced in terms of medical personnel. AIMS: The aim of this study is to verify the interrater reliability of a trained nonmedical personnel and ICU trainee in the collection and calculation APACHE scores. MATERIALS AND METHODS: In a prospective study, two raters who were blinded, one a trained nonmedical ward clerk and another an ICU trainee, assimilated data and calculated APACHE scores for 60 consecutive patients admitted to two tertiary mixed ICUs (with a total of 19 beds). Primary outcomes were to assess interrater and interclass correlation as well as the agreement of scores between the two raters. RESULTS: There was an excellent correlation of APACHE scores (Kappa coefficient of 0.92) and Bland-Altman plot depicted overall good agreement with low bias between raters. CONCLUSIONS: A well-trained and supervised nonmedical research person can assimilate and calculate APACHE II scores with good agreement with an ICU trainee. This may help in deriving data from medically understaffed ICUs in India, thus promoting much-needed research from such ICUs.

Transient cortical blindness following a Hangman's fracture: a case report and review of literature.

We describe a case with transient cortical blindness after trauma with no obvious structural damage to the vertebral artery in the presence of a C2 spondylolisthesis. A patient complaining of blindness in a setting of polytrauma should always alert the possibility of a cervical spine injury with vertebral artery ischaemia.