Co-administration of AYUSH 64 as an adjunct to standard of care in mild and moderate COVID-19: A randomized, controlled, multicentric clinical trial.

OBJECTIVE: Evaluate the efficacy of AYUSH 64, a standard polyherbal Ayurvedic drug in COVID-19. METHODS: During the first pandemic wave, 140 consenting and eligible hospitalized adult participants with mild-moderate symptomatic disease (specific standard RT-PCR assay positive) were selected as per a convenience sample, and randomized (1:1 ratio) to an open-label (assessor blind) two-arm multicentric drug trial; standard of care (SOC as per Indian guidelines) versus AYUSH 64 combined with SOC (AYUSH plus). Participants were assessed daily and discharged once clinical recovery (CR, primary efficacy) was achieved which was based on a predetermined set of criteria (resolution of symptoms, normal peripheral oximetry, and negative specific RT-PCR assay). Each participant was followed using an indigenous software program(mobile phone) and completed a 12-week study period. The dose of AYUSH 64 was 2 tablets oral, 500 mg each, bid for 12 weeks (AYUSH plus only). Significant P was <0.05 (two-sided). On randomization, the groups were found well matched. RESULTS: The mean interval time from randomization to CR was significantly superior in the AYUSH plus group [mean 6.45 days versus 8.26 days, 95% Confidence Interval of the difference -3.02 to -0.59 (P = 0.003, Student's 't test] as per-protocol analysis (134 participants); significant (P = 0.002) on an intention to treat analysis. 70% of the participants in AYUSH plus recovered during the first week (P = 0.046, Chi-square) and showed a significantly better change in physical health, fatigue, and quality of life measures. 48 adverse events, mostly mild and gut related, were reported by each group. There were 20 patient withdrawals (8 in AYUSH plus) but none due to an AE. There were no deaths. Daily assessment (hospitalization) and supervised drug intake ensured robust efficacy data. The open-label design was a concern (study outcome). CONCLUSIONS: AYUSH 64 in combination with SOC hastened recovery, reduced hospitalization, and improved health in COVID-19. It was considered safe and well-tolerated. Further clinical validation (Phase III) is required. TRIAL REGISTRATION: CTRI/2020/06/025557.

Effect of ghrelin on mortality and cardiovascular outcomes in experimental rat and mice models of heart failure: a systematic review and meta-analysis.

BACKGROUND: Heart failure (HF) continues to be a challenging condition in terms of prevention and management of the disease. Studies have demonstrated various cardio-protective effects of Ghrelin. The aim of the study is to determine the effect of Ghrelin on mortality and cardiac function in experimental rats/mice models of HF. METHODS: Data sources: PUBMED, Scopus. We searched the Digital Dissertations and conference proceedings on Web of Science. Search methods: We systematically searched for all controlled trials (upto November 2014) which assessed the effects of Ghrelin (irrespective of dose, form, frequency, duration and route of administration) on mortality and cardiac function in rats/ mice models of HF. Ghrelin administration irrespective of dose, form, frequency, duration and route of administration. Data collection and analysis: Two authors independently assessed each abstract for eligibility and extracted data on characteristics of the experimental model used, intervention and outcome measures. We assessed the methodological quality by SYRCLE's risk of bias tool for all studies and the quality of evidence by GRADEpro. We performed meta-analysis using RevMan 5.3. RESULTS: A total of 325 animals (rats and mice) were analyzed across seven studies. The meta-analysis revealed that the mortality in Ghrelin group was 31.1% and in control group was 40% (RR 0.83, 95% CI 0.46 to 1.47) i.e Ghrelin group had 68 fewer deaths per 1000 (from 216 fewer to 188 more) as compared to the control group. The meta-analysis reveals that the heart rate in rats/mice on Ghrelin was higher (MD 13.11, 95% CI 1.14 to 25.08, P=0.66) while the mean arterial blood pressure (MD -1.38, 95% CI -5.16 to 2.41, P=0.48) and left ventricular end diastolic pressure (MD -2.45, 95% CI -4.46 to -0.43, P=0.02) were lower as compared to the those on placebo. There were insignificant changes in cardiac output (SMD 0.28, 95% CI -0.24 to 0.80, P=0.29) and left ventricular end systolic pressure (MD 1.48, 95% CI -3.86 to 6.82, P=0.59). CONCLUSIONS: The existing data provides evidence to suggest that Ghrelin may lower the risk of mortality and improve cardiovascular outcomes. However; the quality of evidence as assessed by GRADEpro is low to very low. Clinical judgments to administer Ghrelin to patients with HF must be made on better designed animal studies.

Cardioprotective effects of ghrelin in heart failure: from gut to heart.

Chronic heart failure (CHF) is a major cause of morbidity and mortality. Cardioprotective effects of ghrelin, especially in its acylated form have been demonstrated in heart failure (HF) models and exploratory human clinical studies. Hence, it has been proposed for the treatment of HF. However, the underlying mechanism of its protective effects against HF remains unclear. Future researches are needed to evaluate the efficacy of Ghrelin as a new biomarker and prognostic tool and for exploring its therapeutic potential in patients suffering from CHF.

Ghrelin: ghrelin as a regulatory Peptide in growth hormone secretion.

BACKGROUND: Ghrelin is a type of growth hormone (GH) secretagogue that stimulates the release of GH. It is a first hormone linking gastrointestinal-pituitary axis. OBJECTIVE: This review highlights the interaction of ghrelin with GHRH and somatostatin to regulate the secretion of GH and intends to explore the possible physiological role of the ghrelin-pituitary-GH axis linkage system. OBSERVATION: Ghrelin is highly conserved among species and is classified into octanoylated (C8:0), decanoylated (C10:0), decenoylated (C10:1) and nonacylated,ghrelin. Acylated ghrelin is the major active form of human ghrelin. The primary production site of ghrelin is the stomach, and it interacts with stomach ghrelin as well as hypothalamic GHRH and somatostatin in the regulation of pituitary GH secretion. Ghrelin stimulate GH release through the GHS receptor to increase intracellular Ca2+ ([Ca2+] levels via IP3 signal transduction pathway. Ghrelin is a specific endogenous ligand for the GHS receptor and provides a definitive proof of the occurance of a GHS-GHS receptor signalling system in the regulation of GH secretion. CONCLUSION: Studies suggests that ghrelin is a powerful pharmacological agent that exerts a potent, time-dependent stimulation of pulsatile secretion of GH.

Role of antibiotics on surgical site infection in cases of open and laparoscopic cholecystectomy: a comparative observational study.

INTRODUCTION: Surgical site infection (SSI) comes as third most common healthcare related infection which produces morbidity and deaths at large. Still many authors believe that it is better not to use prophylactic antibiotics in simple and uncomplicated cases. Laparoscope, now-a-days is a much used instrument for abdominal surgeries. Even after new aseptic techniques SSI remains to be a major problem. AIMS AND OBJECTIVES: To study the effect of antibiotics on superficial SSI in the cases of open and laparoscopic cholecystectomy. OBSERVATION AND RESULTS: One hundred patients were enrolled for cholecystectomy. The patients were divided into two groups, A and B. Group A consisted of patients in whom laparoscopic cholecystectomy was done and group B in whom open cholecystectomy was done. The male female ratio was 1: 2.23. The mean age of patients in Group A was 46 years and in Group B was 44; Standard deviation (SD) for age was 14.8% and 13.8% in groups A and B respectively; t-value was 0.654 and P value was 0.515 and they were not significant. The number of males and females was 16 and 26 respectively in Group A and 11 and 31 in Group B. The Chi square X(2) = 1.36 and P value was 0.248 and both were insignificant. The rate of superficial surgical site infection was 2.63% in both the groups. CONCLUSION: Our study concludes that there is no difference in the outcome of patients in cases of open as well as laparoscopic cholecystectomy. There is no significant difference in the surgical site infection rate in cases of open as well as laparoscopic cholecystectomy.

Resource utilization in the management of traumatic brain injury patients in a critical care unit: An audit from rural setup of a developing country.

INTRODUCTION: Traumatic brain injuries (TBI) are steadily increasing and are a major cause of mortality and morbidity, particularly in the young population, leading to the loss of life and productivity in the developing countries. Providing critical care to these patients with TBI is a challenge even in well-advanced centers in major cities of India. In the present study, we describe our experience of resource utilization in the management of TBI in a critical care unit (CCU) from a rural setup. MATERIALS AND METHODS: All consecutive patients who were admitted from January 2007 to December 2009 in the CCU for the management of traumatic brain injury were included in the study. The case records of the patients were reviewed retrospectively, and data were collected on age, gender, severity of head injury, associated injuries, total CCU stay, total hospital stay, and outcome. RESULTS: The total duration (days) of hospital stay was 8.96±6.16 days and a median of 8 days, and CCU stay was 3.77±6.34 days with a median of 2 days. No deaths occurred with mild head injury. A total of 73 (19.16%) deaths occurred in 381 admitted subjects in CCU. The risk of death among both the sexes is not significantly different, that is, odds ratio (OR) 1.032 [95% confidence interval (CI) 0.351-3.03], so also the risk of death among the different age groups is also not significant having OR, 0.978 (95% CI, 0.954-1.00). The severity of head injury (mild, moderate, and severe) and CCU stay parameters had significant difference with risk of death [OR, 3.22 (95% CI, 2.49-4.16) and OR, 2.50 (95% CI, 1.9-3.2)]. CONCLUSIONS: Apparently it seems possible to use the existing health care structures in rural areas to improve trauma care. It becomes particularly relevant in poor resource, developing countries, where health care facilities and access to specialized care units are still far below the acceptable standard, there is a need to compare with the reference group to further support the evidence.