Hyperimmune anti-COVID-19 IVIG (C-IVIG) treatment in severe and critical COVID-19 patients: A phase I/II randomized control trial.

BACKGROUND: Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG) is an unexplored therapy amidst the rapidly evolving spectrum of medical therapies for COVID-19 and is expected to counter the three most life-threatening consequences of COVID-19 including lung injury by the virus, cytokine storm and sepsis. METHODS: A single center, phase I/II, randomized controlled, single-blinded trial was conducted at Dow University of Health Sciences, Karachi, Pakistan. Participants were COVID-19 infected individuals, classified as either severely or critically ill with Acute Respiratory Distress Syndrome (ARDS). Participants were randomized through parallel-group design with sequential assignment in a 4:1 allocation to either intervention group with four C-IVIG dosage arms (0.15, 0.20, 0.25, 0.30 g/kg), or control group receiving standard of care only (n = 10). Primary outcomes were 28-day mortality, patient's clinical status on ordinal scale and Horowitz index (HI), and were analysed in all randomized participants that completed the follow-up period (intention-to-treat population). The trial was registered at clinicaltrials.gov (NCT04521309). FINDINGS: Fifty participants were enrolled in the study from June 19, 2020 to February 3, 2021 with a mean age of 56.54±13.2 years of which 22 patients (44%) had severe and 28 patients (56%) had critical COVID-19. Mortality occurred in ten of 40 participants (25%) in intervention group compared to six of ten (60%) in control group, with relative risk reduction in intervention arm I (RR, 0.333; 95% CI, 0.087-1.272), arm II (RR, 0.5; 95% CI, 0.171-1.463), arm III (RR, 0.167; 95% CI, 0.024-1.145), and arm IV (RR, 0.667; 95% CI, 0.268-1.660). In intervention group, median HI significantly improved to 359 mmHg [interquartile range (IQR) 127-400, P = 0.009)] by outcome day, while the clinical status of intervention group also improved as compared to control group, with around 15 patients (37.5%) being discharged by 7th day with complete recovery. Additionally, resolution of chest X-rays and restoration of biomarkers to normal levels were also seen in intervention groups. No drug-related adverse events were reported during the study. INTERPRETATION: Administration of C-IVIG in severe and critical COVID-19 patients was safe, increased the chance of survival and reduced the risk of disease progression. FUNDING: Higher Education Commission (HEC), Pakistan (Ref no. 20-RRG-134/RGM/R&D/HEC/2020).

Parental Refusal to Lumbar Puncture: Effects on Treatment, Hospital Stay and Leave Against Medical Advice.

Introduction Lumbar puncture (LP) is an effective method in the diagnosis and management of central nervous system infections. Refusal to LP is associated with severe consequences. This study aims to examine the impact of parental LP refusal on treatment, the length of hospital stay, and the frequency of patients leaving against medical advice (LAMA). Method A cross-sectional study was conducted at the pediatric department of Civil Hospital, Karachi, from June 2018 to November 2019. All hospitalized patients suspected to have a central nervous system disease, which requires LP, were enrolled. Patients were followed for the duration of antibiotic and antiviral therapy, length of hospital stay, and LAMA. Results A total of 220 patients participated in the study, with the median age of nine (2-47) months. There were 113 (51.1%) males. The median length of hospital stay was 10 (4-14) days. The comparison of parental LP refusal with the length of hospital stay showed a significant difference (p-value <0.001) in the number of days of treatment among patients who received vancomycin (p-value =0.008) and meropenem (p-value =0.012). A significant association of parental LP refusal was also observed with meningoencephalitis and meningitis as provisional diagnosis (p-value =0.006). In particular, LAMA and death were found significantly higher among parents who refused LP (p-value <0.001).  Conclusion LP refusal has a significant effect on the treatment, hospital stay, and disposition outcomes. A large number of parents who declined the procedure left against medical advice or suffered grave medical consequences. Parental education addressing their concerns and beliefs, while explaining the indications, and need for performing LP can help effectively overcome this issue.

Frequency and Associated Factors of Parental Refusal to Perform Lumbar Puncture in Children with Suspected Central Nervous System Infection: A Cross-sectional Study.

Objective Lumbar puncture (LP) is a useful procedure which is performed for both diagnosis and treatment of numerous conditions affecting children and adults. The purpose of this study was to determine the frequency and cause of increased parental refusal to perform LP in the pediatric population. Method A cross-sectional study was conducted from January 2018 to June 2019 at the Civil Hospital, Dow University of Health Sciences, pediatric department, Civil Hospital, Karachi. Over the 18-month time period, a total of 215 patients who had indications of LP were selected from the in-patient pediatrics department; the age range was between newborn to 12 years of age. The mode of research was a questionnaire and interview-based method that was conducted with guardians of minor patients to understand the extent of their knowledge and awareness about the LP procedure as well as its complication and the role of culture, education background, and financial status of the families which may lead to an increased likelihood of refusal. Result The frequency of LP refusal amongst the 215 families of the patients that were interviewed was found to be 32.6%. Mean age of the respondents was 30.98 years. The decision for LP was not significantly affected by the subjects' gender (p=0.1), by the religious communities to which the families belonged (p=0.9), their ethnicities (0.52), or by the families' financial status (p=0.4). It was observed that when indications for performing LP were appropriately explained, there was a significantly greater number of consents given as compared to when they were not made clear (p=0.009). Explaining the complications of the procedure did not considerably impact the decision for refusal of the procedure (p=0.1). The multi-variable logistic regression analysis model was applied to determine the likelihood of variables affecting refusal of LP and the logistic regression model was found to be statistically significant, χ2 (8) = 38.2 p < 0. 001. Conclusion Lack of knowledge about the LP procedure and fear of ramification plays a conspicuous role in the denial of LP procedure by the guardians of minor patients. A better, simpler approach using standardized consent forms by the doctors may lead to the removal of the information gaps and can provide a better understanding about the concerned risks, the primary indications, and the benefits of this procedure to the guardians.

Influence of sibutramine, orlistat and Ispaghula in reducing body weight and total body fat content in obese individuals.

BACKGROUND: The correlations between combined body fat parameters and risk factors of obesity explained a portion of the variation in the weight, BMI and waist circumference, the average number of categorical metabolic risk factors increases progressively with increasing total body fat content. There is currently no data available in which influence of drugs can be assessed on total body fat content. This was a non-randomized, prospective, open-label, parallel group study was conducted to compare the effectiveness of sibutramine, orlistat and ispahgula in reducing body weight and percentage of total body fat content in obese individuals. METHODS: A nonrandomized, open label, prospective, intention to treat clinical trial was conducted from July 2008 to March 2009 in JPMC, Karachi, Pakistan. The study was based on three arms A (ispahgula), B (orlistat) and C (sibutramine) comprising 40 patients in each. The selection criteria has included patients from either sex with age 18 years or more with BMI > or =30 as obese with or without associated risk factors and BMI > or = 27 < 30 as over weight only if any significant risk factor is present. Compliance on diet chart and instruction for life style modification were assessed monthly. RESULTS: The comparison of mean difference in percentage of total body fat content between the groups and within the groups at day 150 is (p-value) 0.029 and difference in body weight is (p-value) 0.042 which is statistically significant. CONCLUSION: Sibutramine is more effective than ispahgula and orlistat in reducing body weight and percentage of total body fat content in obese patients.

Knowledge and skills in community oriented medical education (COME) self-ratings of medical undergraduates in Karachi.

OBJECTIVE: To assess the satisfaction of medical students regarding community oriented knowledge and skills that are proposed to be part of the current undergraduate medical curriculum. METHODS: Competencies listed in the regulations for medical education designed by the Pakistan Medical and Dental Council (PMDC) were used to develop a self-administered questionnaire. Using the questionnaire 220 final year students of 3 public sector medical schools self-rated the knowledge and skills that should be part of the curriculum. For analysis the questions were grouped into courses of Basic, Clinical and Community Health Sciences. Students ranked their perceptions on a Likert scale of 0-4 for each question. Descriptive analysis was done to calculate the proportion of satisfied and dissatisfied students using the median of the highest possible score as the cut off. RESULTS: The analysis of knowledge gained found a greater proportion of satisfied students with the Basic (55.9%) and Clinical Sciences (50.9%) courses than the Community Health Sciences course (45.5%). Analysis of skills acquired uniformly showed a low percentage of satisfied students for Basic (39.1%), Clinical (29.7%) and Community Health Sciences (19.1%). The proportion of students dissatisfied with their knowledge and skills for different courses ranged from 38.2-85%. CONCLUSION: Students perceive that current medical school curricula are unable to meet the required standards. Proper implementation of community oriented curricula is the first step towards effective health care provision.