A Case Report of Cefixime, Paracetamol, and Nimesulide Induced Toxic Epidermal Necrolysis in a Woman with Dengue Infection without any Other Associated Comorbidities.

BACKGROUND: Toxic Epidermal Necrolysis (TEN) is a rare, acute, and life-threatening mucocutaneous disease that occurs after the administration of certain drugs, resulting in extensive keratinocyte cell death, skin involvement at the dermal-epidermal junction, and extensive bullous skin eruptions and sloughing. Many published case reports have observed the presence of fever with a viral infection, drug, and/or genetic association as a possible trigger for TEN but associated with other comorbidities. Physicians still struggle to predict which individuals could be predisposed to TEN. The case report that we present had a history of multiple drug intake and fever due to dengue virus infection but was not associated with any other comorbidity. CASE PRESENTATION: We present an unusual case of a 32-year-old woman of Western Indian origin who had developed dengue infection and suffered toxic epidermal necrolysis following a five-day course of a third-generation cephalosporin antibiotic, cefixime and a three-day course of 2 analgesic drugs, paracetamol (acetaminophen), and nimesulide, with the adverse event occurring on the fifth day of the dengue infection. The offending drugs were stopped, and patient survived with supportive management and hydration. CONCLUSION: The presence of comorbidities may not always be the triggering factor for TEN, though it can affect patient outcomes. Rational drug use is always recommended for patient care. Further research is required to understand the pathomechanism behind the viral-drug-gene interaction.

Vitamin D deficiency in rheumatoid arthritis patients of India - a single-arm meta-analysis.

Background: Vitamin D deficiency is commonly seen in patients with rheumatoid arthritis (RA). Objectives: This meta-analysis is aimed to determine the prevalence of Vitamin D deficiency in RA patients in India and also to evaluate the association between vitamin D level and disease activity. Methods: The relevant works of literature were identified through multiple databases and data was extracted from eligible studies independently. A single-arm meta-analysis was performed to estimate the prevalence of Vitamin D deficiency in RA patients in an Indian setup and its association with disease activity. A total of 15 studies was included in the analyses. Results: The mean serum vitamin D level was 19.99 ng/ml [95% CI 16.49-24.23]. The proportion of patients with low vitamin D level was 0.80 [95% CI 0.65- 0.90], Vitamin D deficiency was 0.56 [95% CI 0.31-0.77] and vitamin D insufficiency was 0.20 [95% CI 0.12- 0.32]. A negative relationship was seen with serum vitamin D and disease activity score. Conclusions: The results demonstrate significant low levels of serum vitamin D levels in patients with RA and established a negative correlation of Vitamin D with RA disease activity. The current evidence suggests a rationale for Vitamin D supplementation in the management of RA.

Public disclosure of clinical trial results at Clinical Trial Registry of India- Need for transparency in research!

Introduction: Since June 15, 2009, clinical trial registration in the Clinical Trial Registry-India (CTRI) has been made mandatory by the Drugs Controller General of India to improve transparency, accountability, conform to accepted ethical standards and reporting of all relevant results of registered trials. In this study, we planned to evaluate the compliance of Indian and global sponsors with clinical trials conducted in India in terms of reporting of clinical trial results at the CTRI. Methods: We included trials registered in the CTRI between January 2018 and January 2020. The CTRI and ClinicalTrials.gov registry was thoroughly searched for all completed interventional studies. A year-wise comparative analysis was performed to evaluate the number of clinical trials reporting results in both the registry. Results: The reporting of completed interventional clinical trial results was 25/112 (22.32%) in year 2018, y, 8/105 (7.6%) in year 2019 and 17/140 (12.14%) in year 2020. There was significantly less reporting of results of Pharmaceutical company sponsored Interventional Studies-Indian at CTRI when compared with ClinicalTrials.gov registry for the year 2019 (odds ratio [OR]-0.17 (95% confidence interval [CI]: 0.08-0.36) and P < 0.0001) and year 2020 (OR-0.45 [95% CI: 0.24-0.82] and P < 0.01). The difference in results reported at CTRI was significantly low for Pharmaceutical company sponsored Interventional Studies-Global only for year 2019 (OR-0.09 [95% CI: 0.005-1.45] and P = 0.04) compared with ClinicalTrials.gov. Conclusion: There is a need to develop the culture of reporting clinical trial results in CTRI to strengthen the transparency in the research for overall benefit of public, health care professionals, and research community.

Impact of sodium-glucose co-transporter 2 inhibitors on renal outcomes in patients of diabetes mellitus: A meta-analysis of landmark renal and cardiovascular outcome trials.

Sodium-glucose co-transporter 2 inhibitors (SGLT2is) are recommended as the next step therapy for the management of diabetes mellitus. The large clinical trials of SGLT2is demonstrated benefits on various renal endpoints. We conducted this meta-analysis of large trials on cardiovascular and renal safety trials to explore the renoprotective effect of this group of drugs. PubMed, Cochrane CENTRAL, and EMBASE databases were searched with specific keywords till January 19, 2021. Randomized trials of SGLT2is that evaluated the cardiovascular or renal composite outcome as a primary outcome measure were eligible. Random-effects model was used to calculate the overall risk ratios. The search yielded 716 studies and 10 studies were included. The SGLT2is reduced the risk of composite renal outcome (risk ratio [RR] = 0.64, 95% confidence interval [CI] = 0.58-0.72), decline in estimated glomerular filtration rate (eGFR) (RR = 0.62, 95% CI = 0.50-0.77), doubling of serum creatinine (RR = 0.67, 95% CI = 0.56-0.81), dialysis or renal replacement therapy (RR = 0.71, 95% CI = 0.59-0.86), sustained eGFR of <15 ml per min per 1.73 m2 for at least 30 days or more (RR = 0.66, 95% CI = 0.55-0.81), end-stage renal disease (RR = 0.70, 95% CI = 0.56-0.87), and acute kidney injury (RR = 0.79, 95% CI = 0.71-0.89). This analysis establishes the renoprotective effect of SGLT2is. This benefit is noted in patients who had eGFR of more or <60 ml per min per 1.73 m2. This benefit was uniform across all the SGLT2 inhibitors except ertugliflozin and sotagliflozin.

Efficacy and safety of AP-Bio®(KalmCold®) in participants with uncomplicated upper respiratory tract viral infection (common cold) - A phase III, double-blind, parallel group, randomized placebo-controlled trial.

INTRODUCTION: Kalmegh (Andrographis paniculata) is commonly used for treating uncomplicated Upper Respiratory Tract Infection (URTI) in complementary and alternative system of medicine. AP-Bio®(KalmCold®) is a standardized extract derived from the leaves of A. paniculata. This study was proposed to evaluate its efficacy using validated scales and objective measures. METHODS: Participants were randomized in a ratio of 1:1:1 to receive either AP-Bio® 200 mg/day, AP-Bio® 400 mg/day or placebo for 7 days. The primary outcome measure was Wisconsin Upper Respiratory Symptom Survey (WURSS-21) score. The secondary outcome measures were nasal mucous weight, nasal muco-ciliary clearance function and Interleukin-8 in nasal wash, as well as safety and tolerability. RESULTS: A total of n = 331 participants were screened and N = 300 participants were enrolled. The absolute WURSS-21 global score [mean (Standard Deviation - SD)] in the AP-Bio® 400 mg group [5.70 (5.31)] was less than the AP-Bio® 200 mg group [5.81 (4.83)] on Day-3. However, it was much higher in the placebo group [9.55 (14.27)]. AP-Bio® 400 mg group (Mean Difference - MD [Standard Error - SE] = -3.85 [1.52]; 95% CI = -6.85, - 0.85; adjusted p = 0.034) and 200 mg group (MD [SE] = -3.74 [1.51]; 95% CI = -6.73, - 0.76; adjusted p = 0.038) had significantly lower score than placebo. Similarly, on Day-3, the change in global score from baseline was significantly better in the AP-Bio® 400 mg group (MD [SE] = -3.91; [1.82] 95% CI = -7.50, - 0.32; adjusted p = 0.038) and AP-Bio® 200 mg group (MD [SE] = -3.84 [1.97]; 95% CI = -7.72, - 0.04; adjusted p = 0.044) in comparison to the placebo group. Nasal mucous weight, tissue paper counts used, and interleukin-8 showed a trend towards AP-Bio® groups having a favourable outcome when compared with placebo but did not reach statistical significance due to a small sample size. None of the study participants complained of any adverse physical symptoms. However, incident eosinophilia was noted in n = 20 participants on day 3. (n = 6 in AP-Bio® 200 mg group, n = 7 in Ap-Bio® 400 mg group and n = 13 in placebo group; p = 0.181). CONCLUSIONS: Participants in both the AP-Bio® dose groups showed positive tendency towards resolution of URTI symptoms when compared with placebo on Day-3 but not on Day-5 and Day-7.

Impact of Educational Intervention on the Knowledge, Attitude, and Practice of Pharmacovigilance Among Nurses at a Tertiary Care Public Hospital.

BACKGROUND: Nursing students and employees remain the first point of contact in case a patient develops an adverse drug reaction in hospital settings. Thus, it is important for nurses to understand the importance of pharmacovigilance activity and implement the same in their practice. They can also contribute to drug safety by reducing medication errors and adverse drug reaction reporting. METHODS: After ethics approval, an observational questionnaire-based study was conducted in 2017 that involved nursing students and nursing employees (N=390) to assess their baseline knowledge, attitude, and practice toward pharmacovigilance. Participants who consented were enrolled and a pre-training survey was conducted. Pharmacovigilance sensitization/ training sessions were conducted in the same year after getting their baseline data. Three years later in 2021, the same questionnaire was distributed to a subset of nursing students and employees (N=299) to analyze any change in their knowledge, attitude, and practice towards the pharmacovigilance activity as a posttest. Pre and post sensitization session questionnaire-based survey data was analyzed to confirm the long-term impact of conducting such pharmacovigilance awareness training. RESULTS: The nurses' overall performance before and after training in each of the domains of knowledge, attitude and practice were 17.53%, 72.86%, 39.69% in the pretest group, respectively, and post test scores were 30.77%, OR-3.04, p=0.0 (Knowledge), 85.92%, OR-0.14, p=0.0 (Attitude) and 37.21%, OR-0.08, p=0.08 (Practice) in the corresponding domain. Overall, there was a declining trend in the practice domain of the nurses response between the pre-test and post intervention groups however this decline was not statistically significant (p=0.08). CONCLUSION: Pharmacovigilance awareness training and sensitization programs had an impact on the knowledge and attitude of nurses but there is a need to ensure that it is implemented in clinical practice.

A comprehensive evaluation of the safety of ipilimumab, nivolumab and their combination therapy: A systematic review and network meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have changed the landscape of management of advanced cancers. It is imperative to evaluate the safety of nivolumab and ipilimumab based therapies. This study was aimed to assess the comparative safety profiles of ipilimumab, nivolumab and their combinations. MATERIALS AND METHODS: We searched PubMed, Embase, and the CENTRAL for randomised controlled trials of ipilimumab and nivolumab. The outcome measures were treatment-related adverse events [TRAEs], TRAEs of grade 3-5, treatment discontinuation due to TRAEs [TDTRAEs], TDTRAEs of grade 3-5, serious adverse events [SAEs] and SAEs of grades 3-5. We performed a network meta-analysis using the Bayesian approach in R version 4.0.3. RESULTS: We identified 42 RCTs for final analysis. The treatment ranking for TRAEs revealed that nivolumab 240 mg/week and nivolumab 3 mg/kg/week were safer (0.84 and 0.81 in SUCRA); for TRAEs of grade 3-5, nivolumab 3 mg/kg/week and nivolumab 240 mg/week were safer (0.83 and 0.75 in SUCRA); for TDTRAEs nivolumab 3 mg/kg/week and ipilimumab in combination with other drugs were safer (0.87 and 0.64 in SUCRA) and for TDTRAEs of grade 3-5, nivolumab 3 mg/kg/week was safer (0.85 in SUCRA). Nivolumab 3 mg/kg/week and nivolumab 240 mg/week were safer (0.79 and 0.76 in SUCRA) for SAEs and nivolumab 3 mg/kg/week was safer for SAEs of grade 3-5 (0.78 in SUCRA). CONCLUSION: Nivolumab 3 mg/kg biweekly, nivolumab 240 mg weekly and nivolumab 3 mg/kg plus ipilimumab 1 mg/kg triweekly could be preferred due to the relatively low risk of TRAEs, TDAEs and SAEs.

Melanocortin Receptors: Emerging Targets for the Treatment of Pigmentation, Inflammation, Stress, Weight Disorders and Sexual Dysfunction.

Melanocortins are tiny protein molecules formed by the post-translational cleavage of proopiomelanocortin. These are bioactive peptides that are responsible for human and lower animal pigmentation patterns, energy homeostasis, and sexual function modulation. These peptides regulate numerous physiological functions by being generated in the central nervous system and peripheral tissues. Melanocortins elicit their varied biological effects by binding to a separate family of G protein, two primary proteolytic enzymes, proconvertases 1 and 2, according to recent research. These breakthroughs have opened up new avenues for research into the role of melanocortins, antagonists, and receptors in a number of physiological activities.

An audit of prescribing pattern of anti-epileptic drugs with its effect on therapeutic drug levels and seizure control at a tertiary care public hospital.

Objective: The study objective was to evaluate the prescription pattern and use of anti-seizure medications (ASMs) in patients with a seizure disorder and to evaluate if a change in the ASM dose had a beneficial effect on seizure control, observed through Therapeutic Drug Monitoring [TDM] level of ASMs. Methods: Details of anti-seizure medications with their therapeutic levels in the blood of patients with seizure disorder were analysed. Design: Hospital-based retrospective analysis of patient case records. Settings: Therapeutic Drug Monitoring OPD of a tertiary care public teaching hospital. Participants: Case records of 918 patients with seizure disorder from 2016-2021. Results: Data of men (53%) and women (47%) aged between 18-75 years was assessed About 62% (566/918) of patients were on levetiracetam, the most frequently prescribed anti-seizure medication. Whenever the ASMs dose was increased or decreased based on TDM levels, it was associated with a significant increase in the frequency of break-through seizures [OR- 5 (95% CI: 1.28-19.46)]. However, significant seizure control was observed when the patients were on the same maintenance dose of the anti-seizure medication [OR- 0.2 (95% CI: 0.06-0.63)]. Whenever an additional new anti-epileptic drug was prescribed or removed from the pre-existing anti-epileptic medications, it did not significantly impact seizure control. Conclusion: Individualising drug therapy and therapeutic drug monitoring for each patient, along with patient factors such as medication compliance, concomitant drug and disease history, and pharmacogenetic assessment, should be the ideal practice in patients with seizures for better seizure control. Funding: None declared.

A Cross-sectional Survey of Public Knowledge and Perspective on Coronavirus Disease, Vaccination, and Related Research in India during the COVID-19 Pandemic.

BACKGROUND AND RATIONALE: The coronavirus disease 2019 (COVID-19) pandemic has left no person unexposed to the wisdom about the need for human preparedness to tackle future pandemics irrespective of individual caste, race, religion, and education status. The extent of this change in knowledge and public perspective is difficult to measure in a populous nation like India subjected to individual freedom and cultural beliefs. Hence, we planned this study with the objective of evaluating the knowledge and perception of the Indian public towards COVID-19 disease, vaccination and research activities associated with the COVID-19 pandemic. MATERIALS AND METHODS: This is an observational, single-center, cross-sectional study (n = 244) conducted after obtaining approval from the Ethics Committee for Academic Research Projects. All consenting study participants, Indian residents aged > 18 years, were administered a prevalidated and structured questionnaire and interviewed for their honest opinion. The outcome measures were to evaluate the knowledge and perception of the study participants in each of the domains of COVID-19 disease, COVID-19 vaccination, and COVID-19-related clinical research. Demographic characteristics were summarized using descriptive statistics. All analyses were done at a 5% significance level using GraphPad InStat version 3.1. Data on the proportion of participants' responses to the questions in each of the three domains of COVID-19 disease (D), COVID-19 vaccination (V), and COVID-19-related research (R) were assessed. RESULTS: Study participants who knew the causative agent for coronavirus disease were 93.03% (227/244), nomenclature (77.45%, 189/244), those who could define pandemic (89.34%, 218/244), preventive measures against covid (96.31%, 235/244), lungs as the most common organ affected (96.31%, 235/244) and all answered that the origin of novel coronavirus was China. The majority of them felt that COVID-19 pandemic waves would never end (39.34%, 96/244), there was no effective drug/vaccine therapy available, and the lack of oxygen/hospital beds (39%) resulted in maximum mortality, and 47.13% (115/244) were worried about future bioterrorism. The lockdown measures were justified by 161/244 (65.98%), and 93.85% supported lockdown measures to curb the spread of infection. The improvement in air quality/environment hygiene, realizing the importance of hygiene, vaccine and disease, and spending quality time with family were the best three things to happen during the pandemic, while the loss of wages, nonavailability of medicines/vaccines/oxygen/hospital beds with mental/physical health deterioration were the worst three things experienced by people. Regarding COVID-19 vaccination, the most common reason to get vaccinated was to prevent infection/critical outcomes of COVID-19 (78.27%, 191/244); 79% already suffered COVID-19 prior to vaccination, while 68.85% suffered a COVID-19 infection after taking the vaccine which was mostly asymptomatic/mild. Almost 56.96% (139/244) participants supported compulsory vaccination for all in the larger interest of society and to prevent fatal COVID-19 outcomes. There were safety concerns mainly with accelerated approval of vaccines (4.1%, 10/244) among the public, and 32.78% (80/244) attributed limited infrastructure/vaccination centers/healthcare staff as the major challenge of a mass vaccination program with 71.72% (175/244) supporting the vehicle/home vaccination drives to meet the vaccination demand in the pandemic. Approximately 38.11% (93/244) blamed the lack of sufficient vaccine manufacturing sites in India as a major vaccine shortage. Almost 82% public knew that vaccines are incapable of providing lifelong immunity or conferring protection against multiple variants, with 34.83% desiring to get polyvalent vaccines that would provide immunity against multiple COVID-19 variants. A total of 57.37% knew about clinical research, believed that the vaccine/drug development process was slow in India (29.91%), that there was a lack of funds invested in COVID-19-related clinical research (62.29%), 47.95% felt no attention was given to the alternative system of medicines, 77.86% supported accelerated drug/vaccine approval in the pandemic. Around 64.34% of the study, participants knew about the available and approved COVID-19 treatment options, such as antiviral drugs, monoclonal antibodies and vaccines. Of the total 244 study participants, 98.36% believed that clinical research is important for science to progress. When asked about their willingness to participate in COVID-19 clinical research, only 40.57% agreed, while 29% opted for non-COVID-19 related clinical research, and 29% refused to participate in any kind of clinical research. Almost 88.93% refused to take medicines without approval by drug regulatory bodies, and 54.51% agreed to participate in a controlled human challenge research study during the pandemic. The majority were of the opinion that lack of financial support (35.24%) was the main hindrance to the conduct of clinical research in India and the reason for lagging behind other countries in research and development (64.34%). CONCLUSION: The survey provides insight into the public awareness and perception of the pandemic that has taught all the lessons for capacity building in automation, construction of robust medical infrastructure, and the need for future preparedness. How to cite this article: Munshi R, Maurya M. A Cross-sectional Survey of Public Knowledge and Perspective on Coronavirus Disease, Vaccination, and Related Research in India during the COVID-19 Pandemic. J Assoc Physicians India 2023;71(9):19-27.

Evaluation of genetic polymorphism of CYP3A5 in normal healthy participants from western India - A cross-sectional study.

BACKGROUND: CYP3A5 enzymes belong to the phase I Group of drug-metabolizing enzymes, which are involved in the metabolism of 50% of the drugs. Participants with CYP3A5 genotype: CYP3A5 *1/*1 are fast metabolizers of drugs and hence will require higher dosing. Whereas those with CYP3A5 * 3/*3 are poor metabolizers of drugs and will require a lower dose to achieve target drug concentration in the blood and those with CYP3A5 * 1/*3 have intermediate drug metabolizing activity. Pharmacogenetic evaluation may improve disease outcomes by maximizing the efficacy and minimizing the toxicity of drugs in patients. MATERIALS AND METHODS: This is a single-center cross-sectional study conducted in the year 2018-2019 to study the population prevalence of genetic polymorphisms of CYP3A5 in healthy participants from western India. Eligible participants willing to give written, informed consent were enrolled in the study. Subsequently, 2 ml venous blood was collected the deoxyribonucleic acid was extracted and then stored at ‒20°C. Genotyping was done by a polymerase chain reaction and restriction fragment length polymorphism. RESULTS: A total of 400 participants with a median age of 22 years (range: 18-58 years) were included. Among them, the genotype prevalence for CYP3A5 * 1/*1 was 17% (n = 67/400); CYP3A5 * 1/*3 was 37% (n = 149/400) and that of CYP3A5 * 3/*3 was 46% (184/400). Out of the total 400 healthy participants analyzed, the allele frequency for CYP3A5 * 1 was 35% (142/400) and that of CYP3A5*3 was 65% (259/400). CONCLUSION: The genotype prevalence for CYP3A5 * 3*3 (46%) and the allele frequency for CYP3A5 * 3 (65%) respectively were the highest among the western Indian population.

Impact of disease-modifying therapies on MRI outcomes in patients with relapsing -remitting multiple sclerosis: A systematic review and network meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating disorder of the central nervous system. The clinical presentation supported by characteristic findings on MRI forms the backbone of the current diagnostic criteria. This study was aimed to investigate the efficacy based on MRI outcomes of FDA approved disease-modifying therapies (DMTs) for relapsing-remitting MS (RRMS). MATERIALS AND METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) of DMTs. The outcome measures were the mean number of T2 [new/enlarging lesions], new T1 [gadolinium-enhancing (Gd+) T1 and hypointense T1] lesions in brain MRI performed at 12 months or 24 months. We performed a network meta-analysis using the frequentist approach in STATA version 16.0. RESULTS: We identified 26 RCTs for final analysis. Interferon ß-1a and placebo were the most common comparison treatment. Ocrelizumab was more effective in reducing the number of Gd+T1 lesions. Dimethyl fumarate 480 mg was relatively better in reducing the number of new T2 lesions. The treatment ranking showed that ocrelizumab and dimethyl fumarate 480 mg were more efficacious (1 and 0.9 in SUCRA, respectively) for reducing the number of new Gd+T1/hypointense lesions; dimethyl fumarate 480 mg/720 mg and natalizumab were more efficacious (1.0, 0.9 and 0.8 in SUCRA, respectively) to reduce the number of new T2 lesions. CONCLUSION: Ocrelizumab, dimethyl fumarate 480/720 mg and natalizumab demonstrated favourable MRI outcomes in patients with the RRMS.

Cobra envenomation in an elderly female mimicking brain death- A case report.

Snake bite envenomation is one of the most toxicology-related cause that can mimic brain death. This is a case report of 73-year-old elderly female, a hypertensive on treatment, who presented with chief complaints of cobra snake bite on the dorsum of right hand. On admission, patient had dyspnea, bilateral ptosis and ophthalmoplegia. In the next 10-15 min, her symptoms got worsened for which she was administered intravenous doses of atropine (2 mg), neostigmine (0.5 mg) and anti-snake venom. She developed respiratory arrest, hence was intubated and was started on mechanical ventilation. On assessment following 12 h post admission, the patient had Glasgow Coma Scale (GCS)-E1V1M1, with pupils bilateral 2.5 mm sluggishly reacting to light. After 36 h post admission, patient began to show signs of recovery. She began to blink her eyes, follow objects and attempted to move her limbs on command. On day 3, Patient was weaned off from the ventilator, extubated two days later and discharged home on Day 7. This case report highlights a unique presentation of cobra bite induced neuroparalytic syndrome mimicking brain death in an elderly patient. Furthermore, the life-threatening presentation of cobra envenomation mandates the use of higher doses of Polyvalent snake antivenom (PSA) to reverse the neuroparalytic toxicity. We should consider the role of anticholinesterase as an adjunctive therapy to PSA in severe cobra envenomation.

A Meta-Analysis of Safety of Different Regimens of Remdesivir in COVID-19 Patients.

Remdesivir is an adenosine analogue drug that targets RNA-dependent RNA polymerase enzyme and inhibits viral replication. As of 22nd October, 2020, US FDA fully approved the drug Remdesivir for the treatment of COVID-19 patients who requires hospitalisation. Many clinical studies reported the derangement in hepatic and renal function tests, which is alarming considering the health conditions of the COVID-19 patients. In view of these results, the present study was envisaged to review the safety of Remdesivir in COVID-19 patients. The PubMed, Embase, and Cochrane databases were searched using the terms 'Remdesivir,' 'veklury,' 'SARS' and 'COVID' till 1st December, 2020. The studies included in this meta-analysis were either randomised or nonrandomised studies that evaluated Remdesivir for the treatment of COVID-19 against Placebo [standard of care]. The Adverse events [AEs], Serious adverse events [SAEs] and Treatment Discontinuation due to Adverse Events (TDAE) were used as primary outcome measures. The quality of studies was evaluated by using the Cochrane Collaboration's tool for the assessment of RoB. Data analysis was performed by two authors (MK & DB) using statistical software Review manager [Revman] version 5.3. The pooled Risk Ratios (RR) and 95% Confidence Intervals (CI) were calculated by using a random-effects model for both primary and secondary outcomes. A total of four RCTs were included for the meta-analysis. Out of the four included clinical trials accepted for its methodological quality, three were of excellent quality and one study was of moderate quality. The pooled estimates of the three studies showed that Remdesivir had a 24% lower risk of SAEs compared to the placebo arm. However, the pooled estimates of two studies showed that 10 days of Remdesivir had 56% higher risk of SAEs compared to 5 days of Remdesivir regimen. Similarly, the 10 days of Remdesivir had two times higher risk of TDAEs compared to 5 days Remdesivir regimen. In conclusion, our meta-analysis demonstrated that Remdesivir is a safe therapeutic option. Our metanalysis revealed 5 days' regimen have better safety profile than 10 days' regimen of drug Remdesivir with respect to SAEs and TDAEs. For hospitalized patients, a 5-day course could be preferable with fewer safety concerns and lower drug costs. PROSPERO Registration ID: CRD 42020224272.

A Systematic Review and Meta-Analysis of the Safety of Hydroxychloroquine in a Randomized Controlled Trial and Observational Studies.

INTRODUCTION: Hydroxychloroquine (HCQ) has recently become the focus of attention in the current COVID-19 pandemic. With an increase in the off-label use of HCQ, concern for the safety of HCQ has been raised. We, therefore, performed this systematic review to analyze the safety data of HCQ against placebo and active treatment in various disease conditions. METHODS: We searched PubMed, Embase, and Cochrane for Randomized Controlled Trials (RCTs) and Observational Studies (OSs) that evaluated HCQ for the treatment of any disease other than COVID19 in adult patients up to May 2020. We assessed the quality of the included studies using Risk of Bias 2 (for RCTs) and Newcastle-Ottawa Scale (for OSs). Data were analyzed with randomeffect meta-analysis. Sensitivity and subgroup analyses were performed to identify heterogeneity. RESULTS: A total of 6641 studies were screened, and 49 studies (40 RCTs and 9 OSs) with a total sample size of 35044 patients were included. The use of HCQ was associated with higher risks of TDAEs as compared to placebo/no active treatment [RR 1.47, 95%CI 1.03-2.08]. When HCQ was compared with active treatments, the risks of AEs [RR 0.74, 95% CI 0.63-0.86] and TDAEs were less in the HCQ arm [RR 0.57, 95% CI 0.39-0.81]. The outcomes did not differ in the sensitivity analysis. CONCLUSION: The results suggest that the use of HCQ was associated with a lower risk of AEs and TDAEs as compared to active treatment, whereas posing higher risk of TDAEs as compared to placebo.

A case report of Arnold Chiari type 1 malformation in acromesomelic dwarf infant.

Arnold Chiari malformation is one of the commonest cause of congenital hydrocephalus. Cause of fetal development of cerebellar tonsils remains unknown and may be diagnosed at later in life. The association of Arnold Chiari malformation with acromesomelic dwarfism is not known. We report male infant diagnosed with acromesomelic dwarfism at end of gestation period on basis of antenatal ultrasonography findings. An ultrasound scan of infant head at fifth month of birth was performed in view of increasing head circumference that revealed aqueductal stenosis with dilated posterior horn of lateral ventricles in brain.