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Background  The flexor hallucis longus (FHL) muscle is crucial in fine motor control of the great toe but the muscle is often sacrificed in free fibula flap (FFF) reconstruction. The aim of this study was to compare great toe movement between complete and partial FHL resection during FFF harvest to see if FHL can be left behind (without undergoing fibrosis) in situ when bulk is not required at the recipient site. Methods  A prospective, cross-sectional, observational study was performed including patients undergoing FFF harvest over a 2-year period. Movement of great toe interphalangeal joint was recorded of operated and unoperated legs in patients undergoing partial and complete FHL harvest and data analyzed. Results  There was a statistically significant ( p  < 0.05) difference between the two groups of patients. Conclusion  FHL can be safely left in situ in patients not requiring bulk at the recipient site as blood supply, nerve supply, and muscle function are not compromised in partial FHL harvest. Further image-based and dye-based studies are warranted., Competing Interests: Conflict of Interest None declared., (Association of Plastic Surgeons of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Snakebite envenomation remains a neglected tropical public health issue claiming thousands of lives every year. It is a common medical emergency and a threat to the impoverished populations of low-income and middle-income countries including India. A combination of ischaemic stroke and deep vein thrombosis is a devastating duo complication of snake bite, with no literature report to date. Here, the authors report an unusual case of a young woman developing ischaemic stroke and deep vein thrombosis following snakebite even after the use of antivenom. MRI brain showed right thalamic infarct with haemorrhagic transformation and, ultrasound Doppler revealed right lower limb deep vein thrombosis. The pathophysiology of deep vein thrombosis and ischaemic stroke is complex. It is believed that the activation of the coagulation cascade, complement system together with endothelial injury and immune activation leads to inflammation, thrombosis and occlusion of smaller and even larger vessels., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Statin monotherapy for dyslipidemia is limited by adverse effects and limited effectiveness in certain subgroups like metabolic syndrome. Add-on therapy with an agent with a known safety profile may improve clinical outcomes, and virgin coconut oil (VCO) may be the candidate agent for improving the cardiometabolic profile. The present study was conducted to evaluate the effect of add-on VCO with atorvastatin in dyslipidemia in adults., Methods: A randomized, double-blind clinical trial was conducted on 150 patients with dyslipidemia who were randomized into control and test groups. The control group received atorvastatin monotherapy, whereas the test group received add-on VCO with atorvastatin for 8 weeks. At baseline, demographic, clinical, and biochemical parameters were assessed and repeated after 8 weeks of therapy. The main outcome measures were lipid profile, cardiovascular risk indices, 10-year cardiovascular risk, body fat compositions, and thiobarbituric acid reactive substances (TBARS)., Results: The increase in HDL in the test group was significantly greater than in the control group (MD: 2.76; 95%CI: 2.43-3.08; p  < 0.001). The changes in the atherogenic index ( p  = 0.003), coronary risk index ( p  < 0.001), cardiovascular risk index ( p  = 0.001), and TBARS ( p  < 0.001) were significantly greater in the test group. The decrease in LDL, total cholesterol and lipoprotein(a), were significantly higher in the control group. There were no significant differences between the groups with respect to the changes in triglyceride, VLDL, and 10-year cardiovascular risk., Conclusions: Add-on VCO (1000 mg/day) with atorvastatin (10 mg/day) can achieve a better clinical outcome in patients with dyslipidemia by increasing HDL and improving oxidative stress cardiovascular risk indices.

Currently, three monoclonal antibodies (MABs) have received regulatory approval from the federal agency, the United States Food and Drug Administration (USFDA), for the medical management of neuromyelitis optica spectrum disorder (NMOSD). Satralizumab was the third approved therapy after MABs like eculizumab and inebilizumab for NMOSD, an uncommon but severe enfeebling autoimmune neurological disease. Satralizumab, a humanized monoclonal antibody, exerts its action in NMOSD by acting against cytokine interleukin-6 (IL-6), a foremost mediator in the pathological process of NMOSD. Two pivotal clinical trials carried out in NMOSD patients had established that satralizumab significantly decreased the rate of relapse in patients suffering from NMOSD as opposed to placebo. The trials also demonstrated that satralizumab is relatively safe. Thus, satralizumab provides an efficacious and safe treatment option for this rare, disabling central nervous system (CNS) disease. Our review aimed to elucidate the pharmacological characteristics of satralizumab and illustrate the available evidence regarding its safety and efficacy in patients with NMOSD., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Meher et al.)

Objectives: To identify factors associated with malnutrition (undernutrition and overnutrition) and determine appropriate cut-off values for mid-arm circumference (MAC) and calf circumference (CC) among community-dwelling Indian older adults., Design: Data from the first wave of harmonised diagnostic assessment of dementia for Longitudinal Ageing Study in India (LASI-DAD) were used. Various sociodemographic factors, comorbidities, geriatric syndromes, childhood financial and health status were included. Anthropometric measurements included body mass index (BMI), MAC and CC., Setting: Nationally representative cohort study including 36 Indian states and union territories., Participants: 4096 older adults aged >60 years from LASI DAD., Outcome Measures: The outcome variable was BMI, categorised as low (<18.5 kg/m 2 ), normal (18.5-22.9 kg/m 2 ) and high (>23 kg/m 2 ). The cut-off values of MAC and CC were derived using ROC curve with BMI as the gold standard., Results: 902 (weighted percentage 20.55%) had low BMI, 1742 (44.25%) had high BMI. Undernutrition was associated with age, wealth-quintile and impaired cognition, while overnutrition was associated with higher education, urban living and comorbidities such as hypertension, diabetes and chronic heart disease. For CC, the optimal lower and upper cut-offs for males were 28.1 cm and >31.5 cm, respectively, while for females, the corresponding values were 26 cm and >29 cm. Similarly, the optimal lower and upper cut-offs for MAC in males were 23.9 cm and >26.9 cm, and for females, they were 22.5 cm and >25 cm., Conclusion: Our study identifies a high BMI prevalence, especially among females, individuals with higher education, urban residents and those with comorbidities. We establish gender-specific MAC and CC cut-off values with significant implications for healthcare, policy and research. Tailored interventions can address undernutrition and overnutrition in older adults, enhancing standardised nutritional assessment and well-being., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The use of conventional glucagon for managing insulin-induced hypoglycemia is obscured by its chemical instability and the need for reconstitution of the lyophilized powder, leading to delayed rescue. Dasiglucagon, a glucagon analog, may potentially overcome these shortcomings., Aims: To evaluate the efficacy and safety of dasiglucagon in insulin-induced hypoglycemia in patients with type 1 diabetes mellitus (T1DM)., Study Design: Meta-analysis., Methods: PubMed/MEDLINE, Scopus, Embase, and Cochrane databases along with clinical trial registries were searched to include data from five randomized controlled trials conducted using dasiglucagon for the treatment of insulin-induced hypoglycemia in T1DM patients published until May 2023. We performed a risk of bias assessment to determine the quality of the included studies and a random-effects model analysis for determining the effect size. Subgroup analysis and meta-regression were done as applicable., Results: The time to recovery (in minutes) with dasiglucagon was earlier than placebo [mean difference (MD): -24.73; 95% confidence interval (CI): -30.94 to -18.52; p < 0.00001) or oral glucose (MD: -15.00; 95% CI: -20.33 to -9.67; p < 0.00001); however, the difference between dasiglucagon and glucagon was not statistically significant (MD: -0.76; 95% CI: -2.19 to 0.66; p = 0.29)., Conclusion: Dasiglucagon is safer and more effective than placebo or oral glucose for insulin-induced hypoglycemia in T1DM patients; however, it is not superior to conventional glucagon.

Malnutrition in low- and middle-income countries causes cognitive decline and other health problems. Harmonized Diagnostic Assessment of Dementia for Longitudinal Aging Study in India (LASI DAD) is an extensive study on late-life cognition and dementia. This study examines the link between nutrition and cognitive abilities in older adults using data from the LASI DAD. We conducted descriptive statistics on nutritional parameters (body-mass index, waist-hip ratio, and Mini-Nutritional Assessment), cognitive functions, and socio-demographic variables in 2,892 adults aged ≥60 years. Cognitive domains assessed included delayed recall, orientation, language, executive function, abstract reasoning, and attention. Cognitive impairment was defined as impaired performance in two or more domains. Mean age was 69.3 ± 7.1 years, 52.9% were female, and 57.5% were illiterate. Low body-mass index (adjusted OR: 1.88, p  < .001), at risk of malnutrition (adjusted OR: 1.89, p  < .001) and malnourished (adjusted OR: 2.86, p  < .001) on Mini-Nutritional Assessment were associated with the presence of cognitive impairment. Better cognitive performance was associated with increased body mass index (adjusted OR: 0.74, p -.03), hemoglobin (adjusted OR: 0.91, p -.006), and serum albumin (adjusted OR: 0.38, p  < .001). This study shows that nutritional status assessed by anthropometric measures and blood markers is strongly linked to cognitive performance in older adults., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Competing Interests: Competing interests: None declared.

Introduction: Prior estimates of dementia prevalence in India were based on samples from selected communities, inadequately representing the national and state populations., Methods: From the Longitudinal Aging Study in India (LASI) we recruited a sample of adults ages 60+ and administered a rich battery of neuropsychological tests and an informant interview in 2018 through 2020. We obtained a clinical consensus rating of dementia status for a subsample (N = 2528), fitted a logistic model for dementia status on this subsample, and then imputed dementia status for all other LASI respondents aged 60+ (N = 28,949)., Results: The estimated dementia prevalence for adults ages 60+ in India is 7.4%, with significant age and education gradients, sex and urban/rural differences, and cross-state variation., Discussion: An estimated 8.8 million Indians older than 60 years have dementia. The burden of dementia cases is unevenly distributed across states and subpopulations and may therefore require different levels of local planning and support., Highlights: The estimated dementia prevalence for adults ages 60+ in India is 7.4%. About 8.8 million Indians older than 60 years live with dementia. Dementia is more prevalent among females than males and in rural than urban areas. Significant cross-state variation exists in dementia prevalence., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction Hypertension (HTN) is one of the most common conditions encountered in daily practice in hospitals. Combination therapy is mostly initiated in the management of HTN when target blood pressure is not achieved with monotherapy. There are few studies comparing the antihypertensive effect of a combination of azilsartan and amlodipine with a combination of amlodipine and other angiotensin receptor blockers (ARBs), however, the results are contradictory. The objective of this study was to compare the efficacy and safety of the azilsartan and amlodipine combination versus the telmisartan and amlodipine combination in hypertensive patients. Methods The present study was a prospective, randomized, active-controlled, open-label, parallel-group clinical trial. Hypertensive patients were randomized into two groups of 25 patients each. Baseline evaluations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and high-sensitivity troponin I (hsTnI) were done. Patients were reassessed after 12 weeks of drug therapy with azilsartan 40 mg and amlodipine 5 mg combination or telmisartan 40 mg once daily (QD) and amlodipine 5 mg combination QD. Results The response rate (defined as a reduction of more than 20 mm Hg in SBP or 10 mm Hg in DBP or both from baseline at 12 weeks) for HTN in the test group and control groups was found to be 88% and 96% respectively. The response rate of the azilsartan amlodipine group was found to be non-inferior to the telmisartan amlodipine group (odds ratio, OR, 0.31, p = 0.61) at the end of 12 weeks of drug therapy. At 12 weeks of follow-up, there was a significant decrease in SBP (p < 0.001), DBP (p < 0.001), and hsTnI levels (p < 0.001) in both groups from baseline values. However, differences between the test and control groups for blood pressure and hsTnI were found to be not statistically significant at 12 weeks of follow-up. The most commonly reported adverse effect in both groups was headache. Conclusion Azilsartan amlodipine combination had an 88% response rate, which was non-inferior to the telmisartan and amlodipine combination. Biomarkers such as hsTnI showed a significant decrease in both groups after 12 weeks of follow-up. However, there was no significant difference between the two groups., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Dash et al.)

Abstract: Agricultural poisons (insecticides and pesticides) are the most common types of poison implicated in the morbidity and mortality associated with acute poisoning. Suicidal ingestion is more frequent than accidental or homicidal poisonings. Pyrethroids are considered relatively safer than other insecticides. Lambda-cyhalothrin (LCH) belongs to the fourth-generation, type II synthetic pyrethroid. To the best of our knowledge, fatalities after LCH exposure have not yet been reported in the literature. Here, we describe a case of LCH poisoning in a 54-year-old male farmer after an accidental pipe burst in a sprayer while spraying in the field. The patient died 10 days after poisoning due to severe neurotoxicity resulting in bilateral parieto-occipital and brainstem infarcts. The histopathological features of the brain associated with LCH poisoning have been discussed in this report., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The purpose of this study is to propose a quantitative assessment scheme to help with surgical bone drilling training. This pilot study gathered and compared motion and force data from expert surgeons (n = 3) and novice residents (n = 6). The experiment used three-dimensional printed bone simulants of young bone (YB) and osteoporotic bone (OB), and drilling overshoot, time, and force were measured. There was no statistically significant difference in overshoot between the two groups (p = 0.217 for YB and 0.215 for OB). The results, however, show that the experts took less time (mean = 4.01 s) than the novices (mean = 9.98 s), with a statistical difference (p = 0.003 for YB and 0.0001 for OB). In addition, the expert group performed more consistently than the novices. The force analysis further revealed that experts used a higher force to drill the first cortical section and a noticeably lower force in the second cortex to control the overshoot (approximate reduction of 5.5 N). Finally, when drilling time and overshoot distance were combined, the motion data distinguished the skill gap between expert and novice drilling; the force data provided insight into the drilling mechanism and performance outcomes. This study lays the groundwork for a data-driven training scheme to prepare novice residents for clinical practice., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia., (© 2023. The Author(s).)

Background Hypothyroidism is associated with hypoadiponectinemia, insulin resistance, and increased cardiovascular risk. The association of adiponectin, insulin resistance, and future cardiovascular risk in clinical hypothyroidism and the effect of levothyroxine are non-conclusive because of the contradictory results. The present prospective cohort study has been conducted to evaluate the effect of levothyroxine on serum adiponectin, insulin resistance, and cardiovascular risk in patients with clinical hypothyroidism. Methods Sixty patients with clinical hypothyroidism who were prescribed levothyroxine were recruited following selection criteria and changes in Zulewski's score, glycemic parameters, homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), lipid profile, serum adiponectin, serum high-sensitivity C-reactive protein (hs-CRP), cardiovascular risk indices, and Framingham risk score were assessed 12 weeks post-levothyroxine therapy. Receiver operating characteristic (ROC) analysis was done to detect the cut-off for adiponectin levels to differentiate between responders and non-responders. Neural network models were created to predict the risk of cardiovascular morbidity. Results Post-levothyroxine therapy, there was a significant improvement in body mass index (BMI) (p = 0.025), diastolic blood pressure (p = 0.021), Zulewski's score (p < 0.001), serum insulin (p = 0.005), fasting sugar (p < 0.001), serum adiponectin (p < 0.001), thyroid profile (p < 0.001), total cholesterol (p < 0.001), low-density lipoprotein (p < 0.001), high-density lipoprotein (p = 0.007), triglycerides (p = 0.002), and subcutaneous fat (p = 0.015). Serum adiponectin showed significant improvement in hypothyroid patients compared to euthyroid individuals (mean difference: -2.21; 95% CI: -2.52 to -1.91; p < 0.001). Mean difference in insulin resistance (HOMA-IR: 0.3, p < 0.001; QUICKI: -0.002, p < 0.001) and cardiovascular risk (atherogenic index: 0.12, p = 0.04; coronary risk index: 0.14, p = 0.038; Framingham risk score: 0.65, p = 0.041) also showed improvement. Serum adiponectin and thyroid-stimulating hormone levels were directly correlated with insulin resistance and cardiovascular risk scores. Conclusion The reduced serum adiponectin level and increased cardiovascular risk in clinical hypothyroidism were improved with hormone replacement, and serum adiponectin level was found to be a good prognostic marker for the treatment response., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Maiti et al.)

Background: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder. Though corticosteroids are the cornerstone of therapy, the Janus kinase inhibitor abrocitinib has shown promise in recent clinical trials for the treatment of AD., Objective: To assess the overall efficacy and safety of abrocitinib in moderate to severe AD., Methods: All randomized controlled trials (RCTs) evaluating the efficacy and safety of abrocitinib in moderate to severe AD were included in the meta-analysis., Results: The pooled analysis revealed a significant proportion of patients achieving Investigator's Global Assessment (IGA) response (RR = 3.52, 95% CI; 2.78-4.46, p  < .00001), Eczema Area and Severity Index (EASI) response (RR = 3.35, 95% CI; 2.54-4.41, p  < .00001), and Peak Pruritus Numerical Rating Score (PP-NRS) response (RR = 2.54,95% CI; 1.95-3.30, p  < .00001) in abrocitinib arm compared to the placebo arm. Moreover, the pooled analysis also suggested that treatment-emergent adverse events (TAEs) were relatively higher with abrocitinib than placebo (R.R. = 1.17; 95% CI; 1.06-1.29, p  = .002)., Conclusions: This meta-analysis showed that abrocitinib had a significant beneficial effect and tolerable adverse effect profile in patients of AD. Dose regimens of 200 and 100 mg seemed to have similar benefits. However, long-term trials are needed for corroboration.Key pointsAbrocitinib is emerging as a potential treatment option for moderate to severe atopic dermatitis.The pooled analysis from 4 RCTs demonstrated significant effectiveness of abrocitinib in both physician and patient-reported outcomes like IGA, EASI, and PP-NRS. The drug was also well-tolerated across the trials.The number needed to treat (NNT) for all efficacy outcomes was low suggesting clinically desirable benefits with the use of abrocitinib. Trial registration : Review registration number PROSPERO database: CRD42021255634.

Background: Medical faculty and residents have a key role in the reporting of adverse events associated with medical devices. However, at present, there are no published data regarding their knowledge, attitude, and practice about materiovigilance in India., Materials and Methods: This was a cross-sectional questionnaire-based survey done among medical faculty and residents of a tertiary care institution of national importance. The questionnaire consists of 15 questions pertaining to knowledge, attitude, and practice of materiovigilance., Results: The questionnaire was administered to 138 medical faculty and residents, out of which 105 responded constituting a 76% response rate. The mean knowledge score of medical faculty and residents was 2.09 ± 1.06 and 2.07 ± 1.02, respectively, and the difference between the two groups was not statistically significant ( P = 0.9). The majority of the participants (92.63%) believed that medical device can cause adverse events; however, very few of them (20.13%) have reported it during their practice., Conclusion: Requisite knowledge and appropriate attitude are essential for developing healthy practice toward reporting of adverse events associated with medical devices. Our study revealed that the knowledge gap exists among medical professionals about the reporting of adverse events and the materiovigilance program. A continuous effort is required to make them aware of the materiovigilance by conducting various training programs such as continuous medical education and workshops by the coordinators of the medical device adverse events monitoring center., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Perspectives in Clinical Research.)

Introduction The complex interplay between the autonomic nervous system, renin-angiotensin-aldosterone system (RAAS), and immunity contributes to the pathogenesis of hypertension in diabetes mellitus. The objective of this study was to investigate and compare the effect of azilsartan and telmisartan on insulin resistance and metabolic biomarkers in patients with both hypertension and type 2 diabetes mellitus. Methods The present study was a prospective, randomized, active-controlled, open-label, parallel-group clinical trial. Patients with grade I or II essential hypertension with type 2 diabetes mellitus were randomized into two groups of 25 patients each. Baseline evaluation of homeostasis model assessment-insulin resistance (HOMA-IR), plasma glucose, insulin, leptin and adiponectin levels, and systolic and diastolic blood pressure (SBP and DBP) of patients was done. Patients were reassessed after 12 weeks of drug therapy with azilsartan 40 mg OD (once daily) or telmisartan 40 mg OD. Results The mean changes in HOMA-IR from the baseline at the end of 12 weeks of treatment were 0.15 (-0.64, 0.94.52) in the azilsartan group and 0.32 (-0.61, 1.26) in the telmisartan group. The mean difference in the changes from the baseline in HOMA-IR between the two groups was 0.3 (-0.87, 1.48), which was not statistically significant. No statistically significant changes were observed between the two groups in metabolic biomarkers (leptin: -0.84, CI: -4.83 to 3.14, and adiponectin: -0.12, CI: -0.62 to 0.37). Systolic (SBP) and diastolic blood pressure (DBP) decreased at the end of the 12-week treatment in both the groups; however, there was no significant difference between the two groups (SBP: -2.6, CI: -10.35 to 5.1, and DBP: -3.0, CI: -7.7 to 1.7). Conclusion Neither azilsartan nor telmisartan had any significant effects on insulin resistance and metabolic biomarkers after 12 weeks of drug therapy in hypertension patients associated with type 2 diabetes mellitus. However, they showed a comparable antihypertensive effect. The adverse effects observed were mild in nature, and their incidence was comparable between the two groups., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Meher et al.)

Background: This study was conducted to evaluate the cost of ambulatory care of diabetes in a non-communicable disease (NCD) clinic in eastern India., Methods: This hospital-based cross-sectional cost description study was conducted from July to August 2018. A total of 192 diagnosed cases aged 18-70 years with a minimum history of one year since diagnosis attending the NCD clinic for the first time were included. Information was collected using a pre-tested schedule based on the cost of illness approach that consisted of socio-demographic details, disease status, and cost of ambulatory care. Cost of the drugs was calculated using a standardized repository of drug costs. The estimated expenditure of previous three months was calculated and extrapolated to one year to calculate yearly expenditure., Results: The mean age of the study participants was 43.93±10.41 years and the mean duration of diabetes was 6.64±6.08 years. The median direct cost due to diabetes was Rs 9560 (136.57 USD) annually. It was higher in females (Rs 10,056, 143.45 USD) than in males (Rs 9020, 128.85 USD). In direct medical costs, a major part was constituted by the drugs, oral hypoglycemic agents, and/or insulin (approximately 70%)., Conclusions: In an ambulatory framework too, diabetes causes a substantial financial burden on the individual in India. In the wake of resource constraints in Indian health settings, the public health system needs to be adequately strengthened by policymakers to address the growing number of diabetics and long-standing complications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Patro et al.)

Objective: Though systemic corticosteroid is used for treatment of COVID 19, questions regarding the appropriate dose, duration and type of corticosteroid use still remain unanswered. This study aimed to address, whether choice of systemic corticosteroid significantly influences the clinical outcome of COVID 19 patients., Materials and Methods: Studies reporting the comparison between clinical outcome of dexamethasone and methylprednisolone in treatment of COVID 19 were searched from inception till April, 2021. Random-effect model was used. Odd's ratio (OR) and 95% confidence interval was expressed. I2 statistics used for test of heterogeneity., Result: Three studies with 373 patients (160 in dexamethasone group and 213 in methyl prednisolone group) were included. Though, statistically significant reduction in all-cause mortality with methyl prednisolone group in comparison to dexamethasone group (OR=1.80, 95%CI: 1.08 to 3.01, P=0.02) estimated, sub group analysis of observational studies did not support the finding (OR=1.60, 95% CI: 0.88 to 2.92, P=0.12). No significant difference in terms of need for invasive ventilator or intensive care unit (ICU) between the 2 groups. The grade of evidence was very low for both the outcomes. Conclusion and Relevance: In the present context, both dexamethasone and methyl prednisolone are equally effective in the management of COVID 19., (© Journal of the Association of Physicians of India 2011.)

Purpose: Till date, only systemic corticosteroids have demonstrated definite mortality benefit in management of COVID 19 in various studies. Still certain questions regarding the appropriate dose, duration and timing of corticosteroids remain unanswered. For this reason, the study was planned to determine the efficacy and safety of the pulse dose methyl prednisolone in management of COVID 19 from the publicly available evidence., Methods: PubMed, the Cochrane library, ClinicalTrials.gov and medRxiv were searched for articles reporting the use of pulse dose methyl prednisolone in COVID 19 from inception till 31st May, 2021. Odds ratios (ORs) were calculated for estimation of pooled effect by using random effect model and heterogeneity was checked by using I2 statistics., Results: Twelve studies (11 observational and 1 RCT) were included in the systematic review. A total of 3110 patients from 9 studies were included in the meta-analysis. Though the use of pulse dose methyl prednisolone demonstrated statistically significant mortality benefit in comparison to usual care (OR=0.71, 95% CI: 0.51 to 0.97, [P=0.03]), (I2= 21%) with calculated Number needed to treat (NNT) of 23.5, there was no statistically significant difference between the use of pulse dose and low dose corticosteroid (OR=0.66, 95% CI: 0.44 to 1.01, [(P=0.05]), (I2= 25%) and the NNT is 23.5. Incidence of adverse events were similar across all the groups. The grade of evidence for primary outcome was of moderate certainty., Conclusion: This meta-analysis concurs with the previous reports regarding the use of corticosteroid in COVID 19 in comparison to usual care. However, for both the primary and secondary outcome, the study did not find any statistically significant difference between the use of pulse dose methyl prednisolone and low dose corticosteroid to treat COVID 19 patients.

Competing Interests: There are no conflicts of interest.

Background: Cerebral malaria is a common presentation of severe Plasmodium falciparum infection and remains an important cause of death in the tropics. Key aspects of its pathogenesis are still incompletely understood, but severe brain swelling identified by magnetic resonance imaging (MRI) was associated with a fatal outcome in African children. In contrast, neuroimaging investigations failed to identify cerebral features associated with fatality in Asian adults., Methods: Quantitative MRI with brain volume assessment and apparent diffusion coefficient (ADC) histogram analyses were performed for the first time in 65 patients with cerebral malaria to compare disease signatures between children and adults from the same cohort, as well as between fatal and nonfatal cases., Results: We found an age-dependent decrease in brain swelling during acute cerebral malaria, and brain volumes did not differ between fatal and nonfatal cases across both age groups. In nonfatal disease, reversible, hypoxia-induced cytotoxic edema occurred predominantly in the white matter in children, and in the basal ganglia in adults. In fatal cases, quantitative ADC histogram analyses also demonstrated different end-stage patterns between adults and children: Severe hypoxia, evidenced by global ADC decrease and elevated plasma levels of lipocalin-2 and microRNA-150, was associated with a fatal outcome in adults. In fatal pediatric disease, our results corroborate an increase in brain volume, leading to augmented cerebral pressure, brainstem herniation, and death., Conclusions: Our findings suggest distinct pathogenic patterns in pediatric and adult cerebral malaria with a stronger cytotoxic component in adults, supporting the development of age-specific adjunct therapies., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Cerebral malaria (CM) affects children and adults, but brain swelling is more severe in children. To investigate features associated with brain swelling in malaria, we performed blood profiling and brain MRI in a cohort of pediatric and adult patients with CM in Rourkela, India, and compared them with an African pediatric CM cohort in Malawi. We determined that higher plasma Plasmodium falciparum histidine rich protein 2 (PfHRP2) levels and elevated var transcripts that encode for binding to endothelial protein C receptor (EPCR) were linked to CM at both sites. Machine learning models trained on the African pediatric cohort could classify brain swelling in Indian children CM cases but had weaker performance for adult classification, due to overall lower parasite var transcript levels in this age group and more severe thrombocytopenia in Rourkela adults. Subgrouping of patients with CM revealed higher parasite biomass linked to severe thrombocytopenia and higher Group A-EPCR var transcripts in mild thrombocytopenia. Overall, these findings provide evidence that higher parasite biomass and a subset of Group A-EPCR binding variants are common features in children and adult CM cases, despite age differences in brain swelling.

Snakebite envenomation in pregnancy is rare. We report two cases of vasculotoxic snakebite in pregnancy and discuss the management challenges in pregnancy for successful maternal and perinatal outcomes. The first case was a 19-year-old woman who was eight weeks of gestation in her second pregnancy when she was bitten. She subsequently delivered by caesarean section at 33 weeks and 3 days because she developed eclampsia. The second case was a 24 year old woman in her third pregnancy, who was bitten at 29 weeks of gestation, who delivered vaginally at 36 weeks of gestation. Both were treated with multidisciplinary team approach including antisnake venom and antibiotics, along with fasciotomy for the second case. Both mothers recovered completely, without evidence of attributable fetal or neonatal morbidity. To conclude, antisnake venom, if indicated, and a multidisciplinary team approach plays an important role for successful maternal and perinatal outcomes in snakebite envenomation in pregnancy., (© The Author(s) 2020.)

Introduction Healthcare workers (HCWs) are vulnerable to getting infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Preventing HCWs from getting infected is a priority to maintain healthcare services. The therapeutic and preventive role of ivermectin in coronavirus disease 2019 (COVID-19) is being investigated. Based on promising results of in vitro studies of oral ivermectin, this study was conducted with the aim to demonstrate the prophylactic role of oral ivermectin in preventing SARS-CoV-2 infection among HCWs at the All India Institute of Medical Sciences (AIIMS) Bhubaneswar. Methods A prospective cohort study was conducted at AIIMS Bhubaneswar, which has been providing both COVID and non-COVID care since March 2020. All employees and students of the institute who provided written informed consent participated in the study. The uptake of two doses of oral ivermectin (300 μg/kg/dose at a gap of 72 hours) was considered as exposure. The primary outcome of the study was COVID-19 infection in the following month of ivermectin consumption, diagnosed as per Government of India testing criteria (real-time reverse transcriptase polymerase chain reaction [RT-PCR]) guidelines. The log-binomial model was used to estimate adjusted relative risk (ARR), and the Kaplan-Meier failure plot was used to estimate the probability of COVID-19 infection with follow-up time. Results Of 3892 employees, 3532 (90.8%) participated in the study. The ivermectin uptake was 62.5% and 5.3% for two doses and single dose, respectively. Participants who took ivermectin prophylaxis had a lower risk of getting symptoms suggestive of SARS-CoV-2 infection (6% vs 15%). HCWs who had taken two doses of oral ivermectin had a significantly lower risk of contracting COVID-19 infection during the following month (ARR 0.17; 95% CI, 0.12-0.23). Females had a lower risk of contracting COVID-19 than males (ARR 0.70; 95% CI, 0.52-0.93). The absolute risk reduction of SARS-CoV-2 infection was 9.7%. Only 1.8% of the participants reported adverse events, which were mild and self-limiting. Conclusion Two doses of oral ivermectin (300 μg/kg/dose given 72 hours apart) as chemoprophylaxis among HCWs reduced the risk of COVID-19 infection by 83% in the following month. Safe, effective, and low-cost chemoprophylaxis has relevance in the containment of pandemic alongside vaccine., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Behera et al.)

Background: Tumour-induced osteomalacia (TIO) or oncogenic osteomalacia is a rare variant of paraneoplastic syndrome secondary to a small benign phosphaturic mesenchymal tumour that secretes phosphaturic substances. Complete tumour excision is often curative. However, the localization of these offending tumours has always remained a challenge because of their small size, slow-growing nature, and presence in atypical locations. We performed a systemic review and meta-analysis on the sensitivity and specificity of F-18 FDG PET/CT and Ga-68 DOTA-SSTR PET/CT to detect tumours causing osteomalacia., Methods: Pub Med, SCOPUS, the Cochrane Library and Web of Science were searched for articles on F-18 FDG and Ga-68 DOTA-SSTR PET/CT in the detection of culprit tumours in TIO till September 2020. Both retrospective and prospective studies having three or more patients were included. The methodological quality of included studies was assessed using the Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. A random-effect model was used for the statistical pooling of sensitivity and specificity. Pooled data were presented with 95% confidence intervals (95% CI) and displayed using Forest plots. Heterogeneity was expressed using the I2 statistic., Results: The pooled sensitivity of Ga-68 DOTA-SSTR PET/CT in detecting the culprit tumour derived from all included studies is 86% (95% CI: 79-91%). There is moderate statistical heterogeneity among the included studies (I2 = 72.7%). The pooled sensitivity of F-18 FDG PET/CT in detecting the offending tumour derived from all included studies is 73% (95% CI: 61-84%) with moderate statistical heterogeneity among the included studies (I2 = 45.4%)., Conclusion: In the detection of offending tumours in TIO, Ga-68 DOTA-SSTR PET/CT has better sensitivity than F-18 FDG PET/CT and should be used as first-line imaging modality due to very high sensitivity., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Since November 2019, SARS Coronavirus 2 disease (COVID-19) pandemic has spread through more than 195 nations worldwide. Though the coronavirus infection affects all age and sex groups, the mortality is skewed towards the elderly population and the cause of death is mostly acute respiratory distress syndrome (ARDS). There are data suggesting the role of excessive immune activation and cytokine storm as the cause of lung injury in COVID-19. The excessive immune activation and cytokine storm usually occurs due to an imbalance in redox homeostasis of the individuals. Considering the antioxidant and free radical scavenging action of N acetyl cysteine (NAC), its use might be useful in COVID-19 patients by decreasing the cytokine storm consequently decreasing the disease severity. Therefore, we reviewed all the available resources pertaining to the role of reactive oxygen species (ROS) in cytokine storm and the mechanism of action of NAC in preventing ROS. We also reviewed the use of NAC in COVID-19.

Background: Ivermectin is one among several potential drugs explored for its therapeutic and preventive role in SARS-CoV-2 infection. The study was aimed to explore the association between ivermectin prophylaxis and the development of SARS-CoV-2 infection among healthcare workers., Methods: A hospital-based matched case-control study was conducted among healthcare workers of AIIMS Bhubaneswar, India, from September to October 2020. Profession, gender, age and date of diagnosis were matched for 186 case-control pairs. Cases and controls were healthcare workers who tested positive and negative, respectively, for COVID-19 by RT-PCR. Exposure was defined as the intake of ivermectin and/or hydroxychloroquine and/or vitamin-C and/or other prophylaxis for COVID-19. Data collection and entry was done in Epicollect5, and analysis was performed using STATA version 13. Conditional logistic regression models were used to describe the associated factors for SARS-CoV-2 infection., Results: Ivermectin prophylaxis was taken by 76 controls and 41 cases. Two-dose ivermectin prophylaxis (AOR 0.27, 95% CI, 0.15-0.51) was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Those involved in physical activity (AOR 3.06 95% CI, 1.18-7.93) for more than an hour/day were more likely to contract SARS-CoV-2 infection. Type of household, COVID duty, single-dose ivermectin prophylaxis, vitamin-C prophylaxis and hydroxychloroquine prophylaxis were not associated with SARS-CoV-2 infection., Conclusion: Two-dose ivermectin prophylaxis at a dose of 300 μg/kg with a gap of 72 hours was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Chemoprophylaxis has relevance in the containment of pandemic., Competing Interests: The authors have declared that no competing interests exist.

Though Convalescent plasma therapy (CPT) is being used for management of COVID-19, the evidence is still equivocal. So, we carried out this study to evaluate the currently available data to provide evidence about CPT in COVD-19 patients. RCTs and observational studies with sample size with more than 5 were included in the analysis. Out of 196 studies, 12 studies were selected for systematic review and meta-analysis was carried out for 6 studies having a control arm. For dichotomous values, risk ratio (RR) and 95% confidence interval was expressed., Main Outcomes: All-cause mortality, clinical improvement by day 7 and viral detection by day 7 were the defined outcome measures before starting of data extraction., Result: For 6 studies (2 RCTs and 4 observational studies) with 474 patients, the overall pooled RR for all-cause mortality was 0.61 (95%CI: 0.37 to 0.99. P= 0.04). Only RCTs and only observational studies for all-cause mortality showed pooled RR of 0.60 (95% CI: 0.33 to 1.10, P=0.10) and 0.48 (95% CI: 0.17 to 1.36, P= 0.17) respectively. There was risk of bias in the studies due to randomization process and confounding. Sensitivity analysis was carried out only for observational studies. The overall pooled RR for clinical improvement by day 7 and viral detection by day 7 were 1.12 (95%CI: 0.96 to 1.31, P=0.16) and 0.19 (95%CI: 0.09 to 0.60, P < 0.0001)., Conclusion and Relevance: Though the review suggests modest utility of CPT in reducing all-cause mortality, improving clinical outcome, and early viral clearance, it should be interpreted cautiously., (© Journal of the Association of Physicians of India 2011.)

The Harmonized Diagnostic Assessment of Dementia for Longitudinal Aging Study in India (LASI-DAD) is a population-representative, prospective cohort study of late-life cognition and dementia. It is part of an ongoing international research collaboration that aims to measure and understand cognitive impairment and dementia risk by collecting a set of cognitive and neuropsychological assessments and informant reports, referred to as the Harmonized Cognitive Assessment Protocol (HCAP). LASI-DAD provides nationally representative data drawn from a subsample of the ongoing Longitudinal Aging Study in India (LASI). One of LASI-DAD's distinctive features is its rich geriatric assessment, including the collection of venous blood samples and brain imaging data for a subsample of respondents. In this paper, we discuss the methodological considerations of developing and implementing the HCAP protocol in India. The lessons we learned from translating and applying the HCAP protocol in an environment where illiteracy and innumeracy are high will provide important insights to researchers interested in measuring and collecting data on late-life cognition and dementia in developing countries. We further developed an innovative blood management system that enables us to follow the collection, transportation, assay, and storage of samples. Such innovation can benefit other population surveys collecting biomarker data.

Background: As future practitioners, undergraduate medical students have a key role in the antimicrobial stewardship program (ASP). However, at present, there are not much data about their knowledge and perception of antibiotic resistance and ASP., Methods: This was a cross-sectional questionnaire-based survey administered to the prefinal- and final-year undergraduate medical students of a tertiary care institution., Results: One hundred and ninety-seven students participated in our study constituting 70% response rate. The mean difference in knowledge score between prefinal- and final-year students was 0.77 (95% confidence interval: 0.30-1.24, P = 0.0016). Thirty-seven (39.7%) prefinal- and 57 (54.8%) final-year students knew the correct definition of antimicrobial stewardship. Majority of the participants, i.e., 66 (70.9%) prefinal-year and 80 (76.9%) final-year students perceived antibiotic resistance as a public health problem. Principal component analysis revealed the greater role of attitude-related questions., Conclusion: Good knowledge and positive attitude are paramount for the effective implementation of the antibiotic stewardship program. Our study revealed that the knowledge gap exists among the undergraduate students about the rational use of the antibiotic stewardship program. It was also revealed that the role of attitude plays a more significant role than knowledge for the proper understanding of the program. A sustained effort is required to make them aware of the rational use of antibiotics by incorporating the knowledge and practice of the ASP into their study curriculum., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Perspectives in Clinical Research.)

The current management of COVID-19 is mostly limited to general supportive care and symptomatic treatment. Ivermectin is a broad-spectrum anti-parasitic drug used widely for the treatment of onchocerciasis and lymphatic filariasis. Apart from its anti-parasitic effect it also exhibits antiviral activity against a number of viruses both in vitro and in vivo. Hence, we conducted this systematic review and meta-analysis to assess the currently available data on the therapeutic potential of ivermectin for the treatment of COVID-19 as add on therapy. A total of 629 patients were included in the 4 studies and all were COVID-19 RT-PCR positive. Among them, 397 patients received ivermectin along with usual therapy. The random effect model showed the overall pooled OR to be 0.53 (95%CI: 0.29 to0.96) for the primary outcome (all-cause mortality) which was statistically significant (P=0.04). Similarly, the random effect model revealed that adding ivermectin led to significant clinical improvement compared to usual therapy (OR=1.98, 95% CI: 1.11 to 3.53, P=0.02).  However, this should be inferred cautiously as the quality of evidence is very low. Currently, many clinical trials are on-going, and definitive evidence for repurposing this drug for COVID-19 patients will emerge only in the future.

Many key biologics are scheduled to lose their patent by the year 2020, which will provide the opportunity to other biopharmaceutical companies to develop the similar biologics. Biosimilar or similar biologic used has increased in the recent year following the approval of the first biosimilar in early 2000. India is one of the leading manufacturers of similar biologics. India has developed a new guideline in 2012 for the pre- and post-marketing approval of similar biologics., Competing Interests: There are no conflicts of interest.

The mechanisms underlying the rapidly reversible brain swelling described in patients with cerebral malaria (CM) are unknown. Using a 1.5-Tesla (T) magnetic resonance imaging (MRI) scanner, we undertook an observational study in Rourkela, India, of 11 Indian patients hospitalized with CM and increased brain volume. Among the 11 cases, there were 5 adults and 6 children. All patients had reduced consciousness and various degrees of cortical swelling at baseline. The latter was predominately posterior in distribution. The findings on diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps were consistent with vasogenic edema in all cases. Reversibility after 48 to 72 h was observed in >90% of cases. DWI/ADC mismatch suggested the additional presence of cytotoxic edema in the basal nuclei of 5 patients; all of these had perfusion parameters consistent with vascular engorgement and not with ischemic infarcts. Our results suggest that an impairment of the blood-brain barrier is responsible for the brain swelling in CM. In 5 cases, vasogenic edema occurred in conjunction with changes in the basal nuclei consistent with venous congestion, likely to be caused by the sequestration of Plasmodium falciparum -infected erythrocytes. While both mechanisms have been individually postulated to play an important role in the development of CM, this is the first demonstration of their concurrent involvement in different parts of the brain. The clinical and radiological characteristics observed in the majority of our patients are consistent with posterior reversible encephalopathy syndrome (PRES), and we show for the first time a high frequency of PRES in the context of CM. IMPORTANCE The pathophysiology and molecular mechanisms underlying cerebral malaria (CM) are still poorly understood. Recent neuroimaging studies demonstrated that brain swelling is a common feature in CM and a major contributor to death in pediatric patients. Consequently, determining the precise mechanisms responsible for this swelling could open new adjunct therapeutic avenues in CM patients. Using an MRI scanner with a higher resolution than the ones used in previous reports, we identified two distinct origins of brain swelling in both adult and pediatric patients from India, occurring in distinct parts of the brain. Our results support the hypothesis that both endothelial dysfunction and microvascular obstruction by Plasmodium falciparum -infected erythrocytes make independent contributions to the pathogenesis of CM, providing opportunities for novel therapeutic interventions.

Diabetes Mellitus (DM) is a metabolic disorder characterized by relative or absolute deficiency of insulin, resulting in hyperglycemia. Subcutaneous insulin and Oral Hypoglycaemic Agents (OHA) constitute the main treatment option for DM. Insulin is administered by injection or continuous infusion to control glucose levels mainly in Type I diabetes. Newer routes both oral and non oral, for insulin administration are current direction of insulin research as insulin injection therapy is burdensome and painful for many patients. Inhalational insulin is an attractive alternative for systemic administration of insulin given its accessibility and large alveolar-capillary network of lungs for drug absorption. Afrezza, inhaled insulin has been recently approved by Food and Drug Administration (FDA). It is a new, quicker acting inhalable insulin with a different and safer pharmacokinetic profile in comparison to previously failed inhaled form of insulin.

Increased heart rate during graded exercise is related to increased sympathetic activity and withdrawal of vagal tone. Return of heart rate towards baseline immediately after exercise is usually due to resurgence of vagal tone. As it is an established fact that cardiovascular morbidity and mortality in part has direct relation with parasympathetic dysfunction, it is natural that reduced heart rate recovery (HRR) after exercise, a parameter of parasympathetic dysfunction, could be a predictor of morbidity and mortality. Accordingly 390 TMT positive patients were analysed for HRR as per standard guidelines and followed up for 5 years. While 244(62.6%) showed a normal HRR, 146(37.4%) showed an abnormal HRR. Abnormal HRR was more common in the elderly, in patients with higher resting heart rate, hypertension, diabetes mellitus, current smoking and prior established coronary artery disease (CAD). There were a total of 36 deaths (9.23%) during the 5 year follow-up period. There was mortality advantage in patients who were subjected to revascularization procedure in general (7.5% deaths in revascularised arm vs 10.4% in conservative arm). Analysis reveals persistence of such benefit in patients having normal HRR (2.85% deaths in revascularised arm vs 7.25% in conservative arm). However, mortality benefit was not observed among both groups of patients with abnormal HRR(16.6% deaths in revascularised vs 15.2% in conservatively managed7rpar;. Secondary end points like recurrent angina, arrhythmia, acute myocardial infarction, hospitalization for cardiovascular cause and heart failure were observed in significantly more number of cases with abnormal HRR in comparison to normal. We therefore conclude the abnormal HRR after TMT is an adverse prognostic indicator in patients with symptomatic CAD on long term follow-up.

M-mode echocardiography has been accepted as gold standard for measuring left atrial (LA) size. Electrocardiography (ECG) offers a simple, non-invasive, cost-effective and reproducible method to assess LA size and it is mostly in agreement with echocardiography though discrepancies exist. ECGs and echocardiograms were obtained in 100 consecutive patients suspected of having left atrial enlargement due to different underlying heart diseases. The diagnostic accuracy of six ECG criteria of LA enlargement were evaluated comparing with LA size in M-mode echo study. Various criteria were found to be poor to mildly sensitive (8% to 78%) but highly specific (85% to 100%) for left atrial enlargement. Morris Index (PTFV1) was found to be the best criterion having 76% sensitivity and 92% specificity. Combination of criteria enhances the sensitivity at the cost of specificity. Overall predictive index of electrocardiogram for left atrial enlargement is not encouraging.

[reaction: see text] A new method for the one-pot asymmetric reductive amination of prochiral aliphatic ketones has been developed. The previously unexplored reagent combination of Ti(O(i)Pr)(4)/Raney Ni/H(2) in the presence of (R)- or (S)-alpha-methylbenzylamine provides good to excellent yield (76-90%) and diastereomeric excess (72-98%). The second step, hydrogenolysis, provides the corresponding primary amine in high yield (88-93%) and with uncompromised enantiomeric excess.