Pharmacogenomics-assisted schizophrenia management: A hybrid type 2 effectiveness-implementation study protocol to compare the clinical utility, cost-effectiveness, and barriers.

OBJECTIVES: The response to antipsychotic therapy is highly variable. Pharmacogenomic (PGx) factors play a major role in deciding the effectiveness and safety of antipsychotic drugs. A hybrid type 2 effectiveness-implementation research will be conducted to evaluate the clinical utility (safety and efficacy), cost-effectiveness, and facilitators and barriers in implementing PGx-assisted management compared to standard of care in patients with schizophrenia attending a tertiary care hospital in eastern India. METHODS: In part 1, a randomized controlled trial will be conducted. Adult patients with schizophrenia will be randomized (2: 1) to receive PGx-assisted treatment (drug and regimen selection depending on the results of single-nucleotide polymorphisms in genes DRD2, HTR1A, HTR2C, ABCB1, CYP2D6, CYP3A5, and CYP1A2) or the standard of care. Serum drug levels will be measured. The patients will be followed up for 12 weeks. The primary endpoint is the difference in the Udvalg for Kliniske Undersøgelser Side-Effect Rating Scale score between the two arms. In part 2, the cost-effectiveness of PGx-assisted treatment will be evaluated. In part 3, the facilitators and barriers to implementing PGx-assisted treatment for schizophrenia will be explored using a qualitative design. EXPECTED OUTCOME: The study findings will help in understanding whether PGx-assisted management has a clinical utility, whether it is cost-effective, and what are the facilitators and barriers to implementing it in the management of schizophrenia. TRIAL REGISTRATION: The study has been registered with the Clinical Trials Registry-India (CTRI/2023/08/056210).

Performance in a Balance Test and Prediction of All-Cause Mortality in Community-Dwelling Elderly Ambulatory Individuals: A Systematic Review and Meta-analysis.

Objective: This systematic review and meta-analysis was performed to evaluate the association between an inability to perform a static balance test and mortality in community-dwelling older ambulatory individuals. Methods: PubMed, Embase, and Scopus were searched for relevant cohort studies. Hazard ratios (HR) were pooled (random-effect model). Meta-regression was performed with independent demographic variables (PROSPERO ID: CRD42022381137). Results: A total of 11,713 articles were screened and 15 were included. An inability to perform a static balance test was significantly associated with a higher risk of mortality irrespective of whether confounding variables were considered [HR, 1.14 (95% CI: 1.07-1.21); p < .001; i2, 87.96% (p < .01)] or not [HR, 1.11 (95% CI: 1.03-1.20); p = .01; i2, 95.28% (p < .01)] (both moderate GRADE evidence). Also, this association was correlated with progressive age. Conclusion: An inability to successfully complete a static balance test was significantly associated with a higher risk of mortality among community-dwelling older ambulatory individuals.

A review of clinical trials registered in India from 2008 to 2022 to describe the first-in-human trials.

Aim: This analysis was conducted to review the number, and describe the characteristics of first-in-human (FIH) Phase 1 clinical trials registered in India from 2008 to 2022. Materials and Methods: The data were extracted from the Clinical Trials Registry - India database for all FIH Phase 1 clinical trials registered between 2008 and 2022. Early-phase trials that were not FIH trials (e.g., pharmacokinetic studies and drug-drug interaction studies) were excluded from the study. Results: A total of 1891 trials were retrieved and 220 were included in the analysis. Most of the investigational products were drugs (55%) followed by vaccines (38.2%). The most common therapeutic class of drugs was cancer chemotherapy (19.8%), followed by antimicrobial chemotherapy and endocrinology (18.2% each). The most common vaccine was the influenza vaccine (21.4%), followed by the measles-mumps-rubella vaccine (15.5%). The pharmaceutical industry was the predominant sponsor for most (91%) of the Phase 1 trials. Of the top five sites where most of the Phase 1 trials were conducted, three were private nonacademic centers (cumulatively 31%) and two were tertiary care medical colleges (cumulatively 9%). Conclusion: Phase 1 clinical trials seem to be conducted in India predominantly with industry sponsorship. There is a need to have an alternate ecosystem to take forward molecules that do not receive adequate attention from the industry and molecules that are of national health priority other than areas such as chemotherapy, antimicrobials, and endocrinology. The Indian Council of Medical Research is setting up Phase 1 clinical trial capacity for molecules that predominantly may arise from nonindustry channels.

The Burden and Correlates of Waterpipe (Hookah) Smoking among Adolescents and Youth: A Systematic Review.

BACKGROUND: This systematic review evaluated the available medical literature on the prevalence and trends of waterpipe tobacco smoking among adolescents and youth in jurisdictionally representative populations. METHODS: PubMed, Embase, and Scopus were searched for relevant studies from inception until 31 December 2022 that reported the burden of waterpipe smoking among adolescents and youth (10-24 years of age). We extracted qualitative data on the demographic characteristics, burden, and correlates of waterpipe smoking (PROSPERO ID: CRD42022310982). RESULTS: A total of 2,197 articles were screened and 62 were included in the analysis. The majority (29) of the studies was from the United States of America and there were no studies from the south-east Asian region. The prevalence of ever waterpipe smoking among the 10-24 years age group was noted to be 18.16% (95% CI, 18.03-18.29). The prevalence of current (30-day) waterpipe smoking was 6.43% (95% CI, 6.34-6.50). The age of initiation of waterpipe smoking was variable. The prevalence of waterpipe smoking was higher among males, among those who belong to the high- and middle-income groups, and among university students. The common risk factors of waterpipe smoking included cigarette smoking, alcohol, and substance use. Waterpipe smoking resulted in increased susceptibility to the use of conventional forms of tobacco (e.g. smoking) among those who were never smokers. CONCLUSION: Waterpipe smoking usage was significantly high among adolescents and young adults. Developing regulatory guidelines for water-pipe smoking, surveillance of its use, intervention, and specific policy frameworks may be considered a public health priority.

Vibrating colon-stimulating capsule to treat chronic constipation: A systematic review.

In August 2022, the United States Food and Drug Administration issued marketing authorization for an orally administered vibrating colon-stimulating capsule for treating chronic idiopathic constipation. We aimed to review the literature systematically and synthesize evidence on the role of the vibrating capsule in chronic idiopathic constipation. A comprehensive search was conducted on PubMed, Embase, International Clinical Trials Registry Platform (World Health Organization), Cochrane Library databases, and two pre-print servers (medRxiv.org and Research Square) until 31 December 2022, to identify published pre-clinical and clinical original studies evaluating the role of the vibrating capsule in patients with chronic constipation. The studies were critically analyzed, and data were extracted. We identified thirty-three articles and five studies (one pre-clinical, one combined, and three clinical). The pre-clinical studies in dogs revealed no adverse effects of the vibrating capsule. In the clinical studies, there were significant findings observed. The number of spontaneous bowel movements per week and the proportion of patients experiencing an increase of at least one complete spontaneous bowel movement per week were both significantly higher in the group receiving the vibrating capsule compared to the group receiving the sham capsule. No treatment-related serious adverse event was noted. The mild adverse events were vibration sensation, diarrhea, and abdominal discomfort. The efficacy and safety profiles of the vibrating colon-stimulating capsule in treating patients with chronic constipation are promising. However, more robust evidence is required by conducting large randomized clinical trials before conclusively determining its wider use.

Efficacy and safety of bempedoic acid lipid-lowering therapy: a systematic review and meta-analysis of randomized controlled trials.

AIM: This systematic review and meta-analysis was conducted to synthesize the efficacy and safety of bempedoic acid in patients requiring lipid-lowering therapy. METHODS: PubMed, Embase, and Scopus databases were searched for randomized controlled trials from inception till June 2023. The primary outcome was major adverse cardiovascular events (MACE), and secondary outcomes were all-cause mortality, serum lipid profile, and adverse events between bempedoic acid and comparators. ROB2 was used for risk of bias assessment. We pooled mean differences or relative risks (RR) along with 95% confidence intervals (random-effects model). RESULTS: Five-hundred and thirty-one studies were screened and 17 (n = 21,131) were included for review. There was a significant reduction in the risk of MACE [RR, 0.88 (95% CI: 0.77 to 0.99), p = 0.03)] and all-cause mortality [RR, 0.90 (95% CI: 0.82 to 0.98), p = 0.02] following bempedoic acid treatment. Treatment with bempedoic acid led to a significant reduction in the mean serum total cholesterol [- 34.41 mg/dl (95% CI: - 42.43 to - 26.39), p < 0.001], low-density lipoprotein cholesterol (LDL-C) [- 33.91 mg/dl (95% CI: - 39.66 to - 28.17), p < 0.001], as well as high-density lipoprotein cholesterol (HDL-C) [- 2.40 mg/dl (95% CI: - 3.09 to - 1.71), p < 0.001] levels. However, there was a significant increase in the risk of hyperuricemia [RR, 2.05 (95% CI: 1.81 to 2.33), p < 0.001] following bempedoic acid treatment. The number needed to harm was large for all safety outcomes. The GRADE of evidence was moderate for all outcomes. CONCLUSION: Bempedoic acid reduces the risk of MACE and all-cause mortality, lowers serum total cholesterol and LDL-C levels, and has a favorable safety profile. Trial registration ClinicalTrial.gov Identifier: CRD42023412837.

Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis.

AIM: This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of 24 weeks of semaglutide treatment in patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). METHODS: PubMed, Embase, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov databases were searched for relevant studies. The primary outcome was the change in the serum alanine transaminase level. The secondary outcomes were changes in liver stiffness, liver function test parameters, metabolic parameters, and safety. Pooled mean differences and relative risks were calculated using random-effects models. RESULTS: Six hundred studies were screened and eight were included (n = 2413). Semaglutide treatment showed a reduction in serum alanine transaminase [mean difference: 14.07 U/L (95% CI: 19.39 to -8.75); p < 0.001] and aspartate transaminase [mean difference: 6.89 U/L (95% CI: 9.14 to -4.63); p < 0.001] levels. There was a significant improvement in liver fat content [mean difference: 4.97% (95% CI: 6.65 to -3.29); p < 0.001] and liver stiffness [mean difference: 0.96 kPa (95% CI: 1.87 to -0.04); p = 0.04]. There were significant improvements in the glycated hemoglobin level and the lipid profile. However, the risk of serious adverse events [relative risk: 1.54 (95% CI: 1.02 to 2.34); p = 0.04] was high following semaglutide treatment as compared to placebo; the most common ones were gastrointestinal (nausea and vomiting, dyspepsia, decreased appetite, constipation, and diarrhea) and gallbladder-related diseases. CONCLUSION: Treatment with 24 weeks of semaglutide could significantly improve liver enzymes, reduce liver stiffness, and improve metabolic parameters in patients with NAFLD/NASH. However, the gastrointestinal adverse effects could be a major concern.

Effects of Vitamin D on Migraine: A Meta-Analysis.

Objective: The aim of this study was to evaluate the difference in mean serum 25-hydroxy vitamin D level between migraineurs and nonmigraineurs, the association between hypovitaminosis D and migraine, and the effects of oral vitamin D supplementation on migraine-related symptoms as compared to placebo. Methods: Relevant databases were searched for observational studies and randomized-controlled trials (RCTs) which evaluated the difference in mean serum 25-hydroxy vitamin D level between migraineurs and nonmigraineurs; the association between hypovitaminosis D and migraine; and the effects of vitamin D supplementation on migraine-frequency, duration, and severity. Pooled mean difference and odds ratio were calculated (random-effects model, RevMan version 5.3). Results: Ten observational studies and two RCTs were included. The serum 25-hydroxy vitamin D level in the migraineurs was significantly lower than that in the nonmigraineurs [mean difference - 4.44 ng/mL (95% CI: -6.11, -2.77)] (low-GRADE evidence). Hypovitaminosis D was found to be significantly associated with migraine [OR: 1.95 (95% CI: 1.07, 3.58)] (low-GRADE evidence). As compared to placebo, oral vitamin D supplementation significantly reduced the monthly migraine-frequency [mean difference: -2.20 (95% CI: -3.04, -1.36)]. ,: although it did not reduce the migraine-duration [mean difference: -16.00 hours per month (95% CI: -42.77, 10.76)] and migraine-severity score [standardized mean difference: -0.23 (95% CI: -0.79, 0.32)] (moderate-GRADE evidence). Conclusion: Serum 25-hydroxy vitamin D level was significantly lower in the migraineurs than that in the nonmigraineurs, and hypovitaminosis D was significantly associated with migraine. Oral vitamin D supplementation significantly reduced migraine-frequency, but not its duration and severity.

Effects of saroglitazar in the treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis.

AIM: This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of 4 mg saroglitazar treatment in patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). METHODS: PubMed, Embase, Scopus, Cochrane CENTRAL, medRxiv (pre-print), bioRxiv (pre-print), and ClinicalTrials.gov databases were searched for relevant studies. The primary outcome was the change in the serum alanine transaminase (ALT) level. The secondary outcomes were changes in liver stiffness, liver function test parameters, and metabolic parameters. Pooled mean differences were calculated using random-effects models. RESULTS: Of 331 studies that were screened, ten were included. Treatment with adjunct saroglitazar showed a reduction in ALT [mean difference: 26.01 U/L (95% CI: 10.67 to 41.35); p = 0.009; i2: 98%; moderate GRADE evidence] and aspartate transaminase [mean difference: 19.68 U/L (95% CI: 8.93 to 30.43); p<0.001; i2: 97%; moderate GRADE evidence] levels. There was a significant improvement in liver stiffness [mean difference: 2.22 kPa (95% CI: 0.80 to 3.63); p = 0.002; i2: 99%; moderate GRADE evidence]. There were significant improvements in glycated hemoglobin [mean difference: 0.59% (95% CI: 0.32 to 0.86); p<0.001; i2: 78%; moderate GRADE evidence], total cholesterol [mean difference: 19.20 (95% CI: 1.54 to 36.87); p = 0.03; i2: 95%; moderate GRADE evidence], and triglyceride [mean difference: 105.49 mg/dL (95% CI: 11.18 to 199.80); p = 0.03; i2: 100%; moderate GRADE evidence] levels. Saroglitazar treatment was safe. CONCLUSION: Treatment with adjunct 4 mg saroglitazar could significantly improve liver enzymes, reduce liver stiffness, and improve metabolic parameters (serum glucose and lipid profile) in patients with NAFLD or NASH.

The epidemiological and mycological profile of superficial mycoses in india from 2015 to 2021: A systematic review.

Background: The epidemiological and mycological patterns of superficial mycoses across various geographic regions of India across the last few years are changing. Objective: This study was performed to evaluate the epidemiological and mycological profile of superficial mycoses in India between 2015 and 2021. Methods: In this systematic review, the PubMed database was searched for all observational studies published between January 1, 2015, and December 31, 2021, which had evaluated the clinico-mycological profile of superficial mycoses among outpatients from various parts of India. Descriptive statistics was used to represent the results. Results: Forty studies (21 from the north, three from the northeast, five from the east, seven from the south, one from the west, and three from multiple regions of India) were included. Male patients and those of the age group of 21-40 years were most commonly affected. The proportion of dermatophytes as causative organisms was consistently high across all regions and throughout the study period (23.6%-100%). Among dermatophytes, the proportion of Trichophyton mentagrophyte (14.0%-97.2%) and Trichophyton rubrum (0%-69.1%) was consistently high across all regions. The prevalence of T. mentagrophyte showed a rising trend, while that T. rubrum showed a declining trend from 2015 to 2021. Conclusions: The epidemiological and mycological pattern of superficial mycoses showed a fairly similar trend across various regions of India from 2015 to 2021. Dermatophytes were the main causative agents of superficial mycoses; the most common species were T. mentagrophyte and T. rubrum. A rising trend of T. Mentagrophyte infection was found.

Acylsilane Directed Rh-Catalyzed Arene C-H Alkylation with Maleimides and Visible-Light-Induced Siloxycarbene-Amide Cyclization: [3 + 2] Carbo-Annulation in Ru Catalysis.

We herein demonstrate the acylsilane-directed Rh-catalyzed arene C-H bond alkylation with maleimides. The resulting derivatives were utilized in visible-light-induced intramolecular siloxycarbene-amide cyclization for the synthesis of new tricyclic γ-lactams. In parallel, we also harnessed the same acylsilane and maleimide units through [3 + 2] carbo-annulation by using Ru-catalysis. A wide range of maleimides and aroylsilanes were used to establish the broadness of these transformations.

Efficacy and safety of lobeglitazone, a new Thiazolidinedione, as compared to the standard of care in type 2 diabetes mellitus: A systematic review and meta-analysis.

AIM: This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of lobeglitazone as compared to the standard of care (SOC) in patients with type 2 diabetes mellitus (T2DM). METHODS: Databases were searched for relevant randomized controlled trials. The primary outcome was the comparison of the glycated hemoglobin (HbA1C) level after 24 weeks. Pooled mean differences and odds ratios were calculated using random-effects models. RESULTS: Of 267 studies that were screened, four were included. Treatment with adjunct lobeglitazone showed a reduction in the HbA1C level [mean difference: -0.23% (95% CI: -0.62 to 0.16); p = 0.24; i2: 87%; moderate GRADE (Grading of Recommendations Assessment, Development and. Evaluation) of evidence], fasting blood glucose level [mean difference: -7.12 mg/dl (95% CI: -20.09 to 5.85); p = 0.28; i2: 87%; moderate GRADE of evidence], and lipid profile as compared to those following treatment with the SOC; however, the changes were not statistically significant. The risk of hypoglycemia was significantly lower [odds ratio: 0.24 (95% CI: 0.08 to 0.70); p < 0.05; i2: 0%; moderate GRADE of evidence] without any significant difference in the risk of drug-related adverse events [odds ratio: 1.59 (95% CI: 0.87 to 2.93); p = 0.13; i2: 0%; moderate GRADE of evidence] following treatment with lobeglitazone as compared to those following treatment with the SOC. CONCLUSION: Treatment with adjunct lobeglitazone showed changes in the blood glycemic status and lipid profile similar to SOC in patients with T2DM, and the results were not statistically significant. Lobeglitazone was well tolerated; its safety profile was comparable to SOC.

A Randomized Double-Blind Placebo-Controlled Trial Evaluating the Efficacy of Oral Cholecalciferol in Improving Renal and Vascular Functions in Vitamin D-Deficient Patients With Type 2 Diabetes Mellitus.

This study was performed to evaluate the efficacy of cholecalciferol in improving renal and vascular functions in vitamin D-deficient patients with type 2 diabetes mellitus (T2DM) along with chronic kidney disease (CKD). One hundred patients (18 - 65 years), having T2DM along with CKD (stage IIIA and IIIB) and hypovitaminosis D were randomized (1:1) to receive either oral cholecalciferol 60,000 IU (Group A) or placebo (Group B) weekly for 8 weeks along with standard background treatment. They were followed up for another 24 weeks. Various parameters of renal and vascular functions were compared. Except for serum calcium and phosphate levels which were significantly higher in Group A (p < 0.001), there was no significant difference in any of the biochemical or vascular parameters between the two groups at 8 weeks. There were comparable changes in urinary albumin-creatinine ratio and carotid-femoral pulse wave velocity in the two groups at 8 and 24 weeks. There was no improvement in any of the vascular parameters from the corresponding baseline values in the two groups at 8 and 32 weeks. No improvement in renal and vascular functions was observed following treatment with oral cholecalciferol in patients with T2DM and CKD.

Facilitators and barriers to the uptake of COVID-19 vaccine precaution dose among adult population: qualitative analysis across six different states of India.

Introduction: India launched the COVID-19 vaccination drive on 16th January 2021 by vaccinating the adult population above 18 years of age. This was followed by the introduction of an additional precaution dose. As on 18th October 2022, 1,02,66,96,808 (1.02 Billion) first dose and 94, 95, 39,516 (949 Million) second doses of COVID-19 vaccine were administered. However, when compared to the uptake of the primary doses, the precaution dose uptake lagged behind with only 21,75, 12,721 (217 million) doses administered. Even though, the uptake of the primary doses remained optimal, irrespective of different interventions by the Government of India, the uptake of the precaution dose remained poor. In this context, the Ministry of Health & Family Welfare wanted to understand the facilitators and Barriers for precaution dose uptake among adults so that future immunization campaigns could address these issues. Methods: An exploratory qualitative study was conducted to assess the facilitators and barriers for COVID-19 precaution dose uptake at community level across 6 different states in India. From each of the states, two districts with the highest and lowest rates of COVID-19 vaccine precaution dose uptake were selected. In each of these districts, 2 block Primary Healthcare Centres (PHCs), one with high and one with low uptake were identified. Within these block PHCs, a PHC field area with high and low precaution dose uptakes was identified. From the identified sites a minimum of four IDIs, four FGDs were conducted among the community members. KIIs of the State Immunization Officers, District Immunisation Officers, PHC Medical Officers, healthcare workers like Accredited Social Health Activist/Auxiliary Nurse Midwife were also conducted. The data was audio recorded and it was transcribed, translated and analysed using framework approach. Results: It was observed that rise in COVID-19 cases prompted the community to take the precaution dose, this along with the cost of hospitalization and the number of productive days being lost as a result of being infected resulted in vaccine uptake. The fear of non-availability of COVID-19 vaccines latter on also prompted people for vaccine uptake. While the barriers were, poor accessibility to vaccination centers, long hours of travel, poor road connectivity and lack of transportation facilities. However, the most prominent barriers observed across all study sites was that a sense of pandemic fatigue and complacency had developed both among the providers as well as the beneficiaries. Other barriers include differences in vaccination schedules and longer duration between the primary doses of some vaccines. Media was identified to be both a barrier and facilitator for Covid-19 Precaution dose uptake. Even though media played an important role in disseminating information in the beginning of the campaign, it was soon followed by the circulation of both misinformation and disinformation. Discussion: The study identified that dissemination of accurate information and community involvement at each stage of planning and implementation are crucial for the success of any campaign. Efforts should be constantly made to address and re-invent strategies that will be most suitable for the needs of the community. Therefore, in order to ensure successful vaccination campaigns, it is crucial that along with political will it is also important to have a decentralized approach with inter-sectoral coordination with different stakeholders such as healthcare workers, community members and the different departments such as the local self-governments, education department, law & order department etc. These lessons learnt from COVID-19 vaccination campaigns must not be forgotten and must be applied in future vaccination campaigns and while framing public health policies.

Association between Polypharmacy and Cardiovascular Autonomic Function among Elderly Patients in an Urban Municipality Area of Kolkata, India: A Record-Based Cross-Sectional Study.

We assessed the association between polypharmacy and cardiovascular autonomic function among community-dwelling elderly patients having chronic diseases. Three hundred and twenty-one patients from an urban municipality area of Kolkata, India were studied in August 2022. The anticholinergic burden and cardiac autonomic function (Valsalva ratio, orthostatic hypotension, change in diastolic blood pressure after an isometric exercise, and heart rate variability during expiration and inspiration) were evaluated. Binary logistic regression analysis was performed to find out the association of polypharmacy and total anticholinergic burden with cardiac autonomic neuropathy. A total of 305 patients (age, 68.9 ± 3.4; 65.9% male) were included. Of these patients, 81 (26.6%) were on polypharmacy. Out of these 81 patients, 42 patients were on ninety-eight potential inappropriate medications. The anticholinergic burden and the proportion of patients with cardiac autonomic neuropathy were significantly higher among patients who were on polypharmacy than those who were not (8.1 ± 2.3 vs. 2.3 ± 0.9; p = 0.03 and 56.8% vs. 44.6%; p = 0.01). The presence of polypharmacy and a total anticholinergic burden of > 3 was significantly associated with cardiac autonomic neuropathy (aOR, 2.66; 95% CI, 0.91−3.98 and aOR, 2.51; 95% CI, 0.99−3.52, respectively). Thus, polypharmacy was significantly associated with cardiac autonomic neuropathy among community-dwelling elderly patients.

An Audit of the Quality of Reporting and Bias of Studies on Yoga in Epilepsy.

Background: Yoga is increasingly being used as a complementary mode of treatment for epilepsy along with pharmacotherapy; however, the quality of reporting and bias of studies on yoga in epilepsy is uncertain. Objective: This study was performed to systematically evaluate the reporting quality and bias of the published studies on yoga in epilepsy. Materials and methods: PubMed and Cochrane databases were searched for studies investigating the efficacy of yoga in epilepsy or describing the patients' or caregivers' knowledge, attitude, influence, and practice of yoga in epilepsy. The reporting qualities of the studies were appraised by standard reporting checklists (CONSORT, STROBE, COREQ, and modified CONSORT) and the risks of bias were assessed using standard tools (Cochrane Collaboration's risk of bias tool, Newcastle-Ottawa scale, and ROBINS-I tool) according to the study designs. Results: Fifteen studies (four randomized control trials, seven observational studies, three non-randomized interventional studies, and one was a mixed-method study) were included. The reporting qualities of the studies which evaluated the role of yoga in epilepsy were comparatively poor from the methodological perspective and the risks of bias were comparatively high than those which described the knowledge, attitude, influence, and practice of yoga in epilepsy. Conclusion: The reporting qualities of studies in relation to yoga and epilepsy were not satisfactory and the risks of bias were high. Hence, it is imperative to be cautious before widely recommending yoga in epilepsy.

Efficacy and safety of baricitinib and tocilizumab in hospitalized patients with COVID-19: A comparison using systematic review and meta-analysis.

Objective: This review was performed to compare the efficacy and safety among hospitalized patients with COVID-19 who received baricitinib and those who received tocilizumab independently with placebo or the standard of care (SOC). Methods: Relevant databases were searched for randomized controlled trials which evaluated the effect of baricitinib or tocilizumab as compared to placebo or the SOC in hospitalized patients with COVID-19. The primary endpoint was the comparison of the 28-day mortality. Risk ratios (RR) and mean differences were compared and pooled for dichotomous and continuous variables, respectively. A two-staged exploratory network meta-analysis using a multivariate meta-analysis was also performed. All analyses were performed in Stata version 16.0. The GRADE approach was used to assess the quality of the generated evidence (PROSPERO ID: CRD42022323363). Results: Treatment with baricitinib [RR, 0.69 (95% CI, 0.50-0.94), p = 0.02, i2 = 64.86%] but not with tocilizumab [RR, 0.87 (95% CI, 0.71-1.07), p = 0.19, i2 = 24.41%] led to a significant improvement in the 28-day mortality as compared to that with the SOC. Treatment with baricitinib or tocilizumab, both independently led to a significant reduction in the duration of hospitalization [baricitinib: mean difference, -1.13 days (95% CI, -1.51 to -0.76), p < 0.001, i2 = 0.00%; tocilizumab: mean difference, -2.80 days (95% CI, -4.17 to -1.43), p < 0.001, i2 = 55.47%] and a significant improvement in the proportion of patients recovering clinically by day 28 [baricitinib: RR, 1.24 (95% CI, 1.03-1.48), p = 0.02, i2 = 27.20%; tocilizumab: RR, 1.41 (95% CI, 1.12-1.78), p < 0.001, i2 = 34.59%] as compared to those with the SOC. From the safety point of view, both these drugs showed similar results. There were fewer patients who experienced any serious adverse event following treatment with barictinib and tocilizumab as compared to those following treatment with the SOC [baricitinib: RR, 0.76 (95% CI, 0.62-0.92), p = 0.01, i2 = 12.63%; tocilizumab: RR, 0.85 (95% CI, 0.72-1.01), p = 0.07, i2 = 0.00%]. Conclusion: As baricitinib and tocilizumab are recommended interchangeably by various guidelines for the management of COVID-19, considering the better 28-day mortality data and other comparable efficacy and safety outcomes, baricitinib may be favored over tocilizumab considering its ease of administration, shorter half-life, and lower cost of treatment.

Synthesis of bridgehead-azacycles via dual C-N/C-C annulation of α-amino acids, aminals and maleimides.

The synthesis of various bridged azacyclic adducts has recently become a reemerging topic due to their bioactive and natural product mimic profiles. Accordingly, herein, we report a method for easy access to succinamide-bridged azacyclic derivatives through the metal-free polarization-controlled dual C-N/C-C annulation of readily available α-amino acids, 2-amino benzaldehydes or pyrrole/indole-2-aldehyde and maleimide substrates. This cascade features a rare dipolarophile-induced diastereo-selective amidative annulation, followed by 3 + 2 cycloaddition as key steps.