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Background Bruxism, characterized by involuntary teeth grinding and jaw clenching, is an uncommon but likely underrecognized adverse effect of selective serotonin reuptake inhibitors. Sertraline is generally considered safe for anxiety disorders, yet individual pharmacogenetic variability in CYP2C19 and CYP2D6 may predispose to serotonergic–dopaminergic imbalance and movement disorders. Case presentation We describe a 42-year-old Indian woman with generalized anxiety disorder (baseline HAM-A 32) who was started on sertraline 25 mg/day and titrated to 50 mg/day on day 5. About 10 days after initiation, she developed severe bruxism with jaw pain despite clear clinical improvement in anxiety (HAM-A 12). The patient’s bruxism was predominantly awake bruxism, characterized by daytime jaw clenching and teeth grinding during stressful periods. A dental evaluation ruled out occlusal abnormalities, temporomandibular joint inflammation, and tooth wear, and a mouthguard was deemed ineffective. A dechallenge with tapering and discontinuation of sertraline led to the resolution of jaw pain and reduction in bruxism. Pharmacogenetic testing showed CYP2C19*2/*17 (intermediate metabolizer) and CYP2D6*2/*41 (normal metabolizer). On the basis of Clinical Pharmacogenetics Implementation Consortium recommendations, she was switched to venlafaxine 37.5 mg twice daily, which achieved anxiety remission (HAM-A 6), but mild teeth grinding persisted. Adjunctive buspirone 5 mg/day led to complete resolution within 4 weeks. The temporal relationship, improvement on withdrawal, and a Naranjo score of 9 supported a probable sertraline-induced bruxism. Conclusion This case highlights sertraline-induced bruxism as a less commonly recognized but clinically significant adverse drug reaction. It shows that pharmacogenetic-guided antidepressant selection, combined with buspirone augmentation, can optimize management in selective serotonin reuptake inhibitor-associated bruxism. Clinicians should screen for bruxism during early sertraline titration, especially in patients with CYP2C19-reduced function alleles.

A COVID-19 patient often presents with multiple comorbidities and is associated with adverse outcomes. A comprehensive assessment of the prevalence of comorbidities in patients with COVID-19 is essential. This study aimed to assess the prevalence of comorbidities, severity and mortality with regard to geographic region, age, gender and smoking status in patients with COVID-19. A systematic review and multistage meta-analyses were reported using PRISMA guidelines. PubMed/MEDLINE, SCOPUS, Google Scholar and EMBASE were searched from January 2020 to October 2022. Cross-sectional studies, cohort studies, case series studies, and case–control studies on comorbidities reporting among the COVID-19 populations that were published in English were included. The pooled prevalence of various medical conditions in COVID-19 patients was calculated based on regional population size weights. Stratified analyses were performed to understand the variations in the medical conditions based on age, gender, and geographic region. A total of 190 studies comprising 105 million COVID-19 patients were included. Statistical analyses were performed using STATA software, version 16 MP (StataCorp, College Station, TX). Meta-analysis of proportion was performed to obtain pooled values of the prevalence of medical comorbidities: hypertension (39%, 95% CI 36–42, n = 170 studies), obesity (27%, 95% CI 25–30%, n = 169 studies), diabetes (27%, 95% CI 25–30%, n = 175), and asthma (8%, 95% CI 7–9%, n = 112). Moreover, the prevalence of hospitalization was 35% (95% CI 29–41%, n = 61), intensive care admissions 17% (95% CI 14–21, n = 106), and mortality 18% (95% CI 16–21%, n = 145). The prevalence of hypertension was highest in Europe at 44% (95% CI 39–47%, n = 68), obesity and diabetes at 30% (95% CI, 26–34, n = 79) and 27% (95%CI, 24–30, n = 80) in North America, and asthma in Europe at 9% (95% CI 8–11, n = 41). Obesity was high among the ≥ 50 years (30%, n = 112) age group, diabetes among Men (26%, n = 124) and observational studies reported higher mortality than case–control studies (19% vs. 14%). Random effects meta-regression found a significant association between age and diabetes ( p  < 0.001), hypertension ( p  < 0.001), asthma ( p  < 0.05), ICU admission ( p  < 0.05) and mortality ( p  < 0.001). Overall, a higher global prevalence of hypertension (39%) and a lower prevalence of asthma (8%), and 18% of mortality were found in patients with COVID-19. Hence, geographical regions with respective chronic medical comorbidities should accelerate regular booster dose vaccination, preferably to those patients with chronic comorbidities, to prevent and lower the severity and mortality of COVID-19 disease with novel SARS-CoV-2 variants of concern (VOC).

Abstract Proton-pump inhibitors (PPIs) are widely prescribed to decrease stomach acid and treat various acid-related Gastrointestinal tract (GIT) diseases. However, genetic variations, particularly in the CYP2C19 gene, affect PPIs metabolism and efficacy. Variants in CYP2C19 can result in different rates of PPI metabolism, influencing their effectiveness. Personalized medicine strategies, such as genotyping for CYP2C19, have the potential to enhance the effectiveness of PPI therapy and patient safety. This review aims to describe the relevance of CYP2C19 genetic profiling in the indian population, including normal function (e.g. CYP2C19*1, *11, *13, *15, *18, *28, and 38), decreased function (e.g., CYP2C19*9, *10, *16, *19, *25, and 26), loss of function (e.g., CYP2C19*2, *3, *4, *5, *6, *7, *8, *22, *24, *35, *36, and *37), and increased function (e.g., CYP2C19*17) variants. This review also examines the clinical pharmacogenomics implementation consortium (CPIC)-CYP2C19-PPI guidelines to highlight the importance of pharmacogenomics (PGx)-informed personalized PPI therapy for gastroesophageal reflux disease and peptic ulcer disease treatment. On average, each person in India possesses eight pharmacogenetic (PGx) variants that can be clinically significant, underscoring the need for preemptive testing. Implementing CYP2C19 genetic testing in India requires expanding laboratory capacity, increasing accessibility in primary care, increasing public awareness, collaboration between pharmacovigilance and PGx programs, investing in advanced sequencing technologies, data management systems, and integration with electronic health records and clinical decision support systems. Addressing challenges such as genetic diversity, socioeconomic factors, health-care access issues, and shortage of trained professionals is essential for implementation. Due to the lack of definitive country-specific policies and PGx guidelines from Indian drug regulatory agencies, guidelines from international consortia such as the Clinical Pharmacogenetics Implementation Consortium and drug labeling offer crucial foundational evidence. This evidence can be used to enhance patient outcomes and ensure the safe and effective use of PPIs in India.

Genetic polymorphisms in CYP2D6 and CYP2C19 significantly influence the metabolism, efficacy, and safety of antidepressant medications. Limited data exist on the prevalence of these actionable pharmacogenetic variants in the Central Indian population. This study aimed to determine the frequency of clinically actionable Tier-1 alleles, genotypes, and metabolizer phenotypes and to evaluate their clinical relevance in patients with common mental disorders (CMDs). A total of 509 adults diagnosed with depression and anxiety disorders and receiving SSRI & SNRI antidepressant therapy were enrolled from the Department of Psychiatry, AIIMS Bhopal. Genotyping was performed using the KASP qPCR assay, and CYP2D6 copy number variations (CNVs) were determined using the TaqMan qPCR assay. Among the Central Indian cohort, the most frequent CYP2D6 alleles were *10 (21.6%), *41 (17.3%), and *4 (10.4%), while *3 (5.7%), *6 (1.9%). CNVs, Gene deletions(*5) and Gene duplications(xN) were detected in 4.2% and 4.1% of the cohort. For CYP2C19, the *2 (37.3%), *3 (2.3%), and *17 (16.1%) alleles were observed. Non-normal metabolizer phenotypes were present in 46.2% for CYP2D6 and 74.2% for CYP2C19; CYP2D6 ultra-rapid metabolizers accounted for 5.3%. Overall, 86% of participants had at least one clinically actionable pharmacogenetic phenotype. Overall, 7.5% of patients carried CYP2D6 variants and 20.6% carried CYP2C19 variants, for which CPIC guidelines recommend alternative drug selection or dose modification. This study demonstrates a high prevalence of actionable CYP2D6 and CYP2C19 variants in the Central Indian population, underscoring the need for pharmacogenetic integration in psychiatric prescribing in Indian clinical settings, to enhance treatment efficacy and minimize adverse events.

Introduction: Remdesivir, an experimental antiviral drug has shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both in vitro and in vivo. The present systematic review and meta-analysis were performed to quantify the safety and tolerability of remdesivir, based on safety outcome findings from randomized controlled trials, observational studies and case reports of remdesivir in coronavirus disease 2019 (COVID-19) patients. Methods: We have performed a systematic search in the PubMed, Google Scholar and Cochrane Library using specific keywords such as ‘COVID-19’ OR ‘SARS CoV-2’ AND ‘Remdesivir’. The study endpoints include total adverse events (AEs), serious adverse events (SAEs), grade 3 and grade 4 AEs, mortality and drug tolerability. Statistical analysis was carried out by using Revman 5.4 software. Results: Total 15 studies were included for systematic review, but only 5 randomized clinical trials (RCTs) (n = 13,622) were included for meta-analysis. Visual inspection of the forest plots for remdesivir 10-day versus placebo and remdesivir 10-day versus 5-day groups revealed that there is a significant difference in SAEs [10-day remdesivir versus control (odds ratio [OR] = 0.55, 0.40–0.74) p = 0.0001; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 0.56, 0.38–0.84) p = 0.005; I2 = 13%]. In grade 4 AEs, there is a significant difference in 10-day remdesivir versus control (OR = 0.32, 0.19–0.54) p = 0.0001; I2 = 0%, but not in comparison to 5-day remdesivir (OR = 0.95, 0.59–1.54) p = 0.85; I2 = 0%. But there is no significant difference in grade 3 AEs [remdesivir 10 day versus control (OR = 0.81, 0.59–1.11) p = 0.19; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.24, 0.86–1.80) p = 0.25; I2 = 0%], in total AEs [remdesivir 10 day versus control (OR = 1.07, 0.66–1.75) p = 0.77; I2 = 79%; remdesivir 10 day versus 5 day (OR = 1.08, 0.70–1.68) p = 0.73; I2 = 54%)], in mortality [10-day remdesivir versus control (OR = 0.93, 0.80–1.08) p = 0.32; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.39, 0.73–2.62) p = 0.32; I2 = 0%)] and tolerability [remdesivir 10 day versus control (OR = 1.05, 0.51–2.18) p = 0.89; I2 = 65%, 10-day remdesivir versus 5-day remdesivir (OR = 0.86, 0.18–4.01) p = 0.85; I2 = 78%]. Discussion & Conclusion: Ten-day remdesivir was a safe antiviral agent but not tolerable over control in the hospitalized COVID-19 patients with a need of administration cautiousness for grade 3 AEs. There was no added benefit of 10- or 5-day remdesivir in reducing mortality over placebo. To avoid SAEs, we suggest for prior monitoring of liver function tests (LFT), renal function tests (RFT), complete blood count (CBC) and serum electrolytes for those with preexisting hepatic and renal impairments and patients receiving concomitant hepatotoxic or nephrotoxic drugs. Furthermore, a number of RCTs of remdesivir in COVID-19 patients are suggested. Plain Language Summary Ten-day remdesivir is a safe antiviral drug with common adverse events in comparison to placebo. The rate of serious adverse events and grade 3 adverse events were significantly lower in 10-day remdesivir in comparison to placebo/5-day remdesivir. There was no significant difference in the rate of tolerability and mortality reduction in 10-day remdesivir over placebo/5-day remdesivir. There were no new safety signals reported in vulnerable populations, paediatric, pregnant and lactating women.

Background The intensive care unit (ICU) represents an important platform for conducting drug utilization analysis using defined daily dose (DDD)/100 bed-days and the financial burden of treatment as patients are seriously ill and are often suffering from chronic critical illnesses. Therefore, in this study, we evaluated the drug utilization patterns and cost of treatment in the ICU. Methods A retrospective observational analysis of the medical records obtained for the medical ICU of an apex tertiary care teaching hospital in central India was conducted for a period of three years from 2017 to 2019. All the patients admitted to the medical ICU during the study tenure were included in the study. Patients hospitalized in neonatal intensive care unit (NICU), pediatric intensive care unit (PICU), and surgical ICU were excluded from the study. The socio-demographic and clinical data, utilization of different classes of drugs, WHO-Anatomic Therapeutic Chemical (WHO-ATC) classification, DDD/100 bed days, hospital stay, etc. were analyzed. A partial pharmaco-economic analysis of the average cost of admission to patients was done. Results Data from 280 patients was assessed. The mean age was 47 ± 19.18 years and 58% were males. Antibiotics and injections were prescribed to 96% and 97.5% of the patients, respectively, during their ICU stay (median: seven days). Antimicrobial drugs were most frequently prescribed (n=1096, 68%); the most common were beta-lactams and carbapenems, followed by drugs acting on the central nervous system (5%) and cardiovascular system (4.3%). Cefoperazone/sulbactum, ceftriaxone, and piperacillin/tazobactam were the most utilized antibiotics with 8, 16, and 6 DDD/100 bed-days, respectively, while proton pump inhibitors, analgesics, and anti-epileptics were the most frequently prescribed non-antimicrobial drug class. The median cost of treatment per ICU admission was Indian Rupees (INR) 23,347 (IQR 12,552- 65,524). Conclusion Drug utilization assessment provides crucial information for understanding the usage of drugs in the settings of the ICU, and should be conducted regularly to help in the proper planning and implementation of rational drug use. Treatment costs reflect the high economic burden seen in ICU admissions.

Phytochemicals and their derivatives are promising target drugs for various ailments and have served as therapeutic agents for several decades. Using in vivo and in vitro models and molecular docking, this study investigated the pharmacological potential of a flavonoid-rich fraction of the ethanolic extract of Sesbania grandiflora (SG). This research aimed to determine whether flavonoid-rich whole-plant extracts of SGs have any cytoprotective or in vivo hepatoprotective effects. Additionally, the study was intended to elucidate the molecular connections between the discovered flavonoid flavonols and PPARα target proteins linked to liver problems, for which an in silico molecular docking investigation was performed. To separate the flavonoid components, the entire Sesbania grandiflora plant was first extracted using ethanol as a solvent by soxhlet extraction. The resulting ethanolic extract was then fractionated. The cytoprotective and hepatoprotective properties were evaluated via in vitro and in vivo experiments. SGOT, SGPT, triglyceride, bilirubin, and total protein levels were used to evaluate hepatotoxicity in animal models. In vitro studies on Hepatocellular Carcinoma G2 (HepG2) cell lines have examined their cytotoxic effects and antioxidant activity. The most promising flavonoid-flavanol compounds were identified by conducting molecular docking studies against PPARα target protein (PDB ID: 3VI8) using MOE software. In vivo, the serum levels of SGOT, SGPT, total triglyceride and total bilirubin were measured in experimental animals treated with the flavonoid-rich ethanolic extract of SG. Significant reductions in the levels of these hepatic injury markers were observed, indicating the hepatoprotective potential of the extract. Elevated levels of liver biomarkers in the untreated group indicated liver injury or dysfunction. The treated groups showed significant restoration of these biomarkers, suggesting the hepatoprotective potential of SG. The IC50 value for the total flavonoid content of SG was 190.28 μg/ml, indicating its safety in inhibiting HepG2 cell growth. Flavonoid treatment decreased cell viability but did not affect antioxidant parameters in hepatocytes. In addition, SG restored the damaged hepatocyte architecture. Molecular docking studies revealed the binding affinities of flavonoids for PPARα. These findings suggest that a promising lead candidate for the development of therapeutic medicines against anti-TB drug-induced hepatotoxicity has been identified. Our findings demonstrate the hepatoprotective potential of the flavonoid-rich fraction of Sesbania grandiflora both in vivo and in vitro. This study provides valuable insights into its mechanism of action, highlighting its promising therapeutic application in the management of liver disorders. This study highlights the hepatoprotective and cytoprotective potential of the total flavonoid-rich fraction of SG.

Low back pain (LBP) is a musculoskeletal condition that affects many individuals. While physiotherapy and acupuncture are frequently used treatments, determining their specific contributions when used alongside integrated yoga and naturopathy (IYN) therapy for relieving chronic LBP symptoms and enhancing quality of life is important. In the present prospective randomized comparative trial, a total of 60 participants were divided into the following two groups: physiotherapy with IYN and acupuncture with IYN. The treatment duration was 10 days, and assessments were conducted both before (baseline) and after the intervention. Various assessment tools, such as the visual analog scale (VAS), Oswestry Disability Index (ODI), fingertip-to-floor test (FTF), State-Trait Anxiety Inventory (STAI), and Short Form 36 (SF-36), were utilized. The statistical analysis was performed using SPSS version 21.0 (Armonk, NY: IBM Corp). The results revealed significant differences in VAS score, ODI, FTF score, STAI score, and SF-36 score between the physiotherapy and acupuncture groups (p<0.001). A t-test for the equality of means and a Mann-Whitney U test were used to compare the two groups; these tests revealed a significant difference in disability levels, range of motion, and state of anxiety. The acupuncture group showed a significant difference in the ODI (15.9 {12.6, 19.3}; p <0.001) and state anxiety (23.0 {20.0, 26.0}; p<0.001) compared to the physiotherapy ODI (22.4 {18.5, 26.4}) and state anxiety (27.5 {25.0, 30.0}). The physiotherapy group showed a significant difference in range of motion (7.7 {5.7, 9.7}; p<0.001) compared to the acupuncture group (11.6 {9.8, 13.5}). The present study findings revealed that both physiotherapy and acupuncture, as interventions along with integrated yoga and naturopathy may be considered an effective treatment strategy for chronic LBP.

Adverse drug reactions (ADRs) are a significant public health concern and a leading cause of hospitalization; they are estimated to be the fourth leading cause of death and increasing healthcare costs worldwide. Carrying a genetic variant could alter the efficacy and increase the risk of ADRs associated with a drug in a target population for commonly prescribed drugs. The use of pre-emptive pharmacogenetic/omic (PGx) testing can improve drug therapeutic efficacy, safety, and compliance by guiding the selection of drugs and/or dosages. In the present narrative review, we examined the current evidence of pre-emptive PGx testing-based treatment for the prevention of ADRs incidence and hospitalization or emergency department visits due to serious ADRs, thus improving patient safety. We then shared our perspective on the importance of preemptive PGx testing in clinical practice for the safe use of medicines and decreasing healthcare costs.