An Evaluation of Medical Students' Perceptions, Knowledge, and Attitudes About People With Disability After Attending the Learning Session on Disability Competency: A Cross-Sectional Study.

Background and objective The Medical Council of India [now replaced by the National Medical Commission (NMC)] has implemented a new competency-based curriculum for medical education. Eight competencies in the curriculum are related to the principles of disability-inclusive compassionate care. This study aimed to evaluate the knowledge, perceptions, and attitudes among undergraduate medical students about people with disability after attending learning sessions on disability competency. Materials and methods After they attended the learning session during the foundation course, participants were evaluated by using a questionnaire involving 26 questions, of which 17 were based on the Likert scale to assess general perceptions towards the person with a disability, while three questions aimed to assess attitudes, and six closed-ended questions tried to assess knowledge about disability. Results In the present study, 79.7% (n=157) of the students thought that people with disabilities faced problems getting involved in society, and 81.2% (n=160) felt that it was harder for them to make friends than others. The majority of the students disagreed with the idea that people with disabilities are a burden on society (n=149, 75.6%) or their families (n=119, 60.4%); 65% (n=128) of the students thought that people with disabilities are more determined than others to reach their goals and achieve more owing to their disability (n=104, 52.85%). A total of 161 (81.7%) students disagreed with the statement that people with disabilities should not be optimistic about their future. A comparison of the pre- and post-test data revealed that students' knowledge regarding disability increased and they gained a more positive attitude towards people with a disability after attending teaching and learning sessions (p<0.0001). Conclusion Our findings showed a significant improvement in the undergraduate medical students' understanding and empathy toward individuals with disabilities following sessions on disability competency. Teaching and learning sessions on disability competencies for newly admitted students in medical school can sensitize, orient, increase knowledge, and develop positive attitudes toward people with disabilities. Further studies on the topic are needed involving different phases of clinical teaching.

Trans-nasal sphenopalatine ganglion block for post-dural puncture headache management: a meta-analysis of randomized trials

Abstract Objective: To evaluate the efficacy and safety of trans-nasal Sphenopalatine Ganglion (SPG) block over other treatments for Post-Dural Puncture Headache (PDPH) management. Methods: A systematic literature search was conducted on databases for Randomized Controlled Trials (RCTs) comparing trans-nasal SPG blockade for the management of PDPH over other treatment modalities. All outcomes were pooled using the Mantel-Haenszel method and random effect model. Analyses of all outcomes were performed as a subgroup based on the type of control interventions (conservative, intranasal lignocaine puffs, sham, and Greater Occipital Nerve [GON] block). The quality of evidence was assessed using the GRADE approach. Results: After screening 1748 relevant articles, 9 RCTs comparing SPG block with other interventions (6 conservative treatments, 1 sham, 1 GON and 1 intranasal lidocaine puff) were included in this meta-analysis. SPG block demonstrated superiority over conservative treatment in pain reduction at 30 min, 1 h, 2 h, 4 h after interventions and treatment failures with "very low" to "moderate" quality of evidence. The SPG block failed to demonstrate superiority over conservative treatment in pain reduction beyond 6 h, need for rescue treatment, and adverse events. SPG block demonstrated superiority over intranasal lignocaine puff in pain reduction at 30 min, 1 h, 6 h, and 24 h after interventions. SPG block did not show superiority or equivalence in all efficacy and safety outcomes as compared to sham and GON block. Conclusion: Very Low to moderate quality evidence suggests the superiority of SPG block over conservative treatment and lignocaine puff for short-term pain relief from PDPH. PROSPERO Registration: CRD42021291707.

Role of Selective Serotonin Reuptake Inhibitors in the Treatment of Hypochondriasis: A Systematic Review.

Hypochondriasis is a condition characterized by an unrealistic fear of having a serious medical illness resulting in health anxiety. Currently, no evidence-based pharmacological treatment options are available for the treatment of hypochondriasis. Since selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment option for anxiety disorders, they may be useful for relieving hypochondriasis symptoms. Moreover, off-label use of SSRIs in these cases is highly prevalent in clinical practice. Thus, in this study, we aimed to review the available literature to assess the role of SSRIs in the treatment of hypochondriacal symptoms. A systematic search was conducted in PubMed, Scopus, ScienceDirect, Embase, and Cochrane Database of Systematic Reviews from the date of inception to December 2022. We included only randomized clinical trials (RCTs) investigating the effect of SSRIs in the treatment of hypochondriacal symptoms. Non-RCTs, observation studies, and animal studies were excluded. The Risk of Bias 2 tool was used to assess the quality of included studies. Out of 2264 articles, six RCTs met our inclusion criteria. Studies have been conducted using different SSRIs in the treatment of primary hypochondriasis and hypochondriacal symptoms associated with other psychiatric disorders. All the studies have found that the use of SSRIs has some beneficial role in improving hypochondriacal symptoms. This suggests that SSRIs may be one of the promising pharmacological interventions in the treatment of hypochondriasis.

Trans-nasal sphenopalatine ganglion block for post-dural puncture headache management: a meta-analysis of randomized trials.

OBJECTIVE: To evaluate the efficacy and safety of trans-nasal Sphenopalatine Ganglion (SPG) block over other treatments for Post-Dural Puncture Headache (PDPH) management. METHODS: A systematic literature search was conducted on databases for Randomized Controlled Trials (RCTs) comparing trans-nasal SPG blockade for the management of PDPH over other treatment modalities. All outcomes were pooled using the Mantel-Haenszel method and random effect model. Analyses of all outcomes were performed as a subgroup based on the type of control interventions (conservative, intranasal lignocaine puffs, sham, and Greater Occipital Nerve [GON] block). The quality of evidence was assessed using the GRADE approach. RESULTS: After screening 1748 relevant articles, 9 RCTs comparing SPG block with other interventions (6 conservative treatments, 1 sham, 1 GON and 1 intranasal lidocaine puff) were included in this meta-analysis. SPG block demonstrated superiority over conservative treatment in pain reduction at 30 min, 1 h, 2 h, 4 h after interventions and treatment failures with "very low" to "moderate" quality of evidence. The SPG block failed to demonstrate superiority over conservative treatment in pain reduction beyond 6 h, need for rescue treatment, and adverse events. SPG block demonstrated superiority over intranasal lignocaine puff in pain reduction at 30 min, 1 h, 6 h, and 24 h after interventions. SPG block did not show superiority or equivalence in all efficacy and safety outcomes as compared to sham and GON block. CONCLUSION: Very Low to moderate quality evidence suggests the superiority of SPG block over conservative treatment and lignocaine puff for short-term pain relief from PDPH. PROSPERO REGISTRATION: CRD42021291707.

Suspected cutaneous adverse drug reactions reported with traditional medicines: analysis of data for United Nations Asia region from WHO VigiBase.

Background: Data on traditional medicine-induced cutaneous adverse drug reactions (ADRs) is very scarce. The current secondary analysis based on the WHO database (VigiBase) of individual case safety reports (ICSRs) focuses on the suspected cutaneous ADRs linked to traditional medicines (TMs). Methods: All the ICSRs reported between 1st January 2016 and 30th June 2021 from the UN Asia region in VigiBase where at least one TM was suspected to cause cutaneous ADRs were included in the study. Data regarding demographic details, suspected drug, adverse reaction as per MedDRA term, the seriousness of the reaction, de-challenge, re-challenge, and clinical outcome for suspected cutaneous ADRs associated with TM were obtained from VigiBase and analyzed for frequency of reported events and suspected medicines. Findings: Total 3,523 ICSRs with 5,761 ADRs related to "skin and subcutaneous tissue disorders" were included in the analysis. Amongst these, 6.8% of ICSRs were reported as serious. Pruritus (29.6%), rash (20.3%), urticaria (18.9%), and hyperhidrosis (3.3%) were commonly reported ADRs. Artemisia argyi H.Lév. and Vaniot. (14.9%), Ginkgo biloba L. (5.1%), Vitis vinifera L. (4%), Vitex agnus-castus L. (3.8%), Silybum marianum (L.), Gaertn (3.5%), and Viscus album L. (2.7%) were some commonly suspected TMs for cutaneous ADRs. There were 46 cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported with TMs during the study period. Death was reported in 5 ICSRs. Interpretation: TMs are linked with various cutaneous ADRS ranging from pruritus to toxic epidermal necrolysis which may have serious consequences. TMs listed as suspected offending agents in this analysis, should be kept in mind while dealing with suspected cutaneous ADRs. Clinicians should be more vigilant in detecting and reporting events associated with TMs.

Dexmedetomidine versus clonidine as an adjuvant to local anaesthetic in brachial plexus blocks: a meta-analysis of randomised controlled trials.

OBJECTIVE: This meta-analysis aimed to compare the efficacy and safety of dexmedetomidine and clonidine as an adjuvant to local anesthetics in BPBs. METHODS: Two investigators independently searched databases to identify all RCTs comparing the efficacy and/or safety of dexmedetomidine and clonidine as an adjuvant to local anesthetics in BPBs. All outcomes were pooled using the inverse variance method with a random-effect model. An I2 test was used to assess heterogeneity. The source of heterogeneity was explored through meta-regression. The quality of the evidence was assessed using the GRADE approach. RESULTS: Out of 123 full texts assessed, 24 studies (1448 patients) were included in the analysis. As compared to clonidine, dexmedetomidine groups showed significantly longer sensory block duration (MD = 173.31; 95% CI 138.02‒208.59; I2 = 99%; GRADE approach evidence: high); motor block duration (MD = 158.35; 95% CI 131.55‒185.16; I2 = 98%; GRADE approach evidence: high), duration of analgesia (MD = 203.92; 95% CI 169.25‒238.58; I2 = 99%; GRADE approach evidence- high), and provided higher grade quality of block (RR = 1.97; 95% CI 1.60‒2.41; I2 = 0%; GRADE approach evidence: moderate). The block positioning technique (regression coefficient: 51.45, p = 0.005) was observed as a significant predictor of the heterogeneity in the case of sensory block duration. No significant difference was observed for the risk of hypotension (RR = 2.59; 95% CI 0.63‒10.66; I2 = %). CONCLUSION: Moderate to high-quality evidence suggests dexmedetomidine is a more efficacious adjuvant to local anesthetic in BPBs than clonidine.

Impact of suspected adverse drug reactions on mortality and length of hospital stay in the hospitalised patients: a meta-analysis.

PURPOSE: To estimate the risk of mortality and length of stay in hospitalised patients who have experienced suspected adverse drug reactions (ADRs) as compared to patients who did not experience suspected ADRs. METHODS: A systematic literature search was conducted on databases for observational and randomised controlled studies conducted in any inpatient setting that reported deaths and/or length of hospital stay in patients who had suspected ADRs and did not have suspected ADRs during hospitalisation. PRISMA guidelines were strictly followed during the review. The methodological quality of included studies was assessed using a tool designed by Smyth et al. for the studies of adverse drug reactions. The meta-analytic summary of all-cause mortality was estimated using odds ratio-OR (95% CI) and length of stay using mean difference-MD (95% CI). Both outcomes were pooled using a random effect model (DerSimonian and Laird method). Subgroup and meta-regression were performed based on study variables: study design, age group, study ward, study region, types of suspected ADRs (ADRAd-suspected ADRs that lead to hospitalisation and ADRIn-suspected ADRs that occur following hospitalisation), study duration, sample size and study period. The statistical analysis was conducted through the 'Review manager software version 5.4.1 and JASP (Version 0.14.1)'. RESULTS: After screening 475 relevant articles, 55 studies were included in this meta-analysis. Patients having suspected ADRs had reported significantly higher odds of all-cause mortality [OR: 1.50 (95% CI: 1.21-1.86; I2 = 100%) than those patients who did not have suspected ADRs during hospitalisation. Study wards, types of suspected ADRs and sample size were observed as significant predictors of all-cause mortality (p < 0.05). Patients having suspected ADRs had reported significantly higher mean difference in hospital stay [MD: 3.98 (95% CI: 2.91, 5.05; I2 = 99%) than those patients who did not have suspected ADRs during hospitalisation. Types of suspected ADRs and study periods were observed as significant predictors of length of stay (p < 0.05). CONCLUSION: Suspected ADRs significantly increase the risk of mortality and length of stay in hospitalised patients. SYSTEMATIC REVIEW REGISTRATION: CRD42020176320.

Dexmedetomidine versus clonidine as an adjuvant to local anaesthetic in brachial plexus blocks: a metaanalysis of randomised controlled trials

Abstract Objective: This meta-analysis aimed to compare the efficacy and safety of dexmedetomidine and Clonidine as an adjuvant to local anesthetics in BPBs. Methods: Two investigators independently searched databases to identify all RCTs comparing the efficacy and/or safety of dexmedetomidine and Clonidine as an adjuvant to local anesthetics in BPBs. All outcomes were pooled using the inverse variance method with a random-effect model. An I2 test was used to assess heterogeneity. The source of heterogeneity was explored through meta-regression. The quality of the evidence was assessed using the GRADE approach. Results: Out of 123 full texts assessed, 24 studies (1448 patients) were included in the analysis. As compared to Clonidine, dexmedetomidine groups showed significantly longer sensory block duration (MD = 173.31; 95% CI 138.02-208.59; I2 = 99%; GRADE approach evidence: high); motor block duration (MD = 158.35; 95% CI 131.55-185.16; I2 = 98%; GRADE approach evidence: high), duration of analgesia (MD = 203.92; 95% CI 169.25-238.58; I2 = 99%; GRADE approach evidence-high), and provided higher grade quality of block (RR = 1.97; 95% CI 1.60-2.41 ; I2 = 0%; GRADE approach evidence: moderate). The block positioning technique (regression coefficient: 51.45, p = 0.005) was observed as a significant predictor of the heterogeneity in the case of sensory block duration. No significant difference was observed for the risk of hypotension (RR = 2.59; 95% CI 0.63-10.66; I2 = %). Conclusion: Moderate to high-quality evidence suggests dexmedetomidine is a more efficacious adjuvant to local anesthetic in BPBs than Clonidine.

Efficacy and safety of intranasal ketamine compared with intranasal dexmedetomidine as a premedication before general anesthesia in pediatric patients: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To compare the efficacy and safety of intranasal ketamine with intranasal dexmedetomidine as a premedication in pediatric patients undergoing general anesthesia for elective surgery or other procedures. SOURCE: We conducted a systematic literature search in PubMed, PubMed Central, Scopus, LILACS, Google Scholar, the Cochrane Database of Systematic Reviews, and trial registries for randomized controlled trials (RCTs) comparing intranasal ketamine with intranasal dexmedetomidine as preanesthetic medication in elective surgery or other procedures in pediatric patients. We used Review Manager software version 5.4.1 for statistical analysis and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We assessed the methodological quality of the included studies with the RoB 2 risk of bias tool. All outcomes were pooled using the Mantle-Haenszel method and a random-effects model. The quality of evidence was assessed using the GRADE approach. PRINCIPAL FINDINGS: Out of 2,445 full texts assessed, we included ten RCTs in the analysis. The efficacy outcomes did not fulfill the comparability criteria between intranasal ketamine and intranasal dexmedetomidine for sedation at parental separation (risk ratio [RR], 0.90; 95% confidence interval [CI], 0.79 to 1.04; I2 = 89%; GRADE evidence, low), mask acceptance (RR, 0.86; 95% CI, 0.66 to 1.13; I2 = 50%; GRADE evidence, low), and iv canulation (RR, 1.16; 95% CI, 0.79 to 1.69; I2 = 69%; GRADE evidence, very low). Intranasal ketamine-treated patients showed a higher incidence of nausea and vomiting (RR, 2.47; 95% CI, 1.24 to 4.91; I2 = 0; GRADE evidence, moderate). Significantly more bradycardia was observed in the intranasal dexmedetomidine group (RR, 0.16; 95% CI, 0.04 to 0.70; I2 = 40%; GRADE evidence, moderate) than in the ketamine group. CONCLUSION: The low to very low-quality evidence in this systematic review and meta-analysis of RCTs neither confirmed nor refuted comparable premedication efficacy of intranasal ketamine and dexmedetomidine in terms of parental separation, mask acceptance, and iv cannulation in a pediatric population. Clinical decision-making is likely to be influenced by differences in gastrointestinal and cardiovascular safety profiles. STUDY REGISTRATION: PROSPERO (CRD42021262516); registered 22 July 2021.

RéSUMé: OBJECTIF: Comparer l'efficacité et l'innocuité de la kétamine intranasale à la dexmédétomidine intranasale comme prémédication chez les patients pédiatriques bénéficiant d'une anesthésie générale pour une chirurgie élective ou d'autres interventions. SOURCES: Nous avons réalisé une recherche documentaire systématique dans les bases de données PubMed, PubMed Central, Scopus, LILACS, Google Scholar, ainsi que dans la base de données Cochrane des revues systématiques et dans les registres d'études pour en tirer les études randomisées contrôlées (ERC) comparant la kétamine intranasale à la dexmédétomidine intranasale comme médicament préanesthésique en chirurgie élective ou pour d'autres interventions chez les patients pédiatriques. Nous avons utilisé la version 5.4.1 du logiciel Review Manager pour l'analyse statistique et nous nous sommes conformés aux lignes directrices PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Nous avons évalué la qualité méthodologique des études incluses à l'aide de l'outil d'évaluation du risque de biais RoB 2. Tous les résultats ont été regroupés à l'aide de la méthode Mantle-Haenszel et d'un modèle à effets aléatoires. La qualité des données probantes a été évaluée à l'aide de l'approche GRADE. CONSTATATIONS PRINCIPALES: Sur les 2445 textes intégraux évalués, nous avons inclus dix ERC dans l'analyse. Les critères d'efficacité ne remplissaient pas les critères de comparabilité entre la kétamine intranasale et la dexmédétomidine intranasale pour la sédation lors de la séparation des parents (risque relatif [RR], 0,90; intervalle de confiance [IC] à 95 %, 0,79 à 1,04; I2 = 89 %; qualité des données probantes selon GRADE, faible), acceptation du masque (RR, 0,86; IC 95 %, 0,66 à 1,13; I2 = 50 %; qualité des données probantes selon GRADE, faible) et canulation IV (RR, 1,16; IC 95 %, 0,79 à 1,69; I2 = 69 %; qualité des données probantes selon GRADE, très faible). Les patients traités par kétamine intranasale ont montré une incidence plus élevée de nausées et vomissements (RR, 2,47; IC 95%, 1,24 à 4,91; I2 = 0; qualité des données probantes selon GRADE, modérée). Une proportion significativement plus élevée de cas de bradycardie a été observée dans le groupe dexmédétomidine intranasale (RR, 0,16; IC 95%, 0,04 à 0,70; I2 = 40 %; qualité des données probantes selon GRADE, modérée) comparativement au groupe kétamine. CONCLUSION: Les données probantes de qualité faible à très faible de cette revue systématique et méta-analyse des ERC n'ont ni confirmé ni infirmé l'efficacité comparable de la prémédication par kétamine ou dexmédétomidine intranasale, que ce soit en termes de séparation parentale, d'acceptation du masque ou de canulation IV dans une population pédiatrique. La prise de décision clinique est susceptible d'être influencée par les différences dans les profils d'innocuité gastro-intestinale et cardiovasculaire. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021262516); enregistrée le 22 juillet 2021.

Drug-related deaths among inpatients: a meta-analysis.

PURPOSE: To estimate the prevalence of drug-related deaths with regard to total hospital mortality and to explore the heterogeneity in its estimation through subgroup analysis, univariate and multivariate analysis. METHODS: Two investigators independently searched the PubMed and Google Scholar databases with appropriate key terms to identify observational and randomised studies assessing drug-related problems. The prevalence of drug-related deaths was estimated using a double arcsine method. The heterogeneity was explored through subgroup and univariate analysis for the following study characteristics: study design, age group, study ward, study region, types of drug-related problems, study duration, sample size and study period. The study variables showing significant effects were further explored through a multivariable regression model. The percentage of preventable drug-related deaths was explored as a secondary objective. RESULTS: Of the 480 full-text articles assessed, 23 studies satisfying the selection criteria were included. The mean percentage of drug-related deaths was 5.6% (95% CI: 3.8-7.6%; I2 = 96%). The univariable analysis showed study design (regression coefficient: 4.31) and study wards (regression coefficient: - 6.37) as heterogeneity modifiers. In the multivariable model, only the study ward was considered a significant predictor of drug-related deaths (regression coefficient: - 5.78; p = 0.04). The mean percentage of preventable drug-related deaths was 45.2% (95% CI: 33.6-57.0%; I2 = 60%). CONCLUSION: Drug-related problems are an important cause of mortality. The variability in its estimation could be explained by admission wards.

Renin-angiotensin-aldosterone system blockers and region-specific variations in COVID-19 outcomes: findings from a systematic review and meta-analysis.

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) has been observed to cause a high mortality in people with cardiometabolic diseases. Renin-angiotensin-aldosterone system (RAAS) blockers enhance the expression of ACE2, the binding receptor of SARS-CoV-2, and can enhance viral infectivity. We aim to provide a pooled estimate of the effect of RAAS blockers on COVID-19 outcomes. METHODS: A literature search was performed using MEDLINE/PubMed, Google Scholar and preprint servers. All clinical studies analyzing the effect of RAAS blockers on clinical outcomes in COVID-19 patients were included in this study. Newcastle-Ottawa scale was used for quality assessment of studies. MOOSE checklist was followed. Mortality and severity outcomes were recorded as pooled odds ratio (OR) with 95% Confidence Intervals (CIs) and level of heterogeneity (I 2). Odds of mortality was the primary outcome. Odds of severity, hospitalization, intensive care unit (ICU) admission, mechanical ventilation (MV), steroid use and acute kidney injury were the secondary outcomes. Severity outcomes were chosen depending upon the definition used by respective authors. Country-specific variations and effects of individual class of RAAS blockers were also explored. RESULTS: In total 47 published studies were included in the final analysis, with a total of 26,432 patients from 31 studies in mortality analysis and 20,127 patients from 23 studies in severity analysis. No increased risk of mortality [Pooled OR 0.91 (0.65-1.26), I 2 = 89%] or severity [Pooled OR 1.08 (0.79-1.46), I 2 = 88%] was seen with RAAS blockers. The drug class was protective in hypertension [pooled OR 0.63 (0.46-0.86), I 2 = 58%]. Severity of COVID-19 outcomes was high for Europeans [Pooled OR 2.08 (1.52-2.85), I 2 = 77%] and US patients [Pooled OR 1.87 (1.62-2.17)]. Nearly 4 times higher risk of hospitalization and 2 times higher risk of ICU admission and MV were observed in US patients. Class-wise, angiotensin receptor blocker use was associated with 1.6 times higher odds of severity, mainly in Europeans. CONCLUSION: RAAS blockers are not associated with increased mortality in COVID-19 patients and should be continued in hypertensives. US and European patients are at higher risk of severe outcomes. Pharmacogenetic differences may explain the ethnicity-related variations. PLAIN LANGUAGE SUMMARY: Effect of RAAS-blocking medicines on COVID-19 Background and aims: Higher deaths have been observed in COVID-19 patients who have other long-term diseases such as heart disease, diabetes, and high blood pressure. Many of these patients are prescribed a class of medicines called RAAS blockers (ramipril, telmisartan, etc). We studied whether the use of these medicines worsens the course of COVID-19 disease in these patients or causes excess deaths.Methods: We conducted a pooled analysis of 47 observational studies on the use of RAAS blocker drugs in COVID-19 patients.Results: We found that RAAS blockers do not cause excess deaths in patients with COVID-19. On the contrary, they have benefits if prescribed to those with high blood pressure. We also found that whereas European and US patients of COVID-19 taking these medicines had higher disease severity, this was not the case for Chinese patients.Conclusion: Theremay be some genetic and other factors responsible for differences by ethnicity.

Efficacy and safety of lopinavir-ritonavir in COVID-19: A systematic review of randomized controlled trials.

BACKGROUND: Lopinavir-ritonavir is a repurposed drug for coronavirus disease-2019 (COVID-19). In this study, a pooled effect of lopinavir-ritonavir on mortality, virological cure, radiological improvement and safety profile in COVID-19 patients has been evaluated. METHODS: The databases were searched for comparative randomized controlled studies evaluating the efficacy and/or safety of lopinavir-ritonavir in COVID-19 patients. The mortality outcome was pooled as a risk difference (RD) with 95% CI. The virological cure, radiological improvement and adverse events were pooled as risk ratio (RR) with 95% CI. All outcomes were pooled using the Mantle-Hanzle method random effect model. The heterogeneity was assessed using the I2 test. RESULTS: Out of 82 full text assessed, seven studies were included in the analysis. The included studies had five different control interventions: supportive care (n=4), umifenovir (arbidol) (n=2), navaferon (recombinant anti-tumour and anti-virus protein) (n=1), lopinavir-ritonavir+novaferon (n=1) and lopinavir-ritonavir+interferon beta 1b+ribavirin (n=1). Lopinavir-ritonavir group did not show significant difference in mortality [RD: 0.00 (95% CI: -0.01, 0.02), I2=0], virological cure [RR: 1.06 (95% CI: 0.85, 1.31), I2=0%], radiological improvement [RR: 0.81 (95% CI: 0.62, 1.05)] and adverse events [RR: 2.59 (95% CI: 0.17, 38.90), I2=75%] than supportive care. Similarly, no difference was observed for any efficacy outcomes between lopinavir-ritonavir and other control interventions. We observed significantly high risk of adverse events with lopinavir-ritonavir as compared to umifenovir [RR: 2.96 (95% CI: 1.42-6.18); I2=0%]. CONCLUSION: There is no benefit of the addition of lopinavir-ritonavir to the standard care in COVID-19 patients.

Comparison of effectiveness of interventions in reducing mortality in patients of toxic epidermal necrolysis: A network meta-analysis.

BACKGROUND: Limited evidence is available about effectiveness and choice of immunomodulating treatment modalities for toxic epidermal necrolysis (TEN). AIMS: To compare the effectiveness of interventions to reduce mortality in patients of toxic epidermal necrolysis through network meta-analysis. METHODS: Studies were retrieved using PubMed, Google Scholar and Cochrane Database of Systematic Reviews from inception to September 18, 2018. Only English language articles were considered. Observational and randomized controlled studies having ≥ 5 TEN patients in each intervention arm were included. Two investigators independently extracted study characteristics, intervention details and mortality data. Bayesian network meta-analysis was performed using the Markov chain Monte Carlo (MCMC) approach through the random effect model. The ranking analysis was done to provide a hierarchy of interventions. The consistency between direct and indirect evidence was assessed through node spit analysis. The primary outcome was to compare the mortality [Odds ratio OR (95% credibility interval CrI)] among all treatment modalities of TEN. RESULTS: Twenty-four studies satisfying the selection criteria were included. The network analysis showed improved survival with cyclosporine as compared to supportive care [OR- 0.19 (95% CrI: 0.05, 0.59)] and intravenous immunoglobulin [OR- 0.21 (95% CrI: 0.05, 0.76)]. The hierarchy of treatments based on "surface under the cumulative ranking curves" (SUCRA) value were cyclosporine (0.93), steroid+intravenous immunoglobulin (0.76), etanercept (0.59), steroids (0.46), intravenous immunoglobulin (0.40), supportive care (0.34) and thalidomide (0.02). No inconsistencies between direct and indirect estimates were observed for any of the treatment pairs. LIMITATIONS: Evidence is mainly based on retrospective studies. CONCLUSION: The use of cyclosporine can reduce mortality in TEN patients. Other promising immunomodulators could be steroid+intravenous immunoglobulin combination and etanercept.

Does Adding of Hydroxychloroquine to the Standard Care Provide any Benefit in Reducing the Mortality among COVID-19 Patients?: a Systematic Review.

Hydroxychloroquine has been promoted for its use in treatment of COVID-19 patients based on in-vitro evidences. We searched the databases to include randomized and observational studies evaluating the effect of Hydroxychloroquine on mortality in COVID-19 patients. The outcome was summarized as odds ratios (OR) with a 95% confidence interval (CI).We used the inverse-variance method with a random effect model and assessed the heterogeneity using I2 test. We used ROBINS-I tool to assess methodological quality of the included studies. We performed the meta-analysis using 'Review manager software version 5.3'. We identified 6 observationalstudies satisfying the selection criteria. In all studies, Hydroxychloroquine was given as add on to the standard care and effect was compared with the standard care alone. A pooled analysis observed 251 deaths in 1331 participants of the Hydroxychloroquine arm and 363 deaths in 1577 participants of the control arm. There was no difference in odds of mortality events amongst Hydroxychloroquine and supportive care arm [1.25 (95% CI: 0.65, 2.38); I2 = 80%]. A similar trend was observed with moderate risk of bias studies [0.95 (95% CI: 0.44, 2.06); I2 = 85%]. The odds of mortality were significantly higher in patients treated with Hydroxychloroquine + Azithromycin than supportive care alone [2.34 (95% CI: 1.63, 3.34); I2 = 0%]. A pooled analysis of recently published studies suggests no additional benefit for reducing mortality in COVID-19 patients when Hydroxychloroquine is given as add-on to the standard care. Graphical Abstract.

Mortality among patients due to adverse drug reactions that occur following hospitalisation: a meta-analysis.

PURPOSE: To estimate the prevalence of mortality among patients that develop adverse drug reactions during hospitalisation (ADRIn), to examine heterogeneity through subgroup analysis and to identify system-organ class (SOC) and their causative drugs. METHODS: Two investigators searched PubMed, Google Scholar and related bibliography for studies reporting ADRIn-related mortality data. The primary outcome was to compute overall prevalence of fatal ADRIn (95% CI) using double arcsine method. We explored the heterogeneity (I2) in its estimation based on study design, study population and data collection methods. The secondary outcomes were the pattern of fatal reactions and their causative drugs. PROSPERO register number-CRD42018090331. RESULTS: Out of 349 full text assessed, 48 studies satisfying the selection criteria were included. The fatal ADRIn prevalence was 0.11% (95% CI 0.06-0.18%; I2 = 93%). The fatal ADRIn prevalence ranged from 0.03% (I2 = 0%) in all ages to 0.27% (I2 = 90%) in elderly population studies. Elderly studies varied for all study characteristics. Among study wards, a higher trend of prevalence was observed in 'internal medicine and ICU' (0.46%, I2 = 51%) and 'neonatal/paediatric ward and ICU' (0.34%, I2 = 58%) studies. The commonly involved SOC were 'gastrointestinal disorders' (28.79%), 'blood and lymphatic system disorders' (19.69%) and 'renal and urinary disorders' (13.64%). Most commonly observed causative drug-fatal ADRIn pairs were antithrombotics and nonsteroidal anti-inflammatory drugs induced gastrointestinal bleeding, and antineoplastic agents induced cytopenia. CONCLUSION: ADRIn is an important cause of mortality. Age groups and study wards have important influence on prevalence of fatal ADRIn and its heterogeneity across studies. Few class drugs contribute to sizable proportion of ADRIn-related mortality.

Mortality among patients due to adverse drug reactions that lead to hospitalization: a meta-analysis.

PURPOSE: The aim of this study was to estimate the prevalence of mortality among patients due to adverse drug reactions that lead to hospitalisation (fatal ADRAd), to explore the heterogeneity in its estimation through subgroup analysis of study characteristics, and to identify system-organ classes involved and causative drugs for fatal ADRAd. METHODS: We identified prospective ADRAd-related studies via screening of the PubMed and Google Scholar databases with appropriate key terms. We estimated the prevalence of fatal ADRAd using a double arcsine method and explored heterogeneity using the following study characteristics: age groups, wards, study region, ADR definitions, ADR identification methods, study duration and sample size. We examined patterns of fatal ADRAd and causative drugs. RESULTS: Among 312 full-text articles assessed, 49 studies satisfied the selection criteria and were included in the analysis. The mean prevalence of fatal ADRAd was 0.20% (95% CI: 0.13-0.27%; I2 = 93%). The age groups and study wards were the important heterogeneity modifiers. The mean fatal ADRAd prevalence varied from 0.01% in paediatric patients to 0.44% in the elderly. Subgroup analysis showed a higher prevalence of fatal ADRAd in intensive care units, emergency departments, multispecialty wards and whole hospitals. Computer-based monitoring systems in combination with other methods detected higher mortality. Intracranial haemorrhage, renal failure and gastrointestinal bleeding accounted for more than 50% of fatal ADRAdcases. Warfarin, aspirin, renin-angiotensin system (RAS) inhibitors and digoxin accounted for 60% of fatal ADRAd. CONCLUSIONS: ADRAd is an important cause of mortality. Strategies targeting the safer use of warfarin, aspirin, RAS inhibitors and digoxin could reduce the large number of fatal ADRAdcases.

Prevalence and pattern of antipsychotic induced movement disorders in a tertiary care teaching hospital in India - a cross-sectional study.

OBJECTIVES: To assess prevalence and pattern of movement disorders among patients taking antipsychotic medications. METHODS: This cross-sectional, intensive monitoring (patient interview, case record form review and clinical examination) study was conducted in patients taking antipsychotic drugs irrespective of duration for the development of movement disorders. The psychiatrist used Modified Simpson-Angus Scale score (10-item scale), Barnes' rating scale and Abnormal Involuntary Movement Scale to diagnose parkinsonism, akathisia and tardive dyskinesia, respectively. We assessed movement disorders for the preventability and seriousness. RESULTS: The overall prevalence of antipsychotic induced movement disorders was 5.67% (95% CI: 4.19-7.62). The prevalence of parkinsonism, akathisia and tardive dyskinesia was 5.10% (95% CI: 3.71-6.98), 0.85% (95% CI: 0.39-1.84) and 0.57% (95% CI: 0.22-1.45), respectively. There was a trend of high proportions of movement disorders in extreme of age group, female gender, patients treated with conventional antipsychotics, on poly therapy, patients of epilepsy with psychosis, schizophrenia and bipolar mood disorder. The movement disorder was lowest with quetiapine (2.02%). CONCLUSIONS: The higher use of atypical antipsychotics had reduced the occurrence of movement disorders in our setup.

Cutaneous Adverse Drug Reactions in a Tertiary Care Teaching Hospital in India: An Intensive Monitoring Study.

BACKGROUND: The epidemiological data based on intensive monitoring studies are limited for the cutaneous adverse drug reactions (CADRs) in terms of incidence. Most of earlier Indian studies focused only on types and causative drugs of CADRs. AIM: The aim of this study is to analyze the CADRs with reference to the incidence, its subgroup analysis, causative drugs, and other clinical characteristics in Indian population. METHODOLOGY: Intensive monitoring study was carried out over a period of 3 years in the dermatology outpatient and inpatient department. CADRs due to only systematically administered drugs were considered. The WHO definition for CADR, the WHO causality definitions, modified Schumock and Thornton's criteria for preventability, and International Conference on Harmonisation E2A guidelines for seriousness were considered. Incidence was expressed in percentage and its 95% confidence interval. The incidence was analyzed on basis of characteristics of study population and CADRs. RESULTS: A total of 171 CADRs were observed from 37,623 patients. The CADR incidence was 0.45% (95% CI: 0.39-0.53). The incidence did not significantly differ in different age groups and gender. Commonly observed CADRs were maculopapular rash (23.98%), urticaria (21.64%), and fixed drug eruptions (FDEs) (18.13%). Antimicrobials (35.18%) and nonsteroidal anti-inflammatory drugs (NSAIDs) were suspected in all common CADRs. Anti-infective and NSAIDs were most commonly suspected drugs in overall CADRs, maculopapular rash, urticaria, FDEs, and erythema multiforme. The exact nature of drugs remained inaccessible in one-fourth cases due to use of the over-the-counter self-medications. The incidence of preventable and serious and fatal CADRs was 0.08% (95% CI: 0.05-0.11), 0.04% (95% CI: 0.02-0.06), and 0.003% (95% CI: 0.000-0.001), respectively. CONCLUSION: Ethnic characteristics should be considered while interpreting incidence from the international studies. The demographic characteristics of study population do not affect the incidence of CADRs. Indian patients should be sensitized about hazards of self-medications.