Efficacy and Safety of Glycopyrrolate in the Management of Organophosphate and Carbamate Poisoning: A Systematic Review.

OBJECTIVE: There is a lack of evidence on the effectiveness of antidotes in the management of organophosphate and carbamate (OPC) poisoning. We aimed to review the efficacy and safety of glycopyrrolate in the management of OPC poisoning. METHODOLOGY: Databases such as PubMed, Scopus, Embase, and Cochrane Library were extensively searched from inception to November 2022 and updated till October 2023. Interventional, observational, and descriptive studies assessing the efficacy and safety of glycopyrrolate administered in any dose, route, and duration for the management of OPC poisoning published in the English language were considered for this review. The treatment with any other regimen that did not include glycopyrrolate was regarded as the comparator. The survival, intensive care unit (ICU) days and ventilatory outcomes were considered efficacy outcomes, and adverse effects were considered safety outcomes. Suitable quality assessment tools were used to assess the risk of bias in the included studies. Two independent reviewers were involved in the study selection, data extraction, and quality assessment and any discrepancies were resolved through mutual discussion or consultation with a third reviewer. RESULTS: A total of 9 studies (2 RCTs, 4 cohorts, 1 case series, and 2 case reports) out of 591 nonduplicate records were considered for this review. Overall, the RCTs were observed to have a moderate quality, and observational studies and descriptive studies were found to have good quality. All the included studies used atropine administration as a standard treatment option along with glycopyrrolate. The OPC patients treated with glycopyrrolate had a fewer hospitalization days with comparable recovery and ventilatory outcomes than those that had not been treated with glycopyrrolate. The occurrence of adverse events and complications was lower in the glycopyrrolate group than in the control group. CONCLUSION: Currently, there is a lack of comparative studies to recommend the use of glycopyrrolate in OPC poisoning, and further interventional studies are required to make an evidencebased recommendation on this topic.

The significance of APACHE II as a predictor of mortality in paraquat poisoning: A systematic review and meta-analysis.

The Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system is utilised as a prognostic method in paraquat poisoning; however, current evidence shows ambiguity. Although some studies have shown APACHE II to be a superior tool, others have reported it inferior to other prognostic markers, such as lactate, severity index of paraquat poisoning and urine paraquat concentration. Hence, to address this ambiguity, we conducted a systematic review and meta-analysis to analyse prognostic accuracy of APACHE II score in predicting mortality in paraquat poisoning. We included twenty studies with 2524 paraquat poisoned patients in the systematic review, after a comprehensive literature search in databases PubMed, Embase, Web of Science, Scopus and Cochrane Library, from which 16 studies were included in the meta-analysis. The survivors of paraquat poisoning were found to have significantly lower APACHE II scores (Mean Difference (MD): -5.76; 95% CI: -7.93 to -3.60 p < 0.0001; n = 16 studies) compared to non-survivors. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) for APACHE II score <9 was found to be 74%, 68%, 2.58, 0.38 and 7.10, respectively (n = 5 studies). The area under the curve (AUC) of the bivariate summary receiver operating characteristic (SROC) curve was found to be 0.80. The pooled sensitivity, specificity, PLR, NLR and DOR for APACHE II score ≥9 was found to be 73%, 86%, 4.69, 0.33 and 16.42, respectively (n = 9 studies). The AUC of the SROC curve was found to be 0.89. Pairwise AUC comparison of APACHE II with other prognostic markers showed serum presepsin to have a significantly better discriminatory ability than APACHE II. Through the findings of this study, we conclude that APACHE II was found to be a good indicator of death in paraquat poisoning patients. However, higher APACHE II scores (≥9) depicted greater specificity in predicting mortality in paraquat poisoning. Thus, APACHE II can be used as a practical tool in the hand of physicians to prognose patients with paraquat poisoning to aid clinical decisions.

Factors contributing to the adverse drug reactions associated with the dipeptidyl peptidase-4 (DPP-4) inhibitors: A scoping review.

BACKGROUND AND AIM: Adverse drug reactions are one of the contributors to increased hospital admission and length of hospital stay. Among the various antidiabetic agents prescribed, dipeptidyl peptidase-4 (DPP-4) inhibitors have gained wide recognition and shown more persistence than other novel hypoglycemic agents. We performed a scoping review to identify the risk factors contributing to the adverse drug reactions with DPP-4 inhibitors. METHODOLOGY: We followed Preferred Reporting Items for Scoping Review (PRISMA-ScR) Guidelines for reporting the findings. Data sources such as PubMed/MEDLINE, Scopus, Embase, and Cochrane were assessed. We included studies that reported the risk factors contributing to the DPP-4 inhibitor-associated adverse drug reactions. The Joanna Briggs Institute (JBI) critical appraisal checklist was used to assess the methodological quality of the studies. RESULTS: Of the 6406 studies retrieved, 11 studies met our inclusion criteria. Of these 11 studies, seven were post-marketing surveillance studies, one nested case-control study, one comparator cohort study, one food and drug administration (FDA) adverse event reporting system (FAERS)-based observational study, and one questionnaire-based cross-sectional survey study. A total of eight factors were identified that contributed to the DPP-4 inhibitor-associated adverse drug reactions. CONCLUSION: The included studies suggested age >65 years, females, grade 4 and 5 renal impairment, concomitant drugs, disease and drug therapy duration, liver disease, non-smokers, and non-hypertension as risk factors. Further studies should be conducted to provide insight into these risk factors so that the appropriate use of DPP-4 inhibitors in the diabetic population can be encouraged to improve the health-related quality of life. PROSPERO REGISTRATION: CRD42022308764.

Impact of COVID-19 pandemic on medicine supply chain for patients with chronic diseases: Experiences of the community pharmacists.

Problem considered: Coronavirus disease(COVID-19) outbroke towards the end of December 2019 in China, soon it started spreading rapidly to various countries leading to an outburst of pandemic. Due to the restrictions imposed to control the spread of the infection, globally the manufacturing, import and export of medicine and the healthcare services to patients with chronic illness had been affected. This study aimed to explore the perspectives of the pharmacists on the medicine supply chain for patients with chronic diseases during COVID-19 pandemic in India. Methods: This study is a prospective, qualitative research involving telephonic, semi-structured in-depth interviews. An interview guide for pharmacists was prepared and validated using "Interview Protocol Refinement" method. Purposive sampling method was used to recruit the pharmacists; a telephonic oral consent was obtained. The interview session was audio recorded and the recordings were transcribed verbatim. Further, transcripts were validated and later analysed using NVivo software. Results: A total of 8 participants were interviewed during our study. Thematic analysis of the transcripts resulted in seven main themes. The study showed that there was deficiency in medicine supply during the COVID-19 pandemic and the pharmacists faced several challenges in procuring and storing the medication, arranging for unavailable medicines, medication dispensing and provision of the services such as medicine delivery, patient counselling. There was also scarcity of manpower leading to extra workload and working overtime. Conclusion: Uninterrupted supply of essential medicine is the backbone of health care system. An effective plan and appropriate strategies are vital to combat such future emergencies.

Systematic review and meta-analysis of global prevalence of neurotoxic and hemotoxic snakebite envenomation.

Background: The World Health Organization estimates that there are approximately 5.4 million snakebites and 1.8-2.7 million cases of envenomation, with 81 410-137 880 deaths each year worldwide. Aims: To estimate the prevalence of neurotoxic and haemotoxic snakebite envenomation through a comprehensive systematic review and meta-analysis. Methods: We searched Medline/PubMed, Scopus and Cochrane Library up to January 2021 using keywords such as snakebite and snake envenomation. Bibliographic and random searches were also performed. Prospective or retrospective observational studies and randomized controlled trials were included for the review. Results: We included 271 of 9711 studies published between 1963 and 2020. The pooled prevalence of snakebite from 188 studies with a total of 207 235 participants showed the highest prevalence in North America (69.20%; 95% confidence interval, CI: 57.06-81.34%) and lowest in Africa (28.10%; 95% CI: 22.22-33.98%). There was a pooled prevalence of 24.94% (95% CI: 22.84-27.03%) for haemotoxicity, with a highest prevalence of coagulopathy (43.76%; 95% CI: 33.15-54.37%). The overall prevalence of neurotoxicity was 38.20% (95% CI: 31.88-44.53%), with a highest prevalence of ptosis (53.57%; 95% CI: 38.51-68.62%). Conclusion: There was a higher prevalence of snakebites in North America. The most prevalent haemotoxicity and neurotoxicity were coagulopathy and ptosis, respectively. The overall quality of evidence was good with a non-significant publication bias.

Proton pump inhibitors use and risk of inflammatory bowel diseases: a meta-analysis of observational studies.

Background and objective: Proton Pump Inhibitors (PPIs) reduce gastric acid production and they are indicated for myriad gastrointestinal conditions. Prolonged use of PPI has been linked to the risk of inflammatory bowel disease (IBD) though this fact is not well established. We aimed to conduct a systematic review and meta-analysis to estimate the risk of IBD occurrence with PPI use. Methodology: The databases such as PubMed, Scopus, and Cochrane Library were accessed from inception to December 2020. Additionally, the bibliographic search and a random search in Google, Google Scholar, and ResearchGate were performed to find additional sources. The observational studies estimating the risk of IBD following the use of PPI, published in the English language were considered for this review. The methodological quality of included studies was assessed using the Modified Downs and Black checklist. Results: Eight out of 2038 studies with 157,758 participants were included in this meta-analysis. A significantly higher risk of IBD (adjusted odds ratio [aOR] 2.43; 95% Confidence Interval [CI] 1.18-5.02; P=0.02; n=6) was observed in participants taking PPIs for any indication. Moreover, a significant association was observed between PPI exposure on the different types of IBD such as ulcerative colitis and Crohn's disease together (aOR: 3.60; 95% CI: 1.10-11.74), collagenous colitis (OR: 4.73; 95% CI: 1.99-11.22) and lymphocytic Colitis (OR: 3.77; 95% CI: 2.91-4.87), but not with ulcerative colitis (P=0.47) and microscopic colitis (P=0.07) alone. Similarly, a significant association was observed among Europeans (aOR: 3.98; 95% CI: 2.36-6.71), but not with North American (aOR: 0.48; 95% CI: 0.01-26.71) studies. Overall the study quality was good. Conclusion: The current evidence indicates that exposure to PPI is significantly associated with increased risk of IBD. Further, adequately powered studies from various parts of the world are needed for better quantification and generalizability of our findings. PROSPERO Protocol Registration Number: CRD42020209674.

Role of human leukocyte antigen in anti-epileptic drugs-induced Stevens-Johnson Syndrome/toxic epidermal necrolysis: A meta-analysis.

PURPOSE: Antiepileptic drugs (AEDs) are extensively used to manage epilepsy and other comorbidities associated with seizures. Human Leukocyte Antigen (HLA) has a strong association with AED-induced severe cutaneous adverse drug reactions. OBJECTIVE: We aimed to perform a systematic review and meta-analysis to identify, critically evaluate, and synthesize the best possible evidence on HLA-associated AED-induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). METHODS: MEDLINE/PubMed, Scopus, and the Cochrane Library were searched for literature from inception up to July 2022. We included case control studies analyzing association between HLA and AED-induced SJS/TEN. We assessed the studies' risk of bias in using Quality of genetic studies (Q-genie) tool. Outcomes focused on association (risk) between HLA and AED-induced SJS/TEN. The estimated risk was presented in the form of odds ratio (OR). RESULTS: We included 37 studies (51,422 participants; 7027 cases and 44,395 controls). There was a significantly higher risk of Carbamazepine-induced SJS/TEN with HLA-A (OR: 1.50; 95% CI: 1.03 to 2.17), HLA-B (OR: 1.94; 95% CI: 1.45 to 2.58), HLA-C (OR: 7.83; 95% CI: 4.72 to 12.98), and HLA-DRB1 (OR: 2.82; 95% CI: 1.94 to 4.12). Lamotrigine-induced SJS/TEN posed a higher risk with HLA-A (OR: 2.38; 95% CI: 1.26 to 4.46) and HLA-B (OR: 2.79; 95% CI: 1.75 to 4.46). Phenytoin-induced SJS/TEN showed a higher risk with HLA-A (OR: 3.47; 95% CI: 2.17 to 5.56), HLA-B (OR: 1.72; 95% CI: 1.38 to 2.15), and HLA-C (OR: 2.92; 95% CI: 1.77 to 4.83). Phenobarbital-induced SJS/TEN had a higher risk with HLA-A (OR: 6.98; 95% CI: 1.81 to 26.84), HLA-B (OR: 2.40; 95% CI: 1.39 to 4.17), and HLA-C (OR: 3.37; 95% CI: 1.03 to 11.01). Zonisamide-induced SJS/TEN was significantly associated with HLA-A*02:07 (OR: 9.77; 95% CI: 3.07 to 31.1), HLA-B*46:01 (OR: 6.73; 95% CI: 2.12 to 21.36), and HLA-DRB1×08:03 (OR: 3.78; 95% CI: 1.20 to 11.97). All other alleles of HLA were observed to have a non-significant association with AED-induced SJS/TEN. All included studies were of good quality, with a score of >50 and a mean score of 54.96 out of 77. CONCLUSION: Our study showed a significant association between few variants of HLA alleles and AED-induced SJS/TEN. Evidences from our study could help in population-based studies and in implementation of individualized treatment regimens. These findings could be part of translational research helping in precision therapy.

Artificial intelligence in acute respiratory distress syndrome: A systematic review.

BACKGROUND AND OBJECTIVE: Acute respiratory distress syndrome (ARDS) is a life-threatening pulmonary disease with a high clinical and cost burden across the globe. Artificial intelligence (AI), an emerging area, has been used for various purposes in ARDS. We aim to summarize the currently available literature on various applications of AI in ARDS through a systematic review. METHODOLOGY: PubMed was searched from inception to February 2021 to collate all the studies. Additionally, a bibliographic search of included studies and a random search on Google, Google Scholar, and Research Gate were performed to identify relevant articles. Studies published in English language that employed data about developing and/or assessing the role of AI in the various aspects of ARDS were considered for this review. Three independent reviewers performed study selection and data extraction; any disagreements were settled through consensus or discussion with another member of the research team. RESULTS: A total of 19 studies published between the year 2002 and 2020 were included. In these included studies, AI was used for various purposes in ARDS such as diagnosis (n = 10; 53 %), risk stratification (n = 1; 5 %), prediction of severity (n = 3; 17 %), management (n = 2; 10 %), prediction of mortality (n = 2; 10 %), and decision making (n = 1; 5 %). The area under the curve among the developed models in the included studies ranged between 0.8 and 1, which is considered to be very good to excellent. CONCLUSION: AI is revolutionizing healthcare and has a wide range of applications in ARDS, such as minimizing cost and enhancing outcomes.

Artificial intelligence in differentiating tropical infections: A step ahead.

BACKGROUND AND OBJECTIVE: Differentiating tropical infections are difficult due to its homogenous nature of clinical and laboratorial presentations among them. Sophisticated differential tests and prediction tools are better ways to tackle this issue. Here, we aimed to develop a clinician assisted decision making tool to differentiate the common tropical infections. METHODOLOGY: A cross sectional study through 9 item self-administered questionnaire were performed to understand the need of developing a decision making tool and its parameters. The most significant differential parameters among the identified infections were measured through a retrospective study and decision tree was developed. Based on the parameters identified, a multinomial logistic regression model and a machine learning model were developed which could better differentiate the infection. RESULTS: A total of 40 physicians involved in the management of tropical infections were included for need analysis. Dengue, malaria, leptospirosis and scrub typhus were the common tropical infections in our settings. Sodium, total bilirubin, albumin, lymphocytes and platelets were the laboratory parameters; and abdominal pain, arthralgia, myalgia and urine output were the clinical presentation identified as better predictors. In multinomial logistic regression analysis with dengue as a reference revealed a predictability of 60.7%, 62.5% and 66% for dengue, malaria and leptospirosis, respectively, whereas, scrub typhus showed only 38% of predictability. The multi classification machine learning model observed to have an overall predictability of 55-60%, whereas a binary classification machine learning algorithms showed an average of 79-84% for one vs other and 69-88% for one vs one disease category. CONCLUSION: This is a first of its kind study where both statistical and machine learning approaches were explored simultaneously for differentiating tropical infections. Machine learning techniques in healthcare sectors will aid in early detection and better patient care.

Use of histamine-2 receptor antagonists and risk of inflammatory bowel diseases: A systematic review and meta-analysis of observational studies.

WHAT IS KNOWN AND OBJECTIVE: The effect of histamine-2 receptor antagonists (H2RAs) use causing inflammatory bowel diseases (IBD) has been reported in few isolated observational studies; however, pooled estimation of IBD risk has not been done. The present study was conducted to estimate the risk of IBD [Crohn's disease (CD), ulcerative colitis (UC) and microscopic colitis (MC)], among H2RAs users. METHODS: Databases such as MEDLINE/PubMed, Scopus and Cochrane Library were searched from inception to January 2021. A bibliographic search of selected articles, random search in Google Scholar and ResearchGate were also performed for any additional studies. The observational studies which assessed the incidence or risk of IBD in H2RA users published in the English language were considered. Modified Downs and Black Checklist was used for quality assessment. Two independent reviewers were involved in study selection, data extraction and quality assessment; any discrepancies were settled through consensus or by consulting a third reviewer. RESULTS: Four studies out of 2,658 articles were included for this meta-analysis. The meta-analysis of 4 studies with 8939 participants revealed a significantly higher risk of IBD (OR: 2.27; 95% CI: 1.70-3.02; p < 0.0001) in H2RA users compared to non-users. Similar significant relationships were observed in the subgroup analysis of adults (p < 0.0001) and paediatrics (p = 0.04). The quality of included studies was observed to be fair to good. WHAT IS NEW AND CONCLUSION: Our findings indicate a significantly higher IBD risk among those who used H2RA compared to non-users both in adults and in paediatrics. Further observational studies involving large populations are required to strengthen these results and to generalize these findings.

Mobile applications in medical education: A systematic review and meta-analysis.

OBJECTIVE: This review evaluates the effectiveness of smartphone applications in improving academic performance and clinical practice among healthcare professionals and students. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles were retrieved from PubMed, Scopus, and Cochrane library through a comprehensive search strategy. Studies that included medical, dental, nursing, allied healthcare professional, undergraduates, postgraduates, and interns from the same disciplines who used mobile applications for their academic learning and/or daily clinical practice were considered. RESULTS: 52 studies with a total of 4057 learner participants were included in this review. 33 studies (15 RCTs, 1 cluster RCT, 7 quasi-experimental studies, 9 interventional cohort studies and 1 cross-sectional study) reported that mobile applications were an effective tool that contributed to a significant improvement in the knowledge level of the participants. The pooled effect of 15 studies with 962 participants showed that the knowledge score improved significantly in the group using mobile applications when compared to the group who did not use mobile applications (SMD = 0.94, 95% CI = 0.57 to1.31, P<0.00001). 19 studies (11 RCTs, 3 quasi-experimental studies and 5 interventional cohort studies) reported that mobile applications were effective in significantly improving skills among the participants. CONCLUSION: Mobile applications are effective tools in enhancing knowledge and skills. They can be considered as effective adjunct tools in medical education by considering their low expense, high versatility, reduced dependency on regional or site boundaries, online and offline, simulation, and flexible learning features of mobile apps.

Adverse drug reactions of GLP-1 agonists: A systematic review of case reports.

BACKGROUND AND AIM: The importance of glucagon-like peptide-1 (GLP-1) agonists is increasing because of its blood sugar controlling and weight loss properties. The data regarding safety of GLP-1 agonists are limited. This study aims to review case reports and case series on adverse drug reactions (ADRs) of GLP-1 agonist. METHODOLOGY: A comprehensive search was performed in PubMed/Medline, Scopus and Embase to identify literatures. Bibliographic search and open search in Google, Google Scholar, SpringerLink and ResearchGate was performed to identify additional studies. Case reports and case series published the ADRs by the use of GLP-1 agonists in type 2 diabetes patients were included in the study. Reviews, experimental studies, observational studies, grey literature and non English studies were excluded. RESULTS: The study identified 120 cases of GLP-1 agonists associated ADRs (liraglutide - 46, exenatide - 46, dulaglutide - 20, semaglutide - 4, albiglutide - 2, lixisenatide - 2). The major ADRs reported was gastrointestinal disorders (n = 40) followed by renal (n = 23), dermatologic (n = 14), hepatic (n = 10), immunologic (n = 13), endocrine/metabolic (n = 7), hematologic (n = 3), angioedema (n = 3), neurologic (n = 2), cardiovascular (n = 2) and 1 from each of psychiatric, reproductive, generalized edema problems. CONCLUSION: Gastrointestinal problems, particularly pancreatitis was the more frequently reported adverse drug reaction associated with GLP-1 agonist. The most adverse drug reactions were observed with liraglutide and exenatide.

Factors affecting the outcomes in patients with acute respiratory distress syndrome in a tertiary care setting.

Purpose: The clinical profile and factors affecting outcomes in acute respiratory distress syndrome (ARDS) from adequately sample-sized Indian studies are still lacking. We aimed to investigate the clinical profile, treatment pattern, outcomes; and to assess factors affecting non-recovery in ARDS patients. Patients and methods: A retrospective observational study was conducted among adult ARDS patients admitted during five year period (January 2014-December 2018) in a South Indian tertiary care setting. The relevant data were collected from the medical records to the data collection form. The univariate and multivariate logistic regression analyses were conducted to identify the predictors of outcomes using SPSS v20. Results: A total of 857 participants including 496 males and 361 females with a mean age of 46.86 ± 15.81 years were included in this study. Fever (70.9%), crepitation (58.3%), breathlessness (56.9%), and cough (45%) were the major clinical presentation. Hypertension (25.2%), kidney disease (23.8%), and diabetes (22.3%) were the major comorbidities; and sepsis (37.6%), pneumonia (33.3%), and septic shock (27.5%) were the major etiological factors observed. Antibiotics and steroids were administered to 97.9% and 52.3% of the population, respectively. The recovery rate was 47.49%. The patients with scrub typhus, dengue, pancreatitis, and oxygen supplementation had significantly lower mortality. The factors such as advanced age, sepsis, septic shock, liver diseases, and ventilation requirements were observed to be the independent predictors of non-recovery in ARDS patients. Conclusion: A comparable recovery rate was observed in our population. Advanced age, sepsis, septic shock, liver diseases, and ventilation requirements were the independent predictors of non-recovery.

Association of proton-pump inhibitor use with adverse health outcomes: A systematic umbrella review of meta-analyses of cohort studies and randomised controlled trials.

AIMS: The aim was to perform an umbrella review to summarise the existing evidence on proton-pump inhibitor (PPI) use and adverse outcomes and to grade the certainty of evidence. METHODS: Electronic databases were searched up to July 2021 for meta-analyses of cohort studies and/or randomised controlled trials (RCTs). Summary effect sizes from a random-effects model, between-study heterogeneity, 95% prediction interval, small-study effect, excess significance and credibility ceilings were devised to classify the credibility of evidence from meta-analyses of cohort studies, whereas the GRADE approach was used for meta-analyses of RCTs. RESULTS: In meta-analyses of cohort studies, 52 of the 91 examined associations were statistically significant (P ≤ .05). Convincing evidence emerged from main analysis for the association between PPI use and risk of all-site fracture and chronic kidney disease in the elderly population. However, none of these associations remained supported by convincing evidence after sensitivity analyses. The use of PPI is also associated with an increased risk of mortality due to COVID-19 infection and other related adverse outcomes, but the quality of evidence was weak. In meta-analyses of RCTs, 38 of the 63 examined associations were statistically significant. However, no associations were supported by high or moderate-quality evidence. CONCLUSION: This study's findings imply that most putative adverse outcomes associated with PPI use may not be supported by high-quality evidence and are likely to have been affected by underlying confounding factors. Future research is needed to confirm the causal association between PPI use and risk of fracture and chronic kidney disease.

N-Acetyl Cysteine in Rodenticide Poisoning: A Systematic Review and Meta-Analysis.

BACKGROUND: Treatment with N-Acetyl Cysteine (NAC) in rodenticide poisoning has not been well established due to mixed study results and insufficient evidence. This review aimed to summarize the clinical benefits of NAC in the management of rodenticide poisoning. METHODS: This review follows the PICOS framework and the PRISMA guidelines. Pub- Med/MEDLINE, Scopus, and the Cochrane library were searched to identify the published literature from inception to September 2020, and a reference search was performed for additional relevant studies. The English language studies addressing the use of NAC in rodenticide poisoning were considered for the review. We considered all experimental and observational studies due to the insufficient number of interventional studies. RESULTS: Ten studies (two RCTs, four observational, and four descriptive) out of 2,178 studies with 492 participants were considered for the review. Only six studies (two RCTs, one prospective, and three retrospective studies) reported recovery and mortality. Pooled results of RCTs (n=2) showed a significant recovery rate (Odds Ratio [OR]: 3.97; 95% Confidence Interval [CI]:1.69-9.30), whereas summary estimates of prospective and retrospective studies recorded a non-significant effect. Metaanalysis of RCTs (OR: 0.25; 95% CI: 0.11-0.59; n=2) and retrospective studies (OR: 0.34; 95% CI: 0.15-0.78; n=3) showed a significant reduction in mortality, whereas pooled analysis of prospective studies recorded a non-significant effect. A significant reduction in intubation or ventilation (OR: 0.25; 95% CI: 0.11-0.60; 2 RCTs) and a non-significant (P=0.41) difference in duration of hospitalization was observed with NAC when compared to the non-NAC treated group. The quality of the included studies appeared to be moderate to high. CONCLUSION: Our findings indicate that NAC showed better survival and lower mortality rate when compared to non-NAC treated group; hence NAC can be considered for the management of rodenticide poisoning.

Intermittent Fasting and Obesity-Related Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials.

Importance: Several meta-analyses of randomized clinical trials (RCTs) have demonstrated the many health benefits of intermittent fasting (IF). However, there has been little synthesis of the strength and quality of this evidence in aggregate to date. Objective: To grade the evidence from published meta-analyses of RCTs that assessed the associations of IF (zero-calorie alternate-day fasting, modified alternate-day fasting, the 5:2 diet, and time-restricted eating) with obesity-related health outcomes. Evidence Review: PubMed, Embase, and Cochrane database of systematic reviews were searched from database inception to January 12, 2021. Data analysis was conducted from April 2021 through July 2021. Meta-analyses of RCTs investigating effects of IF in adults were included. The effect sizes of IF were recalculated using a random-effects model. We assessed the quality of evidence per association by applying the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluations) as high, moderate, low, and very low. Findings: A total of 11 meta-analyses comprising 130 RCTs (median [IQR] sample size, 38 [24-69] participants; median [IQR] follow-up period, 3 [2-5] months) were included describing 104 unique associations of different types of IF with obesity-related health outcomes (median [IQR] studies per association, 4 [3-5]). There were 28 statistically significant associations (27%) that demonstrated the beneficial outcomes for body mass index, body weight, fat mass, low-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting plasma glucose, fasting insulin, homeostatic model assessment of insulin resistance, and blood pressure. IF was found to be associated with reduced fat-free mass. One significant association (1%) supported by high-quality evidence was modified alternate-day fasting for 1 to 2 months, which was associated with moderate reduction in body mass index in healthy adults and adults with overweight, obesity, or nonalcoholic fatty liver disease compared with regular diet. Six associations (6%) were supported by moderate quality evidence. The remaining associations found to be significant were supported by very low (75 associations [72%]) to low (22 associations [21%]) quality evidence. Conclusions and Relevance: In this umbrella review, we found beneficial associations of IF with anthropometric and cardiometabolic outcomes supported by moderate to high quality of evidence, which supports the role of IF, especially modified alternate-day fasting, as a weight loss approach for adults with overweight or obesity. More clinical trials with long-term follow-up are needed to investigate the effects of IF on clinical outcomes such as cardiovascular events and mortality.

Effectiveness of blended learning in pharmacy education: An experimental study using clinical research modules.

BACKGROUND &OBJECTIVES: Though there are studies to evaluate the effectiveness of blended learning in pharmacy education, most of them originate from USA and have used previous year students' scores as control. Also there is less research in comparing use of self -regulated learning strategies between blended and other learning strategies. Primary aim was to evaluate the effectiveness of blended learning on knowledge score using clinical research modules. Secondary objective was designed to compare the use of self-regulated learning strategies between blended learning, web-based e-learning and didactic teaching. MATERIALS AND METHODS: A prospective cluster randomized trial was conducted with didactic teaching as control and web-based e-learning and blended learning as interventions. The target population was final year Pharm D students. Outcome was assessed using a validated knowledge questionnaire, a motivated strategies for learning questionnaire and a feedback form. All statistical analyses were carried out using Statistical Package for Social Science (SPSS) Version 20. RESULTS: A total of 241 students from 12 colleges completed the study. Mean knowledge score of students in blended learning group was higher than those in the didactic teaching and web- based e- learning program (64.26±18.19 Vs 56.65±8.73 Vs 52.11±22.06,p<0.001).Frequency of use of learning strategies namely rehearsal, elaboration, organization and critical thinking was statistically significantly higher in the blended learning group compared to those of didactic and web-based e-learning group (p<0.05) But there were no statistically significant difference of motivational orientations between didactic and blended learning group except strategies of extrinsic goal orientation and self-efficacy. Students preferred blended learning (86.5%) over didactic and web-based e-learning. CONCLUSION: Blended learning approach is an effective way to teach clinical research module. Students of blended learning group employed all motivational and learning strategies more often than students of the didactic and web- based e-learning groups except strategies of intrinsic goal orientation, task value, control of learning belief and help seeking.

Efficacy and safety of corticosteroids in acute respiratory distress syndrome: An overview of meta-analyses.

BACKGROUND: Evidence-based recommendations on the efficacy and safety of corticosteroids in acute respiratory distress syndrome (ARDS) remain a therapeutic challenge. Findings from several systematic reviews and meta-analyses are inconsistent. We aimed to assess the published meta-analyses through a systematic review approach and provide further insight into the current uncertainty and also to perform an updated meta-analysis from all the available primary studies. METHODOLOGY: We followed the Preferred Reporting Items for Systematic Review (PRISMA) guidelines to establish the patients, intervention, control and outcome (PICO) for reviewing published meta-analyses. Data sources such as PubMed/MEDLINE, SCOPUS, Cochrane and Google Scholar from inception to February 2021 were accessed. Prevention of ARDS, mortality, ventilator-free days, ICU stay and safety in terms of occurrence of adverse effects were the patient-related outcomes. The review also assessed meta-analysis design-related outcomes which includes the quality of meta-analysis, factors contributing to the risk of bias, extent and sources of heterogeneity, publication bias and robustness of findings. AMSTAR-2 checklist assessed the quality of published meta-analyses. RESULTS: A total of 18 meta-analyses were reviewed comprising a total of 38 primary studies and 3760 patients. Fourteen studies were in ARDS, three in community-acquired pneumonia and one in critical care. The overall quality of meta-analyses was observed to be critically low to high. A non-significant risk of publication bias and non-significant level of heterogeneity was observed in the reviewed meta-analysis. Corticosteroid was significantly effective in preventing ARDS among CAP patients. The effect of corticosteroids on mortality was observed to be still inconsistent, whereas significant improvement was observed with ICU and ventilator outcomes compared with the control group. Our meta-analysis observed a significant reduction of mortality in RCTs (RR: 0.78; 95% CI: 0.61 to 0.99) and the duration of mechanical ventilation (MD: -4.75; 95% CI: -7.63 to -1.88); and a significant increase in ventilator-free days (MD: 6.03; 95% CI: 3.59 to 8.47) and ICU-free days (MD: 8.04; 95% CI: 2.70 to 13.38) in ARDS patients treated with corticosteroids compared with the control group. CONCLUSION: The quality of included studies ranged from critically low to high demonstrating inconsistency in risk of bias. While older studies found no significant effect, recent meta-analyses of RCTs found a significant mortality reduction in the corticosteroid group with considerable levels of heterogeneity. The updated meta-analysis by our team found a significant reduction in mortality in the pooled estimation of RCTs but not in cohort studies. Corticosteroid therapy was effective in terms of ICU and ventilator outcomes with minimal safety concerns. Future meta-analyses should be well executed with specific research questions and well performed with minimal risk of bias to produce good quality evidence.

Survival Benefits of N-Acetylcysteine in Rodenticide Poisoning: Retrospective Evidence from an Indian Tertiary Care Setting.

RATIONALE & OBJECTIVE: Rodenticide poisoning, either accidental or intentional, is very common in rural India. The absence of a definite antidote made it a major concern with a high mortality rate. Therefore, this study aimed to assess the effectiveness of N-Acetyl Cysteine (NAC) in rodenticide poisoning as there are recent positive shreds of evidence on it. METHODOLOGY: A retrospective study was conducted in a tertiary care teaching hospital on patients admitted with rodenticide poisoning during a period of 2012-2017. The Fischer's exact test and relative risk were measured to analyze the outcome of treatment and risk factors, respectively. RESULTS: A total of 229 patients were enrolled in the study with a mean age of 30.04 ± 15.67 years. The suicidal attack was the major (86.0%) reason for poison consumption. The survival rate was significantly (p ≤ 0.03) higher in the NAC treatment group compared to the non-NAC group. Moreover, the majority (93.4%) of participants did not experience any adverse effects. The mean oral loading dose and maintenance dose was 7580.95 ± 2204.29 mg and 3694.53 ± 2322.58 mg, respectively. Yellow Phosphorus poisoning (Relative Risk [RR] 2.888 (1.179-7.079); p=0.020) and Time lag of ≥ 24 hours (RR 3.479 (1.137-10.645); p=0.029) were the significant risk factors for mortality. CONCLUSION: NAC is shown to have a significant survival benefit with a good safety profile among rodenticide poisoners. Further adequately powered prospective researches with more emphasis on dosing parameters are warranted for better quantification in different settings and for clinical implementation.

Behavioural outcome in children with congenital adrenal hyperplasia: experience of a single centre.

The aim of this study was to determine the behavioral outcome in children with CAH and to identify the risk factors that may influence it. Participants (aged 6-18 years) included 29 girls and 20 boys with CAH and unaffected siblings (25 girls and 17 boys). Psychological adjustment was assessed with parent reports on the Child Behavior Checklist (CBCL). Information about disease characteristics was obtained from medical records. Our study reveals that there was higher incidence of parent-reported problem of anxious/depressed and withdrawn/depressed behaviours, somatic complaints, social, thought, and attention problems, and rule-breaking, aggressive, internalizing, and externalizing behaviour among children with CAH compared to controls. The prevalence of internalizing behaviour problems was higher in CAH boys compared with that of controls. Psychosocial adjustment of girls with CAH was found to be similar to unaffected female controls and was within the normal population range. Family income may be associated with behavioral outcome. Glucocorticoid dose may reflect disease severity which may be associated with behavioral outcome. We conclude that internalizing behavioral problem was prevalent among boys with CAH reflecting maladaptive adjustment in coping with chronic illness. This highlighted the importance of psychological and social support for the patients and their families.