Cannabinoids Used for Medical Purposes in Children and Adolescents: A Systematic Review and Meta-Analysis.

Importance: Cannabinoids are increasingly used for medical purposes in children. Evidence of the safety of cannabinoids in this context is sparse, creating a need for reliable information to close this knowledge gap. Objective: To study the adverse event profile of cannabinoids used for medical purposes in children and adolescents. Data Sources: For this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched for randomized clinical trials published from database inception to March 1, 2024, for subject terms and keywords focused on cannabis and children and adolescents. Search results were restricted to human studies in French or English. Study Selection: Two reviewers independently performed the title, abstract, and full-text review, data extraction, and quality assessment. Included studies enrolled at least 1 individual 18 years or younger, had a natural or pharmaceutical cannabinoid used as an intervention to manage any medical condition, and had an active comparator or placebo. Data Extraction and Synthesis: Two reviewers performed data extraction and quality assessment independently. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline and PRISMA-S guideline were used. Data were pooled using a random-effects model. Main Outcomes and Measures: The primary outcome was the incidence of withdrawals, withdrawals due to adverse events, overall adverse events, and serious adverse events in the cannabinoid and control arms. Secondary outcomes were the incidence of specific serious adverse events and adverse events based on organ system involvement. Results: Of 39 175 citations, 23 RCTs with 3612 participants were included (635 [17.6%] female and 2071 [57.3%] male; data not available from 2 trials); 11 trials (47.8%) included children and adolescents only, and the other 12 trials (52.2%) included children, adolescents, and adults. Interventions included purified cannabidiol (11 [47.8%]), nabilone (4 [17.4%]), tetrahydrocannabinol (3 [13.0%]), cannabis herbal extract (3 [13.0%]), and dexanabinol (2 [8.7%]). The most common indications were epilepsy (9 [39.1%]) and chemotherapy-induced nausea and vomiting (7 [30.4%]). Compared with the control, cannabinoids were associated with an overall increased risk of adverse events (risk ratio [RR], 1.09; 95% CI, 1.02-1.16; I2 = 54%; 12 trials), withdrawals due to adverse events (RR, 3.07; 95% CI, 1.73-5.43; I2 = 0%; 14 trials), and serious adverse events (RR, 1.81; 95% CI, 1.21-2.71; I2 = 59%; 11 trials). Cannabinoid-associated adverse events with higher RRs were diarrhea (RR, 1.82; 95% CI, 1.30-2.54; I2 = 35%; 10 trials), increased serum levels of aspartate aminotransferase (RR, 5.69; 95% CI, 1.74-18.64; I2 = 0%; 5 trials) and alanine aminotransferase (RR, 5.67; 95% CI, 2.23-14.39; I2 = 0%; 6 trials), and somnolence (RR, 2.28; 95% CI, 1.83-2.85; I2 = 8%; 14 trials). Conclusions and Relevance: In this systematic review and meta-analysis, cannabinoids used for medical purposes in children and adolescents in RCTs were associated with an increased risk of adverse events. The findings suggest that long-term safety studies, including those exploring cannabinoid-related drug interactions and tools that improve adverse event reporting, are needed.

A multi-centre, tolerability study of a cannabidiol-enriched Cannabis Herbal Extract for chronic headaches in adolescents: The CAN-CHA protocol.

INTRODUCTION: Cannabis products have been used in the management of headaches in adults and may play a role in pediatric chronic pain. Canadian pediatricians report increasing use of cannabis for the management of chronic headaches, despite no well-controlled studies to inform its dosing, safety, and effectiveness. The aim of our clinical trial is to determine the dosing and safety of a Cannabidiol (CBD)-enriched Cannabis Herbal Extract (CHE) for the treatment of chronic headaches in adolescents. METHODS AND ANALYSIS: Youth, parents, and an expert steering committee co-designed this tolerability study. Twenty adolescents (aged 14 to 17 years), with a chronic migraine diagnosis for more than 6 months that has not responded to other therapies will be enrolled into an open label, dose escalation study across three Canadian sites. Study participants will receive escalating doses of a CBD-enriched CHE (MPL-001 with a THC:CBD of 1:25), starting at 0.2-0.4 mg/kg of CBD per day and escalating monthly up to 0.8-1.0 mg/kg of CBD per day. The primary objective of this study is to determine the safety and tolerability of CBD-enriched CHE in adolescents with chronic migraine. Secondary objectives of this study will inform the development of subsequent randomized controlled trials and include investigating the relationship between the dose escalation and change in the frequency of headache, impact and intensity of pain, changes in sleep, mood, function, and quality of life. Exploratory outcomes include investigating steady-state trough plasma levels of bioactive cannabinoids and investigating how pharmacogenetic profiles affect cannabinoid metabolism among adolescents receiving CBD-enriched CHE. DISCUSSION: This protocol was co-designed with youth and describes a tolerability clinical trial of CBD-enriched CHE in adolescents with chronic headaches that have not responded to conventional therapies. This study is the first clinical trial on cannabis products in adolescents with chronic headaches and will inform the development of future comparative effectiveness clinical trials. TRIAL REGISTRATION: CAN-CHA trial is registered with ClinicalTrials.gov with a number of register NCT05337033.

Use of Potentially Inappropriate Medications among Older Adults with Dementia or Cognitive Impairment Attending Memory Clinics: A Protocol for a Systematic Review and Meta-Analysis.

Introduction: Older adults with dementia who are on multiple medications are more vulnerable to the use of potentially inappropriate medications (PIMs), which can significantly increase the risk of adverse events and drug-related problems. PIMs use is prevalent and varies among older adults with dementia or cognitive impairment (CI) attending memory clinics. However, the prevalence of PIMs, polypharmacy, and hyper-polypharmacy among older adults with dementia or CI who are attending memory clinics is not well understood. We will conduct a systematic review and meta-analyses to examine the overall estimate of the prevalence of the PIMs, polypharmacy, and hyper-polypharmacy use among older adults attending memory clinics, with dementia or CI. The secondary objective of this study will be to compile a list of commonly implicated PIMs and to investigate factors that may be associated with using PIMs in this population. Methods: Ovid MEDLINE, Ovid Embase, Scopus, Cochrane library, EBSCOhost CINAHL, and Ovid International Pharmaceutical Abstracts (IPA) will be systematically searched by a researcher (R.S.) with the help of a librarian (C.C.). All databases will be searched from inception to May 05, 2023. Cross-sectional, cohort, randomized clinical trials, quasi-experimental, and case-control studies will be included if they assess PIM's use among older adults with dementia and/or CI. A step-by-step guide by Pai et al. [Natl Med J India. 2004;17(2):86-95] will be followed when conducting this systematic review (S.R.). The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist will be followed for reporting this SR. Conclusion: The findings from this SR/MA will identify the pooled prevalence of PIMs, providing a more precise estimate of the true prevalence of the PIMs, polypharmacy, hyper-polypharmacy in older adults with dementia or CI who are attending memory clinics at primary, secondary, or tertiary healthcare settings by considering the results of multiple studies.

Vitamin D in Melanoma: Potential Role of Cytochrome P450 Enzymes.

Vitamin D is a promising anticancer agent for the prevention and treatment of several cancers, including melanoma. Low 25-hydroxyvitamin D levels, a routinely used marker for vitamin D, have been suggested as one of the factors in the development and progression of melanoma. The parent vitamin D needs activation by cytochrome P450 (CYP) enzymes to exert its actions via the vitamin D receptor (VDR). This review discusses the role of vitamin D in melanoma and how CYP-mediated metabolism can potentially affect the actions of vitamin D. Through interacting with the retinoid X receptor, VDR signaling leads to anti-inflammatory, antioxidative, and anticancer actions. Calcitriol, the dihydroxylated form of vitamin D3, is the most active and potent ligand of VDR. CYP27A1, CYP27B1, and CYP2R1 are involved in the activation of vitamin D, whereas CYP24A1 and CYP3A4 are responsible for the degradation of the active vitamin D. CYP24A1, the primary catabolic enzyme of calcitriol, is overexpressed in melanoma tissues and cells. Several drug classes and natural health products can modulate vitamin D-related CYP enzymes and eventually cause lower levels of vitamin D and its active metabolites in tissues. Although the role of vitamin D in the development of melanoma is yet to be fully elucidated, it has been proposed that melanoma prevention may be significantly aided by increased vitamin D signaling. Furthermore, selective targeting of the catabolic enzymes responsible for vitamin D degradation could be a plausible strategy in melanoma therapy. Vitamin D signaling can be improved by utilizing dietary supplements or by modulating CYP metabolism. A positive association exists between the intake of vitamin D supplements and improved prognosis for melanoma patients. Further investigation is required to determine the function of vitamin D supplementation and specific enzyme targeting in the prevention of melanoma.

Inappropriate Use of Proton Pump Inhibitor Among Elderly Patients in British Columbia: What are the Long-term Adverse Events?

BACKGROUND: Proton pump inhibitors (PPIs) are one of the most used classes of drugs. For most indications, PPIs are only recommended up to 8 weeks duration. However, PPI use continues to expand. Regular and prolonged use of PPIs should be avoided because of the risk of adverse events. OBJECTIVES: The main objective of this study was to (1) investigate the extent of PPI usage in people aged 65 or older in the province of British Columbia (BC), Canada, (2) provide an overview of the harms associated with the long-term use of PPIs. METHODS: We examined utilization trends of the PPIs in BC since the year 2009 using PharmaNet, BC's medication dispensing database where the information is accessible to community pharmacists. We performed a comprehensive literature search for relevant reviews reporting harms associated with long-term use of PPIs. A search was conducted from January 2014 to June 2022. RESULTS: Between 2000 and 2018 BC's population grew by 20%, but the use of PPIs escalated to 257%. Of these older British Columbians, 62% had a cumulative exposure exceeding 2 years and 42% exceeded 5 years. This is alarming because the recommended treatment duration is 4-12 weeks for common indications including reflux esophagitis, and duodenal and gastric ulcers. Only 13.5% were dispensed PPIs for 90 days or less. Patients on long-term PPI therapy should be reassessed. Adverse events of PPI use are common among older adults. We identified over 217 systematic reviews published during the last 8 years of specific harms associated with long-term daily usage of PPIs. These harms include increased risks of death, cardiovascular disease, acute renal injury, chronic kidney disease, dementia, fractures, hypomagnesemia, iron deficiency, vitamin B12 deficiency, enteric infection (including C. difficile), pneumonia, and neoplasia (gastric cancer, carcinoids, and colon cancer), and drug interactions. CONCLUSION: This study revealed a high prevalence of PPI use among elderly populations in BC, Canada. The overutilization of PPIs is often a result of failure to re-evaluate the need for continuation of therapy. Published studies identified signals of serious harm from long-term PPI exposure. Healthcare providers with patients can reverse the relentless expansion of long-term PPI exposure by discussing the expected benefits and potential harms.

Qualitative Analysis of Patient Perspectives of Buprenorphine After Transitioning From Long-Term, Full-Agonist Opioid Therapy Among Veterans With Chronic Pain.

Guidelines recommend consideration of modification, tapering, or discontinuation of long-term, full-agonist opioid therapy when harms outweigh benefits; one alternative to tapering or discontinuing full-agonist opioids for the management of chronic pain is switching to the partial agonist buprenorphine. As the use of buprenorphine for pain expands, understanding the patient experience during and after the transition to buprenorphine is critical. We conducted 45- to 60-minute semistructured qualitative interviews with 19 patients to understand the experiences of patients with chronic pain actively maintained on buprenorphine after previously receiving full-agonist, long-term opioid therapy. Patients were recruited from 2 medical centers via provider referral. Through thematic analysis, 5 overall themes were identified, including satisfaction with buprenorphine, the importance of preconceptions about buprenorphine, experiences with transitions, patient-provider communication, and potential contributions to racial disparities in pain care. While we heard a range of experiences, most patients were satisfied with buprenorphine, reporting either equivalent pain control to their previous regimens or reporting less analgesia but improved functioning due to a reduction in side effects (eg, mental clarity). Patients also emphasized the importance of a nonjudgmental, patient-centered approach, including education about the risks and benefits of buprenorphine. The few Black patients interviewed all reported limited access to pain care, which is consistent with the well-documented existence of racial disparities in access to pain treatment. As buprenorphine is used more frequently for pain management, provider education focused on pain treatment disparities, patient-centered approaches informed by motivational interviewing, and increasing acceptance of buprenorphine as an option for pain are needed. PERSPECTIVE: Qualitative analyses of patient experiences transitioning from full-agonist opioids to buprenorphine for chronic pain revealed general satisfaction. Patients reflected on functioning, tradeoffs between analgesia and side effects, patient-centered care, and access to treatment, highlighting how future research should focus on outcomes valued by patients.

Cannabinoids for symptom management in children with cancer: A systematic review and meta-analysis.

BACKGROUND: Despite the widespread use of medical cannabis, little is known regarding the safety, efficacy, and dosing of cannabis products in children with cancer. The objective of this study was to systematically appraise the existing published literature for the use of cannabis products in children with cancer. METHODS: This systematic review, registered with the International Prospective Register of Systematic Reviews (CRD42020187433), searched four databases: MEDLINE, Embase, PsycINFO, and the Cochrane Library. Abstracts and full texts were screened in duplicate. Data on types of cannabis products, doses, formulations, frequencies, routes of administration, indications, and clinical and demographic details as well as reported efficacy outcomes were extracted. Data on cannabinoid-related adverse events were also summarized. RESULTS: Out of 34,611 identified citations, 19 unique studies with a total of 1927 participants with cancer were included: eight retrospective chart reviews, seven randomized controlled trials, two open-label studies, and two case reports. The included studies reported the use of various cannabis products for the management of symptoms. Cannabinoids were commonly used for the management of chemotherapy-induced nausea and vomiting (11 of 19 [58%]). In controlled studies, somnolence, dizziness, dry mouth, and withdrawal due to adverse events were more commonly associated with the use of cannabinoids. Across all included studies, no serious cannabis-related adverse events were reported. CONCLUSIONS: Although there is evidence to support the use of cannabis for symptom management, in children with cancer, there is a lack of rigorous evidence to inform the dosing, safety, and efficacy of cannabinoids. Because of the increasing interest in using cannabis, there is an urgent need for more research on medical cannabis in children with cancer.

Global prevalence and effect of comorbidities and smoking status on severity and mortality of COVID-19 in association with age and gender: a systematic review, meta-analysis and meta-regression.

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).

Knowledge, attitude, and practice of medical interns and postgraduate residents on American Geriatric Society updated Beers criteria.

BACKGROUND: Potentially inappropriate medication (PIM) prevalence in older adults is increasing day by day due to lack of knowledge among medical students and professionals. OBJECTIVE: To determine the knowledge of medical students toward American Geriatric Society (AGS) Beers criteria for PIM prescribing. MATERIALS AND METHODS: This cross-sectional study employed a self-administered questionnaire which was validated and designed to assess the knowledge, attitude, and practice of medical interns and postgraduate residents on Beers criteria for PIMs in older adults. The study was conducted in Faridkot region of Punjab in 2019. This study will utilize a purposive sampling strategy and a convenience sampling of up to 183 participants. Mann-Whitney U or Kruskal-Wallis tests were used to compare different issues as appropriate. P values of <0.05 were considered significant. RESULTS: Out of 183 questionnaires distributed, only 155 participants (response rate 84.6%) had filled the survey and were included in the study. 61.3% (n = 95) of the respondents were males. The mean knowledge score of 155 participants was (5.16 ± 1.56), where the highest score was 9 and the lowest score was 2 out of 10. 15.5% (n = 24) of the participant strongly agreed that Beers criteria use is necessary in clinical setting and would be very helpful. While 22.5% (n = 35) of the participants strongly agreed that PIMs cause adverse drug event (ADE) and drug-related problems (DRPs) in older adults. Age of the participant had a significant effect on the knowledge score (p = 0.009), and participant aged between 31 and 40 years had significantly higher knowledge scores compared with participants falls under 20-30 years. CONCLUSION: Medical students and postgraduate residents had average knowledge of PIMs and are unaware of the standard guidelines in older adults such as the Beers criteria. Lack of formal education or training about Beers guidelines was the main reason responsible for average knowledge among participants.

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.

Efficacy and safety of saroglitazar for the management of dyslipidemia: A systematic review and meta-analysis of interventional studies.

BACKGROUND AND OBJECTIVE: Saroglitazar is a newer antidiabetic agent approved to manage dyslipidemia. The objective is tevaluate the efficacy and safety profiles of saroglitazar in patients with dyslipidemia. METHODS: A systematic search was conducted using PubMed, Cochrane Library, Scopus, and Google Scholar from the inception until January 2022. Interventional studies comparing the anti-hyperlipidaemic effect and safety of saroglitazar with or without a control group(s) were included. The efficacy of saroglitazar was assessed concerning its effect on total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL)-cholesterol, triglycerides, fasting plasma glucose, and non-HDL cholesterol. The effects on serum creatinine levels, bodyweight reduction, alanine aminotransferase and aspartate aminotransferase were considered to be safety endpoint.The Cochrane risk of bias assessment tool was used to assess the methodological quality of the included studies. RESULTS: A total of six studies with 581 adults with a mean age ranging from 40.2 to 62.6 years were included in this study. A significant decrease in low-density lipoprotein cholesterol was observed with saroglitazar 4 mg therapy compared to saroglitazar 2 mg [standardized mean difference (SMD): -0.23 mg/dL, 95% CI: -0.47 to 0.00; p = 0.05; 2 studies], and control [SMD: -0.36 mg/dL, 95% CI -0.59 to -0.12; p = 0.0026; 3 studies]. Also, a significant decrease in the total cholesterol was observed with saroglitazar 4 mg therapy compared to saroglitazar 2 mg [SMD - 0.28 mg/dL, 95% CI: - 0.52 to -0.04; p < 0.01; 2 studies], and control [SMD - 0.49 mg/dL, 95% CI: - 0.72 to -0.26; p < 0.0001; 3 studies]. Saroglitazar was not associated with adverse effects such as increase in serum creatinine levels, alanine aminotransferase and aspartate aminotransferase and bodyweight reduction. CONCLUSION: Saroglitazar appeared to be an effective and safer therapeutic option for improving dyslipidemia in patients. However, comparative studies of saroglitazar with the other pharmacological agents are warranted.

Opioid tapering support using a web-based app: Development and protocol for a pilot randomized controlled trial.

BACKGROUND: Given limited efficacy and potential harms of long-term opioid therapy, it is patient-centered and guideline-concordant to offer patients the opportunity to engage in a supportive, patient-centered tapering program. The goal of this study was to develop and pilot an interactive web-based program designed to support patients willing to consider an opioid taper; this manuscript describes the development and the protocol for a pilot randomized trial of Summit. METHODS: We used intervention mapping to develop the Summit program; during the development period we engaged multiple stakeholder groups and conducted usability testing to refine the interactive, theory-informed, multi-component mobile website program which includes education, video testimonials, self-management skills, and access to a peer specialist. We will evaluate the Summit program in a two-arm, 9 month randomized-controlled trial where 64 individuals will be assigned either to the Summit program or to a control group (pain tracking app). As a pilot trial, the primary outcomes are feasibility and acceptability; we will also measure patient-reported outcomes related to pain, quality of life, and opioid use. IMPLICATIONS: We developed an interactive program; results of the pilot trial are pending. If shown to be effective, Summit would be useful both in augmenting care for patients who are engaged in a taper with primary care.

Chronic Kidney Disease (CKD) - A Brand Ambassador/Alarming Bell for Potentially Inappropriate Medication in Elderly Inpatients.

BACKGROUND: Since the past decade, prevalence of Potentially Inappropriate Medication (PIM) among elderly inpatients has increased drastically. However, limited data is available on PIM indicators and PIMs use among the elderly in patients suffering from Chronic Kidney Disease (CKD). OBJECTIVE: The objective of this study is to determine the prevalence of PIMs in elderly hospitalized patients with CKD. METHODS: A cross-sectional study was carried out on 102 patients in a tertiary care hospital. PIMs were identified using Beers criteria 2019. Chi-square test was used to identify the association between variables and PIMs use. RESULTS: PIMs, as assessed according to AGS updated Beers criteria 2019 was found to be in more than 68.6% of patients of median age 65 years and 3 diagnoses and 7 days median length of stay. Most of the patients (47.1%) had ≥4 diagnosis. The most common comorbidities in patient were diabetes mellitus (n=54) and hypertension (n=55). Most of the subjects (66.7%) were on polypharmacy (5-9 medications/day) and 25.5% were on a higher level of polypharmacy (>10 medicines/day). Approximately 90% of the patients were having very low CrCl < 21ml/min (calculated with the help of Cockcroft- Gault formula). A significant association between PIM use and an increased number of diagnoses, polypharmacy or high-level polypharmacy, was observed. CONCLUSION: The prevalence of PIMs in elderly inpatients suffering from CKD is quite high. The study clearly indicates negligence/ lack of awareness amongst physicians leading to increase in PIM use. Authors propose that the CKD patients should attract special attention of physician and should be treated as brand ambassadors/alarming bell for PIM use.

Pattern, severity, and outcome of adverse drug reactions in a tertiary care hospital: an evidence from a cross-sectional study.

OBJECTIVES: Study aim to describe the spontaneous reporting of the adverse drug reactions (ADRs) among the patients admitted to medicine department of a tertiary care hospital. METHODS: A prospective observational study was conducted over a period of four months at the medicine department. On the daily basis, all the patients aged >18 years admitted to the internal medicine department were followed and analyzed for occurrence of ADRs. Naranjo scale was used to determine causal relationship between the ADRs and suspected drugs. The nature of ADRs and its severity was assessed using the Hartwig scale. RESULTS: A total of 4,530 patients were screened for the ADRs, out of which 90 ADRs were developed in the 89 patients. The overall incidence of ADRs was found to be 1.96% in the studied population. The most common ADRs encountered during the study period were type A (augmented). The least number of ADRs were observed in the age group of 31-40 years. Furthermore, the more significant number of male patients suffered from a severe type of ADRs as compared to females. Sixteen ADRs were of the mucocutaneous type of reaction followed by dizziness in 12 cases. The higher number of patients recovering from the ADRs was in the age group 41-60 years. The outcomes of ADRs were not found to be statistically significant with gender and age groups. CONCLUSIONS: There is a strong need to extend the monitoring and reporting of the ADRs to ensure the patient safety. However, the overall incidence of ADRs appeared to be less in our study, highlighting the need for strengthening reporting system of ADRs. The results indicate that elderly patients are at significant risk of developing ADRs.

Methotrexate related cutaneous adverse drug reactions: a systematic literature review.

OBJECTIVES: Recently, there is an increased number of reports being published on Methotrexate (MTX) related cutaneous manifestations. We aimed to identify and critically appraise descriptive studies describing the MTX related skin manifestations, treatment approach, and their outcomes. METHODOLOGY: An extensive literature search was performed in the PubMed, Embase, and Scopus databases from inception to April 2021 without any restrictions along with the bibliographic search of included studies, grey literature search, and a snowball search was performed in Google and Google Scholar to identify the relevant literature. Descriptive studies reporting MTX related cutaneous manifestations were considered for the review. The study selection, data extraction, and quality assessment were conducted by two independent reviewers and any disagreements were settled by consensus with the third reviewer. RESULTS: 31 out of 8,365 descriptive studies including 38 patients (22 females and 16 males) aged between 12 and 78 years prescribed for the management of rheumatoid arthritis, ankylosing spondylitis, and psoriasis were included in this review. Toxic epidermal necrolysis (TEN), papular eruption, vasculitis, erosions of psoriasis, ulcerated psoriatic plaques, local reactions, keratinocyte dystrophy, erythema multiforme, drug rash with eosinophilia and systemic symptoms, Steven Johnson syndrome and photosensitive dermatitis were the majority of MTX induced cutaneous reactions. Immediate withdrawal of MTX, providing appropriate care with anti-inflammatory, topical steroids, and supplementation with folic acid were reported to be effective for the management of the MTX related cutaneous manifestations. CONCLUSIONS: Clinicians and healthcare professionals should be aware of possible acute cutaneous drug reactions induced by MTX to avoid further consequences and fatal conditions. Immediate withdrawal of MTX and supportive care were reported as an efficacious therapeutic management of acute cutaneous drug reactions. PROSPERO REGISTRATION NUMBER: CRD42020220038.

Prevalence and predictors of Potentially Inappropriate Psychotropic Medication in older adults with psychiatric illness.

BACKGROUND: There is limited information available on the use of Potentially Inappropriate Psychotropic (PIP) medication in older adults having a psychiatric illness. OBJECTIVE: To determine the prevalence of and predictors of prescribing PIP medications in older adults with psychiatric illness. METHODS: A cross-sectional study was carried out at a tertiary care hospital on 456 patients of either sex, with a median age of 65 years attending the psychiatry outpatient department. Evaluation of PIP medication was done using Beers criteria 2019 and Screening tool of Older Persons Potentially Inappropriate Medication (STOPP) criteria 2015. Bivariate logistic regression was used to find out the predictors of PIP prescribing. RESULTS: Results of the study reflect that a staggering number of older adults, (more than 91% and 73%) out of a total of 456 patients were prescribed with at least one PIP medication identified by Beers criteria and STOPP criteria, respectively. Long-acting benzodiazepine (LABZD) like clonazepam was identified as one of the most commonly prescribed PIP medications by both sets of criteria. Further analysis revealed that older adults from rural background (Odds Ratio (OR) 2.60, 95% Confidence Interval (CI) 1.20-5.65; P = 0.015), Tricyclic Antidepressant (TCA) (OR 0.30, 95% CI 0.12-0.75; P = 0.010), LABZD (OR 33.72, 95% CI 11.27-100.85; P = < 0.001), atypical antipsychotics (OR 22.35, 95% CI 5.31-93.99; P = < 0.001) use were most common predictors for PIP medication prescribing. CONCLUSION: The study suggests that the Beer criteria detects more PIP medication than the STOPP criteria.

A randomized controlled trial to evaluate a behavioral economic strategy for improving mobility in veterans with chronic pain.

Rates of chronic pain and daily opioid use are higher among veterans relative to civilian populations. Increasing physical activity can reduce pain severity and decrease opioid use among patients with chronic pain. Behavioral economic strategies can improve physical activity levels but have been undertested in veterans with chronic pain. The objective of this study was to evaluate if a financial incentive combined with a loss aversion component-a "regret lottery" in which veterans could win money if they met a set goal or told how much they could have won had they met their goal-would increase physical activity levels among veterans with chronic pain. A 12-week single-blinded randomized controlled trial (ClinicalTrials.gov: NCT04013529) was designed. Veterans with chronic pain (N = 40) receiving care at a specialty pain clinic were eligible for participation, and were randomly assigned (1:1) to either (a) activity trackers and daily text message reminders to increase physical activity ("control arm"), or (b) the same plus a weekly regret lottery ("intervention arm"). For those in the intervention arm, participants who met their activity goal, had a chance to win a small ($30) or large ($100) gift card incentive; those who did not meet their goals were informed of what they would have won had they met their goal. The primary outcome, physical activity, was measured using self-reported physical activity and step counts using activity trackers. Secondary outcomes included changes in physical function, chronic pain severity, depression and opioid use. The sample was primarily white, male and disabled, with an average age of 57 years. No between-arm differences were noted for physical activity, physical function, chronic pain severity, depression or opioid use. Regret lottery-based approaches may be ineffective at increasing physical activity levels in veterans with chronic pain. Trial Registry: NCT04013529.

Knowledge and attitude towards HIV/AIDS in India: A systematic review and meta-analysis of 47 studies from 2010-2020.

Background: Several studies assessed the level of knowledge and general public behavior on human immunodeficiency virus/acquired immuno-deficiency syndrome (HIV/AIDS) in India. However, comprehensive scrutiny of literature is essential for any decision-making process. Our objective was to perform a systematic review and meta-analysis to examine the level of knowledge and attitude towards HIV/AIDS in India. Methods: A systematic search using Medical Subject Headings (MeSH) and free terms was conducted in PubMed/Medline, Scopus, Embase, and Google Scholar databases to investigate the level of knowledge and attitude of HIV/AIDS in India population. Cross-sectional studies published in English from January 2010 to November 2020 were included. The identified articles were screened in multiple levels of title, abstract and full-text and final studies that met the inclusion criteria were retrieved and included in the study. The methodological quality was assessed using the Joanna Briggs Institute's checklist for cross-sectional studies. Estimates with corresponding 95% confidence intervals (CIs) for each domain were pooled to examine the level of knowledge and attitude towards HIV/AIDS in India. Results: A total of 47 studies (n= 307 501) were identified, and 43 studies were included in the meta-analysis. The overall level of knowledge about HIV/AIDS was 75% (95% CI: 69-80%; I2 = 99.8%), and a higher level of knowledge was observed among female sex workers (FSWs) 89% (95% CI: 77-100%, I2 = 99.5%) than students (77%, 95% CI: 67-87%, I2 = 99.6%) and the general population (70%, 95% CI: 62-79%, I2 = 99.2%), respectively. However, HIV/AIDS attitude was suboptimal (60%, 95% CI: 51-69%, I2 = 99.2%). Students (58%, 95% CI: 38-77%, I2 = 99.7%), people living with HIV/AIDS (57%, 95% CI: 44-71%, I2 = 92.7%), the general population (71%, 95% CI: 62-80%, I2 = 94.5%), and healthcare workers (HCWs) (74%, 95% CI: 63-84%, I2 = 0.0%) had a positive attitude towards HIV/AIDS. The methodological quality of included studies was "moderate" according to Joanna Briggs Institute's checklist. Funnel plots are asymmetry and the Egger's regression test and Begg's rank test identified risk of publication bias. Conclusion: The level of knowledge was 75%, and 40% had a negative attitude. This information would help formulate appropriate policies by various departments, ministries and educational institutions to incorporate in their training, capacity building and advocacy programs. Improving the knowledge and changing the attitudes among the Indian population remains crucial for the success of India's HIV/AIDS response.

Prevalence of Polypharmacy, Hyperpolypharmacy and Potentially Inappropriate Medication Use in Older Adults in India: A Systematic Review and Meta-Analysis.

Background: Older people often receive multiple medications for chronic conditions, which often result in polypharmacy (concomitant use of 5‒9 medicines) and hyperpolypharmacy (concomitant use of ≥10 medicines). A limited number of studies have been performed to evaluate the prevalence of polypharmacy, hyperpolypharmacy, and potentially inappropriate medication (PIM) use in older people of developing countries. The present study aimed to investigate regional variations in the prevalence of polypharmacy, hyperpolypharmacy, and PIM use in older people (60 + years) in India. Methods: Studies were identified using Medline/PubMed, Scopus, and Google Scholar databases published from inception (2002) to September 31, 2020. Out of the total 1890 articles, 27 were included in the study. Results: Overall, the pooled prevalence of polypharmacy was 49% (95% confidence interval: 42-56; p < 0.01), hyperpolypharmacy was 31% (21-40; p < 0.01), and PIM use was 28% (24-32; p < 0.01) among older Indian adults. Polypharmacy was more prevalent in North-east India (65%, 50-79), whereas hyperpolypharmacy was prevalent in south India (33%, 17-48). Region-wize estimates for the pooled prevalence of PIM use in India were as follows: 23% (21-25) in East, 33% in West (24-42), 17.8% in North (11-23), and 32% (26-38) in South India. The prevalence of PIM use in adults aged ≥70°years was 35% (28-42), in those taking more medications (≥5.5/day) was 27% (22-31), and in adults using a high number of PIMs (≥3) was 29% (22-36). Subgroup analysis showed that cross-sectional studies had a higher pooled prevalence of polypharmacy 55% (44-65) than cohorts 45% (37-54). Hyperpolypharmacy in inpatient care settings was 37% (26-47), whereas PIM use was higher in private hospitals 31% (24-38) than government hospitals 25% (19-31). Conclusion: Polypharmacy and hyperpolypharmacy are widely prevalent in India. About 28% of older Indian adults are affected by PIM use. Thus, appropriate steps are needed to promote rational geriatric prescribing in India. Systematic Review Registration: https://clinicaltrials.gov, identifier [CRD42019141037].

Ciprofloxacin-induced cutaneous adverse drug events: a systematic review of descriptive studies.

OBJECTIVES: Ciprofloxacin (CIPRO) is a fluroquinolone class antibiotic used commonly for the treatment of various acute and chronic bacterial infections. However, recently there is increase in the case reports of CIPRO-induced Cutaneous Adverse Drug Reactions (CADRs). We aim to systematically review all the descriptive studies of CIPRO induced CADRs. METHODS: Medline (via PubMed) was searched without any language or date restriction from inception to March 2019 using search terms of "Ciprofloxacin" and "Cutaneous reactions." We included only the descriptive studies, which elucidate the CADRs experienced by the patients following the administration of CIPRO. Two reviewers involved in study selection, data extraction and quality assessment of the included studies. Discrepancies were resolved by consensus between the reviewers. RESULTS: Thirty-nine studies (out of 446) were found to be eligible for the final inclusion. The dose of CIPRO among the included studies was ranging from 500 to 1,000 mg/day and duration of treatment was between 7 and 10 days. The most common CADRs observed were toxic epidermal necrolysis, Stevens-Johnson syndrome, fixed drug eruptions, bullous fixed drug reaction, acute generalized pustulosis, erythema multiforme, drug rash with eosinophilia and systemic symptoms and erythema nodosum. CONCLUSIONS: Management of the CIPRO-induced CADRs is recommended with the complete cessation of the CIPRO, followed by supportive management with oral or topical glucocorticoids, emollients, and topical moisturizers. CIPRO is likely to cause CADRs, physicians should be vigilant while prescribing it to the patients.