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.

The Importance of Context: Linking Veteran Outpatients Screening Positive for Housing Instability with Responsive Interventions.

This study aims to explore the relationship between the context of screening for housing instability and Veterans' access to services, with the goal of ensuring effective processes to address housing instability among Veterans. This study used administrative data from 100,022 Veterans' electronic medical records and qualitative data collected during in-depth interviews with 22 health care providers and six Homeless Program staff. A mixed effects logistic regression assessed the relationship between Veterans' screening experiences and connection with services; qualitative data were analyzed using a grounded theory approach to present providers' reflections on administering screening for housing instability and responding to Veterans' positive screens with needed resources. We observed a significant relationship between providers' roles and location of screening with patients' timely linkage with services. Providing additional training related to how to conduct the screen and provide required resources, shifting screening responsibilities to providers with more flexibility to address these needs, and embedding supportive services in the care team may improve post-screening linkage with services.

Knowledge and beliefs towards universal safety precautions during the coronavirus disease (COVID-19) pandemic among the Indian public: a web-based cross-sectional survey.

Background: The novel coronavirus disease 2019 (COVID-19) is considered the most serious global health threat in recent times. As there is a current lack of approved treatments and vaccines, universal safety precautions (USPs) must be taken to deal with this emergency. Objective: The aim of this study was to assess the knowledge and beliefs of the Indian public with regard to USPs during the COVID-19 pandemic. Methods: A cross-sectional, web-based survey was conducted during March 2020. A 20-item self-administered questionnaire was developed, validated and distributed using Google Forms through social media networks. Binary logistic regression analysis was used to identify the factors influencing knowledge regarding COVID-19 USPs. Results: Of the 1117 individuals who participated in the survey, the mean age was 28.8 ± 10.9 years, 32.9% had a post-graduate education, 45% had a professional job, and 40% belonged to the upper-middle economic class. Overall, the mean correct response scores were 63% for USP knowledge and 83% for USP beliefs. All the sociodemographic variables were significantly (p < 0.001) associated with the USP knowledge levels. Importantly, students were less likely to have a lower level of USP knowledge compared with the other occupations (odds ratio 0.35, 95% CI 0.23-0.53; p < 0.001). Conclusion: Although the knowledge and beliefs of the Indian public towards USPs are encouraging, there is a need for long-term educational interventions as the dynamics and severity of COVID-19 rapidly change. These findings could guide public health authorities to make and implement precautionary measures to combat this pandemic.

Screening for Housing Instability: Providers' Reflections on Addressing a Social Determinant of Health.

BACKGROUND: The Veterans Health Administration (VHA) has a long history of addressing social determinants of health, including housing. In 2012, the VA integrated a two-question Homelessness Screening Clinical Reminder (HSCR) into the electronic medical record in outpatient clinics to identify Veterans experiencing housing instability and ensure referral to appropriate services. OBJECTIVE: This study explores perspectives of VA clinical providers regarding administration of the HSCR, their role in addressing housing status, and how a patient's housing status impacts clinical decision-making. DESIGN: We conducted a qualitative study using in-depth semi-structured interviewing. PARTICIPANTS: Twenty-two providers were interviewed (20 physicians and two nurse practitioners) between March and September 2016. APPROACH: Interviews were conducted with Veterans Health Administration (VHA) physician and non-physician practitioners who had administered the HSCR and documented at least five positive screens between 2013 and 2015. Our interview guide investigated provider experiences with administering the HSCR and addressing affirmative responses. The guide also elicited details about how patients' housing instability was identified (if at all) prior to implementation of the screening reminder, and how practices changed following implementation of the HSCR. Transcripts were analyzed using a modified grounded theory approach. KEY RESULTS: Providers reported that the HSCR prompted them to incorporate patient housing status into routine assessment, which they typically did not do prior to its implementation. Providers discussed adverse impacts of housing instability on patients' overall health and described how they factored patients' housing instability into clinical decision-making. Although providers viewed the health system as having an important role in addressing housing concerns, there were mixed opinions on whether it was the role of providers to directly administer the screening. CONCLUSIONS: Integration of a screener for housing instability into the electronic medical record increased provider attention to housing instability into the social history, and positive responses commonly impacted plans of care.

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.

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.

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.

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 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.