Electronic health record-enabled routine assessment of medication adherence after solid organ transplantation: the time is now.

Medication nonadherence after solid organ transplantation is recognized as an important impediment to long-term graft survival. Yet, assessment of adherence is often not part of routine care. In this Personal Viewpoint, we call for the transplant community to consider implementing a systematic process to screen and assess medication adherence. We believe acceptable tools are available to support integrating adherence assessments into the electronic health record. Creating a standard assessment can be done efficiently and cost-effectively if we come together as a community. More importantly, such monitoring can improve outcomes and strengthen provider-patient relationships. We further discuss the practical challenges and potential rebuttals to our position.

Removing barriers to accessing medical cannabis for paediatric patients.

Medical cannabis (MC) may offer therapeutic benefits for children with complex neurological conditions and chronic diseases. In Canada, parents, and caregivers frequently report encountering barriers when accessing MC for their children. These include negative preconceived notions about risks and benefits, challenges connecting with a knowledgeable healthcare provider (HCP), the high cost of MC products, and navigating MC product shortages. In this manuscript, we explore several of these barriers and provide recommendations to decision-makers to enable a family-centered and evidence-based approach to MC medicine and research for children.

A scoping review of pediatric transplant education.

BACKGROUND: Education is crucial for pediatric patients and caregivers throughout the transplant continuum, yet data are lacking around which interventions are effective and in what circumstances. METHODS: We undertook a scoping review with the objectives of (a) describing the types, effects, and outcomes of patient-focused educational interventions before and after pediatric transplant and (b) understanding the educational experiences of patients and caregivers. Five scientific databases were explored for relevant literature using the JBI methodology. Educational interventions published in English, targeting pediatric solid organ transplant patients (0-25 years) and their caregivers were included. Relevant data from eligible articles (n = 27) were extracted and summarized. RESULTS: Eighteen articles describing 17 educational interventions were identified for objective A, and nine articles qualitatively assessing patient or parental learning needs were identified for objective B. Most interventions were directed toward teenage patients and their caregivers post kidney transplant, primarily focusing on medication self-management and adherence, or providing general information on transplant using multicomponent delivery formats. Most interventions achieved statistically significant improvements in knowledge (n = 8/9) and patients or caregivers expressed satisfaction with the intervention (n = 7/7) but health-related outcomes such as medication adherence (n = 2/6) or behavior change (n = 1/3) rarely achieved statistically significant results. In objective B, patients and caregivers described the transplant process as overwhelming, but indicated that social supports and education helped them cope. Participants consistently wanted more information than they received. CONCLUSION: Caregivers and pediatric patients value transplant education, but high-quality studies are limited. Since education is a fundamental part of the transplant process, future research in this area should be prioritized.

Medical cannabis in schools: A qualitative study on the experiences of clinicians.

Objectives: Guidance is lacking for medical cannabis use in Canadian schools in both legislation and approach; the impact of ambiguous policy on patient care is unknown. A qualitative study was undertaken to explore the experiences of clinicians who care for school-aged children who take medical cannabis. Methods: Semi-structured interviews were recorded and transcribed verbatim. Qualitative content analysis performed using the Dedoose qualitative software ascribed meaning units and codes, which were further consolidated into categories and subcategories. Results: Thirteen physicians were interviewed virtually, representing seven provinces in Canada. The physicians provided care for between five and hundreds of school-aged children who took medical cannabis. The most common indications were refractory seizure disorders and autism. The interviews provided rich descriptions on perceptions of medical cannabis in schools, and in general. Five overarching categories were identified across both domains including variability, challenges (subcategories: lack of knowledge, stigma, lack of policy, and pragmatic challenges), potential solutions (subcategories: treat it like other medications, communication, education, and family support), positive experiences and improvements over time. Conclusion: In Canada, cannabis-based medicine use in schools still faces important challenges. Effective education, communication, family support and policy refinements that allow cannabis to be treated like other prescription medications are recommended to improve the status quo. These findings will guide the C4T Medical Cannabis in Schools Working Group's future priorities and initiatives.

Medical cannabis in schools: The experiences of caregivers.

Objectives: Implementing medical cannabis (MC) into a child's daily routine can be challenging and there is a lack of guidance for its therapeutic use in schools in Canada. Our objective was to learn about the experiences of caregivers of school-aged children who require MC. Methods: Qualitative description was used and caregivers were interviewed about MC in schools and in general. The transcripts were entered into Dedoose software for qualitative analysis and content analysis was performed. Sentences and statements were ascribed line by line into meaning units and labelled with codes, and organized according to categories and subcategories. Results: Twelve caregivers of school-aged children who take MC participated. The most common reasons for treatment were drug-resistant epilepsy (DRE), autism, or other developmental disorders. Approximately half of the participants' children (n = 6) took MC during the school day and most (5/6) perceived their experiences to be positive or neutral but reported a lack of knowledge about MC. While data saturation was not reached regarding MC in schools, rich dialogues were garnered about MC in general and three categories were identified: challenges (subcategories stigma, finding an authorizer, cost, dosing, and supply); parents as advocates (subcategories required knowledge, attitudes, skills, and sources of information); and caregiver relief for positive outcomes. Conclusions: Caregivers demonstrate remarkable tenacity despite the many challenges associated with MC use. Education and practice change are needed to ensure that children using MC can benefit from or continue to experience its positive outcomes within the school environment and beyond.

Concerns, beliefs and attitudes of pharmacists and pharmacy students on cannabis use in Canada.

Background: Since cannabis has been legalized in Canada for medical and recreational use, there has been an increased demand on pharmacists for cannabis counselling. The objective of this study was to determine the concerns, beliefs and attitudes of Canadian pharmacists and pharmacy students towards using cannabis. Methods: An online survey was synthesized under 3 broad themes: concerns, beliefs and attitudes about cannabis, consisting of 27 questions capturing demographics and Likert scale responding to survey questions. We examined whether there were differences in responses by geographic location (i.e., Ontario, Quebec, Canada), sex or practice setting (i.e., community, hospital). Results: Across Canada, there were 654 survey respondents, with 399 in Ontario and 95 in Quebec. Approximately 24% indicated they had used cannabis since legalization, 69% indicated they believed cannabis should be available for medical and recreational use and 34% indicated their perceptions towards cannabis had become more positive since legalization. Relative to Quebec or the rest of Canada, respondents from Ontario were significantly more likely to be comfortable providing counselling to and answering questions of patients on the safety and efficacy of medical cannabis use. Examining sex differences across Canada, male respondents were more comfortable than female counselling patients on the safety and efficacy of medical cannabis. Conclusion: The current results reinforce the perceived need by pharmacists and pharmacy students for targeted education, and future research in cannabis education should consider potential gender differences in attitudes and beliefs surrounding cannabis therapy.

Establishing a baseline of interprofessional education perceptions in first year health science students.

Interprofessional education (IPE) is increasingly utilized to prepare students for their future careers in the health sciences as collaborative practitioners. Although it is considered an accreditation requirement in most health science disciplines, little is known about first year student's perceptions of IPE in Canada. In September of 2018, students from dentistry, kinesiology, medicine, nursing, nutrition, pharmacy, and physiotherapy in their first year of their professional program at the University of Saskatchewan were surveyed to obtain a baseline of perspectives and attitudes toward IPE. The survey consisted of an adaptation of the Readiness for Interprofessional Learning Scale (RIPLS) and additional questions to assess students' skills and interest in IPE. Descriptive and univariate statistics were used to determine associations with demographic variables. The response rate was 88% (n= 509). Health science students in all disciplines had positive perceptions of IPE, with overall mean RIPLS scores for domain 1 (teamwork and collaboration), 2 (professional identity), and 3 (roles and responsibilities) of 40.5/45, 33.3/40 and 6.3/10, respectively. Students in kinesiology had significantly lower RIPLS scores than other health science disciplines (p< .05). Female gender, and having a past degree, or previous experience with interprofessional collaboration through school or work were traits that were associated with statistically significantly higher RIPLS scores (p< .05).

Impact of the SIMPL-SYNC Refill Synchronization Program on medication adherence: A pragmatic randomized controlled trial.

OBJECTIVE: To determine the impact of the SIMPL-SYNC refill synchronization (SSRS) service compared with that of usual care (UC) on medication adherence when applied as an opt-out strategy among patients receiving chronic medications. DESIGN: This was a pragmatic randomized controlled trial. SETTING AND PARTICIPANTS: The study was conducted in 2 community pharmacies located in Saskatchewan, Canada. Eligible patients were chronic medication users visiting the study pharmacies. OUTCOME MEASURES: The primary outcome was the percentage of individuals achieving optimal adherence to all eligible study medications. Eligible study medications included 22 commonly used medication classes used to treat diverse conditions. Adherence was assessed for each medication class after 300 days using the proportion of days covered (PDC). Optimal adherence was defined as PDC ≥ 80%. RESULTS: A total of 488 patients were screened for eligibility, and 190 patients were included in the intention-to-treat analysis (95 in SSRS, 95 in UC). The mean age of participants was 59 years, and 34% (65/190) were older than 65 years. A total of 574 individual adherence observations representing the 22 eligible study medication classes were generated from the 190 study participants. The percentage of individuals achieving optimal adherence to all their eligible study medications was 50.5% (48/95) in the SSRS group versus 44.2% (42/95) in the UC group (P = 0.383). Similarly, no statistically significant difference was observed in a per-protocol analysis assessing people who participated fully in the service; the percentage of individuals achieving optimal adherence to all their eligible study medications was 55.1% (38/69) in SSRS versus 40.7% (33/81) in UC (P = 0.080). Patient refusal of the refill synchronization services was common among randomized patients. CONCLUSION: SSRS service failed to detect a robust improvement in medication adherence when delivered using an opt-out strategy. However, small improvements in adherence or benefits to specific subgroups of patients could not be ruled out.

Correction to: Potential cost-savings from the use of the biosimilars filgrastim, infliximab and insulin glargine in Canada: a retrospective analysis.

In the original publication of this article [1], there is a mistake in the Fig. 2a, 2b, and 2c.

Potential cost-savings from the use of the biosimilars filgrastim, infliximab and insulin glargine in Canada: a retrospective analysis.

BACKGROUND: In 2014 and 2015, biosimilars for the drugs filgrastim, infliximab, and insulin glargine were approved for use in Canada. The introduction of biosimilars in Canada could provide significant cost savings for the Canadian healthcare system over originator biologic drugs, however it is known that the use of biosimilars varies widely across the world. The aim of this study was to estimate the use of biosimilars in Canada and potential cost-savings from their use. METHODS: We performed a retrospective analysis of Canadian drug purchases for filgrastim, infliximab, and insulin glargine from July 2016 to June 2018. This was a cross-sectional study and the time horizon was limited to the study period. As a result, no discounting of effects over time was included. Canadian drugstore and hospital purchases data, obtained from IQVIA™, were used to estimate the costs per unit and unit volume for biosimilars and originator biologic drugs within each province. Potential cost-savings were calculated as a product of the units of reference originator product purchased and the cost difference between the originator biologic and its corresponding biosimilar. RESULTS: The purchase of biosimilars varied by each province in Canada, ranging from a low of 0.1% to a high of 81.6% of purchases. In total, $1,048,663,876 Canadian dollars in savings could have been realized with 100% use of biosimilars over the originator products during this 2 year time period. The potential savings are highest in the province of Ontario ($349 million); however, even in smaller markets (PEI and Newfoundland), $28 million could have potentially been saved. Infliximab accounted for the vast majority of the potential cost-savings, whereas the purchases of the biosimilar filgrastim outpaced that of the originator drug in some provinces. In sensitivity analyses assuming only 80% of originator units would be eligible for use as a biosimilar, $838 million dollars in cost savings over this two-year time period would still have been realized. CONCLUSIONS: The overall use of biosimilar drugs in Canada is low. Policy makers, healthcare providers, and patients need to be informed of potential savings by increased use of biosimilars, particularly in an increasingly costly healthcare system.

Development and in vitro characterization of chitosan-coated polymeric nanoparticles for oral delivery and sustained release of the immunosuppressant drug mycophenolate mofetil.

OBJECTIVE: To develop an oral sustained release formulation of mycophenolate mofetil (MMF) for once-daily dosing, using chitosan-coated polylactic acid (PLA) or poly(lactic-co-glycolic) acid (PLGA) nanoparticles. The role of polymer molecular weight (MW) and drug to polymer ratio in encapsulation efficiency (EE) and release from the nanoparticles was explored in vitro. METHODS: Nanoparticles were prepared by a single emulsion solvent evaporation method where MMF was encapsulated with PLGA or PLA at various polymer MW and drug: polymer ratios. Subsequently, chitosan was added to create coated cationic particles, also at several chitosan MW grades and drug: polymer ratios. All the formulations were evaluated for mean diameter and polydispersity, EE as well as in vitro drug release. Differential scanning calorimetry (DSC), surface morphology, and in vitro mucin binding of the nanoparticles were performed for further characterization. RESULTS: Two lead formulations comprise MMF: high MW, PLA: medium MW chitosan 1:7:7 (w/w/w), and MMF: high MW, PLGA: high MW chitosan 1:7:7 (w/w/w), which had high EE (94.34% and 75.44%, respectively) and sustained drug release over 12 h with a minimal burst phase. DSC experiments revealed an amorphous form of MMF in the nanoparticle formulations. The surface morphology of the MMF NP showed spherical nanoparticles with minimal visible porosity. The potential for mucoadhesiveness was assessed by changes in zeta potential after incubation of the nanoparticles in mucin. CONCLUSION: Two chitosan-coated nanoparticles formulations of MMF had high EE and a desirable sustained drug release profile in the effort to design a once-daily dosage form for MMF.

Adverse symptoms of immunosuppressants: A survey of Canadian transplant clinicians.

Adverse symptoms of immunosuppressants (ASI) impact quality of life (QOL) in solid organ transplant recipients; however, standardized approaches for active ASI surveillance and intervention are lacking. While management is highly clinician dependent, clinician views remain largely unexplored. We surveyed Canadian Society of Transplantation members on their perceptions of ASI including frequency, perceived QOL impact, causal attribution, management strategies, and success. Sixty-one clinicians participated in the survey of 12 ASI (tremor, diarrhea, nausea, constipation, dyspepsia, insomnia, edema, dyspnea, arthralgia, acne, mouth sores, paresthesias), for a 22% response rate. Forty-nine completed the survey (80% completion rate). Diarrhea, dyspepsia, and insomnia were most frequent, requiring management in ≥ 2% of patients by 96%, 90%, and 82% of respondents, respectively. Diarrhea, insomnia, and dyspnea were deemed to have an important QOL impact by 92%, 82%, and 69%. Immunosuppressants were universally implicated as causative of tremor, diarrhea, acne, and mouth sores. Over 80% reported success in managing mouth sores, dyspepsia, and constipation. Management strategies included adjustment of immunosuppressant or other medications, drug therapy, and nonpharmacologic approaches and varied according to perceived causal attribution. More study is needed to compare clinician and patient views. These results will be used to establish priorities for further investigation of ASI.

Education Before Kidney Transplantation.

CONTEXT: Poor knowledge about immunosuppressive (IS) medications remains a major problem for patients in the posttransplant setting. Therefore, more effective educational strategies in the pretransplant setting are being considered as a possible method to improve knowledge and readiness for the challenges of posttransplant care. However, the most effective/relevant content of a pretransplant educational program is yet to be determined. OBJECTIVE: To identify pretransplant education topics from the posttransplant patient perspective. DESIGN: A focus group meeting was conducted among 7 high-functioning, stable adult kidney transplant recipients recruited from the Saskatchewan Transplant Program. Demographic information including age, gender, occupation, background/ethnicity, and time since transplant were recorded. A moderator, assistant moderator, and research assistant facilitated the 90-minute focus group meeting using a predetermined semistructured interview guide. The session was audio recorded and transcribed verbatim. Nvivo software was used to code the data and identify emerging themes exploring views of participants relating to the educational information required for pretransplant patients. RESULTS: Patients were satisfied with the education they had received. Ideas were classified into the following major themes-patient satisfaction, transplant waitlist, surgery, medications, posttransplant complications, lifestyle and monitoring, knowledge acquisition, illusion of control, and life changes posttransplant. Knowledge gaps were identified in all areas of the transplantation process and were not exclusive to IS medications. CONCLUSION: Misconceptions regarding transplantation were identified by a group of high-functioning, stable adult recipients who were satisfied with their clinical care. Future educational strategies should aim to address the entire transplantation process and not be limited to medications.

The Health-Care Provider's Perspective of Education Before Kidney Transplantation.

CONTEXT: Adequate patient education is essential for preparing potential recipients for kidney transplantation. Health-care providers play a vital role in education and can identify gaps in patient understanding. OBJECTIVE: To identify deficits in patient knowledge from the perspective of a transplant multidisciplinary care team and determine whether their perceptions align with patients who have previously undergone a transplant. DESIGN: An open call was advertised for health-care providers to attend a focus group discussion regarding the educational needs of pretransplant patients in 1 Canadian center. A predetermined, semistructured set of questions was used to collect the views of transplant caregivers. A moderator, assistant moderator, and research assistant facilitated the discussion, which was transcribed verbatim. Paper surveys were distributed to collect opinions of those unable to attend or uncomfortable to voice their opinion in an open forum. Qualitative analysis software was used to identify any emergent themes. Results were compared to a previous study undertaken in transplant recipients. RESULTS: Despite pre- and posttransplant education, specific themes emerged including misconceptions about the assessment process and time on the wait list and the surgery, incongruency between patient expectations and outcome, and confusion regarding medications. Health-care provider perceptions were remarkably consistent with transplant recipients. CONCLUSION: Health-care providers identified gaps in patient understanding indicating that transplant candidates may not be internalizing what is taught. Innovative educational approaches may be needed to provide more successful patient education. Similarities between health-care provider and patient perceptions suggest that care providers are a valuable source of information.

The community pharmacist's role in cancer screening and prevention.

As the Canadian population continues to age, the incidence of cancer is on the rise. To help alleviate the burden malignancy imposes on our health care system, a shift toward early cancer detection is necessary. Pharmacists are well positioned and willing to assume a more active role in cancer surveillance. Patients are receptive to pharmacist involvement and seem to prefer a convenient community pharmacy-based location for screening programs. The community pharmacist's current and potential role in cancer screening and prevention is summarized in this article. A review of screening recommendations and a discussion of opportunities will hopefully inspire pharmacists to consider incorporating malignancy screening initiatives into their practice.

Association between circulating thrombopoietin levels and cardiovascular risk prediction scores in renal transplant recipients.

BACKGROUND/AIMS: The 7-year Major Adverse Cardiovascular Events Calculator (CRCRTR-MACE) predicts cardiovascular events (CVE) in renal transplant recipients (RTR), and thrombopoietin (TPO) is a humoral inflammatory factor implicated in cardiovascular disease (CVD). The aim of the study was to determine if circulating TPO levels in stable RTR are positively associated with variable(s) in the CRCRTR-MACE score. METHODS: CRCRTR-MACE scores were calculated in 95 stable RTR. TPO levels were measured by multiplexed fluorescent bead-based immunoassay in all patients and 48 controls. Multivariate analysis (MVA) was performed between TPO and CV risk variables and patient demographics. Stepwise regression with backward elimination of insignificant variables estimated the impact of risk variables on TPO levels. Significance was defined at p < 0.05. Normalized data were presented as mean ± SD and non-normalized data as median (maximum to minimum). RESULTS: The risk of a CVE within 7 years as predicted by the median was 9.97% (range 1.93-84.2). The percentage of patients who were above 20% risk for a CVE was 28.4%. Control TPO level of 170.41 (4.4-995.9) pg/ml was significantly lower than that of 237.90 (32.77-1,386.79) pg/ml in RTR (p = 0.010). TPO level correlated significantly with the total CRCRTR-MACE score (R = 0.310, p = 0.004), smoking (p = 0.009) and eGFR (R = -0.275, p = 0.012) but not with age, diabetes, LDL level or history of CVE. Only the total CRCRTR-MACE score (p = 0.013) and smoking (p = 0.009) remained significant in the MVA. Stepwise regression estimated that smoking increased TPO levels by 206.28 pg/ml and each 10% increase in CRCRTR-MACE score increased TPO levels by an additional 44.4 pg/ml. CONCLUSION: TPO levels are increased in RTR with high CRCRTR-MACE, particularly in smokers with diminished eGFR. Circulating TPO may serve as a biomarker and treatment target for CVD in RTR.

Contribution of impaired renal function to cardiovascular risk prediction models in renal transplant recipients.

BACKGROUND: The Framingham risk score (FRS) and cardiovascular risk calculator for renal transplant recipients (CRCRTR-MACE) quantify cardiovascular risk in renal transplant recipients (RTR). In contrast to the FRS, the CRCRTR-MACE includes serum creatinine as a variable in the risk prediction equation. OBJECTIVE: To determine the influence of impaired renal function on performances of the two equations. METHODS: A chart review of 270 RTR transplanted from 1979 to 2012. High risk was defined at scores ≥20%. Standard statistical analyses included multivariate analysis (MVA), stepwise analysis, and odds ratio to estimate contributions of risk factors. RESULTS: Mean transplant duration was 9.51 ± 6.65 yr. Mean eGFR was 59.19 ± 28.26 mL/min/1.73 m(2) . FRS and CRCRTR-MACE scores of least 20% were present in 9.3% and 24.8%, respectively, while 7.2% and 11.2% of RTR with eGFR ≥60 mL/min/1.73 m(2) were high risk, respectively. Mean age, blood pressure, TC:HDL ratio, smoking, and diabetes were evenly distributed in patients with varying eGFR. FRS scores remained similar at wide eGFR range (≤30 mL/min/1.73 m(2) -≥90 mL/min/1.73 m(2) ), while CRCRTR-MACE scores significantly increased as eGFR decreased. CONCLUSIONS: CRCRTR-MACE identified more patients at high cardiovascular risk, even in those with more favorable renal function, suggesting a fundamental difference between the two calculators beyond renal function.

Validity of cardiovascular risk prediction models in kidney transplant recipients.

BACKGROUND: Predicting cardiovascular risk is of great interest in renal transplant recipients since cardiovascular disease is the leading cause of mortality. OBJECTIVE: To conduct a systematic review to assess the validity of cardiovascular risk prediction models in this population. METHODS: Five databases were searched (MEDLINE, EMBASE, SCOPUS, CINAHL, and Web of Science) and cohort studies with at least one year of follow-up were included. Variables that described population characteristics, study design, and prognostic performance were extracted. The Quality in Prognostic Studies (QUIPS) tool was used to evaluate bias. RESULTS: Seven studies met the criteria for inclusion, of which, five investigated the Framingham risk score and three used a transplant-specific model. Sample sizes ranged from 344 to 23,575, and three studies lacked sufficient event rates to confidently reach conclusion. Four studies reported discrimination (as measured by c-statistic), which ranged from 0.701 to 0.75, while only one risk model was both internally and externally validated. CONCLUSION: The Framingham has underestimated cardiovascular events in renal transplant recipients, but these studies have not been robust. A risk prediction model has been externally validated at least on one occasion, but comprehensive validation in multiple cohorts and impact analysis are recommended before widespread clinical application is advocated.

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.

Video Education and Behavior Contract to Improve Outcomes After Renal Transplantation (VECTOR): A Randomized Controlled Trial.

Sub-optimal adherence to immunosuppressant medications reduces graft survival for kidney transplant recipients and adherence-enhancing interventions are resource and time intensive. We performed a multi-center randomized controlled trial to investigate the impact of an electronically delivered intervention on adherence. Of 203 adult kidney transplant recipients who received a de novo kidney transplant n = 173 agreed to participate (intent-to-treat population) and were randomized to the intervention (video education plus behavior contract n = 91) or the control (standard education, n = 82). No significant differences were found between the groups for medication adherence measured by the Basel Assessment of Adherence to Immunosuppressive Medications Scale, intrapatient variability in tacrolimus levels, time in therapeutic range for any immunosuppressant, knowledge, self-efficacy, QOL, or hospitalizations. Among a subgroup of 64 participants randomized to the intervention group who completed a post-intervention questionnaire, two-thirds (67%, n = 43) reported watching at least 80% of the videos and 58% (n = 37) completed the electronic goal setting exercise and adherence contract. An autonomous goal setting exercise and electronic behavioural contract added to standard of care did not improve any outcomes. Our findings reiterate that nonadherence in transplantation is a difficult multifactorial problem that simple solutions will not solve. Trial registration number NCT03540121.