Sex differences exist in the perceived relief of cancer symptoms with medical cannabis: results from the Quebec Cannabis Registry.

PURPOSE: This study explored whether symptom relief differs by sex in patients with cancer receiving medical cannabis (MC) therapy. METHODS: This is an analysis of data collected from patients with cancer enrolled in the Quebec Cannabis Registry. MC was initiated for the therapeutic management of cancer symptoms. Patients completed the revised Edmonton Symptom Assessment System (ESAS-r) questionnaire at baseline and 3-month follow-up. We examined the interaction between sex and time on each ESAS-r symptom and the interaction between time and tetrahydrocannabinol:cannabidiol (THC:CBD) ratios for each sex on total symptom burden. RESULTS: The analysis included 358 patients (M: 171). There were no sex differences in baseline ESAS-r scores. Three months of MC therapy led to significant improvements in pain (M: - 1.4 ± 0.3, p < 0.001; F: - 1.1 ± 0.3, p < 0.01), tiredness (M: - 1.7 ± 0.4, p < 0.001; F: - 1.2 ± 0.4, p < 0.05), anxiety (M: - 1.1 ± 0.4, p < 0.05; F: - 1.2 ± 0.4, p < 0.001), and well-being (M: - 1.2 ± 0.4, p < 0.05; F: - 1.4 ± 0.4, p < 0.01) in both sexes. Only F perceived improved drowsiness (- 1.1 ± 0.4, p < 0.05), nausea (- 0.9 ± 0.3, p < 0.05), lack of appetite (- 1.7 ± 0.4, p < 0.001), and shortness of breath (- 0.9 ± 0.3, p < 0.05). From baseline to 3-month follow-up, THC-dominant MC significantly reduced pain (- 1.52 ± 0.52, p < 0.05) in M, whereas in F it diminished nausea (- 2.52 ± 0.70, p < 0.01) and improved well-being (- 2.41 ± 0.79, p < 0.05). THC:CBD-balanced products significantly reduced pain (- 1.48 ± 0.49, p < 0.05), tiredness (- 1.82 ± 0.62, p < 0.05), anxiety (- 1.83 ± 0.54, p < 0.05), and improved well-being (- 2.01 ± 0.56, p < 0.01) in M. CBD-dominant products did not offer significant symptom relief in either sex. CONCLUSION: The perceived relief of cancer symptoms from MC differs between sexes. More randomized controlled trials are needed to confirm our findings.

Medical cannabis is effective for cancer-related pain: Quebec Cannabis Registry results.

OBJECTIVES: To evaluate the safety and effectiveness of medical cannabis (MC) in reducing pain and concurrent medications in patients with cancer. METHODS: This study analysed data collected from patients with cancer who were part of the Quebec Cannabis Registry. Brief Pain Inventory (BPI), revised Edmonton Symptom Assessment System (ESAS-r) questionnaires, total medication burden (TMB) and morphine equivalent daily dose (MEDD) recorded at 3-month, 6-month, 9-month and 12-month follow-ups were compared with baseline values. Adverse events were also documented at each follow-up visit. RESULTS: This study included 358 patients with cancer. Thirteen out of 15 adverse events reported in 11 patients were not serious; 2 serious events (pneumonia and cardiovascular event) were considered unlikely related to MC. Statistically significant decreases were observed at 3-month, 6-month and 9-month follow-up for BPI worst pain (5.5±0.7 baseline, 3.6±0.7, 3.6±0.7, 3.6±0.8; p<0.01), average pain (4.1±0.6 baseline, 2.4±0.6, 2.3±0.6, 2.7±0.7; p<0.01), overall pain severity (3.7±0.5 baseline, 2.3±0.6, 2.3±0.6, 2.4±0.6; p<0.01) and pain interference (4.3±0.6 baseline, 2.4±0.6, 2.2±0.6, 2.4±0.7, p<0.01). ESAS-r pain scores decreased significantly at 3-month, 6-month and 9-month follow-up (3.7±0.6 baseline, 2.5±0.6, 2.2±0.6, 2.0±0.7, p<0.01). THC:CBD balanced strains were associated with better pain relief as compared with THC-dominant and CBD-dominant strains. Decreases in TMB were observed at all follow-ups. Decreases in MEDD were observed at the first three follow-ups. CONCLUSIONS: Real-world data from this large, prospective, multicentre registry indicate that MC is a safe and effective complementary treatment for pain relief in patients with cancer. Our findings should be confirmed through randomised placebo-controlled trials.

The Quebec Cannabis Registry: Investigating the Safety and Effectiveness of Medical Cannabis.

Objective: To investigate the safety and effectiveness of medical cannabis (MC) in the real-world clinical practice setting. Design: A 4-year prospective noncomparative registry of adult patients who initiated MC for a variety of indications. This paper reports on patients followed for up to 12 months, with interim visits at 3, 6, and 9 months after enrollment. Setting: Public or private outpatient clinics certified to authorize MC in the province of Quebec, Canada. Participants: Overall, 2991 adult (age ≥18 years) patients (mean age 51 years; 50.2% women) were enrolled between May 2015 and October 2018, with the last follow-up ending in May 2019. Interventions/Exposures: Cannabis products (dried, oil, or other) purchased from a Canadian licensed cannabis producer as authorized by physicians. Main Outcome Measures: The primary outcomes were self-reported pain severity, interference and relief (Brief Pain Inventory [BPI]), symptoms using the Revised Edmonton Symptom Assessment System (ESAS-r) and health-related quality of life dimensions (EQ-5D-5L) at baseline and each follow-up visit. The secondary outcomes were self-reported adverse events (AEs) and characteristics of cannabis treatment. Results: All patient-reported outcomes (BPI, ESAS-r, and EQ-5D-5L) showed a statistically significant improvement at 3 months (all p<0.01), which was maintained or further improved (for pain interference, tiredness, and well-being) over the remainder of the 12-month follow-up. Results also revealed clinically significant improvements in pain interference and tiredness, anxiety, and well-being from baseline. There were 79 AE reports (77 patients), 16 met the regulatory definition of seriousness, in which only 8 AEs were certainly or probably related to MC. Conclusions: MC directed by physicians appears to be safe and effective within 3 months of initiation for a variety of medical indications.

Predictors of Pain Reduction Among Fibromyalgia Patients Using Medical Cannabis: A Long-Term Prospective Cohort Study.

OBJECTIVE: Many patients with fibromyalgia (FM) report using cannabis as a strategy to improve pain. Given that pain often co-occurs with symptoms of anxiety and depression (i.e., negative affect) and sleep problems among patients with FM, improvements in these symptoms might indirectly contribute to reductions in pain intensity following cannabis use. The main objective of the study was to examine whether changes in pain intensity following initiation of medical cannabis among patients with FM could be attributed to concurrent changes (i.e., reductions) in negative affect and sleep problems. METHODS: This was a 12-month prospective cohort study among patients with FM (n = 323) initiating medical cannabis under the care of physicians. Patients were assessed at baseline, and follow-up assessment visits occurred every 3 months after initiation of medical cannabis. Patients' levels of pain intensity, negative affect, and sleep problems were assessed across all visits. RESULTS: Multilevel mediation analyses indicated that reductions in patients' levels of pain intensity were partly explained by concurrent reductions in sleep problems and negative affect (both P < 0.001). This remained significant even when accounting for patients' baseline characteristics or changes in medical cannabis directives over time (all P > 0.05). CONCLUSION: Our findings provide preliminary insight into the potential mechanisms of action underlying pain reductions among patients with FM who are using medical cannabis. Given the high attrition rate (i.e., 75%) observed in the present study at 12 months, our findings cannot be generalized to all patients with FM who are using medical cannabis.

Real-world serological responses to extended-interval and heterologous COVID-19 mRNA vaccination in frail, older people (UNCoVER): an interim report from a prospective observational cohort study.

BACKGROUND: The use of COVID-19 vaccines has been prioritised to protect the most vulnerable-notably, older people. Because of fluctuations in vaccine availability, strategies such as delayed second dose and heterologous prime-boost have been used. However, the effectiveness of these strategies in frail, older people are unknown. We aimed to assess the antigenicity of mRNA-based COVID-19 vaccines in frail, older people in a real-world setting, with a rationed interval dosing of 16 weeks between the prime and boost doses. METHODS: This prospective observational cohort study was done across 12 long-term care facilities of the Montréal Centre-Sud - Integrated University Health and Social Services Centre in Montréal, Québec, Canada. Under a rationing strategy mandated by the provincial government, adults aged 65 years and older residing in long-term care facilities in Québec, Canada, with or without previously documented SARS-CoV-2 infection, were administered homologous or heterologous mRNA vaccines, with an extended 16-week interval between doses. All older residents in participating long-term care facilities who received two vaccine doses were eligible for inclusion in this study. Participants were enrolled from Dec 31, 2020, to Feb 16, 2021, and data were collected up to June 9, 2021. Clinical data and blood samples were serially collected from participants at the following timepoints: at baseline, before the first dose; 4 weeks after the first dose; 6-10 weeks after the first dose; 16 weeks after the first dose, up to 2 days before administration of the second dose; and 4 weeks after the second dose. Sera were tested for SARS-CoV-2-specific IgG antibodies (to the trimeric spike protein, the receptor-binding domain [RBD] of the spike protein, and the nucleocapsid protein) by automated chemiluminescent ELISA. Two cohorts were used in this study: a discovery cohort, for which blood samples were collected before administration of the first vaccine dose and longitudinally thereafter; and a confirmatory cohort, for which blood samples were only collected from 4 weeks after the prime dose. Analyses were done in the discovery cohort, with validation in the confirmatory cohort, when applicable. FINDINGS: The total study sample consisted of 185 participants. 65 participants received two doses of mRNA-1273 (Spikevax; Moderna), 36 received two doses of BNT162b2 (Comirnaty; Pfizer-BioNTech), and 84 received mRNA-1273 followed by BNT162b2. In the discovery cohort, after a significant increase in anti-RBD and anti-spike IgG concentrations 4 weeks after the prime dose (from 4·86 log binding antibody units [BAU]/mL to 8·53 log BAU/mL for anti-RBD IgG and from 5·21 log BAU/mL to 8·05 log BAU/mL for anti-spike IgG), there was a significant decline in anti-RBD and anti-spike IgG concentrations until the boost dose (7·10 log BAU/mL for anti-RBD IgG and 7·60 log BAU/mL for anti-spike IgG), followed by an increase 4 weeks later for both vaccines (9·58 log BAU/mL for anti-RBD IgG and 9·23 log BAU/mL for anti-spike IgG). SARS-CoV-2-naive individuals showed lower antibody responses than previously infected individuals at all timepoints tested up to 16 weeks after the prime dose, but achieved similar antibody responses to previously infected participants by 4 weeks after the second dose. Individuals primed with the BNT162b2 vaccine showed a larger decrease in mean anti-RBD and anti-spike IgG concentrations with a 16-week interval between doses (from 8·12 log BAU/mL to 4·25 log BAU/mL for anti-RBD IgG responses and from 8·18 log BAU/mL to 6·66 log BAU/mL for anti-spike IgG responses) than did those who received the mRNA-1273 vaccine (two doses of mRNA-1273: from 8·06 log BAU/mL to 7·49 log BAU/mL for anti-RBD IgG responses and from 6·82 log BAU/mL to 7·56 log BAU/mL for anti-spike IgG responses; mRNA-1273 followed by BNT162b2: from 8·83 log BAU/mL to 7·95 log BAU/mL for anti-RBD IgG responses and from 8·50 log BAU/mL to 7·97 log BAU/mL for anti-spike IgG responses). No differences in antibody responses 4 weeks after the second dose were noted between the two vaccines, in either homologous or heterologous combinations. INTERPRETATION: Interim results of this ongoing longitudinal study show that among frail, older people, previous SARS-CoV-2 infection and the type of mRNA vaccine influenced antibody responses when used with a 16-week interval between doses. In these cohorts of frail, older individuals with a similar age and comorbidity distribution, we found that serological responses were similar and clinically equivalent between the discovery and confirmatory cohorts. Homologous and heterologous use of mRNA vaccines was not associated with significant differences in antibody responses 4 weeks following the second dose, supporting their interchangeability. FUNDING: Public Health Agency of Canada, Vaccine Surveillance Reference Group; and the COVID-19 Immunity Task Force. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Strategies used to engage hard-to-reach populations in childhood disability research: a scoping review.

PURPOSE: We completed a scoping review to: (1) identify strategies that have been used to engage hard-to-reach populations in childhood disability research, and (2) synthesize information as to whether and how these strategies were evaluated. METHODS: Systematic search of six electronic databases and grey literature to identify articles published in the last 10 years. Studies published in English, French, and Spanish reporting on strategies used to engage hard-to-reach populations in childhood disability research were eligible for inclusion. RESULTS: Out of 106 articles selected for full text review, 16 were included. Engagement was more common in earlier stages of research. The populations included in studies were children with disabilities and their parents. Engagement strategies were reported but rarely evaluated. Anecdotal outcomes of engagement were reported in 14/16 studies and included positive outcomes for the children and parents such as empowerment. The challenges with engagement included the increased time needed to engage children with disabilities or their parents. CONCLUSIONS: Our results can guide others who wish to engage a diverse group of children with disabilities and their parents in research. Research on how to engage other hard-to-reach populations within the childhood disability umbrella and evaluation of engagement strategies and outcomes is needed.IMPLICATIONS FOR REHABILITATION• Service providers should be concerned when the research informing their practices does not include families that represent their clients (e.g., families who are low income, Indigenous, ethnic minority, or LGBTQI parents of children with disabilities).• Strategies used to include children with disabilities in research, such as offering varied response methods that include story telling or photography, may also be used to promote participation in clinical services.• Service providers and teachers may have a role in facilitating the recruitment of 'hard-to-reach' families in research and advising researchers on methods to create a comfortable environment with accessible means of data collection for children with disabilities.