Medicinal cannabis for the treatment of chronic refractory pain: An investigation of the adverse event profile and health-related quality of life impact of an oral formulation

Introduction: Medicinal cannabis is prescribed in Australia for patients with chronic refractory pain conditions. However, measures of safety and effectiveness of different cannabinoids are lacking. We designed an observational study to capture effectiveness, adverse events (AEs), and health-related quality of life (HRQoL) measures in patients prescribed an oral medicinal cannabis formulation at Cannabis Access Clinics through the Cannabis Access Clinics Observational study (CACOS). Objectives: We aimed to evaluate effectiveness, reported AEs, and change in patient-reported outcomes in individuals prescribed a cannabinoid oil formulation for management of chronic pain. Methods: A cross-sectional analysis was conducted on patients prescribed an oil formulation of Δ9-tetrahydrocannabinol and cannabidiol for pain symptoms of at least 3-month duration. Clinician-reported AEs were organized by system, organ, class, and frequency. Analysis of patient-reported responses to a questionnaire was conducted using published minimal clinically important differences to determine meaningful change in HRQoL over time. Results: More than half (n = 91/151, 60.3%) of the participants experienced at least one AE during the observation period (mean 133 ± 116 days). No serious AEs were reported. Patient-reported pain impact scores were significantly reduced across the cohort (p = 0.034), and pain intensity scores verged on significance (p = 0.053). The majority of patients saw meaningful improvements in sleep (49.3%) and fatigue (35.6%). Conclusion: This analysis presents real-world data collected as part of standard of care. More than one-third of patients benefited from oral medicinal cannabis, which is impactful given the refractory nature of their pain. Amelioration of the impact of pain confirms continued prescribing of this formulation and validates our observational methodology as a tool to determine the therapeutic potency of medicinal cannabinoids

Parenting and oral health in an inner-city environment: a qualitative pilot study

Background Preventable oral diseases such as dental caries remain common in the United Kingdom. Clustering of poor health is observed within deprived communities, such as inner-city areas, where elevated levels of dental need are associated with lower uptake of dental care. Successful oral health promotion (OHP) initiatives are contingent upon effective community engagement. The aim of this pilot study was to engage with families with young children to explore community views on oral health and dental care and thus tailor OHP initiatives more effectively to their needs. Methods Qualitative research, involving individual interviews and triad focus groups with parents/caregivers, was conducted in a south London inner-city community as part of a ‘Well London’ programme initiative. Results Seventeen parents/caregivers participated in this pilot study. Parents/caregivers described a spectrum of oral health behaviours based on their social history, past dental experiences and cultural influences. All parents described a clear desire to create healthy lives for their children; however, two broad groups were apparent, termed ‘Oral Health Prioritisers’ and ‘Oral Health Non-prioritisers’. The former reported regularly accessing dental care for their children, believing that oral health contributes to systemic health. Non-prioritisers, however, preferentially used key services considered most beneficial to their child’s wellbeing. Dental services were considered a low priority for this group, where oral health was synonymous with absence of pain. Participants in both groups favoured OHP initiatives involving a range of health and social care services, with schools at the epicentre of programmes. First-time parents were proposed as an important group requiring support in future OHP initiatives with evidence suggesting that first-born children may have delayed presentation to a dentist. Conclusions The findings suggest that this inner-city community may contain sub-groups with contrasting perspectives on oral health and oral health behaviours; nevertheless, there was support for a systems approach to oral health promotion initiatives involving a range of health and social care services, including a critcal role for schools, and actively connecting with first-time parents. The findings provide the basis for further research

Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease:relapse and recapture rates, with predictive factors in 237 patients

Background: Thiopurines (azathioprine and mercaptopurine) remain integral to most medical strategies for maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Indefinite use of these drugs is tempered by long-term risks. While clinical relapse is noted frequently following drug withdrawal, there are few published data on predictive factors. Aim: To investigate the success of planned thiopurine withdrawal in patients in sustained clinical remission to identify rates and predictors of relapse. Methods This was a multicentre retrospective cohort study from 11 centres across the UK. Patients included had a definitive diagnosis of IBD, continuous thiopurine use ≥3 years and withdrawal when in sustained clinical remission. All patients had a minimum of 12 months follow-up post drug withdrawal. Primary and secondary end points were relapse at 12 and 24 months respectively. Results: 237 patients were included in the study (129 CD; 108 UC). Median duration of thiopurine use prior to withdrawal was 6.0 years (interquartile range 4.4–8.4). At follow-up, moderate/severe relapse was observed in 23% CD and 12% UC patients at 12 months, 39% CD and 26% UC at 24 months. Relapse rate at 12 months was significantly higher in CD than UC (P = 0.035). Elevated CRP at withdrawal was associated with higher relapse rates at 12 months for CD (P = 0.005), while an elevated white cell count was predictive at 12 months for UC (P = 0.007). Conclusion Thiopurine withdrawal in the context of sustained remission is associated with a 1-year moderate-to-severe relapse rate of 23% in Crohn's disease and 12% in ulcerative colitis

Genetic association analysis reveals differences in the contribution of NOD2 variants to the clinical phenotypes of orofacial granulomatosis

Background Orofacial granulomatosis (OFG) is a rare, inflammatory disorder of the mouth, in which some patients also have intestinal Crohn’s disease (CD). The etiology remains largely unknown, although there is a high prevalence of atopy, and oral granulomas are also seen in other immune disorders particularly CD and sarcoidosis. We investigated whether genetic variants associated with an increased risk of CD, sarcoidosis, or atopy were also associated with susceptibility to OFG. Methods Patients were stratified clinically as isolated oral manifestations (OFG only) or concurrent intestinal CD (OFG+CD). We genotyped 201 patients and 1023 healthy controls for risk variants in NOD2, IRGM, IL23R, ATG16L1 (CD), BTNL2 (sarcoidosis), and FLG (atopy). The coding regions of the NOD2 gene were screened for rare, potentially pathogenic variants in OFG. Results A combined analysis of 3 CD-risk variants in NOD2 showed no association with any OFG subgroup. NOD2 p.L1007insC was associated with OFG +CD (P = 0.023) and IL23R p.R381Q with all OFG (P ¼ 0.031). The sarcoidosis risk variant rs2076530 in BTNL2 was associated with all OFG (P = 0.013). We identified 7 rare missense NOD2 alleles in 8 individuals with OFG, 4 OFG-only patients and 4 patients with OFG+CD. There was a significant enrichment of NOD2 variants in the OFG+CD group compared to the OFG-only group (P = 0.008, common variants; P = 0.04, all common and rare variants). Conclusions Our findings suggest that genetic variants in NOD2 are only associated with OFG in patients with concurrent intestinal disease. A genome-wide association scan is needed to fully define the genetic architecture of OFG.</p

Genetic association analysis reveals differences in the contribution of NOD2 variants to the clinical phenotypes of orofacial granulomatosis

Background Orofacial granulomatosis (OFG) is a rare, inflammatory disorder of the mouth, in which some patients also have intestinal Crohn’s disease (CD). The etiology remains largely unknown, although there is a high prevalence of atopy, and oral granulomas are also seen in other immune disorders particularly CD and sarcoidosis. We investigated whether genetic variants associated with an increased risk of CD, sarcoidosis, or atopy were also associated with susceptibility to OFG. Methods Patients were stratified clinically as isolated oral manifestations (OFG only) or concurrent intestinal CD (OFG+CD). We genotyped 201 patients and 1023 healthy controls for risk variants in NOD2, IRGM, IL23R, ATG16L1 (CD), BTNL2 (sarcoidosis), and FLG (atopy). The coding regions of the NOD2 gene were screened for rare, potentially pathogenic variants in OFG. Results A combined analysis of 3 CD-risk variants in NOD2 showed no association with any OFG subgroup. NOD2 p.L1007insC was associated with OFG +CD (P = 0.023) and IL23R p.R381Q with all OFG (P ¼ 0.031). The sarcoidosis risk variant rs2076530 in BTNL2 was associated with all OFG (P = 0.013). We identified 7 rare missense NOD2 alleles in 8 individuals with OFG, 4 OFG-only patients and 4 patients with OFG+CD. There was a significant enrichment of NOD2 variants in the OFG+CD group compared to the OFG-only group (P = 0.008, common variants; P = 0.04, all common and rare variants). Conclusions Our findings suggest that genetic variants in NOD2 are only associated with OFG in patients with concurrent intestinal disease. A genome-wide association scan is needed to fully define the genetic architecture of OFG.</p