Patient-reported outcomes in those consuming medical cannabis: a prospective longitudinal observational study in chronic pain patients.

PURPOSE: We investigated patients with chronic pain seeking medical cannabis. We assessed their demographics, patterns of cannabis use, and the long-term effectiveness of cannabis on their pain and functional domains. METHODS: This observational study enrolled patients between 8 September 2015 and 31 July 2018 from community-based cannabis clinics in Ontario, Canada. In addition to collecting demographic information, the primary outcomes studied were pain intensity and pain-related interference scores assessed at baseline, three, six, and 12 months. Using validated questionnaires, we also assessed anxiety, depression, quality of life (QoL), general health symptoms, neuropathic pain, self-reported opioid consumption, and adverse events. RESULTS: Of the 1,000 patients consented, 757 (76%) participated at one or more of the study time points. At six and 12 months, 230 (30.4%) and 104 (13.7%) of participants were followed up, respectively. Most participants were female (62%), Caucasian (91%), and sought cannabis for pain relief (88%). Time was a significant factor associated with improvement in pain intensity (P < 0.001), pain-related interference scores (P < 0.001), QoL (P < 0.001), and general health symptoms (P < 0.001). Female sex was significantly associated with worse outcomes than male sex including pain intensity (P < 0.001) and pain-related interference (P < 0.001). The proportion of individuals who reported using opioids decreased by half, from 40.8% at baseline to 23.9% at 12 months. CONCLUSION: Despite significant challenges to collecting long-term observational data on patients who attempted a trial of cannabis products, approximately one-third of patients in the cohort remained on medical cannabis for six months. In this cohort, pain intensity and pain-related interference scores were reduced and QoL and general health symptoms scores were improved compared with baseline.

RéSUMé: OBJECTIF: Nous avons étudié des patients souffrant de douleur chronique et cherchant à obtenir du cannabis médical. Nous avons évalué leurs données démographiques, leurs habitudes de consommation de cannabis et l'efficacité à long terme du cannabis sur leur douleur et leurs domaines fonctionnels. MéTHODE: Cette étude observationnelle a recruté des patients entre le 8 septembre 2015 et le 31 juillet 2018 dans des cliniques communautaires de cannabis en Ontario, au Canada. En plus de recueillir des renseignements démographiques, les critères d'évaluation principaux étudiés étaient l'intensité de la douleur et les scores d'interférence liés à la douleur évalués au début de l'étude et à trois, six et 12 mois. À l'aide de questionnaires validés, nous avons également évalué l'anxiété, la dépression, la qualité de vie (QdV), les symptômes généraux de santé, la douleur neuropathique, la consommation d'opioïdes rapportée et les effets indésirables. RéSULTATS: Sur les 1000 patients consentants, 757 (76 %) ont participé à un ou plusieurs des points d'analyse de l'étude. À six et douze mois, 230 (30,4 %) et 104 (13,7 %) patients ont participé, respectivement. La plupart des participants étaient des femmes (62 %) d'origine caucasienne (91 %) et cherchaient à soulager leur douleur avec du cannabis (88 %). Le temps était un facteur important associé à l'amélioration de l'intensité de la douleur (P < 0,001), aux scores d'interférence liés à la douleur (P < 0,001), à la QdV (P < 0,001), et aux symptômes de santé généraux (P < 0,001). Le sexe féminin a été significativement associé à des pronostics moins bons que le sexe masculin, y compris en matière d'intensité de la douleur (P < 0,001) et d'interférences liées à la douleur (P < 0,001). La proportion de personnes qui ont déclaré utiliser des opioïdes a diminué de moitié, passant de 40,8 % au début de l'étude à 23,9 % à 12 mois. CONCLUSION: Malgré des défis importants dans la collecte de données observationnelles à long terme concernant les patients qui participent à une étude sur les produits du cannabis, environ un tiers des patients de la cohorte ont continué à prendre du cannabis médical pendant six mois. Dans cette cohorte, l'intensité de la douleur et les scores d'interférence liés à la douleur ont été réduits, et les scores de QdV et de symptômes généraux de santé se sont améliorés par rapport au début de la période à l'étude.

RNA expression profiling reveals PRAME, a potential immunotherapy target, is frequently expressed in solitary fibrous tumors.

Solitary fibrous tumors are a type of translocation-associated sarcoma with up to 30% rates of metastasis and poor response to conventional chemotherapy. Other translocation-associated sarcomas have been shown to display elevated expression of various cancer-testis antigens which may render them susceptible to immunotherapy strategies such as cancer vaccines and adoptive T-cell therapy. After an RNA sequencing assay brought the cancer-testis antigen Preferentially Expressed Antigen In Melanoma (PRAME) to our attention as possibly being upregulated in aggressive TERT promoter-mutated solitary fibrous tumors, we used tissue microarrays to asses PRAME expression in a large series of previously characterized solitary fibrous tumors, with correlation to various clinicopathologic features, as well as with tumor-infiltrating macrophages and the associated signal regulatory protein α (SIRPα)-CD47 regulatory checkpoint. We found that PRAME was expressed in 165/180 solitary fibrous tumors, with high expression seen in 58%, irrespective of TERT promoter status. Elevated PRAME expression was more frequent in primary intrathoracic solitary fibrous tumors and correlated with older age at primary diagnosis. Elevated PRAME was also associated with features suggestive of immune evasion, including lower numbers of antigen-presenting CD163+ and CD68+ macrophages, and expression of the "don't eat me" receptor CD47 on tumor cells. Taken together, these features suggest that strategies targeting PRAME with or without concomitant SIRPα-CD47 axis inhibition may represent a potential future therapeutic option in aggressive solitary fibrous tumor.

Perioperative Pain and Addiction Interdisciplinary Network (PAIN): consensus recommendations for perioperative management of cannabis and cannabinoid-based medicine users by a modified Delphi process.

In many countries, liberalisation of the legislation regulating the use of cannabis has outpaced rigorous scientific studies, and a growing number of patients presenting for surgery consume cannabis regularly. Research to date suggests that cannabis can impact perioperative outcomes. We present recommendations obtained using a modified Delphi method for the perioperative care of cannabis-using patients. A steering committee was formed and a review of medical literature with respect to perioperative cannabis use was conducted. This was followed by the recruitment of a panel of 17 experts on the care of cannabis-consuming patients. Panellists were blinded to each other's participation and were provided with rater forms exploring the appropriateness of specific perioperative care elements. The completed rater forms were analysed for consensus. The expert panel was then unblinded and met to discuss the rater form analyses. Draft recommendations were then created and returned to the expert panel for further comment. The draft recommendations were also sent to four independent reviewers (a surgeon, a nurse practitioner, and two patients). The collected feedback was used to finalise the recommendations. The major recommendations obtained included emphasising the importance of eliciting a history of cannabis use, quantifying it, and ensuring contact with a cannabis authoriser (if one exists). Recommendations also included the consideration of perioperative cannabis weaning, additional postoperative nausea and vomiting prophylaxis, and additional attention to monitoring and maintaining anaesthetic depth. Postoperative recommendations included anticipating increased postoperative analgesic requirements and maintaining vigilance for cannabis withdrawal syndrome.

Perioperative Pain and Addiction Interdisciplinary Network (PAIN) clinical practice advisory for perioperative management of buprenorphine: results of a modified Delphi process.

Until recently, the belief that adequate pain management was not achievable while patients remained on buprenorphine was the impetus for the perioperative discontinuation of buprenorphine. We aimed to use an expert consensus Delphi-based survey technique to 1) specify the need for perioperative guidelines in this context and 2) offer a set of recommendations for the perioperative management of these patients. The major recommendation of this practice advisory is to continue buprenorphine therapy in the perioperative period. It is rarely appropriate to reduce the buprenorphine dose irrespective of indication or formulation. If analgesia is inadequate after optimisation of adjunct analgesic therapies, we recommend initiating a full mu agonist while continuing buprenorphine at some dose. The panel believes that before operation, physicians must distinguish between buprenorphine use for chronic pain (weaning/conversion from long-term high-dose opioids) and opioid use disorder (OUD) as the primary indication for buprenorphine therapy. Patients should ideally be discharged on buprenorphine, although not necessarily at their preoperative dose. Depending on analgesic requirements, they may be discharged on a full mu agonist. Overall, long-term buprenorphine treatment retention and harm reduction must be considered during the perioperative period when OUD is a primary diagnosis. The authors recognise that inter-patient variability will require some individualisation of clinical practice advisories. Clinical practice advisories are largely based on lower classes of evidence (level 4, level 5). Further research is required in order to implement meaningful changes in practitioner behaviour for this patient group.