Views on and experiences with medicinal cannabis among Canadian veterans who live with pain: A qualitative study.

Background: During fiscal year 2021-2022, Veterans Affairs Canada (VAC) reimbursed 18,388 veterans for medicinal cannabis at a cost of $153 million. Yet, it is not known whether the reimbursement program is producing a net benefit for veterans. Aims: This study investigated the views and experiences Canadian that veterans who live with pain have about medicinal cannabis use, including its use for the management of chronic pain, poor sleep, and emotional distress. Methods: Twelve Canadian veterans who live with pain-eight men, four women; split across four focus groups-were recruited to participate in a semistructured discussion around their experiences with medicinal cannabis use. Results: Using inductive thematic analysis, seven broad categories were identified: (1) cannabis use behaviors, (2) reasons for cannabis use, (3) outcomes from cannabis use, (4) facilitators of cannabis use, (5) barriers to cannabis use, (6) stigma around cannabis use, and (7) questions and concerns about cannabis use. Conclusions: Most veterans initiated cannabis use to manage the symptoms of preexisting medical and/or mental health conditions. Despite some negative side effects, most veterans reported improvements in their overall quality of life, sleep, relationships, mood, and pain. Concern remains around the discrepancy between veterans' qualitative reports of beneficial outcomes from medicinal cannabis use and equivocal findings around the benefit-to-harm ratio in the wider literature. Currently, the VAC reimbursement program remains challenged by unclear indication for which veterans, with what condition(s), at what dose, and in what form medical cannabis is most beneficial.

Contexte: Au cours de l'exercice 2021­2022, Anciens Combattants Canada (ACC) a remboursé 18 388 anciens combattants pour le cannabis médicinal, pour un coût de 153 millions de dollars. Pourtant, on ne sait pas si le programme de remboursement donne lieu à un bénéfice net pour les anciens combattants.Objectifs: Cette étude porte sur les points de vue et les expériences des anciens combattants canadiens qui vivent avec la douleur sur la consommation de cannabis médicinal, y compris son utilisation pour la gestion de la douleur chronique, les problèmes de sommeil et la détresse émotionnelle.Méthodes: Douze anciens combattants canadiens qui vivent avec la douleur - huit hommes et quatre femmes répartis en quatre groupes de discussion - ont été recrutés pour participer à une discussion semi-structurée autour de leurs expériences avec la consommation de cannabis médicinal.Résultats: Une analyse thématique inductive a permis d'établir sept grandes catégories : (1) les comportements de consommation de cannabis, (2) les raisons de la consommation de cannabis, (3) résultats de la consommation de cannabis, (4) les facteurs qui facilitent la consommation de cannabis, (5) les obstacles à la consommation de cannabis, (6) la stigmatisation autour de la consommation de cannabis et (7) les questions et préoccupations concernant la consommation de cannabis.Conclusions: La plupart des anciens combattants ont commencé à consommer du cannabis pour gérer les symptômes de maladies préexistantes et/ou des problèmes de santé mentale. Malgré certains effets secondaires négatifs, la plupart des anciens combattants ont signalé une amélioration de leur qualité de vie globale, de leur sommeil, de leurs relations, de leur humeur et de leur douleur. La préoccupation demeure autour de l'écart entre les rapports qualitatifs des anciens combattants décrivant les résultats bénéfiques de la consommation de cannabis médicinal et les résultats équivoques autour du rapport bénéfice/effet néfaste dans la littérature plus large. Actuellement, le programme de remboursement d'ACC reste contesté en raison d'indications peu claires concernant pour quels vétérans, atteints de quelles affections, à quelle dose et sous quelle forme le cannabis médical est le plus bénéfique.

Implementing One-at-a-Time Therapy in community addiction and mental health centres: a retrospective exploration of the implementation process and initial outcomes.

BACKGROUND: The Department of Health of the Government of New Brunswick and Regional Health Authorities elected to implement Stepped Care 2.0 (SC2.0) in 2021, and began with One-at-a-Time (OAAT) therapy in Community Addiction and Mental Health Centres (CAMHCs) to facilitate rapid access to addiction and mental healthcare. This study: 1) explicated the process of implementing OAAT therapy as it aligned to evidence-based implementation frameworks and strategies; 2) assessed readiness for change among providers during the implementation; and 3) evaluated initial client and system outcomes. METHODS: The process of implementing OAAT therapy within CAMHCs was documented and retrospectively aligned with the Active Implementation Frameworks-Stages of Implementation, Consolidated Framework for Implementation Research, and incorporated strategies endorsed by the Expert Recommendations for Implementing Change. Providers working in CAMHCs completed online asynchronous courses in OAAT therapy and SC2.0, and were recruited to participate in research on perceptions of organizational readiness. Initial outcomes of the implementation were evaluated through client satisfaction surveys administered in CAMHCs and system performance indicators. RESULTS: Aligning with implementation stages, key strategies included: 1) continuously monitoring readiness and soliciting stakeholder feedback for iterative improvement; 2) building a representative implementation team with engaged leaders; 3) creating a comprehensive implementation plan on staff training, communication, and system changes; and 4) supporting sustainability. Providers who participated in research (N = 170, ~ 50% response rate) agreed that their organization was ready for implementation, and that OAAT therapy delivered within a SC2.0 framework was acceptable, appropriate, and feasible. More than 3,600 OAAT therapy sessions were delivered during the initial implementation stage, and waitlists were reduced by 64.1%. The majority of clients who completed surveys (N = 1240, ~ 35% response rate) reported that their OAAT therapy session was helpful, with a minority reporting that additional intervention was needed. CONCLUSIONS: Thoughtful planning and execution, aligned with evidence-based implementation frameworks and strategies, played an important role in this provincial change initiative. Implementation steps outlined can help inform others looking to enact large-scale change.

Impact of Pregnancy on Hidradenitis Suppurativa Disease Course: A Systematic Review and Meta-Analysis.

BACKGROUND: Hormones are thought to play a role in hidradenitis suppurativa (HS). However, data on the HS disease course during pregnancy and the postpartum period has not been well established. The objective of this study is to analyze the available literature to determine HS disease activity during pregnancy and the postpartum period. METHODS: The PubMed and Embase databases were systematically searched for relevant articles from database inception until November 22, 2020. The inclusion criteria were a study population with the diagnosis of HS and discussion of pregnancy impact on the HS disease course or postpartum flare. Study characteristics, patient demographics, HS severity, and HS disease course during pregnancy and the postpartum period were extracted by 2 independent reviewers. The quality of included studies was assessed using the Newcastle-Ottawa Scale for observational studies. Heterogeneity was assessed using Cochran's Q statistic and I2 index. The random-effects meta-analytical model was used. The primary study outcome was the pooled odds ratio of improvement or of worsening of HS disease activity during pregnancy. RESULTS: The systematic search identified 8 studies for analysis. There was a total of 672 cases for which data on the patient-reported HS disease course during pregnancy were available, and 164 cases for which data on patient-reported postpartum flare were available. In the meta-analyses, the rate of HS disease improvement was 24% (95% CI 0.13-0.40) and the rate of HS disease worsening was 20% (95% CI 0.11-0.34). Sixty percent (99/164) of patients experienced a postpartum flare. CONCLUSION: While about a quarter of women will experience an improvement in HS during pregnancy, the majority will have a stable or worsened disease course, and over half of patients will experience a postpartum flare. Close monitoring of HS patients is needed during pregnancy and postpartum periods, as patients may need continued, or even escalated, disease management.

Intralesional biologics for inflammatory dermatoses: A systematic review.

Biologic medications are systemic therapeutic options for inflammatory dermatoses. Local forms of administration are less well-studied. To provide a summary of intralesional (IL) administration of biologics for various non-malignant inflammatory dermatologic conditions reported in the literature. A systematic review was performed in the PubMed and Embase databases from 2000 to 2020. Inclusion criteria included the local use of biologic medications for non-malignant cutaneous conditions. Quality was assessed with the modified Oxford Centre for Evidence-Based Medicine ratings. A total of 19 articles describing the use of 5 biologic medications in 9 dermatologic conditions were identified, comprising 172 patients. Conditions successfully treated with intralesional biologics included pemphigus vulgaris (rituximab), granuloma faciale (rituximab), perianal Crohn's disease (infliximab), lichen sclerosus (adalimumab), and necrobiosis lipoidica (etanercept and infliximab). Intralesional etanercept reduced pruritus associated with keloids. A case report of the use of infliximab for pyoderma gangrenosum did not demonstrate any efficacy. There was no consistent effect noted with treatments for sarcoidosis (infliximab) or cutaneous lymphoid hyperplasia (rituximab). Local administration of biologic medications may offer an additional method of treating refractory inflammatory dermatoses, but further study is needed to develop standardized dosing protocols, clarify efficacy rates, and identify optimal treatment candidates.

Bibliometric Analysis of the 50 Most Cited Publications in Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) has historically been a neglected disease. However, research in this field has grown exponentially in the past decade. METHODS: The top-cited HS articles from 1950 to 2020 were analyzed for authorship, study topic, study design, and senior author country of origin. RESULTS: We found that nearly half of the top 50 cited articles were published in the last decade, with a recent increase in the number of highly cited randomized controlled trials. Medical treatment is the most cited topic, with more attention on biologics over time. The past decade has seen an increase in highly cited articles on HS comorbidities, pathogenesis, and clinical practice guidelines. There has been a predominance of highly cited HS research from Europe; highly cited studies from Africa, Asia, Australia, and South America are lacking. CONCLUSIONS: Recent advances in HS research have focused on investigating HS pathogenesis and drug development, highlighting disease comorbidities, and improving evidence-based care. Studies in pathogenesis have translated into a paradigm shift in medical treatment from antibiotics to incorporation of targeted therapies in recent years. Encouraging growth of HS research in countries outside of North America and Europe may help to optimize HS care globally.

Guselkumab in the treatment of concomitant hidradenitis suppurativa, psoriasis, and Crohn's disease.

BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating skin condition whose pathogenesis is poorly understood, although interleukin (IL)-23 may play a role. IL-23 is also implicated in the pathogenesis of Crohn's disease (CD) and psoriasis, both of which can occur in patients with HS. CASE REPORT: We present the case of a 28-year-old woman with HS, psoriasis, and CD, who was successfully treated with guselkumab after failing multiple other biologic agents. CONCLUSION: Guselkumab represents a promising therapeutic option for recalcitrant HS patients with inflammatory comorbidities in which IL-23 plays a role.

Safe and effective treatment of atopic dermatitis using dupilumab over 23 months in a patient with HIV.

In 2017, the Food and Drug Administration approved dupilumab for patients with moderate to severe atopic dermatitis (AD) refractory to topical therapies; however, clinical trials specifically excluded patients with human immunodeficiency virus (HIV). Here, we describe the effective and uncomplicated treatment of AD with dupilumab over a 23-month period in a patient with HIV. Throughout the treatment duration, the patient demonstrated marked improvement in AD severity, while maintaining stable CD4 T cell counts and viral load. These results suggest that dupilumab represents a safe and effective treatment option for AD in patients with HIV.

Endocrinopathies with use of cancer immunotherapies.

BACKGROUND: Immunomodulatory therapies, including CTLA-4 and PD-1 inhibitors, provide a directed attack against cancer cells by preventing T cell deactivation. However, these drugs also prevent the downregulation of auto-reactive T cells, resulting in immune-related adverse events (IRAEs). Reports show a varied incidence of endocrine IRAEs, ranging from 0% to 63%. OBJECTIVE: To describe the frequency and clinical characteristics of endocrine IRAEs in patients taking cancer immunomodulatory therapies. DESIGN: Retrospective cohort study. PATIENTS: A total of 388 patients aged ≥18 years who were prescribed ipilimumab, nivolumab and/or pembrolizumab between 2009 and 2016 at our institution. MEASUREMENTS: Biochemical criteria were used to define endocrine IRAEs, including thyroid, pituitary, pancreas and adrenal dysfunction, following use of immunomodulatory therapies. RESULTS: Fifty endocrine IRAEs occurred in our cohort, corresponding to a rate of 12.9%. The most common endocrine IRAEs were thyroid dysfunction (11.1%), with a lower incidence of pituitary dysfunction (1.8% of patients). CONCLUSIONS: Over 12% of patients receiving ipilimumab, nivolumab and/or pembrolizumab in our study sample developed an endocrine IRAE. Patients who undergo treatment with immunomodulatory therapies should be monitored for the development of endocrine IRAEs.

SERUM THYROTROPIN CONCENTRATIONS ARE NOT PREDICTIVE OF AGGRESSIVE BREAST CANCER BIOLOGY IN EUTHYROID INDIVIDUALS.

OBJECTIVE: The potential influence of hypothyroidism on breast cancer remains incompletely understood. The objective of this study was to investigate the relationship between serum thyrotropin (thyroid-stimulating hormone, TSH) concentration and markers of aggressive breast cancer biology as defined by receptor expression profile, tumor grade, and American Joint Committee on Cancer (AJCC) stage characteristics. METHODS: This was a retrospective cohort study of patients from 2002 to 2014. All breast cancer patients who had complete receptor (estrogen receptor, ER; progesterone receptor, PR; and human epidermal growth factor receptor 2, Her2/neu) and prediagnosis serum TSH data (n = 437) were included. All patients had 1 of 6 receptor profiles: ER+ PR+ Her2/neu-, ER+ PR- Her2/neu-, ER+ PR+ Her2/neu+, ER+ PR- Her2/neu+, ER- PR- Her2/neu+, or ER- PR- Her2/neu-. Log-transformed serum TSH concentrations were analyzed using multinomial and logistic regressions to identify potential relationships with markers of breast cancer aggressiveness. RESULTS: Increasing serum TSH concentration was associated with a lower probability of having the receptor expression profile ER+ PR+ Her2/neu+ compared to patients with the ER+ PR+ Her2/neu- profile (odds ratio [OR] = 0.52, P = .0045). No significant associations between other receptor expression profiles and serum TSH concentration were found. All time-weighted and unweighted median serum TSH concentrations were within normal limits. No significant associations between serum TSH concentration and tumor grade, overall AJCC stage, tumor size (T), lymph node positivity (N), or presence of metastasis (M) were observed. CONCLUSIONS: Serum TSH was not associated with markers of breast cancer aggressiveness in our cohort.

No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins.

Contactins and Contactin-Associated Proteins, and Contactin-Associated Protein-Like 2 (CNTNAP2) in particular, have been widely cited as autism risk genes based on findings from homozygosity mapping, molecular cytogenetics, copy number variation analyses, and both common and rare single nucleotide association studies. However, data specifically with regard to the contribution of heterozygous single nucleotide variants (SNVs) have been inconsistent. In an effort to clarify the role of rare point mutations in CNTNAP2 and related gene families, we have conducted targeted next-generation sequencing and evaluated existing sequence data in cohorts totaling 2704 cases and 2747 controls. We find no evidence for statistically significant association of rare heterozygous mutations in any of the CNTN or CNTNAP genes, including CNTNAP2, placing marked limits on the scale of their plausible contribution to risk.