Clinical Practice Guidelines for Cannabis and Cannabinoid-Based Medicines in the Management of Chronic Pain and Co-Occurring Conditions.

Background: One in five individuals live with chronic pain globally, which often co-occurs with sleep problems, anxiety, depression, and substance use disorders. Although these conditions are commonly managed with cannabinoid-based medicines (CBM), health care providers report lack of information on the risks, benefits, and appropriate use of CBM for therapeutic purposes. Aims: We present these clinical practice guidelines to help clinicians and patients navigate appropriate CBM use in the management of chronic pain and co-occurring conditions. Materials and Methods: We conducted a systematic review of studies investigating the use of CBM for the treatment of chronic pain. Articles were dually reviewed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical recommendations were developed based on available evidence from the review. Values and preferences and practical tips have also been provided to support clinical application. The GRADE system was used to rate the strength of recommendations and quality of evidence. Results: From our literature search, 70 articles met inclusion criteria and were utilized in guideline development, including 19 systematic reviews and 51 original research studies. Research typically demonstrates moderate benefit of CBM in chronic pain management. There is also evidence for efficacy of CBM in the management of comorbidities, including sleep problems, anxiety, appetite suppression, and for managing symptoms in some chronic conditions associated with pain including HIV, multiple sclerosis, fibromyalgia, and arthritis. Conclusions: All patients considering CBM should be educated on risks and adverse events. Patients and clinicians should work collaboratively to identify appropriate dosing, titration, and administration routes for each individual. Systematic Review Registration: PROSPERO no. 135886.

Why a distinct medical stream is necessary to support patients using cannabis for medical purposes.

BACKGROUND: Since 2001, Canadians have been able to obtain cannabis for medical purposes, initially through the Access to Cannabis for Medical Purposes Regulations (ACMPR). The Cannabis Act (Bill C-45) came into force on October 17, 2018, replacing the ACMPR. The Cannabis Act enables Canadians to possess cannabis purchased from a licensed retailer without authorization for either medical or nonmedical purposes. The Cannabis Act is currently the guiding legislation which governs both medical and nonmedical access. The Cannabis Act contains some improvements for patients but is essentially the same as its previous legislation. Beginning in October 2022, the federal government is conducting a review of the Cannabis Act and is questioning whether a distinct medical cannabis stream is still required, given the ease of access to cannabis and cannabis products. Although there is overlap in the reasons for medical and recreational cannabis use, the distinct legislation of medical versus recreational use of cannabis in Canada may be under threat. MAIN BODY: A large segment of the medical, academic, research, and lay communities agree that there is a need for distinct medical and recreational cannabis streams. Perhaps most importantly, separation of these streams is necessary to ensure that both medical cannabis patients and healthcare providers receive the required support needed to optimize benefits while minimizing risks associated with medical cannabis use. Preservation of distinct medical and recreational streams can help to ensure that needs of different stakeholders are met. For example, patients require guidance in the form of assessing the appropriateness of cannabis use, selection of appropriate products and dosage forms, dosing titration, screening for drug interactions, and safety monitoring. Healthcare providers require access to undergraduate and continuing health education as well as support from their professional organizations to ensure medical cannabis is appropriately prescribed. Although there are challenges in conducing research, as motives for cannabis use frequently straddle boundaries between medical versus recreational cannabis use, maintenance of a distinct medical stream is also necessary to ensure adequate supply of cannabis products appropriate for medical use, to reduce stigma associated with cannabis in both patients and providers, to help enable reimbursement for patients, to facilitate removal of taxation on cannabis used for medical purposes, and to promote research on all aspects of medical cannabis. CONCLUSION: Cannabis products for medical and recreational purposes have different objectives and needs, requiring different methods of distribution, access, and monitoring. HCPs, patients, and the commercial cannabis industry would serve Canadians well to continue to advocate to policy makers to ensure the continued existence of two distinct streams and must strive to make ongoing improvements to the current programs.

Validation of a Case Definition to Identify Patients Diagnosed With Cardiovascular Disease in Canadian Primary Care Practices.

Background: Cardiovascular disease (CVD) is a leading cause of death globally. This study validates a primary care-based electronic medical record case definition for CVD. Methods: This retrospective, cross-sectional study explores electronic medical record data from 1574 primary care providers participating in the Canadian Primary Care Sentinel Surveillance Network. A reference standard was created by reviewing medical records of a subset of patients in this network (n = 2017) for coronary artery disease (CAD), cerebrovascular disease (CeVD), and peripheral vascular disease (PVD). Together, these data produced a CVD reference. We applied validated case definitions to an active patient population (≥ 1 visit between January 1, 2018 and December 31, 2019) to estimate prevalence using the exact binomial test (N = 689,301). Descriptive statistics, χ2 tests, and t tests characterized patients with vs without CVD. Results: The optimal CVD Case Definition 2 had a sensitivity of 68.5% (95% Confidence Interval [CI]: 61.6%-74.8%), a specificity of 97.8% (95% CI: 97.0%-98.4%), a positive predictive value of 77.7% (95% CI: 71.6%-82.7%), and a negative predictive value of 96.5% (95% CI: 95.8%-97.1%). Included in this CVD definition was a strong CAD case definition with sensitivity of 91.6% (95% CI: 84.6%-96.1%), specificity of 98.3% (95% CI: 97.6%-98.8%), a PPV of 74.8% (95% CI: 67.8%-80.7%), and an NPV of 99.5% (95% CI: 99.1%-99.7%). This CVD definition also included CeVD and PVD case definitions with low sensitivity (77.6% and 36.6%) but high specificity (98.6% and 99.0%). The estimated prevalence of CVD among primary care patients is 11.2% (95% CI, 11.1%-11.3%; n = 77,064); the majority had CAD (6.4%). Conclusions: This study validated a definition of CVD and its component parts-CAD, CeVD, and PVD. Understanding the prevalence and disease burden for patients with CVD within primary care settings can improve prevention and disease management.

Contexte: La maladie cardiovasculaire (MCV) est l'une des premières causes de décès dans le monde. Cette étude valide une définition de cas dans les dossiers médicaux électroniques en soins primaires pour la MCV. Méthodologie: Cette étude intersectionnelle rétrospective explore les données provenant des dossiers médicaux électroniques de 1 574 fournisseurs de soins primaires participant au Réseau canadien de surveillance sentinelle en soins primaires. Une norme de référence a été créée en vérifiant les dossiers médicaux d'un sous-ensemble de patients dans ce réseau (n = 2017) à la recherche d'une coronaropathie, d'une maladie cérébrovasculaire ou d'une maladie vasculaire périphérique. Ensemble, ces données ont produit une référence pour la MCV. Nous avons appliqué des définitions de cas validées à une population de patients actifs (≥ 1 consultation entre le 1er janvier 2018 et le 31 décembre 2019) pour estimer la prévalence à l'aide du test binomial exact (N = 689 301). Des statistiques descriptives, des tests de χ2, et des tests t ont permis de caractériser les patients atteints ou non de MCV. Résultats: La définition de cas no 2 optimale pour la MCV avait une sensibilité de 68,5 % (intervalle de confiance [IC] à 95 % : de 61,6 à 74,8 %), une spécificité de 97,8 % (IC à 95 % : de 97,0 à 98,4 %), une valeur prédictive positive de 77,7 % (IC à 95 % : de 71,6 à 82,7 %) et une valeur prédictive négative de 96,5 % (IC à 95 % : de 95,8 à 97,1 %). On a inclus à cette définition de MCV une définition d'un cas de coronaropathie puissante, avec une sensibilité de 91,6 % (IC à 95 % : de 84,6 à 96,1 %), une spécificité de 98,3 % (IC à 95 % : de 97,6 à 98,8 %), une valeur prédictive positive de 74,8 % (IC à 95 % : de 67,8 à 80,7 %) et une valeur prédictive négative de 99,5 % (IC à 95 % : de 99,1 à 99,7 %). Cette définition de la MCV incluait aussi des cas de maladie cérébrovasculaire et de maladie vasculaire périphérique ayant une faible sensibilité (77,6 % et 36,6 %), mais une spécificité élevée (98,6 % et 99,0 %). La prévalence estimée de la MCV parmi les patients en soins primaires est de 11,2 % (IC à 95 % : de 11,1 à 11,3 %; n = 77 064); la majorité présentant une coronaropathie (6,4 %). Conclusions: Cette étude validait une définition de la MCV et de ses composantes ­ coronaropathie, maladie cérébrovasculaire et maladie vasculaire périphérique. Une compréhension de la prévalence et du fardeau de la maladie pour les patients atteints de MCV en soins primaires peut améliorer la prévention et la prise en charge de cette maladie.

Approach to atrial fibrillation: Essentials for primary care.

OBJECTIVE: To support family physicians in preventing atrial fibrillation (AF) in patients at risk and in identifying and managing those with established AF; and to summarize key recommendations for ideal screening and care of patients. SOURCES OF INFORMATION: The 2020 Canadian Cardiovascular Society and Canadian Heart Rhythm Society comprehensive guidelines for the management of AF, based on current evidence and clinical experience related to AF. MAIN MESSAGE: Atrial fibrillation, which is estimated to affect at least 500,000 Canadians, is associated with high risks of stroke, heart failure, and death. Primary care clinicians occupy a central role in the management of this chronic condition, focusing on the challenges of preventing AF and identifying, diagnosing, treating, and following patients with AF. Evidence-based guidelines that provide optimal management strategies have been published by the Canadian Cardiovascular Society and Canadian Heart Rhythm Society to assist in these tasks. Messages critical to primary care are offered to support effective knowledge translation. CONCLUSION: Most patients with AF can be managed effectively in primary care. Family physicians not only play an important role in ensuring patients with AF receive timely diagnoses, but they are also key to providing initial and ongoing care, especially in patients with comorbid conditions.

Clinical Practice Guidelines for Cannabis and Cannabinoid-Based Medicines in the Management of Chronic Pain and Co-Occurring Conditions

One in five individuals live with chronic pain globally, which often co-occurs with sleep problems, anxiety, depression, and substance use disorders. Although these conditions are commonly managed with cannabinoid-based medicines (CBM), health care providers report lack of information on the risks, benefits, and appropriate use of CBM for therapeutic purposes. Aims: We present these clinical practice guidelines to help clinicians and patients navigate appropriate CBM use in the management of chronic pain and co-occurring conditions. Materials and Methods: We conducted a systematic review of studies investigating the use of CBM for the treatment of chronic pain. Articles were dually reviewed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical recommendations were developed based on available evidence from the review. Values and preferences and practical tips have also been provided to support clinical application. The GRADE system was used to rate the strength of recommendations and quality of evidence. Results: From our literature search, 70 articles met inclusion criteria and were utilized in guideline development, including 19 systematic reviews and 51 original research studies. Research typically demonstrates moderate benefit of CBM in chronic pain management. There is also evidence for efficacy of CBM in the management of comorbidities, including sleep problems, anxiety, appetite suppression, and for managing symptoms in some chronic conditions associated with pain including HIV, multiple sclerosis, fibromyalgia, and arthritis. Conclusions: All patients considering CBM should be educated on risks and adverse events. Patients and clinicians should work collaboratively to identify appropriate dosing, titration, and administration routes for each individual.

Management of Type 2 Diabetic Kidney Disease in 2022: A Narrative Review for Specialists and Primary Care.

Purpose of review: Kidney disease is present in almost half of Canadian patients with type 2 diabetes (T2D), and it is also the most common first cardiorenal manifestation of T2D. Despite clear guidelines for testing, opportunities are being missed to identify kidney diseases, and many Canadians are therefore not receiving the best available treatments. This has become even more important given recent clinical trials demonstrating improvements in both kidney and cardiovascular (CV) endpoints with sodium-glucose cotransporter 2 (SGLT2) inhibitors and a nonsteroidal mineralocorticoid receptor antagonist, finerenone. The goal of this document is to provide a narrative review of the current evidence for the treatment of diabetic kidney disease (DKD) that supports this new standard of care and to provide practice points. Sources of information: An expert panel of Canadian clinicians was assembled, including 9 nephrologists, an endocrinologist, and a primary care practitioner. The information the authors used for this review consisted of published clinical trials and guidelines, selected by the authors based on their assessment of their relevance to the questions being answered. Methods: Panelists met virtually to discuss potential questions to be answered in the review and agreed on 10 key questions. Two panel members volunteered as co-leads to write the summaries and practice points for each of the identified questions. Summaries and practice points were distributed to the entire author list by email. Through 2 rounds of online voting, a second virtual meeting, and subsequent email correspondence, the authors reached consensus on the contents of the review, including all the practice points. Key findings: It is critical that DKD be identified as early as possible in the course of the disease to optimally prevent disease progression and associated complications. Patients with diabetes should be routinely screened for DKD with assessments of both urinary albumin and kidney function. Treatment decisions should be individualized based on the risks and benefits, patients' needs and preferences, medication access and cost, and the degree of glucose lowering needed. Patients with DKD should be treated to achieve targets for A1C and blood pressure. Renin-angiotensin-aldosterone system blockade and treatment with SGLT2 inhibitors are also key components of the standard of care to reduce the risk of kidney and CV events for these patients. Finerenone should also be considered to further reduce the risk of CV events and chronic kidney disease progression. Education of patients with diabetes prescribed SGLT2 inhibitors and/or finerenone is an important component of treatment. Limitations: No formal guideline process was used. The practice points are not graded and are not intended to be viewed as having the weight of a clinical practice guideline or formal consensus statement. However, most practice points are well aligned with current clinical practice guidelines.

Justification: L'insuffisance rénale est présente chez près de la moitié des patients canadiens atteints de diabète de type 2 (DT2). Il s'agit également de la première manifestation cardiorénale la plus fréquente du DT2. Bien qu'il existe des lignes directrices claires pour son dépistage, des occasions de diagnostiquer l'insuffisance rénale sont manquées, ce qui fait en sorte que de nombreux Canadiens ne reçoivent pas les meilleurs traitements disponibles. Cette préoccupation a pris de l'importance puisque de récents essais cliniques ont démontré des améliorations dans les paramètres rénaux et cardiovasculaires (CV) avec la prise de finérénone, un antagoniste non stéroïdien des récepteurs minéralocorticoïdes (nsMRA), et d'inhibiteurs du cotransporteur de glucose de sodium 2 (SGLT2). L'objectif de cet article est de fournir une revue narrative des données probantes actuelles appuyant cette nouvelle norme de soins pour le traitement de l'insuffisance rénale diabétique (IRD), ainsi que des points de pratique. Sources de l'information: Un groupe d'experts composé de cliniciens canadiens, dont neuf néphrologues, un endocrinologue et un prestataire de soins primaires, a été formé. Les auteurs de cette revue ont utilisé des lignes directrices et des essais cliniques publiés comme sources; ceux-ci ont été choisis sur la base d'une évaluation de leur pertinence pour les questions auxquelles ils avaient répondu. Méthodologie: Les panélistes se sont réunis virtuellement pour discuter de potentielles questions à répondre dans le cadre de cette revue, et se sont entendus sur dix questions clés. Deux membres du panel se sont portés volontaires pour être co-responsables et rédiger les résumés et les points de pratique pour chacune des questions identifiées. Ces derniers ont été distribués par courriel à l'ensemble des auteurs. Après deux tours de vote en ligne, une deuxième réunion virtuelle et la correspondance électronique qui a suivi, les auteurs sont parvenus à un consensus sur le contenu de la revue narrative, y compris sur tous les points de pratique. Principaux résultats: Il est essentiel que l'IRD soit diagnostiquée le plus tôt possible afin de prévenir de façon optimale la progression de la maladie et les complications qui y sont associées. On devrait procéder au dépistage systématique de l'IRD chez les patients diabétiques par l'évaluation de l'albumine urinaire ET de la fonction rénale. Les décisions relatives au traitement devraient être individualisées en fonction des risques et des avantages pour le patient, de ses besoins et préférences, de l'accès aux médicaments et des coûts, ainsi que du degré nécessaire de réduction de la glycémie. Les patients atteints d'IRD devraient être traités pour atteindre les cibles d'A1c et de pression artérielle. Le blocage du SRAA et le traitement avec des inhibiteurs du SGLT2 sont également des composantes clés de la norme de soins visant à réduire le risque d'événements rénaux et CV pour ces patients. La finérénone devrait également être envisagée pour réduire encore davantage les risques d'événements CV et de progression vers l'IRC. L'éducation des patients diabétiques auxquels on prescrit des inhibiteurs du SGLT2 et/ou de la finérénone est un élément important du traitement. Limites: Aucun processus officiel de directives n'a été utilisé. Les points de pratique ne sont pas notés et ne sont pas destinés à être considérés comme ayant le poids d'une directive de pratique clinique ou d'une déclaration de consensus officielle. Cependant, la plupart des points de pratique sont bien alignés avec les lignes directrices actuelles de pratique clinique.

Ups and downs of hypertension control in Canada: critical factors and lessons learned.

As the leading risk for death, population control of increased blood pressure represents a major challenge for all countries of the Americas. In the early 1990's, Canada had a hypertension control rate of 13%. The control rate increased to 68% in 2010, accompanied by a sharp decline in cardiovascular disease. The unprecedented improvement in hypertension control started around the year 2000 when a comprehensive program to implement annually updated hypertension treatment recommendations started. The program included a comprehensive monitoring system for hypertension control. After 2011, there was a marked decrease in emphasis on implementation and evaluation and the hypertension control rate declined, driven by a reduction in control in women from 69% to 49%. A coalition of health and scientific organizations formed in 2011 with a priority to develop advocacy positions for dietary policies to prevent and control hypertension. By 2015, the positions were adopted by most federal political parties, but implementation has been slow. This manuscript reviews key success factors and learnings. Some key success factors included having broad representation on the program steering committee, multidisciplinary engagement with substantive primary care involvement, unbiased up to date credible recommendations, development and active adaptation of education resources based on field experience, extensive implementation of primary care resources, annual review of the program and hypertension indicators and developing and emphasizing the few interventions important for hypertension control. Learnings included the need for having strong national and provincial government engagement and support, and retaining primary care organizations and clinicians in the implementation and evaluation.

La hipertensión arterial representa el principal riesgo de muerte; controlarla a nivel de la población constituye un desafío importante para todos los países de la Región de las Américas. A principios de la década de 1990, Canadá presentaba una tasa de control de la hipertensión del 13%. La tasa de control aumentó al 68% en el 2010, lo que vino acompañado por una disminución importante de las enfermedades cardiovasculares. Esta mejora sin precedentes en el control de la hipertensión empezó alrededor del año 2000 cuando se inició un programa integral para aplicar las recomendaciones sobre el tratamiento de la hipertensión, actualizadas anualmente. El programa incluyó un sistema de monitoreo integral para el control de la hipertensión. Después del 2011, hubo una marcada disminución del énfasis en la implementación y la evaluación, y la tasa de control de la hipertensión disminuyó, impulsada por una reducción en el control en las mujeres, que pasó del 69% al 49%. En el 2011, se formó una coalición de organizaciones científicas y de salud con la prioridad de elaborar una campaña de defensa y promoción de las políticas alimentarias para prevenir y controlar la hipertensión. Para el año 2015, esta postura fue adoptada por la mayoría de los partidos políticos federales, aunque la implementación ha sido lenta.En este artículo se revisan los factores clave de éxito y las lecciones aprendidas. Algunos factores clave de éxito fueron tener una amplia representación en el comité directivo del programa; el compromiso multidisciplinario con la participación sustantiva del sector de la atención primaria; unas recomendaciones creíbles, imparciales y actualizadas; el desarrollo y la adaptación activa de recursos educativos basados en la experiencia en el terreno; la amplia implementación de los recursos de la atención primaria; la revisión anual del programa y de los indicadores de hipertensión; y el desarrollo y el énfasis en unas pocas intervenciones importantes para el control de la hipertensión. Entre las lecciones aprendidas se encontró la necesidad de contar con un fuerte compromiso y apoyo del gobierno nacional y provincial, y de mantener a las organizaciones de atención primaria y al personal médico en la implementación y la evaluación.

O controle populacional da hipertensão arterial ­ o maior fator de risco de morte ­ representa um grande desafio para todos os países das Américas. No início da década de 1990, o Canadá tinha uma taxa de controle de hipertensão de 13%. Esse índice aumentou para 68% em 2010, acompanhado por um declínio acentuado das doenças cardiovasculares. A melhoria sem precedentes no controle da hipertensão começou por volta do ano 2000, quando teve início um programa abrangente para implementar recomendações de tratamento de hipertensão atualizadas anualmente. O programa incluía um sistema integral de monitoramento do controle da hipertensão. Após 2011, houve uma acentuada redução da ênfase na implementação e avaliação, e a taxa de controle de hipertensão caiu, principalmente às custas de uma redução deste controle em mulheres (de 69% para 49%). Uma coalizão de organizações científicas e de saúde formou-se em 2011 com a prioridade de desenvolver posições de defesa de políticas alimentares para prevenir e controlar a hipertensão. Até 2015, essas posições haviam sido adotadas pela maioria dos partidos políticos federais, mas a implementação tem sido lenta.Este manuscrito examina fatores-chave de sucesso e aprendizados. Alguns fatores-chave de sucesso incluíram uma ampla representatividade no comitê diretor do programa, engajamento multidisciplinar (com envolvimento significativo da atenção primária), recomendações imparciais e confiáveis, elaboração e adaptação ativa de recursos didáticos com base na experiência de campo, ampla implementação dos recursos da atenção primária, revisão anual do programa e dos indicadores de hipertensão e desenvolvimento e ênfase das poucas intervenções realmente importantes para o controle da hipertensão. As lições aprendidas incluíram a necessidade de ter forte envolvimento e apoio dos governos nacional e subnacionais e manter organizações e médicos da atenção primária engajados na implementação e avaliação.

Treatment with the P2X3-Receptor Antagonist Gefapixant for Acute Cough in Induced Viral Upper Respiratory Tract Infection: A Phase 2a, Randomized, Placebo-Controlled Trial.

INTRODUCTION: Available therapies for acute cough, a condition frequently caused by a viral upper respiratory tract infection (URTI), have shown limited evidence of efficacy. Gefapixant, a P2X3-receptor antagonist, has demonstrated efficacy and safety in studies of the treatment of refractory or unexplained chronic cough, but its efficacy for treating acute cough has not been previously studied. METHODS: This was a phase 2a, randomized, double-blind, placebo-controlled, parallel-group, pilot study. Healthy volunteers were randomized 1:1 to receive twice-daily gefapixant 45 mg or placebo and inoculated with human rhinovirus 16 to induce URTI and cough. Participants were observed while quarantined for 7 days after the start of treatment. The primary endpoint was awake cough frequency on day 3, which was objectively measured with a cough-recording device. Secondary endpoints included change from baseline to day 3 in subjective cough severity measures (cough severity visual analog scale, Cough Severity Diary) and cough-specific quality of life (Leicester Cough Questionnaire-acute). RESULTS: Of the 46 participants who met inclusion criteria [mean (standard deviation, SD) age, 24.6 (6.5) years; females, n = 8], 40 completed the study (gefapixant, n = 21; placebo, n = 19). There was no significant difference in awake cough frequency on day 3 between the gefapixant and placebo groups [least squares means, 2.4 versus 2.7 coughs per hour, respectively; mean difference (95% confidence interval, CI), -0.3 (-2.3, 1.7); P = 0.75]. There were no significant between-group differences for any of the secondary endpoints. Peak cough frequency was low and occurred later in the study than expected (days 4-5). The safety profile was consistent with that of previous studies of gefapixant. CONCLUSION: Compared with placebo, gefapixant did not reduce the frequency or severity of acute cough secondary to induced URTI. Induced viral URTI produced mild symptoms, including lower cough frequency than observed in previous studies of patients selected for acute cough associated with naturally occurring URTI. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03569033; EudraCT, 2017-000472-28; protocol number, MK-7264-013.

Ups and downs of hypertension control in Canada: critical factors and lessons learned

[ABSTRACT]. As the leading risk for death, population control of increased blood pressure represents a major challenge for all countries of the Americas. In the early 1990’s, Canada had a hypertension control rate of 13%. The control rate increased to 68% in 2010, accompanied by a sharp decline in cardiovascular disease. The unprece- dented improvement in hypertension control started around the year 2000 when a comprehensive program to implement annually updated hypertension treatment recommendations started. The program included a com- prehensive monitoring system for hypertension control. After 2011, there was a marked decrease in emphasis on implementation and evaluation and the hypertension control rate declined, driven by a reduction in control in women from 69% to 49%. A coalition of health and scientific organizations formed in 2011 with a priority to develop advocacy positions for dietary policies to prevent and control hypertension. By 2015, the positions were adopted by most federal political parties, but implementation has been slow. This manuscript reviews key success factors and learnings. Some key success factors included having broad representation on the program steering committee, multidisciplinary engagement with substantive primary care involvement, unbiased up to date credible recommendations, development and active adaptation of education resources based on field experience, extensive implementation of primary care resources, annual review of the program and hypertension indicators and developing and emphasizing the few interventions important for hypertension control. Learnings included the need for having strong national and provincial government engagement and support, and retaining primary care organizations and clinicians in the imple- mentation and evaluation.

[RESUMEN]. La hipertensión arterial representa el principal riesgo de muerte; controlarla a nivel de la población constituye un desafío importante para todos los países de la Región de las Américas. A principios de la década de 1990, Canadá presentaba una tasa de control de la hipertensión del 13%. La tasa de control aumentó al 68% en el 2010, lo que vino acompañado por una disminución importante de las enfermedades cardiovasculares. Esta mejora sin precedentes en el control de la hipertensión empezó alrededor del año 2000 cuando se inició un programa integral para aplicar las recomendaciones sobre el tratamiento de la hipertensión, actualizadas anualmente. El programa incluyó un sistema de monitoreo integral para el control de la hipertensión. Después del 2011, hubo una marcada disminución del énfasis en la implementación y la evaluación, y la tasa de control de la hipertensión disminuyó, impulsada por una reducción en el control en las mujeres, que pasó del 69% al 49%. En el 2011, se formó una coalición de organizaciones científicas y de salud con la prioridad de elaborar una campaña de defensa y promoción de las políticas alimentarias para prevenir y controlar la hipertensión. Para el año 2015, esta postura fue adoptada por la mayoría de los partidos políticos federales, aunque la implementación ha sido lenta. En este artículo se revisan los factores clave de éxito y las lecciones aprendidas. Algunos factores clave de éxito fueron tener una amplia representación en el comité directivo del programa; el compromiso multidisci- plinario con la participación sustantiva del sector de la atención primaria; unas recomendaciones creíbles, imparciales y actualizadas; el desarrollo y la adaptación activa de recursos educativos basados en la expe- riencia en el terreno; la amplia implementación de los recursos de la atención primaria; la revisión anual del programa y de los indicadores de hipertensión; y el desarrollo y el énfasis en unas pocas intervenciones importantes para el control de la hipertensión. Entre las lecciones aprendidas se encontró la necesidad de contar con un fuerte compromiso y apoyo del gobierno nacional y provincial, y de mantener a las organi- zaciones de atención primaria y al personal médico en la implementación y la evaluación.

[RESUMO]. O controle populacional da hipertensão arterial – o maior fator de risco de morte – representa um grande desafio para todos os países das Américas. No início da década de 1990, o Canadá tinha uma taxa de controle de hipertensão de 13%. Esse índice aumentou para 68% em 2010, acompanhado por um declínio acentuado das doenças cardiovasculares. A melhoria sem precedentes no controle da hipertensão começou por volta do ano 2000, quando teve início um programa abrangente para implementar recomendações de tratamento de hipertensão atualizadas anualmente. O programa incluía um sistema integral de monitoramento do controle da hipertensão. Após 2011, houve uma acentuada redução da ênfase na implementação e aval- iação, e a taxa de controle de hipertensão caiu, principalmente às custas de uma redução deste controle em mulheres (de 69% para 49%). Uma coalizão de organizações científicas e de saúde formou-se em 2011 com a prioridade de desenvolver posições de defesa de políticas alimentares para prevenir e controlar a hiper- tensão. Até 2015, essas posições haviam sido adotadas pela maioria dos partidos políticos federais, mas a implementação tem sido lenta. Este manuscrito examina fatores-chave de sucesso e aprendizados. Alguns fatores-chave de sucesso incluíram uma ampla representatividade no comitê diretor do programa, engajamento multidisciplinar (com envolvimento significativo da atenção primária), recomendações imparciais e confiáveis, elaboração e adap- tação ativa de recursos didáticos com base na experiência de campo, ampla implementação dos recursos da atenção primária, revisão anual do programa e dos indicadores de hipertensão e desenvolvimento e ênfase das poucas intervenções realmente importantes para o controle da hipertensão. As lições aprendidas incluíram a necessidade de ter forte envolvimento e apoio dos governos nacional e subnacionais e manter organizações e médicos da atenção primária engajados na implementação e avaliação.

Gestational heat stress alters skeletal muscle gene expression profiles and vascularity in fetal pigs in a sexually dimorphic manner.

BACKGROUND: There is evidence that sow heat stress (HS) during gestation affects fetal development with implications for impaired muscle growth. We have previously demonstrated that maternal HS during early to mid-gestation compromised muscle fibre hyperplasia in developing fetal pigs. Thus, we hypothesised these phenotypic changes are associated with a change in expression of genes regulating fetal skeletal muscle development and metabolism. To test this, at d 60 of gestation, RNA sequencing and immunohistochemistry were performed on fetal longissimus dorsi (LD) muscle biopsies collected from pregnant gilts that had experienced either thermoneutral control (CON, 20 °C, n = 7 gilts, 18 LD samples) or controlled HS (cyclic 28 to 33 °C, n = 8 gilts, 23 LD samples) conditions for 3 weeks. RESULTS: A total of 282 genes were differentially expressed between the HS and CON groups in female LD muscles (false discovery rate (FDR) ≤ 0.05), whereas no differentially expressed genes were detected in male LD muscles between the two groups (FDR > 0.05). Gestational HS increased the expression of genes associated with transcription corepressor activity, adipogenesis cascades, negative regulation of angiogenesis and pro-inflammatory signalling in female LD muscles. Immunohistochemical analyses revealed a decreased muscle vascularity density in fetuses from HS group for both sexes compared to those from the CON group (P = 0.004). CONCLUSIONS: These results reveal gilt HS during early to mid-gestation altered gene expression profiles in fetal LD muscles in a sexually dimorphic manner. The molecular responses, including transcription and angiogenesis repressions and enhanced adipogenesis cascades, were exclusively observed in females. However, the associated reductions in muscle vascularity were observed independently of sexes. Collectively this may indicate female fetal pigs are more adaptive to gestational HS in terms of gene expression changes, and/or there may be sexually dimorphic differences with respect to the timing of muscle molecular responses to gestational HS.

A retrospective observational study of osteoporosis management after a fragility fracture in primary care.

In many countries, osteoporosis is predominantly managed by primary care physicians; however, management after a fragility fracture has not been widely investigated. We describe osteoporosis care gaps in a real-world patient cohort. Our findings help inform initiatives to identify and overcome obstacles to effective management of patients after fragility fracture. PURPOSE: A fragility fracture is a major risk factor for subsequent fracture in adults aged ≥ 50 years. This retrospective observational study aimed to characterize post-fracture management in Canadian primary care. METHODS: A total of 778 patients with an index fragility fracture (low-trauma, excluding small bones) occurring between 2014 and 2016 were identified from medical records at 76 primary care centers in Canada, with follow-up until January 2018. RESULTS: Of 778 patients (80.5% female, median age [IQR] 73 [64-80]), 215 were on osteoporosis treatment and 269 had osteoporosis diagnosis recorded prior to their index fracture. The median follow-up was 363 (IQR 91-808) days. Of patients not on osteoporosis treatment at their index fracture, 60.2% (n = 339/563) remained untreated after their index fracture and 62.2% (n = 23/37) continued untreated after their subsequent fracture. After their index fracture, fracture risk assessment (FRAX or CAROC) was not performed in 83.2% (n = 647/778) of patients, and 59.9% (n = 466/778) of patients did not receive bone mineral density testing. Of patients without osteoporosis diagnosis recorded prior to their index date, 61.3% (n = 300/489) remained undiagnosed after their index fracture. At least one subsequent fracture occurred in 11.5% (n = 86/778) of patients. CONCLUSION: In the primary care setting, fragility fracture infrequently resulted in osteoporosis treatment or fracture risk assessment, even after multiple fragility fractures. These results suggest a fragility fracture is not recognized as a major risk factor for subsequent fracture and its occurrence does not prompt primary care physicians to intervene. These data urge initiatives to identify and overcome obstacles to primary care physicians' effective management of patients after fragility fractures.

Ups and downs of hypertension control in Canada: critical factors and lessons learned / Altibajos en el control de la hipertensión en Canadá: factores críticos y lecciones aprendidas / Altos e baixos no controle da hipertensão no Canadá: fatores críticos e lições aprendidas

ABSTRACT As the leading risk for death, population control of increased blood pressure represents a major challenge for all countries of the Americas. In the early 1990's, Canada had a hypertension control rate of 13%. The control rate increased to 68% in 2010, accompanied by a sharp decline in cardiovascular disease. The unprecedented improvement in hypertension control started around the year 2000 when a comprehensive program to implement annually updated hypertension treatment recommendations started. The program included a comprehensive monitoring system for hypertension control. After 2011, there was a marked decrease in emphasis on implementation and evaluation and the hypertension control rate declined, driven by a reduction in control in women from 69% to 49%. A coalition of health and scientific organizations formed in 2011 with a priority to develop advocacy positions for dietary policies to prevent and control hypertension. By 2015, the positions were adopted by most federal political parties, but implementation has been slow. This manuscript reviews key success factors and learnings. Some key success factors included having broad representation on the program steering committee, multidisciplinary engagement with substantive primary care involvement, unbiased up to date credible recommendations, development and active adaptation of education resources based on field experience, extensive implementation of primary care resources, annual review of the program and hypertension indicators and developing and emphasizing the few interventions important for hypertension control. Learnings included the need for having strong national and provincial government engagement and support, and retaining primary care organizations and clinicians in the implementation and evaluation.

RESUMEN La hipertensión arterial representa el principal riesgo de muerte; controlarla a nivel de la población constituye un desafío importante para todos los países de la Región de las Américas. A principios de la década de 1990, Canadá presentaba una tasa de control de la hipertensión del 13%. La tasa de control aumentó al 68% en el 2010, lo que vino acompañado por una disminución importante de las enfermedades cardiovasculares. Esta mejora sin precedentes en el control de la hipertensión empezó alrededor del año 2000 cuando se inició un programa integral para aplicar las recomendaciones sobre el tratamiento de la hipertensión, actualizadas anualmente. El programa incluyó un sistema de monitoreo integral para el control de la hipertensión. Después del 2011, hubo una marcada disminución del énfasis en la implementación y la evaluación, y la tasa de control de la hipertensión disminuyó, impulsada por una reducción en el control en las mujeres, que pasó del 69% al 49%. En el 2011, se formó una coalición de organizaciones científicas y de salud con la prioridad de elaborar una campaña de defensa y promoción de las políticas alimentarias para prevenir y controlar la hipertensión. Para el año 2015, esta postura fue adoptada por la mayoría de los partidos políticos federales, aunque la implementación ha sido lenta. En este artículo se revisan los factores clave de éxito y las lecciones aprendidas. Algunos factores clave de éxito fueron tener una amplia representación en el comité directivo del programa; el compromiso multidisciplinario con la participación sustantiva del sector de la atención primaria; unas recomendaciones creíbles, imparciales y actualizadas; el desarrollo y la adaptación activa de recursos educativos basados en la experiencia en el terreno; la amplia implementación de los recursos de la atención primaria; la revisión anual del programa y de los indicadores de hipertensión; y el desarrollo y el énfasis en unas pocas intervenciones importantes para el control de la hipertensión. Entre las lecciones aprendidas se encontró la necesidad de contar con un fuerte compromiso y apoyo del gobierno nacional y provincial, y de mantener a las organizaciones de atención primaria y al personal médico en la implementación y la evaluación.

RESUMO O controle populacional da hipertensão arterial - o maior fator de risco de morte - representa um grande desafio para todos os países das Américas. No início da década de 1990, o Canadá tinha uma taxa de controle de hipertensão de 13%. Esse índice aumentou para 68% em 2010, acompanhado por um declínio acentuado das doenças cardiovasculares. A melhoria sem precedentes no controle da hipertensão começou por volta do ano 2000, quando teve início um programa abrangente para implementar recomendações de tratamento de hipertensão atualizadas anualmente. O programa incluía um sistema integral de monitoramento do controle da hipertensão. Após 2011, houve uma acentuada redução da ênfase na implementação e avaliação, e a taxa de controle de hipertensão caiu, principalmente às custas de uma redução deste controle em mulheres (de 69% para 49%). Uma coalizão de organizações científicas e de saúde formou-se em 2011 com a prioridade de desenvolver posições de defesa de políticas alimentares para prevenir e controlar a hipertensão. Até 2015, essas posições haviam sido adotadas pela maioria dos partidos políticos federais, mas a implementação tem sido lenta. Este manuscrito examina fatores-chave de sucesso e aprendizados. Alguns fatores-chave de sucesso incluíram uma ampla representatividade no comitê diretor do programa, engajamento multidisciplinar (com envolvimento significativo da atenção primária), recomendações imparciais e confiáveis, elaboração e adaptação ativa de recursos didáticos com base na experiência de campo, ampla implementação dos recursos da atenção primária, revisão anual do programa e dos indicadores de hipertensão e desenvolvimento e ênfase das poucas intervenções realmente importantes para o controle da hipertensão. As lições aprendidas incluíram a necessidade de ter forte envolvimento e apoio dos governos nacional e subnacionais e manter organizações e médicos da atenção primária engajados na implementação e avaliação.

Controlled Human Infection Studies: Proposals for guidance on how to design, develop and produce a challenge strain.

There is an increasing need to establish quality principles for designing, developing and manufacturing challenge agents as currently these agents are classified differently by various jurisdictions. Indeed, considerations for challenge agent manufacturing vary between countries due to differences in regulatory oversight, the categorization of the challenge agent and incorporation into medicinal/vaccine development processes. To this end, a whitepaper on the guidance has been produced and disseminated for consultation to researchers, regulatory experts and regulatory or advisory bodies. This document is intended to discuss fundamental principles of selection, characterization, manufacture, quality control and storage of challenge agents for international reference. In the development phase, CMC documentation is needed for a candidate challenge agent, while standard operating procedure documentation is needed to monitor and control the manufacturing process, followed by use of qualified methods to test critical steps in the manufacturing process, or the final product itself. These activities are complementary: GMP rules, which intervene only at the time of the routine manufacturing of batches, do not contribute to the proper development and qualification of the candidate product. Some considerations regarding suitability of premises for challenge manufacturing was discussed in the presentation dedicated to "routine manufacturing".

Assessment of the educational competencies for the Hypertension Canada Professional Certification Program (HC-PCP) designed for implementation of hypertension guidelines into primary care.

BACKGROUND: The uptake of clinical practice guidelines into practice is limited for many chronic conditions, including hypertension. The aim of this study was to ascertain the importance of the educational competencies for the development of the Hypertension Canada Professional Certification Program (HC-PCP) among frontline, primary care professionals (e.g., pharmacists, physicians, nurses). METHODS: A group of hypertension experts developed 15 competencies believed to be important for primary care professionals to master when providing hypertension management. These competencies were surveyed for consensus by frontline clinicians through the Hypertension Canada e-newsletter in 2018. Clinicians were asked to rank the importance of each competency for a primary care provider to acquire when undertaking a certification in hypertension management, using a Likert scale from 1 (not important) to 5 (very important). RESULTS: A total of 121 clinicians responded to the survey. Of these, 38% were pharmacists, 31.4% were registered nurses, 10.7% were physicians and 7% were nurse practitioners. There was at least 1 respondent from each Canadian province and territory, except for the Northwest Territories. All 15 competencies received a mean rank of at least 4. The competency with the highest ranking was Competency 6: Ability to screen and identify hypertension (mean 4.83 [0.04]). The competencies with the lowest average ranks were Competency 1: Demonstrates a sound knowledge of the epidemiology of hypertension (mean 4.07 [0.85]) and Competency 5: Demonstrates an understanding of the validation process for blood pressure devices (mean 4.15 [0.08]). CONCLUSIONS: Clinicians generally ranked all 15 competencies to be of high importance for a provider who is certified in hypertension management to possess. These competencies and the current Hypertension Canada guidelines were used as the foundation for the development of an education program called the Hypertension Canada Professional Certification Program. Can Pharm J (Ott) 2021;154:xx-xx.

Compensatory feeding during early gestation for sows with a high weight loss after a summer lactation increased piglet birth weight but reduced litter size.

Sows mated in summer produce a greater proportion of born-light piglets (<1.1 kg) which contributes to increased carcass fatness in the progeny population. The reasons for the low birth weight of these piglets remain unclear, and there have been few successful mitigation strategies identified. We hypothesized that: 1) the low birth weight of progeny born to sows mated in summer may be associated with weight loss during the previous summer lactation; and 2) increasing early gestation feed allowance for the sows with high lactational weight loss in summer can help weight recovery and improve progeny birth weight. Sows were classified as having either low (av. 1%) or high (av. 7%) lactational weight loss in their summer lactation. All the sows with low lactational weight loss (LLStd) and half of the sows with high lactational weight loss received a standard gestation feeding regime (HLStd) (2.6 kg/d; day 0-30 gestation), whereas the rest of the sows with high lactational weight loss received a compensatory feed allowance (HLComp) (3.5 kg/d; day 0-30 gestation). A comparison of LLStd (n = 75) versus HLStd sows (n = 78) showed that this magnitude of weight loss over summer lactation did not affect the average piglet or litter birth weight, but such results may be influenced by the higher litter size (P = 0.030) observed in LLStd sows. A comparison of HLStd versus HLComp (n = 81) sows showed that the compensatory feeding increased (P = 0.021) weight gain of gestating sows by 6 kg, increased (P = 0.009) average piglet birth weight by 0.12 kg, tended to reduce (P = 0.054) the percentage of born-light piglets from 23.5% to 17.1% but reduced the litter size by 1.4 (P = 0.014). A subgroup of progeny stratified as born-light (0.8-1.1 kg) or -normal (1.3-1.7 kg) from each sow treatment were monitored for growth performance from weaning until 100 kg weight. The growth performance and carcass backfat of progeny were not affected by sow treatments. Born-light progeny had lower feed intake, lower growth rate, higher G:F, and higher carcass backfat than born-normal progeny (all P < 0.05). In summary, compensatory feeding from day 0 to 30 gestation in the sows with high weight loss during summer lactation reduced the percentage of born-light progeny at the cost of a lower litter size, which should improve growth rate and carcass leanness in the progeny population born to sows with high lactational weight loss.

Colchicine for Prevention of Atherothrombotic Events in Patients With Coronary Artery Disease: Review and Practical Approach for Clinicians.

A better understanding of the central role of inflammation in the development of coronary artery disease (CAD) has been the impetus for the evaluation of therapeutic strategies targeting the interleukin-1ß/interleukin-6 cytokine signaling pathway, involved in both chronic atherogenesis and in triggering of atherosclerotic plaque rupture. As an inexpensive pharmacologic agent with relatively few adverse effects that tend to be mild and tolerable, the role of colchicine in secondary prevention of atherothrombotic events has been the focus of multiple recent large-scale randomized controlled trials involving patients with stable CAD (Low-Dose Colchicine [LoDoCo] and LoDoCo2 trials), a recent myocardial infarction (Colchicine Cardiovascular Outcome Trial [COLCOT], Colchicine in Patients With Acute Coronary Syndrome [COPS], and Colchicine and Spironolactone in Patients With Myocardial Infarction/Synergy Stent Registry [CLEAR SYNERGY] trials), and undergoing percutaneous coronary interventions (Colchicine in Percutaneous Coronary Intervention [COLCHICINE-PCI] trial). Based on this evidence, low-dose colchicine (0.5 mg once daily) should be considered in patients with recent myocardial infarctions-within 30 days and, ideally, within 3 days-or with stable CAD to improve cardiovascular outcomes. Colchicine should not be used in patients with severe renal or hepatic disease because of the risk of severe toxicity. No serious adverse effect was associated with the combined use of colchicine and high-intensity statin therapy in large trials. The impact of colchicine in high-risk populations of patients with peripheral arterial disease and in those with diabetes for the primary prevention of CAD remains to be established.

Consensus recommendations on dosing and administration of medical cannabis to treat chronic pain: results of a modified Delphi process.

BACKGROUND: Globally, medical cannabis legalization has increased in recent years and medical cannabis is commonly used to treat chronic pain. However, there are few randomized control trials studying medical cannabis indicating expert guidance on how to dose and administer medical cannabis safely and effectively is needed. METHODS: Using a multistage modified Delphi process, twenty global experts across nine countries developed consensus-based recommendations on how to dose and administer medical cannabis in patients with chronic pain. RESULTS: There was consensus that medical cannabis may be considered for patients experiencing neuropathic, inflammatory, nociplastic, and mixed pain. Three treatment protocols were developed. A routine protocol where the clinician initiates the patient on a CBD-predominant variety at a dose of 5 mg CBD twice daily and titrates the CBD-predominant dose by 10 mg every 2 to 3 days until the patient reaches their goals, or up to 40 mg/day. At a CBD-predominant dose of 40 mg/day, clinicians may consider adding THC at 2.5 mg and titrate by 2.5 mg every 2 to 7 days until a maximum daily dose of 40 mg/day of THC. A conservative protocol where the clinician initiates the patient on a CBD-predominant variety at a dose of 5 mg once daily and titrates the CBD-predominant dose by 10 mg every 2 to 3 days until the patient reaches their goals, or up to 40 mg/day. At a CBD-predominant dose of 40 mg/day, clinicians may consider adding THC at 1 mg/day and titrate by 1 mg every 7 days until a maximum daily dose of 40 mg/day of THC. A rapid protocol where the clinician initiates the patient on a balanced THC:CBD variety at 2.5-5 mg of each cannabinoid once or twice daily and titrates by 2.5-5 mg of each cannabinoid every 2 to 3 days until the patient reaches his/her goals or to a maximum THC dose of 40 mg/day. CONCLUSIONS: In summary, using a modified Delphi process, expert consensus-based recommendations were developed on how to dose and administer medical cannabis for the treatment of patients with chronic pain.