Association of chronic poststernotomy pain and health-related quality of life: a prospective cohort study.

PURPOSE: Chronic poststernotomy pain (CPSP) after cardiac surgery is multifactorial and impacts patient recovery. We aimed to evaluate the association between CPSP severity and health-related quality of life at six months after cardiac surgery. METHODS: This was a single-centre prospective cohort study of patients who underwent cardiac surgery with median sternotomy between September 2020 and March 2021. Telephone interviews were conducted at six and 12 months postoperatively using the Short Form McGill Pain Questionnaire and the EQ-5D-5L. Strength of correlation was described using Spearman's correlation coefficient. Multivariable regression analysis was used to account for confounding variables. RESULTS: A total of 252 patients responded to the six-month interview (response rate, 65%). The mean (standard deviation) age of respondents was 65 (13) yr. Twenty-nine percent of respondents (72/252) reported CPSP at six months, and 14% (41/252) reported more than mild pain (score ≥ 2/5). At 12 months, of the 89% (64/72) patients who responded, 47% (30/64) still reported pain. The strength of the correlation between pain scores and EQ-5D-5L was weak (Spearman's correlation coefficient, -0.3). Risk factors for CPSP at six months included higher pain score on postoperative day 1, history of chronic pain prior to surgery, and history of depression. Intraoperative infusion of dexmedetomidine or ketamine was associated with a reduced risk of CPSP at six months. CONCLUSION: Chronic poststernotomy pain still affects patient recovery at six and 12 months after cardiac surgery. The severity of that pain is poorly correlated with patients' quality of life. STUDY REGISTRATION: www.osf.io ( https://osf.io/52rsw ); registered 14 May 2022.

RéSUMé: OBJECTIF: La douleur chronique post-sternotomie (DCPS) après une chirurgie cardiaque est multifactorielle et a un impact sur le rétablissement des patient·es. Nous avons cherché à évaluer l'association entre la sévérité de la DCPS et la qualité de vie liée à la santé six mois après la chirurgie cardiaque. MéTHODE: Il s'agissait d'une étude de cohorte prospective monocentrique portant sur des patient·es ayant bénéficié d'une chirurgie cardiaque avec sternotomie médiane entre septembre 2020 et mars 2021. Des entrevues téléphoniques ont été menées à six et 12 mois après l'opération en se servant du questionnaire abrégé de McGill sur la douleur et de l'EQ-5D-5L. La force de corrélation a été décrite à l'aide du coefficient de corrélation de Spearman. Une analyse de régression multivariée a été utilisée pour tenir compte des variables confondantes. RéSULTATS: Au total, 252 patient·es ont répondu à l'entrevue à six mois (taux de réponse de 65 %). L'âge moyen (écart type) des répondant·es était de 65 (13) ans. Vingt-neuf pour cent des personnes répondantes (72/252) ont déclaré avoir été atteintes de DCPS à six mois, et 14 % (41/252) ont signalé une douleur plus que légère (score ≥ 2/5). À 12 mois, sur les 89 % (64/72) personnes ayant répondu, 47 % (30/64) signalaient encore de la douleur. La force de la corrélation entre les scores de douleur et l'EQ-5D-5L était faible (coefficient de corrélation de Spearman, −0,3). Les facteurs de risque de DCPS à six mois comprenaient un score de douleur plus élevé au jour 1 postopératoire, des antécédents de douleur chronique avant la chirurgie et des antécédents de dépression. Une perfusion peropératoire de dexmédétomidine ou de kétamine a été associée à une réduction du risque de DCPS à six mois. CONCLUSION: La douleur chronique post-sternotomie affecte toujours le rétablissement des patient·es six et 12 mois après la chirurgie cardiaque. La sévérité de cette douleur est faiblement corrélée à la qualité de vie des patient·es. ENREGISTREMENT DE L'éTUDE: www.osf.io ( https://osf.io/52rsw ); enregistrée le 14 mai 2022.

Identification of high-impact gene-drug pairs for pharmacogenetic testing in Alberta, Canada.

OBJECTIVES: To facilitate decision-making and priority-setting related to Alberta's Pharmacogenomics (PGx) testing implementation strategy by identifying gene-drug pairs with the highest potential impact on prescribing practices in Alberta. PATIENTS AND METHODS: Annual drug dispensing data for Alberta from 2012 to 2016 for 57 medications with PGx-based prescribing guidelines were obtained, along with population estimates and demographics (age and ethnicity). Frequencies of actionable PGx genotypes by ethnicity were obtained from the Pharmacogenomics Knowledgebase (PharmGKB). Annual dispensing activity for each of the 57 medications was calculated for the full population (all ages) and children/youth (0-19 years). Alberta ethnicity data were cross-referenced with genetic frequency data for each of the main ethnic groups from PharmGKB to estimate the proportion of individuals with actionable genotypes. Actionable genotype proportions and drug dispensing frequencies were collectively used to identify high impact gene-drug pairs. RESULTS: We found (a) half of the drugs with PGx-based prescribing guidelines, namely, analgesics, proton pump inhibitors, psychotropics, and cardiovascular drugs, were dispensed at high frequencies (>1% of the entire population), (b) the dispensing rate for about one-third of these drugs increased over the 5-year study period, (c) between 1.1 and 45% of recipients of these drugs carried actionable genotypes, and (d) the gene-drug pairs with greatest impact in Alberta predominatly included CYP2C19 or CYP2D6. CONCLUSIONS: We uncovered specific patterns in drug dispensing and identified important gene-drug pairs that will inform the planning and development of an evidenced-based PGx testing service in Alberta, Canada. Adaptation of our approach may facilitate the process of evidence-based PGx testing implementation in other jurisdictions.

Estimating the Potential Impact of CYP2C19 and CYP2D6 Genetic Testing on Protocol-Based Care for Depression in Canada and the United States.

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) algorithm is the most recognized protocol-based care approach for moderate to severe depression. However, its implementation results in one-third of individuals receiving modest to no symptom remission. One possible explanation is the inter-individual differences in antidepressant metabolism due to CYP2C19 and CYP2D6genetic variation. Here, we aimed to determine the potential benefit of pairing CYP2C19 and CYP2D6testing with the five-step STAR*D algorithm. To estimate the proportion of individuals that could benefit from CYP2C19 and CYP2D6 testing, we simulated the STAR*D algorithm using ethnicity-specific phenotype (e.g., metabolizer status) frequencies published by the Clinical Pharmacogenetics Implementation Consortium and census data from the Canada and the US. We found that up to one-third of the US and Canadian populations being treated for depression could benefit from the addition of CYP2C19and CYP2D6 genetic testing. The potential benefit varied for each step of the algorithm and for each province, territory, and state. CYP2C19 genotyping had the greatest potential impact within the first two steps of the algorithm, while CYP2D6 genotyping had the most notable impact in Steps 3, 4, and 5. Our findings suggest the implementation of CYP2C19and CYP2D6 genetic testing alongside the STAR*D treatment algorithm may improve depression treatment outcomes in Canada and the US.

Pharmacogenetic Testing Options Relevant to Psychiatry in Canada: Options de tests pharmacogénétiques pertinents en psychiatrie au Canada.

OBJECTIVE: To identify and assess pharmacogenetic testing options relevant to psychiatry in Canada. METHOD: Searches of published literature, websites, and Standard Council of Canada's Laboratory Directory were conducted to identify pharmacogenetic tests available in Canada. Identified tests were assessed on 8 key questions related to analytical validity, accessibility, test ordering, delivery of test results, turnaround time, cost, clinical trial evidence, and gene/allele content. RESULTS: A total of 13 pharmacogenetic tests relevant to psychiatry in Canada were identified. All tests were highly accessible, and most were conducted in accredited laboratories. Both direct-to-consumer and clinician-gated testing were identified, with turnaround times and cost ranging from 2 to 40 days and CAD$199 to CAD$2310, respectively. Two tests were supported by randomized controlled trials. All tests met minimum gene and allele panel recommendations for psychiatry, but no 2 panels were identical. No test was unequivocally superior to all other tests. CONCLUSIONS: Pharmacogenetic testing in Canada is readily available but highly variable in terms of ordering procedures, delivery of results, turnaround times, cost, and gene/allele content. As such, it is important for psychiatrists and other health-care providers to understand the differences between the available tests to ensure appropriate selection and implementation within their practice.

Commercial Pharmacogenetic Tests in Psychiatry: Do they Facilitate the Implementation of Pharmacogenetic Dosing Guidelines?

INTRODUCTION: Expert groups have created dosing guidelines to facilitate the implementation of pharmacogenetic knowledge into clinical practice and commercial pharmacogenetic tests are becoming increasingly accessible. However, the extent to which these commercial tests facilitate the implementation of dosing guidelines is not clear. METHODS: Gene-drug pairs included on 22 commercial pharmacogenetic test panels were extracted and cross-referenced with the 74 gene-drug pairs with dosing guidelines in the Pharmacogenetics Knowledgebase, with particular attention given to the 28 gene-drug pairs relevant to psychiatry. RESULTS: On average, 70% of the 28 gene-drug pairs most relevant to psychiatry were covered by the examined tests. Six gene-drug pairs (CYP2D6-venlafaxine, CYP2D6-paroxetine, CYP2D6-amitriptyline, CYP2C19-sertraline, CYP2C19-citalopram, CYP2C19-amitriptyline) were included by all tests. Gene-drug pairs included on less than half of the test panels included HLA-B-phenytoin (14%), HLA-A-carbamazepine (24%), HLA-B-carbamazepine (29%), and CYP2D6-zuclopenthixol (43%). DISCUSSION: Most commercial pharmacogenetic tests we examined are well-equipped to facilitate implementation of the majority of dosing guidelines relevant to psychiatry but are limited in their ability to facilitate implementation of the full spectrum of dosing guidelines currently available.