As if one pain problem was not enough: prevalence and patterns of coexisting chronic pain conditions and their impact on treatment outcomes

M Gabrielle Pagé,1,2 Maude Fortier,1 Mark A Ware,3–5 Manon Choinière1,6 1Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), 2Department of Biomedical Sciences, Faculty of Medicine, Université de Montréal, 3Department of Family Medicine, 4Department of Anesthesia, Faculty of Medicine, 5Alan Edwards Centre for Research on Pain, McGill University, 6Department of Anesthesiology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada Introduction: The presence of multiple coexisting chronic pain (CP) conditions (eg, low-back pain and migraines) within patients has received little attention in literature. The goals of this observational longitudinal study were to determine the prevalence of coexisting CP conditions, identify the most frequent ones and patterns of coexistence, investigate the relationships among patients’ biopsychosocial characteristics and number of CP conditions, and determine the impact of coexisting CP conditions on treatment response.Patients and methods: A total of 3,966 patients attending multidisciplinary pain-treatment centers who were enrolled in the Quebec Pain Registry were included. Patients completed self-report and nurse-administered questionnaires before their first visit and 6 months later. Results were analyzed using descriptive statistics, factor and cluster analyses, negative binomials with log-link generalized linear models, and linear mixed-effect models.Results: A third of patients reported coexisting CP conditions. No specific patterns of comorbidities emerged. The presence of coexisting CP conditions was associated with longer pain duration, older age, being female, and poorer quality of life. The presence of more than one CP condition did not have a clinically significant impact on treatment responses.Discussion: The novelty of the study results relate to the heterogeneity that was found in the patterns of coexistence of CP conditions and the fact that having multiple CP conditions did not clinically impact treatment response. These results highlight the need for future research that examines causes of coexistence among CP conditions across the spectrum of CP, as opposed to focusing on specific conditions, and to examine whether multiple CP conditions impact on additional domains, such as treatment satisfaction. These results highlight the importance of studying the pathophysiological mechanisms underlying the development of coexisting CP conditions, in order eventually to prevent/minimize their occurrence and/or develop optimal treatment and management approaches. Keywords: chronic pain, coexisting pain conditions, comorbidities, Quebec Pain Registry, cluster analysi

Just how much does it cost? A cost study of chronic pain following cardiac surgery

Jason Robert Guertin,1,2,* M Gabrielle Pagé,3,4,* Jean-Éric Tarride,5 Denis Talbot,1,2 Judy Watt-Watson,6 Manon Choinière3,4 1Department of Social and Preventive Medicine, Faculty of Medicine, Université Laval, Quebec City, QC, Canada; 2Centre de recherche du Centre hospitalier universitaire de Québec, Université Laval, Quebec City, QC, Canada; 3Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, Canada; 4Department of Anesthesiology and Pain Medicine, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada; 5Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; 6Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada *These authors contributed equally to this work Objective: The study objective was to determine use of pain-related health care resources and associated direct and indirect costs over a two-year period in cardiac surgery patients who developed chronic post-surgical pain (CPSP). Methods: This multicentric observational prospective study recruited patients prior to cardiac surgery; these patients completed research assistant-administered questionnaires on pain and psychological characteristics at 6, 12 and 24 months post-operatively. Patients reporting CPSP also completed a one-month pain care record (PCR) (self-report diary) at each follow-up. Data were analyzed using descriptive statistics, multivariable logistic regression models, and generalized linear models with log link and gamma family adjusting for sociodemographic and pain intensity. Results: Out of 1,247 patients, 18%, 13%, and 9% reported experiencing CPSP at 6, 12, and 24 months, respectively. Between 16% and 28% of CPSP patients reported utilizing health care resources for their pain over the follow-up period. Among all CPSP patients, mean monthly pain-related costs were CAN$207 at 6 months and significantly decreased thereafter. More severe pain and greater levels of pain catastrophizing were the most consistent predictors of health care utilization and costs. Discussion: Health care costs associated with early management of CPSP after cardiac surgery seem attributable to a minority of patients and decrease over time for most of them. Results are novel in that they document for the first time the economic burden of CPSP in this population of patients. Longer follow-up time that would capture severe cases of CPSP as well as examination of costs associated with other surgical populations are warranted. Summary: Economic burden of chronic post-surgical pain may be substantial but few patients utilize resources. Health utilization and costs are associated with pain and psychological characteristics. Keywords: CARD-PAIN, chronic post-surgical pain, health care utilization, costs, cardiac surger

Acute postoperative opioid consumption trajectories and long-term outcomes in pediatric patients after spine surgery

Mandy MJ Li,1,2 Don Daniel Ocay,2,3 Alisson R Teles,2,4 Pablo M Ingelmo,5,6 Jean A Ouellet,1–2,7 M Gabrielle Pagé,8,9 Catherine E Ferland2,4–6,101Faculty of Medicine, McGill University, Montreal, Quebec, Canada; 2Department of Clinical Research, Shriners Hospitals for Children-Canada, Montreal, Quebec, Canada; 3Department of Experimental Surgery, McGill University, Montreal, Quebec, Canada; 4Integrated Program in Neurosciences, McGill University, Montreal, Quebec, Canada; 5Chronic Pain Services, Montreal Children’s Hospital, Montreal, Quebec, Canada; 6Department of Anesthesia, McGill University, Montreal, Quebec, Canada; 7Division of Orthopaedic Surgery, McGill University, Montreal, Quebec, Canada; 8Département d’anesthésiologie, Université de Montréal, Montreal, Quebec, Canada; 9Carrefour de l’innovation et de l’évaluation en santé, Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, Quebec, Canada; 10Child Health and Human Development Research Axis, Research Institute-McGill University Health Centre, Montreal, Quebec, CanadaBackground: The days following surgery are a critical period where the use of opioids predicts long-term outcomes in adults. It is currently unknown as to whether opioid consumption throughout the acute postoperative period is associated with long-term outcomes in pediatric patients. The aims of this study were to characterize opioid consumption trajectories in the acute postoperative period, identify predictors of trajectory membership and determine associations between opioid consumption trajectories and long-term patient outcomes.Materials and methods: Medication use, pain and mental health status were assessed at baseline in adolescents with idiopathic scoliosis who were scheduled for spinal fusion surgery. Cumulative 6-hr opioid consumption was recorded for up to 5 days after spinal surgery. At 6 months after surgery, medication use, pain and functional activity were evaluated. Growth mixture modeling was used to identify opioid trajectories.Results: One hundred and six patients were included in the study. Mean cumulative 6-hr opioid consumption in the acute postoperative period was 13.23±5.20 mg/kg. The model with the best fit contained 5 acute postoperative trajectories and a quadratic term (AIC =6703.26, BIC =6767.19). Two types of patient behaviors were identified: high opioid consumers (trajectories 4 and 5) and low opioid consumers (trajectories 1, 2 and 3). Intraoperative intrathecal morphine dose was a predictor of trajectory membership (p=0.0498). Opioid consumption during the acute postoperative period was not significantly associated with pain, functional activity or pain medication use at 6 months after surgery.Conclusion: In pediatric patients, intraoperative intrathecal morphine dose predicts opioid consumption in the acute postoperative period. Importantly, opioid consumption during this period does not affect long-term outcomes in pediatric patients after a spine surgery.Keywords: opioids, pediatrics, postsurgical pain, trajectories, adolescent idiopathic scoliosis, spinal fusion surger

Sensitivity to Pain Traumatization Scale: development, validation, and preliminary findings

Joel Katz,1,2 Samantha R Fashler,1 Claire Wicks,1 M Gabrielle Pagé,3 Kaley M Roosen,1 Valery Kleiman,1 Hance Clarke2 1Department of Psychology, York University, 2Department of Anesthesia and Pain Management, Toronto General Hospital, Toronto, ON, 3Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, Canada Background: This article reports three studies describing the development and validation of the 12-item Sensitivity to Pain Traumatization Scale (SPTS-12). SPT refers to the anxiety-related cognitive, emotional, and behavioral reactions to pain that resemble the features of a traumatic stress reaction.Methods: In Study 1, a preliminary set of 79 items was administered to 116 participants. The data were analyzed by using combined nonparametric and parametric item response theory resulting in a 12-item scale with a one-factor structure and good preliminary psychometric properties. Studies 2 and 3 assessed the factor structure and psychometric properties of the SPTS-12 in a community sample of 823 participants (268 with chronic pain and 555 pain-free) and a clinical sample of 345 patients (126 with chronic post-surgical pain, 92 with other nonsurgical chronic pain, and 127 with no chronic pain) at least 6 months after undergoing coronary artery bypass graft surgery, respectively. Results: The final SPTS-12 derived from Study 1 comprised 12 items that discriminated between individuals with different levels of SPT, with the overall scale showing good to very good reliability and validity. The results from Studies 2 and 3 revealed a one-factor structure for chronic pain and pain-free samples, excellent reliability and concurrent validity, and moderate convergent and discriminant validity. Conclusion: The results of the three studies provide preliminary evidence for the validity and reliability of the SPTS-12. Keywords: chronic pain, chronic post-surgical pain, trauma, psychology, scale development, measurement, item response theory analysis, factor analysi

Polypharmacy and Excessive Polypharmacy Among Persons Living with Chronic Pain: A Cross-Sectional Study on the Prevalence and Associated Factors

Ghita Zahlan,1 Gwenaelle De Clifford-Faugère,1 Hermine Lore Nguena Nguefack,1 Line Guénette,2,3 M Gabrielle Pagé,4,5 Lucie Blais,6 Anaïs Lacasse1 1Département des sciences de la santé, Université du Québec en Abitibi-Témiscamingue, Rouyn-Noranda, Quebec, Canada; 2Faculté de pharmacie, Université Laval, Quebec, Quebec, Canada; 3Centre de recherche, CHU de Québec - Université Laval, Quebec, Quebec, Canada; 4Centre de recherche, Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, Quebec, Canada; 5Département d’anesthésiologie et de médecine de la douleur, Faculté de médecine, Université de Montréal, Montreal, Quebec, Canada; 6Faculté de pharmacie, Université de Montréal, Montreal, Quebec, CanadaCorrespondence: Anaïs Lacasse, Département des sciences de la santé, Université du Québec en Abitibi-Témiscamingue, 445, boul. de l’Université, Rouyn-Noranda, Qc, J9X 5E4, Canada, Tel +1 819 762-0971, 2722, Email [email protected]: Polypharmacy can be defined as the concomitant use of ≥ 5 medications and excessive polypharmacy, as the use of ≥ 10 medications. Objectives were to (1) assess the prevalence of polypharmacy and excessive polypharmacy among persons living with chronic pain, and (2) identify sociodemographic and clinical factors associated with excessive polypharmacy.Patients and Methods: This cross-sectional study used data from 1342 persons from the ChrOnic Pain trEatment (COPE) Cohort (Quebec, Canada). The self-reported number of medications currently used by participants (regardless of whether they were prescribed or taken over-the-counter, or were used for treating pain or other health issues) was categorized to assess polypharmacy and excessive polypharmacy.Results: Participants reported using an average of 6 medications (median: 5). The prevalence of polypharmacy was 71.4% (95% CI: 69.0– 73.8) and excessive polypharmacy was 25.9% (95% CI: 23.6– 28.3). No significant differences were found across gender identity groups. Multivariable logistic regression revealed that factors associated with greater chances of reporting excessive polypharmacy (vs < 10 medications) included being born in Canada, using prescribed pain medications, and reporting greater pain intensity (0– 10) or pain relief from currently used pain treatments (0– 100%). Factors associated with lower chances of excessive polypharmacy were using physical and psychological pain treatments, reporting better general health/physical functioning, considering pain to be terrible/feeling like it will never get better, and being employed.Conclusion: Polypharmacy is the rule rather than the exception among persons living with chronic pain. Close monitoring and evaluation of the different medications used are important for all persons, especially those with limited access to care.Keywords: chronic pain, polypharmacy, excessive polypharmacy, prevalence, associated factors, determinant

Taking advantage of tumor cell adaptations to hypoxia for developing new tumor markers and treatment strategies

Cancer cells in hypoxic areas of solid tumors are to a large extent protected against the action of radiation as well as many chemotherapeutic drugs. There are, however, two different aspects of the problem caused by tumor hypoxia when cancer therapy is concerned: One is due to the chemical reactions that molecular oxygen enters intoin therapeutically targeted cells. This results in a direct chemical protection against therapy by the hypoxic microenvironment which has little to do with cellular biological regulatory processes. This part of the protective effect of hypoxia has been known for more than half a century and has been studied extensively. However, in recent years more focus has been put into the other aspect of hypoxia, namely the effect of this microenvironmental condition on selecting cells with certain genetical pre-requisites that are negative with respect to patient prognosis. There are adaptive mechanisms, where hypoxia induces regulatory cascades in cells resulting in a changed metabolism or changes in extra cellular signalling. These processes may lead to changes in cellular intrinsic sensitivity to treatment irrespective of oxygenation and furthermore, may also have consequences for tissue organization. Thus, the adaptive mechanisms induced by hypoxia itself may have a selective effect on cells with a fine-tuned protection against damage and stress of many kinds. It therefore could be that the adaptive mechanisms may be taken advantage of for new tumor labelling/imaging and treatment strategies. One of the Achilles’ heels of hypoxia research has always been exact measurements of tissue oxygenation as well as control of oxygenation in biological tumor models. Thus, development of technology that can ease this control is vital in order to study mechanisms and perform drug development under relevant conditions. An integrated EU Framework project 2004-2009, termed Euroxy, demonstrates several pathways involved in transcription and translation control of the hypoxic cell phenotype and evidence of cross talk with responses to pH and redox changes. The carbon anhydrase isoenzyme CA IX was selected for further studies due to its expression on the surface of many types of hypoxic tumors. The effort has lead to marketable culture flaks with sensors and incubation equipment and the synthesis of new drug candidates against new molecular targets. New labelling/imaging methods for cancer diagnosing and imaging of hypoxic cancer tissue now are being tested in xeno-graft models and also are in early clinical testing while new potential anticancer drugs are undergoing tests using xenografted tumor cancers. The present paper describes the above results in individual consortium partner presentations