Publications by authors named "James S Khan"

23 Publications

  • Page 1 of 1

Efficacy and Safety of N-acetylcysteine for the Management of Chronic Pain in Adults: A Systematic Review & Meta-analysis.

Pain Med 2021 Feb 9. Epub 2021 Feb 9.

Mount Sinai Hospital, Department of Anesthesia and Pain Medicine, University of Toronto, Toronto, Canada.

Objective: To assess the efficacy and safety of N-acetylcysteine in the treatment of chronic pain.

Methods: A systematic search was carried out until April 2020 for clinical studies of N-acetylcysteine in the management of any persistent or recurrent chronic pain condition for adults ≥ 18 years old. Risk of Bias was assessed using the validated risk of bias tools. When appropriate, a meta-analysis using a random-effects model was performed, with a fixed-effect model for sensitivity analysis.

Results: Nine studies (n = 863) were included (5 randomized controlled trials [RCTs], 2 open-label non-comparative studies and 2 comparative studies), that evaluated patients with sickle cell disease (3), complex regional pain syndrome (1), pelvic pain/endometriosis (2), rheumatoid arthritis (1), diabetic neuropathy (1), and chronic neuropathic pain (1). In the pooled analysis of 3 RCTs, N-acetylcysteine did not reduce pain intensities (SMD -0.21, 95% CI -0.33 to 0.75, random-effects), improve functional outcomes (SMD 0.21, 95% CI -0.33 to 0.75) or quality of life (SMD 0.60, 95% CI -4.44 to 5.64); however, sensitivity analysis with a fixed effect model demonstrated an effect for pain intensities and function. Due to adverse events being inconsistently reported, no conclusion could be made regarding safety of N-acetylcysteine in chronic pain.

Conclusions: While there is some evidence to indicate N-acetylcysteine may provide analgesic efficacy for certain pain conditions, there is insufficient evidence to provide definitive evidence on NAC in chronic pain management. Larger-size RCTs spanning a variety of chronic pain conditions are needed to determine N-acetylcysteine's role, if any, in pain medicine.
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http://dx.doi.org/10.1093/pm/pnab042DOI Listing
February 2021

Naltrexone's Impact on Cancer Progression and Mortality: A Systematic Review of Studies in Humans, Animal Models, and Cell Cultures.

Adv Ther 2021 02 18;38(2):904-924. Epub 2020 Dec 18.

Department of Anesthesiology, Faculty of Health Sciences, McMaster University, Hamilton, Canada.

Background: Naltrexone (NTX) is an opioid antagonist traditionally used as a treatment for alcohol and opioid use disorders, but various studies have documented its involvement in cancer progression, exploring possible anticancer potential, when administered at high doses or as low dose naltrexone (LDN). Herein we present a systematic review of cancer-related outcomes from case reports, clinical trials, and retrospective and prospective studies conducted using cell cultures, animal models, and human subjects receiving NTX/LDN.

Methods: A systematic search of NTX in cancer therapy was conducted. Outcomes including tumor size and number, latency to tumor development, survival duration, progression of disease, and scan results were assessed in clinical and animal studies, and cell number was used as the outcome measure of culture studies.

Results: Several case reports demonstrate notable survival durations and metastatic resolutions in patients with late stage cancer when administered an average LDN dose of 3-5 mg/day. Animal and cell culture studies suggest an overarching principle of NTX involvement in cancer pharmacophysiology, suggesting that high doses and continuous administration can foster cancer progression, whereas low doses and intermittent treatment may hinder cell proliferation, impede tumorigenesis, and have potential anticancer efficacy.

Conclusion: This review emphasizes the value of potential future research on NTX in cancer therapy, and warrants need for a better understanding of underlying mechanisms. Future controlled studies with more robust sample sizes, particularly in humans, are needed to fully elucidate its potential in cancer therapy.
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http://dx.doi.org/10.1007/s12325-020-01591-9DOI Listing
February 2021

Effect of Perioperative Active Body Surface Warming Systems on Analgesic and Clinical Outcomes: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Anesth Analg 2020 11;131(5):1430-1443

Department of Health Research Methods, Evidence and Impact.

Background: Inadvertent perioperative hypothermia is a common complication of surgery, and active body surface warming (ABSW) systems are used to prevent adverse clinical outcomes. Prior data on certain outcomes are equivocal (ie, blood loss) or limited (ie, pain and opioid consumption). The objective of this study was to provide an updated review on the effect of ABSW on clinical outcomes and temperature maintenance.

Methods: We conducted a systematic review of randomized controlled trials evaluating ABSW systems compared to nonactive warming controls in noncardiac surgeries. Outcomes studied included postoperative pain scores and opioid consumption (primary outcomes) and other perioperative clinical variables such as temperature changes, blood loss, and wound infection (secondary outcomes). We searched Ovid MEDLINE daily, Ovid MEDLINE, EMBASE, CINHAL, Cochrane CENTRAL, and Web of Science from inception to June 2019. Quality of evidence (QoE) was rated according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Subgroup analysis sought to determine the effect of preoperative + intraoperative warming versus intraoperative warming alone. Metaregression evaluated the effect of year of publication, use of neuromuscular blockers, anesthesia, and surgery type on outcomes.

Results: Fifty-four articles (3976 patients) were included. Pooled results demonstrated that ABSW maintained normothermia compared to controls, during surgery (30 minutes postinduction [mean difference {MD}: 0.3°C, 95% confidence interval {CI}, 0.2-0.4, moderate QoE]), end of surgery (MD: 1.1°C, 95% CI, 0.9-1.3, high QoE), and up to 4 hours postoperatively (MD: 0.3°C, 95% CI, 0.2-0.5, high QoE). ABSW was not associated with difference in pain scores (<24 hours postoperatively, moderate to low QoE) or perioperative opioid consumption (very low QoE). ABSW increased patient satisfaction (MD: 2.2 points, 95% CI, 0.9-3.6, moderate QoE), reduced blood transfusions (odds ratio [OR] = 0.6, 95% CI, 0.4-1.0, moderate QoE), shivering (OR = 0.2, 95% CI, 0.1-0.4, high QoE), and wound infections (OR = 0.3, 95% CI, 0.2-0.7, high QoE). No significant differences were found for fluid administration (low QoE), blood loss (very low QoE), major adverse cardiovascular events (very low QoE), or mortality (very low QoE). Subgroup analysis and metaregression suggested increased temperature benefit with pre + intraoperative warming, use of neuromuscular blockers, and recent publication year. ABSW seemed to confer less temperature benefit in cesarean deliveries and neurosurgical/spinal cases compared to abdominal surgeries.

Conclusions: ABSW is effective in maintaining physiological normothermia, decreasing wound infections, shivering, blood transfusions, and increasing patient satisfaction but does not appear to affect postoperative pain and opioid use.
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http://dx.doi.org/10.1213/ANE.0000000000005145DOI Listing
November 2020

Prevalence and intensity of persistent post-surgical pain following breast cancer surgery: a systematic review and meta-analysis of observational studies.

Br J Anaesth 2020 09 28;125(3):346-357. Epub 2020 Jun 28.

Department of Anesthesia, McMaster University, Hamilton, ON, Canada; Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada; Michael G. DeGroote Centre for Medicinal Cannabis Research, McMaster University, Hamilton, ON, Canada; Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, ON, Canada.

Background: The prevalence and intensity of persistent post-surgical pain (PPSP) after breast cancer surgery are uncertain. We conducted a systematic review and meta-analysis to further elucidate this issue.

Methods: We searched MEDLINE, Embase, CINAHL, and PsycINFO, from inception to November 2018, for observational studies reporting persistent pain (≥3 months) after breast cancer surgery. We used random-effects meta-analysis and the Grading of Recommendations, Assessment, Development and Evaluations approach to rate quality of evidence.

Results: We included 187 observational studies with 297 612 breast cancer patients. The prevalence of PPSP ranged from 2% to 78%, median 37% (inter-quartile range: 22-48%); the pooled prevalence was 35% (95% confidence interval [CI]: 32-39%). The pooled pain intensity was 3.9 cm on a 10 cm visual analogue scale (95% CI: 3.6-4.2 cm). Moderate-quality evidence supported the subgroup effects of PPSP prevalence for localized pain vs any pain (29% vs 44%), moderate or greater vs any pain (26% vs 44%), clinician-assessed vs patient-reported pain (23% vs 36%), and whether patients underwent sentinel lymph node biopsy vs axillary lymph node dissection (26% vs 43%). The adjusted analysis found that the prevalence of patient-reported PPSP (any severity/location) was 46% (95% CI: 36-56%), and the prevalence of patient-reported moderate-to-severe PPSP at any location was 27% (95% CI: 10-43%).

Conclusions: Moderate-quality evidence suggests that almost half of all women undergoing breast cancer surgery develop persistent post-surgical pain, and about one in four develop moderate-to-severe persistent post-surgical pain; the higher prevalence was associated with axillary lymph node dissection. Future studies should explore whether nerve sparing for axillary procedures reduces persistent post-surgical pain after breast cancer surgery.
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http://dx.doi.org/10.1016/j.bja.2020.04.088DOI Listing
September 2020

Electronic Data Capture Versus Conventional Data Collection Methods in Clinical Pain Studies: Systematic Review and Meta-Analysis.

J Med Internet Res 2020 06 16;22(6):e16480. Epub 2020 Jun 16.

Child Health Evaluative Sciences, Hospital for Sick Children, Toronto, ON, Canada.

Background: The most commonly used means to assess pain is by patient self-reported questionnaires. These questionnaires have traditionally been completed using paper-and-pencil, telephone, or in-person methods, which may limit the validity of the collected data. Electronic data capture methods represent a potential way to validly, reliably, and feasibly collect pain-related data from patients in both clinical and research settings.

Objective: The aim of this study was to conduct a systematic review and meta-analysis to compare electronic and conventional pain-related data collection methods with respect to pain score equivalence, data completeness, ease of use, efficiency, and acceptability between methods.

Methods: We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), and Cochrane Central Register of Controlled Trials (CENTRAL) from database inception until November 2019. We included all peer-reviewed studies that compared electronic (any modality) and conventional (paper-, telephone-, or in-person-based) data capture methods for patient-reported pain data on one of the following outcomes: pain score equivalence, data completeness, ease of use, efficiency, and acceptability. We used random effects models to combine score equivalence data across studies that reported correlations or measures of agreement between electronic and conventional pain assessment methods.

Results: A total of 53 unique studies were included in this systematic review, of which 21 were included in the meta-analysis. Overall, the pain scores reported electronically were congruent with those reported using conventional modalities, with the majority of studies (36/44, 82%) that reported on pain scores demonstrating this relationship. The weighted summary correlation coefficient of pain score equivalence from our meta-analysis was 0.92 (95% CI 0.88-0.95). Studies on data completeness, patient- or provider-reported ease of use, and efficiency generally indicated that electronic data capture methods were equivalent or superior to conventional methods. Most (19/23, 83%) studies that directly surveyed patients reported that the electronic format was the preferred data collection method.

Conclusions: Electronic pain-related data capture methods are comparable with conventional methods in terms of score equivalence, data completeness, ease, efficiency, and acceptability and, if the appropriate psychometric evaluations are in place, are a feasible means to collect pain data in clinical and research settings.
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http://dx.doi.org/10.2196/16480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351264PMC
June 2020

Treating Persistent Pain After Breast Cancer Surgery.

Drugs 2020 Jan;80(1):23-31

Department of Anaesthesia and Pain Management, Pain Research Unit, Toronto General Hospital, Toronto, ON, M5G 2C4, Canada.

Breast cancer is one of the most commonly diagnosed cancers among women, and since the prognosis of breast cancer has substantially improved in past decades, complications of management are becoming increasingly apparent. Persistent pain lasting greater than 3 months after breast cancer surgery is unfortunately a common complication affecting approximately 30% of patients after tumour resection. Persistent breast cancer pain has neuropathic features and is typically mild-to-moderate in intensity, with approximately 10% suffering from severe pain. There is an increasing need to prevent persistent pain through the use of transitional pain programmes and perioperative interventions, and to identify novel treatment modalities to reduce suffering in those who unfortunately develop persistent pain. This review serves to provide an overview on persistent pain after breast cancer surgery, its pathophysiology, and current management strategies.
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http://dx.doi.org/10.1007/s40265-019-01227-5DOI Listing
January 2020

Effects of smoking on patients with chronic pain: a propensity-weighted analysis on the Collaborative Health Outcomes Information Registry.

Pain 2019 10;160(10):2374-2379

Division of Pain Medicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Palo Alto, CA, Canada.

Tobacco smoking is associated with adverse health effects, and its relationship to pain is complex. The longitudinal effect of smoking on patients attending a tertiary pain management center is not well established. Using the Collaborative Health Outcomes Information Registry of patients attending the Stanford Pain Management Center from 2013 to 2017, we conducted a propensity-weighted analysis to determine independent effects of smoking on patients with chronic pain. We adjusted for covariates including age, sex, body mass index, depression and anxiety history, ethnicity, alcohol use, marital status, disability, and education. We compared smokers and nonsmokers on pain intensity, physical function, sleep, and psychological and mood variables using self-reported NIH PROMIS outcomes. We also conducted a linear mixed-model analysis to determine effect of smoking over time. A total of 12,368 patients completed the CHOIR questionnaire of which 8584 patients had complete data for propensity analysis. Smokers at time of pain consultation reported significantly worse pain intensities, pain interference, pain behaviors, physical functioning, fatigue, sleep-related impairment, sleep disturbance, anger, emotional support, depression, and anxiety symptoms than nonsmokers (all P < 0.001). In mixed-model analysis, smokers tended to have worse pain interference, fatigue, sleep-related impairment, anger, emotional support, and depression over time compared with nonsmokers. Patients with chronic pain who smoke have worse pain, functional, sleep, and psychological and mood outcomes compared with nonsmokers. Smoking also has prognostic importance for poor recovery and improvement over time. Further research is needed on tailored therapies to assist people with chronic pain who smoke and to determine an optimal strategy to facilitate smoking cessation.
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http://dx.doi.org/10.1097/j.pain.0000000000001631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768701PMC
October 2019

Relationship between Perioperative Hypotension and Perioperative Cardiovascular Events in Patients with Coronary Artery Disease Undergoing Major Noncardiac Surgery.

Anesthesiology 2019 05;130(5):756-766

From the Lilibeth Caberto London Kidney Clinical Research Unit, London Health Sciences Centre, London, Canada (P.S.R.) the Department of Medicine (P.S.R., T.S., E.D., V.T., P.J.D.) Department of Health Research Methods, Evidence and Impact (P.S.R., E.D., P.J.D.), McMaster University, Hamilton, Canada the Population Health Research Institute, Hamilton, Canada (E.D., P.J.D.) the Division of General Internal Medicine, McGill University Health Center, Montreal, Canada (A.B.) the Department of Anesthesia and Intensive Care, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China (M.T.V.C.) the Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (C.B.) the Department of Medicine, University of Ottawa Heart Institute, Ottawa, Canada (B.J.W.C.) the Department of Radiology, University of Ottawa, Ottawa, Canada (B.J.W.C.) the Department of Anesthesia, University of Toronto, Toronto, Canada (J.S.K).

Background: Perioperative hypotension is associated with cardiovascular events in patients having noncardiac surgery. It is unknown if the severity of preexisting coronary artery disease determines susceptibility to the cardiovascular risks of perioperative hypotension.

Methods: In this retrospective exploratory analysis of a substudy of an international prospective blinded cohort study, 955 patients 45 yr of age or older with history or risk factors for coronary artery disease underwent coronary computed tomographic angiography before elective inpatient noncardiac surgery. The authors evaluated the potential interaction between angiographic findings and perioperative hypotension (defined as systolic blood pressure less than 90 mmHg for a total of 10 min or more during surgery or for any duration after surgery and for which intervention was initiated) on the composite outcome of time to myocardial infarction or cardiovascular death up to 30 days after surgery. Angiography assessors were blinded to study outcomes; patients, treating clinicians, and outcome assessors were blinded to angiography findings.

Results: Cardiovascular events (myocardial infarction or cardiovascular death within 30 days after surgery) occurred in 7.7% of patients (74/955), including in 2.7% (8/293) without obstructive coronary disease or hypotension compared to 6.7% (21/314) with obstructive coronary disease but no hypotension (hazard ratio, 2.51; 95% CI, 1.11 to 5.66; P = 0.027), 8.8% (14/159) in patients with hypotension but without obstructive coronary disease (hazard ratio, 3.85; 95% CI, 1.62 to 9.19; P = 0.002), and 16.4% (31/189) with obstructive coronary disease and hypotension (hazard ratio, 7.34; 95% CI, 3.37 to 15.96; P < 0.001). Hypotension was independently associated with cardiovascular events (hazard ratio, 3.17; 95% CI, 1.99 to 5.06; P < 0.001). This association remained in patients without obstructive disease and did not differ significantly across degrees of coronary disease (P value for interaction, 0.599).

Conclusions: In patients having noncardiac surgery, perioperative hypotension was associated with cardiovascular events regardless of the degree of coronary artery disease on preoperative coronary computed tomographic angiography.
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http://dx.doi.org/10.1097/ALN.0000000000002654DOI Listing
May 2019

Perioperative Pregabalin and Intraoperative Lidocaine Infusion to Reduce Persistent Neuropathic Pain After Breast Cancer Surgery: A Multicenter, Factorial, Randomized, Controlled Pilot Trial.

J Pain 2019 08 5;20(8):980-993. Epub 2019 Mar 5.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Population Health Research Institute, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Persistent postsurgical pain is defined as pain localized to the area of surgery of a duration of ≥2 months and is, unfortunately, a common complication after breast cancer surgery. Although there is insufficient evidence to support any preventative strategy, prior literature suggests the possible efficacy of intravenous lidocaine and perioperative pregabalin in preventing persistent pain after surgery. To determine feasibility of conducting a larger definitive trial, we conducted a multicenter 2 × 2 factorial, randomized, placebo-controlled pilot trial of 100 female patients undergoing breast cancer surgery. Patients were randomized to receive an intraoperative lidocaine infusion (1.5 mg/kg bolus followed by 2 mg/kg/h) or placebo and perioperative pregabalin (300 mg preoperatively, 75 mg twice daily for 9 days) or placebo. All feasibility criteria were surpassed; recruitment of 100 patients was accomplished within 42 weeks, with a follow-up rate of 100% and study drug compliance of ≥80%. At 3 months, 53% of patients reported persistent neuropathic pain. Although there was no interaction between lidocaine and pregabalin, lidocaine decreased the development of persistent neuropathic pain (43.1% vs 63.3%; relative risk = .68; 95% confidence interval = .47-1.0). Pregabalin did not reduce persistent pain (60% vs 46%; relative risk = 1.3; 95% confidence interval = .90-1.90) and neither pregabalin nor lidocaine impacted acute postoperative pain, opioid consumption, pain interference, or quality of life. Our pilot trial successfully demonstrated feasibility and provided promising data for conducting further trials of intraoperative lidocaine infusions during breast cancer surgeries. Clinical trial number: NCT02240199 PERSPECTIVE: This article reports the findings of a pilot randomized, controlled trial evaluating the effects of perioperative pregabalin and intraoperative lidocaine infusions in patients undergoing breast cancer surgery. This trial demonstrated the feasibility of conducting a larger trial and provided promising data that these interventions may decrease the development of persistent pain.
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http://dx.doi.org/10.1016/j.jpain.2019.02.010DOI Listing
August 2019

A Case Report of Combined Ultrasound and Fluoroscopic-Guided Percutaneous Radiofrequency Lesioning of the Obturator and Femoral Articular Branches in the Treatment of Persistent Hip Pain in a Pediatric Patient.

Pain Pract 2019 01 9;19(1):52-56. Epub 2018 Jul 9.

Department of Anesthesiology, Perioperative, and Pain Medicine, Division of Pain Medicine, Stanford University, Palo Alto, California, U.S.A.

Hip denervation comprising radiofrequency lesioning of the obturator and femoral articular branches is used in adults with refractory hip pain who are not surgical candidates. Persistent hip pain occurs infrequently in pediatric patients, and there are limited data on the safety and efficacy of this procedure in a pediatric population. We provide a case report of a successful ultrasound and fluoroscopic-guided hip denervation procedure in an 11-year-old girl with persistent right hip pain after septic arthritis refractory to conservative and surgical management. At an 18-week follow-up, hip denervation provided improvement in pain, mobility, and reduced opioid consumption by 20%.
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http://dx.doi.org/10.1111/papr.12724DOI Listing
January 2019

Predictors of Unemployment After Breast Cancer Surgery: A Systematic Review and Meta-Analysis of Observational Studies.

J Clin Oncol 2018 06 14;36(18):1868-1879. Epub 2018 May 14.

Li Wang, Yaping Chang, Samantha Craigie, Rachel J. Couban, Susan Reid, Michael McGillion, and Jason W. Busse, McMaster University, Hamilton; Sean A. Kennedy and Chris J. Hong, University of Toronto, Toronto; Brian Y. Hong, University of Ottawa, Ottawa, Ontario, Canada; Li Wang, West China Hospital, Sichuan University, Chengdu, People's Republic of China; Henry Y. Kwon, Wayne State University School of Medicine, Detroit, MI; Beatriz Romerosa, University Hospital of Toledo, Toledo, Spain; James S. Khan, Stanford University, Palo Alto, CA; and Victoria Blinder, Memorial Sloan Kettering Cancer Center, New York, NY.

Purpose Breast cancer surgery is associated with unemployment. Identifying high-risk patients could help inform strategies to promote return to work. We systematically reviewed observational studies to explore factors associated with unemployment after breast cancer surgery. Methods We searched MEDLINE, EMBASE, CINAHL, and PsycINFO to identify studies that explored risk factors for unemployment after breast cancer surgery. When possible, we pooled estimates of association for all independent variables reported by more than one study. Results Twenty-six studies (46,927 patients) reported the association of 127 variables with unemployment after breast cancer surgery. Access to universal health care was associated with higher rates of unemployment (26.6% v 15.4%; test of interaction P = .05). High-quality evidence showed that unemployment after breast cancer surgery was associated with high psychological job demands (odds ratio [OR], 4.26; 95% CI, 2.27 to 7.97), childlessness (OR, 1.30; 95% CI, 1.11 to 1.53), lower education level (OR, 1.15; 95% CI, 1.05 to 1.25), lower income level (OR, 1.46; 95% CI, 1.24 to 1.73), cancer stage II, III or IV (OR, 1.43; 95% CI, 1.13 to 1.82), and mastectomy versus breast-conserving surgery (OR, 1.18; 95% CI, 1.07 to 1.30). Moderate-quality evidence suggested an association with high physical job demands (OR, 2.11; 95%CI, 1.52 to 2.93), African-American ethnicity (OR, 1.89; 95% CI, 1.21 to 2.96), and receipt of chemotherapy (OR, 1.95; 95% CI, 1.36 to 2.79). High-quality evidence demonstrated no significant association with part-time hours, blue-collar work, tumor size, positive lymph nodes, or receipt of radiotherapy or endocrine therapy; moderate-quality evidence suggested no association with age, marital status, or axillary lymph node dissection. Conclusion Addressing high physical and psychological job demands may be important in reducing unemployment after breast cancer surgery.
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http://dx.doi.org/10.1200/JCO.2017.77.3663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804906PMC
June 2018

Preoperative pregabalin or gabapentin for acute and chronic postoperative pain among patients undergoing breast cancer surgery: A systematic review and meta-analysis of randomized controlled trials.

J Plast Reconstr Aesthet Surg 2017 Oct 9;70(10):1317-1328. Epub 2017 Jun 9.

Department of Anesthesia and Pain Medicine, Toronto General Hospital, Toronto, Canada; Department of Anesthesia, University of Toronto, Toronto, Canada.

Background And Objective: Breast cancer surgery is associated with acute and chronic pain. We sought to systematically evaluate the effects of gabapentin and pregabalin on postoperative pain among patients undergoing breast cancer surgery.

Databases And Data Treatment: We searched MEDLINE, EMBASE, CENTRAL, Web of Science, and ProQuest from the inception of each database to November 2015. We included studies enrolling adult patients undergoing breast cancer surgery who were randomly assigned to preoperative gabapentin or pregabalin versus placebo or active control and assessed acute (≤24 h) or chronic (≥2 months) pain. We conducted meta-analyses when possible and rated the quality of evidence (QoE) by using the GRADE approach.

Results: Twelve studies were eligible for review, of which eight evaluated gabapentin (n = 516) and four pregabalin (n = 209). Gabapentin reduced pain scores in the recovery room (mean difference [MD] -1.68 on a 0-10 Numeric Rating Scale (NRS), 95% CI -2.59 to -0.77; minimally important difference is 1 point; relative risk [RR] for mild pain (<4/10) 1.71, 95% CI 1.33-2.02; moderate QoE) and 24 h postoperatively (MD -0.52, 95% CI -1.02 to -0.01; RR for mild pain 1.07, 95% CI 1.00-1.13; very low QoE). Pregabalin reduced pain and morphine consumption in the recovery room (MD -6.71 mg, 95% CI -10.73 to -2.70; low QoE). No significant difference was observed in pain score at 24 h (MD -0.38, 95%, CI -0.96 to 0.21; moderate QoE). Neither drug reduced the rate of chronic postoperative pain.

Conclusions: Gabapentin and pregabalin seem to reduce opioid consumption in the recovery room. Gabapentin, but not pregabalin, reduces pain at 24 h after breast cancer surgery. Neither drug affects the development of chronic postoperative pain.

Significance: Gabapentin and pregabalin administered perioperatively in patients undergoing breast cancer surgery improve acute postoperative pain as indicated by the reduction in opioid consumption. Further data are needed on reducing chronic postoperative pain.
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http://dx.doi.org/10.1016/j.bjps.2017.05.054DOI Listing
October 2017

Technology-Enabled Remote Monitoring and Self-Management - Vision for Patient Empowerment Following Cardiac and Vascular Surgery: User Testing and Randomized Controlled Trial Protocol.

JMIR Res Protoc 2016 Aug 1;5(3):e149. Epub 2016 Aug 1.

McMaster University, Hamiltion, ON, Canada.

Background: Tens of thousands of cardiac and vascular surgeries (CaVS) are performed on seniors in Canada and the United Kingdom each year to improve survival, relieve disease symptoms, and improve health-related quality of life (HRQL). However, chronic postsurgical pain (CPSP), undetected or delayed detection of hemodynamic compromise, complications, and related poor functional status are major problems for substantial numbers of patients during the recovery process. To tackle this problem, we aim to refine and test the effectiveness of an eHealth-enabled service delivery intervention, TecHnology-Enabled remote monitoring and Self-MAnagemenT-VIsion for patient EmpoWerment following Cardiac and VasculaR surgery (THE SMArTVIEW, CoVeRed), which combines remote monitoring, education, and self-management training to optimize recovery outcomes and experience of seniors undergoing CaVS in Canada and the United Kingdom.

Objective: Our objectives are to (1) refine SMArTVIEW via high-fidelity user testing and (2) examine the effectiveness of SMArTVIEW via a randomized controlled trial (RCT).

Methods: CaVS patients and clinicians will engage in two cycles of focus groups and usability testing at each site; feedback will be elicited about expectations and experience of SMArTVIEW, in context. The data will be used to refine the SMArTVIEW eHealth delivery program. Upon transfer to the surgical ward (ie, post-intensive care unit [ICU]), 256 CaVS patients will be reassessed postoperatively and randomly allocated via an interactive Web randomization system to the intervention group or usual care. The SMArTVIEW intervention will run from surgical ward day 2 until 8 weeks following surgery. Outcome assessments will occur on postoperative day 30; at week 8; and at 3, 6, 9, and 12 months. The primary outcome is worst postop pain intensity upon movement in the previous 24 hours (Brief Pain Inventory-Short Form), averaged across the previous 14 days. Secondary outcomes include a composite of postoperative complications related to hemodynamic compromise-death, myocardial infarction, and nonfatal stroke- all-cause mortality and surgical site infections, functional status (Medical Outcomes Study Short Form-12), depressive symptoms (Geriatric Depression Scale), health service utilization-related costs (health service utilization data from the Institute for Clinical Evaluative Sciences data repository), and patient-level cost of recovery (Ambulatory Home Care Record). A linear mixed model will be used to assess the effects of the intervention on the primary outcome, with an a priori contrast of weekly average worst pain intensity upon movement to evaluate the primary endpoint of pain at 8 weeks postoperation. We will also examine the incremental cost of the intervention compared to usual care using a regression model to estimate the difference in expected health care costs between groups.

Results: Study start-up is underway and usability testing is scheduled to begin in the fall of 2016.

Conclusions: Given our experience, dedicated industry partners, and related RCT infrastructure, we are confident we can make a lasting contribution to improving the care of seniors who undergo CaVS.
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http://dx.doi.org/10.2196/resprot.5763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999307PMC
August 2016

Resting heart rate and wearable technology.

CMAJ 2016 07;188(10):755

University of Toronto, Toronto, Ont.

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http://dx.doi.org/10.1503/cmaj.1150109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938694PMC
July 2016

Predictors of persistent pain after breast cancer surgery: a systematic review and meta-analysis of observational studies.

CMAJ 2016 Oct 11;188(14):E352-E361. Epub 2016 Jul 11.

Michael G. DeGroote Institute for Pain Research and Care (Wang, Craigie, Couban, Busse), Department of Anesthesia (Wang, Busse), Department of Clinical Epidemiology and Biostatistics (Guyatt, Kaushal, Chang, Izhar, Busse), Michael G. DeGroote School of Business (Izhar), Department of Surgery (Reid) and School of Nursing (McGillion), McMaster University, Hamilton, Ont.; Chinese Cochrane Centre (Wang), West China Hospital, Sichuan University, Chengdu, China; Department of Diagnostic Radiology (Kennedy) and Department of Anesthesiology (Khan), University of Toronto, Toronto, Ont.; Department of Anesthesia and Critical Care (Romerosa), University Hospital of Toledo, Toledo, Spain; Wayne State University School of Medicine (Kwon), Detroit, Mich.; Respiratory Sciences Program (de Almeida), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; School of Medicine (Parascandalo), University College Cork, Cork, Ireland

Background: Persistent pain after breast cancer surgery affects up to 60% of patients. Early identification of those at higher risk could help inform optimal management. We conducted a systematic review and meta-analysis of observational studies to explore factors associated with persistent pain among women who have undergone surgery for breast cancer.

Methods: We searched the MEDLINE, Embase, CINAHL and PsycINFO databases from inception to Mar. 12, 2015, to identify cohort or case-control studies that explored the association between risk factors and persistent pain (lasting ≥ 2 mo) after breast cancer surgery. We pooled estimates of association using random-effects models, when possible, for all independent variables reported by more than 1 study. We reported relative measures of association as pooled odds ratios (ORs) and absolute measures of association as the absolute risk increase.

Results: Thirty studies, involving a total of 19 813 patients, reported the association of 77 independent variables with persistent pain. High-quality evidence showed increased odds of persistent pain with younger age (OR for every 10-yr decrement 1.36, 95% confidence interval [CI] 1.24-1.48), radiotherapy (OR 1.35, 95% CI 1.16-1.57), axillary lymph node dissection (OR 2.41, 95% CI 1.73-3.35) and greater acute postoperative pain (OR for every 1 cm on a 10-cm visual analogue scale 1.16, 95% CI 1.03-1.30). Moderate-quality evidence suggested an association with the presence of preoperative pain (OR 1.29, 95% CI 1.01-1.64). Given the 30% risk of pain in the absence of risk factors, the absolute risk increase corresponding to these ORs ranged from 3% (acute postoperative pain) to 21% (axillary lymph node dissection). High-quality evidence showed no association with body mass index, type of breast surgery, chemotherapy or endocrine therapy.

Interpretation: Development of persistent pain after breast cancer surgery was associated with younger age, radiotherapy, axillary lymph node dissection, greater acute postoperative pain and preoperative pain. Axillary lymph node dissection provides the only high-yield target for a modifiable risk factor to prevent the development of persistent pain after breast cancer surgery.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5047835PMC
http://dx.doi.org/10.1503/cmaj.151276DOI Listing
October 2016

In Reply: Fellowships and subspecialization in anesthesia: Are they good, bad, or both?

Can J Anaesth 2016 07 5;63(7):889-90. Epub 2016 Apr 5.

Department of Anesthesia, University of Toronto, Toronto, ON, Canada.

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http://dx.doi.org/10.1007/s12630-016-0628-8DOI Listing
July 2016

In reply: Anesthesia research training: preparing for the future of our specialty.

Can J Anaesth 2016 May 21;63(5):635. Epub 2016 Jan 21.

Duke Clinical Research Institute, Duke University, Durham, NC, USA.

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http://dx.doi.org/10.1007/s12630-016-0593-2DOI Listing
May 2016

Preoperative celecoxib in noncardiac surgery: A systematic review and meta-analysis of randomised controlled trials.

Eur J Anaesthesiol 2016 Mar;33(3):204-14

From the Department of Anaesthesia, Sunnybrook Health Sciences Centre, University of Toronto, Toronto (JSK, CM, SC), Department of Clinical Epidemiology and Biostatistics, McMaster University (JSK, PJD), Population Health Research Institute (JSK, PJD), Michael G. DeGroote Institute for Pain Research and Care (JSK), Department of Medicine, McMaster University, Hamilton (PJD), Department of Anaesthesia and Pain Management, University Health Network, University of Toronto, Toronto (HC), and McMaster University, Hamilton, Canada (AM).

Background: Postoperative pain continues to be undertreated after noncardiac surgery. Preoperative analgesic administration may enhance postoperative analgesia.

Objective: To determine the effects of preoperative administration of celecoxib in noncardiac surgery on pain and postoperative outcomes.

Design: Systematic review and meta-analysis of randomised controlled trials.

Data Sources: MEDLINE, EMBASE, CENTRAL, CINHAL Web of Sciences and ProQuest databases were searched from inception to 2014. Reference lists of retrieved articles and grey literature were searched for additional trials.

Eligibility Criteria: Articles were included if they enrolled patients of at least 18 years of age and randomised patients to receive celecoxib within 4 h of noncardiac surgery. Studies were excluded if they were animal studies, reviews/meta-analyses, did not report pain as an outcome or used epidural analgesia.

Results: Twenty trials met the eligibility criteria. Preoperative celecoxib in 14 studies (994 patients) amenable to meta-analysis demonstrated a significant decrease in 24-h parenteral morphine-equivalent consumption (mean difference -4.13 mg, 95% confidence interval -5.58 to -2.67, I = 94%). Eleven studies (755 patients) assessed postoperative pain scores at 24 h and found a significant decrease with celecoxib use [mean difference (on a 0-10 pain scale) -1.02, 95% confidence interval -1.54 to -0.50, I = 99%]. The risks of postoperative nausea and vomiting were also decreased by 44% (P = 0.01) and 38% (P = 0.03), respectively. Preoperative celecoxib did not improve patient satisfaction or length of recovery room stay, or increase intraoperative bleeding. Subgroup analyses indicated no difference between celecoxib 200 and 400 mg or between a single preoperative dose and continued postoperative dosing.

Conclusion: Results of this study are limited by significant heterogeneity and inclusion of mainly small trials. However, there appears to be a slight to modest benefit of preoperative celecoxib on reducing postoperative morphine consumption, pain, nausea and vomiting.
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http://dx.doi.org/10.1097/EJA.0000000000000346DOI Listing
March 2016

An estimation for an appropriate end time for an intraoperative intravenous lidocaine infusion in bowel surgery: a comparative meta-analysis.

J Clin Anesth 2016 Feb 3;28:95-104. Epub 2015 Sep 3.

Department of Anesthesia and Pain Medicine, University of Toronto, Toronto, Canada; Department of Anesthesia, Mount Sinai Hospital, Toronto, Canada.

Study Objective: There exists no commonly accepted regimen for an intravenous lidocaine infusion (IVLI). This study aims to determine an appropriate end time for an IVLI during bowel surgery.

Design: A systematic search for randomized controlled trials assessing IVLI for bowel surgery was conducted using Ovid MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL, Google Scholar, hand-searching references, and grey literature. Data were pooled for studies that stopped IVLI ≤60 minutes (intraoperative IVLI) after skin closure and where IVLI continued >60 minutes after surgery (postoperative continued IVLI). Quantitative analysis was done using the random-effects model.

Main Results: Seven studies (n = 362) were identified after the systematic search. Three studies (n = 160) and 4 studies (n = 202) used an intraoperative and postoperative continued IVLI, respectively. An intraoperative IVLI significantly reduced pain scores at rest for 48 hours (standardized mean difference on a 0-10 scale, -1.24; 95% confidence interval, -1.93 to -0.56) and 72 hours (standardized mean difference, -1.12; 95% confidence interval, -1.79 to -0.44) compared with postoperative IVLI (test for interaction: P < .001 and P = .003, respectively). Although intraoperative IVLI reduced 24-hour pain scores on movement, this was not statistically different than pain scores in the postoperative IVLI group (test of interaction: P = 0.68). There were no differences between intraoperative IVLI and postoperative IVLI for postoperative in-hospital nausea, vomiting, time to bowel movement, and length of hospital stay.

Conclusion: Continuing an IVLI beyond 60 minutes after surgery has no added analgesic or gastrointestinal benefit. Further research is needed to clarify an optimal IVLI regimen and end time.
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http://dx.doi.org/10.1016/j.jclinane.2015.07.007DOI Listing
February 2016

Preoperative Stress Tests--Superfluous Investigations Resulting in Excessive Treatment Delay: A Teachable Moment.

JAMA Intern Med 2015 Oct;175(10):1610-1

Mazankowski Alberta Heart Institute, Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada.

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http://dx.doi.org/10.1001/jamainternmed.2015.4420DOI Listing
October 2015

Is crowdfunding a viable source of clinical trial research funding?

Lancet 2015 Jul;386(9991):338

McMaster University, Hamilton, ON, Canada; Population Health Research Institute, Hamilton General Hospital, East Hamilton, ON, Canada.

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http://dx.doi.org/10.1016/S0140-6736(15)61407-6DOI Listing
July 2015

Nasal packing after septoplasty: cardiopulmonary impact.

JAMA Otolaryngol Head Neck Surg 2014 Mar;140(3):253-8

Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada.

Importance: Bilateral anterior nasal packing is used after septoplasty with the goals of decreasing the risk of postoperative bleeding and adhesions. However, multiple studies caution against the use of nasal packing because of the risk of cardiopulmonary complications.

Objective: To evaluate the cardiopulmonary risks associated with bilateral anterior nasal packing after septoplasty.

Evidence Review: A literature review was conducted by 2 independent reviewers using EMBASE, Ovid, Medline, PubMed, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and reference list review from January 1966 to September 2012 to identify studies assessing nasal packing after septoplasty. The studies were reviewed and assigned an Oxford level of evidence grade, Detsky score, and Methodological Index for Nonrandomized Studies (MINORS) score. Data were extracted for arterial blood gases, oxygen desaturations, oxygen saturations, and adverse outcomes. Pooled estimates for randomized studies were performed when possible.

Findings: Fourteen studies conducted between 1973 and 2011 were included: 2 randomized clinical trials (RCTs) with a total of 119 patients and 12 prospective observational studies with a total of 356 patients. Nine studies showed a significant change within 1 of the cardiopulmonary parameters investigated. However, there was no consistency in changes across both observational and randomized studies. Furthermore, pooled estimates for cardiopulmonary parameters were all nonsignificant: standard mean differences of the pooled results of the RCTs were 0.05 (95% CI, -0.31 to 0.41) for arterial pH, 0.08 (95% CI, -0.30 to 0.46) for Paco2, and -0.32 (95% CI, -1.28 to 0.63) for Pao2. There were no major cardiopulmonary complications after nasal packing.

Conclusions And Relevance: Bilateral anterior nasal packing does not seem to cause adverse cardiopulmonary changes after septoplasty.
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http://dx.doi.org/10.1001/jamaoto.2013.6335DOI Listing
March 2014