Samantha Craigie

Guideline for opioid therapy and chronic noncancer pain

Chronic noncancer pain includes any painful condition that persists for at least three months and is not associated with malignant disease.[1][1] According to seven national surveys conducted between 1994 and 2008, 15%–19% of Canadian adults live with chronic noncancer pain.[2][2] Chronic

Procedure-specific Risks of Thrombosis and Bleeding in Urological Non-cancer Surgery: Systematic Review and Meta-analysis

CONTEXT Pharmacological thromboprophylaxis involves a trade-off between a reduction in venous thromboembolism (VTE) and increased bleeding. No guidance specific for procedure and patient factors exists in urology. OBJECTIVE To inform estimates of absolute risk of symptomatic VTE and bleeding requiring reoperation in urological non-cancer surgery. EVIDENCE ACQUISITION We searched for contemporary observational studies and estimated the risk of symptomatic VTE or bleeding requiring reoperation in the 4 wk after urological surgery. We used the GRADE approach to assess the quality of the evidence. EVIDENCE SYNTHESIS The 37 eligible studies reported on 11 urological non-cancer procedures. The duration of prophylaxis varied widely both within and between procedures; for example, the median was 12.3 d (interquartile range [IQR] 3.1-55) for open recipient nephrectomy (kidney transplantation) studies and 1 d (IQR 0-1.3) for percutaneous nephrolithotomy, open prolapse surgery, and reconstructive pelvic surgery studies. Studies of open recipient nephrectomy reported the highest risks of VTE and bleeding (1.8-7.4% depending on patient characteristics and 2.4% for bleeding). The risk of VTE was low for 8/11 procedures (0.2-0.7% for patients with low/medium risk; 0.8-1.4% for high risk) and the risk of bleeding was low for 6/7 procedures (≤0.5%; no bleeding estimates for 4 procedures). The quality of the evidence supporting these estimates was low or very low. CONCLUSIONS Although inferences are limited owing to low-quality evidence, our results suggest that extended prophylaxis is warranted for some procedures (eg, kidney transplantation procedures in high-risk patients) but not others (transurethral resection of the prostate and reconstructive female pelvic surgery in low-risk patients). PATIENT SUMMARY The best evidence suggests that the benefits of blood-thinning drugs to prevent clots after surgery outweigh the risks of bleeding in some procedures (such as kidney transplantation procedures in patients at high risk of clots) but not others (such as prostate surgery in patients at low risk of clots).

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

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.

Systematic reviews of observational studies of risk of thrombosis and bleeding in urological surgery (ROTBUS): introduction and methodology

BackgroundPharmacological thromboprophylaxis in the peri-operative period involves a trade-off between reduction in venous thromboembolism (VTE) and an increase in bleeding. Baseline risks, in the absence of prophylaxis, for VTE and bleeding are known to vary widely between urological procedures, but their magnitude is highly uncertain. Systematic reviews and meta-analyses addressing baseline risks are uncommon, needed, and require methodological innovation. In this article, we describe the rationale and methods for a series of systematic reviews of the risks of symptomatic VTE and bleeding requiring reoperation in urological surgery.Methods/designWe searched MEDLINE from January 1, 2000 until April 10, 2014 for observational studies reporting on symptomatic VTE or bleeding after urological procedures. Additional studies known to experts and studies cited in relevant review articles were added. Teams of two reviewers, independently assessed articles for eligibility, evaluated risk of bias, and abstracted data. We derived best estimates of risk from the median estimates among studies rated at the lowest risk of bias. The primary endpoints were 30-day post-operative risk estimates of symptomatic VTE and bleeding requiring reoperation, stratified by procedure and patient risk factors.DiscussionThis series of systematic reviews will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding. Our work advances standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at best estimates of risk (including modeling of timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate certainty in estimates of risk. The results will be incorporated in the upcoming European Association Urology Guideline on Thromboprophylaxis.Systematic review registrationPROSPERO CRD42014010342.

Adherence to mechanical thromboprophylaxis after surgery: A systematic review and meta-analysis

BACKGROUND Many clinical practice guidelines, while recommending mechanical thromboprophylaxis after surgery, have raised concerns that discomfort may result in nonadherence. We therefore addressed adherence to mechanical thromboprophylaxis after surgery. METHODS We searched MEDLINE from January 1, 2000 to May 21, 2015 for English-language observational studies that assessed patient adherence to mechanical thromboprophylaxis after surgery. We conducted a meta-analysis to estimate average adherence rates. RESULTS We identified 8 studies (7 for compression devices, 1 for stockings) with median follow up time of 3days. The pooled estimate of adherence for compression devices was 75% (median 78%, range 40%-89%). Studies with shorter follow-up (≤3days, n=4, pooled adherence 75%) and longer follow-up (>3days, n=3, pooled adherence 75%) reported similar adherence (p=0.99). The studies varied in definitions of adherence, frequency of assessment, length of follow-up and completeness of reporting. No study followed patients after discharge. CONCLUSIONS Up to one fourth of patients are nonadherent to mechanical thromboprophylaxis while hospitalized. Clinicians considering the relative merits of mechanical versus pharmacologic prophylaxis should address the issue of adherence. Strategies to improve adherence merit investigation.

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

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.

Predictors of in-hospital mortality among patients with pulmonary tuberculosis: a protocol of systematic review and meta-analysis of observational studies

Introduction Tuberculosis (TB) continues to be a major public health issue worldwide, with 1.4 million deaths occurring annually. There is uncertainty regarding which factors are associated with in-hospital mortality among patients with pulmonary TB. This knowledge gap complicates efforts to identify and improve the management of those individuals with TB at greatest risk of death. The aim of this systematic review and meta-analysis is to establish predictors of in-hospital mortality among patients with pulmonary TB to enhance the evidence base for public policy. Methods and analysis Studies will be identified by a MEDLINE, EMBASE and Global Health search. Eligible studies will be cohort and case–control studies that report predictors or risk factors for in-hospital mortality among patients with pulmonary TB and an adjusted analysis to explore factors associated with in-hospital mortality. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to summarise the findings of some reported predictors. Teams of 2 reviewers will screen the titles and abstracts of all citations identified in our search, independently and in duplicate, extract data, and assess scientific quality using standardised forms quality assessment and tools tailored. We will pool all factors that were assessed for an association with mortality that were reported by >1 study, and presented the OR and the associated 95% CI. When studies provided the measure of association as a relative risk (RR), we will convert the RR to OR using the formula provided by Wang. For binary data, we will calculate a pooled OR, with an associated 95% CI. Ethics and dissemination This study is based on published data, and therefore ethical approval is not a requirement. Findings will be disseminated through publication in peer-reviewed journals and conference presentations at relevant conferences. Trial registration number CRD42015025755.

Hormone Replacement Therapy and Opioid Tapering for Opioid-Induced Hypogonadism Among Patients with Chronic Noncancer Pain: A Systematic Review

Objective To systematically review evidence addressing the efficacy of testosterone replacement therapy (TRT) and opioid tapering for opioid-induced hypogonadism among patients with chronic noncancer pain. Study Design Systematic review of randomized controlled trials (RCTs) and observational studies. Methods We searched MEDLINE, CINAHL, AMED, CENTRAL, CINAHL, DARE, EMBASE, and PsycINFO through August 2017. Eligible studies enrolled ≥10 patients with chronic noncancer pain and opioid-induced hypogonadism and reported the effect of TRT or opioid tapering on a patient-important outcome collected ≥14 days after treatment. Pairs of reviewers independently screened for eligible studies, assessed risk of bias, and extracted data. We used the GRADE approach to rate quality of evidence. Results Of 666 abstracts reviewed, five studies including one RCT (N = 84) and four observational studies (N = 157) were eligible. No studies explored the effect of opioid tapering for opioid-induced hypogonadism. Very low-quality evidence found that TRT was associated with improvements in pain (median reduction of 2 points on the 11-point numerical rating scale for pain; 95% confidence interval [CI] = -1.4 to -2.6; minimally important difference [MID] = 2 points), and emotional functioning (mean increase of 9 points on the 100-point SF-36 Mental Component Summary score; 95% CI = 4.40 to 13.60; MID = 5 points). Low-quality evidence suggested that TRT had no effect on sleep quality, sexual function, physical functioning, role functioning, or social functioning; very low-quality evidence suggested no association with depressive symptoms. Conclusions Low-quality to very low-quality evidence suggests that TRT may improve pain and emotional functioning, but not other outcomes, in chronic noncancer pain patients with opioid-induced hypogonadism.

Patient Values and Preferences Regarding Opioids for Chronic Noncancer Pain: A Systematic Review

Objective Shared-care decision-making between patients and clinicians involves making trade-offs between desirable and undesirable consequences of management strategies. Although patient values and preferences should provide the basis for these trade-offs, few guidelines consider the relevant evidence when formulating recommendations. To inform a guideline for use of opioids in patients with chronic noncancer pain, we conducted a systematic review of studies exploring values and preferences of affected patients toward opioid therapy. Methods We searched MEDLINE, CINAHL, EMBASE, and PsycINFO from the inception of each database through October 2016. We included studies examining patient preferences for alternative approaches to managing chronic noncancer pain and studies that assessed how opioid-using chronic noncancer pain patients value alternative health states and their experiences with treatment. We compiled structured summaries of the results. Results Pain relief and nausea and vomiting were ranked as highly significant outcomes across studies. When considered, the adverse effect of personality changes was rated as equally important. Constipation was assessed in most studies and was an important outcome, secondary to pain relief and nausea and vomiting. Of only two studies that evaluated addiction, both found it less important to patients than pain relief. No studies examined opioid overdose, death, or diversion. Conclusion Our findings suggest that the adverse effects of opioids, especially nausea and vomiting, may reduce or eliminate any net benefit of opioid therapy unless pain relief is significant (>2 points on a 10-point scale). Further research should investigate patient values and preferences regarding opioid overdose, diversion, and death.

A systematic survey on reporting and methods for handling missing participant data for continuous outcomes in randomized controlled trials

OBJECTIVE To assess analytic approaches randomized controlled trial (RCT) authors use to address missing participant data (MPD) for patient-important continuous outcomes. STUDY DESIGN AND SETTING We conducted a systematic survey of RCTs published in 2014 in the core clinical journals that reported at least one patient-important outcome analyzed as a continuous variable. RESULTS Among 200 studies, 187 (93.5%) trials explicitly reported whether MPD occurred. In the 163 (81.5%) trials that reported the occurrence of MPD, the median and interquartile ranges of the percentage of participants with MPD were 11.4% (2.5%-22.6%).Among the 147 trials in which authors made clear their analytical approach to MPD, the approaches chosen included available data only (109, 67%); mixed-effect models (10, 6.1%); multiple imputation (9, 4.5%); and last observation carried forward (9, 4.5). Of the 163 studies reporting MPD, 16 (9.8%) conducted sensitivity analyses examining the impact of the MPD and (18, 11.1%) discussed the risk of bias associated with MPD. CONCLUSION RCTs reporting continuous outcomes typically have over 10% of participant data missing. Most RCTs failed to use optimal analytic methods, and very few conducted sensitivity analyses addressing the possible impact of MPD or commented on how MPD might influence risk of bias.Yuqing Zhang, Ivan D. Flórez, Luis E. Colunga Lozano, Fazila Abu Bakar Aloweni, Sean Alexander Kennedy, Aihua Li, Samantha Craigie, Shiyuan Zhang, Arnav Agarwal, Luciane C. Lopes, Tahira Devji, Wojtek Wiercioch, John J. Riva, Mengxiao Wang, Xuejing Jin, Yutong Fei, Paul Alexander, Gian Paolo Morgano, Yuan Zhang, Alonso Carrasco-Labra, Lara A. Kahale, Elie A. Akl, Holger J. Schünemann, Lehana Thabane, Gordon Guyatt