International Delphi Study on Wound Closure and Incision Management in Joint Arthroplasty Part 2: Total Hip Arthroplasty.

BACKGROUND: This modified Delphi study aimed to develop a consensus on optimal wound closure and incision management strategies for total hip arthroplasty (THA). Given the critical nature of wound care and incision management in influencing patient outcomes, this study sought to synthesize evidence-based best practices for wound care in THA procedures. METHODS: An international panel of 20 orthopedic surgeons from Europe, Canada, and the United States evaluated a targeted literature review of 18 statements (14 specific to THA and 4 related to both THA and total knee arthroplasty). There were 3 rounds of anonymous voting per topic using a modified 5-point Likert scale with a predetermined consensus threshold of ≥ 75% agreement necessary for a statement to be accepted. RESULTS: After 3 rounds of voting, consensus was achieved for all 18 statements. Notable recommendations for THA wound management included (1) the use of barbed sutures over non-barbed sutures (shorter closing times and overall cost savings); (2) the use of subcuticular sutures over skin staples (lower risk of superficial infections and higher patient preferences, but longer closing times); (3) the use of mesh-adhesives over silver-impregnated dressings (lower rate of wound complications); (4) for at-risk patients, the use of negative pressure wound therapy over other dressings (lower wound complications and reoperations, as well as fewer dressing changes); and (5) the use of triclosan-coated sutures (lower risk of surgical site infection) over standard sutures. CONCLUSIONS: Through a structured modified Delphi approach, a panel of 20 orthopedic surgeons reached consensus on all 18 statements pertaining to wound closure and incision management in THA. This study provides a foundational framework for establishing evidence-based best practices, aiming to reduce variability in patient outcomes and to enhance the overall quality of care in THA procedures.

International Delphi Study on Wound Closure and Dressing Management in Joint Arthroplasty: Part 1: Total Knee Arthroplasty.

BACKGROUND: The purpose of this modified Delphi study was to obtain consensus on wound closure and dressing management in total knee arthroplasty (TKA). METHODS: The Delphi panel included 20 orthopaedic surgeons from Europe and North America. There were 26 statements identified using a targeted literature review. Consensus was developed for the statements with up to three rounds of anonymous voting per topic. Panelists ranked their agreement with each statement on a five-point Likert scale. An a priori threshold of ≥ 75% was required for consensus. RESULTS: All 26 statements achieved consensus after three rounds of anonymous voting. Wound closure-related interventions that were recommended for use in TKA included: 1) closing in semi-flexion versus extension (superior range of motion); 2) using aspirin for venous thromboembolism prophylaxis over other agents (reduces wound complications); 3) barbed sutures over non-barbed sutures (lower wound complications, better cosmetic appearances, shorter closing times, and overall cost savings); 4) mesh-adhesives over other skin closure methods (lower wound complications, higher patient satisfaction scores, lower rates of readmission); 5) silver-impregnated dressings over standard dressings (lower wound complications, decreased infections, fewer dressing changes); 6) in high-risk patients, negative pressure wound therapy over other dressings (lower wound complications, decreased reoperations, fewer dressing changes); and 7) using triclosan-coated over non-antimicrobial-coated sutures (lower risks of surgical site infection). CONCLUSIONS: Using a modified Delphi approach, the panel achieved consensus on 26 statements pertaining to wound closure and dressing management in TKA. This study forms the basis for identifying critical evidence supported by clinical practice for wound management to help reduce variability, advance standardization, and ultimately improve outcomes during TKA. The results presented here can serve as the foundation for knowledge, education, and improved clinical outcomes for surgeons performing TKAs.

A Systematic Literature Review of Health-Related Quality of Life Outcomes and Associated Utility Values in Relapsed and/or Refractory Large B Cell Lymphoma.

BACKGROUND: In this ever-expanding treatment landscape, there is a lack of consolidated health-related quality of life (HRQOL) outcomes and utility reports in relapsed or refractory (R/R) large B cell lymphoma (LBCL) to inform health care policy and decision-maker assessments for both old and new products. These assessments can have a direct effect on what treatment options are available to patients and physicians. OBJECTIVE: A systematic literature review (SLR) was performed to understand the HRQOL evidence for treatments in R/R LBCL and identify associated health utility values. METHODS: The SLR searched and screened literature published from 1 January 2003 to 2 May 2022. Studies were screened based on Population, Intervention, Comparator, Outcome, Study design criteria established a priori and were assessed by two independent reviewers; quality assessments of the evidence were performed in accordance with health technology assessment recommendations from the National Institute for Health and Care Excellence. Several types of therapies were included, such as chimeric antigen receptor (CAR) T cell products (lisocabtagene maraleucel, axicabtagene ciloleucel, tisagenlecleucel), novel therapies (selinexor, nivolumab, polatuzumab vedotin, and bendamustine), salvage therapies, and rituximab. RESULTS: The review identified 33 unique studies reporting HRQOL, including 15 economic studies that reported health state utility values, 9 clinical trials, 7 health technology assessment reports, and 1 each of a vignette-based study and a point-in-time survey. Improvements in general and/or lymphoma-specific HRQOL measures were observed with CAR T cell therapy in both the second-line and third-line or later settings. On-treatment utility values for CAR T cell therapies ranged from 0.50 to 0.74. Values for remission/progression-free survival (0.70-0.90) and for disease progression (0.39-0.59) were similar across studies. For novel therapies, utility values were 0.83 for progression-free survival and ranged from 0.39 to 0.71 for disease progression. On-treatment utility values for salvage chemotherapy ranged from 0.63 to 0.67. CONCLUSIONS: Overall, the evidence synthesized in this SLR provides a comprehensive understanding of the HRQOL evidence in R/R LBCL. This article identified several sources for utility values in the published literature showing variation in the HRQOL outcomes for patients across a variety of therapeutics. Treatment of R/R LBCL with CAR T cell therapies was associated with improvement in health utility values. Mixed results were found for novel therapies and salvage therapies. More data are needed as new therapies are used in this patient population to inform treatment decision-making.

Systematic Reviews and Meta-analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery.

OBJECTIVE: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. BACKGROUND: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. METHODS: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. RESULTS: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. CONCLUSIONS: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.

Unmet Need in People with Psoriasis and Skin of Color in Canada and the United States.

The experience of dermatological conditions such as psoriasis is different for people with skin of color (SoC) than for white individuals. The objective of this literature review was to understand challenges and unmet needs associated with access to care, diagnosis, and treatment of psoriasis among people with SoC in Canada and the United States. The review focused on studies published in the last 5 years. After screening 919 unique records, 26 studies were included. Importantly, lack of culturally competent care was identified as a key unmet need for psoriasis among people with SoC. In addition, cost of care and cultural views of psoriasis may influence decisions to seek care among people with SoC. Baseline patient characteristics in psoriasis studies and the prevalence/incidence of psoriasis vary across racial/ethnic groups, which may reflect differences in the rate and/or timing of diagnosis. The presentation of psoriasis differs across racial/ethnic groups, which may contribute to challenges in proper and timely diagnosis. Compared with white patients with psoriasis, individuals with SoC may be less familiar with and have different rates of treatment with biologic therapies for psoriasis, are more likely to be hospitalized for psoriasis, and their access to physicians may differ. Further, people with SoC are underrepresented in clinical trials of psoriasis therapies. Overall, the results of this literature review suggest that people with psoriasis and SoC face unique challenges in their disease experience. It is essential that clinicians and other stakeholders recognize and address these disparities to ensure equitable care.

Skin conditions such as psoriasis are experienced differently by people with skin of color (SoC) compared with white individuals. Although it is known that psoriasis can vary in how it appears between these groups, other factors that affect care for patients with SoC are not well understood. For this review, we focused on challenges associated with accessing healthcare, receiving a diagnosis, and receiving treatment for psoriasis among people with SoC. A search of the academic literature identified several such challenges for people with SoC in Canada and the United States. A major challenge for people with psoriasis and SoC is having access to care that is compatible with their cultural values and practices. The cost of healthcare and cultural views of psoriasis may influence whether individuals with SoC decide to seek care. People with SoC are more likely to be hospitalized for psoriasis, and their access to physicians may differ compared with white individuals. In addition, differences in how psoriasis appears across racial/ethnic groups may hinder diagnosis. Psoriasis treatments that patients with SoC receive may differ from those that white individuals receive, and people with SoC may be less likely to be properly represented in clinical trials evaluating psoriasis therapies. Taken together, the findings of our review indicate that people with psoriasis and SoC face unique challenges in how they receive medical care for their condition. It is essential that clinicians and other stakeholders in the healthcare system recognize these challenges and work to address them.

Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS): introduction and methodology.

BACKGROUND: Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. METHODS: We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. DISCUSSION: This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021234119.

Medical cannabis or cannabinoids for chronic non-cancer and cancer related pain: a systematic review and meta-analysis of randomised clinical trials.

OBJECTIVE: To determine the benefits and harms of medical cannabis and cannabinoids for chronic pain. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, AMED, PsycInfo, CENTRAL, CINAHL, PubMed, Web of Science, Cannabis-Med, Epistemonikos, and trial registries up to January 2021. STUDY SELECTION: Randomised clinical trials of medical cannabis or cannabinoids versus any non-cannabis control for chronic pain at ≥1 month follow-up. DATA EXTRACTION AND SYNTHESIS: Paired reviewers independently assessed risk of bias and extracted data. We performed random-effects models meta-analyses and used GRADE to assess the certainty of evidence. RESULTS: A total of 32 trials with 5174 adult patients were included, 29 of which compared medical cannabis or cannabinoids with placebo. Medical cannabis was administered orally (n=30) or topically (n=2). Clinical populations included chronic non-cancer pain (n=28) and cancer related pain (n=4). Length of follow-up ranged from 1 to 5.5 months. Compared with placebo, non-inhaled medical cannabis probably results in a small increase in the proportion of patients experiencing at least the minimally important difference (MID) of 1 cm (on a 10 cm visual analogue scale (VAS)) in pain relief (modelled risk difference (RD) of 10% (95% confidence interval 5% to 15%), based on a weighted mean difference (WMD) of -0.50 cm (95% CI -0.75 to -0.25 cm, moderate certainty)). Medical cannabis taken orally results in a very small improvement in physical functioning (4% modelled RD (0.1% to 8%) for achieving at least the MID of 10 points on the 100-point SF-36 physical functioning scale, WMD of 1.67 points (0.03 to 3.31, high certainty)), and a small improvement in sleep quality (6% modelled RD (2% to 9%) for achieving at least the MID of 1 cm on a 10 cm VAS, WMD of -0.35 cm (-0.55 to -0.14 cm, high certainty)). Medical cannabis taken orally does not improve emotional, role, or social functioning (high certainty). Moderate certainty evidence shows that medical cannabis taken orally probably results in a small increased risk of transient cognitive impairment (RD 2% (0.1% to 6%)), vomiting (RD 3% (0.4% to 6%)), drowsiness (RD 5% (2% to 8%)), impaired attention (RD 3% (1% to 8%)), and nausea (RD 5% (2% to 8%)), but not diarrhoea; while high certainty evidence shows greater increased risk of dizziness (RD 9% (5% to 14%)) for trials with <3 months follow-up versus RD 28% (18% to 43%) for trials with ≥3 months follow-up; interaction test P=0.003; moderate credibility of subgroup effect). CONCLUSIONS: Moderate to high certainty evidence shows that non-inhaled medical cannabis or cannabinoids results in a small to very small improvement in pain relief, physical functioning, and sleep quality among patients with chronic pain, along with several transient adverse side effects, compared with placebo. The accompanying BMJ Rapid Recommendation provides contextualised guidance based on this body of evidence. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/3pwn2.

An International Survey on the Use of Thromboprophylaxis in Urological Surgery.

BACKGROUND: The use of perioperative thromboprophylaxis in urological surgery is common but not standardized. OBJECTIVE: To characterize international practice variation in thromboprophylaxis use in urological surgery. DESIGN, SETTING, AND PARTICIPANTS: We conducted a scenario-based survey addressing the use of mechanical and pharmacological thromboprophylaxis in urological cancer procedures (radical cystectomy [RC], radical prostatectomy [RP], and radical nephrectomy [RN]) among practicing urologists in Canada, Finland, and Japan. The survey presented patient profiles reflecting a spectrum of risk for venous thromboembolism; the respondents described their clinical practice. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The proportion of respondents who routinely used (1) mechanical, (2) pharmacological, and (3) extended pharmacological prophylaxis was stratified by procedure. A logistic regression identified characteristics associated with thromboprophylaxis use. RESULTS AND LIMITATIONS: Of 1051 urologists contacted, 570 (54%) participated in the survey. Japanese urologists were less likely to prescribe pharmacological prophylaxis than Canadian or Finnish urologists (p < 0.001 for all procedures). Canadian and Finnish urologists exhibited large variation for extended pharmacological prophylaxis for RP and RN. Finnish urologists were most likely to prescribe extended prophylaxis versus Canadian and Japanese urologists (RC 98%, 84%, and 26%; Open RP 25%, 8%, and 3%; robotic RP 11%, 9%, and 0%; and RN 43%, 7%, and 1%, respectively; p < 0.001 for each procedure). Less variation was found regarding the prescription of mechanical prophylaxis, which was most commonly used until ambulation or discharge. The length of hospital stay was longer in Japan and may bias estimates of extended prophylaxis in Japan. CONCLUSIONS: We found large variation in clinical practice regarding pharmacological thromboprophylaxis within and between countries. Knowledge translation of evidence-based guidelines may reduce problematic international variation in practice. PATIENT SUMMARY: Use of medications to decrease blood clots after urological cancer surgery differs within and between countries. Closer adherence to urology guidelines addressing the prevention of blood clots may decrease this variation and improve patient outcomes.

Management of Acute Pain From Non-Low Back, Musculoskeletal Injuries : A Systematic Review and Network Meta-analysis of Randomized Trials.

BACKGROUND: Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries. PURPOSE: To assess the comparative effectiveness of outpatient treatments for acute pain from non-low back, musculoskeletal injuries by performing a network meta-analysis of randomized clinical trials (RCTs). DATA SOURCES: MEDLINE, EMBASE, CINAHL, PEDro (Physiotherapy Evidence Database), and Cochrane Central Register of Controlled Trials to 2 January 2020. STUDY SELECTION: Pairs of reviewers independently identified interventional RCTs that enrolled patients presenting with pain of up to 4 weeks' duration from non-low back, musculoskeletal injuries. DATA EXTRACTION: Pairs of reviewers independently extracted data. Certainty of evidence was evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. DATA SYNTHESIS: The 207 eligible studies included 32 959 participants and evaluated 45 therapies. Ninety-nine trials (48%) enrolled populations with diverse musculoskeletal injuries, 59 (29%) included patients with sprains, 13 (6%) with whiplash, and 11 (5%) with muscle strains; the remaining trials included various injuries ranging from nonsurgical fractures to contusions. Topical nonsteroidal anti-inflammatory agents (NSAIDs) proved to have the greatest net benefit, followed by oral NSAIDs and acetaminophen with or without diclofenac. Effects of these agents on pain were modest (around 1 cm on a 10-cm visual analogue scale, approximating the minimal important difference). Regarding opioids, compared with placebo, acetaminophen plus an opioid improved intermediate pain (1 to 7 days) but not immediate pain (≤2 hours), tramadol was ineffective, and opioids increased the risk for gastrointestinal and neurologic harms (all moderate-certainty evidence). LIMITATIONS: Only English-language studies were included. The number of head-to-head comparisons was limited. CONCLUSION: Topical NSAIDs, followed by oral NSAIDs and acetaminophen with or without diclofenac, showed the most convincing and attractive benefit-harm ratio for patients with acute pain from non-low back, musculoskeletal injuries. No opioid achieved benefit greater than that of NSAIDs, and opioids caused the most harms. PRIMARY FUNDING SOURCE: National Safety Council. (PROSPERO: CRD42018094412).

Decision Aids for Prostate Cancer Screening Choice: A Systematic Review and Meta-analysis.

IMPORTANCE: US guidelines recommend that physicians engage in shared decision-making with men considering prostate cancer screening. OBJECTIVE: To estimate the association of decision aids with decisional outcomes in prostate cancer screening. DATA SOURCES: MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL were searched from inception through June 19, 2018. STUDY SELECTION: Randomized trials comparing decision aids for prostate cancer screening with usual care. DATA EXTRACTION AND SYNTHESIS: Independent duplicate assessment of eligibility and risk of bias, rating of quality of the decision aids, random-effects meta-analysis, and Grading of Recommendations, Assessment, Development and Evaluations rating of the quality of evidence. MAIN OUTCOMES AND MEASURES: Knowledge, decisional conflict, screening discussion, and screening choice. RESULTS: Of 19 eligible trials (12 781 men), 9 adequately concealed allocation and 8 blinded outcome assessment. Of 12 decision aids with available information, only 4 reported the likelihood of a true-negative test result, and 3 presented the likelihood of false-negative test results or the next step if the screening test result was negative. Decision aids are possibly associated with improvement in knowledge (risk ratio, 1.38; 95% CI, 1.09-1.73; I2 = 67%; risk difference, 12.1; low quality), are probably associated with a small decrease in decisional conflict (mean difference on a 100-point scale, -4.19; 95% CI, -7.06 to -1.33; I2 = 75%; moderate quality), and are possibly not associated with whether physicians and patients discuss prostate cancer screening (risk ratio, 1.12; 95% CI, 0.90-1.39; I2 = 60%; low quality) or with men's decision to undergo prostate cancer screening (risk ratio, 0.95; 95% CI, 0.88-1.03; I2 = 36%; low quality). CONCLUSIONS AND RELEVANCE: The results of this study provide moderate-quality evidence that decision aids compared with usual care are associated with a small decrease in decisional conflict and low-quality evidence that they are associated with an increase in knowledge but not with whether physicians and patients discussed prostate cancer screening or with screening choice. Results suggest that further progress in facilitating effective shared decision-making may require decision aids that not only provide education to patients but are specifically targeted to promote shared decision-making in the patient-physician encounter.

Management of acute musculoskeletal pain (excluding low back pain): protocol for a systematic review and network meta-analysis of randomised trials.

INTRODUCTION: Acute, non-low back-related musculoskeletal pain is common and associated with significant socioeconomic costs. No review has evaluated all interventional studies for acute musculoskeletal pain, which limits attempts to make inferences regarding the relative effectiveness of treatments. METHODS AND ANALYSIS: We will conduct a systematic review of all randomised controlled trials evaluating therapies for acute musculoskeletal pain (excluding low back pain). We will identify eligible, English-language, trials by a systematic search of the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Medline, Physiotherapy Evidence Database (PEDro) and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to February 2018. Eligible trials will: (1) enrol patients presenting with acute, non-low back-related musculoskeletal pain (duration of pain ≤4 weeks), and (2) randomise patients to alternative interventions or an intervention and a placebo/sham arm. Fractures will be considered ineligible, unless they are non-surgical and therapy is directed at pain relief. Pairs of reviewers will, independently and in duplicate, screen titles and abstracts of identified citations, review the full texts of potentially eligible trials and extract information from eligible trials. We will use a modified Cochrane instrument to evaluate risk of bias. Disagreements will be resolved through discussion to achieve consensus. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to evaluate the quality of evidence supporting treatment effects. When possible, we will conduct: (1) in direct comparisons, a random-effect meta-analysis to establish the effectiveness of therapeutic interventions on patient-important outcomes; and (2) multiple treatment comparison meta-analysis to assess the relative effects of treatments. We will use a priori hypotheses to explain heterogeneity between studies. We will use STATA V.14.2 for all analyses. ETHICS AND DISSEMINATION: No research ethics approval is required for this systematic review, as no confidential patient data will be used. The results of this systematic review will be disseminated through publication in a peer-reviewed journal, conference presentations and will inform a clinical practice guideline. PROSPERO REGISTRATION NUMBER: CRD42018094412.

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.

Opioids for Chronic Noncancer Pain: A Systematic Review and Meta-analysis.

Importance: Harms and benefits of opioids for chronic noncancer pain remain unclear. Objective: To systematically review randomized clinical trials (RCTs) of opioids for chronic noncancer pain. Data Sources and Study Selection: The databases of CENTRAL, CINAHL, EMBASE, MEDLINE, AMED, and PsycINFO were searched from inception to April 2018 for RCTs of opioids for chronic noncancer pain vs any nonopioid control. Data Extraction and Synthesis: Paired reviewers independently extracted data. The analyses used random-effects models and the Grading of Recommendations Assessment, Development and Evaluation to rate the quality of the evidence. Main Outcomes and Measures: The primary outcomes were pain intensity (score range, 0-10 cm on a visual analog scale for pain; lower is better and the minimally important difference [MID] is 1 cm), physical functioning (score range, 0-100 points on the 36-item Short Form physical component score [SF-36 PCS]; higher is better and the MID is 5 points), and incidence of vomiting. Results: Ninety-six RCTs including 26 169 participants (61% female; median age, 58 years [interquartile range, 51-61 years]) were included. Of the included studies, there were 25 trials of neuropathic pain, 32 trials of nociceptive pain, 33 trials of central sensitization (pain present in the absence of tissue damage), and 6 trials of mixed types of pain. Compared with placebo, opioid use was associated with reduced pain (weighted mean difference [WMD], -0.69 cm [95% CI, -0.82 to -0.56 cm] on a 10-cm visual analog scale for pain; modeled risk difference for achieving the MID, 11.9% [95% CI, 9.7% to 14.1%]), improved physical functioning (WMD, 2.04 points [95% CI, 1.41 to 2.68 points] on the 100-point SF-36 PCS; modeled risk difference for achieving the MID, 8.5% [95% CI, 5.9% to 11.2%]), and increased vomiting (5.9% with opioids vs 2.3% with placebo for trials that excluded patients with adverse events during a run-in period). Low- to moderate-quality evidence suggested similar associations of opioids with improvements in pain and physical functioning compared with nonsteroidal anti-inflammatory drugs (pain: WMD, -0.60 cm [95% CI, -1.54 to 0.34 cm]; physical functioning: WMD, -0.90 points [95% CI, -2.69 to 0.89 points]), tricyclic antidepressants (pain: WMD, -0.13 cm [95% CI, -0.99 to 0.74 cm]; physical functioning: WMD, -5.31 points [95% CI, -13.77 to 3.14 points]), and anticonvulsants (pain: WMD, -0.90 cm [95% CI, -1.65 to -0.14 cm]; physical functioning: WMD, 0.45 points [95% CI, -5.77 to 6.66 points]). Conclusions and Relevance: In this meta-analysis of RCTs of patients with chronic noncancer pain, evidence from high-quality studies showed that opioid use was associated with statistically significant but small improvements in pain and physical functioning, and increased risk of vomiting compared with placebo. Comparisons of opioids with nonopioid alternatives suggested that the benefit for pain and functioning may be similar, although the evidence was from studies of only low to moderate quality.

Certainty ranges facilitated explicit and transparent judgments regarding evidence credibility.

OBJECTIVES: The Grading of Recommendations Assessment, Development and Evaluation approach to rating certainty of evidence includes five domains of reasons for rating down certainty. Only one of these, precision, is easily amenable-through the confidence interval-to quantitation. The other four (risk of bias, inconsistency, indirectness, and publication bias) are not. Nevertheless, conceptually, one could consider a quantified "certainty range" within which the true effect lies. The certainty range would be at least as wide as the confidence interval and would expand with each additional reason for uncertainty. STUDY DESIGN AND SETTING: We have applied this concept to rating the certainty of evidence in the baseline risk of venous thromboembolism (VTE) and bleeding in patients undergoing urological surgery. We considered rating up moderate or low quality evidence when the net benefit of VTE prophylaxis was unequivocally positive, that is, when the smallest plausible value of VTE reduction was greater than the largest plausible value of increased bleeding. To establish whether the net benefit was unequivocally positive, we expanded the range of plausible values by 20% for each of the four nonquantitative domains in which there were serious limitations. RESULTS: We present how we applied these methods to examples of open radical cystectomy and laparoscopic partial nephrectomy. In high-VTE risk laparoscopic partial nephrectomy patients and high- and medium-VTE risk open radical cystectomy patients, results proved robust to expanded certainty intervals, justifying rating up quality of evidence. In low-risk patients, the results were not robust, and rating up was therefore not appropriate. CONCLUSION: This work represents the first empirical application in a decision-making context of the previously suggested concept of certainty ranges and should stimulate further exploration of the associated theoretical and practical issues.

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.

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.

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

CONTEXT: Pharmacological thromboprophylaxis involves balancing a lower risk of venous thromboembolism (VTE) against a higher risk of bleeding, a trade-off that critically depends on the risks of VTE and bleeding in the absence of prophylaxis (baseline risk). OBJECTIVE: To provide estimates of the baseline risk of symptomatic VTE and bleeding requiring reoperation in urological cancer surgery. EVIDENCE ACQUISITION: We identified contemporary observational studies reporting symptomatic VTE or bleeding after urological procedures. We used studies with the lowest risk of bias and accounted for use of thromboprophylaxis and length of follow-up to derive best estimates of the baseline risks within 4 wk of surgery. We used the GRADE approach to assess the quality of the evidence. EVIDENCE SYNTHESIS: We included 71 studies reporting on 14 urological cancer procedures. The quality of the evidence was generally moderate for prostatectomy and cystectomy, and low or very low for other procedures. The duration of thromboprophylaxis was highly variable. The risk of VTE in cystectomies was high (2.6-11.6% across risk groups) whereas the risk of bleeding was low (0.3%). The risk of VTE in prostatectomies varied by procedure, from 0.2-0.9% in robotic prostatectomy without pelvic lymph node dissection (PLND) to 3.9-15.7% in open prostatectomy with extended PLND. The risk of bleeding was 0.1-1.0%. The risk of VTE following renal procedures was 0.7-2.9% for low-risk patients and 2.6-11.6% for high-risk patients; the risk of bleeding was 0.1-2.0%. CONCLUSIONS: Extended thromboprophylaxis is warranted in some procedures (eg, open and robotic cystectomy) but not others (eg, robotic prostatectomy without PLND in low-risk patients). For "close call" procedures, decisions will depend on values and preferences with regard to VTE and bleeding. PATIENT SUMMARY: Clinicians often give blood thinners to patients to prevent blood clots after surgery for urological cancer. Unfortunately, blood thinners also increase bleeding. This study provides information on the risk of clots and bleeding that is crucial in deciding for or against giving blood thinners.

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).

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.