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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. 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. 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. 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.

Objective To investigate the risk of pancreatitis associated with the use of incretin-based treatments in patients with type 2 diabetes mellitus.Design Systematic review and meta-analysis.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov.Eligibility criteria Randomised and non-randomised controlled clinical trials, prospective or retrospective cohort studies, and case-control studies of treatment with glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors in adults with type 2 diabetes mellitus compared with placebo, lifestyle modification, or active anti-diabetic drugs.Data collection and analysis Pairs of trained reviewers independently screened for eligible studies, assessed risk of bias, and extracted data. A modified Cochrane tool for randomised controlled trials and a modified version of the Newcastle-Ottawa scale for observational studies were used to assess bias. We pooled data from randomised controlled trials using Peto odds ratios, and conducted four prespecified subgroup analyses and a post hoc subgroup analysis. Because of variation in outcome measures and forms of data, we describe the results of observational studies without a pooled analysis.Results 60 studies (n=353 639), consisting of 55 randomised controlled trials (n=33 350) and five observational studies (three retrospective cohort studies, and two case-control studies; n=320 289) were included. Pooled estimates of 55 randomised controlled trials (at low or moderate risk of bias involving 37 pancreatitis events, raw event rate 0.11%) did not suggest an increased risk of pancreatitis with incretins versus control (odds ratio 1.11, 95% confidence interval 0.57 to 2.17). Estimates by type of incretin suggested similar results (1.05 (0.37 to 2.94) for GLP-1 agonists v control; 1.06 (0.46 to 2.45) for DPP-4 inhibitors v control). Analyses according to the type of control, mode, duration of treatment, and individual incretin agents suggested no differential effect by subgroups, and sensitivity analyses by alternative statistical modelling and effect measures did not show important differences in effect estimates. Three retrospective cohort studies (moderate to high risk of bias, involving 1466 pancreatitis events, raw event rate 0.47%) also did not suggest an increased risk of pancreatitis associated with either exenatide (adjusted odds ratios 0.93 (0.63 to 1.36) in one study and 0.9 (0.6 to 1.5) in another) or sitagliptin (adjusted hazard ratio 1.0, 0.7 to 1.3); a case-control study at moderate risk of bias (1003 cases, 4012 controls) also suggested no significant association (adjusted odds ratio 0.98, 0.69 to 1.38). Another case-control study (1269 cases, 1269 controls) at moderate risk of bias, however, suggested that the use of either exenatide or sitagliptin was associated with significantly increased odds of acute pancreatitis (use within two years v no use, adjusted odds ratio 2.07, 1.36 to 3.13).Conclusions The available evidence suggests that the incidence of pancreatitis among patients using incretins is low and that the drugs do not increase the risk of pancreatitis. Current evidence, however, is not definitive, and more carefully designed and conducted observational studies are warranted to definitively establish the extent, if any, of increased risk.

Cognitive behavioural therapy (CBT) has been shown to be effective for several psychiatric and somatic conditions; however, most randomized controlled trials (RCTs) have administered treatment in person and whether remote delivery is similarly effective remains uncertain. We sought to compare the effectiveness of therapist-guided remote CBT and in-person CBT. We systematically searched MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to July 4, 2023, for RCTs that enrolled adults (aged ≥ 18 yr) presenting with any clinical condition and that randomized participants to either therapist-guided remote CBT (e.g., teleconference, videoconference) or in-person CBT. Paired reviewers assessed risk of bias and extracted data independently and in duplicate. We performed random-effects model meta-analyses to pool patient-important primary outcomes across eligible RCTs as standardized mean differences (SMDs). We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance to assess the certainty of evidence and used the Instrument to Assess the Credibility of Effect Modification Analyses (ICEMAN) to rate the credibility of subgroup effects. We included 54 RCTs that enrolled a total of 5463 patients. Seventeen studies focused on treatment of anxiety and related disorders, 14 on depressive symptoms, 7 on insomnia, 6 on chronic pain or fatigue syndromes, 5 on body image or eating disorders, 3 on tinnitus, 1 on alcohol use disorder, and 1 on mood and anxiety disorders. Moderate-certainty evidence showed little to no difference in the effectiveness of therapist-guided remote and in-person CBT on primary outcomes (SMD −0.02, 95% confidence interval −0.12 to 0.07). Moderate-certainty evidence showed little to no difference in the effectiveness of in-person and therapist-guided remote CBT across a range of mental health and somatic disorders, suggesting potential for the use of therapist-guided remote CBT to facilitate greater access to evidence-based care. Systematic review registration: Open Science Framework (https://osf.io/7asrc)

Clear definitions are essential in science, particularly in the study of abstract phenomena like creativity. Due to its inherent complexity and domain-specific nature, the study of creativity has been complicated, as evidenced by the various definitions used to describe it and the multitude of tools which claim to measure it. Surgery is a safety-critical profession where creativity could be useful in navigating unforeseen problems and circumstances, as well as developing new innovations to improve patient outcomes. To validly and reliably study creativity in surgery, a surgery-specific definition is required. We aim to develop a consensus definition of creativity in surgery, utilizing the existing creativity literature and surgeon input. The objective of this study is to generate a consensus definition of creativity in surgery. We will first conduct a focus group comprised of 4-12 highly experienced surgeons to generate knowledge on surgeons' perceptions, attitudes and beliefs about creativity in surgery, collect real-world examples of creativity in surgery, and obtain opinions on the existing definitions of creativity in the literature. The selection of focus group participants will be performed using purposive sampling of the chairs and/or chiefs of each surgical sub-specialty at our home institution. Several questions relating to creativity in surgery will be posed to the focus group, to be rated using a 7-point Likert scale and used as prompts for group discussion. We will also search MEDLINE, PsycINFO and EMBASE to find definitions of creativity in the scientific literature. Six definitions, chosen based on citation frequency and relevancy to surgery, will be presented to the focus group for ranking and discussion. Lastly, in addition to novelty and effectiveness, which are widely accepted as necessary components of creativity, the focus group will be asked to consider the necessity of other components for creativity in surgery, sourced from the scientific literature. Descriptive and thematic analyses are planned for the quantitative and qualitative data, respectively. The results of the focus group will be incorporated in the drafting of five definitions of creativity in surgery, which will be presented as initial Delphi statements in the Delphi study. For the Delphi panel, we will perform non-probability purposive sampling of surgeons and surgeon trainees at our home institution, with a minimum panel size of 12. Panellists will be asked to select the definition of creativity most relevant to surgery, with each Delphi round electronically delivered. After each round, the steering committee will meet to review the results and adjust the statements for the next round based on the feedback. A maximum of 5 rounds will be performed, or until consensus is reached (≥75% agreement). Recruitment is scheduled to begin on 1 August 2024. All focus group and panellists will be given written and verbal information on the study and provide signed, informed consent. We plan to publish the results of our study in a creativity science- or surgery-focused journal to disseminate the results of our study to relevant stakeholders. We also plan to present the results of our research at local, national, and international conferences.

The properties of creative products-novelty and usefulness-are generally agreed upon by researchers. Yet, consensus is lacking on which personal and environmental factors contribute to an individual's creative potential, or to what extent. substantial research work has been conducted in this area, leading to the publication of many systematic reviews and meta-analyses collating the available evidence. However, many of these reviews have differing methodological and theoretical characteristics, and often report conflicting results. To summarize the current review literature on factors associated with creativity and better understand the similarities and discrepancies among reviews on the same topic, we plan to conduct an umbrella review of reviews. This protocol has been registered in Open Science Framework (DOI: 10.17605/OSF.IO/H78YS). We will search MEDLINE, PsycINFO, Web of Science, EMBASE, and Google Scholar for peer-reviewed reviews exploring factors associated with creativity. The quality of the included reviews will be assessed using the Risk of Bias Assessment Tool for Systematic Reviews (ROBIS), and the degree of study overlap across reviews assessed through calculation of the corrected covered area (CCA). Descriptive analyses will be performed to synthesize the results of the included reviews. We plan to use the results to create a holistic framework of the factors associated with creativity, which could be used to cross-validate existing creativity theories, or create new ones. The results of this umbrella review will be published in a relevant psychology-focused journal and presented at local, national and international conferences. As all data is peer-reviewed and presented in aggregate, we will not require ethics approval.

Creativity fuels societal progress and innovation, particularly in the field of medicine. The scientific study of creativity in medicine is critical to understanding how creativity contributes to medical practice, processes, and outcomes. An appraisal of the current scientific literature on the topic, and its gaps, will expand our understanding of how creativity and medicine interact, and guide future research. We aimed to assess the quantity, trends, distribution, and methodological features of the peer-reviewed on creativity in medicine. We searched the MEDLINE, EMBASE, and PsycINFO databases for peer-reviewed primary research publications on creativity in medicine. Screening, full-text review, and data extraction were performed independently and in duplicate by pairs of reviewers, with discrepancies resolved by a third reviewer. We performed descriptive analyses, graphically displaying the data using charts and maps where appropriate. Eighty-one studies were eligible for review, enrolling a total of 18,221 physicians, nurses and midwifes across all studies. Most research on creativity in medicine was published in the last decade, predominately in the field of nursing (75%). Researchers from Taiwan (22%) and the United States (21%) produced the most eligible publications, and the majority research was cross-sectional in nature (54%). There was substantial variability in the definitions of creativity adopted, and most studies failed to specify a definition of creativity. Forty-five different measurement tools were used to assess creativity, the most popular being divergent thinking tests such as the Torrance Test of Creative Thinking (24%) and Guilford Creativity Tests (16%). Peer-reviewed scientific research on creativity in medicine, mostly conducted in the nursing profession, is sparse and performed on variable methodological grounds. Further scientific research on the topic, as well as the development of medicine-specific definitions and measurement tools, is required to uncover the utility of creativity in the medical domain.

Network meta-analysis (NMA) is an increasingly popular statistical method of synthesising evidence to assess the comparative benefits and harms of multiple treatments in a single analysis. Several automated software packages facilitate conducting NMA using either of two alternative approaches, Bayesian or frequentist frameworks. Researchers must choose a framework for conducting NMA (Bayesian or frequentist) and select appropriate model(s), and those conducting NMA need to understand the assumptions and limitations of different approaches. Bayesian models are more frequently used and can be more flexible but require checking additional assumptions and greater statistical expertise that are often ignored. The present paper describes the important theoretical aspects of Bayesian and frequentist models for NMA and the applications and considerations of contrast-synthesis and arm-synthesis NMAs. In addition, we present evidence from a limited number of simulation and empirical studies that compared different frequentist and Bayesian models and provide an overview of available automated software packages to perform NMA. We will conclude that when analysts choose appropriate models, there are seldom important differences in the results of Bayesian and frequentist approaches and that network meta-analysts should therefore focus on model features rather than the statistical framework.

Objective To determine the efficacy of low intensity pulsed ultrasound (LIPUS) for healing of fracture or osteotomy.Design Systematic review and meta-analysis.Data sources Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and trial registries up to November 2016.Study selection Randomized controlled trials of LIPUS compared with sham device or no device in patients with any kind of fracture or osteotomy.Review methods Two independent reviewers identified studies, extracted data, and assessed risk of bias. A parallel guideline committee (BMJ Rapid Recommendation) provided input on the design and interpretation of the systematic review, including selection of outcomes important to patients. The GRADE system was used to assess the quality of evidence.Results 26 randomized controlled trials with a median sample size of 30 (range 8-501) were included. The most trustworthy evidence came from four trials at low risk of bias that included patients with tibia or clavicle fractures. Compared with control, LIPUS did not reduce time to return to work (percentage difference: 2.7% later with LIPUS, 95% confidence interval 7.7% earlier to 14.3% later; moderate certainty) or the number of subsequent operations (risk ratio 0.80, 95% confidence interval 0.55 to 1.16; moderate certainty). For pain, days to weight bearing, and radiographic healing, effects varied substantially among studies. For all three outcomes, trials at low risk of bias failed to show a benefit with LIPUS, while trials at high risk of bias suggested a benefit (interaction P<0.001). When only trials at low risk of bias trials were considered, LIPUS did not reduce days to weight bearing (4.8% later, 4.0% earlier to 14.4% later; high certainty), pain at four to six weeks (mean difference on 0-100 visual analogue scale: 0.93 lower, 2.51 lower to 0.64 higher; high certainty), and days to radiographic healing (1.7% earlier, 11.2% earlier to 8.8% later; moderate certainty).Conclusions Based on moderate to high quality evidence from studies in patients with fresh fracture, LIPUS does not improve outcomes important to patients and probably has no effect on radiographic bone healing. The applicability to other types of fracture or osteotomy is open to debate.Systematic review registration PROSPERO CRD42016050965

Opioid analgesics are commonly prescribed after total knee and hip arthroplasty to manage pain. Rates of opioid prescribing after arthroplasty differ by country, suggesting differences in policies or surgeons’ practices. We adopted a qualitative description design to explore and compare Canadian, Dutch, and Japanese orthopaedic surgeons’ perceptions of facilitators and barriers to opioid reduction after total joint arthroplasty. We used a combination of convenience and purposive sampling, and snowball recruitment to facilitate 27 semi-structured interviews online or via a phone call. We concurrently collected and analyzed data using conventional (inductive) content analysis. In our sample, all Canadian surgeons and almost all Dutch surgeons prescribed opioids to all arthroplasty patients post-discharge. Surgeons in Japan showed much greater variability, with half of those interviewed prescribing opioids to only a minority or no patients post-discharge. Japanese surgeons indicated that a 10–30-day hospital stay was typical after surgery and believed that opioids were often unnecessary for managing postoperative pain. Dutch surgeons described using an institutional standard pain management protocol, while Canadian and Japanese surgeons noted high variability in the type and dose of opioids prescribed, even within the same institution. Orthopaedic surgeons in each country identified challenges and facilitators to reduced postoperative opioid use in six key areas: (1) opioid prescribing practices, (2) patient factors, (3) collaborative care, (4) opioid prescribing policies/guidelines, (5) surgeon education, and (6) personal perceptions/beliefs. Canadian, Dutch, and Japanese orthopedic surgeons in our study described a range of individual, patient, and system level contributors to variability in opioid prescribing after joint replacement surgery. These findings suggest that multifactorial and context-specific approaches may be required to address barriers and optimize postoperative use of opioids.

ObjectiveTo assess the efficacy and harms of adding medical cannabis to prescription opioids among people living with chronic pain.DesignSystematic review.Data sourcesCENTRAL, EMBASE and MEDLINE.Main outcomes and measuresOpioid dose reduction, pain relief, sleep disturbance, physical and emotional functioning and adverse events.Study selection criteria and methodsWe included studies that enrolled patients with chronic pain receiving prescription opioids and explored the impact of adding medical cannabis. We used Grading of Recommendations Assessment, Development and Evaluation to assess the certainty of evidence for each outcome.ResultsEligible studies included five randomised trials (all enrolling chronic cancer-pain patients) and 12 observational studies. All randomised trials instructed participants to maintain their opioid dose, which resulted in a very low certainty evidence that adding cannabis has little or no impact on opioid use (weighted mean difference (WMD) −3.4 milligram morphine equivalent (MME); 95% CI (CI) −12.7 to 5.8). Randomised trials provided high certainty evidence that cannabis addition had little or no effect on pain relief (WMD −0.18 cm; 95% CI −0.38 to 0.02; on a 10 cm Visual Analogue Scale (VAS) for pain) or sleep disturbance (WMD −0.22 cm; 95% CI −0.4 to −0.06; on a 10 cm VAS for sleep disturbance; minimally important difference is 1 cm) among chronic cancer pain patients. Addition of cannabis likely increases nausea (relative risk (RR) 1.43; 95% CI 1.04 to 1.96; risk difference (RD) 4%, 95% CI 0% to 7%) and vomiting (RR 1.5; 95% CI 1.01 to 2.24; RD 3%; 95% CI 0% to 6%) (both moderate certainty) and may have no effect on constipation (RR 0.85; 95% CI 0.54 to 1.35; RD −1%; 95% CI −4% to 2%) (low certainty). Eight observational studies provided very low certainty evidence that adding cannabis reduced opioid use (WMD −22.5 MME; 95% CI −43.06 to −1.97).ConclusionOpioid-sparing effects of medical cannabis for chronic pain remain uncertain due to very low certainty evidence.PROSPERO registration numberCRD42018091098.