Short- and long-term effects of imatinib in hospitalised COVID-19 patients: A randomised trial.

OBJECTIVES: We studied the short- and long-term effects of imatinib in hospitalised COVID-19 patients. METHODS: Participants were randomised to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomised trials studying imatinib for 30-day mortality in hospitalised COVID-19 patients. RESULTS: We randomised 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year and in SoC 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47-3.90). At 1-year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78-1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32-1.63; low certainty evidence). CONCLUSIONS: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalised COVID-19 patients.

Clinical Practice Guideline for Red Blood Cell Transfusion Thresholds in Very Preterm Neonates.

Importance: Red blood cell (RBC) transfusion is a common medical intervention to treat anemia in very preterm neonates; however, best transfusion practices, such as thresholds, remain uncertain. Objective: To develop recommendations for clinicians on the use of RBC transfusions in very preterm neonates. Evidence Review: An international steering committee reviewed evidence from a systematic review of 6 randomized clinical trials (RCTs) that compared high vs low hemoglobin-based or hematocrit-based transfusion thresholds. The steering committee reached consensus on certainty-of-evidence ratings and worked with a panel from stakeholder organizations on reviewing the evidence. With input from parent representatives and the stakeholder panel, the steering committee used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to develop recommendations. Findings: A systematic review of 6 RCTs encompassing 3483 participants (1759 females [51.3%]; mean [SD] age range, 25.9-29.8 [1.5-3.0] weeks) was used as the basis of the recommendations. The ranges for higher hemoglobin concentration (liberal) vs lower hemoglobin concentration (restrictive) threshold study arms were similar across the trials. However, specific thresholds differed based on the severity of illness, which was defined using variable criteria in the trials. There was moderate certainty of evidence that low transfusion thresholds likely had little to no difference in important short-term and long-term outcomes. The recommended hemoglobin thresholds varied on the basis of postnatal week and respiratory support needs. At postnatal weeks 1, 2, and 3 or more, for neonates on respiratory support, the recommended thresholds were 11, 10, and 9 g/dL, respectively; for neonates on no or minimal respiratory support, the recommended thresholds were 10, 8.5, and 7 g/dL, respectively (to convert hemoglobin to grams per liter, multiply by 10.0). Conclusions and Relevance: This consensus statement recommends a restrictive RBC transfusion strategy, with moderate certainty of evidence, for preterm neonates with less than 30 weeks' gestation.

Leukotriene receptor antagonists as add-on therapy to antihistamines for urticaria: Systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: The benefits and harms of adding antileukotrienes to H1 antihistamines (AHs) for the management of urticaria (hives, itch, and/or angioedema) remain unclear. OBJECTIVE: We sought to systematically synthesize the treatment outcomes of antileukotrienes in combination with AHs versus AHs alone for acute and chronic urticaria. METHODS: As part of updating American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters urticaria guidelines, we searched Medline, Embase, Central, LILACS, WPRIM, IBECS, ICTRP, CBM, CNKI, VIP, Wanfang, US Food and Drug Administration, and European Medicines Agency databases from inception to December 18, 2023, for randomized controlled trials (RCTs) evaluating antileukotrienes and AHs versus AHs alone in patients with urticaria. Paired reviewers independently screened citations, extracted data, and assessed risk of bias. Random effects models pooled effect estimates for urticaria activity, itch, wheal, sleep, quality of life, and harms. The GRADE approach informed certainty of evidence ratings. The study was registered at the Open Science Framework (osf.io/h2bfx/). RESULTS: Thirty-four RCTs enrolled 3324 children and adults. Compared to AHs alone, the combination of a leukotriene receptor antagonist with AHs probably modestly reduces urticaria activity (mean difference, -5.04; 95% confidence interval, -6.36 to -3.71; 7-day urticaria activity score) with moderate certainty. We made similar findings for itch and wheal severity as well as quality of life. Adverse events were probably not different between groups (moderate certainty); however, no RCT reported on neuropsychiatric adverse events. CONCLUSION: Among patients with urticaria, adding leukotriene receptor antagonists to AHs probably modestly improves urticaria activity with little to no increase in overall adverse events. The added risk of neuropsychiatric adverse events in this population with leukotriene receptor antagonists is small and uncertain.

Panel stacking is a threat to consensus statement validity.

Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members towards one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but non-financial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analysing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated towards COVID-19 elimination (zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases towards advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided.

Reporting Conflicts of Interest and Funding in Health Care Guidelines: The RIGHT-COI&F Checklist.

BACKGROUND: Conflicts of interest (COIs) of contributors to a guideline project and the funding of that project can influence the development of the guideline. Comprehensive reporting of information on COIs and funding is essential for the transparency and credibility of guidelines. OBJECTIVE: To develop an extension of the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement for the reporting of COIs and funding in policy documents of guideline organizations and in guidelines: the RIGHT-COI&F checklist. DESIGN: The recommendations of the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) network were followed. The process consisted of registration of the project and setting up working groups, generation of the initial list of items, achieving consensus on the items, and formulating and testing the final checklist. SETTING: International collaboration. PARTICIPANTS: 44 experts. MEASUREMENTS: Consensus on checklist items. RESULTS: The checklist contains 27 items: 18 about the COIs of contributors and 9 about the funding of the guideline project. Of the 27 items, 16 are labeled as policy related because they address the reporting of COI and funding policies that apply across an organization's guideline projects. These items should be described ideally in the organization's policy documents, otherwise in the specific guideline. The remaining 11 items are labeled as implementation related and they address the reporting of COIs and funding of the specific guideline. LIMITATION: The RIGHT-COI&F checklist requires testing in real-life use. CONCLUSION: The RIGHT-COI&F checklist can be used to guide the reporting of COIs and funding in guideline development and to assess the completeness of reporting in published guidelines and policy documents. PRIMARY FUNDING SOURCE: The Fundamental Research Funds for the Central Universities of China.

Efficacy and Safety of Systemic Corticosteroids for Urticaria: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Short courses of adjunctive systemic corticosteroids are commonly used to treat acute urticaria and chronic urticaria flares (both with and without mast cell-mediated angioedema), but their benefits and harms are unclear. OBJECTIVE: To evaluate the efficacy and safety of treating acute urticaria or chronic urticaria flares with versus without systemic corticosteroids. METHODS: We searched the MEDLINE, EMBASE, CENTRAL, CNKI, VIP, Wanfang, and CBM databases from inception to July 8, 2023, for randomized controlled trials of treating urticaria with versus without systemic corticosteroids. Paired reviewers independently screened records, extracted data, and appraised risk of bias with the Cochrane 2.0 tool. We performed random-effects meta-analyses of urticaria activity, itch severity, and adverse events. We assessed certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach. RESULTS: We identified 12 randomized trials enrolling 944 patients. For patients with low or moderate probability (17.5%-64%) to improve with antihistamines alone, add-on systemic corticosteroids likely improve urticaria activity by a 14% to 15% absolute difference (odds ratio [OR], 2.17, 95% confidence interval [CI]: 1.43-3.31; number needed to treat [NNT], 7; moderate certainty). Among patients with a high chance (95.8%) for urticaria to improve with antihistamines alone, add-on systemic corticosteroids likely improved urticaria activity by a 2.2% absolute difference (NNT, 45; moderate certainty). Corticosteroids may improve itch severity (OR, 2.44; 95% CI: 0.87-6.83; risk difference, 9%; NNT, 11; low certainty). Systemic corticosteroids also likely increase adverse events (OR, 2.76; 95% CI: 1.00-7.62; risk difference, 15%; number needed to harm, 9; moderate certainty). CONCLUSIONS: Systemic corticosteroids for acute urticaria or chronic urticaria exacerbations likely improve urticaria, depending on antihistamine responsiveness, but also likely increase adverse effects in approximately 15% more.

Proton pump inhibitors for gastrointestinal bleeding prophylaxis in critically ill patients: A systematic review protocol.

BACKGROUND: Proton pump inhibitors (PPIs) are the most commonly prescribed drugs for preventing upper gastrointestinal bleeding in critically ill patients. However, concerns have arisen about the possible harms of using PPIs, including potentially increased risk of pneumonia, Clostridioides difficile infection, and more seriously, an increased risk of death in the most severely ill patients. Triggered by the REVISE trial, which is a forthcoming large randomized trial comparing pantoprazole to placebo in invasively mechanically ventilated patients, we will conduct this systematic review to evaluate the efficacy and safety of PPIs versus no prophylaxis for critically ill patients. METHODS: We will systematically search randomized trials that compared gastrointestinal bleeding prophylaxis with PPIs versus placebo or no prophylaxis in adults in the intensive care unit (ICU). Pairs of reviewers will independently screen the literature, and for those eligible trials, extract data and assess risk of bias. We will perform meta-analyses using a random-effects model, and calculate relative risks for dichotomous outcomes and mean differences for continuous outcomes, and the associated 95% confidence intervals. We will conduct subgroup analysis to explore whether the impact of PPIs on mortality differs in more and less severely ill patients. We will assess certainty of evidence using the GRADE approach. DISCUSSION: This systematic review will provide the most up-to-date evidence regarding the merits and limitations of stress ulcer prophylaxis with PPIs in critically ill patients in contemporary practice.

Factors Impacting Physician Prognostic Accuracy in Heart Failure Patients With Reduced Left Ventricular Ejection Fraction.

BACKGROUND: A recent study showed that the accuracy of heart failure (HF) cardiologists and family doctors to predict mortality in outpatients with HF proved suboptimal, performing less well than models. OBJECTIVES: The authors sought to evaluate patient and physician factors associated with physician accuracy. METHODS: The authors included outpatients with HF from 11 HF clinics. Family doctors and HF cardiologists estimated patient 1-year mortality. They calculated predicted mortality using the Seattle HF Model and followed patients for 1 year to record mortality (or urgent heart transplant or ventricular assist device implant as mortality-equivalent events). Using multivariable logistic regression, the authors evaluated associations among physician experience and confidence in estimates, duration of patient-physician relationship, patient-physician sex concordance, patient race, and predicted risk, with concordant results between physician and model predictions. RESULTS: Among 1,643 patients, 1-year event rate was 10% (95% CI: 8%-12%). One-half of the estimates showed discrepant results between model and physician predictions, mainly owing to physician risk overestimation. Discrepancies were more frequent with increasing patient risk from 38% in low-risk to ∼75% in high-risk patients. When making predictions on male patients, female HF cardiologists were 26% more likely to have discrepant predictions (OR: 0.74; 95% CI: 0.58-0.94). HF cardiologist estimates in Black patients were 33% more likely to be discrepant (OR: 0.67; 95% CI: 0.45-0.99). Low confidence in predictions was associated with discrepancy. Analyses restricted to high-confidence estimates showed inferior calibration to the model, with risk overestimation across risk groups. CONCLUSIONS: Discrepant physician and model predictions were more frequent in cases with perceived increased risk. Model predictions outperform physicians even when they are confident in their predictions. (Predicted Prognosis in Heart Failure [INTUITION]; NCT04009798).

The GRADE Working Group and CINeMA approaches provided inconsistent certainty of evidence ratings for a network meta-analysis of opioids for chronic noncancer pain.

OBJECTIVES: Assessment of the certainty of evidence (CoE) from network meta-analysis is critical to convey the strength of inferences for clinical decision-making. Both the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group (GWG) and the Confidence in Network Meta-Analysis (CINeMA) framework have been designed to assess the CoE of treatment effects informed by network meta-analysis; however, the concordance of results is uncertain. STUDY DESIGN AND SETTING: We assessed the CoE for treatment effects of individual opioids on pain relief and physical functioning from a network meta-analysis for chronic noncancer pain using the GWG approach and the CINeMA framework. Both approaches evaluate the CoE as high, moderate, low or very low. We quantified the number of discrepant CoE ratings between approaches and the magnitude of the difference (ie, one level, two levels, or three levels). RESULTS: Across 105 comparisons among individual opioids for pain relief, the GWG and CINeMA approaches provided different CoE ratings in 34% of cases (36 of 105). Across 66 comparisons for physical functioning, there was discordance in 17% of cases (11 of 66). All discrepancies were separated by one level. The CINeMA framework typically provided lower CoE ratings compared to the GWG approach, predominantly because of differences in the assessment of transitivity and heterogeneity. CONCLUSION: Our findings suggest there are differences between the CoE ratings provided by the GWG and CINeMA approaches when applied to network meta-analyses. Further research is needed to replicate or refute our findings in other network meta-analyses and assess the implications for clinical 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.

Risk of thrombosis and bleeding in gynecologic noncancer surgery: systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide procedure-specific estimates of the risk for symptomatic venous thromboembolism and major bleeding in noncancer gynecologic surgeries. DATA SOURCES: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar. Furthermore, we performed separate searches for randomized trials that addressed the effects of thromboprophylaxis. STUDY ELIGIBILITY CRITERIA: Eligible studies were observational studies that enrolled ≥50 adult patients who underwent noncancer gynecologic surgery procedures and that reported the absolute incidence of at least 1 of the following: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding that required reintervention (including re-exploration and angioembolization), bleeding that led to transfusion, or postoperative hemoglobin level <70 g/L. METHODS: A teams of 2 reviewers independently assessed eligibility, performed data extraction, and evaluated the risk of bias of the eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine the cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors and used the Grading of Recommendations Assessment, Development and Evaluation approach to rate the evidence certainty. RESULTS: We included 131 studies (1,741,519 patients) that reported venous thromboembolism risk estimates for 50 gynecologic noncancer procedures and bleeding requiring reintervention estimates for 35 procedures. The evidence certainty was generally moderate or low for venous thromboembolism and low or very low for bleeding requiring reintervention. The risk for symptomatic venous thromboembolism varied from a median of <0.1% for several procedures (eg, transvaginal oocyte retrieval) to 1.5% for others (eg, minimally invasive sacrocolpopexy with hysterectomy, 1.2%-4.6% across patient venous thromboembolism risk groups). Venous thromboembolism risk was <0.5% for 30 (60%) of the procedures; 0.5% to 1.0% for 10 (20%) procedures; and >1.0% for 10 (20%) procedures. The risk for bleeding the require reintervention varied from <0.1% (transvaginal oocyte retrieval) to 4.0% (open myomectomy). The bleeding requiring reintervention risk was <0.5% in 17 (49%) procedures, 0.5% to 1.0% for 12 (34%) procedures, and >1.0% in 6 (17%) procedures. CONCLUSION: The risk for venous thromboembolism in gynecologic noncancer surgery varied between procedures and patients. Venous thromboembolism risks exceeded the bleeding risks only among selected patients and procedures. Although most of the evidence is of low certainty, the results nevertheless provide a compelling rationale for restricting pharmacologic thromboprophylaxis to a minority of patients who undergo gynecologic noncancer procedures.

Compelling evidence from meta-epidemiological studies demonstrates overestimation of effects in randomized trials that fail to optimize randomization and blind patients and outcome assessors.

OBJECTIVES: To investigate the impact of potential risk of bias elements on effect estimates in randomized trials. STUDY DESIGN AND SETTING: We conducted a systematic survey of meta-epidemiological studies examining the influence of potential risk of bias elements on effect estimates in randomized trials. We included only meta-epidemiological studies that either preserved the clustering of trials within meta-analyses (compared effect estimates between trials with and without the potential risk of bias element within each meta-analysis, then combined across meta-analyses; between-trial comparisons), or preserved the clustering of substudies within trials (compared effect estimates between substudies with and without the element, then combined across trials; within-trial comparisons). Separately for studies based on between- and within-trial comparisons, we extracted ratios of odds ratios (RORs) from each study and combined them using a random-effects model. We made overall inferences and assessed certainty of evidence based on Grading of Recommendations, Assessment, development, and Evaluation and Instrument to assess the Credibility of Effect Modification Analyses. RESULTS: Forty-one meta-epidemiological studies (34 of between-, 7 of within-trial comparisons) proved eligible. Inadequate random sequence generation (ROR 0.94, 95% confidence interval [CI] 0.90-0.97) and allocation concealment (ROR 0.92, 95% CI 0.88-0.97) probably lead to effect overestimation (moderate certainty). Lack of patients blinding probably overestimates effects for patient-reported outcomes (ROR 0.36, 95% CI 0.28-0.48; moderate certainty). Lack of blinding of outcome assessors results in effect overestimation for subjective outcomes (ROR 0.69, 95% CI 0.51-0.93; high certainty). The impact of patients or outcome assessors blinding on other outcomes, and the impact of blinding of health-care providers, data collectors, or data analysts, remain uncertain. Trials stopped early for benefit probably overestimate effects (moderate certainty). Trials with imbalanced cointerventions may overestimate effects, while trials with missing outcome data may underestimate effects (low certainty). Influence of baseline imbalance, compliance, selective reporting, and intention-to-treat analysis remain uncertain. CONCLUSION: Failure to ensure random sequence generation or adequate allocation concealment probably results in modest overestimates of effects. Lack of patients blinding probably leads to substantial overestimates of effects for patient-reported outcomes. Lack of blinding of outcome assessors results in substantial effect overestimation for subjective outcomes. For other elements, though evidence for consistent systematic overestimate of effect remains limited, failure to implement these safeguards may still introduce important bias.

Risk of thrombosis and bleeding in gynecologic cancer surgery: systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide procedure-specific estimates of the risk of symptomatic venous thromboembolism and major bleeding in the absence of thromboprophylaxis, following gynecologic cancer surgery. DATA SOURCES: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar for observational studies. We also reviewed reference lists of eligible studies and review articles. We performed separate searches for randomized trials addressing effects of thromboprophylaxis and conducted a web-based survey on thromboprophylaxis practice. STUDY ELIGIBILITY CRITERIA: Observational studies enrolling ≥50 adult patients undergoing gynecologic cancer surgery procedures reporting absolute incidence for at least 1 of the following were included: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding requiring reintervention (including reexploration and angioembolization), bleeding leading to transfusion, or postoperative hemoglobin <70 g/L. METHODS: Two reviewers independently assessed eligibility, performed data extraction, and evaluated risk of bias of eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors. The GRADE approach was applied to rate evidence certainty. RESULTS: We included 188 studies (398,167 patients) reporting on 37 gynecologic cancer surgery procedures. The evidence certainty was generally low to very low. Median symptomatic venous thromboembolism risk (in the absence of prophylaxis) was <1% in 13 of 37 (35%) procedures, 1% to 2% in 11 of 37 (30%), and >2.0% in 13 of 37 (35%). The risks of venous thromboembolism varied from 0.1% in low venous thromboembolism risk patients undergoing cervical conization to 33.5% in high venous thromboembolism risk patients undergoing pelvic exenteration. Estimates of bleeding requiring reintervention varied from <0.1% to 1.3%. Median risks of bleeding requiring reintervention were <1% in 22 of 29 (76%) and 1% to 2% in 7 of 29 (24%) procedures. CONCLUSION: Venous thromboembolism reduction with thromboprophylaxis likely outweighs the increase in bleeding requiring reintervention in many gynecologic cancer procedures (eg, open surgery for ovarian cancer and pelvic exenteration). In some procedures (eg, laparoscopic total hysterectomy without lymphadenectomy), thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding venous thromboembolism and bleeding.

Guideline panel social dynamics influence the development of clinical practice recommendations: a mixed-methods systematic review.

OBJECTIVES: To synthesize empirical studies that investigate the cognitive and social processes involved in the deliberation process of guideline development meetings and determine the distribution of deliberated topics. STUDY DESIGN AND SETTING: We conducted a mixed-method systematic review using a convergent segregated approach. We searched for empirical studies that investigate the intragroup dynamics of guideline development meetings indexed in bibliographic databases. RESULTS: Of the 5,899 citations screened, 12 studies from six countries proved eligible. Chairs, cochairs, and methodologists contributed to at least one-third of the discussion time in guideline development meetings; patient partners contributed the least. In interdisciplinary groups, male gender and occupation as a physician were positively associated with the amount of contribution. Compared to groups that used the Grading of Recommendations Assessment, Development and Evaluation approach, for groups that did not, when faced with insufficient or low-quality evidence, relied more on their clinical experience. The presence of a cognitive "yes" bias was apparent in meetings: panelists tended to acquiesce with positive statements that required less cognitive effort than negative statements. CONCLUSION: The social dynamics of the discussions were linked to each panelist's activity role, professional background, and gender, all of which influenced the level of contributions they made in guideline development meetings.

Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE- and Institute of Medicine-based recommendations.

BACKGROUND: Guidance addressing atopic dermatitis (AD) management, last issued in 2012 by the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force, requires updating as a result of new treatments and improved guideline and evidence synthesis methodology. OBJECTIVE: To produce evidence-based guidelines that support patients, clinicians, and other decision-makers in the optimal treatment of AD. METHODS: A multidisciplinary guideline panel consisting of patients and caregivers, AD experts (dermatology and allergy/immunology), primary care practitioners (family medicine, pediatrics, internal medicine), and allied health professionals (psychology, pharmacy, nursing) convened, prioritized equity, diversity, and inclusiveness, and implemented management strategies to minimize influence of conflicts of interest. The Evidence in Allergy Group supported guideline development by performing systematic evidence reviews, facilitating guideline processes, and holding focus groups with patient and family partners. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed rating the certainty of evidence and strength of recommendations. Evidence-to-decision frameworks, subjected to public comment, translated evidence to recommendations using trustworthy guideline principles. RESULTS: The panel agreed on 25 recommendations to gain and maintain control of AD for patients with mild, moderate, and severe AD. The eAppendix provides practical information and implementation considerations in 1-2 page patient-friendly handouts. CONCLUSION: These evidence-based recommendations address optimal use of (1) topical treatments (barrier moisturization devices, corticosteroids, calcineurin inhibitors, PDE4 inhibitors [crisaborole], topical JAK inhibitors, occlusive [wet wrap] therapy, adjunctive antimicrobials, application frequency, maintenance therapy), (2) dilute bleach baths, (3) dietary avoidance/elimination, (4) allergen immunotherapy, and (5) systemic treatments (biologics/monoclonal antibodies, small molecule immunosuppressants [cyclosporine, methotrexate, azathioprine, mycophenolate, JAK inhibitors], and systemic corticosteroids) and UV phototherapy (light therapy).

Management of chronic pain secondary to temporomandibular disorders: a systematic review and network meta-analysis of randomised trials.

OBJECTIVE: We explored the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD). DESIGN: Systematic review and network meta-analysis of randomised clinical trials (RCTs). DATA SOURCES: MEDLINE, EMBASE, CINAHL, CENTRAL, and SCOPUS were searched to May 2021, and again in January 2023. STUDY SELECTION: Interventional RCTs that enrolled patients presenting with chronic pain associated with TMD. DATA EXTRACTION AND SYNTHESIS: Pairs of reviewers independently identified eligible studies, extracted data, and assessed risk of bias. We captured all reported patient-important outcomes, including pain relief, physical functioning, emotional functioning, role functioning, social functioning, sleep quality, and adverse events. We conducted frequentist network meta-analyses to summarise the evidence and used the GRADE approach to rate the certainty of evidence and categorise interventions from most to least beneficial. RESULTS: 233 trials proved eligible for review, of which 153-enrolling 8713 participants and exploring 59 interventions or combinations of interventions-were included in network meta-analyses. All subsequent effects refer to comparisons with placebo or sham procedures. Effects on pain for eight interventions were supported by high to moderate certainty evidence. The three therapies probably most effective for pain relief were cognitive behavioural therapy (CBT) augmented with biofeedback or relaxation therapy (risk difference (RD) for achieving the minimally important difference (MID) in pain relief of 1 cm on a 10 cm visual analogue scale: 36% (95% CI 33 to 39)), therapist-assisted jaw mobilisation (RD 36% (95% CI 31 to 40)), and manual trigger point therapy (RD 32% (29 to 34)). Five interventions were less effective, yet more effective than placebo, showing RDs ranging between 23% and 30%: CBT, supervised postural exercise, supervised jaw exercise and stretching, supervised jaw exercise and stretching with manual trigger point therapy, and usual care (such as home exercises, self stretching, reassurance).Moderate certainty evidence showed four interventions probably improved physical functioning: supervised jaw exercise and stretching (RD for achieving the MID of 5 points on the short form-36 physical component summary score: 43% (95% CI 33 to 51)), manipulation (RD 43% (25 to 56)), acupuncture (RD 42% (33 to 50)), and supervised jaw exercise and mobilisation (RD 36% (19 to 51)). The evidence for pain relief or physical functioning among other interventions, and all evidence for adverse events, was low or very low certainty. CONCLUSION: When restricted to moderate or high certainty evidence, interventions that promote coping and encourage movement and activity were found to be most effective for reducing chronic TMD pain. REGISTRATION: PROSPERO (CRD42021258567).

Management of chronic pain associated with temporomandibular disorders: a clinical practice guideline.

CLINICAL QUESTION: What is the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD)? CURRENT PRACTICE: TMD are the second most common musculoskeletal chronic pain disorder after low back pain, affecting 6-9% of adults globally. TMD are associated with pain affecting the jaw and associated structures and may present with headaches, earache, clicking, popping, or crackling sounds in the temporomandibular joint, and impaired mandibular function. Current clinical practice guidelines are largely consensus-based and provide inconsistent recommendations. RECOMMENDATIONS: For patients living with chronic pain (≥3 months) associated with TMD, and compared with placebo or sham procedures, the guideline panel issued: (1) strong recommendations in favour of cognitive behavioural therapy (CBT) with or without biofeedback or relaxation therapy, therapist-assisted mobilisation, manual trigger point therapy, supervised postural exercise, supervised jaw exercise and stretching with or without manual trigger point therapy, and usual care (such as home exercises, stretching, reassurance, and education); (2) conditional recommendations in favour of manipulation, supervised jaw exercise with mobilisation, CBT with non-steroidal anti-inflammatory drugs (NSAIDS), manipulation with postural exercise, and acupuncture; (3) conditional recommendations against reversible occlusal splints (alone or in combination with other interventions), arthrocentesis (alone or in combination with other interventions), cartilage supplement with or without hyaluronic acid injection, low level laser therapy (alone or in combination with other interventions), transcutaneous electrical nerve stimulation, gabapentin, botulinum toxin injection, hyaluronic acid injection, relaxation therapy, trigger point injection, acetaminophen (with or without muscle relaxants or NSAIDS), topical capsaicin, biofeedback, corticosteroid injection (with or without NSAIDS), benzodiazepines, and ß blockers; and (4) strong recommendations against irreversible oral splints, discectomy, and NSAIDS with opioids. HOW THIS GUIDELINE WAS CREATED: An international guideline development panel including patients, clinicians with content expertise, and methodologists produced these recommendations in adherence with standards for trustworthy guidelines using the GRADE approach. The MAGIC Evidence Ecosystem Foundation (MAGIC) provided methodological support. The panel approached the formulation of recommendations from the perspective of patients, rather than a population or health system perspective. THE EVIDENCE: Recommendations are informed by a linked systematic review and network meta-analysis summarising the current body of evidence for benefits and harms of conservative, pharmacologic, and invasive interventions for chronic pain secondary to TMD. UNDERSTANDING THE RECOMMENDATION: These recommendations apply to patients living with chronic pain (≥3 months duration) associated with TMD as a group of conditions, and do not apply to the management of acute TMD pain. When considering management options, clinicians and patients should first consider strongly recommended interventions, then those conditionally recommended in favour, then conditionally against. In doing so, shared decision making is essential to ensure patients make choices that reflect their values and preference, availability of interventions, and what they may have already tried. Further research is warranted and may alter recommendations in the future.

Practice Variation in the Management of Adult Hydroceles: A Multinational Survey.

Background: Although hydrocele is one of the most common urologic pathologies, it is seldom studied, and the major urologic associations have no guidelines for the management of adult hydroceles. Objective: To characterize international practice variation in the treatment of adult hydroceles. Design setting and participants: An international survey was conducted addressing the management of hydroceles among urologists in Belgium, Denmark, Finland, Iceland, Japan, and the Netherlands from September to December 2020. We invited a random sample of 170 urologists from each country (except Iceland). Outcome measurements and statistical analysis: Urologists' treatment options, factors relevant for decision-making, expected patient satisfaction, and outcomes after aspiration versus surgery were assessed. Results and limitations: Of the 864 urologists contacted, 437 (51%) participated. Of the respondents, 202 (53%) performed both hydrocelectomies and aspiration, 147 (39%) performed hydrocelectomies only, and 30 (8%) performed aspiration only. In Belgium (83%), the Netherlands (75%), and Denmark (55%), urologists primarily performed hydrocelectomies only, whereas in Finland (84%), Japan (61%), and Iceland (91%), urologists performed both hydrocelectomies and aspiration. Urologists favored hydrocelectomy for large hydroceles (78.8% vs 37.5% for small), younger patients (66.0% for patients <50 yr vs 41.2% for ≥70 yr), patients with few or no comorbidities (62.3% vs 23.1% with multiple comorbidities), and patients without antithrombotic agents (53.5% vs 36.5% with antithrombotic agents). Most urologists considered patient satisfaction to be highest after hydrocelectomy (53.8% vs 9.9% after aspiration) despite believing that hydrocelectomy is more likely to cause complications (hematoma 77.8% vs 8.8% after aspiration). Estimates varied between countries. Conclusions: We found a large variation in the treatment of adult hydroceles within and between countries. Optimization of hydrocele management globally will require future studies. Patient summary: Our international survey shows that treatment of adult hydrocele varies considerably within and between countries.