UNASSIGNED: The American Academy of Orthopaedic Surgeons (AAOS) has developed a clinical practice guideline (CPG) for management of anterior cruciate ligament (ACL) injuries. Primary studies such as randomized controlled trials (RCTs) are cited as evidence for the guidelines. Given the influence that these trials have on patient care, adherence to standardized protocols for conducting and reporting RCTs is essential.
UNASSIGNED: To evaluate the CONSORT (Consolidated Standards of Reporting Trials) Extension for Harms-related reporting of RCTs cited as supporting evidence for the AAOS CPG on the management of ACL tears.
UNASSIGNED: Cross-sectional study.
UNASSIGNED: The reference section of the AAOS guideline for ACL tears was first screened for RCTs cited in the CPG. Next, each RCT was evaluated for adherence to the CONSORT Extension for Harms checklist. Both identification of RCTs and assessment of adherence were performed in a masked and duplicate process. Descriptive statistics were used to summarize adherence to CONSORT Extension for Harms items. A Pearson correlation test was conducted to assess the relationship between the year of publication and adherence to CONSORT harms reporting.
UNASSIGNED: The sample included 113 RCTs, of which 16 (14.2%) were published before the CONSORT Extension for Harms was implemented in 2004. Sample sizes ranged from 24 to 4564 participants, with a mean of 228. None of the included RCTs included all 18 items in the CONSORT Extension for Harms checklist. The mean number of checklist items reported was 4 (of 18; 22.2%). A moderate, positive, and statistically significant correlation was found between the RCT publication year and the adherence with reporting of the CONSORT Extension for Harms (t111 = 3.54; P < .001) (r = 0.32; 95% CI, 0.14-0.47).
UNASSIGNED: Harms were infrequently reported in RCTs cited as supporting evidence in the AAOS CPG for the management of ACL tears. One encouraging finding was the positive correlation between the year when RCTs were published and how well they adhered to reporting harms. Efforts to improve adverse event reporting are warranted, as RCTs are commonly used to make clinical decisions in orthopaedic surgery.

BACKGROUND: Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc.
METHODS: A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed.
RESULTS: Six recommendations were elaborated regarding the pharmacological treatment of Raynaud\'s phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found.
CONCLUSIONS: These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice.

OBJECTIVE: This article explores recent developments in left main revascularization, with a focus on appraising the latest American and European guidelines.
RESULTS: Recent pooled data analysis from four major randomized controlled trials (RCTs) for left main coronary artery stenosis indicate an advantage for CABG over PCI in regard to freedom from major adverse cardiovascular events, despite no significant difference in mortality observed at 5 years. Additional data support the use of CABG for patients with left ventricular dysfunction, complex left main lesions, diffuse coronary disease, and diabetes.
CONCLUSIONS: The data underpinning the guidelines on each revascularization modality (PCI versus CABG) must consider factors such as lesion complexity, diabetes, and left ventricular dysfunction. Additionally, the findings of the four major RCTs upon which the guidelines are based must be ascertained in light of the latest advancements in these revascularization techniques.

BACKGROUND: Chemotherapy for breast cancer can cause neutropenia, increasing the risk of febrile neutropenia (FN) and serious infections. The use of granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis has been explored to mitigate these risks. To evaluate the efficacy and safety of primary G-CSF prophylaxis in patients with invasive breast cancer undergoing chemotherapy.
METHODS: A systematic literature review was conducted according to the \"Minds Handbook for Clinical Practice Guideline Development\" using PubMed, Ichushi-Web, and the Cochrane Library databases. Randomized controlled trials (RCTs) and cohort studies assessing using G-CSF as primary prophylaxis in invasive breast cancer were included. The primary outcomes were overall survival (OS) and FN incidence. Meta-analyses were performed for outcomes with sufficient data.
RESULTS: Eight RCTs were included in the qualitative analysis, and five RCTs were meta-analyzed for FN incidence. The meta-analysis showed a significant reduction in FN incidence with primary G-CSF prophylaxis (risk difference [RD] = 0.22, 95% CI: 0.01-0.43, p = 0.04). Evidence for improvement in OS with G-CSF was inconclusive. Four RCTs suggested a tendency for increased pain with G-CSF, but statistical significance was not reported.
CONCLUSIONS: Primary prophylactic use of G-CSF is strongly recommended for breast cancer patients undergoing chemotherapy, as it has been shown to reduce the incidence of FN. While the impact on OS is unclear, the benefits of reducing FN are considered to outweigh the potential harm of increased pain.

To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN).
Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion.
All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy.
This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil.

UNASSIGNED: A comprehensive review of the evidence exploring the outcomes of enhanced recovery after surgery (ERAS) guidelines has not been completed.
UNASSIGNED: To evaluate if ERAS guidelines are associated with improved hospital length of stay, hospital readmission, complications, and mortality compared with usual surgical care, and to understand differences in estimates based on study and patient factors.
UNASSIGNED: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central were searched from inception until June 2021.
UNASSIGNED: Titles, abstracts, and full-text articles were screened by 2 independent reviewers. Eligible studies were randomized clinical trials that examined ERAS-guided surgery compared with a control group and reported on at least 1 of the outcomes.
UNASSIGNED: Data were abstracted in duplicate using a standardized data abstraction form. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Risk of bias was assessed in duplicate using the Cochrane Risk of Bias tool. Random-effects meta-analysis was used to pool estimates for each outcome, and meta-regression identified sources of heterogeneity within each outcome.
UNASSIGNED: The primary outcomes were hospital length of stay, hospital readmission within 30 days of index discharge, 30-day postoperative complications, and 30-day postoperative mortality.
UNASSIGNED: Of the 12 047 references identified, 1493 full texts were screened for eligibility, 495 were included in the systematic review, and 74 RCTs with 9076 participants were included in the meta-analysis. Included studies presented data from 21 countries and 9 ERAS-guided surgical procedures with 15 (20.3%) having a low risk of bias. The mean (SD) Reporting on ERAS Compliance, Outcomes, and Elements Research checklist score was 13.5 (2.3). Hospital length of stay decreased by 1.88 days (95% CI, 0.95-2.81 days; I2 = 86.5%; P < .001) and the risk of complications decreased (risk ratio, 0.71; 95% CI, 0.59-0.87; I2 = 78.6%; P < .001) in the ERAS group. Risk of readmission and mortality were not significant.
UNASSIGNED: In this meta-analysis, ERAS guidelines were associated with decreased hospital length of stay and complications. Future studies should aim to improve implementation of ERAS and increase the reach of the guidelines.

UNASSIGNED: 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.
UNASSIGNED: To develop recommendations for clinicians on the use of RBC transfusions in very preterm neonates.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: This consensus statement recommends a restrictive RBC transfusion strategy, with moderate certainty of evidence, for preterm neonates with less than 30 weeks\' gestation.

. The management of diabetic foot: the new guidelines of the International Working Group on Diabetic Foot. The publication of the new guidelines on the diabetic foot are an opportunity for a fine-tuning of the (few) new developments, but of the soundness of the evidence and knowledge known so far. Compared to the previous 2019 guidelines, the 2023 update included the analysis of randomised clinical trials only, a more accurate application of the GRADE method, a leaner and more current bibliography, and an update of the strength of some recommendations from low to conditional. The real big news in the 2023 update is the publication of a specific guideline for the diagnosis and treatment of Charcot neuro-osteoarthropathy in people with diabetes, neuropathy and in the absence of skin lesions.

BACKGROUND: The SAVVY project aims to improve the analyses of adverse events (AEs) in clinical trials through the use of survival techniques appropriately dealing with varying follow-up times and competing events (CEs). This paper summarizes key features and conclusions from the various SAVVY papers.
METHODS: Summarizing several papers reporting theoretical investigations using simulations and an empirical study including randomized clinical trials from several sponsor organizations, biases from ignoring varying follow-up times or CEs are investigated. The bias of commonly used estimators of the absolute (incidence proportion and one minus Kaplan-Meier) and relative (risk and hazard ratio) AE risk is quantified. Furthermore, we provide a cursory assessment of how pertinent guidelines for the analysis of safety data deal with the features of varying follow-up time and CEs.
RESULTS: SAVVY finds that for both, avoiding bias and categorization of evidence with respect to treatment effect on AE risk into categories, the choice of the estimator is key and more important than features of the underlying data such as percentage of censoring, CEs, amount of follow-up, or value of the gold-standard.
CONCLUSIONS: The choice of the estimator of the cumulative AE probability and the definition of CEs are crucial. Whenever varying follow-up times and/or CEs are present in the assessment of AEs, SAVVY recommends using the Aalen-Johansen estimator (AJE) with an appropriate definition of CEs to quantify AE risk. There is an urgent need to improve pertinent clinical trial reporting guidelines for reporting AEs so that incidence proportions or one minus Kaplan-Meier estimators are finally replaced by the AJE with appropriate definition of CEs.

BACKGROUND: Providing secondary prevention through structured and comprehensive cardiac rehabilitation programmes to patients after a myocardial infarction (MI) reduces mortality and morbidity and improves health-related quality of life. Cardiac rehabilitation has the highest recommendation in current guidelines. While treatment target attainment rates at Swedish cardiac rehabilitation centres is among the highest in Europe, there are considerable differences in service delivery and variations in patient-level outcomes between centres. In this trial, we aim to study whether centre-level guideline adherence and patient-level outcomes across Swedish cardiac rehabilitation centres can be improved through a) regular audit and feedback of cardiac rehabilitation structure and processes through a national quality registry and b) supporting cardiac rehabilitation centres in implementing guidelines on secondary prevention. Furthermore, we aim to evaluate the implementation process and costs.
METHODS: The study is an open-label cluster-randomized effectiveness-implementation hybrid trial including all 78 cardiac rehabilitation centres (attending to approximately 10 000 MI patients/year) that report to the SWEDEHEART registry. The centres will be randomized 1:1:1 to three clusters: 1) reporting cardiac rehabilitation structure and process variables to SWEDEHEART every six months (audit intervention) and being offered implementation support to implement guidelines on secondary prevention (implementation support intervention); 2) audit intervention only; or 3) no intervention offered. Baseline cardiac rehabilitation structure and process variables will be collected. The primary outcome is an adherence score measuring centre-level adherence to secondary prevention guidelines. Secondary outcomes include patient-level secondary prevention risk factor goal attainment at one-year after MI and major adverse coronary outcomes for up to five-years post-MI. Implementation outcomes include barriers and facilitators to guideline adherence evaluated using semi-structured focus-group interviews and relevant questionnaires, as well as costs and cost-effectiveness assessed by a comparative health economic evaluation.
CONCLUSIONS: Optimizing cardiac rehabilitation centres\' delivery of services to meet standards set in guidelines may lead to improvement in cardiovascular risk factors, including lifestyle factors, and ultimately a decrease in morbidity and mortality after MI.
BACKGROUND: ClinicalTrials.gov. Identifier: NCT05889416 . Registered 2023-03-23.