Low-quality Evidence Research Articles

Recent advances in peritoneal dialysis catheter placement: the association between method of insertion, operator, and prior abdominal surgery and outcomes.

Peritoneal dialysis (PD) is associated with comparable outcomes to hemodialysis and is much less expensive to provide in most parts of the world. A well functioning PD catheter is required, but complications are frequent, and while there are guidelines for the placement and care of a PD access, they are based on low-quality evidence. Data reporting the outcomes of percutaneous, as compared to surgical pathways for placement of catheters and the role of operator type in determining outcomes are examined. The impact of prior abdominal procedures on patient selection and the prognostic importance of the presence of adhesions at the time of catheter insertion are reviewed. There are conflicting data about the relative merits of percutaneous as compared to surgical placement of catheters that may relate to differences in patient selection, operator experience, or operator volume. Prior abdominal procedures are not associated with worse PD catheter outcomes and likely should not influence patient selection, except in exceptional circumstances. Finally, the presence of adhesions is associated with a higher risk of complications. However, even in the presence of adhesions, the termination of PD therapy and need for re-intervention occurs in <20% of patients.

A pragmatic approach to selecting a grading system for clinical practice recommendations in palliative care.

The limited palliative care evidence base is poorly amenable to existing grading schemes utilized in guidelines. Many recommendations are based on expert consensus or clinical practice standards, which are often considered 'low-quality' evidence. Reinforcing provider hesitancy in translating recommendations to practice has implications for patient care. To rationalize the selection of an appropriate grading system for rating evidence to support recommendations made in palliative care clinical practice guidelines. Review of the methodology sections of international palliative care guidelines published in English identified five grading systems comparison: Grading of Recommendations, Assessment, Development and Evaluations (GRADE); the Scottish Intercollegiate Guidelines Network (SIGN); Infectious Diseases Society of America-European Society for Medical Oncology (IDSA-ESMO); Confidence in the Evidence from Reviews of Qualitative research (CERQual) and the National Service Framework for Long Term Conditions (NSF-LTC). There is heterogeneity among grading systems used in published palliative care or terminal symptom management guidelines. GRADE has been increasingly adopted for its methodological rigour and inter-guideline consistency with other medical associations. CERQual has the potential to support recommendations informed by qualitative evidence, but its role in clinical guidelines is less defined. The IDSA-ESMO system has an intuitive typology with the ability to categorize tiers of lower-quality evidence. It is challenging to apply commonly used grading systems to the palliative care evidence base, which often lacks robust randomized controlled trials (RCTs). Adoption of IDSA-ESMO offers a feasible and practical alternative for lower-resourced guideline developers and palliative clinicians without a prerequisite for methodological expertise.

Perioperative intravenous lignocaine for pediatric postoperative pain-A systematic review and meta-analysis.

Intravenous lignocaine has been used as an analgesic adjunct in pediatric surgical patients, although its efficacy is still unclear. We aimed to clarify the efficacy of perioperative intravenous lignocaine (bolus followed by an infusion) on pediatric postoperative pain outcomes. A systematic review and meta-analysis. PubMed, EMBASE, Web of Science, Google Scholar (inception to June 2024). Studies involving pediatric patients (≤18 years) undergoing surgery under general anesthesia with one group receiving perioperative intravenous lignocaine (bolus followed by infusion) and the other group receiving placebo. The primary outcome was 24-h postoperative opioid consumption. Postoperative pain scores and the need for rescue analgesia were the secondary outcomes. Seven studies (n = 415) were included in the final meta-analysis. The use of intravenous lignocaine significantly reduced the morphine consumption in the first 24 h after surgery, compared to placebo (SMD -1.31, 95% CI -2.18 to -0.43, p = 0.003). A meta-analysis could not be performed for the secondary outcomes. There is low quality evidence to suggest that perioperative intravenous lignocaine bolus followed by an infusion significantly reduced the opioid consumption on the first postoperative day in pediatric surgical patients. The effects of perioperative lignocaine on postoperative pain scores and the need for rescue analgesia are uncertain.

AI-PEDURO – Artificial intelligence in pediatric urology: Protocol for a living scoping review and online repository

BackgroundArtificial intelligence (AI) and machine learning (ML) methods are increasingly being applied in pediatric urology across a growing number of settings, with more extensive databases and wider interest for use in clinical practice. More than 30 ML models have been published in the pediatric urology literature, but many lack items required by contemporary reporting frameworks to be high quality. For example, most studies lack multi-institution validation, validation over time, and validation within the clinical environment, resulting in a large discrepancy between the number of models developed versus the number of models deployed in a clinical setting, a phenomenon known as the AI chasm. Furthermore, pediatric urology is a unique subspecialty of urology with low frequency conditions and complex phenotypes where clinical management can rely on a lower quality of evidence. ObjectiveTo establish the AI in PEDiatric UROlogy (AI-PEDURO) collaborative, which will carry out a living scoping review and create an online repository (www.aipeduro.com) for models in the field and facilitate an evidence synthesis of AI models in pediatric urology. Methods and AnalysisThe scoping review will follow PRISMA-ScR guidelines. We will include ML models identified through standardized search methods of four databases, hand-search papers, and user-submitted models. Retrieved records will be included if they involve ML algorithms for prediction, classification, or risk stratification for pediatric urology conditions. The results will be tabulated and assessed for trends within the literature. Based on data availability, models will be divided into clinical disease sections (e.g. hydronephrosis, hypospadias, vesicoureteral reflux). A risk assessment will be performed using the APPRAISE-AI tool. The retrieved model cards (brief summary model characteristics in table form) will be uploaded to the online repository for open access to clinicians, patients, and data scientists, and will be linked to the Digital Object Identifier (DOI) for each article. Discussion and ConclusionWe hope this living scoping review and online repository will offer a valuable reference for pediatric urologists to assess disease-specific ML models' scope, validity, and credibility to encourage opportunities for collaboration, external validation, clinical testing, and responsible deployment. In addition, the repository may aid in identifying areas in need of further research.

The efficacy of azithromycin in the treatment of influenza A infection: A systematic review

Background The WHO recommendation against the use of macrolides reflects the little low-quality evidence about the effect of azithromycin (AZ) on influenza A infection. Considering recent reports about AZ use despite the WHO’s unfavorable recommendations, we aimed to test the evidence for the usage of AZ in the treatment of influenza A infection. Methods Various online databases were searched till August 2023 and thorough text and evidence evaluation resulted in selecting 7 studies. Results The selected reports included randomized control trials (two), cohort (three), case/control (one) studies, and one case report. Pooling of the results was unattainable due to the variability among studies in patient criteria, study outcomes, and study designs. Based on the limited reports with insufficient evidence, a recommendation for the use of AZ in the treatment regimen was not possible despite the associated reduction in inflammatory cytokines by AZ administration and the absence of significant adverse effects or mortality in hospital-admitted or ICU patients. While these findings support the current guidelines for the treatment of influenza A infection, the evidence behind these guidelines and treatment characteristics were illustrated. Conclusion AZ shows a potential symptom improvement and pro-inflammatory laboratory indices in influenza A patients. Another positive aspect is the absence of complications associated with AZ administration to critically ill patients and acceptable prognosis. However, it is crucial to have more quality research on this matter that focuses on the indication of the use of AZ, and the timing of initiation, dosage, and duration of treatment while monitoring adverse events.

Immunosuppression protocols for emerging oncological indications in liver transplantation: A systematic review and pooled analysis.

The evolving field of liver transplant (LT) oncology calls for tailored immunosuppression protocols to minimize the risk of tumor recurrence. We systematically reviewed the available evidence from inception to May 2023 regarding immunosuppression protocols used in patients undergoing LT for cholangiocarcinoma, neuroendocrine tumors (NET), hepatic-endothelial hemangioendothelioma (HEHE) and colorectal liver metastases (CRLM), to identify common practices and to evaluate their association with oncological outcomes. Studies not involving humans, case reports and short case series (i.e., n < 10) were excluded. Among 3,374 screened references, we included 117 studies involving 6,797 patients distributed as follows: cholangiocarcinoma (58.1%), NETs (18.8%), HEHE (7.7%), CRLM (6.8%), mixed neoplasms (6.8%) or others (1.7%). Only 41% of the studies disclosed details of the immunosuppression protocol, and 20.8% of studies provided drug trough concentrations during follow-up. The immunosuppression protocols described were heterogeneous and broadly mirrored routine practices for non-tumoral indications. The only exception was CRLM where tacrolimus minimization -or even withdrawal- in combination with inhibitors of the mammalian target of rapamycin (mTORi) were consistently reported. None of the studies evaluated the relationship between the immunosuppression protocol and oncological outcomes. In conclusion, based on low-quality and indirect scientific evidence, patients with tumoral indications for LT should receive the lowest tacrolimus level tolerated under close surveillance. The combination with mTORi titrated to achieve the top therapeutic range of trough concentrations could allow complete tacrolimus withdrawal. This approach may be particularly useful in patients with cholangiocarcinoma and CRLM, in whom tumor recurrence is the main cause of death. We propose a tool for reporting immunosuppression protocols which could be implemented in future transplant oncology studies.

Efficacy and safety of laminoplasty combined with C3 laminectomy for patients with multilevel degenerative cervical myelopathy: a systematic review and meta-analysis.

Laminoplasty (LP) combined with C3 laminectomy (LN) can effectively achieve spinal cord decompression while maintaining the integrity of the posterior ligament-muscle complex, thereby minimizing cervical muscle damage. However, its necessity and safety remain controversial. This study aimed to compare the safety and efficacy of LP and LP combined with C3 LN in the treatment of patients with multilevel degenerative cervical spondylotic myelopathy (DCM). A systematic review and meta-analysis of the literature was performed. A search of PubMed, Web of Science, Embase, and the Cochrane Library databases was conducted from inception through December 2023 and updated in February 2024. Search terms included laminoplasty, laminectomy, C3 and degenerative cervical spondylosis. The literature search yielded 14 studies that met our inclusion criteria. Outcomes included radiographic results, neck pain, neurologic function, surgical parameters, and postoperative complications. We also assessed methodologic quality, publication bias, and quality of evidence. Fourteen studies were identified, including 590 patients who underwent LP combined with C3 LN (modified group, MG) compared to 669 patients who underwent LP (traditional group, TG). The results of the study indicated a statistically significant improvement in cervical range of motion (WMD = 3.62, 95% CI: 0.39 to 6.85) and cervical sagittal angle (WMD = 2.07, 95% CI: 0.40 to 3.74) in the MG compared to the TG at the last follow-up (very low-level evidence). The TG had a higher number of patients with complications, especially C2-3 bone fusion. There was no significant difference found in improvement of neck pain, JOA, NDI, cSVA, T1 slope at latest follow-up. LP combined with C3 LN is an effective and necessary surgical method for multilevel DCM patients to maintain cervical sagittal balance. However, due to the low quality of evidence in existing studies, more and higher quality research on the technology is needed in the future.

Efficacy and safety of vancomycin compared with those of alternative treatments for methicillin-resistant Staphylococcus aureus infections: An umbrella review.

To summarize the evidence on the efficacy and safety of vancomycin compared with those of alternative treatments in adult patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. PubMed, Embase, and Web of Science were searched up to December 15, 2023, for systematic reviews and meta-analyses comparing vancomycin with alternative MRSA treatments. Primary outcomes included clinical cure and microbiological eradication rates. Organ-specific safety outcomes were assessed. Summary estimates were recalculated using a random-effects model. Evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. This study was registered in PROSPERO (CRD42022340359). This umbrella review included 19 studies and 71 meta-analyses (46 efficacy and 25 safety) comparing vancomycin with 10 alternative treatments across different MRSA infection types and populations. GRADE assessment showed that 29.58% of the meta-analyses were of high quality. Linezolid and daptomycin showed higher efficacy in MRSA-induced skin and soft tissue infections and pneumonia (moderate evidence quality) and bacteremia (very low evidence quality), respectively, compared with that of vancomycin. Cephalosporins had a higher risk of nausea, whereas linezolid had a higher risk of nausea, diarrhea, and thrombocytopenia than that of vancomycin. Vancomycin posed a higher risk of rash, pruritus, red man syndrome, and nephrotoxicity than that of alternatives. The quality of evidence supporting the higher efficacy of alternative treatment over vancomycin for MRSA infection was not high. Given varying safety profiles and advancements in therapeutic monitoring, careful consideration of patient-specific factors and pharmacokinetics is crucial when selecting treatment alternatives to vancomycin.

Effects of probiotics supplementation on glycemic profile in adults with type 2 diabetes mellitus: A grade-assessed systematic review and dose–response meta-analysis of randomized controlled trials

BackgroundDisturbed glycemia and the resulting type 2 diabetes (T2D) are significant health concerns. Various approaches have been examined to improve glycemic control in patients with T2D. Modification of gut microbiome via administering probiotics has been extensively studied. The present study aims to sum up the existing literature which investigated the effect of probiotics on glycemic indices in individuals with T2D in the format of randomized controlled trials (RCTs). MethodsOnline medical databases (PubMed, Scopus, and Web of Science) were searched from inception to January 2024. Eligible studies were included using pre-defined inclusion and exclusion criteria. Outcome variables included fasting blood sugar (FBS), insulin, hemoglobin A1c (HbA1c), and homeostatic model of insulin resistance (HOMA-IR). Weighted mean differences (WMDs) were estimated. Subgroup and dose-response analyses were conducted. P-values <0.05 were considered as statistically significant. ResultsOut of 5,636 records retrieved by the initial search, thirty-two RCTs were included in the final analyses. Supplementation with probiotics was observed to significantly improve indices of glycemic control; including FBS (WMD: -13.27 mg/dl; 95% CI: -18.31, -8.22), HbA1c (WMD: -0.44 %; 95% CI: -0.59, -0.28), insulin (WMD: -1.33 μIU/ml; 95% CI: -2.57, -0.08), and HOMA-IR (WMD: -0.95; 95% CI: -1.71, -0.18). Dose-response analysis revealed that increased duration of intervention results in a larger reduction only in FBS. ConclusionSupplementation with probiotics seems to improve indices of glycemic control. Nonetheless, taken into account the notable heterogeneity (with regard to dosage, duration, and the species/strains used) between the included studies and low quality of evidence, caution must be considered, especially when long-term clinical implications are intended.

Inhaled analgesics for the treatment of prehospital acute pain-A systematic review.

Many prehospital emergency patients receive suboptimal treatment for their moderate to severe pain. Various factors may contribute. We aim to systematically review literature pertaining to prehospital emergency adult patients with acute pain and the pain-reducing effects, adverse events (AEs), and safety issues associated with inhaled analgetic agents compared with other prehospital analgesic agents. As part of an initiative from the Scandinavian Society of Anaesthesia and Intensive Care Medicine, we conducted a systematic review (PROSPERO CRD42018114399), applying the PRISMA guidelines, Grading of Recommendations Assessment, Development, and Evaluation (GRADE), and Cochrane methods, searching the Cochrane Library, Epistemonikos, Centre for Reviews and Dissemination, PubMed, and EMBASE databases (updated March 2024). Inclusion criteria were the use of inhaled analgesic agents in adult patients with acute pain in the prehospital emergency care setting. All steps were performed by minimum of two individual researchers. The primary outcome was pain reduction; secondary outcomes were speed of onset, duration of effect, and relevant AEs. We included seven studies (56,535 patients in total) that compared inhaled agents (methoxyflurane [MF] and nitrous oxide [N2O]) to other drugs or placebo. Study designs were randomized controlled trial (1; n = 60), randomized non-blinded study (1; n = 343), and randomized open-label study (1; n = 270). The remaining were prospective or retrospective observational studies. The evidence according to GRADE was of low or very low quality. No combined meta-analysis was possible. N2O may reduce pain compared to placebo, but not compared to intravenous (IV) paracetamol, and may be less effective compared to morphine and MF. MF may reduce pain compared to paracetamol, ketoprofen, tramadol, and fentanyl. Both agents may be associated with marked but primarily mild AEs. We found low-quality evidence suggesting that both MF and N2O are safe and may have a role in the management of pain in the prehospital setting. There is low-quality evidence to support MF as a short-acting single analgesic or as a bridge to IV access and the administration of other analgesics. There may be occupational health issues regarding the prehospital use of N2O.

Corticosteroids for Managing Pediatric Sepsis and Septic Shock: A Systematic Review and Meta-analysis.

To assess the efficacy and safety of corticosteroids for the management of pediatric sepsis and septic shock. Ovid MEDLINE, Ovid Embase, CENTRAL, Web of Science (Core Collection) and China National Knowledge Infrastructure were systematically searched up to September 2023. Preprint servers, clinical trial registries and the reference sections of previous reviews were hand-searched. Randomized controlled trials that enrolled pediatric sepsis, septic shock or systemic inflammatory response syndrome patients, compared the use of corticosteroid regimens against standard sepsis care and reported eligible outcomes were included. Title/abstract and full-text screening were conducted in-duplicate. Eligible articles were extracted using a standardized form in-duplicate. Outcomes extracted include mortality incidence, hospital and pediatric intensive care unit length of stay, duration of shock, incidence of adverse events and serious adverse events and incidence of corticosteroid-related adverse events. The risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Assessing Randomized Trials. Random-effects meta-analyses were conducted, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. Sixteen randomized controlled trials (N = 973) were included. Corticosteroid use may be associated with reduced mortality risks (risk ratio: 0.65, 95% CI: 0.50-0.85), shorter length of hospital stay (MD: -3.76 days, 95% CI: -6.66 to -0.86), and shorter pediatric intensive care unit length of stay (MD -2.34 days, 95% CI: -3.14 to -1.53 days). Corticosteroid use may be associated with gastrointestinal bleeding but not a higher risk of secondary infection. No studies reported on serious adverse events. All findings were based on low to very low quality of evidence. While corticosteroids show promise for managing pediatric sepsis and septic shock, the question of how to select the best candidate and the most optimal regimen remains unanswered. Future trials need to focus on assessing corticosteroid-related adverse events and stratifying patient inclusion by sepsis subphenotypes.

Systematic review of Janus kinases inhibitors for rheumatoid arthritis: methodology, reporting, and quality of evidence evaluation.

To evaluate the methodological, reporting and evidence quality of systematic reviews or meta-analyses of Janus kinases (JAK) inhibitors for the treatment of rheumatoid arthritis (RA). Our study systematically retrieved reviews from various databases, spanning from inception to June 2024. Two evaluators independently assessed the methodological, reporting, and evidence quality of each review using the AMSTAR-2 and PRIAMA2020 tools. The evidence quality was evaluated according to GRADE criteria. Six aspects were evaluated: publication year, study type, homogeneity, risk of publication bias, AMSTAR-2 methodology, and PRIAMA2020 reporting quality. Excel 2016 facilitated conversion of scores into radar plots. Following stringent selection criteria, a total of 18 relevant studies were identified. The AMSTAR-2 scores ranged from 4 to 13 points, with five studies rated as low quality and the remaining 13 as critically low quality. All studies encompassed populations, interventions, controls, and outcome measures, demonstrating commendable integrity. However, there is room for improvement in study protocol development and registration, comprehensive search strategies, inclusion and exclusion criteria, conflict of interest disclosure, and discussion of heterogeneity. PRIAMA2020 assessments ranged from 14.5 to 21 points, with two studies scoring below 15 points due to increased bias risk from data transformation and sensitivity analysis. Notably, all reviews (100%) adhered to PRIAMA2020 guidelines for certain items but none met all criteria. GRADE evaluation included 446 outcome measures, with 158 of moderate, 156 of low, and 132 of very low quality, indicating JAK inhibitors is effective in improving RA. According to radar chart, the average rank score was 13.13. One study achieved a balanced score across all dimensions, while 11 exceeded the average, five showed significant differences in PRIAMA2020 scores, and four in AMSTAR two scores. Despite summarizing the efficacy and safety of JAK inhibitors in treating RA, the included studies exhibited poor methodological and reporting quality, along with low-quality evidence overall. Therefore, caution is warranted among decision-makers regarding the use of JAK inhibitors in RA treatment. Urgent requirements include high-quality, multicenter studies investigating JAK inhibitors for RA. https://www.crd.york.ac.uk/PROSPERO, identifier 413415.

A scoping review of coaching in occupational therapy: Mapping methods, populations and outcomes.

Coaching is proposed as a core enabling skill of occupational therapy and increasingly suggested for a diverse range of health populations. In recent years, research on coaching has proliferated, emerging from within and outside of occupational therapy. Yet, concern has been raised about the absence of theoretical underpinning and diversity of descriptions of coaching in occupational therapy, as well as low-quality evidence supporting its effectiveness. The aim of this study is to map the use of coaching by occupational therapists from 2007 to 2022 to identify the populations, settings and outcomes it is applied to, differences between coaching interventions and evidence supporting its use. This systematic scoping review applied Arksey and O'Malley's five-stage methodological framework with further methodological direction using the Levac framework. There was no consumer involvement in undertaking this review. Findings from 60 research publications on coaching indicate its use with populations across the lifespan in primarily community settings to improve occupational performance, participation and self-efficacy. A wide range of coaching interventions are designed or used by occupational therapists, with Occupational Performance Coaching being the most researched (16/27, 59% of named interventions). Common elements of coaching interventions included collaborative goal setting and problem-solving; however, a lack of described theory or coaching methods persists. High-quality study designs indicate its effectiveness; however, an absence of fidelity definition or monitoring limits interpretation of many studies. The language of coaching is becoming common practice within occupational therapy, and evidence indicates effectiveness of some coaching interventions. Advances in coaching research and use by occupational therapists will be aided by an explicit statement of the theoretical basis for coaching interventions, with congruent coaching methods, mechanisms and outcomes stated. This scoping review maps the use of coaching by occupational therapists in current published research. Key aspects of coaching examined include how coaching is defined, who it is used with and how effective it is. The kinds of outcomes that coaching is intended to improve are also reported. From 633 publications, 60 research publications were fully analysed. The use of coaching by occupational therapists has grown rapidly over the past 10years. Strong evidence of its effectiveness exists for achieving the personal goals of people receiving occupational therapy when goals describe changes in everyday life activities. Coaching is being used with people across the lifespan with a variety of disabilities and chronic conditions and their caregivers/parents, most commonly parents of children with developmental issues. The key features of coaching interventions used by occupational therapists include collaborative goal setting, shared problem-solving and client-led action planning. Some elements of coaching are also used within other interventions with a wider range of methods. Coaching is believed to work by supporting an individual's self-belief that they can make changes. Theories that underpin coaching vary but commonly focus on self-determination, behaviour change and occupational therapy theory. However, many of the coaching interventions do not describe any theoretical basis nor coaching methods in detail. Future research on coaching in occupational therapy should ensure a clear explanation of the theory that underpins it, coaching methods and monitoring of how well coaching is applied.

Evaluation of Fracture Resistance of Reattached Tooth Fragments Restored Using Fiber-reinforced Composites: A Systematic Review.

This systematic review examined the current literature to evaluate the fracture resistance of the tooth fragments reattached using fiber-reinforced composites (FRC). An electronic search was performed on Scopus, PubMed, and Web of Science databases according to specific inclusion and exclusion criteria to identify relevant articles to be included until January 2023. Articles with full text available in the English language for randomized control studies, observational studies, retrospective studies, and in vitro studies conducted on permanent human teeth were selected. The risk of bias was assessed in all studies using the OHAT tool. Out of 16 search results, seven in vitro studies with a total of 415 samples were included in the review. Three studies reported that reinforcement using rigid FRC posts improves fracture resistance of reattached anterior teeth, three studies reported that reinforcement using flexible fiber bundles enhances the fracture strength of reattached posterior teeth and one study reported that the use of flexible polyethylene fibers improves fracture resistance in molars with reattached cusps. Within the limitations of the studies included in the review, there is low-quality evidence that reinforcement of reattached fragments using FRC posts or fibers improves fracture resistance. The reattached fractured fragments may be susceptible to re-fracture. The use of FRC to reinforce the resin composite used for reattachment may enhance the bond strength and increase resistance to fracture. How to cite this article: Albar NHM. Evaluation of Fracture Resistance of Reattached Tooth Fragments Restored Using Fiber-reinforced Composites: A Systematic Review. J Contemp Dent Pract 2024;25(6):605-615.

Lip Symmetry After Cleft Lip Repair Fisher in Unilateral Cleft Lip: A Systematic Review

The purpose of this research is to learn the outcomes of lip symmetry after cleft lip repair by Fisher in unilateral cleft lip compared with other techniques. This systematic review searched English full-text available articles in 4 databases: Cochrane, PubMed, ScienceDirect, and Google Scholar, and hand searched through grey literature and reference lists. Subjects were those with unilateral cleft lip without syndromic disorders who had primary cleft lip repair. The authors compared the technique by Fisher with other cleft lip repair techniques. Outcomes were lip symmetry determined quantitatively by lip anthropometric measurement and qualitatively by the Steffensen grading criteria. Four studies were included with a total of 150 cleft lip repairs, comparing the technique by Fisher with techniques by Millard, Mohler, and modified Millard. The 4 studies underwent critical appraisal, data analysis, qualitative synthesis, and meta-analysis. Assessment with Cochrane Risk of Bias 2 for randomized controlled trials and “Risk of Bias in Nonrandomized Studies–of Interventions” for nonrandomized studies displayed an overall high risk of bias in the included studies. “Grading of recommendations, assessment, development, and evaluation” revealed a very low quality of evidence for this review. All 4 studies noted better subjective lip symmetry in the technique by Fisher, but lip and vermilion height were better after the technique by Millard. This review found superior lip symmetry quality but inferior lip symmetry anthropometry after the technique by Fisher compared with the technique by Millard and its modifications, with a low quality of evidence.

Effect of non-steroidal anti-inflammatory drugs on the management of postoperative pain after cardiac surgery: a multicenter, randomized, controlled, double-blind trial (KETOPAIN Study)

BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) are recommended for the management of acute postoperative pain as part of a multimodal strategy to reduce opioid use, relieve pain, and reduce chronic pain in non-cardiac surgery. However, significant concerns arise in cardiac surgery due to the potential adverse effects of NSAID including increased bleeding and acute kidney injury (AKI). We hypothesized that NSAIDs are effective against pain and safe in the early postoperative period following cardiac surgery, taking contraindications into account.MethodsThe KETOPAIN trial is a prospective, double blind, 1:1 ratio, versus placebo multicentric trial, randomizing 238 patients scheduled for cardiac surgery. Written consent will be obtained for all participants. The inclusion criterion is patients more than 18 years old undergoing for elective cardiac surgery under cardiopulmonary bypass (CPB). Patients will be allocated to the intervention (ketoprofen) group (n = 119) or the control (placebo) group (n = 119). In the intervention group, in addition to the standard treatment, patients will receive NSAIDs (ketoprofen) at a dose of 100 mg each 12 h 48 h after. The control group, in addition to the standard treatment, will receive a placebo of NSAIDs every 12 h for 48 h after surgery. An intention-to-treat analysis will be performed. The primary endpoint will be the intensity of acute postoperative pain at rest at 24 h from the end of surgery. Pain will be assessed using the numerous rating scale. The secondary endpoints will be postoperative pain on coughing during chest physiotherapy, postoperative pain until day 7, the pain trajectory between day 3 and day 7, cumulative opioid consumption within 48 h after surgery, nausea and vomiting, the occurrence of postoperative pulmonary complications within the first 7 days after surgery, neuropathic pain at 3 months, and quality of life at 3 months.DiscussionNSAIDs function as non-selective, reversible inhibitors of the cyclooxygenase enzyme and play a role in a multimodal pain management approach. While there are recommendations supporting the use of NSAIDs in major non-cardiac surgery, recent guidelines do not favor their use in cardiac surgery. However, this is based on low-quality evidence. Major concerns regarding NSAID use in cardiac surgery patients are potential increase in postoperative bleeding or AKI. However, few studies support the possible use of NSAIDs without the risk of bleeding and/or AKI. Also, in a recent French survey, many anesthesiologists reported using NSAIDs in cardiac surgery. To date, no large randomized study has been conducted to evaluate the efficacy of NSAIDs in the management of postoperative pain in cardiac surgery. The expected outcome of this study is an improvement in the management of acute postoperative pain in cardiac surgery with a multimodal strategy including the use of NSAIDs.Trial registrationClinicalTrials.gov NCT06381063. Registered on April 24, 2024.

Sex Differences in Ambulatory Biomechanics: A Meta-Analysis Providinga Mechanistic Insight into Knee Osteoarthritis.

Females typically present with a higher prevalence of knee osteoarthritis (KOA), and such a higher prevalence may be due to unique knee biomechanics during walking. However, the sex-dependent ambulatory mechanics has been yet to be clarified. To address this critical knowledge gap, this study implemented a series of computational approaches (1) to identify sex-related knee joint biomechanics during ambulation in persons with KOA and (2) to compare these biomechanical measures between individuals with vs. without KOA, stratified by sex. We searched five electronic databases for studies reporting sex-specific knee biomechanics in persons with and/or without KOA. Summary estimates were computed using random-effects meta-analysis and stratified by sex. The systematic review identified eighteen studies (308 males and 383 females with KOA; 740 males and 995 females without KOA). A series of meta-analyses identified female-specific knee biomechanics in a disease-dependent manner. Females with KOA had lower first peak knee adduction moment and peak knee adduction compared to male counterparts. On the other hand, healthy females had lower peak knee flexion moment than male counterparts. Effect estimate in each meta-analysis display poor quality of evidence according to the GRADE approach. The current study is the first to consider sex as a biological variable into ambulatory mechanics in the development of KOA. We discovered that sex-dependent alterations in knee biomechanics is a function of the presence of KOA, indicating that KOA disease may be a driver of the sex-dependent biomechanical alterations or vice versa. Although no strong conclusion can be drawn because of the low quality of evidence, these findings provide new insight into the sex differences in ambulatory knee biomechanics and progression of KOA.

Recommendations from the 2024 Australian evidence-based guideline for unexplained infertility: ADAPTE process from the ESHRE evidence-based guideline on unexplained infertility.

The 2024 Australian evidence-based guideline for unexplained infertility provides clinicians with evidence-based recommendations for the optimal diagnostic workup for infertile couples to establish the diagnosis of unexplained infertility and optimal therapeutic approach to treat couples diagnosed with unexplained infertility in the Australian health care setting. The guideline recommendations were adapted for the Australian context from the rigorous, comprehensive European Society of Human Reproduction and Embryology (ESHRE) 2023 Evidence-based guideline: unexplained infertility, using the ADAPTE process and have been approved by the Australian National Health and Medical Research Council. The guideline includes 40 evidence-based recommendations, 21 practice points and three research recommendations addressing: definition - defining infertility and frequency of intercourse, infertility and age, female and male factor infertility; diagnosis - ovulation, ovarian reserve, tubal factor, uterine factor, laparoscopy, cervical/vaginal factor, male factor, additional testing for systemic conditions; and treatment - expectant management, active treatment, mechanical-surgical procedures, alternative therapeutic approaches, quality of life. CHANGES IN ASSESSMENT AND MANAGEMENT RESULTING FROM THE GUIDELINE: This guideline refines the definition of unexplained infertility and addresses basic diagnostic procedures for infertility assessment not considered in previous guidelines on unexplained infertility. For therapeutic approaches, consideration of evidence quality, efficacy, safety and, in the Australian setting, feasibility, acceptability, cost, implementation and ultimately recommendation strength were integrated across multidisciplinary expertise and consumer perspectives in adapting recommendations to the Australian context by using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework, which had not been used in past guidelines on unexplained infertility to formulate recommendations. The Australian process also included an established data integrity check to ensure evidence could be trusted to guide practice. Practice points were added and expanded to consider the Australian setting. No evidence-based recommendations were underpinned by high quality evidence, with most having low or very low quality evidence. In this context, research recommendations were made including those for the Australian context. The full guideline and technical report are publicly available online and can be accessed at https://www.monash.edu/medicine/mchri/infertility and are supported by extensive translation resources, including the free patient ASKFertility mobile application (https://www.askfertility.org/).

Practice review: Pharmacological management of severe chronic breathlessness in adults with advanced life-limiting diseases.

Severe and refractory chronic breathlessness is a common and burdensome symptom in patients with advanced life-limiting disease. Its clinical management is challenging because of the lack of effective interventions. To provide practice recommendations on the safe use of pharmacological therapies for severe chronic breathlessness. Scoping review of (inter)national guidelines and systematic reviews. We additionally searched for primary studies where no systematic review could be identified. Consensus on the recommendations was reached by 75% approval within an international expert panel. Searches in MEDLINE, Cochrane Library and Guideline International Network until March 2023. Inclusion of publications on the use of antidepressants, benzodiazepines, opioids or corticosteroids for chronic breathlessness in adults with cancer, chronic obstructive pulmonary disease, interstitial lung disease or chronic heart failure. Overall, the evidence from eight guidelines, 14 systematic reviews and 3 randomised controlled trials (RCTs) on antidepressants is limited. There is low quality evidence favouring opioids in patients with chronic obstructive pulmonary disease, cancer and interstitial lung disease. For chronic heart failure, evidence is inconclusive. Benzodiazepines should only be considered for anxiety associated with severe breathlessness. Antidepressants and corticosteroids should not be used. Management of breathlessness remains challenging with only few pharmacological options with limited and partially conflicting evidence. Therefore, pharmacological treatment should be reserved for patients with advanced disease under monitoring of side effects, after optimisation of the underlying condition and use of evidence-based non-pharmacological interventions as first-line treatment.

Retesting Intervals for Tryptase

What Is the Issue? Tryptase is a serine protease primarily produced and released by mast cells. Tryptase measures are most used to diagnose and manage anaphylaxis and mastocytosis, and the timing of tryptase measurement is crucial for its utility. The clinical utility of tryptase remains unclear, and available evidence showed that more than 30% of patients with acute anaphylaxis did not exhibit an elevated tryptase level, which suggests that repeated tryptase testing may be overused in this population. Appropriate retesting intervals or frequency for tryptase retesting in patients with anaphylaxis or mastocytosis remain unclear. What Did We Do? To inform decisions about the use and timing of repeat tryptase testing for patients with confirmed or suspected anaphylaxis and patients with cutaneous or systemic mastocytosis, we identified and summarized related recommendations and publications on the potential biological or physiological factors that may impact retesting intervals in these populations. We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2014. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included evidence-based guidelines, and narratively summarized the findings. What Did We Find? For patients with suspected anaphylaxis, identified guidelines suggest measuring tryptase levels 1 to 2 times during the event onset (e.g., immediately or within 4 hours) and 1 to 2 times after resolution of symptoms (e.g., after 24 hours) to establish baseline tryptase levels. These recommendations were based on very low certainty of evidence. For patients with systemic mastocytosis, 1 evidence-based guideline in Brazil recommends testing tryptase once a year, which is based on very low certainty of evidence. Baseline tryptase level varies very little over time within the same individual and is determined by their genetic background. For patients with anaphylaxis, the timing of the peak tryptase level is from 1 minute to 6 hours (median 30 minutes), and the half-life of serum tryptase is about 1.5 hours to 2.5 hours and needs up to 24 hours to return to baseline level. We did not find any recommendations that met our inclusion criteria regarding the minimum retesting interval for tryptase testing or the use of repeat or serial tryptase testing in patients with confirmed or suspected anaphylaxis or with cutaneous or systemic mastocytosis. What Does It Mean? The available recommendations suggest testing blood tryptase at the acute (1 or 2 times) and baseline phases (1 or 2 times) for patients with suspected anaphylaxis. There is little rationale for the ongoing monitoring of tryptase levels beyond the recommended 4 time points for patients with anaphylaxis. For patients with mastocytosis, the guidelines recommend retesting tryptase only once a year and do not support frequent repeat tryptase testing within a year. Decision-makers and clinicians should consider the cost of tryptase testing, potential burden on health care resources, local lab capacity, or accessibility of testing facilities when making decisions regarding tryptase retesting. Given the very low-quality evidence regarding measuring tryptase and the unclear utility of tryptase testing for patients with anaphylaxis, future research that focuses on the clinical utility of tryptase relative to clinical assessment for anaphylaxis is needed.