Grading Of Recommendations Assessment , Development And Evaluation Research Articles

Consensus guidelines for the diagnosis and management of succinic semialdehyde dehydrogenase deficiency

Succinic semialdehyde dehydrogenase deficiency (SSADHD) (OMIM #271980) is a rare autosomal recessive metabolic disorder caused by pathogenic variants of ALDH5A1. Deficiency of SSADH results in accumulation of γ-aminobutyric acid (GABA) and other GABA-related metabolites. The clinical phenotype of SSADHD includes a broad spectrum of non-pathognomonic symptoms such as cognitive disabilities, communication and language deficits, movement disorders, epilepsy, sleep disturbances, attention problems, anxiety, and obsessive-compulsive traits. Current treatment options for SSADHD remain supportive, but there are ongoing attempts to develop targeted genetic therapies. This study aimed to create consensus guidelines for the diagnosis and management of SSADHD. Thirty relevant statements were initially addressed by a systematic literature review, resulting in different evidence levels of strength according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. The highest level of evidence (level A), based on randomized controlled trials, was unavailable for any of the statements. Based on cohort studies, Level B evidence was available for 12 (40%) of the statements. Thereupon, through a process following the Delphi Method and directed by the Appraisal of Guidelines for Research and Evaluation (AGREE II) criteria, expert opinion was sought, and members of an SSADHD Consensus Group evaluated all the statements. The group consisted of neurologists, epileptologists, neuropsychologists, neurophysiologists, metabolic disease specialists, clinical and biochemical geneticists, and laboratory scientists affiliated with 19 institutions from 11 countries who have clinical experience with SSADHD patients and have studied the disorder. Representatives from parent groups were also included in the Consensus Group. An analysis of the survey's results yielded 25 (83%) strong and 5 (17%) weak agreement strengths. These first-of-their-kind consensus guidelines intend to consolidate and unify the optimal care that can be provided to individuals with SSADHD.

Effect of level of sedation on outcomes in critically ill adult patients: a systematic review of clinical trials with meta-analysis and trial sequential analysis

Sedation is routinely administered to critically ill patients to alleviate anxiety, discomfort, and patient-ventilator asynchrony. However, it must be balanced against risks such as delirium and prolonged intensive care stays. This study aimed to investigate the effects of different levels of sedation in critically ill adults. Systematic review with meta-analysis and trial sequential analysis (TSA) of randomised clinical trials including critically ill adults admitted to the intensive care unit. CENTRAL, MEDLINE, Embase, LILACS, and Web of Science were searched from their inception to 13 June 2023. Risks of bias were assessed using the Cochrane risk of bias tool. Primary outcome was all-cause mortality. Aggregate data were synthesised with meta-analyses and TSA, and the certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO: CRD42023386960. Fifteen trials randomising 4352 patients were included, of which 13 were assessed high risk of bias. Meta-analyses comparing lighter to deeper sedation showed no evidence of a difference in all-cause mortality (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.83-1.06; p=0.28; 15 trials; moderate certainty evidence), serious adverse events (RR 0.99, CI 0.92-1.06; p=0.80; 15 trials; moderate certainty evidence), or delirium (RR 1.01, 95% CI 0.94-1.09; p=0.78; 11 trials; moderate certainty evidence). TSA showed that when assessing mortality, a relative risk reduction of 16% or more between the compared interventions could be rejected. The level of sedation has not been shown to affect the risks of death, delirium, and other serious adverse events in critically ill adult patients. While TSA suggests that additional trials are unlikely to significantly change the conclusion of the meta-analyses, the certainty of evidence was moderate. This suggests a need for future high-quality studies with higher methodological rigor. None.

Programmed Death Ligand-1 and Tumor Mutation Burden Testing of Patients With Lung Cancer for Selection of Immune Checkpoint Inhibitor Therapies: Guideline From the College of American Pathologists, Association for Molecular Pathology, International Association for the Study of Lung Cancer, Pulmonary Pathology Society, and LUNGevity Foundation.

Rapid advancements in the understanding and manipulation of tumor-immune interactions have led to the approval of immune therapies for patients with non-small cell lung cancer. Certain immune checkpoint inhibitor therapies require the use of companion diagnostics, but methodologic variability has led to uncertainty around test selection and implementation in practice. To develop evidence-based guideline recommendations for the testing of immunotherapy/immunomodulatory biomarkers, including programmed death ligand-1 (PD-L1) and tumor mutation burden (TMB), in patients with lung cancer. The College of American Pathologists convened a panel of experts in non-small cell lung cancer and biomarker testing to develop evidence-based recommendations in accordance with the standards for trustworthy clinical practice guidelines established by the National Academy of Medicine. A systematic literature review was conducted to address 8 key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, recommendations were created from the available evidence, certainty of that evidence, and key judgments as defined in the GRADE Evidence to Decision framework. Six recommendation statements were developed. This guideline summarizes the current understanding and hurdles associated with the use of PD-L1 expression and TMB testing for immune checkpoint inhibitor therapy selection in patients with advanced non-small cell lung cancer and presents evidence-based recommendations for PD-L1 and TMB testing in the clinical setting.

Predictive factors of clot propagation in patients with superficial venous thrombosis towards deep venous thrombosis and pulmonary embolism: a systematic review and meta-analysis

ObjectiveA subset of patients with superficial venous thrombosis (SVT) experiences clot propagation towards deep venous thrombosis (DVT) and/or pulmonary embolism (PE). The aim of this systematic review is to identify...

Effects of aloe vera on burn injuries: A systematic review and meta-analysis of randomized controlled trials.

Burn injuries cause severe pain, infection risks, psychological distress, financial burdens, and mortality, necessitating effective care. Aloe vera, a traditional burn remedy, shows wound healing potential, but its analgesic effects and efficacy with varying burn severity are uncertain. This study aims to investigate aloe vera's impact on wound healing, pain management, and infection prevention in burn patients. A systematic search on PubMed, Embase, and CENTRAL was performed on 9th October 2023 for randomized controlled trials (RCTs). The risk of bias was examined using the Cochrane risk-of-bias tool (version 2), and the meta-analysis was carried out using a random-effects model. The primary outcome was wound healing time, with secondary outcomes examining pain severity and wound infection. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence for each outcome. Nine RCTs were included in the current study, of which six provided data on the primary outcome. Aloe vera significantly reduced mean wound healing time compared to other topicals [mean difference (MD) -3.76 days; 95% confidence interval (CI) -5.69 to -1.84]. Additionally, the meta-analysis of the secondary outcomes found no significant differences in pain reduction (MD -0.76 points; 95% CI -1.53 to 0.01) and wound infection risk (risk ratio 1.10; 95% CI 0.34 to 3.59) between aloe vera and control groups. In conclusion, aloe vera expedites wound healing in second-degree burn patients without increased infection risk compared to other antimicrobial agents. The analgesic effects on burn injuries remain uncertain.

Mediterranean diet for cardiovascular disease: an evidence mapping study.

This study aimed to evaluate the methodological quality of existing meta-analyses (MAs) and the quality of evidence for outcome indicators to in order to provide an updated overview of the evidence concerning the therapeutic efficacy of the Mediterranean diet (MD) for various types of Cardiovascular diseases (CVD). We conducted comprehensive searches of PubMed, Cochrane Library, and Embase databases. The quality of the MAs was assessed using the A Measurement Tool to Assess Systematic Reviews 2(AMSTAR 2) checklist, while the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence evaluation system was employed to evaluate the quality of evidence for significant outcomes. The burden of CVD remains a significant contributor to global mortality, garnering widespread attention. Multiple MAs have consistently demonstrated the efficacy of medical interventions in managing CVD. However, due to variations in the scope, quality, and outcomes of these reviews, definitive conclusions are yet to be established. This study included a total of eleven studies, consisting of five randomized trials and twelve nonrandomized studies, with a combined participant population of 716,318. The eligible MAs underwent evaluation using the AMSTAR 2 checklist, which revealed that 54.55% of the studies demonstrated high quality, while 9.09% exhibited low quality and 36.36% were deemed critically low quality. Additionally, there was moderate evidence supporting a positive correlation between MD and coronary heart disease/acute myocardial infarction (CHD/AMI), stroke, heart failure, cardiovascular events, coronary events, and major adverse cardiovascular events (MACE). This study indicates that although recognizing the potential efficacy of MD in managing CVD, the quality of the methodology and the evidence for the outcome indicators remain unsatisfactory. To establish the true benefits of MD for CVD patients, future research should not only adhere to rigorous methodological requirements but also prioritize enhancing the quality of primary studies and conducting patient-centered meta-analyses.

Physical Activity Is Associated With A Decreased Risk Of Developing Inflammatory Bowel Disease: A Systematic Review And Meta-Analysis.

Modifiable risk factors in Inflammatory Bowel Disease (IBD), such as physical activity, may be utilised as prevention strategies. However, the findings of previous studies on the association between physical activity and IBD risk have been inconsistent. We aimed to perform a systematic review and meta-analysis to estimate the effect of physical activity on IBD risk. A search was conducted for relevant studies published before April 2023 that assessed the effect of pre-IBD diagnosis levels of physical activity on IBD incidence. Individual summary statistics (relative risks; RR), and confidence intervals (CI) were extracted with forest plots generated. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. 10 observational studies were included. For cohort studies, there were 1,182 Crohn's disease (CD) and 2,361 ulcerative colitis (UC) patients, with 860,992 participants without IBD. For case-control studies, there were 781 CD to 2,636 controls, and 1,127 UC to 3,752 controls. Compared to individuals with low physical activity levels, the RRs of CD in individuals with high physical activity levels for cohort and case-control studies were 0.78 (95% CI 0.68-0.88, P = 0.0001) and 0.87 (95% CI 0.79-0.95, P = 0.003), respectively. For UC, the RRs were 0.62 (95% CI 0.43-0.88, P = 0.008) and 0.74 (95% CI 0.51-1.07, P = 0.11). This meta-analysis suggests that physical activity is inversely associated with the risk of developing IBD, more so in CD than in UC.

Long-Term Effect of Salt Substitution for Cardiovascular Outcomes : A Systematic Review and Meta-Analysis.

Salt substitution is a simple yet increasingly promising strategy to improve cardiovascular outcomes. To evaluate the long-term effects of salt substitution on cardiovascular outcomes. PubMed, EMBASE, Cochrane CENTRAL, and CINAHL searched from inception to 23 August 2023. Trial registries, citation analysis, and hand-search were also done. Randomized controlled trials (RCTs) comparing provision of or advice to use a salt substitute with no intervention or use of regular salt among adults for 6 months or longer in total study duration. Two authors independently screened articles, extracted data, and assessed risk of bias. Primary outcomes include mortality, major cardiovascular events (MACE), and adverse events at 6 months or greater. Secondary and post hoc outcomes include blood pressure, cause-specific mortality, and urinary excretion at 6 months or greater. Random-effects meta-analyses were done and certainty of effect estimates were assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Of the 16 included RCTs, 8 reported on primary outcomes. Most (n = 7 of 8) were done in China or Taiwan, 3 were done in residential facilities, and 7 included populations of older age (average 62 years) and/or with higher-than-average cardiovascular risk. In this population, salt substitute may reduce risk for all-cause mortality (6 RCTs; 27 710 participants; rate ratio [RR], 0.88 [95% CI, 0.82 to 0.93]; low certainty) and cardiovascular mortality (4 RCTs; 25 050 participants; RR, 0.83 [CI, 0.73 to 0.95]; low certainty). Salt substitute may result in a slight reduction in MACE (3 RCTs; 23 215 participants; RR, 0.85 [CI, 0.71 to 1.00]; very low certainty), with very low-certainty evidence of serious adverse events (6 RCTs; 27 995 participants; risk ratio, 1.04 [CI, 0.87 to 1.25]). The evidence base is dominated by a single, large RCT. Most RCTs were from China or Taiwan and involved participants with higher-than-average cardiovascular risk; therefore, generalizability to other populations is very limited. Salt substitution may reduce all-cause or cardiovascular mortality, but the evidence for reducing cardiovascular events and for not increasing serious adverse events is uncertain, particularly for a Western population. The certainty of evidence is higher among populations at higher cardiovascular risk and/or following a Chinese diet. National Health and Medical Research Council. (PROSPERO: CRD42022327566).

The Efficacy of Physical Therapy to Alleviate Symptomatic Thoracic Radiculopathy: A Systematic Review and Meta-Narrative Analysis.

To evaluate the efficacy of physical therapy (PT) to alleviate symptomatic thoracic radiculopathy (TR) without the use of invasive procedures. Database search was conducted by an experienced medical librarian from inception until January 27, 2023, in EBSCO CINAHL with Full Text, Ovid Cochrane Central Register of Controlled Trials, Ovid Embase, Ovid MEDLINE, Scopus, and Web of Science Core Collection. Inclusion criteria included studies that involved adult patients (age≥18) who had a magnetic resonance imaging-confirmed TR and underwent a structured, supervised PT program of any length. All types of studies were included. Study quality and risk of bias were assessed using the National Heart, Lung, and Blood Institute (NHLBI) Study Quality of Assessment Tool. Certainty in evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. A meta-analysis was not performed. A total of 1,491 studies were screened and 7 studies met inclusion criteria, 5 case studies and 2 cohort studies. All studies showed improvement or resolution of the TR with PT. Quantitative improvements were not noted in most studies and PT regimens were sparsely described. Overall quality assessment demonstrated 3 studies had "good," 1 "fair," and 3 "poor" quality evidence. Certainty of evidence was "low" due to risk of bias. A dedicated PT program may help to alleviate symptomatic TR; however due to limited evidence, risk of bias, and low certainty in evidence, the data is too weak to support a definite conclusion.

Umbilical cord milking and delayed cord clamping for the prevention of neonatal hypoglycaemia: a systematic review and meta-analysis.

Placental management strategies such as umbilical cord milking and delayed cord clamping may provide a range of benefits for the newborn. The aim of this review was to assess the effectiveness of umbilical cord milking and delayed cord clamping for the prevention of neonatal hypoglycaemia. Three databases and five clinical trial registries were systematically reviewed to identify randomised controlled trials comparing umbilical cord milking or delayed cord clamping with control in term and preterm infants. The primary outcome was neonatal hypoglycaemia (study defined). Two independent reviewers conducted screening, data extraction and quality assessment. Quality of the included studies was assessed using the Cochrane Risk of Bias tool (RoB-2). Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Meta-analysis using a random effect model was done using Review Manager 5.4. The review was registered prospectively on PROSPERO (CRD42022356553). Data from 71 studies and 14 268 infants were included in this review; 22 (2 537 infants) compared umbilical cord milking with control, and 50 studies (11 731 infants) compared delayed with early cord clamping. For umbilical cord milking there were no data on neonatal hypoglycaemia, and no differences between groups for any of the secondary outcomes. We found no evidence that delayed cord clamping reduced the incidence of hypoglycaemia (6 studies, 444 infants, RR = 0.87, CI: 0.58 to 1.30, p = 0.49, I2 = 0%). Delayed cord clamping was associated with a 27% reduction in neonatal mortality (15 studies, 3 041 infants, RR = 0.73, CI: 0.55 to 0.98, p = 0.03, I2 = 0%). We found no evidence for the effect of delayed cord clamping for any of the other outcomes. The certainty of evidence was low for all outcomes. We found no data for the effectiveness of umbilical cord milking on neonatal hypoglycaemia, and no evidence that delayed cord clamping reduced the incidence of hypoglycaemia, but the certainty of the evidence was low.

Home versus in-centre haemodialysis for people with kidney failure.

Home haemodialysis (HHD) may be associated with important clinical, social or economic benefits. However, few randomised controlled trials (RCTs) have evaluated HHD versus in-centre HD (ICHD). The relative benefits and harms of these two HD modalities are uncertain. This is an update of a review first published in 2014. This update includes non-randomised studies of interventions (NRSIs). To evaluate the benefits and harms of HHD versus ICHD in adults with kidney failure. We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 9 October 2022 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. We searched MEDLINE (OVID) and EMBASE (OVID) for NRSIs. RCTs and NRSIs evaluating HHD (including community houses and self-care) compared to ICHD in adults with kidney failure were eligible. The outcomes of interest were cardiovascular death, all-cause death, non-fatal myocardial infarction, non-fatal stroke, all-cause hospitalisation, vascular access interventions, central venous catheter insertion/exchange, vascular access infection, parathyroidectomy, wait-listing for a kidney transplant, receipt of a kidney transplant, quality of life (QoL), symptoms related to dialysis therapy, fatigue, recovery time, cost-effectiveness, blood pressure, and left ventricular mass. Two authors independently assessed if the studies were eligible and then extracted data. The risk of bias was assessed, and relevant outcomes were extracted. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Meta-analysis was performed on outcomes where there was sufficient data. From the 1305 records identified, a single cross-over RCT and 39 NRSIs proved eligible for inclusion. These studies were of varying design (prospective cohort, retrospective cohort, cross-sectional) and involved a widely variable number of participants (small single-centre studies to international registry analyses). Studies also varied in the treatment prescription and delivery (e.g. treatment duration, frequency, dialysis machine parameters) and participant characteristics (e.g. time on dialysis). Studies often did not describe these parameters in detail. Although the risk of bias, as assessed by the Newcastle-Ottawa Scale, was generally low for most studies, within the constraints of observational study design, studies were at risk of selection bias and residual confounding. Many study outcomes were reported in ways that did not allow direct comparison or meta-analysis. It is uncertain whether HHD, compared to ICHD, may be associated with a decrease in cardiovascular death (RR 0.92, 95% CI 0.80 to 1.07; 2 NRSIs, 30,900 participants; very low certainty evidence) or all-cause death (RR 0.80, 95% CI 0.67 to 0.95; 9 NRSIs, 58,984 patients; very low certainty evidence). It is also uncertain whether HHD may be associated with a decrease in hospitalisation rate (MD -0.50 admissions per patient-year, 95% CI -0.98 to -0.02; 2 NRSIs, 834 participants; very low certainty evidence), compared with ICHD. Compared with ICHD, it is uncertain whether HHD may be associated with receipt of kidney transplantation (RR 1.28, 95% CI 1.01 to 1.63; 6 NRSIs, 10,910 participants; very low certainty evidence) and a shorter recovery time post-dialysis (MD -2.0 hours, 95% CI -2.73 to -1.28; 2 NRSIs, 348 participants; very low certainty evidence). It remains uncertain if HHD may be associated with decreased systolic blood pressure (SBP) (MD -11.71 mm Hg, 95% CI -21.11 to -2.46; 4 NRSIs, 491 participants; very low certainty evidence) and decreased left ventricular mass index (LVMI) (MD -17.74 g/m2, 95% CI -29.60 to -5.89; 2 NRSIs, 130 participants; low certainty evidence). There was insufficient data to evaluate the relative association of HHD and ICHD with fatigue or vascular access outcomes. Patient-reported outcome measures were reported using 18 different measures across 11 studies (QoL: 6 measures; mental health: 3 measures; symptoms: 1 measure; impact and view of health: 6 measures; functional ability: 2 measures). Few studies reported the same measures, which limited the ability to perform meta-analysis or compare outcomes. It is uncertain whether HHD is more cost-effective than ICHD, both in the first (SMD -1.25, 95% CI -2.13 to -0.37; 4 NRSIs, 13,809 participants; very low certainty evidence) and second year of dialysis (SMD -1.47, 95% CI -2.72 to -0.21; 4 NRSIs, 13,809 participants; very low certainty evidence). Based on low to very low certainty evidence, HHD, compared with ICHD, has uncertain associations or may be associated with decreased cardiovascular and all-cause death, hospitalisation rate, slower post-dialysis recovery time, and decreased SBP and LVMI. HHD has uncertain cost-effectiveness compared with ICHD in the first and second years of treatment. The majority of studies included in this review were observational and subject to potential selection bias and confounding, especially as patients treated with HHD tended to be younger with fewer comorbidities. Variation from study to study in the choice of outcomes and the way in which they were reported limited the ability to perform meta-analyses. Future research should align outcome measures and metrics with other research in the field in order to allow comparison between studies, establish outcome effects with greater certainty, and avoid research waste.

Predictors of health-related quality of life one year after stroke: a systematic review with meta-analysis.

The objective was to investigate, through a systematic review, which independent variables predict health-related quality of life (HRQoL) one year after stroke. Searches were conducted in LILACS, MEDLINE, Scielo, Web of Science, and PEDro. The inclusion criteria were observational longitudinal studies, which included at least one independent variable measured at baseline, as a potential predictor of HRQoL measured 12 months after stroke. The predictors of interest were variables across all domains of the International Classification of Function, Disability and Health. The quality of evidence was rated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). A total of 17 papers were included, involving 8338 participants, and 10 possible predictors of the HRQoL one year after stroke. The meta-analysis was performed for six of them (cognition, depression, neurological deficit, stroke severity, motor impairment, and limitation in activities of daily living), and significant results were found only for limitation in activities of daily living (odds ratio, 1.30 [95% confidence interval, 1.09-1.57]; I2 = 72%; P < 0.01). The descriptive analysis of the remaining four predictors suggested a significant predictive value of balance and functional independence, whereas the results for trunk control were not significant and for social participation were unclear. In conclusion, individuals within the first 11.5 weeks after stroke with lower limitation in activities of daily living, higher functional independence, and better balance, are more likely to have a higher HRQoL one year after stroke. Thus, these predictors, all modifiable factors, need to be targeted during acute rehabilitation.

Opioid-Sparing Anesthesia Versus Opioid-Free Anesthesia for the Prevention of Postoperative Nausea and Vomiting after Laparoscopic Bariatric Surgery: A Systematic Review and Network Meta-Analysis.

Patients who undergo laparoscopic bariatric surgery (LBS) are susceptible to postoperative nausea and vomiting (PONV). Opioid-free anesthesia (OFA) or opioid-sparing anesthesia (OSA) protocols have been proposed as solutions; however, differences between the 2 alternative opioid protocols for anesthesia maintenance in obese patients remain uncertain. A network meta-analysis was conducted to compare the impacts of OFA and OSA on PONV. Systematic searches were conducted using Embase, PubMed, MEDLINE, and Cochrane Library databases to identify randomized controlled trials (RCTs) comparing OFA and OSA strategies. After screening according to the inclusion and exclusion criteria, we used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the credibility of the evidence. The main concern of this review was the difference between OFA and OSA in reducing PONV. The primary outcome was any PONV occurrence within 24 hours. Secondary outcomes included postoperative pain intensity, opioid consumption, opioid-related adverse events, and length of hospital stay. Fifteen RCTs involving 1310 patients were identified for a network meta-analysis from 1776 articles that compared OFA, OSA, and traditional opioid-based anesthesia (OBA) strategies in LBS. Twelve RCTs (80%) with 922 participants (70%) were eligible for the occurrence of PONV. These included 199 (22%) patients who received OFA and 476 (52%) and 247 (27%) patients who received OSA and OBA, respectively. OFA was more effective at reducing PONV (relative risks [RR], 0.6, 95% confidence interval [CI], 0.5-0.9, moderate-quality evidence) compared to OSA. No differences were observed in postoperative pain control or opioid consumption between the OFA and OSA strategies (very low-to high-quality evidence). Notably, OFA is associated with a higher risk of bradycardia than OSA (RR, 2.6, 95% CI, 1.2-5.9, moderate-quality evidence). OFA is more effective than OSA in reducing the occurrence of PONV during the early postoperative period of LBS, although it may associate with an increased risk of bradycardia. Patients who received either opioid-alternative strategy demonstrated similar effects in reducing postoperative opioid consumption and alleviating pain intensity.

Clinical guideline on reversal of direct oral anticoagulants in patients with life threatening bleeding.

Anticoagulation is essential for the treatment and prevention of thromboembolic events. Current guidelines recommend direct oral anticoagulants (DOACs) over vitamin K antagonists in DOAC-eligible patients. The major complication of anticoagulation is serious or life-threatening haemorrhage, which may necessitate prompt haemostatic intervention. Reversal of DOACs may also be required for patients in need of urgent invasive procedures. This guideline from the European Society of Anaesthesiology and Intensive Care (ESAIC) aims to provide evidence-based recommendations and suggestions on how to manage patients on DOACs undergoing urgent or emergency procedures including the treatment of DOAC-induced bleeding. A systematic literature search was performed, examining four drug comparators (dabigatran, rivaroxaban, apixaban, edoxaban) and clinical scenarios ranging from planned to emergency surgery with the outcomes of mortality, haematoma growth and thromboembolic complications. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology was used to assess the methodological quality of the included studies. Consensus on the wording of the recommendations was achieved by a Delphi process. So far, no results from prospective randomised trials comparing two active comparators (e.g. a direct reversal agent and an unspecific haemostatic agent such as prothrombin complex concentrate: PCC) have been published yet and the majority of publications were uncontrolled and observational studies. Thus, the certainty of evidence was assessed to be either low or very low (GRADE C). Thirty-five recommendations and clinical practice statements were developed. During the Delphi process, strong consensus (>90% agreement) was achieved in 97.1% of recommendations and consensus (75 to 90% agreement) in 2.9%. DOAC-specific coagulation monitoring may help in patients at risk for elevated DOAC levels, whereas global coagulation tests are not recommended to exclude clinically relevant DOAC levels. In urgent clinical situations, haemostatic treatment using either the direct reversal or nonspecific haemostatic agents should be started without waiting for DOAC level monitoring. DOAC levels above 50 ng ml-1 may be considered clinically relevant necessitating haemostatic treatment before urgent or emergency procedures. Before cardiac surgery under activated factor Xa (FXa) inhibitors, the use of andexanet alfa is not recommended because of inhibition of unfractionated heparin, which is needed for extracorporeal circulation. In the situation of DOAC overdose without bleeding, no haemostatic intervention is suggested, instead measures to eliminate the DOACs should be taken. Due to the lack of published results from comparative prospective, randomised studies, the superiority of reversal treatment strategy vs. a nonspecific haemostatic treatment is unclear for most urgent and emergency procedures and bleeding. Due to the paucity of clinical data, no recommendations for the use of recombinant activated factor VII as a nonspecific haemostatic agent can be given. In the clinical scenarios of DOAC intake before urgent procedures and DOAC-induced bleeding, practitioners should evaluate the risk of bleeding of the procedure and the severity of the DOAC-induced bleeding before initiating treatment. Optimal reversal strategy remains to be determined in future trials for most clinical settings.

The association between serum vitamin D levels and abnormal lipid profile in pediatrics: A GRADE-assessed systematic review and dose-response meta-analysis of epidemiologic studies.

Several studies have investigated the relationship between serum vitamin D and dyslipidemia in children and adolescents, but the findings have been contradictory. The current systematic review and dose-response meta-analysis investigated the serum vitamin D - dyslipidemia relationship in children and adolescents. ISI Web of Science, Scopus, MEDLINE (PubMed), EMBASE databases, and Google Scholar, were searched up to December 2022. Observational studies that investigated the odds of dyslipidemia in categories of serum vitamin D levels in children were included, and their data were extracted. Pooling of 17 effect sizes from 15 studies (39 342 participants) showed that subjects with higher serum vitamin D had 27% lower odds of hypertriglyceridemia (odds ratio [OR] = 0.73; 95% confidence interval [CI]: 0.60, 0.88). A meta-analysis of 18 effect sizes from 16 studies (39 718 participants) illustrated that highest vs lowest serum vitamin D was related to 22% lower odds of low high-density lipoprotein cholesterol (HDL-c) (OR = 0.78; 95% CI: 0.66, 0.91). Also, a nonlinear association between serum vitamin D and odds of abnormal lipid profile was found: elevating values of 25-hydroxyvitamin D from 35 nmol/L to 55 nmol/L was associated with a decreasing trend in odds of hypertriglyceridemia, hyper low-density lipoprotein cholesterolemia, hypercholesterolemia, and hypo HDL-cholesterolemia. However, no significant linear association was observed. Based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE), the certainty of all evidence was rated as high. This meta-analysis revealed that the level of 25-hydroxyvitamin D was inversely related to odds of abnormal serum triglycerides and HDL-c in children and adolescents. Increasing serum vitamin D from 35 nmol/L to 55 nmol/L was associated with a decreasing trend in the odds of abnormal serum triglycerides, HDL-c, low-density lipoprotein cholesterol, and total cholesterol in children. PROSPERO registration no. 42023400787.

The association between inflammatory biomarkers and low back disorder: a systematic review and meta-analysis

Introduction Low back disorder (LBD) is a major cause of disability worldwide. Inflammation results in proliferation of cytokines or consequent degradation products (collectively known as inflammatory biomarkers) that activate pain pathways which can result in non-specific LBD. This systematic review and meta-analysis aim to evaluate the relationship between inflammatory biomarkers and clinical outcomes in patients with LBD. Methods The PRISMA guideline was followed for the systematic reivew. Three online databases were searched. Four RCTs and sixteen observational studies with 1142 LBD patients were analysed. The primary outcomes were back and leg pain scores, back-specific disability scores and expression of inflammatory biomarkers. Standardized mean difference (SMD) and their 95% confidence intervals (CI) were evaluated. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to summarize the strength of evidence. Results Four RCTs and sixteen observational studies were included in the analysis of 1142 patients with LBD. There was a statistically significant reduction in back pain score and IL-1 beta and increase in the expression of CTX-1 and IL-10 levels post treatment. There was a significant relationship between increase in the expression of MCP- and reduction in the expression of hsCRP with increase in back pain. Significant relationship was also observed between increase in the expression of MCP-1 and reduction in the expression of IL-6 with increase in leg pain. Increase in the expression of IL-8 and reduction in the expression of hsCRP was also associated with increased disability score. Conclusion Inflammatory biomarkers play a significant role in the pathogenesis of LBD. CTX-1, IL-10 and IL-1 beta may be responsible for the decrease in back pain scores post treatment. There is a relationship between MCP-1, IL-6, IL-8 and hsCRP with clinical and functional assessments for LBD. Further studies will improve understanding of the pathogenesis of LBD and aid in targeted management strategies.

A practical evidence-based approach to management of type 2 diabetes in children and young people (CYP): UK consensus

BackgroundType 2 diabetes in young people is an aggressive disease with a greater risk of complications leading to increased morbidity and mortality during the most productive years of life. Prevalence in the UK and globally is rising yet experience in managing this condition is limited. There are no consensus guidelines in the UK for the assessment and management of paediatric type 2 diabetes.MethodsMultidisciplinary professionals from The Association of Children’s Diabetes Clinicians (ACDC) and the National Type 2 Diabetes Working Group reviewed the evidence base and made recommendations using the Grading Of Recommendations, Assessment, Development and Evaluation (GRADE) methodology.Results and discussionYoung people with type 2 diabetes should be managed within a paediatric diabetes team with close working with adult diabetes specialists, primary care and other paediatric specialties. Diagnosis of diabetes type can be challenging with many overlapping features. Diabetes antibodies may be needed to aid diagnosis. Co-morbidities and complications are frequently present at diagnosis and should be managed holistically. Lifestyle change and metformin are the mainstay of early treatment, with some needing additional basal insulin. GLP1 agonists should be used as second-line agents once early ketosis and symptoms are controlled. Glycaemic control improves microvascular but not cardiovascular risk. Reduction in excess adiposity, smoking prevention, increased physical activity and reduction of hypertension and dyslipidaemia are essential to reduce major adverse cardiovascular events.ConclusionsThis evidence-based guideline aims to provide a practical approach in managing this condition in the UK.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update – XII – Recommendations on milk formula supplements with and without probiotics for infants and toddlers with CMA

BackgroundCow's milk allergy (CMA) is the most common food allergy in infants. The replacement with specialized formulas is an established clinical approach to ensure adequate growth and minimize the risk of severe allergic reactions when breastfeeding is not possible. Still, given the availability of multiple options, such as extensively hydrolyzed cow's milk protein formula (eHF-CM), amino acid formula (AAF), hydrolyzed rice formula (HRF) and soy formulas (SF), there is some uncertainty as to the most suitable choice with respect to health outcomes. Furthermore, the addition of probiotics to a formula has been proposed as a potential approach to maximize benefit. ObjectiveThese evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of milk specialized formulas, with and without probiotics, for individuals with CMA. MethodsWAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to review by stakeholders. ResultsAfter reviewing the summarized evidence and thoroughly discussing the different management options, the WAO guideline panel suggests: a) using an extensively hydrolyzed (cow's milk) formula or a hydrolyzed rice formula as the first option for managing infants with immunoglobulin E (IgE) and non-IgE-mediated CMA who are not being breastfed. An amino-acid formula or a soy formula could be regarded as second and third options respectively; b) using either a formula without a probiotic or a casein-based extensively hydrolyzed formula containing Lacticaseibacillus rhamnosus GG (LGG) for infants with either IgE or non-IgE-mediated CMA.The issued recommendations are labeled as “conditional” following the GRADE approach due to the very low certainty about the health effects based on the available evidence. ConclusionsIf breastfeeding is not available, clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable consequences of each formula in infants with CMA, integrating them with the patients' and caregivers’ values and preferences, local availability, and cost, before deciding on a treatment option. We also suggest what research is needed to determine with greater certainty which formulas are likely to be the most beneficial, cost-effective, and equitable.

Formulation of international standards of Chinese medicine technology: clinical practice guide of Chinese medicine for cough.

To formulate the first clinical practice guideline for the treatment of cough using Chinese medicine based on the grading of recommendations assessment, development, and evaluation (GRADE) systematic approach, including clinical evidence, evaluation of ancient literature, and expert consensus. In the process of development, the regulation of "evidence-based, consensus-assisted, and empirical" was followed, and a comprehensive systematic approach of recommendation assessment, GRADE, evidence-based evaluation, expert consensus, and the Delphi method was used. In the process of guideline development, evidence-based evaluation of ancient literature was included for the first time, and clinical evidence was fully integrated with clinical expert consensus. The clinical practice guidelines for the treatment of cough with Chinese herbal medicine were developed after a comprehensive consideration of evidence-based evaluation and expert opinions. The guideline recommendations focused on recommending herbal compound decoctions and Chinese patent medicines for cough in different conditions. Based on the GRADE systematic approach, we conducted an evidence-based evaluation of the recommended Chinese patent medicines one by one; meanwhile, the expert consensus method was used to unify the recommendations of both. Based on clinical evidence, ancient literature evaluation, and expert consensus, a clinical practice guideline for Traditional Chinese Medicine (TCM) in the treatment of cough was developed, providing the first current clinical practice guideline for domestic and foreign TCM and Western medicine practitioners, especially respiratory professionals at home and abroad.

Non-operative management of high-grade splenic injury: a systematic review protocol.

The objective of this review is to establish whether embolization is more effective than clinical observation for adult patients with grade III-V splenic injuries. The findings will be used to guide future practice and, if necessary, inform future research design and conduct. The spleen is one of the most frequently injured intra-abdominal organs, with a reported adult mortality of 7% to 18% following trauma. Non-operative management has become a standard of care for hemodynamically stable patients. In clinical practice, the decision whether to prophylactically embolize or manage high-grade injuries with observation alone remains controversial. Sources including adult patients with grade III-V splenic injuries secondary to blunt trauma will be included in this review. Eligible studies must include comparisons between 2 cohorts of patients undergoing either prophylactic embolization or clinical observation only. Outcomes will include mortality rate, failure of treatment, intensive care unit admission, length of hospital stay, blood transfusion requirements, and patient satisfaction. A systematic review with meta-analysis will be conducted. PubMed, Embase, and CINAHL will be searched for eligible studies, as will trial registries and sources of gray literature. Study selection, quality appraisal, and data extraction of outcomes will be performed in duplicate. Methodological quality will be evaluated using JBI critical appraisal tools. Studies will, where possible, be pooled in statistical meta-analysis. A random effects model will be used and statistical analysis will be performed. The certainty of the findings will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. PROSPERO CRD42023420220.