Assessing the Certainty of the Evidence in Systematic Reviews: Importance, Process, and Use.

When interpreting results and drawing conclusions, authors of systematic reviews should consider the limitations of the evidence included in their review. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach provides a framework for the explicit consideration of the limitations of the evidence included in a systematic review, and for incorporating this assessment into the conclusions. Assessments of certainty of evidence are a methodological expectation of systematic reviews. The certainty of the evidence is specific to each outcome in a systematic review, and can be rated as high, moderate, low, or very low. Because it will have an important impact, before conducting certainty of evidence, reviewers must clarify the intent of their question: are they interested in causation or association. Serious concerns regarding limitations in the study design, inconsistency, imprecision, indirectness, and publication bias can decrease the certainty of the evidence. Using an example, this article describes and illustrates the importance and the steps for assessing the certainty of evidence and drawing accurate conclusions in a systematic review.

Enhancing the quality of evidence, comparability, and reproducibility in brain arteriovenous malformations treated with open surgery research: a systematic review and proposal of a reporting guideline for surgical and clinical outcomes.

Brain Arteriovenous Malformations (bAVMs) are rare but high-risk developmental anomalies of the vascular system. Microsurgery through craniotomy is believed to be the mainstay standard treatment for many grades of bAVMs. However, a significant challenge emerges in the existing body of clinical studies on open surgery for bAVMs: the lack of reproducibility and comparability. This study aims to assess the quality of studies reporting clinical and surgical outcomes for bAVMs treated by open surgery and develop a reporting guideline checklist focusing on essential elements to ensure comparability and reproducibility. This is a systematic literature review that followed the PRISMA guidelines with the search in Medline, Embase, and Web of Science databases, for studies published between January 1, 2018, and December 1, 2023. Included studies were scrutinized focusing on seven domains: (1) Assessment of How Studies Reported on the Baseline Characteristics of the Patient Sample; (2) Assessment and reporting on bAVMs grading, anatomical characteristics, and radiological aspects; (3) Angioarchitecture Assessment and Reporting; (4) Reporting on Pivotal Concepts Definitions; (5) Reporting on Neurosurgeon(s) and Staff Characteristics; (6) Reporting on Surgical Details; (7) Assessing and Reporting Clinical and Surgical Outcomes and AEs. A total of 47 studies comprising 5,884 patients were included. The scrutiny of the studies identified that the current literature in bAVM open surgery is deficient in many aspects, ranging from fundamental pieces of information of methodology to baseline characteristics of included patients and data reporting. Included studies demonstrated a lack of reproducibility that hinders building cumulative evidence. A bAVM Open Surgery Reporting Guideline with 65 items distributed across eight domains was developed and is proposed in this study aiming to address these shortcomings. This systematic review identified that the available literature regarding microsurgery for bAVM treatment, particularly in studies reporting clinical and surgical outcomes, lacks rigorous scientific methodology and quality in reporting. The proposed bAVM Open Surgery Reporting Guideline covers all essential aspects and is a potential solution to address these shortcomings and increase transparency, comparability, and reproducibility in this scenario. This proposal aims to advance the level of evidence and enhance knowledge regarding the Open Surgery treatment for bAVMs.

Effects of timing of umbilical cord clamping for mother and newborn: a narrative review.

OBJECTIVE: This narrative review was performed to evaluate the correct timing of umbilical cord clamping for term infants. It was intended to determine any advantages or disadvantages from early or delayed cord clamping for newborns, infants or mothers. METHODS: A systematic search on two databases was conducted using the PICO pattern to define a wide search. Out of 43 trials, 12 were included in this review. Three of the included studies are meta-analyses, nine are randomized controlled trials. RESULTS: Early or delayed cord clamping was defined differently in all the included trials. However, there are many advantages from delayed cord clamping of at least > 60 s for newborns and infants up to 12 months of age. The trials showed no disadvantages for newborns or mothers from delayed cord clamping, except for a lightly increased risk of jaundice or the need for phototherapy. CONCLUSION: Delayed umbilical cord clamping for term infants should be performed. Further research is needed to improve knowledge on physiological timing of umbilical cord clamping in term infants, which also leads to the same advantages as delayed cord clamping.

Cost-effectiveness of clinical interventions for delirium: A systematic literature review of economic evaluations.

OBJECTIVE: Little is known about the economic value of clinical interventions for delirium. This review aims to synthesise and appraise available economic evidence, including resource use, costs, and cost-effectiveness of interventions for reducing, preventing, and treating delirium. METHODS: Systematic review of published and grey literature on full and partial economic evaluations. Study quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). RESULTS: Fourteen economic evaluations (43% full, 57% partial) across nine multicomponent and nonpharmacological intervention types met inclusion criteria. The intervention costs ranged between US$386 and $553 per person in inpatient settings. Multicomponent delirium prevention intervention and the Hospital Elder Life Program (HELP) reported statistically significant cost savings or cost offsets somewhere else in the health system. Cost savings related to inpatient, outpatient, and out-of-pocket costs ranged between $194 and $6022 per person. The average CHEERS score was 74% (±SD 10%). CONCLUSION: Evidence on a joint distribution of costs and outcomes of delirium interventions was limited, varied and of generally low quality. Directed expansion of health economics towards the evaluation of delirium care is necessary to ensure effective implementation that meets patients' needs and is cost-effective in achieving similar or better outcomes for the same or lower cost.

One-Third of Systematic Reviews in Rehabilitation Applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) System to Evaluate Certainty of Evidence: A Meta-Research Study.

OBJECTIVE: To determine how many systematic reviews (SRs) of the literature in rehabilitation assess the certainty of evidence (CoE) and how many apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to do this. DATA SOURCES: For this meta-research study, we searched PubMed and Cochrane Database of Systematic Reviews databases for SRs on rehabilitation published in 2020. STUDY SELECTION AND DATA EXTRACTION: Two reviewers independently selected the SRs and extracted the data. Reporting characteristics and appropriate use of the GRADE system were assessed. DATA SYNTHESIS: The search retrieved 827 records: 29% (239/827) SRs evaluated CoE, 68% (163/239) of which applied the GRADE system. GRADE was used by SRs of randomized controlled trials (RCTs, 88%; 144/163), non-randomized intervention studies (NRIS, 2%; 3/163), and both RCT and NRIS (10%; 16/163). In the latter case, a separate GRADE assessment according to the study design was not provided in 75% (12/16). The reasons for GRADE judgment were reported in 82% (134/163) of SRs. CONCLUSIONS: One-third of SRs in rehabilitation assessed CoE with the GRADE system. GRADE assessment was presented transparently by most SRs. Journal editors and funders should encourage the uptake of the GRADE system when considering SRs in rehabilitation for publication. The authors should pre-define GRADE assessment in a registered and/or published protocol.

Quality of athlete screening for high-risk cardiovascular conditions-A systematic review.

BACKGROUND: Sudden cardiac death (SCD) is the leading medical cause of death in athletes. To prevent SCD, screening for high-risk cardiovascular conditions (HRCC) is recommended. Screening strategies are based on a limited number of studies and expert consensus. However, evidence and efficacy of athlete HRCC screening is unclear. OBJECTIVE: To determine methodological quality and quality of evidence of athlete screening, and screening efficacy to detect HRCC in a systematic review. METHODS: We performed a systematic search of Medline, Embase, Scopus and Cochrane Library up to June 2021. We included articles containing original data of athlete cardiovascular screening, providing details of screening strategies, test results and HRCC detection. We assessed methodological quality of the included articles by QUADAS-2, quality of evidence of athlete HRCC screening by GRADE, and athlete HRCC screening efficacy by SWiM. RESULTS: Of 2720 citations, we included 33 articles (1991-2018), comprising 82 417 athletes (26.7% elite, 73.4% competitive, 21.7% women, 75.2% aged ≤35). Methodological quality was 'very low' (33 articles), caused by absence of data blinding and inappropriate statistical analysis. Quality of evidence was 'very low' (33 articles), due to observational designs and population heterogeneity. Screening efficacy could not be reliably established. The prevalence of HRCC was 0.43% with false positive rate (FPR) 13.0%. CONCLUSIONS: Methodological quality and quality of evidence on athlete screening are suboptimal. Efficacy could not be reliably established. The prevalence of screen detected HRCC was very low and FPR high. Given the limitations of the evidence, individual recommendations need to be prudent.

Editor's Choice - European Society for Vascular Surgery Clinical Practice Guideline Development Scheme: An Overview of Evidence Quality Assessment Methods, Evidence to Decision Frameworks, and Reporting Standards in Guideline Development.

OBJECTIVE: A structured and transparent approach is instrumental in translating research evidence to health recommendations and evidence informed clinical decisions. The aim was to conduct an overview and analysis of principles and methodologies for health guideline development. METHODS: A literature review on methodologies, strategies, and fundamental steps in the process of guideline development was performed. The clinical practice guideline development process and methodology adopted by the European Society for Vascular Surgery are also presented. RESULTS: Sophisticated methodologies for health guideline development are being applied increasingly by national and international organisations. Their overarching principle is a systematic, structured, transparent, and iterative process that is aimed at making well informed healthcare choices. Critical steps in guideline development include the assessment of the certainty of the body of evidence; evidence to decision frameworks; and guideline reporting. The goal of strength of evidence assessments is to provide well reasoned judgements about the guideline developers' confidence in study findings, and several evidence hierarchy schemes and evidence rating systems have been described for this purpose. Evidence to decision frameworks help guideline developers and users conceptualise and interpret the construct of the quality of the body of evidence. The most widely used evidence to decision frameworks are those developed by the GRADE Working Group and the WHO-INTEGRATE, and are structured into three distinct components: background; assessment; and conclusions. Health guideline reporting tools are employed to ensure methodological rigour and transparency in guideline development. Such reporting instruments include the AGREE II and RIGHT, with the former being used for guideline development and appraisal, as well as reporting. CONCLUSION: This guide will help guideline developers/expert panels enhance their methodology, and patients/clinicians/policymakers interpret guideline recommendations and put them in context. This document may be a useful methodological summary for health guideline development by other societies and organisations.

The Grading of Recommendations, assessment, development, and evaluation approach was rarely followed and inconsistently applied in pressure injury prevention guidelines development: A cross-sectional survey.

INTRODUCTION: The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was developed to assess the certainty (or quality) of evidence and strength of recommendations in guidelines and endorsed internationally as a standard. Some guidelines had been developed to promote pressure injury prevention. AIMS: We explored whether and to what extent the development of pressure injury prevention guidelines had followed or been informed by the GRADE approach. If this approach was not used, we examined which other methods were used instead. METHODS: A cross-sectional study of pressure injury prevention guidelines was conducted. PubMed, Embase, CINAHL, and Chinese databases as well as guideline repositories and websites of professional bodies were searched for guidelines from 1990 to 2020. The grading systems of the certainty (or quality) of evidence and strength of recommendations of included guidelines were extracted. For the GRADE approach guidelines, compliance was assessed with the GRADE application criteria. RESULTS: Twenty guidelines were identified. Among them, four guidelines (20%) indicated the use of the GRADE approach. The compliance rate ranged from 33.3%-94.4%. Other approaches, such as the Scottish Intercollegiate Guidelines Network (SIGN) approach, were also used. CONCLUSION: The GRADE approach is rarely followed and inconsistently applied in pressure injury prevention guidelines. Other systems, such as the SIGN approach, are being used despite being outdated or inconsistent. Strategies for further uptake and appropriate application of the GRADE approach among guideline developers are needed in the future.

Evidence supporting recommendations from international guidelines on treatment, diagnosis, and prevention of HAP and VAP in adults.

Clinical practice guidelines (CPGs) are intended to support clinical decisions and should be based on high-quality evidence. The objective of the study was to evaluate the quality of evidence supporting the recommendations issued in CPGs for therapy, diagnosis, and prevention of hospital-acquired and ventilator-associated pneumonia (HAP/VAP). CPGs released by international scientific societies after year 2000, using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology, were analyzed. Number and strength of recommendations and quality of evidence (high, moderate, low, and very low) were extracted and indexed in the aforementioned sections. High-quality evidence was based on randomized control trials (RCT) without important limitations and exceptionally on rigorous observational studies. Eighty recommendations were assessed, with 7 (8.7%), 24 (30.0%), 29 (36.3%), and 20 (25.0%) being supported by high, moderate, low, and very low-quality evidence, respectively. Highest evidence degree was reported for 26 prevention recommendations, with 7 (26.9%) supported by high-quality evidence and no recommendation based on very low-quality evidence. In contrast, among 9 recommendations for diagnosis and 45 for therapy, none was supported by high-quality evidence, in spite of being recommended as strong in 33.3% and 46.7%, respectively. Among HAP/VAP diagnosis recommendations, the majority of evidence was rated as low or very low-quality (55.6% and 22.2%, respectively) whereas among HAP/VAP therapy recommendations, 4/5 were rated as low and very low-quality (40% each). In conclusion, among HAP/VAP international guidelines, most recommendations, particularly in therapy, remain supported by observational studies, case reports, and expert opinion. Well-designed RCTs are urgently needed.

Effect on perinatal outcome of prophylactic antibiotics in preterm prelabor rupture of membranes: network meta-analysis of randomized controlled trials.

OBJECTIVES: Prophylactic antibiotics are recommended routinely for preterm prelabor rupture of membranes (PPROM), but there is an abundance of potential treatments and a paucity of comparative information. The aims of this network meta-analysis were to compare the efficiency of different antibiotic regimens on perinatal outcomes and to assess the quality of the current evidence. METHODS: This was a network meta-analysis of randomized controlled trials comparing prophylactic antibiotics, or regimens of antibiotics, with each other or with placebo/no treatment, in women with PPROM. MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, US Registry of Clinical Trials ( www.ClinicalTrials.gov) and gray literature sources were searched. The primary outcomes were neonatal mortality and chorioamnionitis; secondary outcomes included other measures of perinatal morbidity. Relative effect sizes were estimated using risk ratios (RR) and the relative ranking of the interventions was obtained using cumulative ranking curves. The quality of evidence for the primary outcomes was assessed according to GRADE guidelines, adapted for network meta-analysis. RESULTS: The analysis included 20 studies (7169 participants randomized to 15 therapeutic regimens). For the outcome of chorioamnionitis, clindamycin + gentamycin (network RR, 0.19 (95% CI, 0.05-0.83)), penicillin (RR, 0.31 (95% CI, 0.16-0.6)), ampicillin/sulbactam + amoxicillin/clavulanic acid (RR, 0.32 (95% CI, 0.12-0.92)), ampicillin (RR, 0.52 (95% CI, 0.34-0.81)) and erythromycin + ampicillin + amoxicillin (RR, 0.71 (95% CI, 0.55-0.92)) were superior to placebo/no treatment. Erythromycin was the only effective drug for neonatal sepsis (RR, 0.74 (95% CI, 0.56-0.97)). Clindamycin + gentamycin (RR, 0.32 (95% CI, 0.11-0.89)) and erythromycin + ampicillin + amoxicillin (RR, 0.83 (95% CI, 0.69-0.99)) were the only effective regimens for respiratory distress syndrome, whereas ampicillin (RR, 0.42 (95% CI, 0.20-0.92)) and penicillin (RR, 0.49 (95% CI, 0.25-0.96)) were effective in reducing the rates of Grade-3/4 intraventricular hemorrhage. None of the antibiotics appeared significantly more effective than placebo/no treatment in reducing the rates of neonatal death, perinatal death and necrotizing enterocolitis. No network RR could be estimated for neonatal intensive care unit admission. The overall quality of the evidence, according to GRADE guidelines, was moderate to very low, depending on the outcome and comparison. CONCLUSIONS: Several antibiotics appear to be more effective than placebo/no treatment in reducing the rate of chorioamnionitis after PPROM. However, none of them is clearly and consistently superior compared to other antibiotics, and most are not superior to placebo/no treatment for other outcomes. The overall quality of the evidence is low and needs to be updated, as microbial resistance may have emerged for some antibiotics, while others are underrepresented in the existing evidence. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Are clinical practice guidelines for low back pain interventions of high quality and updated? A systematic review using the AGREE II instrument.

BACKGROUND: Clinical practice guidelines (CPGs) provide recommendations for practice, but the proliferation of CPGs issued by multiple organisations in recent years has raised concern about their quality. The aim of this study was to systematically appraise CPGs quality for low back pain (LBP) interventions and to explore inter-rater reliability (IRR) between quality appraisers. The time between systematic review search and publication of CPGs was recorded. METHODS: Electronic databases (PubMed, Embase, PEDro, TRIP), guideline organisation databases, websites, and grey literature were searched from January 2016 to January 2020 to identify GPCs on rehabilitative, pharmacological or surgical intervention for LBP management. Four independent reviewers used the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool to evaluate CPGs quality and record the year the CPGs were published and the year the search strategies were conducted. RESULTS: A total of 21 CPGs met the inclusion criteria and were appraised. Seven (33%) were broad in scope and involved surgery, rehabilitation or pharmacological intervention. The score for each AGREE II item was: Editorial Independence (median 67%, interquartile range [IQR] 31-84%), Scope and Purpose (median 64%, IQR 22-83%), Rigour of Development (median 50%, IQR 21-72%), Clarity and Presentation (median 50%, IQR 28-79%), Stakeholder Involvement (median 36%, IQR 10-74%), and Applicability (median 11%, IQR 0-46%). The IRR between the assessors was nearly perfect (interclass correlation 0.90; 95% confidence interval 0.88-0.91). The median time span was 2 years (range, 1-4), however, 38% of the CPGs did not report the coverage dates for systematic searches. CONCLUSIONS: We found methodological limitations that affect CPGs quality. In our opinion, a universal database is needed in which guidelines can be registered and recommendations dynamically developed through a living systematic reviews approach to ensure that guidelines are based on updated evidence. LEVEL OF EVIDENCE: 1 TRIAL REGISTRATION: REGISTRATION PROSPERO DETAILS: CRD42019127619 .

Quality of evidence matters: is it well reported and interpreted in infertility journals?

PURPOSE: To evaluate if the authors of published systematic reviews (SRs) reported the level of quality of evidence (QoE) in the top 5 impact factor infertility journals and to analyze if they used an appropriate wording to describe it. METHODS: This is a cross-sectional study. We searched in PubMed for SRs published in 2017 in the five infertility journals with the highest impact factor. We analyzed the proportion of SRs published in the top 5 impact factor infertility journals that reported the SRs' QoE, and the proportion of those SRs in which authors used consistent wording to describe QoE and magnitude of effect. RESULTS: The QoE was reported in only 21.4% of the 42 included SRs and in less than 10% of the abstracts. Although we did not find important differences in the report of QoE of those that showed statistically significant differences or not, p value was associated with the wording chosen by the authors. We found inconsistent reporting of the size the effect estimate in 54.8% (23/42) and in the level of QoE in 92.9% (39/42). Whereas the effect size was more consistently expressed in studies with statistically significant findings, QoE was better expressed in those cases in which the p value was over 0.05. CONCLUSION: We found that in 2017, less than 25% of the authors reported the overall QoE when publishing SRs. Authors focused more on statistical significance as a binary concept than on methodological limitations like study design, imprecision, indirectness, inconsistency, and publication bias. Authors should make efforts to report the QoE and interpret results accordingly.

Application of next-generation sequencing to improve cancer management: A review of the clinical effectiveness and cost-effectiveness.

Uptake of next-generation sequencing (NGS) has increased dramatically due to significant cost reductions and broader community acceptance of NGS. To systematically review the evidence on both the clinical effectiveness and the cost-effectiveness of applying NGS to cancer care. A systematic search for full-length original research articles on the clinical effectiveness and cost-effectiveness of NGS in MEDLINE and EMBASE. Articles that focussed on cancer care and involved the application of NGS were included for the review of clinical effectiveness. For the cost-effectiveness review, we only included the articles with economic evaluations of NGS in cancer care. We report the rate of successfully detecting mutations from the clinical studies. The incremental cost-effectiveness ratio and sensitivity analysis outcomes are reported for the cost-effectiveness articles. Fifty-six articles reported that sequencing patient samples using targeted gene panels, and 83% of the successfully sequenced patients harboured at least 1 mutation. Only 6 studies reported on the cost-effectiveness of the application of NGS in cancer care. NGS is an effective tool for identifying mutation in cancer patients. However, more rigorous cost-effectiveness studies of NGS applied to cancer management are needed to determine whether NGS can improve patient outcomes cost-effectively.

Assessing FDG-PET diagnostic accuracy studies to develop recommendations for clinical use in dementia.

BACKGROUND: FDG-PET is frequently used as a marker of synaptic damage to diagnose dementing neurodegenerative disorders. We aimed to adapt the items of evidence quality to FDG-PET diagnostic studies, and assess the evidence available in current literature to assist Delphi decisions for European recommendations for clinical use. METHODS: Based on acknowledged methodological guidance, we defined the domains, specific to FDG-PET, required to assess the quality of evidence in 21 literature searches addressing as many Population Intervention Comparison Outcome (PICO) questions. We ranked findings for each PICO and fed experts making Delphi decisions for recommending clinical use. RESULTS: Among the 1435 retrieved studies, most lacked validated measures of test performance, an adequate gold standard, and head-to-head comparison of FDG-PET and clinical diagnosis, and only 58 entered detailed assessment. Only two studies assessed the accuracy of the comparator (clinical diagnosis) versus any kind of gold-/reference-standard. As to the index-test (FDG-PET-based diagnosis), an independent gold-standard was available in 24% of the examined papers; 38% used an acceptable reference-standard (clinical follow-up); and 38% compared FDG-PET-based diagnosis only to baseline clinical diagnosis. These methodological limitations did not allow for deriving recommendations from evidence. DISCUSSION: An incremental diagnostic value of FDG-PET versus clinical diagnosis or lack thereof cannot be derived from the current literature. Many of the observed limitations may easily be overcome, and we outlined them as research priorities to improve the quality of current evidence. Such improvement is necessary to outline evidence-based guidelines. The available data were anyway provided to expert clinicians who defined interim recommendations.

Determinants Used to Justify the Strength of Recommendations among Korean Clinical Practice Guidelines.

BACKGROUND: A standardized systematic approach to grade evidence and the strength of recommendations is important for guideline users to minimize bias and help interpret the most suitable decisions at the point of care. The study aims to identify and classify determinants used to make judgement for the strength of recommendations among 56 Korean clinical practice guidelines (CPGs), and explore strong recommendations based on low quality of evidence. METHODS: Determinants used in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach among 34 CPGs which have reported both strength of recommendations and level of evidence were reviewed. RESULTS: Five of 34 CPGs (14.7%) considered quality of evidence, benefits and harms, patients' values and preferences, and costs. And 24 of 34 CPGs (70.6%) considered both magnitude of effect and feasibility as additional determinants. Judgement table was not widely provided for use to translate evidence into recommendations. Eighty-two of 121 recommendations (67.8%, ranged 20.0% to 100.0%) among 11 CPGs using the same judgement scheme showed 'strong' strength of recommendations based on low or very low quality of evidence. Among 5 paradigmatic situations that justify strong recommendations based on low or very low evidence, situation classified as 'potential equivalence, one option clearly less risky or costly' was 87.8% for 82 strong recommendations. Situation classified as 'uncertain benefit, certain harm' was 4.9%. CONCLUSION: There is a need to introduce and systematize an evidence-based grading system. Using judgement table to justify the strength of recommendations and applying the 5 paradigmatic situations mentioned above is also recommended in the near future.

Evidence Underlying KDIGO (Kidney Disease: Improving Global Outcomes) Guideline Recommendations: A Systematic Review.

BACKGROUND: The KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guidelines establish international recommendations for the definition and treatment of kidney disease. Our objective was to characterize the strength of evidence supporting the KDIGO guidelines, the class of recommendations made, and the relationship between these. STUDY DESIGN: We reviewed and abstracted the level of evidence and strength of recommendations in the currently available KDIGO guidelines. SETTING & POPULATION: KDIGO clinical practice guidelines target care of patients with kidney disease to improve outcomes. SELECTION CRITERIA FOR STUDIES: All KDIGO guidelines published on the KDIGO website as of November 2013 were included. PREDICTOR: Recommendations pertaining to disease, diagnosis, or treatment. OUTCOMES: Levels of evidence and strength of recommendations. RESULTS: Of 853 recommendations in 9 guidelines, 5% were supported by level A quality evidence; 17%, level B; 31%, level C; 18%, level D; and 20%, ungraded evidence. The strength of recommendations was class 1 for 25%, class 2 for 54%, and ungraded for 20%. Only 3% of recommendations were class 1 in strength and supported by level A evidence. Of the recommendations, 2% concerned disease definition and classification; 29%, diagnosis; and 69%, treatment. LIMITATIONS: Our study included only the KDIGO guidelines. We did not assess historical changes in nephrology guidelines recommendations. CONCLUSIONS: KDIGO recommendations were based largely on weak evidence, reflecting expert opinion. Few recommendations were both strong and supported by high-level evidence.

Methodological review: quality of randomized controlled trials in health literacy.

BACKGROUND: The growing move towards patient-centred care has led to substantial research into improving the health literacy skills of patients and members of the public. Hence, there is a pressing need to assess the methodology used in contemporary randomized controlled trials (RCTs) of interventions directed at health literacy, in particular the quality (risk of bias), and the types of outcomes reported. METHODS: We conducted a systematic database search for RCTs involving interventions directed at health literacy in adults, published from 2009 to 2014. The Cochrane Risk of Bias tool was used to assess quality of RCT implementation. We also checked the sample size calculation for primary outcomes. Reported evidence of efficacy (statistical significance) was extracted for intervention outcomes in any of three domains of effect: knowledge, behaviour, health status. Demographics of intervention participants were also extracted, including socioeconomic status. RESULTS: We found areas of methodological strength (good randomization and allocation concealment), but areas of weakness regarding blinding of participants, people delivering the intervention and outcomes assessors. Substantial attrition (losses by monitoring time point) was seen in a third of RCTs, potentially leading to insufficient power to obtain precise estimates of intervention effect on primary outcomes. Most RCTs showed that the health literacy interventions had some beneficial effect on knowledge outcomes, but this was typically for less than 3 months after intervention end. There were far fewer reports of significant improvements in substantive patient-oriented outcomes, such as beneficial effects on behavioural change or health (clinical) status. Most RCTs featured participants from vulnerable populations. CONCLUSIONS: Our evaluation shows that health literacy trial design, conduct and reporting could be considerably improved, particularly by reducing attrition and obtaining longer follow-up. More meaningful RCTs would also result if health literacy trials were designed with public and patient involvement to focus on clinically important patient-oriented outcomes, rather than just knowledge, behaviour or skills in isolation.

Treatment of adult patients with schizophrenia and complex mental health needs - A national clinical guideline.

BACKGROUND AND AIM: The Danish Health and Medicines Authority assembled a group of experts to develop a national clinical guideline for patients with schizophrenia and complex mental health needs. Within this context, ten explicit review questions were formulated, covering several identified key issues. METHODS: Systematic literature searches were performed stepwise for each review question to identify relevant guidelines, systematic reviews/meta-analyses, and randomized controlled trials. The quality of the body of evidence for each review question was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Clinical recommendations were developed on the basis of the evidence, assessment of the risk-benefit ratio, and perceived patient preferences. RESULTS: Based on the identified evidence, a guideline development group (GDG) recommended that the following interventions should be offered routinely: antipsychotic maintenance therapy, family intervention and assertive community treatment. The following interventions should be considered: long-acting injectable antipsychotics, neurocognitive training, social cognitive training, cognitive behavioural therapy for persistent positive and/or negative symptoms, and the combination of cognitive behavioural therapy and motivational interviewing for cannabis and/or central stimulant abuse. SSRI or SNRI add-on treatment for persistent negative symptoms should be used only cautiously. Where no evidence was available, the GDG agreed on a good practice recommendation. CONCLUSIONS: The implementation of this guideline in daily clinical practice can facilitate good treatment outcomes within the population of patients with schizophrenia and complex mental health needs. The guideline does not cover all available interventions and should be used in conjunction with other relevant guidelines.

Rating the quality of evidence: the GRADE system in systematic reviews/meta-analyses of AKI.

BACKGROUND: The method of systematic reviews/meta-analyses (SRs/MAs) has been widely used in acute kidney injury (AKI) studies. However, it is not quite clear about the quality of the evidence and existing problems. OBJECTIVES: To grade the evidence quality of published SRs/MAs of AKI by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, understand the current situation of evidence rating and analyze the possible problems. METHODS: Researchers systematically searched for articles about SRs/MAs of AKI published in the following four Chinese databases and four English databases, including Chinese Biomedicine Literature Database, Wanfang Database, China National Knowledge Internet Database, VIP Database, Pubmed, EMBASE, the Cochrane Library and Web of Science. RESULTS: Totally, 81 SRs/MAs were included in this study and the overall quality of evidence was not satisfactory. The number of literatures of low and very low evidence quality was 33 (40.7%) and 41 (50.6%), respectively. Limitation was the main factor which caused the quality of research evidence degrading (92.6%), and other degradation factors were inconsistency (56.8%), publication bias (44.4%), indirectness (35.8%) and imprecision (32.1%). The quality of evidence for AKI has been significantly improved after the publication of the GRADE system in 2004. CONCLUSIONS: Since 2004 when the GRADE system was published, the quality of evidence of AKI has been increased clearly. But quality of AKI evidence of SRs/MAs for intervention is still not satisfactory. Limitation and inconsistency were two major factors leading to degradation.

What is the level of evidence substantiating the Medicare local coverage determinations?

Total joint arthroplasty (TJA) accounts for large expenditures of Medicare resources. Recovery audit contractors (RACs) utilize Local Coverage Determinations (LCDs) documents to retrospectively assess the medical necessity of performed procedures. The Florida LCD requires 3 months of documented unsuccessful nonoperative care prior to TJA. The purpose of our study was to evaluate the applicability and quality of the evidence cited in the Florida LCD for patients undergoing TJA. Applicability was assessed by evaluating the efficacy of nonoperative treatment in candidates for TJA. There were 23 citations, of which 11 mentioned nonoperative treatment and only 5 provided references. No citations provided Level I or II evidence substantiating the effectiveness of 3 months of nonoperative treatment in patients who would otherwise be candidates for TJA.