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Background: Frequent hemodialysis provided more than three times per week may lower mortality and improve health-related quality of life. Yet, the evidence is inconclusive. We evaluated the benefits and harms of frequent hemodialysis in people with kidney failure compared with standard hemodialysis. Methods: We performed a systematic review of randomized controlled trials including adults on hemodialysis with highly sensitive searching in MEDLINE, Embase, CENTRAL, and Google Scholar on 3 January 2024. Data were pooled using random-effects meta-analysis. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. We adjudicated evidence certainty using GRADE. Results: From 11,142 unique citations, only seven studies involving 518 participants proved eligible. The effects of frequent hemodialysis on physical and mental health were imprecise due to few data. Frequent hemodialysis probably had uncertain effect on death from all cause compared with standard hemodialysis (relative risk 0.79, 95% confidence interval 0.33–1.91, low certainty evidence). Data were not reported for death from cardiovascular causes, major cardiovascular events, fatigue or vascular access. Conclusion: The evidentiary basis for frequent hemodialysis is incomplete due to clinical trials with few or no events reported for mortality and cardiovascular outcome measures and few participants in which patient-reported outcomes including health-related quality of life and symptoms were reported. [ABSTRACT FROM AUTHOR]

Left ventricular diastolic dysfunction (LVDD) commonly coexists with kidney dysfunction. In this study, we investigated the presence of abnormalities in echocardiography parameters indicative of LVDD across stages of kidney function. Methods: We selected patients who visited a university hospital and had a serum creatinine and echocardiography reported in their medical records. Participants were categorized based on their kidney function: normal (estimated glomerular filtration rate [eGFR] ≥ 90 mL/min/1.73 m2), mildly decreased (eGFR: 60–90), moderately decreased (eGFR: 30–60), and severely decreased (eGFR < 30). The relationship between kidney function and echocardiography parameters was examined using logistic and linear regressions. Results: Among 4022 patients (age: 66.5 years [SD: 12.1], 41% women), 26%, 50%, 20%, and 4% had a normal, mildly, moderately, and severely decreased kidney function, respectively. Compared to patients with normal kidney function, patients with mildly decreased kidney function had higher odds for an abnormal E/e′ ratio (OR: 1.51 [95% CI: 1.13, 2.02]). Patients with moderately decreased kidney function presented a higher risk of abnormal E/e′ (OR: 2.90 [95% CI: 2.08, 4.04]), LAVI (OR: 1.62 [95% CI: 1.13, 2.33]), TR velocity (OR: 2.31 [95% CI: 1.49, 3.57]), and LVMI (OR: 1.70 [95% CI: 1.31, 2.20]), while patients with severely decreased kidney function had higher odds for abnormal E/e′ (OR: 2.95 [95% CI: 1.68, 5.17]) and LVMI > 95 g/m2 in women or >115 g/m2 in men (OR: 2.07 [95% CI: 1.27, 3.38]). The linear regression showed a significant inverse association between eGFR and echocardiography parameters, meaning that with worse kidney function, the parameters for LVDD worsened as well. Conclusions: Abnormal echocardiography parameters of LVDD were present even in patients with mildly decreased kidney function. As the kidney function worsened, there was a gradual increase in the risk of abnormal parameters of LVDD. [ABSTRACT FROM AUTHOR]

COVID‐19 is not only associated with substantial acute liver and kidney injuries, but also with an elevated risk of post‐acute sequelae involving the kidney and liver system. We aimed to investigate whether COVID‐19 exposure increases the long‐term risk of kidney and liver disease, and what are the magnitudes of these associations. We searched PubMed, Embase, Web of Science, ClinicalTrials.gov, and the Living Overview of the Evidence COVID‐19 Repository for cohort studies estimating the association between COVID‐19 and kidney and liver outcomes. Random‐effects meta‐analyses were performed to combine the results of the included studies. We assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Fifteen cohort studies with more than 32 million participants were included in the systematic review COVID‐19 was associated with a 35% greater risk of kidney diseases (10 more per 1000 persons; low certainty evidence) and 54% greater risk of liver disease (3 more per 1000 persons; low certainty evidence). The absolute increases due to COVID‐19 for acute kidney injury, chronic kidney disease, and liver test abnormality were 3, 8, and 3 per 1000 persons, respectively. Subgroup analyses found no differences between different type of kidney and liver diseases. The findings provide further evidence for the association between COVID‐19 and incident kidney and liver conditions. The absolute magnitude of the effect of COVID‐19 on kidney and liver outcomes was, however, relatively small. [ABSTRACT FROM AUTHOR]

Aims: We aim to investigate the association between kidney dysfunction and left ventricular diastolic dysfunction parameters and heart failure with preserved ejection fraction (HFpEF) and whether this is sex‐specific. Methods and results: We included participants from the HELPFul observational study. Outpatient clinical care data, including echocardiography, and an expert panel judgement on HFpEF was collected. Estimated glomerular filtration rate (eGFR) was calculated by creatinine and cystatin C without race. The association between eGFR with E/e′, left ventricular mass index, relative wall thickness, and stage C/D heart failure was tested by multivariable adjusted regression models, stratified by sex, reporting odds ratios and 95% confidence intervals (95% confidence interval). We analysed 880 participants, mean age 62.9 (standard deviation: 9.3) years, 69% female. Four hundred six participants had mild (37.6%) kidney dysfunction (eGFR: 60–89 mL/min/1.73 m2) or moderate (8.5%) kidney dysfunction (eGFR: 30–59 mL/min/1.73 m2). HFpEF was significantly more prevalent in participants with mild and moderate kidney dysfunction (10.3% and 16.0%, respectively) than participants with normal kidney function (3.4%). A lower kidney function was associated with higher E/e′ and higher relative wall thickness values. Participants with moderate kidney dysfunction had a higher likelihood of American College of Cardiology/American Heart Association stage C/D HF (odds ratio: 2.07, 95% confidence interval: 1.23, 3.49) than participants with normal kidney functions. Conclusions: Both mild and moderate kidney dysfunction are independently associated with left ventricular diastolic dysfunction parameters and HFpEF. This association is independent of sex and strongest for moderate kidney dysfunction. Considering mild‐to‐moderate kidney dysfunction as risk factor for HFpEF may help identify high‐risk groups benefiting most from early intervention. [ABSTRACT FROM AUTHOR]

Background: E-cigarettes (electronic nicotine delivery system, ENDS) have been presented as a harm reduction strategy for people who smoke tobacco cigarettes but who cannot achieve abstinence, or for those who wish to continue to enjoy nicotine and the habit of smoking. What are the health effects of the substitution of ENDS for tobacco cigarettes? This systematic review evaluates the evidence of human clinical tests on the respiratory effects of ENDS use in participants who smoke tobacco cigarettes. Methods: A registered and published protocol was developed conforming to PRISMA 2020 and AMSTAR2 standards. The literature search was conducted in PubMed, Scopus, and the CENTRAL Cochrane Library and updated to May 2022. Three supplementary searches and a grey literature search were performed. Studies were evaluated with the JBI quality tools and the Oxford Catalogue of Bias. Due to the heterogeneity (diversity) of the studies, a narrative data synthesis was performed on the test findings plus three sub-group analyses. Results: The review consists of sixteen studies and twenty publications. Spirometry tests comprised the majority of the data. In total, 66 respiratory test measurements were reported, out of which 43 (65%) were not significant. Statistically significant findings were mixed, with 9 tests showing improvements and 14 measuring declines, none of which was clinically relevant. Ten studies were rated at a high risk of bias, and six had some concerns primarily due to inadequate research designs and the conduct of the studies. Reporting bias was documented in thirteen studies. Conclusions: Most of the studies showed no difference in respiratory parameters. This indicates that ENDS substitution for smoking likely does not result in additional harm to respiratory health. Due to the low quality of the studies, confidence in the conclusions is rated as low. Robust studies with a longer duration and sufficient power are required to validate any potential benefits or possible harms of ENDS substitution. Registration PROSPERO #CRD42021239094, International Registered Report Identifier (IRRID): DERR1-10.2196/29084. [ABSTRACT FROM AUTHOR]

Review Purpose: This systematic review aims to summarise clustering studies in heart failure (HF) and guide future clinical trial design and implementation in routine clinical practice. Findings: 34 studies were identified (n = 19 in HF with preserved ejection fraction (HFpEF)). There was significant heterogeneity invariables and techniques used. However, 149/165 described clusters could be assigned to one of nine phenotypes: 1) young, low comorbidity burden; 2) metabolic; 3) cardio-renal; 4) atrial fibrillation (AF); 5) elderly female AF; 6) hypertensive-comorbidity; 7) ischaemic-male; 8) valvular disease; and 9) devices. There was room for improvement on important methodological topics for all clustering studies such as external validation and transparency of the modelling process. Summary: The large overlap between the phenotypes of the clustering studies shows that clustering is a robust approach for discovering clinically distinct phenotypes. However, future studies should invest in a phenotype model that can be implemented in routine clinical practice and future clinical trial design. HF = heart failure, EF = ejection fraction, HFpEF = heart failure with preserved ejection fraction, HFrEF = heart failure with reduced ejection fraction, CKD = chronic kidney disease, AF = atrial fibrillation, IHD = ischaemic heart disease, CAD = coronary artery disease, ICD = implantable cardioverter-defibrillator, CRT = cardiac resynchronization therapy, NT-proBNP = N-terminal pro b-type natriuretic peptide, BMI = Body Mass Index, COPD = Chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of reducing saturated fat or fatty foods, or replacing saturated fat with unsaturated fat, carbohydrate or protein, on the risk of mortality and major cancer and cardiometabolic outcomes in adults. Methods: We searched MEDLINE, EMBASE, CINAHL, and references of included studies for systematic reviews and meta-analyses (SRMAs) of randomized controlled trials (RCTs) and observational studies in adults published in the past 10 years. Eligible reviews investigated reducing saturated fat or fatty foods or replacing saturated fat with unsaturated fat, carbohydrate or protein, on the risk of cancer and cardiometabolic outcomes and assessed the certainty of evidence for each outcome using, for example, the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach. We assessed the quality of SRMAs using a modified version of AMSTAR-2. Results were summarized as absolute estimates of effect together with the certainty of effects using a narrative synthesis approach. Results: We included 17 SRMAs (13 reviews of observational studies with follow-up 1 to 34 years; 4 reviews of RCTs with follow-up 1 to 17 years). The quality of two-thirds of the SRMAs was critically low to moderate; the main limitations included deficient reporting of study selection, absolute effect estimates, sources of funding, and a priori subgroups to explore heterogeneity. Our included reviews reported > 100 estimates of effect across 11 critically important cancer and cardiometabolic outcomes. High quality SRMAs consistently and predominantly reported low to very low certainty evidence that reducing or replacing saturated fat was associated with a very small risk reduction in cancer and cardiometabolic endpoints. The risk reductions where approximately divided, some being statistically significant and some being not statistically significant. However, based on 2 moderate to high quality reviews, we found moderate certainty evidence for a small but important effect that was statistically significant for two outcomes (total mortality events [20 fewer events per 1000 followed] and combined cardiovascular events [16 fewer per 1000 followed]). Conversely, 4 moderate to high quality reviews showed very small effects on total mortality, with 3 of these reviews showing non-statistically significant mortality effects. Conclusion: Systematic reviews investigating the impact of SFA on mortality and major cancer and cardiometabolic outcomes almost universally suggest very small absolute changes in risk, and the data is based primarily on low and very low certainty evidence. Systematic review registration: PROSPERO CRD42020172141 [ABSTRACT FROM AUTHOR]

Background In chronic haemodialysis (HD) patients, the relationship between long-term peridialytic blood pressure (BP) changes and mortality has not been investigated. Methods To evaluate whether long-term changes in peridialytic BP are related to mortality and whether treatment with HD or haemodiafiltration (HDF) differs in this respect, the combined individual participant data of three randomized controlled trials comparing HD with HDF were used. Time-varying Cox regression and joint models were applied. Results During a median follow-up of 2.94 years, 609 of 2011 patients died. As for pre-dialytic systolic BP (pre-SBP), a severe decline (≥21 mmHg) in the preceding 6 months was independently related to increased mortality [hazard ratio (HR) 1.61, P  = .01] when compared with a moderate increase. Likewise, a severe decline in post-dialytic diastolic BP (DBP) was associated with increased mortality (adjusted HR 1.96, P  < .0005). In contrast, joint models showed that every 5-mmHg increase in pre-SBP and post-DBP during total follow-up was related to reduced mortality (adjusted HR 0.97, P  = .01 and 0.94, P  = .03, respectively). No interaction was observed between BP changes and treatment modality. Conclusion Severe declines in pre-SBP and post-DBP in the preceding 6 months were independently related to mortality. Therefore peridialytic BP values should be interpreted in the context of their changes and not solely as an absolute value. [ABSTRACT FROM AUTHOR]

Protein-bound uremic toxins (PBUTs) are associated with the progression of chronic kidney disease (CKD) and its associated morbidity and mortality. The conventional dialysis techniques are unable to efficiently remove PBUTs due to their plasma protein binding. Therefore, novel approaches are being developed, but these require validation in animals before clinical trials can begin. We conducted a systematic review to document PBUT concentrations in various models and species. The search strategy returned 1163 results for which abstracts were screened, resulting in 65 full-text papers for data extraction (rats (n = 41), mice (n = 17), dogs (n = 3), cats (n = 4), goats (n = 1), and pigs (n = 1)). We performed descriptive and comparative analyses on indoxyl sulfate (IS) concentrations in rats and mice. The data on large animals and on other PBUTs were too heterogeneous for pooled analysis. Most rodent studies reported mean uremic concentrations of plasma IS close to or within the range of those during kidney failure in humans, with the highest in tubular injury models in rats. Compared to nephron loss models in rats, a greater rise in plasma IS compared to creatinine was found in tubular injury models, suggesting tubular secretion was more affected than glomerular filtration. In summary, tubular injury rat models may be most relevant for the in vivo validation of novel PBUT-lowering strategies for kidney failure in humans. [ABSTRACT FROM AUTHOR]

Background: De-implementation of low-value care can increase health care sustainability. We evaluated the reporting of direct costs of de-implementation and subsequent change (increase or decrease) in health care costs in randomized trials of de-implementation research. Methods: We searched MEDLINE and Scopus databases without any language restrictions up to May 2021. We conducted study screening and data extraction independently and in duplicate. We extracted information related to study characteristics, types and characteristics of interventions, de-implementation costs, and impacts on health care costs. We assessed risk of bias using a modified Cochrane risk-of-bias tool. Results: We screened 10,733 articles, with 227 studies meeting the inclusion criteria, of which 50 included information on direct cost of de-implementation or impact of de-implementation on health care costs. Studies were mostly conducted in North America (36%) or Europe (32%) and in the primary care context (70%). The most common practice of interest was reduction in the use of antibiotics or other medications (74%). Most studies used education strategies (meetings, materials) (64%). Studies used either a single strategy (52%) or were multifaceted (48%). Of the 227 eligible studies, 18 (8%) reported on direct costs of the used de-implementation strategy; of which, 13 reported total costs, and 12 reported per unit costs (7 reported both). The costs of de-implementation strategies varied considerably. Of the 227 eligible studies, 43 (19%) reported on impact of de-implementation on health care costs. Health care costs decreased in 27 studies (63%), increased in 2 (5%), and were unchanged in 14 (33%). Conclusion: De-implementation randomized controlled trials typically did not report direct costs of the de-implementation strategies (92%) or the impacts of de-implementation on health care costs (81%). Lack of cost information may limit the value of de-implementation trials to decision-makers. Trial registration: OSF (Open Science Framework): https://osf.io/ueq32. [ABSTRACT FROM AUTHOR]

Background: The timing at which venous thromboembolism (VTE) occurs after major surgery has major implications for the optimal duration of thromboprophylaxis. The aim of this study was to perform a systematic review and meta-analysis of the timing of postoperative VTE up to 4 weeks after surgery. Methods: A systematic search of MEDLINE, Scopus, and CINAHL databases was performed between 1 January 2009 and 1 April 2022. Prospective studies that recruited patients who underwent a surgical procedure and reported at least 20 symptomatic, postoperative VTE events by time were included. Two reviewers independently selected studies according to the eligibility criteria, extracted data, and evaluated risk of bias. Data were analysed with a Poisson regression model, and the GRADE approach was used to rate the certainty of evidence. Results: Some 6258 studies were evaluated, of which 22 (11 general, 5 urological, 4 mixed, and 2 orthopaedic postoperative surgical populations; total 1 864 875 patients and 24 927 VTE events) were eligible. Pooled evidence of moderate certainty showed that 47.1 per cent of the VTE events occurred during the first, 26.9 per cent during the second, 15.8 per cent during the third, and 10.1 per cent during the fourth week after surgery. The timing of VTE was consistent between individual studies. Conclusion: Although nearly half of symptomatic VTE events in first 4 weeks occur during the first postoperative week, a substantial number of events occur several weeks after surgery. These data will inform clinicians and guideline developers about the duration of postoperative thromboprophylaxis. [ABSTRACT FROM AUTHOR]

Background: The health effects of dietary fats are a controversial issue on which experts and authoritative organizations have often disagreed. Care providers, guideline developers, policy-makers, and researchers use systematic reviews to advise patients and members of the public on optimal dietary habits, and to formulate public health recommendations and policies. Existing reviews, however, have serious limitations that impede optimal dietary fat recommendations, such as a lack of focus on outcomes important to people, substantial risk of bias (RoB) issues, ignoring absolute estimates of effects together with comprehensive assessments of the certainty of the estimates for all outcomes. Objective: We therefore propose a methodologically innovative systematic review using direct and indirect evidence on diet and food-based fats (i.e., reduction or replacement of saturated fat with monounsaturated or polyunsaturated fat, or carbohydrates or protein) and the risk of important health outcomes. Methods: We will collaborate with an experienced research librarian to search MEDLINE, EMBASE, CINAHL, and the Cochrane Database of Systematic Reviews (CDSR) for randomized clinical trials (RCTs) addressing saturated fat and our health outcomes of interest. In duplicate, we will screen, extract results from primary studies, assess their RoB, conduct de novo meta-analyses and/or network meta-analysis, assess the impact of missing outcome data on meta-analyses, present absolute effect estimates, and assess the certainty of evidence for each outcome using the GRADE contextualized approach. Our work will inform recommendations on saturated fat based on international standards for reporting systematic reviews and guidelines. Conclusion: Our systematic review and meta-analysis will provide the most comprehensive and rigorous summary of the evidence addressing the relationship between saturated fat modification for people-important health outcomes. The evidence from this review will be used to inform public health nutrition guidelines. Trial registration: PROSPERO Registration: CRD42023387377. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic kidney disease (CKD) require a personalised strategy for cardiovascular risk management (CVRM) to reduce their high risk of cardiovascular morbidity and mortality. Despite their high risk, patients with CKD appear to be underrepresented in randomised controlled trials (RCTs) for pharmacological CVRM interventions to reduce cardiovascular risk (pharmacological CVRM interventions). As a result, it remains unclear whether the efficacy of these interventions found in patients without CKD is similarly applicable to patients with CKD. This evidence map aims to provide an overview of the availability of the evidence from pharmacological CVRM trials for patients with CKD by assessing how often patients with reduced kidney function are specifically excluded or included from RCTs on pharmacological CVRM interventions and whether studies report efficacy estimates of interventions specifically for kidney patients. Methods: We will perform a systematic literature search in ClinicalTrials.gov to identify relevant planned, ongoing, and completed RCTs on a broad range of CVRM medications after which we will retrieve the published protocols and papers via ClinicalTrials.gov itself, Embase, MEDLINE, or Google Scholar. We will include RCTs that investigate the efficacy of platelet inhibitors, anticoagulants, antihypertensives, glucose-lowering medication, and lipid-lowering medication on all-cause mortality, cardiovascular mortality, cardiovascular morbidity, and end-stage kidney disease in patients with a cardiovascular history or a major risk factor for cardiovascular disease. Two reviewers will independently screen trial records and their corresponding full-text publications to determine eligibility and extract data. Outcomes of interest are the exclusion of patients with reduced kidney function from RCTs and whether the study population was restricted to kidney patients or subgroup analyses were performed on kidney function. Results will be visualised in an evidence map. Discussion: The availability of evidence on the efficacy and safety of pharmacological CVRM interventions in patients with CKD might be limited. Hence, we will identify knowledge gaps for future research. At the same time, the availability of evidence, or lack thereof, might warrant caution from healthcare decision-makers in making strong recommendations based on the extrapolation of results from studies to patients who were explicitly excluded from participation. Systematic review registration: PROSPERO CRD42022296746. [ABSTRACT FROM AUTHOR]

Background: Healthcare costs are rising, and a substantial proportion of medical care is of little value. De-implementation of low-value practices is important for improving overall health outcomes and reducing costs. We aimed to identify and synthesize randomized controlled trials (RCTs) on de-implementation interventions and to provide guidance to improve future research.Methods: MEDLINE and Scopus up to May 24, 2021, for individual and cluster RCTs comparing de-implementation interventions to usual care, another intervention, or placebo. We applied independent duplicate assessment of eligibility, study characteristics, outcomes, intervention categories, implementation theories, and risk of bias.Results: Of the 227 eligible trials, 145 (64%) were cluster randomized trials (median 24 clusters; median follow-up time 305 days), and 82 (36%) were individually randomized trials (median follow-up time 274 days). Of the trials, 118 (52%) were published after 2010, 149 (66%) were conducted in a primary care setting, 163 (72%) aimed to reduce the use of drug treatment, 194 (85%) measured the total volume of care, and 64 (28%) low-value care use as outcomes. Of the trials, 48 (21%) described a theoretical basis for the intervention, and 40 (18%) had the study tailored by context-specific factors. Of the de-implementation interventions, 193 (85%) were targeted at physicians, 115 (51%) tested educational sessions, and 152 (67%) multicomponent interventions. Missing data led to high risk of bias in 137 (60%) trials, followed by baseline imbalances in 99 (44%), and deficiencies in allocation concealment in 56 (25%).Conclusions: De-implementation trials were mainly conducted in primary care and typically aimed to reduce low-value drug treatments. Limitations of current de-implementation research may have led to unreliable effect estimates and decreased clinical applicability of studied de-implementation strategies. We identified potential research gaps, including de-implementation in secondary and tertiary care settings, and interventions targeted at other than physicians. Future trials could be improved by favoring simpler intervention designs, better control of potential confounders, larger number of clusters in cluster trials, considering context-specific factors when planning the intervention (tailoring), and using a theoretical basis in intervention design.Registration: OSF Open Science Framework hk4b2. [ABSTRACT FROM AUTHOR]

Background Previous studies suggest that haemodiafiltration reduces mortality compared with haemodialysis in patients with end-stage kidney disease (ESKD), but the controversy surrounding its benefits remains and it is unclear to what extent individual patients benefit from haemodiafiltration. This study is aimed to develop and validate a treatment effect prediction model to determine which patients would benefit most from haemodiafiltration compared with haemodialysis in terms of all-cause mortality. Methods Individual participant data from four randomized controlled trials comparing haemodiafiltration with haemodialysis on mortality were used to derive a Royston-Parmar model for the prediction of absolute treatment effect of haemodiafiltration based on pre-specified patient and disease characteristics. Validation of the model was performed using internal-external cross validation. Results The median predicted survival benefit was 44 (Q1–Q3: 44–46) days for every year of treatment with haemodiafiltration compared with haemodialysis. The median survival benefit with haemodiafiltration ranged from 2 to 48 months. Patients who benefitted most from haemodiafiltration were younger, less likely to have diabetes or a cardiovascular history and had higher serum creatinine and albumin levels. Internal–external cross validation showed adequate discrimination and calibration. Conclusion Although overall mortality is reduced by haemodiafiltration compared with haemodialysis in ESKD patients, the absolute survival benefit can vary greatly between individuals. Our results indicate that the effects of haemodiafiltration on survival can be predicted using a combination of readily available patient and disease characteristics, which could guide shared decision-making. [ABSTRACT FROM AUTHOR]

Hemodiafiltration (HDF), in which both convective and diffusion methods are combined, yields an increased overall solute clearance compared with hemodialysis (HD), specifically for medium and larger molecular weight uremic toxins. Due to uncertainty in the treatment effects, the nephrology community still perceives the implementation of HDF and the achievement of high convective volume as complex. In this article, we review practical aspects of the implementation of HDF that can effectively deliver a high‐volume HDF therapy and assure clinical performance to most patients. We also present an overview of the impact of high‐volume HDF (compared to HD) on a series of relevant biochemical, patient‐reported, and clinical outcomes, including uremic toxin removal, phosphate, Inflammation and oxidative stress, hemodynamic stability, cardiac outcomes, nutritional effects, health‐related quality of life, morbidity, and mortality. [ABSTRACT FROM AUTHOR]

Background. Women with lower-extremity arterial disease (LEAD) are often underdiagnosed, present themselves with more advanced disease at diagnosis, and fare worse than men. Objective. To investigate to what extent potential gender differences exist in the frequency and reasons for general practitioner (GP) consultation six months prior to the diagnosis of LEAD, as potential indicators of diagnostic delay. Methods. Individuals older than 18 years diagnosed with LEAD, sampled from the Julius General Practitioner's Network (JGPN), were included and compared with a reference population, matched (1:2.6 ratio) in terms of age, sex, and general practice. We applied a zero-inflated negative binomial (ZINB) regression model. Results. The study population comprised 4044 patients with LEAD (43.5% women) and 10,486 subjects in the reference population (46.3% women). In the LEAD cohort, the number of GP contacts was 2.70 (95% CI: 2.42, 3.02) in women and 2.54 (2.29, 2.82) in men. In the reference cohort, 1.77 (95% CI: 1.62, 1.94) in women and 1.63 (95% CI: 1.50, 1.78) in men. In the LEAD cohort, 21.9% of GP contacts occurred one month prior to diagnosis. In both cohorts and both sexes, the most common cause of consultation during the last month before the index date was cardiovascular problems. Conclusions. Six months preceding the initial diagnosis of LEAD, patients visit the GP more often than a similar population without LEAD, regardless of gender. Reported gender differences in the severity of LEAD at diagnosis do not seem to be explained by a delay in presentation to the GP. [ABSTRACT FROM AUTHOR]

Haemodiafiltration (HDF) provides a greater removal of larger solutes and protein-bound compounds than conventional high-flux haemodialysis (HD). There are indications that the patients receiving the highest convection volumes of HDF result in improved survival compared with HD. However, the comparative efficacy of HDF versus HD remains unproven. Here we provide a comparative account of the methodology and aims of 'the comparison of high-dose HDF with high-flux HD' (CONVINCE) study in the context of the totality of evidence and how this study will contribute to reaching a higher level of certainty regarding the comparative efficacy of HDF versus HD in people with end-stage kidney disease. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Recommendations for preventing and diagnosing recurrent urinary tract infection (UTI) tend to vary between clinical practice guidelines (CPGs) because of low-quality scientific evidence, potentially leading to practice variation and suboptimal care. We assessed the quality of existing CPGs for recurrent UTI. Methods: A systematic search was performed from January 2000 to June 2021 in PubMed and EMBASE for CPGs on recurrent UTI prevention or hospital diagnostics in Dutch, English, and Spanish. Each CPG was assessed by four appraisers in a multidisciplinary review team, using the Appraisal of Guidelines, Research, and Evaluation II (AGREE II) instrument. Results: We identified and assessed eight CPGs published between 2013 and 2021. The scope and purpose (mean and standard deviation: 67.3 ± 21.8) and clarity of presentation (74.8 ± 17.6) domains scored highly. However, issues with methods, patient participation, conflict of interests, and facilitators and barriers were common and resulted in lower scores for the rigour of development (56.9 ± 25.9), applicability (19.6 ± 23.4), stakeholder involvement (50.4 ± 24.6), and editorial independence (62.1 ± 23.1) domains. Overall, two CPGs were recommended, three were recommended with modifications, and three were not recommended. Conclusions: Significant room for improvement exists in the quality of CPGs for recurrent UTI, with most displaying serious limitations in the stakeholder involvement, rigour of development, and applicability domains. These aspects must be improved to decrease diagnostic and therapeutic uncertainty. Developers could benefit from using checklists and following guidelines when developing de novo CPGs. [ABSTRACT FROM AUTHOR]

Sudden cardiac death (SCD) represents a major cause of death in end-stage kidney disease (ESKD). The precise estimate of its incidence is difficult to establish because studies on the incidence of SCD in ESKD are often combined with those related to sudden cardiac arrest (SCA) occurring during a haemodialysis (HD) session. The aim of the European Dialysis Working Group of ERA-EDTA was to critically review the current literature examining the causes of extradialysis SCD and intradialysis SCA in ESKD patients and potential management strategies to reduce the incidence of such events. Extradialysis SCD and intradialysis SCA represent different clinical situations and should be kept distinct. Regarding the problem, numerically less relevant, of patients affected by intradialysis SCA, some modifiable risk factors have been identified, such as a low concentration of potassium and calcium in the dialysate, and some advantages linked to the presence of automated external defibrillators in dialysis units have been documented. The problem of extra-dialysis SCD is more complex. A reduced left ventricular ejection fraction associated with SCD is present only in a minority of cases occurring in HD patients. This is the proof that SCD occurring in ESKD has different characteristics compared with SCD occurring in patients with ischaemic heart disease and/or heart failure and not affected by ESKD. Recent evidence suggests that the fatal arrhythmia in this population may be due more frequently to bradyarrhythmias than to tachyarrhythmias. This fact may partly explain why several studies could not demonstrate an advantage of implantable cardioverter defibrillators in preventing SCD in ESKD patients. Electrolyte imbalances, frequently present in HD patients, could explain part of the arrhythmic phenomena, as suggested by the relationship between SCD and timing of the HD session. However, the high incidence of SCD in patients on peritoneal dialysis suggests that other risk factors due to cardiac comorbidities and uraemia per se may contribute to sudden mortality in ESKD patients. [ABSTRACT FROM AUTHOR]

Background: Due to a critical shortage of available kidney grafts, most patients with Stage 5 Chronic Kidney Disease (CKD5) require bridging dialysis support. It remains unclear whether treatment by different dialysis modalities changes the selection and/or preparation of a potential transplant candidate. Therefore, we assessed whether the likelihood of receiving kidney transplant (both living or deceased kidney donors) differs between haemodialysis (HD) and online haemodiafiltration (HDF) in patients with CKD5D.Methods: Individual participant data from four randomised controlled trials comparing online HDF with HD were used. Information on kidney transplant was obtained during follow-up. The likelihood of receiving a kidney transplant was compared between HD and HDF, and evaluated across different subgroups: age, sex, diabetes, history of cardiovascular disease, albumin, dialysis vintage, fistula, and level of convection volume standardized to body surface area. Hazard ratios (HRs), with corresponding 95% confidence intervals (95% CI), comparing the effect of online HDF versus HD on the likelihood of receiving a kidney transplant, were estimated using Cox proportional hazards models with a random effect for study.Results: After a median follow-up of 2.5 years (Q1 to Q3: 1.9-3.0), 331 of the 1620 (20.4%) patients with CKD5D received a kidney transplant. This concerned 22% (n = 179) of patients who were treated with online HDF compared with 19% (n = 152) of patients who were treated with HD. No differences in the likelihood of undergoing a kidney transplant were found between the two dialysis modalities in both the crude analyse (HR: 1.07, 95% CI: 0.86-1.33) and adjusted analysis for age, sex, diabetes, cardiovascular history, albumin, and creatinine (HR: 1.15, 95%-CI: 0.92-1.44). There was no evidence for a differential effect across subgroups based on patient- and disease-characteristics nor in different categories of convection volumes.Conclusions: Treatment with HD and HDF does not affect the selection and/or preparation of CKD5D patients for kidney transplant given that the likelihood of receiving a kidney transplant does not differ between the dialysis modalities. These finding persisted across a variety of subgroups differing in patient and disease characteristics and is not affected by the level of convection volume delivered during HDF treatment sessions. [ABSTRACT FROM AUTHOR]

Introduction End-stage kidney disease (ESKD) is a major public health problem affecting more than 2 million people worldwide. It is one of the most severe chronic non-communicable diseases. Haemodialysis (HD) is the most common therapeutic option but is also associated with a risk of cardiovascular events, hospitalisation and suboptimal quality of life. Over the past decades, haemodiafiltration (HDF) has become available. Although high-dose HDF has shown some promising survival advantage compared to conventional HD, the evidence remains controversial. A Cochrane systematic review found, in low-quality trials, with various convective forms of dialysis, a reduction in cardiovascular, but not all-cause mortality and the effects on non-fatal cardiovascular events and hospitalisation were uncertain. In contrast, an individual patient data analysis suggested that high-dose HDF reduced both all-cause and cardiovascular mortality compared to HD. In view of these discrepant results, a definitive trial is required to determine whether high-dose HDF is preferable to high-flux HD. The comparison of high-dose HDF with high-flux HD (CONVINCE) study will assess the benefits and harms of high-dose HDF versus a conventional high-flux HD in adults with ESKD. Methods and analysis This international, prospective, open label, randomised controlled trial aims to recruit 1800 ESKD adults treated with HD in nine European countries. Patients will be randomised 1:1 to high-dose HDF versus continuation of conventional high-flux HD. The primary outcome will be all-cause mortality at 3 years’ follow-up. Secondary outcomes will include cause-specific mortality, cardiovascular events, all-cause and infection-related hospitalisations, patient-reported outcomes (eg, health-related quality of life) and cost-effectiveness. Ethics and dissemination The CONVINCE study will address the question of benefits and harms of high-dose HDF compared to high-flux HD for kidney replacement therapy in patients with ESKD with a focus on survival, patient perspectives and cost-effectiveness. [ABSTRACT FROM AUTHOR]

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Background: Many interventions have shown effectiveness in reducing the duration of acute diarrhea and gastroenteritis (ADG) in children. Yet, there is lack of comparative efficacy of interventions that seem to be better than placebo among which, the clinicians must choose. Our aim was to determine the comparative effectiveness and safety of the pharmacological and nutritional interventions for reducing the duration of ADG in children. Methods: Data sources included Medline, Embase, CENTRAL, CINAHL, LILACS, and Global-Health up to May 2017. Eligible trials compared zinc (ZN), vitamin A, micronutrients (MN), probiotics, prebiotics, symbiotics, racecadotril, smectite(SM), loperamide, diluted milk, lactose-free formula(LCF), or their combinations, to placebo or standard treatment (STND), or among them. Two reviewers independently performed screening, review, study selection and extraction. The primary outcome was diarrhea duration. Secondary outcomes were stool frequency at day 2, diarrhea at day 3, vomiting and side effects. We performed a random effects Bayesian network meta-analysis to combine the direct and indirect evidence for each outcome. Mean differences and odds ratio with their credible intervals(CrI) were calculated. Coherence and transitivity assumptions were assessed. Meta-regression, subgroups and sensitivity analyses were conducted to explore the impact of effect modifiers. Summary under the cumulative curve (SUCRA) values with their CrI were calculated. We assessed the evidence quality and classified the best interventions using the Grading of Recommendations, Assessment, Development & Evaluation (GRADE) approach for each paired comparison. Results: A total of 174 studies (32,430 children) proved eligible. Studies were conducted in 42 countries of which most were low-and middle-income countries (LMIC). Interventions were grouped in 27 categories. Most interventions were better than STND. Reduction of diarrhea varied from 12.5 to 51.1 hours. The combinations Saccharomyces boulardii (SB)+ZN, and SM+ZN were considered the best interventions (i.e., GRADE quality of evidence: moderate to high, substantial superiority to STND, reduction in duration of 35 to 40 hours, and large SUCRA values), while symbiotics (combination of probiotics+prebiotics), ZN, loperamide and combinations ZN+MN and ZN+LCF were considered inferior to the best and better than STND [Quality: moderate to high, superior to STND, and reduction of 17 to 25 hours]. In subgroups analyses, effect of ZN was higher in LMIC and was not present in high-income countries (HIC). Vitamin A, MN, prebiotics, kaolin-pectin, and diluted milk were similar to STND [Quality: moderate to high]. The remainder of the interventions had low to very-low evidence quality. Loperamide was the only intervention with more side effects than STND [Quality: moderate]. Discussion/Conclusion: Most interventions analyzed (except vitamin A, micronutrients, prebiotics, and kaolin-pectin) showed evidence of superiority to placebo in reducing the diarrhea. With moderate-to high-quality of evidence, SB+ZN and SM+ZN, demonstrated the best combination of evidence quality and magnitude of effect while symbiotics, loperamide and zinc proved being the best single interventions, and loperamide was the most unsafe. Nonetheless, the effect of zinc, SB+ZN and SM+ZN might only be applied to children in LMIC. Results suggest no further role for studies comparing interventions against no treatment or placebo, or studies testing loperamide, MN, kaolin-pectin, vitamin A, prebiotics and diluted milk. PROSPERO registration: . [ABSTRACT FROM AUTHOR]

Decisions regarding the primary treatment of prostate cancer depend on several patient‐ and disease‐specific factors. Several international guidelines regarding the primary treatment of prostate cancer exist; however, they have not been formally compared. As guidelines often contradict each other, we aimed to systematically compare recommendations regarding the different primary treatment modalities of prostate cancer between guidelines. We searched Medline, the National Guidelines Clearinghouse, the library of the Guidelines International Network, and the websites of major urological associations for prostate cancer treatment guidelines. In total, 14 guidelines from 12 organisations were included in the present article. One of the main discrepancies concerned the definition of ‘localised’ prostate cancer. Localised prostate cancer was defined as cT1–cT3 in most guidelines; however, this disease stage was defined in other guidelines as cT1–cT2, or as any T‐stage as long as there is no lymph node involvement (N0) or metastases (M0). In addition, the risk stratification of localised cancer differed considerably between guidelines. Recommendations regarding radical prostatectomy and hormonal therapy were largely consistent between the guidelines. However, recommendations regarding active surveillance, brachytherapy, and external beam radiotherapy varied, mainly as a result of the inconsistencies in the risk stratification. The differences in year of publication and the methodology (i.e. consensus‐based or evidence‐based) for developing the guidelines might partly explain the differences in recommendations. It can be assumed that the observed variation in international clinical practice regarding the primary treatment of prostate cancer might be partly due to the inconsistent recommendations in different guidelines. [ABSTRACT FROM AUTHOR]

Objectives To investigate men's values and preferences regarding prostate-specific antigen (PSA)-based screening for prostate cancer. Design Systematic review. Data sources We searched MEDLINE, EMBASE, PsycINFO and grey literature up to 2 September 2017. Eligibility criteria Primary studies of men's values and preferences regarding the benefits and harms of PSA screening. Data extraction and synthesis Two independent reviewers extracted data and assessed risk of bias with a modified version of a risk of bias tool for values and preferences studies, the International Patient Decision Aid Standards instrument V.3 and the Cochrane Collaboration risk of bias tool. results We identified 4172 unique citations, of which 11 studies proved eligible. Five studies investigated PSA screening using a direct choice study design, whereas six used decisions aids displaying patient-important outcomes. The direct choice studies used different methodologies and varied considerably in the reporting of outcomes. Two studies suggested that men were willing to forego screening with a small benefit in prostate cancer mortality if it would decrease the likelihood of unnecessary treatment or biopsies. In contrast, one study reported that men were willing to accept a substantial overdiagnosis to reduce their risk of prostate cancer mortality. Among the six studies involving decision aids, willingness to undergo screening varied substantially from 37% when displaying a hypothetical reduction in mortality of 10 per 1000 men, to 44% when displaying a reduction in mortality of 7 per 1000. We found no studies that specifically investigated whether values and preferences differed among men with family history, of African descent or with lower socioeconomic levels. Conclusion The variability of men's values and preferences reflect that the decision to screen is highly preference sensitive. Our review highlights the need for shared decision making in men considering prostate cancer screening. trial registration number CRD42018095585. [ABSTRACT FROM AUTHOR]

Background: The high impact of a cancer diagnosis on patients and their families and the increasing costs of cancer treatment call for optimal and efficient oncological care. To improve the quality of care and to minimize healthcare costs and its economic burden, many healthcare organizations introduce care pathways to improve efficiency across the continuum of cancer care. However, there is limited research on the effects of cancer care pathways in different settings. Methods: The aim of this systematic review and meta-analysis described in this protocol is to synthesize existing literature on the effects of oncological care pathways. We will conduct a systematic search strategy to identify all relevant literature in several biomedical databases, including Cochrane library, MEDLINE, Embase, and CINAHL. We will follow the methodology of Cochrane Effective Practice and Organisation of Care (EPOC), and we will include randomized trials, non-randomized trials, controlled before-after studies, and interrupted time series studies. In addition, we will include full economic evaluations (cost-effectiveness analyses, cost-utility analyses, and costbenefit analyses), cost analyses, and comparative resource utilization studies, if available. Two reviewers will independently screen all studies and evaluate those included for risk of bias. From these studies, we will extract data regarding patient, professional, and health systems outcomes. Our systematic review will follow the PRISMA set of items for reporting in systematic reviews and meta-analyses. Discussion: Following the protocol outlined in this article, we aim to identify, assess, and synthesize all available evidence in order to provide an evidence base on the effects of oncological care pathways as reported in the literature. [ABSTRACT FROM AUTHOR]

Objective: We performed a cohort study in seven hospitals in Spain to determine the clinical characteristics of incident patients with bladder cancer, the diagnostic process, and the conditions that might affect health care interval times. Results: 314 patients with bladder cancer were included, 70.3 (Standard Deviation [SD] 11.2) years old and 85.0% male. Clinical stage was T1 in 45.9% of patients. The median interval time between first consultation and diagnosis was of 104.0 days (Inter quartile range [IQR]:112.0; range from 0 to 986), being shorter for those patients who attended a hospital for their first consultation. The median interval time between diagnosis and first treatment was of 0.0 days (IQR: 0.0; range from 0 to 366), being longer when the patient had a pathologic tumor stage ≥ T2a. [ABSTRACT FROM AUTHOR]

Background: The Checklist for the Reporting of Updated Guidelines (CheckUp) was recently developed. However, so far, no systematic assessment of the reporting of updated clinical guidelines (CGs) exists. We aimed to examine (1) the completeness of reporting the updating process in CGs and (2) the inter-observer reliability of CheckUp.Methods: We conducted a systematic assessment of the reporting of the updating process in a sample of updated CGs using CheckUp. We performed a systematic search to identify updated CGs published in 2015, developed by a professional society, reporting a systematic review of the evidence, and containing at least one recommendation. Three reviewers independently assessed the CGs with CheckUp (16 items). We calculated the median score per item, per domain, and overall, converting scores to a 10-point scale. Multiple linear regression analyses were used to identify differences according to country, type of organisation, scope, and health topic of updated CGs. We calculated the intraclass coefficient (ICC) and 95% confidence interval (95% CI) for domains and overall score.Results: We included in total 60 updated CGs. The median domain score on a 10-point scale for presentation was 5.8 (range 1.7 to 10), for editorial independence 8.3 (range 3.3 to 10), and for methodology 5.7 (range 0 to 10). The median overall score on a 10-point scale was 6.3 (range 3.1 to 10). Presentation and justification items at recommendation level (respectively reported by 27 and 38% of the CGs) and the methods used for the external review and implementing changes in practice were particularly poorly reported (both reported by 38% of the CGs). CGs developed by a European or international institution obtained a statistically significant higher overall score compared to North American or Asian institutions (p = 0.014). Finally, the agreement among the reviewers on the overall score was excellent (ICC 0.88, 95% CI 0.75 to 0.95).Conclusions: The reporting of updated CGs varies considerably with significant room for improvement. We recommend using CheckUp to assess the updating process in updated CGs and as a blueprint to inform methods and reporting strategies in updating. [ABSTRACT FROM AUTHOR]

Introduction Due to a continuous emergence of new evidence, clinical guidelines (CGs) require regular surveillance of evidence to maintain their trustworthiness. The updating of CGs is resource intensive and time consuming; therefore, updating may include a prioritisation process to efficiently ensure recommendations remain up to date. The objective of our project is to develop a pragmatic tool to prioritise clinical questions for updating within a CG. Methods and analysis To develop the tool, we will use the results and conclusions of a systematic review of methodological research on prioritisation processes for updating and will adopt a methodological approach we have successfully implemented in a previous experience. We will perform a multistep process including (1) generation of an initial version of the tool, (2) optimisation of the tool (feasibility test of the tool, semistructured interviews, Delphi consensus survey, external review by CG methodologists and users and pilot test of the tool) and (3) approval of the final version of the tool. At each step of the process, we will (1) calculate absolute frequencies and proportions (quantitative data), (2) use content analysis to summarise and draw conclusions (qualitative data) and (3) draft a final report, discuss results and refine the previous versions of the tool. Finally, we will calculate intraclass coefficients with 95% CIs for each item and overall as indicators of agreement among reviewers. Ethics and dissemination We have obtained a waiver of approval from the Clinical Research Ethics Committee at the Hospital de la Santa Creu i Sant Pau (Barcelona). The results of the study will be published in peer-reviewed journal and communicated to interested stakeholders. The tool could support the standardisation of prioritisation processes for updating CGs and therefore have important implications for a more efficient use of resources in the CG field. [ABSTRACT FROM AUTHOR]

Background: Guidelines support health care decision-making and high quality care and outcomes. However, their implementation is sub-optimal. Theory-informed, tailored implementation is associated with guideline use. Few guideline implementation studies published up to 1998 employed theory. This study aimed to describe if and how theory is now used to plan or evaluate guideline implementation among physicians.Methods: A scoping review was conducted. MEDLINE, EMBASE, and The Cochrane Library were searched from 2006 to April 2016. English language studies that planned or evaluated guideline implementation targeted to physicians based on explicitly named theory were eligible. Screening and data extraction were done in duplicate. Study characteristics and details about theory use were analyzed.Results: A total of 1244 published reports were identified, 891 were unique, and 716 were excluded based on title and abstract. Among 175 full-text articles, 89 planned or evaluated guideline implementation targeted to physicians; 42 (47.2%) were based on theory and included. The number of studies using theory increased yearly and represented a wide array of countries, guideline topics and types of physicians. The Theory of Planned Behavior (38.1%) and the Theoretical Domains Framework (23.8%) were used most frequently. Many studies rationalized choice of theory (83.3%), most often by stating that the theory described implementation or its determinants, but most failed to explicitly link barriers with theoretical constructs. The majority of studies used theory to inform surveys or interviews that identified barriers of guideline use as a preliminary step in implementation planning (76.2%). All studies that evaluated interventions reported positive impact on reported physician or patient outcomes.Conclusions: While the use of theory to design or evaluate interventions appears to be increasing over time, this review found that one half of guideline implementation studies were based on theory and many of those provided scant details about how theory was used. This limits interpretation and replication of those interventions, and seems to result in multifaceted interventions, which may not be feasible outside of scientific investigation. Further research is needed to better understand how to employ theory in guideline implementation planning or evaluation. [ABSTRACT FROM AUTHOR]

Background: High body mass index (BMI) is an important contributor to the global burden of ill-health and health inequality. Lower socioeconomic position (SEP) in both childhood and adulthood is associated with higher adult BMI, but how these associations have changed across time is poorly understood. We used longitudinal data to examine how childhood and adult SEP relates to BMI across adulthood in three national British birth cohorts.Methods and Findings: The sample comprised up to 22,810 participants with 77,115 BMI observations in the 1946 MRC National Survey of Health and Development (ages 20 to 60-64), the 1958 National Child Development Study (ages 23 to 50), and the 1970 British Cohort Study (ages 26 to 42). Harmonized social class-based SEP data (Registrar General's Social Class) was ascertained in childhood (father's class at 10/11 y) and adulthood (42/43 years), and BMI repeatedly across adulthood, spanning 1966 to 2012. Associations between SEP and BMI were examined using linear regression and multilevel models. Lower childhood SEP was associated with higher adult BMI in both genders, and differences were typically larger at older ages and similar in magnitude in each cohort. The strength of association between adult SEP and BMI did not vary with age in any consistent pattern in these cohorts, but were more evident in women than men, and inequalities were larger among women in the 1970 cohort compared with earlier-born cohorts. For example, mean differences in BMI at 42/43 y amongst women in the lowest compared with highest social class were 2.0 kg/m2 (95% CI: -0.1, 4.0) in the 1946 NSHD, 2.3 kg/m2 (1.1, 3.4) in the 1958 NCDS, and 3.9 kg/m2 (2.3, 5.4) the in the 1970 BCS; mean (SD) BMI in the highest and lowest social classes were as follows: 24.9 (0.8) versus 26.8 (0.7) in the 1946 NSHD, 24.2 (0.4) versus 26.5 (0.4) in the 1958 NCDS, and 24.2 (0.3) versus 28.1 (0.8) in the 1970 BCS. Findings did not differ whether using overweight or obesity as an outcome. Limitations of this work include the use of social class as the sole indicator of SEP-while it was available in each cohort in both childhood and adulthood, trends in BMI inequalities may differ according to other dimensions of SEP such as education or income. Although harmonized data were used to aid inferences about birth cohort differences in BMI inequality, differences in other factors may have also contributed to findings-for example, differences in missing data.Conclusions: Given these persisting inequalities and their public health implications, new and effective policies to reduce inequalities in adult BMI that tackle inequality with respect to both childhood and adult SEP are urgently required. [ABSTRACT FROM AUTHOR]

Background: Self-management is an important component of care for patients or consumers (henceforth termed patients) with chronic conditions. Research shows that patients view guidelines as potential sources of self-management support. However, few guidelines provide such support. The primary purpose of this study was to characterize effective types of self-management interventions that could be packaged as resources in (i.e., appendices) or with guidelines (i.e., accompanying products).Methods: We conducted a meta-review of systematic reviews that evaluated self-management interventions. MEDLINE, EMBASE, and the Cochrane Library were searched from 2005 to 2014 for English language systematic reviews. Data were extracted on study characteristics, intervention (content, delivery, duration, personnel, single or multifaceted), and outcomes. Interventions were characterized by the type of component for different domains (inform, activate, collaborate). Summary statistics were used to report the characteristics, frequency, and impact of the types of self-management components. A Measurement Tool to Assess Systematic Reviews (AMSTAR) was used to assess the methodological quality of included reviews.Results: Seventy-seven studies were included (14 low, 44 moderate, 18 high risk of bias). Reviews addressed numerous clinical topics, most frequently diabetes (23, 30 %). Fifty-four focused on single (38 educational, 16 self-directed) and 21 on multifaceted interventions. Support for collaboration with providers was the least frequently used form of self-management. Most conditions featured multiple types of self-management components. The most frequently occurring type of self-management component across all studies was lifestyle advice (72 %), followed by psychological strategies (69 %), and information about the condition (49 %). In most reviews, the intervention both informed and activated patients (57, 76 %). Among the reviews that achieved positive results, 83 % of interventions involved activation alone, 94 % in combination with information, and 95 % in combination with information and collaboration. No trends in the characteristics and impact of self-management by condition were observed.Conclusions: This study revealed numerous opportunities for enhancing guidelines with resources for both patients and providers to support self-management. This includes single resources that provide information and/or prompt activation. Further research is needed to more firmly establish the statistical association between the characteristics of self-management support and outcomes; and to and optimize the design of self-management resources that are included in or with guidelines, in particular, resources that prompt collaboration with providers. [ABSTRACT FROM AUTHOR]

Background Updating clinical practice guidelines (CPGs) is a crucial process for maintaining the validity of recommendations. Methodological handbooks should provide guidance on both developing and updating CPGs. However, little is known about the updating guidance provided by these handbooks. Methods We conducted a systematic review to identify and describe the updating guidance provided by CPG methodological handbooks and included handbooks that provide updating guidance for CPGs. We searched in the Guidelines International Network library, US National Guidelines Clearinghouse and MEDLINE (PubMed) from 1966 to September 2013. Two authors independently selected the handbooks and extracted the data. We used descriptive statistics to analyze the extracted data and conducted a narrative synthesis. Results We included 35 handbooks. Most handbooks (97.1%) focus mainly on developing CPGs, including variable degrees of information about updating. Guidance on identifying new evidence and the methodology of assessing the need for an update is described in 11 (31.4%) and eight handbooks (22.8%), respectively. The period of time between two updates is described in 25 handbooks (71.4%), two to three years being the most frequent (40.0%). The majority of handbooks do not provide guidance for the literature search, evidence selection, assessment, synthesis, and external review of the updating process. Conclusions Guidance for updating CPGs is poorly described in methodological handbooks. This guidance should be more rigorous and explicit. This could lead to a more optimal updating process, and, ultimately to valid trustworthy guidelines. [ABSTRACT FROM AUTHOR]

Background: Pathways are frequently used to improve care for cancer patients. However, there is little evidence about the effects of pathways used in oncological care. Therefore, we performed a systematic review and meta-analysis aiming to identify and synthesize existing literature on the effects of pathways in oncological care. Methods: All patients diagnosed with cancer in primary and secondary/tertiary care whose treatment can be characterized as the strategy "care pathways" are included in this review. A systematic search in seven databases was conducted to gather evidence. Studies were screened by two independent reviewers. Study outcomes regarding patients, professionals, and system level were extracted from each study. Results: Out of 13,847 search results, we selected 158 articles eligible for full text assessment. One hundred fifty studies were excluded and the remaining eight studies represented 4786 patients. Most studies were conducted in secondary/tertiary care. Length of stay (LOS) was the most common used indicator, and was reported in five studies. Meta-analysis based on subgroups showed an overall shorter LOS regarding gastric cancer (weighted mean difference (WMD)): − 2.75, CI: − 4.67 to − 0.83) and gynecological cancer (WMD: − 1.58, CI: − 2.10 to − 1.05). Costs were reported in six studies and most studies reported lower costs for pathway groups. Conclusions: Despite the differences between the included studies, we were able to present an evidence base for cancer care pathways performed in secondary/tertiary care regarding the positive effects of LOS in favor of cancer care pathways. Systematic review registration: PROSPERO CRD42017057592. [ABSTRACT FROM AUTHOR]

Background: Hypertension, a major risk factor of cardiovascular mortality, is a critical issue for public health. Although Baduanjin (Eight Brocades, EB), a traditional Chinese exercise, might influence blood pressure, glucose, and lipid status, the magnitude of true effects and subgroup differences remains unclear. Therefore, we performed a systematic review of relevant randomized controlled trials (RCTs) to evaluate the effect of EB on patient-important outcomes. Methods: We systematically searched PubMed, the Cochrane Library, Web of Science, and Chinese databases since inception until March 30, 2020. Meta-analysis was carried out using "meta" package in R 3.4.3 software. A prespecified subgroup analysis was done according to the type of comparisons between groups, and the credibility of significant subgroup effects (P < 0.05) were accessed using a five-criteria list. A GRADE evidence profile was constructed to illustrate the certainty of evidence. Results: Our meta-analysis, including 14 eligible trials with 1058 patients, showed that compared with routine treatment or health education as control groups, the mean difference (MD) in systolic blood pressure (SBP) of the EB groups was − 8.52 mmHg (95%CI:[− 10.65, − 6.40], P < 0.01) and diastolic blood pressure (DBP) was − 4.65 mmHg (95%CI: [− 6.55, − 2.74], P < 0.01). For blood pressure, the evidence was, however, of low certainty because of risk of bias and inconsistency, and for the outcomes of most interest to patients (cardiovascular morbidity and mortality directly), of very low certainty (measurement of surrogate only). Subgroup analysis showed there was no significant interaction effect between different type of comparisons (SBP P = 0.15; DBP P = 0.37), so it could be easily attributed to chance. Conclusion: Regularly EB exercising may be helpful to control blood pressure, but the evidence is only low certainty for blood pressure and very low certainty for cardiovascular morbidity and mortality. Rigorously designed RCTs that carry out longer follow-up and address patient-important outcomes remain warranted. Trial registration: PROSPERO Registration number: CRD42018095854. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are pivotal regulators of extracellular matrix (ECM) composition and could, due to their dynamic activity, function as prognostic tools for fibrosis and cardiac function in left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF). We conducted a systematic review on experimental animal models of LVDD and HFpEF published in MEDLINE or Embase. Twenty-three studies were included with a total of 36 comparisons that reported established LVDD, quantification of cardiac fibrosis and cardiac MMP or TIMP expression or activity. LVDD/HFpEF models were divided based on underlying pathology: hemodynamic overload (17 comparisons), metabolic alteration (16 comparisons) or ageing (3 comparisons). Meta-analysis showed that echocardiographic parameters were not consistently altered in LVDD/HFpEF with invasive hemodynamic measurements better representing LVDD. Increased myocardial fibrotic area indicated comparable characteristics between hemodynamic and metabolic models. Regarding MMPs and TIMPs; MMP2 and MMP9 activity and protein and TIMP1 protein levels were mainly enhanced in hemodynamic models. In most cases only mRNA was assessed and there were no correlations between cardiac tissue and plasma levels. Female gender, a known risk factor for LVDD and HFpEF, was underrepresented. Novel studies should detail relevant model characteristics and focus on MMP and TIMP protein expression and activity to identify predictive circulating markers in cardiac ECM remodeling. [ABSTRACT FROM AUTHOR]