Prognostic Factors Associated with Mortality in Cardiogenic Shock - A Systematic Review and Meta-Analysis.

BACKGROUND: Cardiogenic shock remains highly associated with early mortality, with mortality often exceeding 50%. We sought to determine the association between prognostic factors and in-hospital and 30-day mortality in cardiogenic shock. METHODS: We performed a systematic review and meta-analysis of prognostic factors in cardiogenic shock, searching MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for records up to June 5, 2023. English-language studies that investigated prognostic factors and in-hospital and/or 30-day mortality in cardiogenic shock were included. Studies were excluded if they evaluated the pediatric population, were postmortem studies, or included fewer than 100 patients. The primary aim was to identify modifiable and non-modifiable prognostic factors associated with in-hospital and 30-day mortality in cardiogenic shock. RESULTS: We identified 160 studies, including 2,459,703 patients with a median in-hospital mortality of 41.4% (interquartile range, 33.6% to 49.2%). The majority were retrospective cohort studies. Patient factors potentially associated with an increase in early mortality included an age greater than or equal to 75 years of age, peripheral arterial disease, chronic kidney disease, and female sex. Procedural and presentation factors potentially associated with increased mortality included out-of-hospital cardiac arrest, left main culprit artery, left ventricular ejection fraction less than 30%, dialysis, and need for mechanical circulatory support. Revascularization in the form of coronary artery bypass graft and percutaneous coronary intervention were potentially associated with reduced in-hospital mortality. CONCLUSIONS: This analysis quantifies the association between patient, presentation, and treatment-related factors and early mortality in cardiogenic shock. Increased certainty in the association of these prognostic factors with cardiogenic shock outcomes can aid in clinical risk assessment, development of risk tools, and analysis of clinical trials.

Assessment of the quality and content of clinical practice guidelines for vitamin D and for immigrants using the AGREE II instrument: global systematic review.

BACKGROUND: Worldwide, more immigrants experience vitamin D (vitD) deficiency than non-immigrants. Recommendations in current clinical practice guidelines (CPGs) concerning vitD are inadequate to address vitD deficiency among immigrants, and there are concerns regarding the quality of guidance in these CPGs. OBJECTIVES: This study aimed to identify and evaluate the quality of published CPGs addressing vitD and immigrants' health using the Appraisal of Guidelines for Research and Evaluation-II (AGREE II) tool and clarify the recommendations pertaining to vitD and immigrant populations in these CPGs. METHODS: We performed a systematic search to identify the most recent CPGs across various databases (Ovid MEDLINE ALL, Embase and Turning Research Into Practice), guideline repositories and grey literature. Two reviewers independently conducted study selection and data abstraction and evaluated the quality of the included guidelines using the AGREE II tool. RESULTS: We identified 25 relevant CPGs; 21 focused on vitD and 4 covered immigrants' health. Around one-quarter of the included CPGs were high quality (≥60% in at least four of the six domains, including 'rigour of development'). The highest mean scores among the six AGREE II domains were for 'clarity of presentation' and 'scope and purpose'. About 4.8% (1/21) of the CPGs on vitD had immigrant-related recommendations. VitD recommendations were emphasised in one out of the four immigrant health CPGs (25%). CPGs covering immigrants' health and vitD were inadequately systematically appraised. Moreover, recommendations regarding vitD were insufficient to address the growing epidemic of vitD deficiency among immigrant populations. CONCLUSION: The insufficient recommendations for vitD fail to address the rising vitD deficiency among immigrants, highlighting a critical gap in healthcare provisions. Urgent national and international efforts are needed to develop comprehensive CPGs, bridging research, policy and practice disparities. Future guidelines must prioritise routine vitD screening, supplementation protocols for vulnerable immigrant groups, and culturally appropriate interventions to improve health outcomes for immigrants globally. PROSPERO REGISTRATION NUMBER: CRD42021240562.

Delta QRS and outcomes post CRT in the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial.

BACKGROUND: For patients with left ventricular systolic dysfunction and prolonged QRS duration, cardiac resynchronization therapy (CRT) can improve cardiac electromechanical synchrony and prevent adverse clinical outcomes. OBJECTIVE: This study sought to investigate the role of delta QRS duration (ΔQRSd) in predicting clinical response to CRT. METHODS: The RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure Trial) study randomized 1798 patients to CRT with defibrillator or implantable cardioverter-defibrillator alone. Those who received CRT and had electrocardiograms available at baseline and after CRT implantation were included in this analysis. ΔQRSd was calculated as the absolute difference between QRS duration at baseline and with CRT pacing. The primary outcome was the composite of death and heart failure hospitalization. RESULTS: There were 813 patients included in this analysis. The median age was 67 years, and 125 patients (15.2%) were female. The median ΔQRSd was -2 ms (-20 to 18 ms), and 447 (55%) patients had a ΔQRSd ≤0 after implantation. ΔQRSd was an independent predictor of the composite outcome for patients with CRT (hazard ratio, 1.012; 95% confidence interval, 1.008-1.017). CRT recipients with ΔQRSd >0 had higher rates of the composite outcome than patients randomized to implantable cardioverter-defibrillator alone. CONCLUSION: For patients receiving CRT for heart failure with left ventricular systolic dysfunction and QRS prolongation, ΔQRSd was an independent predictor of long-term mortality and heart failure hospitalization.

Efficacy of stellate ganglion block in treatment of electrical storm: a systematic review and meta-analysis.

Electrical storm (ES) is a life-threatening condition of recurrent ventricular arrhythmias (VA) in a short period of time. Percutaneous stellate ganglion blockade (SGB) is frequently used - however the efficacy is undefined. The objective of our systematic review was to determine the efficacy of SGB in reducing VA events and mortality among patients with ES. A search of Medline, EMBASE, Scopus, CINAHL and CENTRAL was performed on February 29, 2024 to include studies with adult patients (≥ 18 years) with ES treated with SGB. Our outcomes of interest were VA burden pre- and post-SGB, and in-hospital/30-day mortality. A total of 553 ES episodes in 542 patients from 15 observational studies were included. Treated VAs pre- and post-SGB were pooled from eight studies including 383 patients and demonstrated a decrease from 3.5 (IQR 2.25-7.25) to 0 (IQR 0-0) events (p = 0.008). Complete resolution after SGB occurred in 190 of 294 patients (64.6%). Despite this, in-hospital or 30-day mortality remained high occurring in 140 of 527 patients (random effects prevalence 22%). Repeat SGB for recurrent VAs was performed in 132 of 490 patients (random effects prevalence 21%). In conclusion, observational data suggests SGB may be effective in reducing VAs in ES. Definitive studies for SGB in VA management are needed. Study protocol: PROSPERO - registration number CRD42023430031.

Advancing composite outcome measures: Insights on weighting components from OMERACT 2023.

OBJECTIVE: The OMERACT Composite Working Group hosted a workshop at OMERACT 2023 to explore the complexities of weighting components in the development of composite outcomes. This study presents the methodology and findings of this workshop, exploring the complexities of weighting the individual components of composite outcome measures. METHODS: The workshop featured a multifaceted program, beginning with a plenary session that introduced the concept of composite outcomes, shared a patient's journey with rheumatic disease through a narrative, illustrated a composite outcome for Osteoarthritis Flares, and outlined the five domains selected for this composite outcome. A breakout exercise engaged participants in ranking and assigning weights to these domains, followed by group discussions to reach a consensus on weights. The workshop concluded with another plenary session that discussed various weighting approaches, including discrete choice and conjoint analysis from the ANCA-Associated Vasculitis working group, and outlined future directions for research on composite outcome methods. RESULTS: The breakout exercise revealed the challenges in assigning relative importance to different domains, highlighting the variability in participant perspectives. Consensus discussions highlighted the diversity in approaches to weighting, the need for appropriate methods to determine domain weights and the impact of such weights on the interpretation of composite scores. CONCLUSION: The OMERACT 2023 workshop underscored the significance of a systematic approach to weighting components in composite outcome development. It highlighted the complexity of achieving consensus on the importance of domains and the role of incorporating the perspectives of patient research partners in this process. Future research directions include refining weighting methodologies, moving composites through the OMERACT Filter and enhancing understanding of their implications for clinical trials. The findings contribute to the ongoing discourse on optimizing composite outcome measures in rheumatology and beyond, advocating for a balanced integration of scientific rigour and patient-centeredness in their development.

A Multicentre Prospective Cohort Study to Identify High-Risk Transient Ischemic Attack/Minor Stroke Patients Benefitting from Echocardiography.

BACKGROUND: We aimed to derive a clinical decision rule to identify patients with transient ischemic attack (TIA) or minor stroke most likely to benefit from echocardiography. METHODS: This multicentre prospective cohort study enrolled adults diagnosed with TIA/minor stroke in the emergency department who underwent echocardiograms within 90 days, from 13 Canadian academic emergency departments from October 2006 to May 2017. Our outcome was clinically significant echocardiogram findings. RESULTS: In 7149 eligible patients, a clinically significant finding was found in 556 (7.8%). There were a further 2421 (33.9%) with potentially significant findings. History of heart failure (adjusted odds ratio [OR], 3.9) or coronary artery disease (OR, 2.7) were the factors most strongly associated with clinically significant echocardiogram findings, whereas young age, male sex, valvular heart disease, and infarct (any age) on neuroimaging were modestly associated (OR, 1.3-1.9). The model combining these predictors into a score (range: 0-15), had a C-statistic of 0.67 (95% confidence interval [CI], 0.65-0.70). A cut point of 6 points or more classified 6.6% of cases as high likelihood, defined as > 15% for clinically significant echocardiogram findings. CONCLUSIONS: Echocardiography is a very useful test in the investigations of patients with TIA/minor stroke. We identified high-risk clinical features-combined to create a clinical decision rule-to identify which patients with TIA/minor stroke are likely to have clinically significant echocardiogram findings requiring an immediate change in management. These patients should have echocardiography prioritized, whereas others may continue to have echocardiography conducted in a less urgent fashion.

Derivation of a clinical prediction score for the diagnosis of clinically significant symptomatic carotid artery disease.

OBJECTIVES: Emergent vascular imaging identifies a subset of patients requiring immediate specialized care (i.e. carotid stenosis > 50%, dissection or free-floating thrombus). However, most TIA patients do not have these findings, so it is inefficient to image all TIA patients in crowded emergency departments (ED). Our objectives were to derive and internally validate a clinical prediction score for clinically significant carotid artery disease in TIA patients. METHODS: This was a planned secondary analysis of a prospective cohort study from 14 Canadian EDs. Among 11555 consecutive adult ED patients with TIA/minor stroke symptoms over 12 years, 9882 had vascular imaging and were included in the analysis. Our main outcome was clinically significant carotid artery disease, defined as extracranial internal carotid stenosis ≥ 50%, dissection, or thrombus in the internal carotid artery, with contralateral symptoms. RESULTS: Of 9882 patients, 888 (9.0%) had clinically significant carotid artery disease. Logistic regression was used to derive a 13-variable reduced model. We simplified the model into a score (Symcard [Symptomatic carotid artery disease] Score), with suggested cut-points for high, medium, and low-risk stratification. A substantial portion (38%) of patients were classified as low-risk, 33.8% as medium risk, and 28.2% as high risk. At the low-risk cut-point, sensitivity was 92.9%, specificity 41.1%, and diagnostic yield 1.7%. CONCLUSIONS: This simple score can predict carotid artery disease in TIA patients using readily available information. It identifies low-risk patients who can defer vascular imaging to an outpatient or specialty clinic setting. Medium-risk patients may undergo imaging immediately or with slight delay, depending on local resources. High-risk patients should undergo urgent vascular imaging.

RéSUMé: OBJECTIFS: L'imagerie vasculaire émergente permet d'identifier un sous-ensemble de patients nécessitant des soins spécialisés immédiats (c.-à-d. sténose carotidienne >50 %, dissection ou thrombus flottant). Cependant, la plupart des patients atteints de RTI ne présentent pas ces résultats, il est donc inefficace d'effectuer une imagerie de tous les patients atteints de RTI dans les services d'urgence (ER) surpeuplés. Nos objectifs étaient de calculer et de valider en interne un score de prédiction clinique pour la maladie carotide cliniquement significative chez les patients atteints d'une AIT MéTHODES: Il s'agissait d'une analyse secondaire planifiée d'une étude de cohorte prospective menée auprès de 14 DE canadiens. Parmi les 11555 patients adultes consécutifs atteints d'un EI présentant des symptômes d'AIT/AVC mineur au cours des 12 dernières années, 9882 ont reçu une imagerie vasculaire et ont été inclus dans l'analyse. Notre principal critère de jugement était la maladie carotide cliniquement significative, définie comme une sténose extracrânienne de la carotide interne à 50 %, une dissection ou un thrombus dans l'artère carotide interne, avec des symptômes contralatéraux. RéSULTATS: Sur 9882 patients, 888 (9,0 %) présentaient une maladie de l'artère carotide cliniquement significative. La régression logistique a été utilisée pour obtenir un modèle réduit à 13 variables. Nous avons simplifié le modèle en un score (Symcard [Symptomatic carotid artery disease] Score), avec des points de coupure suggérés pour la stratification à risque élevé, moyen et faible. Une proportion importante (38,0 %) des patients ont été classés à faible risque, 33,8 % à risque moyen et 28,2 % à risque élevé. Au seuil de faible risque, la sensibilité était de 92,9 %, la spécificité de 41,1 % et le rendement diagnostique de 1,7 %. CONCLUSIONS: Ce score simple permet de prédire la maladie de l'artère carotide chez les patients atteints d'AIT en utilisant des informations facilement disponibles. Il identifie les patients à faible risque qui peuvent reporter l'imagerie vasculaire à un établissement de consultation externe ou de spécialité. Les patients à risque moyen peuvent subir une imagerie immédiatement ou avec un léger délai, selon les ressources locales. Les patients à haut risque doivent subir une imagerie vasculaire urgente.

Benefit of isolated surgical valve repair or replacement for functional tricuspid regurgitation and long-term outcomes stratified by the TRI-SCORE.

BACKGROUND AND AIMS: Severe tricuspid regurgitation (TR) is associated with increased mortality rates, but benefit of its correction and ideal timing are not clearly determined. This study aimed to identify patient subsets who might benefit from surgery. METHODS: In TRIGISTRY, an international cohort study of consecutive patients with severe isolated functional TR (33 centers, 10 countries), survival rates up to 10 years were compared between patients who underwent isolated tricuspid valve (TV) surgery (repair or replacement) and those conservatively managed, overall and according to TRI-SCORE category (low: ≤3, intermediate: 4-5, high: ≥6). RESULTS: 1,217 were managed conservatively, and 551 underwent isolated TV surgery (200 repairs, 351 replacements). TRI-SCORE distribution was 33% low, 32% intermediate, and 35% high. At 10 years, survival rates were similar between surgical and conservative management (41% vs. 36%; hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.88-1.08, P=0.57). Surgery improved survival compared to conservative management in the low TRI-SCORE category (72% vs. 44%; HR 0.27; 95% CI 0.20-0.37, P<0.0001), but not in the intermediate (36% vs. 37%, HR 1.17; 95%CI 0.98-1.40, P=0.09) or high categories (20% vs. 24%; HR 1.06; 95% CI 0.91-1.25, P=0.45). Both repair and replacement improved survival in the low TRI-SCORE category (84% and 61% vs. 44%; HR 0.11; 95% CI 0.06-0.19, P<0.0001, and HR 0.65; 95% CI 0.47-0.90, P=0.009). Repair showed benefit in the intermediate category (59% vs. 37%; HR 0.49; 95% CI 0.35-0.68, P<0.0001) while replacement was possibly harmful (25% vs. 37%; HR 1.43; 95% CI 1.18-1.72, P=0.0002). CONCLUSIONS: Higher survival rates were observed with repair than replacement and benefit of intervention declined as TRI-SCORE increased with no benefit of any type of surgery in the high TRI-SCORE category. These results emphasize the importance of timely intervention and patient selection to achieve the best outcomes and the need for randomized controlled trials. TRIAL REGISTRATION: TRIGISTRY: ClinicalTrials.gov, NCT05825898.

Is it time to start moving soil microbial fuel cell research out of the lab and into the field?

Soil microbial fuel cells (SMFCs) function as bioelectrochemical energy harvesters that convert electrons stored in soil organic matter into useful electrical energy. Broadly, an SMFC comprises three essential components: an anode buried in the soil (the negative terminal), a colony of exoelectrogenic microorganisms residing on this anode, and a cathode (the positive terminal). As the exoelectrogens respire, they release electrons to the anode, which acts as an external receptor. These released electrons then flow through a load (e.g. a resistor), connecting the anode and cathode. Though minuscule, the electrical power produced by SMFCs has a number of potential applications such as sustaining low-power embedded electronics, pollutant remediation, or as a bio-sensing proxy for soil qualities and microbial activity. This discussion aims to emphasize the potential of SMFCs in addressing real-world environmental issues and to generate interest in the larger scientific community for broad interdisciplinary research efforts, particularly in field deployments.

Engineered nanomaterials exert sublethal bacterial stress at very low doses: Effects of concentration, light, and media on cell membrane permeability.

Engineered nanomaterials (ENMs) can alter surface properties of cells and disturb cellular functions and gene expression through direct and indirect contact, exerting unintended impacts on human and ecological health. However, the effects of interactions among environmental factors, such as light, surrounding media, and ENM mixtures, on the mechanisms of ENM toxicity, especially at sublethal concentrations, are much less explored and understood. Therefore, we evaluated cell viability and outer membrane permeability of E. coli as a function of exposure to environmentally relevant concentrations of ENMs, including metal (n-Ag) and metal oxide (n-TiO2, n-Al2O3, n-ZnO, n-CuO, and n-SiO2) nanoparticles under dark and simulated sunlight illumination in MOPS, a synthetic buffer, and Lake Michigan Water (LMW), a freshwater medium. We found that light activates the phototoxicity of n-TiO2 and n-Ag by inducing significant increases in bacterial outer membrane permeability at sublethal doses (< 1 mg/L). Other ENMs, including n-ZnO, n-CuO, n-Al2O3, and n-SiO2, have small to minimal impacts. Toxicities of ENMs were greater in LMW than MOPS due to their different ionic strength and chemical composition. Physical and chemical interactions between n-TiO2 and n-Ag lead to amplified toxic effects of the ENM mixtures that are greater than the additive effects of individual ENMs acting alone. Our results revealed the significant sublethal bacterial stress exerted by ENMs and ENM mixtures at the cell surface in natural environments at low doses, which can potentially lead to further cellular damage and eventually impact overall ecological health.

Effects of guaranteed basic income interventions on poverty-related outcomes in high-income countries: A systematic review and meta-analysis.

Background: High-income countries offer social assistance (welfare) programs to help alleviate poverty for people with little or no income. These programs have become increasingly conditional and stringent in recent decades based on the premise that transitioning people from government support to paid work will improve their circumstances. However, many people end up with low-paying and precarious jobs that may cause more poverty because they lose benefits such as housing subsidies and health and dental insurance, while incurring job-related expenses. Conditional assistance programs are also expensive to administer and cause stigma. A guaranteed basic income (GBI) has been proposed as a more effective approach for alleviating poverty, and several experiments have been conducted in high-income countries to investigate whether GBI leads to improved outcomes compared to existing social programs. Objectives: The aim of this review was to conduct a synthesis of quantitative evidence on GBI interventions in high-income countries, to compare the effectiveness of various types of GBI versus "usual care" (including existing social assistance programs) in improving poverty-related outcomes. Search Methods: Searches of 16 academic databases were conducted in May 2022, using both keywords and database-specific controlled vocabulary, without limits or restrictions on language or date. Sources of gray literature (conference, governmental, and institutional websites) were searched in September 2022. We also searched reference lists of review articles, citations of included articles, and tables of contents of relevant journals in September 2022. Hand searching for recent publications was conducted until December 2022. Selection Criteria: We included all quantitative study designs except cross-sectional (at one timepoint), with or without control groups. We included studies in high income countries with any population and with interventions meeting our criteria for GBI: unconditional, with regular payments in cash (not in-kind) that were fixed or predictable in amount. Although two primary outcomes of interest were selected a priori (food insecurity, and poverty level assessed using official, national, or international measures), we did not screen studies on the basis of reported outcomes because it was not possible to define all potentially relevant poverty-related outcomes in advance. Data Collection and Analysis: We followed the Campbell Collaboration conduct and reporting guidelines to ensure a rigorous methodology. The risk of bias was assessed across seven domains: confounding, selection, attrition, motivation, implementation, measurement, and analysis/reporting. We conducted meta-analyses where results could be combined; otherwise, we presented the results in tables. We reported effect estimates as standard mean differences (SMDs) if the included studies reported them or provided sufficient data for us to calculate them. To compare the effects of different types of interventions, we developed a GBI typology based on the characteristics of experimental interventions as well as theoretical conceptualizations of GBI. Eligible poverty-related outcomes were classified into categories and sub-categories, to facilitate the synthesis of the individual findings. Because most of the included studies analyzed experiments conducted by other researchers, it was necessary to divide our analysis according to the "experiment" stage (i.e., design, recruitment, intervention, data collection) and the "study" stage (data analysis and reporting of results). Main Results: Our searches yielded 24,476 records from databases and 80 from other sources. After screening by title and abstract, the full texts of 294 potentially eligible articles were retrieved and screened, resulting in 27 included studies on 10 experiments. Eight of the experiments were RCTs, one included both an RCT site and a "saturation" site, and one used a repeated cross-sectional design. The duration ranged from one to 5 years. The control groups in all 10 experiments received "usual care" (i.e., no GBI intervention). The total number of participants was unknown because some of the studies did not report exact sample sizes. Of the studies that did, the smallest had 138 participants and the largest had 8019. The risk of bias assessments found "some concerns" for at least one domain in all 27 studies and "high risk" for at least one domain in 25 studies. The risk of bias was assessed as high in 21 studies due to attrition and in 22 studies due to analysis and reporting bias. To compare the interventions, we developed a classification framework of five GBI types, four of which were implemented in the experiments, and one that is used in new experiments now underway. The included studies reported 176 poverty-related outcomes, including one pre-defined primary outcome: food insecurity. The second primary outcome (poverty level assessed using official, national, or international measures) was not reported in any of the included studies. We classified the reported outcomes into seven categories: food insecurity (as a category), economic/material, physical health, psychological/mental health, social, educational, and individual choice/agency. Food insecurity was reported in two studies, both showing improvements (SMD = -0.57, 95% CI: -0.65 to -0.49, and SMD = -0.41, 95% CI: -0.57 to -0.26) which were not pooled because of different study designs. We conducted meta-analyses on four secondary outcomes that were reported in more than one study: subjective financial well-being, self-rated overall physical health, self-rated life satisfaction, and self-rated mental distress. Improvements were reported, except for overall physical health or if the intervention was similar to existing social assistance. The results for the remaining 170 outcomes, each reported in only one study, were summarized in tables by category and subcategory. Adverse effects were reported in some studies, but only for specific subgroups of participants, and not consistently, so these results may have been due to chance. Authors' Conclusions: The results of the included studies were difficult to synthesize because of the heterogeneity in the reported outcomes. This was due in part to poverty being multidimensional, so outcomes covered various aspects of life (economic, social, psychological, educational, agency, mental and physical health). Evidence from future studies would be easier to assess if outcomes were measured using more common, validated instruments. Based on our analysis of the included studies, a supplemental type of GBI (provided along with existing programs) may be effective in alleviating poverty-related outcomes. This approach may also be safer than a wholesale reform of existing social assistance approaches, which could have unintended consequences.

Antithrombotic therapy for durable left ventricular assist devices: protocol for a living systematic review with indirect comparison/network meta-analysis.

BACKGROUND: Left ventricular assist devices (LVADs) have emerged as a successful treatment option for patients with end-stage heart failure. Compared with the best medical therapy, LVADs improve survival and enhance functional capacity and quality of life. However, two major complications compromise this patient population's outcomes: thrombosis and bleeding. Despite technological innovations and better hemocompatibility, these devices alter the rheology, triggering the coagulation cascade and, therefore, require antithrombotic therapy. Anticoagulation and antiplatelet therapies represent the current standard of care. Still, inconsistency in the literature exists, especially whether antiplatelet therapy is required, whether direct oral anticoagulants can replace vitamin K antagonists and even whether phosphodiesterase type 5 inhibitors with their antithrombotic effects could be added to the regimen of anticoagulation. METHODS AND ANALYSIS: We will perform a living systematic review with network meta-analysis and indirect comparison between current antithrombotic therapies, which have and have not been directly compared within clinical trials and observational studies. We will systematically search the following electronic sources: Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica Database (EMBASE). We will exclusively examine studies published in English from 2016 to the present. Studies conducted before 2016 will be omitted since our primary focus is evaluating continuous flow devices. Two independent reviewers will assess the articles by title, abstract and full text; any disagreement will be resolved through discussion, and a third reviewer will be involved if necessary. The Cochrane Risk of Bias tool will be used to assess the risk of bias. We will then conduct a pairwise meta-analysis; if the assumption of transitivity is satisfied, we will proceed with network meta-analysis using Bayesian methodology. ETHICS AND DISSEMINATION: Formal ethical approval is not required as no primary data are collected. This systematic review and network meta-analysis will delineate the risks of stroke, thromboembolic events, pump thrombosis, gastrointestinal bleeding and mortality in patients equipped with LVADs who are subjected to various antithrombotic regimens. The findings will be disseminated via a peer-reviewed publication and presented at conference meetings. This will enhance clinical practice and guide future research on anticoagulation strategies within this distinct patient cohort. PROSPERO REGISTRATION NUMBER: CRD42023465288.

A scoping review shows that no single existing risk of bias assessment tool considers all sources of bias for cross-sectional studies.

OBJECTIVES: Different tools to assess the potential risk of bias (RoB) for cross-sectional studies have been developed, but it is unclear whether all pertinent bias concepts are addressed. We aimed to identify RoB concepts applicable to cross-sectional research validity and to explore coverage for each in existing appraisal tools. STUDY DESIGN AND SETTING: This scoping review followed the Joanna Briggs Institute methodology. We included records of any study design describing or reporting methods, concepts or tools used to consider RoB in health research reported to be descriptive/prevalence survey or analytic/association (cross-sectional) study designs. Synthesis included quantitative and qualitative analysis. RESULTS: Of the 4556 records screened, 90 were selected for inclusion; 67 (74%) described the development of, or validation process for, appraisal tools, 15 (17%) described methodological content or theory relevant to RoB for cross-sectional studies and 8 (9%) records of methodological systematic reviews. Review of methodological reports identified important RoB concepts for both descriptive/prevalence and analytic/association studies. Tools identified (n = 64 unique tools) were either intended to appraise quality or assess RoB in multiple study designs including cross-sectional studies (n = 21; 33%) or cross-sectional designs alone (n = 43; 67%). Several existing tools were modified (n = 17; 27%) for application to cross-sectional studies. The RoB items most frequently addressed in the RoB tools were validity and reliability of the exposure (53%) or outcome (65%) measurement and representativeness of the study population (59%). Most tools did not consider nonresponse or missingness appropriately or at all. CONCLUSION: Assessing cross-sectional studies involve unique RoB considerations. We identified RoB tools designed for broad applicability across various study designs as well as those specifically tailored for cross-sectional studies. However, none of the identified tools comprehensively address all potential biases pertinent to cross-sectional studies. Our findings indicate a need for continued improvement of RoB tools and suggest that the development of context-specific or more precise tools for this study design may be necessary.

Additive toxicity arising from combined use of immune checkpoint inhibitors and tyrosine kinase inhibitors in patients with renal or endometrial carcinoma: Protocol for a rapid systematic review.

The combined use of immune checkpoint inhibitors and tyrosine kinase inhibitors (ICI/TKI) is an effective treatment strategy for some cancers. A better understanding of the potential additive toxicity for ICI/TKI combinations is needed to inform patient and provider treatment decisions. We aim to evaluate the safety of ICI/TKI combinations for individuals with renal cell or endometrial carcinoma. This rapid systematic review (SR) protocol follows PRISMA guidelines. A systematic search will be designed, peer reviewed and executed by experienced information specialists (Cochrane Central, MEDLINE, Embase) to identify published SRs and primary studies published since the most recent SR search. Randomized, quasi- or non-randomized controlled trials and comparative cohort studies are eligible if they compare ICI/TKI combinations to monotherapy or standard of care in participants with renal cell or endometrial carcinoma. The primary outcome is grade ≥ 3 treatment-related adverse-effects. Studies will be screened, selected, extracted and assessed for risk of bias by a single reviewer and checked completely by a second. Where feasible and appropriate, we will pool studies separately by design and indication using meta-analysis and test robustness of effects using prespecified subgroup and sensitivity analyses. Results will be summarized descriptively and presented in tables and figures. (PROSPERO ID: CRD42023416388).•This will be a comprehensive systematic review of the additive toxicity arising from the combined use of ICI/TKIs in patients with renal-cell or endometrial carcinoma.•We will consider treatment-related, treatment-emergent adverse events (Grade 3 or higher).•Identified safety profile may be used to inform patient or provider treatment decisions.

Prognostic Implications of Residual Tricuspid Regurgitation Grading After Transcatheter Tricuspid Valve Repair.

BACKGROUND: The safety profile of transcatheter tricuspid valve (TTV) repair techniques is well established, but residual tricuspid regurgitation (TR) remains a concern. OBJECTIVES: The authors sought to assess the impact of residual TR severity post-TTV repair on survival. METHODS: We evaluated the survival rate at 2 years of 613 patients with severe isolated functional TR who underwent TTV repair in TRIGISTRY according to the severity of residual TR at discharge using a 3-grade (mild, moderate, and severe) or 4-grade scheme (mild, mild to moderate, moderate to severe, and severe). RESULTS: Residual TR was none/mild in 33%, moderate in 52%, and severe in 15%. The 2-year adjusted survival rates significantly differed between the 3 groups (85%, 70%, and 44%, respectively; restricted mean survival time [RMST]: P = 0.0001). When the 319 patients with moderate residual TR were subdivided into mild to moderate (n = 201, 33%) and moderate to severe (n = 118, 19%), the adjusted survival rate was also significantly different between groups (85%, 80%, 55%, and 44%, respectively; RMST: P = 0.001). Survival was significantly lower in patients with moderate to severe residual TR compared to patients with mild to moderate residual TR (P = 0.006). No difference in survival rates was observed between patients with no/mild and mild to moderate residual TR (P = 0.67) or between patients with moderate to severe and severe residual TR (P = 0.96). CONCLUSIONS: The moderate residual TR group was heterogeneous and encompassed patients with markedly different clinical outcomes. Refining TR grade classification with a more granular 4-grade scheme improved outcome prediction. Our results highlight the importance of achieving a mild to moderate or lower residual TR grade during TTV repair, which could define a successful intervention.

Cost-effectiveness of population screening for aortic stenosis.

BACKGROUND AND AIMS: Aortic stenosis (AS) is a progressive disease predominantly affecting elderly patients that carries significant morbidity and mortality without aortic valve replacement, the only proven treatment. Our objective was to determine the cost-effectiveness of AS screening using transthoracic echocardiography (TTE) in a geriatric population from the perspective of the publicly funded healthcare system in Canada. METHODS: Markov models estimating the cost-effectiveness ratio (ICER) for AS screening with a one-time TTE were developed. The model included diagnosed and undiagnosed AS health states, hospitalizations, TAVR and post-TAVR health states. Primary analysis included screening at 70 and 80 years of age with intervention at symptom onset, with scenario analysis included for early intervention at the time of severe asymptomatic AS diagnosis. Monte Carlo simulation of 5000 replications was completed with a lifetime horizon and 1.5% discount for costs and outcomes. RESULTS: Screening for AS at the age of 70 years was associated with an ICER of $156,722 and screening at 80 years of age was associated with an ICER of $28,005, suggesting that screening at 80 years of age is cost-effective when willingness-to-pay per QALY is $50,000. Scenario analysis with early intervention was not cost-effective with an ICER of $142,157 at 70 years, and $124,651 at 80 years. CONCLUSION: Screening for AS at 80 years of age with a one-time TTE, in a Canadian population, improves quality of life and is cost-effective in a publicly funded healthcare system providing TAVR is reserved for symptomatic patients.

A randomized clinical trial of catheter ablation and antiarrhythmic drug therapy for suppression of ventricular tachycardia in ischemic cardiomyopathy: The VANISH2 trial.

BACKGROUND: Recurrent ventricular tachycardia (VT) in patients with prior myocardial infarction is associated with adverse quality of life and clinical outcomes, despite the presence of implanted defibrillators (ICDs). Suppression of recurrent VT can be accomplished with antiarrhythmic drug therapy or catheter ablation. The Ventricular Tachycardia Antiarrhythmics or Ablation In Structural Heart Disease 2 (VANISH2) trial is designed to determine whether ablation is superior to antiarrhythmic drug therapy as first line therapy for patients with ischemic cardiomyopathy and VT. METHODS: The VANISH2 trial enrolls patients with prior myocardial infarction and VT (with one of: ≥1 ICD shock; ≥3 episodes treated with antitachycardia pacing (ATP) and symptoms; ≥5 episodes treated with ATP regardless of symptoms; ≥3 episodes within 24 hours; or sustained VT treated with electrical cardioversion or pharmacologic conversion). Enrolled patients are classified as either sotalol-eligible, or amiodarone-eligible, and then are randomized to either catheter ablation or to that antiarrhythmic drug therapy, with randomization stratified by drug-eligibility group. Drug therapy, catheter ablation procedures and ICD programming are standardized. All patients will be followed until two years after randomization. The primary endpoint is a composite of mortality at any time, appropriate ICD shock after 14 days, VT storm after 14 days, and treated sustained VT below detection of the ICD after 14 days. The outcomes will be analyzed according to the intention-to-treat principle using survival analysis techniques RESULTS: The results of the VANISH2 trial are intended to provide data to support clinical decisions on how to suppress VT for patients with prior myocardial infarction. CLINICALTRIALS: gov registration NCT02830360.

Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

BACKGROUND: Osteoporosis is an abnormal reduction in bone mass and bone deterioration, leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts - bone cells that break down bone tissue. This is an update of a Cochrane review first published in 2008. For clinical relevance, we investigated etidronate's effects on postmenopausal women stratified by fracture risk (low versus high). OBJECTIVES: To assess the benefits and harms of intermittent/cyclic etidronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women at lower and higher risk of fracture, respectively. SEARCH METHODS: We searched the Cochrane Central Register of Control Trials (CENTRAL), MEDLINE, Embase, two clinical trial registers, the websites of drug approval agencies, and the bibliographies of relevant systematic reviews. We identified eligible trials published between 1966 and February 2023. SELECTION CRITERIA: We included randomized controlled trials that assessed the benefits and harms of etidronate in the prevention of fractures for postmenopausal women. Women in the experimental arms must have received at least one year of etidronate, with or without other anti-osteoporotic drugs and concurrent calcium/vitamin D. Eligible comparators were placebo (i.e. no treatment; or calcium, vitamin D, or both) or another anti-osteoporotic drug. Major outcomes were clinical vertebral, non-vertebral, hip, and wrist fractures, withdrawals due to adverse events, and serious adverse events. We classified a study as secondary prevention if its population fulfilled one or more of the following hierarchical criteria: a diagnosis of osteoporosis, a history of vertebral fractures, a low bone mineral density T-score (≤ -2.5), or aged 75 years or older. If none of these criteria were met, we considered the study to be primary prevention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The review has three main comparisons: (1) etidronate 400 mg/day versus placebo; (2) etidronate 200 mg/day versus placebo; (3) etidronate at any dosage versus another anti-osteoporotic agent. We stratified the analyses for each comparison into primary and secondary prevention studies. For major outcomes in the placebo-controlled studies of etidronate 400 mg/day, we followed our original review by defining a greater than 15% relative change as clinically important. For all outcomes of interest, we extracted outcome measurements at the longest time point in the study. MAIN RESULTS: Thirty studies met the review's eligibility criteria. Of these, 26 studies, with a total of 2770 women, reported data that we could extract and quantitatively synthesize. There were nine primary and 17 secondary prevention studies. We had concerns about at least one risk of bias domain in each study. None of the studies described appropriate methods for allocation concealment, although 27% described adequate methods of random sequence generation. We judged that only 8% of the studies avoided performance bias, and provided adequate descriptions of appropriate blinding methods. One-quarter of studies that reported efficacy outcomes were at high risk of attrition bias, whilst 23% of studies reporting safety outcomes were at high risk in this domain. The 30 included studies compared (1) etidronate 400 mg/day to placebo (13 studies: nine primary and four secondary prevention); (2) etidronate 200 mg/day to placebo (three studies, all secondary prevention); or (3) etidronate (both dosing regimens) to another anti-osteoporotic agent (14 studies: one primary and 13 secondary prevention). We discuss only the etidronate 400 mg/day versus placebo comparison here. For primary prevention, we collected moderate- to very low-certainty evidence from nine studies (one to four years in length) including 740 postmenopausal women at lower risk of fractures. Compared to placebo, etidronate 400 mg/day probably results in little to no difference in non-vertebral fractures (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.20 to 1.61); absolute risk reduction (ARR) 4.8% fewer, 95% CI 8.9% fewer to 6.1% more) and serious adverse events (RR 0.90, 95% CI 0.52 to 1.54; ARR 1.1% fewer, 95% CI 4.9% fewer to 5.3% more), based on moderate-certainty evidence. Etidronate 400 mg/day may result in little to no difference in clinical vertebral fractures (RR 3.03, 95% CI 0.32 to 28.44; ARR 0.02% more, 95% CI 0% fewer to 0% more) and withdrawals due to adverse events (RR 1.41, 95% CI 0.81 to 2.47; ARR 2.3% more, 95% CI 1.1% fewer to 8.4% more), based on low-certainty evidence. We do not know the effect of etidronate on hip fractures because the evidence is very uncertain (RR not estimable based on very low-certainty evidence). Wrist fractures were not reported in the included studies. For secondary prevention, four studies (two to four years in length) including 667 postmenopausal women at higher risk of fractures provided the evidence. Compared to placebo, etidronate 400 mg/day may make little or no difference to non-vertebral fractures (RR 1.07, 95% CI 0.72 to 1.58; ARR 0.9% more, 95% CI 3.8% fewer to 8.1% more), based on low-certainty evidence. The evidence is very uncertain about etidronate's effects on hip fractures (RR 0.93, 95% CI 0.17 to 5.19; ARR 0.0% fewer, 95% CI 1.2% fewer to 6.3% more), wrist fractures (RR 0.90, 95% CI 0.13 to 6.04; ARR 0.0% fewer, 95% CI 2.5% fewer to 15.9% more), withdrawals due to adverse events (RR 1.09, 95% CI 0.54 to 2.18; ARR 0.4% more, 95% CI 1.9% fewer to 4.9% more), and serious adverse events (RR not estimable), compared to placebo. Clinical vertebral fractures were not reported in the included studies. AUTHORS' CONCLUSIONS: This update echoes the key findings of our previous review that etidronate probably makes or may make little to no difference to vertebral and non-vertebral fractures for both primary and secondary prevention.

Comparing methanol and glycerol as carbon sources for mainstream partial denitrification/anammox in an IFAS process.

This study explored the implementation of mainstream partial denitrification with anammox (PdNA) in the second anoxic zone of a wastewater treatment process in an integrated fixed film activated sludge (IFAS) configuration. A pilot study was conducted to compare the use of methanol and glycerol as external carbon sources for an IFAS PdNA startup, with a goal to optimize nitrogen removal while minimizing carbon usage. The study also investigated the establishment of anammox bacteria on virgin carriers in IFAS reactors without the use of seeding, and it is the first IFAS PdNA startup to use methanol as an external carbon source. The establishment of anammox bacteria was confirmed in both reactors 102 days after startup. Although the glycerol-fed reactor achieved a higher steady-state maximum ammonia removal rate because of anammox bacteria (1.6 ± 0.3 g/m2/day) in comparison with the methanol-fed reactor (1.2 ± 0.2 g/m2/day), both the glycerol- and methanol-fed reactors achieved similar average in situ ammonia removal rates of 0.39 ± 0.2 g/m2/day and 0.40 ± 0.2 g/m2/day, respectively. Additionally, when the upstream ammonia versus NOx (AvN) control system maintained an ideal ratio of 0.40-0.50 g/g, the methanol-fed reactor attained a lower average effluent TIN concentration (3.50 ± 1.2 mg/L) than the glycerol-fed reactor (4.43 ± 1.6 mg/L), which was prone to elevated nitrite concentrations in the effluent. Overall, this research highlights the potential for PdNA in IFAS configurations as an efficient and cost-saving method for wastewater treatment, with methanol as a viable carbon source for the establishment of anammox bacteria. PRACTITIONER POINTS: Methanol is an effective external carbon source for an anammox startup that avoids the need for costly alternative carbon sources. The methanol-fed reactor demonstrated higher TIN removal compared with the glycerol-fed reactor because of less overproduction of nitrite. Anammox bacteria was established in an IFAS reactor without seeding and used internally stored carbon to reduce external carbon addition. Controlling the influent ammonia versus NOx (AvN) ratio between 0.40 and 0.50 g/g allowed for low and stable TIN effluent conditions.

Defining domains: developing consensus-based definitions for foundational domains in OMERACT core outcome sets.

OBJECTIVE: To develop a set of detailed definitions for foundational domains commonly used in OMERACT (Outcome Measures in Rheumatology) core domain sets. METHODS: We identified candidate domain definitions from prior OMERACT publications and websites and publications of major organizations involved in outcomes research for six domains commonly used in OMERACT Core Domain Sets: pain intensity, pain interference, physical function, fatigue, patient global assessment, and health-related quality of life. We conducted a two-round survey of OMERACT working groups, patient research partners, and then the OMERACT Technical Advisory Group to establish their preferred domain definitions. Results were presented at the OMERACT 2023 Methodology Workshop, where participants discussed their relevant lived experience and identified potential sources of variability giving the needed detail in our domain definitions. RESULTS: One-hundred four people responded to both rounds of the survey, and a preferred definition was established for each of the domains except for patient global assessment for which no agreement was reached. Seventy-five participants at the OMERACT 2023 Methodology Workshop provided lived experience examples, which were used to contextualise domain definition reports for each of the five domains. CONCLUSION: Using a consensus-based approach, we have created a detailed definition for five of the foundational domains in OMERACT core domain sets; patient global assessment requires further research. These definitions, although not mandatory for working groups to use, may facilitate the initial domain-match assessment step of instrument selection, and reduce the time and resources required by future OMERACT groups when developing core outcome sets.