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Circulation. Cardiovascular... Oct 2023Hemodynamically unstable high-risk, or massive, pulmonary embolism (PE) has a reported in-hospital mortality of over 25%. Systemic thrombolysis is the...
BACKGROUND
Hemodynamically unstable high-risk, or massive, pulmonary embolism (PE) has a reported in-hospital mortality of over 25%. Systemic thrombolysis is the guideline-recommended treatment despite limited evidence. The FLAME study (FlowTriever for Acute Massive PE) was designed to generate evidence for interventional treatments in high-risk PE.
METHODS
The FLAME study was a prospective, multicenter, nonrandomized, parallel group, observational study of high-risk PE. Eligible patients were treated with FlowTriever mechanical thrombectomy (FlowTriever Arm) or with other contemporary therapies (Context Arm). The primary end point was an in-hospital composite of all-cause mortality, bailout to an alternate thrombus removal strategy, clinical deterioration, and major bleeding. This was compared in the FlowTriever Arm to a prespecified performance goal derived from a contemporary systematic review and meta-analysis.
RESULTS
A total of 53 patients were enrolled in the FlowTriever Arm and 61 in the Context Arm. Context Arm patients were primarily treated with systemic thrombolysis (68.9%) or anticoagulation alone (23.0%). The primary end point was reached in 9/53 (17.0%) FlowTriever Arm patients, significantly lower than the 32.0% performance goal (<0.01). The primary end point was reached in 39/61 (63.9%) Context Arm patients. In-hospital mortality occurred in 1/53 (1.9%) patients in the FlowTriever Arm and in 18/61 (29.5%) patients in the Context Arm.
CONCLUSIONS
Among patients selected for mechanical thrombectomy with the FlowTriever System, a significantly lower associated rate of in-hospital adverse clinical outcomes was observed compared with a prespecified performance goal, primarily driven by low all-cause mortality of 1.9%.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT04795167.
Topics: Humans; Multicenter Studies as Topic; Observational Studies as Topic; Prospective Studies; Pulmonary Embolism; Thrombectomy; Thrombolytic Therapy; Treatment Outcome
PubMed: 37847768
DOI: 10.1161/CIRCINTERVENTIONS.123.013406 -
Journal of Renal Nutrition : the... Nov 2023The nutritional status and management of children with chronic kidney disease (CKD) are complex and require a combined pediatric nephrology team work approach with... (Review)
Review
The nutritional status and management of children with chronic kidney disease (CKD) are complex and require a combined pediatric nephrology team work approach with physicians, nutritionists, nurses, and physical/occupational therapists. Prospective observational studies such as Children with CKD in the US, the 4C study in Europe and the International Pediatric Peritoneal Dialysis Network have advanced the field. However, most recommendations and guidelines from international task forces such as Kidney Diseases Improving Global Outcomes and Pediatric Renal Nutrition Taskforce are opinion-based rather than evidence-based. There is exciting ongoing research to improve nutrition in children with CKD to help them thrive.
Topics: Child; Humans; Nutritional Status; Renal Insufficiency, Chronic; Kidney; Peritoneal Dialysis; Nephrology; Renal Dialysis; Observational Studies as Topic
PubMed: 37558172
DOI: 10.1053/j.jrn.2023.07.006 -
JAMA Network Open Sep 2023Observational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but...
IMPORTANCE
Observational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice.
OBJECTIVE
To assess the reporting of observational studies that explicitly aimed to emulate a target trial.
EVIDENCE REVIEW
We searched Medline, Embase, PsycINFO, and Web of Science for observational studies published between March 2012 and October 2022 that explicitly aimed to emulate a target trial of a health or medical intervention. Two reviewers double-screened and -extracted data on study characteristics, key predefined components of the target trial protocol and its emulation (eligibility criteria, treatment strategies, treatment assignment, outcome[s], follow-up, causal contrast[s], and analysis plan), and other items related to the target trial emulation.
FINDINGS
A total of 200 studies that explicitly aimed to emulate a target trial were included. These studies included 26 subfields of medicine, and 168 (84%) were published from January 2020 to October 2022. The aim to emulate a target trial was explicit in 70 study titles (35%). Forty-three studies (22%) reported use of a published reporting guideline (eg, Strengthening the Reporting of Observational Studies in Epidemiology). Eighty-five studies (43%) did not describe all key items of how the target trial was emulated and 113 (57%) did not describe the protocol of the target trial and its emulation.
CONCLUSION AND RELEVANCE
In this systematic review of 200 studies that explicitly aimed to emulate a target trial, reporting of how the target trial was emulated was inconsistent. A reporting guideline for studies explicitly aiming to emulate a target trial may improve the reporting of the target trial protocols and other aspects of these emulation attempts.
Topics: Randomized Controlled Trials as Topic; Observational Studies as Topic
PubMed: 37755828
DOI: 10.1001/jamanetworkopen.2023.36023 -
Kidney International Oct 2023Vitamin D supplements have long been advocated for people with chronic kidney disease based on data from observational studies among the general population and people... (Review)
Review
Vitamin D supplements have long been advocated for people with chronic kidney disease based on data from observational studies among the general population and people with chronic kidney disease. These data consistently suggested that higher circulating concentrations of 25-hydroxyvitamin D are associated with improved fracture, cardiovascular, cancer, and mortality outcomes. In the past few years, large clinical trials have been conducted to assess the effects of vitamin D supplements on a range of clinically relevant outcomes. Most of these studies were performed in the general population, but they also enrolled people with chronic kidney disease. Virtually all of these trials were negative and contradicted the observational data. In this review, the key observational data and clinical trials are summarized, and potential explanations for the discrepancies between these studies are discussed.
Topics: Humans; Dietary Supplements; Fractures, Bone; Renal Insufficiency, Chronic; Vitamin D; Observational Studies as Topic
PubMed: 37541585
DOI: 10.1016/j.kint.2023.07.010 -
BMC Medical Research Methodology Aug 2023When conducting randomised controlled trials is impractical, an alternative is to carry out an observational study. However, making valid causal inferences from... (Review)
Review
BACKGROUND
When conducting randomised controlled trials is impractical, an alternative is to carry out an observational study. However, making valid causal inferences from observational data is challenging because of the risk of several statistical biases. In 2016 Hernán and Robins put forward the 'target trial framework' as a guide to best design and analyse observational studies whilst preventing the most common biases. This framework consists of (1) clearly defining a causal question about an intervention, (2) specifying the protocol of the hypothetical trial, and (3) explaining how the observational data will be used to emulate it.
METHODS
The aim of this scoping review was to identify and review all explicit attempts of trial emulation studies across all medical fields. Embase, Medline and Web of Science were searched for trial emulation studies published in English from database inception to February 25, 2021. The following information was extracted from studies that were deemed eligible for review: the subject area, the type of observational data that they leveraged, and the statistical methods they used to address the following biases: (A) confounding bias, (B) immortal time bias, and (C) selection bias.
RESULTS
The search resulted in 617 studies, 38 of which we deemed eligible for review. Of those 38 studies, most focused on cardiology, infectious diseases or oncology and the majority used electronic health records/electronic medical records data and cohort studies data. Different statistical methods were used to address confounding at baseline and selection bias, predominantly conditioning on the confounders (N = 18/49, 37%) and inverse probability of censoring weighting (N = 7/20, 35%) respectively. Different approaches were used to address immortal time bias, assigning individuals to treatment strategies at start of follow-up based on their data available at that specific time (N = 21, 55%), using the sequential trial emulations approach (N = 11, 29%) or the cloning approach (N = 6, 16%).
CONCLUSION
Different methods can be leveraged to address (A) confounding bias, (B) immortal time bias, and (C) selection bias. When working with observational data, and if possible, the 'target trial' framework should be used as it provides a structured conceptual approach to observational research.
Topics: Humans; Biomedical Research; Selection Bias; Databases, Factual; MEDLINE; Medical Oncology; Observational Studies as Topic
PubMed: 37587484
DOI: 10.1186/s12874-023-02000-9 -
Journal of the American Heart... Sep 2023Background Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However,...
Background Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However, associations with stroke subtypes are inconsistent, and the causality is unclear. Methods and Results We analyzed data of the UK Biobank and EPIC-CVD (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204 244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196 361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD, 5.8), and pooled mean age at menopause was 47.8 years (SD, 6.2). Over a median follow-up of 12.6 years (interquartile range, 11.8-13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5 years younger age at menopause were 1.09 (95% CI, 1.07-1.12) for stroke, 1.09 (95% CI, 1.06-1.13) for ischemic stroke, 1.10 (95% CI, 1.04-1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08-1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84-1.20) for subarachnoid hemorrhage. When using 2-sample Mendelian randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke. Conclusions In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.
Topics: Female; Humans; Middle Aged; Cerebral Hemorrhage; Hemorrhagic Stroke; Ischemic Stroke; Mendelian Randomization Analysis; Menopause; Postmenopause; Prospective Studies; Stroke; Observational Studies as Topic
PubMed: 37681566
DOI: 10.1161/JAHA.123.030280 -
Frontiers in Endocrinology 2023SGLT2 inhibitors (SGLT2i) are now the mainstay therapy for both diabetes and heart failure. publications, meta-analysis, and conference presentations of the eight... (Review)
Review
SGLT2 inhibitors (SGLT2i) are now the mainstay therapy for both diabetes and heart failure. publications, meta-analysis, and conference presentations of the eight SGLT2i Cardiovascular Outcomes trials (CVOTS) done in diabetic patients constantly echo that this class of drug decreases mortality, reduces cardiovascular events, and prevents heart failure and kidney disease. This review of medical agencies' SGLT2i analysis (FDA and EMA) helps to understand the reality of SGLT2i results in those trials, avoiding to consider observational and statistically undemonstrated endpoints as validated. They also confirmed the unique diuretic mode of action of SGLT2i, promoting osmotic diuresis, and its potential adverse events secondary to hypovolemia and hematocrit increase. They also support the understanding that the beliefs in SGLT2i morbi-mortality benefits are largely overstated mostly based on undemonstrated endpoints. Finally, it is clear that SGLT2i's antidiabetic action, secondary to its renal mode of action, plateaued after a few months and decreased strongly over time, questioning its long-term goal of maintaining diabetic patients' HbA1c below 7%. Also, this effect in patients with renal impairment is quasi null. We think that this review would be very helpful to every physician treating diabetic patients to better balance belief and reality of SGLT2i prescription effects.
Topics: Humans; Canagliflozin; Diabetes Mellitus, Type 2; Diuretics; Glucosides; Heart Failure; Observational Studies as Topic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37547306
DOI: 10.3389/fendo.2023.1174692 -
BMJ Open Jul 2023Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international...
Prevalence, management and efficacy of treatment in portal vein obstruction after paediatric liver transplantation: protocol of the retrospective international multicentre PORTAL registry.
INTRODUCTION
Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international study is to assess the prevalence, current management practices and efficacy of treatment in patients with PVO.
METHODS AND ANALYSIS
The Portal vein Obstruction Revascularisation Therapy After Liver transplantation registry will facilitate an international, retrospective, multicentre, observational study, with 25 centres around the world already actively involved. Paediatric patients (aged <18 years) with a diagnosed PVO between 1 January 2001 and 1 January 2021 after liver transplantation will be eligible for inclusion. The primary endpoints are the prevalence of PVO, primary and secondary patency after PVO intervention and current management practices. Secondary endpoints are patient and graft survival, severe complications of PVO and technical success of revascularisation techniques.
ETHICS AND DISSEMINATION
Medical Ethics Review Board of the University Medical Center Groningen has approved the study (METc 2021/072). The results of this study will be disseminated via peer-reviewed publications and scientific presentations at national and international conferences.
TRIAL REGISTRATION NUMBER
Netherlands Trial Register (NL9261).
Topics: Humans; Child; Liver Transplantation; Portal Vein; Retrospective Studies; Prevalence; Liver Diseases; Vascular Diseases; Registries; Observational Studies as Topic; Multicenter Studies as Topic
PubMed: 37500271
DOI: 10.1136/bmjopen-2022-066343 -
Annual Review of Nutrition Aug 2023Childhood undernutrition is a major global health burden that is only partially resolved by nutritional interventions. Both chronic and acute forms of child... (Review)
Review
Childhood undernutrition is a major global health burden that is only partially resolved by nutritional interventions. Both chronic and acute forms of child undernutrition are characterized by derangements in multiple biological systems including metabolism, immunity, and endocrine systems. A growing body of evidence supports a role of the gut microbiome in mediating these pathways influencing early life growth. Observational studies report alterations in the gut microbiome of undernourished children, while preclinical studies suggest that this can trigger intestinal enteropathy, alter host metabolism, and disrupt immune-mediated resistance against enteropathogens, each of which contribute to poor early life growth. Here, we compile evidence from preclinical and clinical studies and describe the emerging pathophysiological pathways by which the early life gut microbiome influences host metabolism, immunity, intestinal function, endocrine regulation, and other pathways contributing to child undernutrition. We discuss emerging microbiome-directed therapies and consider future research directions to identify and target microbiome-sensitive pathways in child undernutrition.
Topics: Child; Humans; Child Nutrition Disorders; Defecation; Gastrointestinal Microbiome; Malnutrition; Microbiota; Observational Studies as Topic
PubMed: 37207356
DOI: 10.1146/annurev-nutr-061121-091234 -
Journal of Translational Medicine Oct 2023Controversy over treatment for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a barrier to appropriate treatment. Energy management or pacing... (Review)
Review
BACKGROUND
Controversy over treatment for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a barrier to appropriate treatment. Energy management or pacing is a prominent coping strategy for people with ME/CFS. Whilst a definitive definition of pacing is not unanimous within the literature or healthcare providers, it typically comprises regulating activity to avoid post exertional malaise (PEM), the worsening of symptoms after an activity. Until now, characteristics of pacing, and the effects on patients' symptoms had not been systematically reviewed. This is problematic as the most common approach to pacing, pacing prescription, and the pooled efficacy of pacing was unknown. Collating evidence may help advise those suffering with similar symptoms, including long COVID, as practitioners would be better informed on methodological approaches to adopt, pacing implementation, and expected outcomes.
OBJECTIVES
In this scoping review of the literature, we aggregated type of, and outcomes of, pacing in people with ME/CFS.
ELIGIBILITY CRITERIA
Original investigations concerning pacing were considered in participants with ME/CFS.
SOURCES OF EVIDENCE
Six electronic databases (PubMed, Scholar, ScienceDirect, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials [CENTRAL]) were searched; and websites MEPedia, Action for ME, and ME Action were also searched for grey literature, to fully capture patient surveys not published in academic journals.
METHODS
A scoping review was conducted. Review selection and characterisation was performed by two independent reviewers using pretested forms.
RESULTS
Authors reviewed 177 titles and abstracts, resulting in 17 included studies: three randomised control trials (RCTs); one uncontrolled trial; one interventional case series; one retrospective observational study; two prospective observational studies; four cross-sectional observational studies; and five cross-sectional analytical studies. Studies included variable designs, durations, and outcome measures. In terms of pacing administration, studies used educational sessions and diaries for activity monitoring. Eleven studies reported benefits of pacing, four studies reported no effect, and two studies reported a detrimental effect in comparison to the control group.
CONCLUSIONS
Highly variable study designs and outcome measures, allied to poor to fair methodological quality resulted in heterogenous findings and highlights the requirement for more research examining pacing. Looking to the long COVID pandemic, our results suggest future studies should be RCTs utilising objectively quantified digitised pacing, over a longer duration of examination (i.e. longitudinal studies), using the core outcome set for patient reported outcome measures. Until these are completed, the literature base is insufficient to inform treatment practises for people with ME/CFS and long COVID.
Topics: Humans; Fatigue Syndrome, Chronic; Pandemics; Post-Acute COVID-19 Syndrome; COVID-19; Exercise Therapy; Observational Studies as Topic
PubMed: 37838675
DOI: 10.1186/s12967-023-04587-5