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Structural Heart : the Journal of the... Jul 2023Transcatheter aortic valve replacement (TAVR) is a treatment option for patients with symptomatic severe aortic stenosis across the entire spectrum of surgical risk.... (Review)
Review
Transcatheter aortic valve replacement (TAVR) is a treatment option for patients with symptomatic severe aortic stenosis across the entire spectrum of surgical risk. Recent trial data have led to the expansion of TAVR into lower-risk patients. With iterative technological advances and successive increases in procedural experience, the occurrence of complications following TAVR has declined. One of the most feared complications remains stroke, and patients consider stroke a worse outcome than death. There has therefore been great interest in strategies to mitigate the risk of stroke in patients undergoing TAVR. In this paper, we will discuss mechanisms and predictors of stroke after TAVR and describe the currently available cerebral embolic protection devices, including their design and relevant clinical studies pertaining to their use. We will also review the current overall evidence base for cerebral embolic protection during TAVR and ongoing randomized controlled trials. Finally, we will discuss our pragmatic recommendations for the use of cerebral embolic protection devices in patients undergoing TAVR.
PubMed: 37520138
DOI: 10.1016/j.shj.2023.100169 -
Anesthesia and Analgesia Jan 2024Cannabis products (CPs) and cannabis-based medicines (CBMs) are becoming increasingly available and are commonly used for pain management. The growing societal... (Review)
Review
Cannabis products (CPs) and cannabis-based medicines (CBMs) are becoming increasingly available and are commonly used for pain management. The growing societal acceptance of cannabis and liberalization of cannabis laws allows patients to access CPs with minimal clinical oversight. While there is mechanistic plausibility that CPs and CBMs may be useful for pain management, the clinical trial literature is limited and does not refute or support the use of CBMs for pain management. Complicating matters, a large and growing body of observational literature shows that many people use CPs for pain management and in place of other medications. However, products and dosing regimens in existing trials are not generalizable to the current cannabis market, making it difficult to compare and reconcile these 2 bodies of literature. Given this complexity, clinicians need clear, pragmatic guidance on how to appropriately educate and work with patients who are using CBMs for pain management. In this review, we narratively synthesize the evidence to enable a clear view of current landscape and provide pragmatic advice for clinicians to use when working with patients. This advice revolves around 3 principles: (1) maintaining the therapeutic alliance; (2) harm reduction and benefit maximization; and (3) pragmatism, principles of patient-centered care, and use of best clinical judgment in the face of uncertainty. Despite the lack of certainty CPs and chronic pain management use, we believe that following these principles can make most of the clinical opportunity presented by discussions around CPs and also enhance the likelihood of clinical benefit from CPs.
Topics: Humans; Chronic Pain; Pain Management; Cannabis; Analgesics; Palliative Care
PubMed: 38100797
DOI: 10.1213/ANE.0000000000005904 -
European Heart Journal. Acute... Aug 2023Extracorporeal cardiopulmonary resuscitation is a promising treatment for refractory out-of-hospital cardiac arrest. Three recent randomized trials (ARREST trial, Prague... (Randomized Controlled Trial)
Randomized Controlled Trial
Extracorporeal cardiopulmonary resuscitation is a promising treatment for refractory out-of-hospital cardiac arrest. Three recent randomized trials (ARREST trial, Prague OHCA study, and INCEPTION trial) that addressed the clinical benefit of extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest yielded seemingly diverging results. The evidence for extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest, derived from three recent randomized controlled trials, is not contradictory but rather complementary. Excellent results can be achieved with a very high level of dedication, provided that strict selection criteria are applied. However, pragmatic implementation of extracorporeal cardiopulmonary resuscitation does not necessarily lead to improved outcome of refractory out-of-hospital cardiac arrest. Centres that are performing extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest or aspire to do so should critically evaluate whether they are able to meet the pre-requisites that are needed to conduct an effective extracorporeal cardiopulmonary resuscitation programme.
Topics: Humans; Cardiopulmonary Resuscitation; Out-of-Hospital Cardiac Arrest; Randomized Controlled Trials as Topic
PubMed: 37480551
DOI: 10.1093/ehjacc/zuad071 -
Journal of the American Geriatrics... Nov 2023Advance care planning (ACP) is a process that involves discussing a person's goals, values, and preferences; it is particularly important for persons living with... (Review)
Review
BACKGROUND
Advance care planning (ACP) is a process that involves discussing a person's goals, values, and preferences; it is particularly important for persons living with dementia (PLWD) given that dementia is incurable and progressive. To ensure results that will impact real-world practices, ACP outcome measures must be psychometrically strong, meaningful to key partners, and pragmatic to collect. Therefore, we conducted a scoping review of outcome measures utilized in ACP randomized controlled clinical trials (RCTs) enrolling PLWD or their care partners and evaluated their pragmatic characteristics.
METHODS
We searched MEDLINE/PubMed, EMBASE, CINAHL, PsycINFO, and Web of Science for peer-reviewed ACP RCTs enrolling PLWD or their care partners from 2011 to 2021. We abstracted characteristics of primary and secondary outcome measures, including pragmatic characteristics using an adapted Psychometric and Pragmatic Evidence Rating Scale and ACP outcome domains using the standardized ACP Outcome Framework (i.e., process, action, healthcare, or quality of care).
RESULTS
We included 21 ACP RCTs. Trials included 103 outcome measures (39 primary and 64 secondary), of which 11% measured process, 14% measured action, 49% measured healthcare, and 26% measured quality of care. Twenty-four (23%) outcome measures were highly pragmatic, the majority of which (67%) reflected healthcare outcome measures. Sixty-one (59%) outcomes were assessed as highly relevant to PLWD or their care partners. Only 20% (n = 21) of outcome measures were embedded into clinical practice. Most (62%) RCTs were conducted in nursing homes, and 33% were focused PLWD with advanced stage disease.
CONCLUSIONS
In RCTs testing ACP interventions to support PLWD, only 23% of outcome measures were highly pragmatic, and most of these measured healthcare utilizations. Outcome assessments were rarely integrated into the EHR during routine clinical care. New outcome measures that address the lived experience of PLWD and their care partners plus have high pragmatic characteristics are needed for embedded pragmatic clinical trials.
Topics: Humans; Advance Care Planning; Nursing Homes; Outcome Assessment, Health Care; Patient Acceptance of Health Care; Dementia
PubMed: 37439456
DOI: 10.1111/jgs.18495 -
Journal of Medical Internet Research Sep 2023eHealth is increasingly considered an important tool for supporting pharmacotherapy management. (Review)
Review
BACKGROUND
eHealth is increasingly considered an important tool for supporting pharmacotherapy management.
OBJECTIVE
We aimed to assess the (1) use of eHealth in pharmacotherapy management with patients with asthma or chronic obstructive pulmonary disease (COPD), diabetes, or cardiovascular disease (CVD); (2) effectiveness of these interventions on pharmacotherapy management and clinical outcomes; and (3) key factors contributing to the success of eHealth interventions for pharmacotherapy management.
METHODS
We conducted a scoping review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping review) statement. Databases searched included Embase, MEDLINE (PubMed), and Cochrane Library. Screening was conducted by 2 independent researchers. Eligible articles were randomized controlled trials and cohort studies assessing the effect of an eHealth intervention for pharmacotherapy management compared with usual care on pharmacotherapy management or clinical outcomes in patients with asthma or COPD, CVD, or diabetes. The interventions were categorized by the type of device, pharmacotherapy management, mode of delivery, features, and domains described in the conceptual model for eHealth by Shaw at al (Health in our Hands, Interacting for Health, Data Enabling Health). The effectiveness on pharmacotherapy management outcomes and patient- and clinician-reported clinical outcomes was analyzed per type of intervention categorized by number of domains and features to identify trends.
RESULTS
Of 63 studies, 16 (25%), 31 (49%), 13 (21%), and 3 (5%) included patients with asthma or COPD, CVD, diabetes, or CVD and diabetes, respectively. Most (38/63, 60%) interventions targeted improving medication adherence, often combined for treatment plan optimization. Of the 16 asthma or COPD interventions, 6 aimed to improve inhaled medication use. The majority (48/63, 76%) of the studies provided an option for patient feedback. Most (20/63, 32%) eHealth interventions combined all 3 domains by Shaw et al, while 25% (16/63) combined Interacting for Health with Data Enabling Health. Two-thirds (42/63, 67%) of the studies showed a positive overall effect. Respectively, 48% (23/48), 57% (28/49), and 39% (12/31) reported a positive effect on pharmacotherapy management and clinician- and patient-reported clinical outcomes. Pharmacotherapy management and patient-reported clinical outcomes, but not clinician-reported clinical outcomes, were more often positive in interventions with ≥3 features. There was a trend toward more studies reporting a positive effect on all 3 outcomes with more domains by Shaw et al. Of the studies with interventions providing patient feedback, more showed a positive clinical outcome, compared with studies with interventions without feedback. This effect was not seen for pharmacotherapy management outcomes.
CONCLUSIONS
There is a wide variety of eHealth interventions combining various domains and features to target pharmacotherapy management in asthma or COPD, CVD, and diabetes. Results suggest feedback is key for a positive effect on clinician-reported clinical outcomes. eHealth interventions become more impactful when combining domains.
Topics: Humans; Cardiovascular Diseases; Asthma; Pulmonary Disease, Chronic Obstructive; Diabetes Mellitus; Databases, Factual; Randomized Controlled Trials as Topic
PubMed: 37751232
DOI: 10.2196/42474 -
European Journal of Clinical Nutrition Dec 2023Evidence-based nutritional recommendations address the health impact of suboptimal nutritional status. Efficacy randomized controlled trials (RCTs) have traditionally... (Review)
Review
Evidence-based nutritional recommendations address the health impact of suboptimal nutritional status. Efficacy randomized controlled trials (RCTs) have traditionally been the preferred method for determining the effects of nutritional interventions on health outcomes. Nevertheless, obtaining a holistic understanding of intervention efficacy and effectiveness in real-world settings is stymied by inherent constraints of efficacy RCTs. These limitations are further compounded by the complexity of nutritional interventions and the intricacies of the clinical context. Herein, we explore the advantages and limitations of alternative study designs (e.g., adaptive and pragmatic trials), which can be incorporated into RCTs to optimize the efficacy or effectiveness of interventions in clinical nutrition research. Efficacy RCTs often lack external validity due to their fixed design and restrictive eligibility criteria, leading to efficacy-effectiveness and evidence-practice gaps. Adaptive trials improve the evaluation of nutritional intervention efficacy through planned study modifications, such as recalculating sample sizes or discontinuing a study arm. Pragmatic trials are embedded within clinical practice or conducted in settings that resemble standard of care, enabling a more comprehensive assessment of intervention effectiveness. Pragmatic trials often rely on patient-oriented primary outcomes, acquire outcome data from electronic health records, and employ broader eligibility criteria. Consequently, adaptive and pragmatic trials facilitate the prompt implementation of evidence-based nutritional recommendations into clinical practice. Recognizing the limitations of efficacy RCTs and the potential advantages of alternative trial designs is essential for bridging efficacy-effectiveness and evidence-practice gaps. Ultimately, this awareness will lead to a greater number of patients benefiting from evidence-based nutritional recommendations.
Topics: Humans; Nutritional Status; Research Design; Pragmatic Clinical Trials as Topic; Adaptive Clinical Trials as Topic
PubMed: 37715007
DOI: 10.1038/s41430-023-01330-7 -
American Heart Journal Nov 2023Electronic health records contain vast amounts of cardiovascular data, including potential clues suggesting unrecognized conditions. One important example is the...
A pragmatic clinical trial assessing the effect of a targeted notification and clinical support pathway on the diagnostic evaluation and treatment of individuals with left ventricular hypertrophy (NOTIFY-LVH).
BACKGROUND
Electronic health records contain vast amounts of cardiovascular data, including potential clues suggesting unrecognized conditions. One important example is the identification of left ventricular hypertrophy (LVH) on echocardiography. If the underlying causes are untreated, individuals are at increased risk of developing clinically significant pathology. As the most common cause of LVH, hypertension accounts for more cardiovascular deaths than any other modifiable risk factor. Contemporary healthcare systems have suboptimal mechanisms for detecting and effectively implementing hypertension treatment before downstream consequences develop. Thus, there is an urgent need to validate alternative intervention strategies for individuals with preexisting-but potentially unrecognized-LVH.
METHODS
Through a randomized pragmatic trial within a large integrated healthcare system, we will study the impact of a centralized clinical support pathway on the diagnosis and treatment of hypertension and other LVH-associated diseases in individuals with echocardiographic evidence of concentric LVH. Approximately 600 individuals who are not treated for hypertension and who do not have a known cardiomyopathy will be randomized. The intervention will be directed by population health coordinators who will notify longitudinal clinicians and offer to assist with the diagnostic evaluation of LVH. Our hypothesis is that an intervention that alerts clinicians to the presence of LVH will increase the detection and treatment of hypertension and the diagnosis of alternative causes of thickened myocardium. The primary outcome is the initiation of an antihypertensive medication. Secondary outcomes include new hypertension diagnoses and new cardiomyopathy diagnoses. The trial began in March 2023 and outcomes will be assessed 12 months from the start of follow-up.
CONCLUSION
The NOTIFY-LVH trial will assess the efficacy of a centralized intervention to improve the detection and treatment of hypertension and LVH-associated diseases. Additionally, it will serve as a proof-of-concept for how to effectively utilize previously collected electronic health data to improve the recognition and management of a broad range of chronic cardiovascular conditions.
TRIAL REGISTRATION
NCT05713916.
PubMed: 37454754
DOI: 10.1016/j.ahj.2023.06.014 -
Clinical and Translational Science Jun 2024Specific selective serotonin reuptake inhibitors (SSRIs) metabolism is strongly influenced by two pharmacogenes, CYP2D6 and CYP2C19. However, the effectiveness of... (Randomized Controlled Trial)
Randomized Controlled Trial
Specific selective serotonin reuptake inhibitors (SSRIs) metabolism is strongly influenced by two pharmacogenes, CYP2D6 and CYP2C19. However, the effectiveness of prospectively using pharmacogenetic variants to select or dose SSRIs for depression is uncertain in routine clinical practice. The objective of this prospective, multicenter, pragmatic randomized controlled trial is to determine the effectiveness of genotype-guided selection and dosing of antidepressants on control of depression in participants who are 8 years or older with ≥3 months of depressive symptoms who require new or revised therapy. Those randomized to the intervention arm undergo pharmacogenetic testing at baseline and receive a pharmacy consult and/or automated clinical decision support intervention based on an actionable phenotype, while those randomized to the control arm have pharmacogenetic testing at the end of 6-months. In both groups, depression and drug tolerability outcomes are assessed at baseline, 1 month, 3 months (primary), and 6 months. The primary end point is defined by change in Patient-Reported Outcomes Measurement Information System (PROMIS) Depression score assessed at 3 months versus baseline. Secondary end points include change inpatient health questionnaire (PHQ-8) measure of depression severity, remission rates defined by PROMIS score < 16, medication adherence, and medication side effects. The primary analysis will compare the PROMIS score difference between trial arms among those with an actionable CYP2D6 or CYP2C19 genetic result or a CYP2D6 drug-drug interaction. The trial has completed accrual of 1461 participants, of which 562 were found to have an actionable phenotype to date, and follow-up will be complete in April of 2024.
Topics: Humans; Cytochrome P-450 CYP2D6; Selective Serotonin Reuptake Inhibitors; Pharmacogenomic Testing; Cytochrome P-450 CYP2C19; Depression; Prospective Studies; Female; Male; Pharmacogenomic Variants; Adult; Pragmatic Clinical Trials as Topic; Antidepressive Agents
PubMed: 38860639
DOI: 10.1111/cts.13822 -
BMJ Open Jan 2024It is encouraged to estimate the effectiveness of components within the enhanced recovery after surgery (ERAS) protocol through patient-reported outcomes, alongside...
Effectiveness of general anaesthesia with remimazolam tosilate on intraoperative haemodynamics and postoperative recovery: study protocol for a randomised, positive-controlled, pragmatic clinical trial (GARTH trial).
INTRODUCTION
It is encouraged to estimate the effectiveness of components within the enhanced recovery after surgery (ERAS) protocol through patient-reported outcomes, alongside doctor-reported outcomes and length of hospital stay. At present, studies on the contributions of optimal anaesthetic drugs within the ERAS protocol to patient-reported and doctor-reported outcomes are limited. Therefore, this study aims to pragmatically evaluate the effectiveness and safety of general anaesthesia (GA) with remimazolam tosilate within the ERAS protocol on intraoperative haemodynamics and postoperative recovery in adults undergoing elective surgeries, compared with propofol.
METHODS AND ANALYSIS
This study is a single-centre, randomised, blinded, positive-controlled, pragmatic clinical trial. A total of 900 patients, aged ≥18 years old, scheduled for an elective surgical procedure under GA will be included. Patients will be randomised in a 1:1 ratio to the remimazolam group (the GA with remimazolam tosilate within the ERAS protocol group) or propofol group (the GA with propofol within the ERAS protocol group), stratified by general surgery, thoracic surgery and other surgeries (including urological surgery and otolaryngology surgery). The primary outcomes include the 24-hour postoperative quality of recovery-40 score and the rate of intraoperative hypotension. Secondary endpoints include the rate of sedative hypotension requiring treatment, the haemodynamic profiles, the 72-hour postoperative quality of recovery-40 score, the functional anaesthetic capability, adverse events and complications, quality of life within 3 months as well as economic health outcomes.
ETHICS AND DISSEMINATION
This study protocol has been approved by the ethics committee of Guangdong Provincial People's Hospital (KY-H-2022-005-03-08). Dissemination plans will be presented at scientific meetings and in scientific publications.
TRIAL REGISTRATION NUMBER
ChiCTR2200062520.
Topics: Adolescent; Adult; Humans; Anesthesia, General; Anesthetics; Hemodynamics; Hypotension; Postoperative Complications; Propofol; Quality of Life; Randomized Controlled Trials as Topic; Pragmatic Clinical Trials as Topic
PubMed: 38176870
DOI: 10.1136/bmjopen-2023-073024 -
Trials Jul 2023The incidence of maternal opioid use in the USA has increased substantially since 2000. As a consequence of opioid use during pregnancy, the incidence of neonatal opioid... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The incidence of maternal opioid use in the USA has increased substantially since 2000. As a consequence of opioid use during pregnancy, the incidence of neonatal opioid withdrawal syndrome (NOWS) has increased fivefold between 2002 and 2012. Pharmacological therapy is indicated when signs of NOWS cannot be controlled, and the objective of pharmacological therapy is to control NOWS signs. Once pharmacologic therapy has started, there is great variability in strategies to wean infants. An important rationale for studying weaning of pharmacological treatment for NOWS is that weaning represents the longest time interval of drug treatment. Stopping medications too early may not completely treat NOWS symptoms.
METHODS
This will be a pragmatic, randomized, blinded trial of opioid weaning to determine whether more rapid weaning, compared to slow wean, will reduce the number of days of opioid treatment in infants receiving morphine or methadone as the primary treatment for NOWS.
DISCUSSION
The proposed study is a pragmatic trial to determine whether a rapid-weaning intervention reduces the number of days of opioid treatment, compared to a slow-weaning intervention, and we powered the proposed study to detect a 2-day difference in the length of treatment. Hospitals will be able to use either morphine or methadone with the knowledge that we may find a positive treatment effect for both, one, or neither drugs.
TRIAL REGISTRATION
NCT04214834. Registered January 2, 2020.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Analgesics, Opioid; Family; Methadone; Morphine; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Research Design
PubMed: 37480087
DOI: 10.1186/s13063-023-07378-x