-
JAMA May 2024
Topics: Humans; Male; Middle Aged; Biopsy; Early Detection of Cancer; Kallikreins; Magnetic Resonance Imaging; Mass Screening; Overdiagnosis; Overtreatment; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Watchful Waiting; Aged
PubMed: 38581253
DOI: 10.1001/jama.2024.4089 -
Current Opinion in Critical Care Aug 2023Cardiogenic shock (CS) results in persistently high short-term mortality and a lack of evidence-based therapies. Several trials of novel interventions have failed to... (Review)
Review
PURPOSE OF REVIEW
Cardiogenic shock (CS) results in persistently high short-term mortality and a lack of evidence-based therapies. Several trials of novel interventions have failed to show an improvement in clinical outcomes despite promising preclinical and physiologic principles. In this review, we highlight the challenges of CS trials and provide suggestions for the optimization and harmonization of their design.
RECENT FINDINGS
CS clinical trials have been plagued by slow or incomplete enrolment, heterogeneous or nonrepresentative patient cohorts, and neutral results. To achieve meaningful, practice-changing results in CS clinical trials, an accurate CS definition, a pragmatic staging of its severity for appropriate patient selection, an improvement in informed consent process, and the use of patient-centered outcomes are required. Future optimizations include the use of predictive enrichment using host response biomarkers to unravel the biological heterogeneity of the CS syndrome and identify subphenotypes most likely to benefit from individualized treatment to allow a personalized medicine approach.
SUMMARY
Accurate characterization of CS severity and its pathophysiology are crucial to unravel heterogeneity and identify the patients most likely to benefit from a tested treatment. Implementation of biomarker-stratified adaptive clinical trial designs (i.e., biomarker or subphenotype-based therapy) might provide important insights into treatment effects.
Topics: Humans; Shock, Cardiogenic; Biomarkers
PubMed: 37338937
DOI: 10.1097/MCC.0000000000001066 -
Trials Jun 2024Parents of children with a neurodevelopmental disorder (NDD) experience more stress than parents of typically developing children. In a cocreation process with experts...
Effectiveness of a positive psychology and mindfulness-based app on mental health for parents of children with a neurodevelopmental disorder: study protocol of a pragmatic international randomized controlled trial.
INTRODUCTION
Parents of children with a neurodevelopmental disorder (NDD) experience more stress than parents of typically developing children. In a cocreation process with experts and parents, a low-threshold application that uses exercises based on the principles of positive psychology and mindfulness was developed. This application, called "Adappt," aims at enhancing the ability to adapt of the parents and caregivers of children with NDDs and at supporting their mental health. This protocol describes the evaluation study of the effectiveness of Adappt, its core working mechanisms and user experiences.
METHOD
A pragmatic international multicenter randomized controlled trial will compare the effectiveness of Adappt with a (delayed) waitlist control condition. At least 212 parents or primary caregivers of children younger than 18 years diagnosed with or suspected of a NDD will be randomly assigned to the intervention or waitlist control condition. Participants are excluded if they have severe anxiety or depression levels or are in treatment for mental health issues. Measures will be collected online at baseline, post-intervention (1 month after baseline), and 4 and 7 months after baseline. The primary outcome is the improvement in generic sense of ability to adapt as measured with the Generic Sense of Ability to Adapt Scale (GSAAS; (Front Psychol 14:985408, 2023)) at 4-month follow-up. Secondary outcomes are mental well-being, (parental) distress, and client satisfaction with "Adappt."
DISCUSSION
Results of this study will contribute to knowledge on the effectiveness of a low-threshold application for parents of children with a NDD in multiple countries. If the application is found to be effective in improving mental health, recommendations will be made for implementation in health care.
TRIAL REGISTRATION
This study is registered on clinicaltrials.gov (NCT06248762) on February 8, 2024, and the Open Science Framework ( https://osf.io/5znqv ).
Topics: Humans; Mindfulness; Parents; Mental Health; Neurodevelopmental Disorders; Child; Pragmatic Clinical Trials as Topic; Multicenter Studies as Topic; Mobile Applications; Psychology, Positive; Adolescent; Stress, Psychological; Treatment Outcome; Adaptation, Psychological; Randomized Controlled Trials as Topic
PubMed: 38926739
DOI: 10.1186/s13063-024-08256-w -
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 -
Chronobiology International Aug 2023The conduct of molecular and laboratory animal circadian rhythm research has increased exponentially in the past few decades, such that today investigations are being... (Review)
Review
Critical appraisal of recent translational chronopharmacology and chronotherapeutic reviews, meta-analyses, and pragmatic patient trials discloses significant deficiencies of design and conduct and suspect findings.
The conduct of molecular and laboratory animal circadian rhythm research has increased exponentially in the past few decades, such that today investigations are being performed by scientists of many diverse disciplines. Knowledge gained from past works is now being explored for translational applications to clinical medicine, often termed "circadian medicine," through the implementation of patient trials. However, these trials are being led, more often than not, by investigators who have little or no formal training and in-depth expertise in the methods of human circadian rhythm research, causing them to be deficient in design and produce dubious findings that have already led to unnecessary medical controversy at the expense of advances in patient care. Evidence of the very significant shortcomings of today's translational circadian medicine research is exemplified in two recent publications in well-read reputable medical journals concerning the chronotherapy of blood pressure (BP) medications: one a review and meta-analysis by Maqsood et al. published in the journal in 2023 that pertains to ingestion-time differences in the extent of BP reduction exerted by hypertensive medications and the other a report by Mackenzie et al. in the journal in 2022 that details the results of the pragmatic TIME study that assessed ingestion-time differences in cardiovascular disease outcomes. Herein, we appraise the inaccurate trial selection, lack of quality assessment, and the numerous other shortcomings that culminated in suspect findings and faulty conclusions of the former, as well as the deficiencies in design and conduct of the latter using as reference the eight items identified in 2021 by a working committee of the International Society for Chronobiology and American Association for Medical Chronobiology and Chronotherapeutics as being necessary for high-quality research of circadian rhythm-dependencies of the therapeutic effects of BP-lowering medications. The TIME study when rated for its quality according to the extent to which its investigational methods satisfy all of the eight recommended items attains a very low overall score of + 1 out of a possible range of -1 to + 7. Moreover, our review of the methods of the currently ongoing pragmatic BedMed trial discloses major deficiencies of the same sort rending a poor quality score of + 0.5. Although the focus of this article is the appraisal of the quality of contemporary circadian medicine hypertension chronotherapy research, it additionally exposes the inadequacies and dubious quality of the critique of such manuscripts submitted for publication to influential journals, in that some peer reviewers might also be deficient in the knowledge required to properly rate their merit.
Topics: Animals; Humans; Blood Pressure; Chronotherapy; Circadian Rhythm; Drug Chronotherapy; Hypertension
PubMed: 37674275
DOI: 10.1080/07420528.2023.2253288 -
Contemporary Clinical Trials Nov 2023Guidelines recommend screening for colorectal cancer (CRC), but participation and abnormal test follow up rates are suboptimal, with disparities by demography....
BACKGROUND
Guidelines recommend screening for colorectal cancer (CRC), but participation and abnormal test follow up rates are suboptimal, with disparities by demography. Evidence-based interventions exist to promote screening, but community adoption and implementation are limited.
METHODS
The San Diego Accelerating Colorectal Cancer Screening and Follow-up through Implementation Science (ACCSIS) program is an academic-community partnership testing regional implementation of a Hub-and-Spoke model for increasing CRC screening and follow-up. The "hub" is a non-academic, non-profit organization that includes 17 community health center (CHC) systems, serving over 190 rural and urban clinic sites. The "spokes" are 3 CHC systems that oversee 11-28 clinics each, totaling over 60 clinics. Using a cluster-randomized trial design, 9 clinics were randomized to intervention and 16 to usual care. Within intervention clinics, approximately 5000 eligible patients not up-to-date with CRC screening per year were identified for intervention. Interventions include an invitation primer, a mailed fecal immunochemical test with completion instructions, and phone and text-based reminders (hub) and patient navigation protocol to promote colonoscopy completion after abnormal FIT (spoke). Outcomes include: 1) proportion of patients up-to-date with screening after three years in intervention versus non-intervention clinics; 2) proportion of patients with abnormal FIT completing colonoscopy within six months of the abnormal result. Implementation science measures are collected to assess acceptability, intervention and usual care adaptations, and sustainability of the intervention strategies.
CONCLUSION
This large-scale, regional cluster randomized trial among CHCs serving diverse populations is anticipated to accelerate progress in CRC prevention in underserved populations.
TRIAL REGISTRATION
NCT04941300.
Topics: Humans; Early Detection of Cancer; Mass Screening; Colorectal Neoplasms; Ambulatory Care Facilities; Community Health Centers; Occult Blood; Randomized Controlled Trials as Topic
PubMed: 37802222
DOI: 10.1016/j.cct.2023.107353 -
Trials Apr 2024To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In... (Randomized Controlled Trial)
Randomized Controlled Trial
Prednisolone Versus Colchicine for Acute Gout in Primary Care: statistical analysis plan for the pragmatic, multicenter, randomized, and double-blinded COPAGO non-inferiority trial.
BACKGROUND
To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In addition, in previous trials of treating acute gout patients with concomitant comorbidities were often excluded due to contraindications to naproxen.
STUDY DESIGN
This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial compares prednisolone with colchicine in terms of non-inferiority in patients with acute gout. Patients presenting to their general practitioner with acute gout can be included if the gout attack has occurred within the last 2 days. A total of 60 practices in the vicinity of three university medical centers (Greifswald, Göttingen, and Würzburg) participate in the study. The intervention group receives 30 mg prednisolone for 5 days, while the group of standard care receives low-dose colchicine (day 1: 1.5 mg; days 2-5: 1 mg). The first dose of treatment is provided at day 0 when patients present to the general practitioner due to an acute gout attack. From day 0 to day 6, patients will be asked to complete a study diary on daily basis regarding pain quantification. For safety reasons, potential side effects and the course of systolic blood pressure are also assessed.
STATISTICAL ANALYSIS PLAN
N = 314 patients have to be recruited to compensate for 10% of dropout and to allow for showing non-inferiority of prednisolone compared to colchicine with a power of 90%. We use permuted block randomization with block sizes of 2, 4, and 6 to avoid imbalanced treatment arms in this multi-center study; patients are randomized in a 1:1 ratio. The absolute level of pain on day 3 (in the last 24 h) is the primary outcome and measured on a numerical rating scale (NRS: 0-10). Using a multiple linear regression model adjusted for age, sex, and pain at baseline, prednisolone is considered non-inferior if the effect estimate including the confidence intervals is lower than a margin of 1 unit on the NRS. Average response to treatment, joint swelling and tenderness, physical function of the joint, and patients' global assessment of treatment success are secondary outcomes.
DISCUSSION
The trial will provide evidence from a direct comparison of colchicine and prednisolone regarding their efficacy of pain reduction in acute gout patients of primary care and to indicate possible safety signals.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered).
Topics: Humans; Arthritis, Gouty; Colchicine; Gout; Pain; Prednisolone; Primary Health Care; Prospective Studies; Treatment Outcome; Male; Female
PubMed: 38570873
DOI: 10.1186/s13063-024-08066-0 -
Mayo Clinic Proceedings Mar 2024Frontline primary care teams face important challenges in seeking to transform the quality of care delivered to patients and to reduce clerical burden for clinicians.... (Review)
Review
Frontline primary care teams face important challenges in seeking to transform the quality of care delivered to patients and to reduce clerical burden for clinicians. Digital technologies using artificial intelligence hold substantial promise to aid in this transformation. Both pragmatic clinical trials and implementation science are key tools to successfully introduce, evaluate, and sustain innovations in real-world primary care practices. Previous articles in this thematic series have provided an in-depth overview of pragmatic trials and implementation science. This paper demonstrates and provides a framework for how these concepts, together with digital transformation, can be used to solve many of the challenges facing primary care. This framework is conceived as the collaboration of frontline primary care teams with innovators in academic institutions and industry through pragmatic trials and implementation science.
Topics: Humans; Digital Technology; Artificial Intelligence; Capacity Building; Primary Health Care
PubMed: 38432751
DOI: 10.1016/j.mayocp.2023.07.011 -
Contemporary Clinical Trials Aug 2023Suicide is a leading cause of death in adolescents and adults in the US. Follow-up support delivered when patients return home after an emergency department (ED) or...
Comparative effectiveness of safety planning intervention with instrumental support calls (ISC) versus safety planning intervention with two-way text message caring contacts (CC) in adolescents and adults screening positive for suicide risk in emergency departments and primary care clinics:...
BACKGROUND
Suicide is a leading cause of death in adolescents and adults in the US. Follow-up support delivered when patients return home after an emergency department (ED) or primary care encounter can significantly reduce suicidal ideation and attempts. Two follow-up models to augment usual care including the Safety Planning Intervention have high efficacy: Instrumental Support Calls (ISC) and Caring Contacts (CC) two-way text messages, but they have never been compared to assess which works best. This protocol for the Suicide Prevention Among Recipients of Care (SPARC) Trial aims to determine which model is most effective for adolescents and adults with suicide risk.
METHODS
The SPARC Trial is a pragmatic randomized controlled trial comparing the effectiveness of ISC versus CC. The sample includes 720 adolescents (12-17 years) and 790 adults (18+ years) who screen positive for suicide risk during an ED or primary care encounter. All participants receive usual care and are randomized 1:1 to ISC or CC. The state suicide hotline delivers both follow-up interventions. The trial is single-masked, with participants unaware of the alternative treatment, and is stratified by adolescents/adults. The primary outcome is suicidal ideation and behavior, measured using the Columbia Suicide Severity Rating Scale (C-SSRS) screener at 6 months. Secondary outcomes include C-SSRS at 12 months, and loneliness, return to crisis care for suicidality, and utilization of outpatient mental health services at 6 and 12 months.
DISCUSSION
Directly comparing ISC and CC will determine which follow-up intervention is most effective for suicide prevention in adolescents and adults.
Topics: Adolescent; Adult; Humans; Emergency Service, Hospital; Primary Health Care; Suicidal Ideation; Suicide; Suicide Prevention; Text Messaging; Pragmatic Clinical Trials as Topic
PubMed: 37321352
DOI: 10.1016/j.cct.2023.107268 -
Pediatric Critical Care Medicine : a... Nov 2023The recent NITRIC and STRESS trials demonstrate opportunities to perform pragmatic large randomized trials in congenital heart disease. We discuss lessons learnt from...
The recent NITRIC and STRESS trials demonstrate opportunities to perform pragmatic large randomized trials in congenital heart disease. We discuss lessons learnt from these trials which can inform future trial design and conduct in the field of pediatric heart surgery.
Topics: Humans; Infant; Cardiopulmonary Bypass; Randomized Controlled Trials as Topic; Heart Defects, Congenital; Cardiac Surgical Procedures
PubMed: 37607086
DOI: 10.1097/PCC.0000000000003344