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Drugs Jun 2024Spinal muscular atrophy (SMA) is a rare neurodegenerative neuromuscular disorder with a wide phenotypic spectrum of severity. SMA was previously life limiting for...
Spinal muscular atrophy (SMA) is a rare neurodegenerative neuromuscular disorder with a wide phenotypic spectrum of severity. SMA was previously life limiting for patients with the most severe phenotype and resulted in progressive disability for those with less severe phenotypes. This has changed dramatically in the past few years with the approvals of three disease-modifying treatments. We review the evidence supporting the use of currently approved SMA treatments (nusinersen, onasemnogene abeparvovec, and risdiplam), focusing on mechanisms of action, side effect profiles, published clinical trial data, health economics, and pending questions. Whilst there is robust data from clinical trials of efficacy and side effect profile for individual drugs in select SMA populations, there are no comparative head-to-head clinical trials. This presents a challenge for clinicians who need to make recommendations on the best treatment option for an individual patient and we hope to provide a pragmatic approach for clinicians across each SMA profile based on current evidence.
PubMed: 38878146
DOI: 10.1007/s40265-024-02051-2 -
The American Journal on Addictions Jun 2024Although concurrent stimulant use is common among people with opioid use disorder (OUD), there is little evidence on its impacts on opioid agonist therapy (OAT)...
Impact of baseline methamphetamine/amphetamine use on discontinuation of methadone and buprenorphine/naloxone among people with prescription-type opioid use disorder in Canada.
BACKGROUND AND OBJECTIVES
Although concurrent stimulant use is common among people with opioid use disorder (OUD), there is little evidence on its impacts on opioid agonist therapy (OAT) outcomes. This study sought to determine the impact of baseline methamphetamine/amphetamine use on discontinuation of OAT among individuals with prescription-type OUD (POUD) initiating methadone or buprenorphine/naloxone as part of a pragmatic randomized trial in Canada.
METHODS
Secondary analysis of a pan-Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take-home dosing buprenorphine/naloxone models of care. Cox proportional hazard models were used to evaluate the effect of baseline methamphetamine/amphetamine use (measured by urine drug test [UDT]) on two discontinuation outcomes (i.e., assigned OAT discontinuation, any OAT discontinuation).
RESULTS
Two hundred nine (n = 209) participants initiated OAT, of which 96 (45.9%) had positive baseline methamphetamine/amphetamine UDT. Baseline methamphetamine/amphetamine use was associated with shorter median times in assigned OAT (21 vs. 168 days, hazard ratio [aHR] = 2.45, 95% confidence interval [CI] = 1.60-3.76) and any OAT (25 days vs. 168 days, aHR = 2.06, CI = 1.32-3.24). No interaction between methamphetamine/amphetamine and assigned OAT was observed for either outcome (p > .05).
CONCLUSION AND SCIENTIFIC SIGNIFICANCE
This study offers novel insights on the impact of methamphetamine/amphetamine use on OAT outcomes among people with POUD. Methamphetamine/amphetamine use was common and was associated with increased risk of OAT discontinuation. Supplementary interventions, including treatment for stimulant use, are needed to improve retention in OAT and optimize treatment outcomes in this population.
PubMed: 38877969
DOI: 10.1111/ajad.13619 -
Midwifery Jun 2024A pragmatic randomised controlled trial has confirmed the effectiveness of Urinary Incontinence for Women (UIW) app-based intervention in improving postpartum urinary...
Self-efficacy with Pelvic floor muscle training mediates the effect of an App-based intervention on improving postpartum urinary incontinence severity among pregnant women: A causal mediation analysis from a randomised controlled trial.
BACKGROUND
A pragmatic randomised controlled trial has confirmed the effectiveness of Urinary Incontinence for Women (UIW) app-based intervention in improving postpartum urinary incontinence (UI) severity among pregnant women. However, the causal mechanisms underlying this intervention effect remain unclear.
OBJECTIVE
To examine the mediating role of self-efficacy with pelvic floor muscle training (PFMT) on the effect of the UIW app-based intervention in improving postpartum UI severity.
METHODS
This was a secondary causal mediation analysis of a single-center, 2-arm, unblinded pragmatic randomised controlled trial. Singleton pregnant women without UI before pregnancy aged ≥18 years and between 24 and 28 weeks of gestation were recruited from a tertiary public hospital in China and randomised to receive the UIW app intervention plus oral PFMT instructions (n = 63) or oral PFMT instructions alone (n = 63). The primary outcome was postpartum changes in UI severity at 6 weeks. Changes in self-efficacy with PFMT 2 months after randomisation were a hypothesised mediator. Causal mediation analysis was used to estimate the average causal mediation effect (ACME), average direct effect (ADE), average total effect (ATE), and proportion mediated. A sensitivity analysis was conducted to examine the robustness of the ACME in relation to potential unmeasured confounding.
RESULTS
Data from 103 participants were analyzed. The ATE of UIW app-based intervention on postpartum UI severity was 2.91 points (95 % confidence intervals [CI] 1.69 to 4.12), with ADE of 1.97 points (95 % CI 0.63 to 3.41) and the ACME 0.94 points (95 % CI 0.27 to 1.72). The proportion of ATE mediated by self-efficacy with PFMT was 0.32 (95 % CI 0.08 to 0.67). Sensitivity analysis revealed the robust ACME with respect to the potential effects of unmeasured confounding.
CONCLUSION
An increase in self-efficacy with PFMT partially mediated the effect of the UIW app intervention on improvements in postpartum UI severity.
TRIAL REGISTRATION
The original trial was prospectively registered in the Chinese Clinical Trial Registry under the reference number ChiCTR1800016171 on 16/05/2018. Further details can be accessed at: http://www.chictr.org.cn/showproj.aspx?proj=27455.
PubMed: 38875972
DOI: 10.1016/j.midw.2024.104052 -
PloS One 2024Emulation of the "target trial" (TT), a hypothetical pragmatic randomized controlled trial (RCT), using observational data can be used to mitigate issues commonly...
Designing target trials using electronic health records: A case study of second-line disease-modifying anti-rheumatic drugs and cardiovascular disease outcomes in patients with rheumatoid arthritis.
BACKGROUND
Emulation of the "target trial" (TT), a hypothetical pragmatic randomized controlled trial (RCT), using observational data can be used to mitigate issues commonly encountered in comparative effectiveness research (CER) when randomized trials are not logistically, ethically, or financially feasible. However, cardiovascular (CV) health research has been slow to adopt TT emulation. Here, we demonstrate the design and analysis of a TT emulation using electronic health records to study the comparative effectiveness of the addition of a disease-modifying anti-rheumatic drug (DMARD) to a regimen of methotrexate on CV events among rheumatoid arthritis (RA) patients.
METHODS
We used data from an electronic medical records-based cohort of RA patients from Northwestern Medicine to emulate the TT. Follow-up began 3 months after initial prescription of MTX (2000-2020) and included all available follow-up through June 30, 2020. Weighted pooled logistic regression was used to estimate differences in CVD risk and survival. Cloning was used to handle immortal time bias and weights to improve baseline and time-varying covariate imbalance.
RESULTS
We identified 659 eligible people with RA with average follow-up of 46 months and 31 MACE events. The month 24 adjusted risk difference for MACE comparing initiation vs non-initiation of a DMARD was -1.47% (95% confidence interval [CI]: -4.74, 1.95%), and the marginal hazard ratio (HR) was 0.72 (95% CI: 0.71, 1.23). In analyses subject to immortal time bias, the HR was 0.62 (95% CI: 0.29-1.44).
CONCLUSION
In this sample, we did not observe evidence of differences in risk of MACE, a finding that is compatible with previously published meta-analyses of RCTs. Thoughtful application of the TT framework provides opportunities to conduct CER in observational data. Benchmarking results of observational analyses to previously published RCTs can lend credibility to interpretation.
Topics: Humans; Arthritis, Rheumatoid; Antirheumatic Agents; Electronic Health Records; Cardiovascular Diseases; Female; Male; Middle Aged; Methotrexate; Aged; Treatment Outcome; Randomized Controlled Trials as Topic; Comparative Effectiveness Research; Adult
PubMed: 38875273
DOI: 10.1371/journal.pone.0305467 -
PLOS Global Public Health 2024[This corrects the article DOI: 10.1371/journal.pgph.0000425.].
[This corrects the article DOI: 10.1371/journal.pgph.0000425.].
PubMed: 38875225
DOI: 10.1371/journal.pgph.0003395 -
Journal of Clinical Psychology Jun 2024Dialectical behavior therapy (DBT) is an evidence-based treatment for people with emerging borderline personality disorder (BPD). In "real world" clinical settings,...
OBJECTIVES
Dialectical behavior therapy (DBT) is an evidence-based treatment for people with emerging borderline personality disorder (BPD). In "real world" clinical settings, standard DBT is resource intensive. Emerging evidence suggests that group-based DBT skills training alone can lead to promising outcomes. This hybrid type 1 effectiveness-implementation trial directly compared the effectiveness of an 8-week group DBT-skills training program and a 16-week DBT-informed program including individual treatment and group-based skills training.
METHODS
This pragmatic trial employed a staggered, parallel-groups design. We recruited 104 participants, aged 16-25 years, with emotion dysregulation or emerging BPD symptoms. Participants were randomized to receive either program at a youth mental health service located in the Gold Coast, Australia. Data was collected via online surveys at baseline, 8-week, 16-week, and 24-week follow-up. Mixed effect linear models compared groups on the primary outcomes of emotion dysregulation and BPD symptoms, and secondary outcomes of suicidal ideation, coping skills, depression, anxiety, and stress.
RESULTS
Across groups there were significant and sustained improvements relating to emotion dysregulation, BPD symptoms, stress, depression, and emotion-focused coping; but not suicide risk, anxiety, or task-focused coping. There was no significant time by group differences between the 8-week and 16-week interventions on any primary or secondary outcome.
CONCLUSION
The more intensive mode of delivering DBT was not more effective than the brief group-based skills training. Both interventions resulted in significant improvements across both primary and most secondary outcomes. These results have implications for clinical practice regarding length and intensity of DBT treatment in young people.
PubMed: 38874116
DOI: 10.1002/jclp.23725 -
Resuscitation Plus Sep 2024Prospective, trial-based data comparing health-related quality of life (HRQoL) in patients surviving out-of-hospital cardiac arrest (OHCA) through extracorporeal...
BACKGROUND
Prospective, trial-based data comparing health-related quality of life (HRQoL) in patients surviving out-of-hospital cardiac arrest (OHCA) through extracorporeal cardiopulmonary resuscitation (ECPR) or conventional CPR (CCPR) are scarce. We aimed to determine HRQoL during 1-year after refractory OHCA in patients treated with ECPR and CCPR.
METHODS
We present a secondary analysis of the multicenter INCEPTION-trial, which studied the effectiveness of ECPR versus CCPR in patients with refractory OHCA. HRQoL was prospectively assessed using the EQ-5D-5L questionnaire. Poor HRQoL was pragmatically defined as an EQ-5D-5L health utility index (HUI) > 1 SD below the age-adjusted norm. We used mixed linear models to assess the difference in HRQoL over time and univariable analyses to assess factors potentially associated with poor HRQoL.
RESULTS
A total of 134 patients were enrolled, and hospital survival was 20% (27 patients). EQ-5D-5L data were available for 25 patients (5 ECPR and 20 CCPR). One year after OHCA, the estimated mean HUI was 0.73 (0.05) in all patients, 0.84 (0.12) in ECPR survivors, and 0.71 (0.05) in CCPR survivors (p-value 0.31). Eight (32%) survivors had a poor HRQoL. HRQoL was good in 17 (68%) patients, with 100% in ECPR survivors versus 60% in CCPR survivors (p-value 0.14).
CONCLUSION
One year after refractory OHCA, 68% of the survivors had a good HRQoL. We found no statistically significant difference in HRQoL one year after OHCA in patients treated with ECPR compared to CCPR. However, numerical differences may be clinically relevant in favor of ECPR.
PubMed: 38873275
DOI: 10.1016/j.resplu.2024.100669 -
BMJ Open Jun 2024Clinical assessment in emergency departments (EDs) for possible acute myocardial infarction (AMI) requires at least one cardiac troponin (cTn) blood test. The...
Protocol for Improving Care by FAster risk-STratification through use of high sensitivity point-of-care troponin in patients presenting with possible acute coronary syndrome in the EmeRgency department (ICare-FASTER): a stepped-wedge cluster randomised quality improvement initiative.
INTRODUCTION
Clinical assessment in emergency departments (EDs) for possible acute myocardial infarction (AMI) requires at least one cardiac troponin (cTn) blood test. The turn-around time from blood draw to posting results in the clinical portal for central laboratory analysers is ~1-2 hours. New generation, high-sensitivity, point-of-care cardiac troponin I (POC-cTnI) assays use whole blood on a bedside (or near bedside) analyser that provides a rapid (8 min) result. This may expedite clinical decision-making and reduce length of stay. Our purpose is to determine if utilisation of a POC-cTnI testing reduces ED length of stay. We also aim to establish an optimised implementation process for the amended clinical pathway.
METHODS AND ANALYSIS
This quality improvement initiative has a pragmatic multihospital stepped-wedge cross-sectional cluster randomised design. Consecutive patients presenting to the ED with symptoms suggestive of possible AMI and having a cTn test will be included. Clusters (comprising one or two hospitals each) will change from their usual-care pathway to an amended pathway using POC-cTnI-the 'intervention'. The dates of change will be randomised. Changes occur at 1 month intervals, with a minimum 2 month 'run-in' period. The intervention pathway will use a POC-cTnI measurement as an alternate to the laboratory-based cTn measurement. Clinical decision-making steps and logic will otherwise remain unchanged. The POC-cTnI is the Siemens (Erlangen Germany) Atellica VTLi high-sensitivity cTnI assay. The primary outcome is ED length of stay. The safety outcome is cardiac death or AMI within 30 days for patients discharged directly from the ED.
ETHICS AND DISSEMINATION
Ethics approval has been granted by the New Zealand Southern Health and Disability Ethics Committee, reference 21/STH/9. Results will be published in a peer-reviewed journal. Lay and academic presentations will be made. Māori-specific results will be disseminated to Māori stakeholders.
TRIAL REGISTRATION NUMBER
ACTRN12619001189112.
Topics: Humans; Emergency Service, Hospital; Quality Improvement; Acute Coronary Syndrome; Point-of-Care Systems; Cross-Sectional Studies; Risk Assessment; Troponin I; Myocardial Infarction; Length of Stay; Point-of-Care Testing; Biomarkers; Clinical Decision-Making
PubMed: 38871661
DOI: 10.1136/bmjopen-2023-083752 -
International Journal of Infectious... Aug 2024
Topics: Humans; Influenza Vaccines; Influenza, Human; Aged; Public Health; Vaccine Efficacy; Vaccination; Aged, 80 and over
PubMed: 38871602
DOI: 10.1016/j.ijid.2024.107103 -
JMIR Formative Research Jun 2024Chronic kidney disease (CKD) is a major public health concern. Adequate self-management skills are vital to reduce CKD burden, optimize patient health outcomes, and...
BACKGROUND
Chronic kidney disease (CKD) is a major public health concern. Adequate self-management skills are vital to reduce CKD burden, optimize patient health outcomes, and control health care expenditures. Using eHealth to support CKD self-management has the potential to promote healthy behaviors and improve health outcomes of patients with CKD. However, knowledge of the implementation of such interventions in general, and in China specifically, is still limited.
OBJECTIVE
This study aims to develop a tailored eHealth self-management intervention for patients with CKD in China based on the Dutch Medical Dashboard (MD) eHealth self-management intervention.
METHODS
We used an intervention mapping approach. In phase 1, a systematic review and 2 qualitative studies were conducted to examine the needs, beliefs, and perceptions of patients with CKD and health care professionals regarding CKD self-management and eHealth interventions. Afterward, key factors gathered from the aforementioned studies were categorized following the 5 domains of the Consolidated Framework for Implementation Research (CFIR). In phase 2, we specified program outcomes, performance objectives, determinants, theory-based methods, and practical strategies. Knowledge obtained from previous results was combined to complement core components of the MD self-management intervention and adapt them for Chinese patients with CKD. Additionally, the CFIR-Expert Recommendations for Implementing Change Matching Tool was pragmatically used to generate a list of potential implementation strategies to address the key factors influencing the implementation of eHealth CKD self-management interventions, and implementation strategies were discussed and finalized with the intervention monitoring group.
RESULTS
An overview of the CFIR domains showed the essential factors influencing the implementation of eHealth CKD self-management interventions in Chinese settings, including "knowledge and beliefs" in the domain "individual characteristics," "quality and advantage of eHealth intervention" in the domain "intervention characteristics," "compatibility" in the domain "inner setting," and "cultural context" in the domain "outer setting." To ensure the effectiveness of the Dutch MD-based self-management intervention, we did not change the core self-management intervention components of MD that underlie its effectiveness, such as self-monitoring. We identified surface-level cultural adaptations involving customizing intervention content, messages, and approaches to the observable cultural characteristics of the local population to enhance the intervention's appeal, receptivity, and feasibility, such as providing video or voice call options to support interactions with health care professionals. Furthermore, the adapted modules such as Knowledge Center and My Self-Monitoring were developed in a mobile health app.
CONCLUSIONS
Our study resulted in the delivery of a culturally tailored, standardized eHealth self-management intervention for patients with CKD in China that has the potential to optimize patients' self-management skills and improve health status and quality of life. Moreover, our study's research approach and results can inform future research on the tailoring and translation of evidence-based, eHealth self-management interventions to various contexts.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04212923; https://classic.clinicaltrials.gov/ct2/show/NCT04212923.
PubMed: 38869943
DOI: 10.2196/48605