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Real-world biologics response and super-response in the International Severe Asthma Registry cohort.Allergy Jun 2024Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on...
BACKGROUND
Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma.
METHODS
Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day.
RESULTS
5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria.
CONCLUSIONS
Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.
PubMed: 38923444
DOI: 10.1111/all.16178 -
JAMA Cardiology Jun 2024The appropriate follow-up surveillance strategy for patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) remains...
IMPORTANCE
The appropriate follow-up surveillance strategy for patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) remains unknown.
OBJECTIVE
To assess clinical outcomes in patients with and without ACS who have undergone high-risk PCI according to a follow-up strategy of routine stress testing at 12 months after PCI vs standard care alone.
DESIGN, SETTING, AND PARTICIPANTS
The POST-PCI (Pragmatic Trial Comparing Symptom-Oriented vs Routine Stress Testing in High-Risk Patients Undergoing Percutaneous Coronary Intervention) trial was a randomized clinical trial that compared follow-up strategies of routine functional testing vs standard care alone 12 months after high-risk PCI. Patients were categorized as presenting with or without ACS. Patients were enrolled in the trial from November 2017 through September 2019, and patients were randomized from 11 sites in South Korea; data analysis was performed in 2022.
INTERVENTION
Patients categorized as presenting with or without ACS were randomized to either a routine functional testing or standard care alone follow-up strategy 12 months after high-risk PCI.
MAIN OUTCOMES AND MEASURES
The primary outcome was a composite of death from any cause, myocardial infarction, or hospitalization for unstable angina at 2 years following randomization. Kaplan-Meier event rates through 2 years and Cox model hazard ratios (HRs) were generated, and interactions were tested.
RESULTS
Of 1706 included patients, 350 patients (20.5%) were female, and the mean (SD) patient age was 64.7 (10.3) years. In total, 526 patients (30.8%) presented with ACS. Compared with those without ACS, patients with ACS had a 55% greater risk of the primary outcome (HR, 1.55; 95% CI, 1.03-2.33; P = .03) due to higher event rates in the first year. The 2-year incidences of the primary outcome were similar between strategies of routine functional testing or standard care alone in patients with ACS (functional testing: 16 of 251 [6.6%]; standard care: 23 of 275 [8.5%]; HR, 0.76; 95% CI, 0.40-1.44; P = .39) and in patients without ACS (functional testing: 30 of 598 [5.1%]; standard care: 28 of 582 [4.9%]; HR, 1.04; 95% CI, 0.62-1.74; P = .88) (P for interaction for ACS = .45). Although a landmark analysis suggested that the rates of invasive angiography and repeat revascularization were higher after 1 year in the routine functional testing group, the formal interactions between ACS status and either invasive angiography or repeat revascularization were not significant.
CONCLUSION AND RELEVANCE
Despite being at higher risk for adverse clinical events in the first year after PCI than patients without ACS, patients with ACS who had undergone high-risk PCI did not derive incremental benefit from routine surveillance stress testing at 12 months compared with standard care alone during follow-up.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03217877.
PubMed: 38922632
DOI: 10.1001/jamacardio.2024.1556 -
JAMA Network Open Jun 2024Determining how individuals engage with digital health interventions over time is crucial to understand and optimize intervention outcomes. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Determining how individuals engage with digital health interventions over time is crucial to understand and optimize intervention outcomes.
OBJECTIVE
To identify the engagement trajectories with a mobile chat-based smoking cessation intervention and examine its association with biochemically validated abstinence.
DESIGN, SETTING, AND PARTICIPANTS
A secondary analysis of a pragmatic, cluster randomized clinical trial conducted in Hong Kong with 6-month follow-up. From June 18 to September 30, 2017, 624 adult daily smokers were recruited from 34 community sites randomized to the intervention group. Data were analyzed from March 6 to October 30, 2023.
INTERVENTION
Chat-based cessation support delivered by a live counselor via a mobile instant messaging app for 3 months from baseline.
MAIN OUTCOMES AND MEASURES
Group-based trajectory modeling was used to identify engagement trajectories using the participants' weekly responses to the messages from the counselor over the 3-month intervention period. The outcome measures were biochemically validated tobacco abstinence at 3-month (end of treatment) and 6-month follow-ups. Covariates included sex, age, educational level, nicotine dependence, past quit attempt, and intention to quit at baseline.
RESULTS
Of 624 participants included in the analysis, 479 were male (76.8%), and the mean (SD) age was 42.1 (16.2) years. Four distinct engagement trajectories were identified: low engagement group (447 [71.6%]), where participants maintained very low engagement throughout; rapid-declining group (86 [13.8%]), where participants began with moderate engagement and rapidly decreased to a low level; gradual-declining group (58 [9.3%]), where participants had high initial engagement and gradually decreased to a moderate level; and high engagement group (58 [5.3%]), where participants maintained high engagement throughout. Compared with the low engagement group, the 6-month validated abstinence rates were significantly higher in the rapid-declining group (adjusted relative risk [ARR], 3.30; 95% CI, 1.39-7.81), gradual-declining group (ARR, 5.17; 95% CI, 2.21-12.11), and high engagement group (ARR, 4.98; 95% CI, 1.82-13.60). The corresponding ARRs (95% CI) of 3-month validated abstinence were 4.03 (95% CI, 1.53-10.59), 5.25 (95% CI, 1.98-13.88), and 9.23 (95% CI, 3.29-25.86).
CONCLUSIONS AND RELEVANCE
The findings of this study suggest that higher levels of engagement with the chat-based smoking cessation intervention were associated with greater biochemically validated tobacco abstinence. Improving engagement with digital interventions may increase intervention benefits.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03182790.
Topics: Humans; Smoking Cessation; Male; Female; Adult; Hong Kong; Middle Aged; Text Messaging; Mobile Applications
PubMed: 38922618
DOI: 10.1001/jamanetworkopen.2024.17796 -
Revista Gaucha de Enfermagem 2024To analyze the effectiveness of Bach flower therapy compared to placebo in reducing perceived stress levels in primary health care nursing professionals. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To analyze the effectiveness of Bach flower therapy compared to placebo in reducing perceived stress levels in primary health care nursing professionals.
METHOD
Pragmatic, parallel randomized clinical trial conducted with 87 primary care nursing professionals with self-identified stress, from October 2021 to June 2022, in the cities of Osasco and São Paulo, Brazil. The intervention group (n=43) received the collective flower formula, and the placebo group (n=44) received only the diluent. Data analysis was performed using the linear mixed model, and effect size was measured by partial Eta squared, significance level 5%.
RESULTS
Data analysis showed a significant reduction in perceived stress levels within groups (p=0.038). However, there was no significant difference between the study groups (p=0.750). Participants in the intervention group reported a greater perception of changes than participants in the placebo group, but without statistical significance (p=0,089).
CONCLUSION
The floral formula was not more effective than the placebo formula in reducing perceived stress. There was a significant stress reduction among nursing professionals in both study groups, although with a small effect size.
Topics: Humans; Female; Male; Adult; Flowers; Primary Care Nursing; Middle Aged; Occupational Stress; Phytotherapy; Stress, Psychological; Brazil
PubMed: 38922232
DOI: 10.1590/1983-1447.2024.20230132.en -
Critical Care Medicine Jun 2024Despite the recommendation for lung-protective mechanical ventilation (LPMV) in pediatric acute respiratory distress syndrome (PARDS), there is a lack of robust...
OBJECTIVES
Despite the recommendation for lung-protective mechanical ventilation (LPMV) in pediatric acute respiratory distress syndrome (PARDS), there is a lack of robust supporting data and variable adherence in clinical practice. This study evaluates the impact of an LPMV protocol vs. standard care and adherence to LPMV elements on mortality. We hypothesized that LPMV strategies deployed as a pragmatic protocol reduces mortality in PARDS.
DESIGN
Multicenter prospective before-and-after comparison design study.
SETTING
Twenty-one PICUs.
PATIENTS
Patients fulfilled the Pediatric Acute Lung Injury Consensus Conference 2015 definition of PARDS and were on invasive mechanical ventilation.
INTERVENTIONS
The LPMV protocol included a limit on peak inspiratory pressure (PIP), delta/driving pressure (DP), tidal volume, positive end-expiratory pressure (PEEP) to Fio2 combinations of the low PEEP acute respiratory distress syndrome network table, permissive hypercarbia, and conservative oxygen targets.
MEASUREMENTS AND MAIN RESULTS
There were 285 of 693 (41·1%) and 408 of 693 (58·9%) patients treated with and without the LPMV protocol, respectively. Median age and oxygenation index was 1.5 years (0.4-5.3 yr) and 10.9 years (7.0-18.6 yr), respectively. There was no difference in 60-day mortality between LPMV and non-LPMV protocol groups (65/285 [22.8%] vs. 115/406 [28.3%]; p = 0.104). However, total adherence score did improve in the LPMV compared to non-LPMV group (57.1 [40.0-66.7] vs. 47.6 [31.0-58.3]; p < 0·001). After adjusting for confounders, adherence to LPMV strategies (adjusted hazard ratio, 0.98; 95% CI, 0.97-0.99; p = 0.004) but not the LPMV protocol itself was associated with a reduced risk of 60-day mortality. Adherence to PIP, DP, and PEEP/Fio2 combinations were associated with reduced mortality.
CONCLUSIONS
Adherence to LPMV elements over the first week of PARDS was associated with reduced mortality. Future work is needed to improve implementation of LPMV in order to improve adherence.
PubMed: 38920618
DOI: 10.1097/CCM.0000000000006357 -
Geriatrics (Basel, Switzerland) Jun 2024The importance of oral health in older adults, especially those in long-term care institutions (LTCIs), has been widely recognized. This study aimed to evaluate the...
BACKGROUND
The importance of oral health in older adults, especially those in long-term care institutions (LTCIs), has been widely recognized. This study aimed to evaluate the sustainability of an oral health educational program (OHEP) for healthcare providers by measuring changes in their knowledge, attitudes, and practice (KAP) towards oral care provision 3 and 6 months after completing the OHEP.
METHODS
A pragmatic direct care nursing education trial with a control group was conducted to evaluate the sustainability of an OHEP by examining changes in KAP 3 and 6 months after the OHEP. The OHEP comprised both knowledge and skills related to oral care, whereas the control group received standard support in accordance with usual oral care practice.
RESULTS
The study included 20 healthcare providers in the intervention group and 20 in the control group. At 6 months post-OHEP, a significant difference in knowledge was observed between the two groups, with the intervention group maintaining a positive effect (mean 13.90). Conversely, the control group showed a significant decline in knowledge (from mean 14.25 to 12.10). Both groups showed an improvement in attitudes regarding oral health, with the intervention group exhibiting better results 3 months post-OHEP. Intervention group participants rated oral care as a higher priority.
CONCLUSIONS
An OHEP program for LTCI direct care staff provides enhanced knowledge and attitudes toward oral health care. Regular training in direct care and additional support may be needed to sustain optimal effects on oral care practice.
PubMed: 38920440
DOI: 10.3390/geriatrics9030084 -
Geriatrics (Basel, Switzerland) Jun 2024Pragmatic trials aim to assess intervention efficacy in usual patient care settings, contrasting with explanatory trials conducted under controlled conditions. In aging... (Review)
Review
Pragmatic trials aim to assess intervention efficacy in usual patient care settings, contrasting with explanatory trials conducted under controlled conditions. In aging research, pragmatic trials are important designs for obtaining real-world evidence in elderly populations, which are often underrepresented in trials. In this review, we discuss statistical considerations from a frequentist approach for the design and analysis of pragmatic trials. When choosing the dependent variable, it is essential to use an outcome that is highly relevant to usual medical care while also providing sufficient statistical power. Besides traditionally used binary outcomes, ordinal outcomes can provide pragmatic answers with gains in statistical power. Cluster randomization requires careful consideration of sample size calculation and analysis methods, especially regarding missing data and outcome variables. Mixed effects models and generalized estimating equations (GEEs) are recommended for analysis to account for center effects, with tools available for sample size estimation. Multi-arm studies pose challenges in sample size calculation, requiring adjustment for design effects and consideration of multiple comparison correction methods. Secondary analyses are common but require caution due to the risk of reduced statistical power and false-discovery rates. Safety data collection methods should balance pragmatism and data quality. Overall, understanding statistical considerations is crucial for designing rigorous pragmatic trials that evaluate interventions in elderly populations under real-world conditions. In conclusion, this review focuses on various statistical topics of interest to those designing a pragmatic clinical trial, with consideration of aspects of relevance in the aging research field.
PubMed: 38920431
DOI: 10.3390/geriatrics9030075 -
Annals of the Academy of Medicine,... Feb 2024We presented the key findings from Singapore's Changi General Hospital Breast Centre's lymphedema surveillance strategy that used patients' reported symptoms, standard...
INTRODUCTION
We presented the key findings from Singapore's Changi General Hospital Breast Centre's lymphedema surveillance strategy that used patients' reported symptoms, standard arm circumference measurements and clinical assessment in the diagnosis of breast cancer-related lymphedema (BCRL). Our secondary aim was to highlight and discuss important elements of a surveillance strategy that can be implemented to track this outcome measure of breast cancer treatment for future research.
METHOD
We conducted a cross-sectional study of 511 breast cancer patients to assess the prevalence of BCRL and its associated risk factors. We defined BCRL prevalence rates based on patients' self-reporting, objective arm circumference measure-ments and clinical diagnosis based on International Society of Lymphology (ISL) staging.
RESULTS
The median follow-up of patients was 88.8 months. The cumulative prevalence rate in the cohort was 30.9%. The cohort of BCRL patients were older (58.4 versus [vs] 54.9 years), had higher mean Body Mass Index (27.7 vs 25.2), higher proportion of mastectomy (77% vs 64.3%), axillary clearance, less likely breast reconstruction, higher-grade tumour, more lymph nodes excised, more advanced nodal disease, and had undergone adjuvant chemotherapy. However, clinically apparent BCRL was only 6.5% (33 out of 511 patients). The proportion of clinically significant BCRL in patients undergoing sentinel lymph node biopsy (SLNB) or axillary sampling was 1.7% compared to 9.9% in patients who had undergone axillary clearance. Majority of the BCRL were subclinical or mild in severity.
CONCLUSION
Our study showed that our rates of BCRL were comparable to international rates and highlighted similar patient profiles who were at risk of developing the disease. Having a comprehensive lymphedema surveillance strategy is paramount in paving the way for future studies.
Topics: Humans; Female; Middle Aged; Prevalence; Cross-Sectional Studies; Risk Factors; Singapore; Breast Cancer Lymphedema; Mastectomy; Aged; Breast Neoplasms; Arm; Adult; Body Mass Index; Lymph Node Excision; Neoplasm Staging; Lymphedema; Self Report; Population Surveillance
PubMed: 38920232
DOI: 10.47102/annals-acadmedsg.2023264 -
Cortex; a Journal Devoted To the Study... Jun 2024Prediction has a fundamental role in language processing. However, predictions can be made at different levels, and it is not always clear whether speech sounds,...
Prediction has a fundamental role in language processing. However, predictions can be made at different levels, and it is not always clear whether speech sounds, morphemes, words, meanings, or communicative functions are anticipated during dialogues. Previous studies reported specific brain signatures of communicative pragmatic function, in particular enhanced brain responses immediately after encountering an utterance used to request an object from a partner, but relatively smaller ones when the same utterance was used for naming the object. The present experiment now investigates whether similar neuropragmatic signatures emerge in recipients before the onset of upcoming utterances carrying different predictable communicative functions. Trials started with a context question and object pictures displayed on the screen, raising the participant's expectation that words from a specific semantic category (food or tool) would subsequently be used to either name or request one of the objects. Already 600 msec before utterance onset, a larger prediction potential was observed when a request was anticipated relative to naming expectation. As this result is congruent with the neurophysiological difference previously observed right after the critical utterance, the anticipatory brain activity may index predictions about the social-communicative function of upcoming utterances. In addition, we also found that the predictable semantic category of the upcoming word was likewise reflected in the anticipatory brain potential. Thus, the neurophysiological characteristics of the prediction potential can capture different types of upcoming linguistic information, including semantic and pragmatic aspects of an upcoming utterance and communicative action.
PubMed: 38917725
DOI: 10.1016/j.cortex.2024.05.011 -
Clinical Trials (London, England) Jun 2024There is growing interest in using embedded research methods, particularly pragmatic clinical trials, to address well-known evidentiary shortcomings afflicting the...
There is growing interest in using embedded research methods, particularly pragmatic clinical trials, to address well-known evidentiary shortcomings afflicting the health care system. Reviews of pragmatic clinical trials published between 2014 and 2019 found that 8.8% were conducted with waivers of informed consent; furthermore, the number of trials where consent is obtained is increasing with time. From a regulatory perspective, waivers of informed consent are permissible when certain conditions are met, including that the study involves no more than minimal risk, that it could not practicably be carried out without a waiver, and that waiving consent does not violate participants' rights and welfare. Nevertheless, when research is conducted with a waiver of consent, several ethical challenges arise. We must consider how to: address empirical evidence showing that patients and members of the public generally prefer prospective consent, demonstrate respect for persons using tools other than consent, promote public trust and investigator integrity, and ensure an adequate level of participant protections. In this article, we use examples drawn from real pragmatic clinical trials to argue that prospective consultation with representatives of the target study population can address, or at least mitigate, many of the ethical challenges posed by waivers of informed consent. We also consider what consultation might involve to illustrate its feasibility and address potential objections.
PubMed: 38916109
DOI: 10.1177/17407745241259360