Pragmatic and Observational Research最新文献

Purpose: The St George's Respiratory Questionnaire (SGRQ) measures health status in obstructive airways disease. Starkie et al proposed an algorithm for mapping the SGRQ to EQ-5D-5L, a preference-based utility measure, in chronic obstructive pulmonary disease (COPD) (Value Health 2011;14:354-60); only SGRQ total score, its squared value, and sex were included as covariates. We aimed to determine if including additional covariates could improve the performance of this algorithm type and whether amendments were required to extend this mapping to asthma or asthma+COPD.

Patients and methods: SGRQ and EQ-5D-5L were measured from a large, global, prospective, longitudinal study in asthma and/or COPD (NOVELTY; NCT02760329). We fitted six longitudinal linear mixed models to the development sample (baseline and Year 1 data), with EQ-5D-5L as the response variable. Each model had a different combination of covariates. Mixed model repeated measures methodology was used to enable the accommodation of within-patient correlation among measurements. Restricted maximum likelihood and an unstructured covariance matrix were used to fit all models. Performance (mean square errors [MSE]) was evaluated relative to the Starkie et al algorithm in the validation sample (Year 2 and Year 3 data).

Results: A total of 6813 patients (asthma: 3546; asthma+COPD: 872; COPD: 2395) with available EQ-5D-5L and SGRQ data were included at baseline. MSEs indicated good performance, were similar across models (Year 2: 0.0302-0.0308 [45-46% variance explained]; Year 3: 0.0272-0.0277 [47-48% variance explained]), and were modestly smaller than those obtained by Starkie et al (Year 2: 0.0340; Year 3: 0.0296). Performance was similar across models in the asthma and COPD subgroups.

Conclusion: Including additional covariates and SGRQ domains resulted in similar model performance to Starkie et al, suggesting their covariates are adequate for mapping in asthma and/or COPD. NOVELTY coefficients broaden the population with chronic airways disease for whom this mapping can be applied.

Medifilm is a company that blisters drug therapies recorded by pharmacists in the Medifilm software. The Medifilm dataset collates this information and provides details on drug substances, dosages, pharmacotherapy duration, the sequence of therapies, as well as demographic data on the patients. This article aims to provide an overview of the database, to describe the contents, and to demonstrate possibilities for researchers. The database and the recorded information were described. Furthermore, the data coverage was characterized in terms of the number of available pharmacies, patients, and their drug regimens. The database has been recording data since 2013 and has registered 470,801 blistered therapies for 45,594 patients ordered by 441 pharmacies so far. The longitudinal nature of the database allows researchers to study drug utilization, including medication changes, initiations, and discontinuations over time.

Purpose: To understand steroidal mineralocorticoid receptor antagonists (sMRAs) treatment patterns and side effects from patients' perspectives.

Methods: The RELICS-PS study, a complement to the claims-based RELICS study, used a cross-sectional patient survey targeting adults with commercial or Medicare Advantage health insurance who had at least one pharmacy claim for sMRAs (spironolactone or eplerenone) between July 2021 and June 2022. It used the Healthcare Integrated Research Database (HIRD^®) as the sampling frame to identify eligible patients. A total of 600 completed surveys were targeted from current and past sMRA users between November and December 2022. The survey collected data on demographics, chronic conditions, prespecified side effects, and reasons for discontinuation among past sMRA users, describing the data without inferential testing.

Results: Of 600 respondents, 49.2% reported at least one side effect. Side effects varied from 5.5% (weak pulse and chest pains) to 40.0% (sluggishness or fatigue). Reports of symptoms of male gynecomastia were noticeably higher than in medical claims in RELICS (17.4% vs 2.9%). Past users, consisting of 24.3% of respondents, were more likely to report experiencing side effects, experiencing them more frequently, and being more affected by them. Approximately a third of these respondents reported side effects as a deciding factor for discontinuation. Healthcare providers' recommendations, often informed by medication effectiveness and patient tolerance, were the most cited reason for discontinuation.

Conclusion: Although half of the respondents reported experiencing side effects, 39.0% of past users identified side effects as a reason for discontinuation. This suggests a gap between patient experience and perceived reasons for discontinuation. A notable finding from the study is the significant role of healthcare providers in influencing the decisions to start or stop sMRA treatment. Therefore, future research should focus on exploring the factors that shape healthcare providers' decision-making processes when initiating and discontinuing treatment options.

Purpose: This article examines the implementation of the Toddler Oral Health Intervention (TOHI) protocol, emphasizing feasibility, recruitment, retention, and protocol adherence rather than clinical outcomes. It discusses encountered challenges, necessary adjustments, and key lessons learned during the shift from a traditional randomized controlled trial (RCT) to a pragmatic RCT, thereby offering guidance for future research on similar complex interventions.

Methods: The methods of the RCT study protocol are presented, including (1) recruitment of well-baby clinics and oral health coaches, (2) recruitment of the study population; (3) implementation of the intervention and (4) outcome measures, alongside with the process of implementation and gathered feedback needed for required adjustments. A systematic analysis identified key protocol elements, modifications made, and lessons learned.

Results: Specific protocol modifications, including adjustments due to the COVID-19 pandemic, demonstrate how a traditional RCT can be adapted to real-world conditions without compromising outcome reliability. Key lessons include the necessity of robust contingency planning to manage unforeseen disruptions, effective recruitment and retention strategies to sustain participant and interventionists engagement, and the adoption of standardized data collection processes to ensure data integrity. These findings underscore the importance of addressing practical and contextual factors alongside measuring effectiveness, ensuring that study outcomes are both applicable and useful in clinical practice.

Conclusion: The findings demonstrate that carefully planned and documented pragmatic adjustments not only preserve scientific rigor but also enhance the relevance and applicability of the results, maintaining the methodological robustness expected of traditional RCTs.

Background: Oral corticosteroids (OCS) are commonly used to treat asthma but increase the risks for multiple morbidities; reducing OCS exposure may benefit patients. We analysed independent risk factors and longitudinal changes in OCS usage among patients with asthma to predict future risks of OCS-related adverse outcomes.

Methods: Optimum Patient Care Research Database United Kingdom primary care electronic medical records (EMR) from January 1990 to June 2021 were used to select adults (18-93 years) with asthma who had follow-up data from ≥2 years before to ≥3 years after an index visit for active symptoms; this date was defined by the largest pre-visit to post-visit change in mean annual OCS use. OCS usage during every follow-up year was categorised as none, low (mean <2 prescriptions/year), or high (mean ≥2 prescriptions/year). Pre-index to post-index changes between usage categories were calculated. Risk modelling selected cohorts without 17 morbidities (documented pre-index) reported to be associated with OCS exposure, including type 2 diabetes, osteoporosis, hypertension, and pneumonia. Cox regression analyses selected published risk factors associated with each condition and available in EMR for inclusion in proportional hazards models.

Results: The pre-index to post-index OCS usage category remained unchanged in 38.6% of patients, increased in 39.2%, and decreased in 22.2%, with 20.7% having no further OCS prescriptions. In models, the risks of all adverse outcomes increased with projected categoric OCS use; for example, hazard ratios for a one-category increment (none to low, low to high) were 1.55 (1.42-1.69) for type 2 diabetes, 1.56 (1.36-1.78) for post-menopausal osteoporosis, 1.05 (1.00-1.10) for hypertension, and 1.67 (1.52-1.83) for pneumonia (all p < 0.001).

Conclusion: OCS exposure in this primary care asthma population usually continued longitudinally. Our models predict increased risk of multiple morbidities with higher projected OCS exposure. These findings support early initiation of strategies to minimise OCS use in asthma.

Movement disorders present a substantial challenge by adversely affecting daily routines and overall well-being through a diverse spectrum of motor symptoms. Traditionally, motor symptoms have been evaluated through manual observational methods and patient-reported outcomes. While those approaches are valuable, they are limited by their subjectivity. In contrast, wearable technologies (wearables) provide objective assessments while actively supporting rehabilitation through continuous tracking, real-time feedback, and personalized physical therapy-based interventions. The aim of this literature review is to examine current research on the use of wearables in the rehabilitation of motor symptoms, focusing on their features, applications, and impact on improving motor function. By exploring research protocols, metrics, and study findings, this review aims to provide a comprehensive overview of how wearables are being used to support and optimize rehabilitation outcomes. To achieve that aim, a systematic search of the literature was conducted. Findings reveal that gait disturbance and postural balance are the primary motor symptoms extensively studied with tremor and freezing of gait (FoG) also receiving attention. Wearable sensing ranges from bespoke inertial and/or electromyography to commercial units such as personal devices (ie, smartwatch). Interactive (virtual reality, VR and augmented reality, AR) and immersive technologies (headphones), along with wearable robotic systems (exoskeletons), have proven to be effective in improving motor skills. Auditory cueing (via smartwatches or headphones), aids gait training with rhythmic feedback, while visual cues (via VR and AR glasses) enhance balance exercises through real-time feedback. The development of treatment protocols that incorporate personalized cues via wearables could enhance adherence and engagement to potentially lead to long-term improvements. However, evidence on the sustained effectiveness of wearable-based interventions remains limited.

Background: Biologics targeting immunoglobulin E, interleukin (IL)-4/IL-13 or IL-5 signaling are effective at treating severe asthma; however, individual patients' responses may be suboptimal, leading to therapy switching or stopping. The CLEAR study aimed to assess real-world biologic use patterns and associated clinical outcomes in patients receiving care for severe asthma.

Methods: CLEAR was a multicenter, observational study that included adults (≥18 years old) from 23 countries enrolled in the International Severe Asthma Registry between December 2015 and August 2021. Patients who initiated biologic therapy were categorized as continuing the initial biologic for 6 months, switching to another biologic within 6 months or stopping biologic treatment within 6 months. Outcomes were assessed using the closest available data to 12 months after biologic initiation, using propensity score-weighted multivariable regression models.

Results: Among 1,859 patients who initiated biologic therapy, 1,116 (60.0%) continued, 474 (25.5%) switched and 269 (14.5%) stopped treatment. Patients who switched or stopped therapy had a higher annualized asthma exacerbation rate post-initiation than those who continued (adjusted incidence rate ratio [aIRR] [95% confidence interval]: switched, 1.83 [1.51, 2.22]; stopped, 1.53 [1.19, 1.95]) and were more likely to have uncontrolled asthma at last assessment (adjusted odds ratio: switched, 5.40 [3.12, 9.33]; stopped, 4.02 [2.32, 6.98]). Compared with those who continued therapy, patients who switched had a higher long-term daily oral corticosteroid dose (adjusted β: 3.77 [1.71, 4.37] mg) and higher rates of hospitalizations (aIRR: 2.58 [1.52, 4.37]) and emergency room visits (aIRR: 2.12 [1.39, 3.24]).

Conclusion: Switching or stopping biologic therapy was associated with worse clinical outcomes than continuing the initial therapy.

Introduction: Atopic dermatitis (AD) is a common inflammatory skin disorder that affects both children and adults, characterized by pruritus and scaly, dry eczematous lesions. This study aimed to gather knowledge on the actual use and effectiveness of Pimecrolimus (PIM) in Chinese patients with mild-to-moderate AD affecting sensitive skin areas in routine clinical practice.

Methods: This multicentre and non-interventional study included 130 subjects from China, divided into two age groups (2-12 years and ≥12 years). The primary endpoint was the change in SCORAD index, in AD areas from inclusion to the end of the PIM treatment period.

Results: The primary efficacy analysis showed a significant reduction in the SCORAD index from baseline to the end of the PIM treatment period (p < 0.0001). The mean change in SCORAD index (SD) from baseline at visit 2 and visit 3 was -15.4 (10.50) and -18.6 (11.57), respectively. The mean Investigator's Global Assessment (IGA) score decreased from 2.3 at baseline to 0.7 at the end of the study, while the mean itching score decreased from 4.7 at baseline to 0.9 at the end of the study. The mean duration of PIM use was 38.3 days, with similar durations for patients above and below 12 years. There was progressive improvement in the quality of life of the patients with PIM treatment. The median time to first flare was 100 days and no adverse drug reactions or significant adverse events were reported during the study.

Discussion: This study provides robust real-world evidence that PIM 1% cream is effective for the treatment of mild-to-moderate AD in Chinese patients, particularly in sensitive skin areas and paediatric population. PIM also offers a TCS-sparing approach, making it a valuable option for managing mild-to-moderate AD.

Purpose: This study aimed to describe the characteristics, treatment patterns, adverse events (AEs), and clinical outcomes of patients starting steroidal mineralocorticoid receptor antagonists (sMRAs) in real-world settings.

Methods: The RELICS study, complementing the survey-based RELICS-PS study, was a retrospective cohort study conducted using the Healthcare Integrated Research Database (HIRD^®), a single-payer healthcare database with medical and pharmacy claims from health insurance plans across the United States. A cohort of adults initiating sMRAs from January 2016 to June 2021 was divided into six subgroups: three mutually exclusive heart failure (HF) subgroups, two mutually exclusive chronic kidney disease (CKD) subgroups, and "all other patients" subgroup, which included those without documented HF or CKD. Outcomes assessed from the first sMRA fill until death, health-plan disenrollment, or June 2022 (whichever came first) included analysis of treatment patterns, AEs, and clinical outcomes. Factors associated with sMRA discontinuation were evaluated with multivariate logistic regression.

Results: Of the 224,100 sMRA initiators identified, 76.4% did not have documented HF or CKD (ie, "all other patients" subgroup). This subgroup was younger and primarily female. Across all initiators, 72.3% were nonadherent, and 73.0% discontinued treatment within a median of 90 days of initiation. Of these discontinuers, 44.2% restarted treatment within a median of 91 days of discontinuation. Factors decreasing odds of discontinuation across most subgroups included a higher comorbidity burden, use of other cardiovascular medications, and cardiologist prescribing. These findings were consistent across subgroups. AEs and clinical outcomes varied across subgroups in line with baseline comorbidity profiles. Patients with a higher comorbidity burden, such as those with both CKD and T2D rather than CKD alone, experienced worse outcomes.

Conclusion: High rates of treatment discontinuation and subsequent restart were observed across all subgroups, implying fluctuating sMRA use. However, heightened cardiovascular risk may decrease the odds of discontinuation.

Background: The National Death Index (NDI) is the gold standard for mortality data in the United States (US) but has a time lag and can be operationally intensive. This validation study assesses the accuracy of various mortality data sources with the NDI.

Methods: This validation study is a secondary analysis of an advanced cancer cohort in the US between January 2010 and December 2018, with an established NDI linkage. Mortality data sources, inpatient discharge, disenrollment, death master file (DMF), Center for Medicare and Medicaid Services (CMS), Utilization management data (U.M.), and online obituary data were compared to NDI.

Results: Among 40,692 patients, 25,761 (63.3%) had a death date using NDI; the composite algorithm had a sensitivity of 88.9% (95% CI = 88.5%, 89.3%), specificity was 89.1% (95% CI = 88.6%, 89.6%). At the same time, positive predictive value (PPV) was 93.4% (95% CI = 93.1%, 93.7%), negative predictive value (NPV) was 82.3% (95% CI = 81.7%, 82.9%), and when comparing each individual source, each had a high PPV but limited sensitivity.

Conclusion: The composite algorithm was demonstrated to be a sensitive and precise measure of mortality, while individual database sources were accurate but had limited sensitivity.