Real-world effectiveness of elexacaftor/tezacaftor/ivacaftor on the burden of illness in adolescents and adults with cystic fibrosis.

Background: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and efficacious in people with cystic fibrosis (CF) aged ≥2 years. Here, we describe results from an observational study assessing change in burden of illness following initiating ELX/TEZ/IVA in real-world settings.

Methods: This US-based, multicenter, observational study used data from electronic medical records to evaluate real-world burden of illness before and after ELX/TEZ/IVA initiation in people with CF aged ≥12 years heterozygous for and a minimal function mutation (/MF) or an uncharacterized mutation.

Psychometric performance of the CFQ-R-8D compared to the EQ-5D-3L and SF-6D in people with cystic fibrosis.

Objective: This study aimed to compare the psychometric performance of the Cystic Fibrosis Questionnaire-Revised-8 Dimensions (CFQ-R-8D), a new, condition-specific, preference-based measure, with that of generic preference-based measures EQ-5D-3L and Short Form 6 dimensions (SF-6D).

Methods: Data from three trials of participants with CF aged ≥ 14 years who completed the CFQ-R and EQ-5D-3L or SF-6D were used. Analyses were undertaken to evaluate convergent validity based on correlations with CFQ-R domain scores.

Evaluation of Intratumoral Response Heterogeneity in Metastatic Colorectal Cancer and Its Impact on Patient Overall Survival: Findings from 10,551 Patients in the ARCAD Database.

Unlabelled: Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into consideration response heterogeneity. We explored and developed lesion-based measurement response criteria to evaluate their prognostic effect on overall survival (OS).

EFFECT OF ELEXACAFTOR/TEZACAFTOR/IVACAFTOR ON ANNUAL RATE OF LUNG FUNCTION DECLINE IN PEOPLE WITH CYSTIC FIBROSIS.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in people with cystic fibrosis (CF) with ≥ 1 F508del-CFTR allele in Phase 3 clinical trials. ELX/TEZ/IVA treatment led to improved lung function, with increases in percent predicted forced expiratory volume in 1 second (ppFEV) and Cystic Fibrosis Questionnaire-Revised respiratory domain score. Here, we evaluated the impact of ELX/TEZ/IVA on the rate of lung function decline over time by comparing changes in ppFEV in participants from the Phase 3 trials with a matched group of people with CF from the US Cystic Fibrosis Foundation Patient Registry not eligible for cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy.

Development of the Cystic Fibrosis Questionnaire-Revised-8 Dimensions: Estimating Utilities From the Cystic Fibrosis Questionnaire-Revised.

Objectives: Cystic fibrosis (CF) limits survival and negatively affects health-related quality of life (HRQOL). Cost-effectiveness analysis (CEA) may be used to make reimbursement decisions for new CF treatments; nevertheless, generic utility measures used in CEA, such as EQ-5D, are insensitive to meaningful changes in lung function and HRQOL in CF. Here we develop a new, CF disease-specific, preference-based utility measure based on the adolescent/adult version of the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a widely used, CF-specific, patient-reported measure of HRQOL.

Efficacy and safety of elexacaftor plus tezacaftor plus ivacaftor versus tezacaftor plus ivacaftor in people with cystic fibrosis homozygous for F508del-CFTR: a 24-week, multicentre, randomised, double-blind, active-controlled, phase 3b trial.

Background: Elexacaftor plus tezacaftor plus ivacaftor is a triple-combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimen shown to be generally safe and efficacious in people with cystic fibrosis aged 12 years or older with at least one F508del-CFTR allele. We aimed to assess the magnitude and durability of the clinical effects of this triple combination regimen in people with cystic fibrosis homozygous for the F508del-CFTR mutation.

Methods: We conducted a multicentre, randomised, double-blind, active-controlled, phase 3b trial of elexacaftor plus tezacaftor plus ivacaftor at 35 medical centres in Australia, Belgium, Germany, and the UK.

The Contribution of Patient, Primary Care Physician, and Primary Care Clinic Factors to Good Bone Health Care.

Background/objective: Patient, provider, and system factors can contribute to chronic care management and outcomes. Few studies have examined these multilevel associations with osteoporosis care and outcomes. We examined how key process and structural factors at the patient, primary care physician (PCP), and primary care clinic (PCC) levels were associated with guideline concordant osteoporosis pharmacotherapy, daily calcium intake, vitamin D supplementation, and weekly exercise sessions at 52 weeks following enrollment in a cluster randomized controlled trial.

Assessing the ratio of means as a causal estimand in clinical endpoint bioequivalence studies in the presence of intercurrent events.

In clinical endpoint bioequivalence studies, the observed per-protocol (PP) population (compliers and completers in general) is usually used in the primary analysis for equivalence assessment. However, intercurrent events, ie, missingness and noncompliance, are not properly handled. The resulting estimand is not causal.

Characteristics of older adults using patient web portals to view their DXA results.

Background: Sharing test results with patients via patient web portals is a new trend in healthcare. No research has been done examining patient web portal use with bone density test results. The objective of our study was to identify patient characteristics associated with the use of patient web portals to view their bone density test results.

The prevalence of overtreatment of osteoporosis: results from the PAADRN trial.

Unlabelled: Overtreatment of osteoporosis increases costs and puts patients at unnecessary risk of experiencing adverse drug events. In the Patient Activation After DXA Receipt Notification (PAADRN) trial, we found that 8% of individuals with no indication for therapy were recommended a new osteoporosis medication or continuation of an existing medication.

Purpose: There is a robust body of literature addressing undertreatment in osteoporosis, but limited data addressing overtreatment.

Estimation of causal effects in clinical endpoint bioequivalence studies in the presence of intercurrent events: noncompliance and missing data.

In clinical endpoint bioequivalence (BE) studies, the primary analysis for assessing equivalence between a generic and an innovator product is based on the observed per-protocol (PP) population (usually completers and compliers). However, missing data and noncompliance are post-randomization intercurrent events and may introduce selection bias. Therefore, PP analysis is generally not causal.

Diet and exercise changes following bone densitometry in the Patient Activation After DXA Result Notification (PAADRN) study.

Unlabelled: Calcium and vitamin D intake and exercise are suboptimal among older adults. Following bone densitometry, a letter communicating individualized fracture risk accompanied by an educational brochure improved participants' lifestyle-but no more than existing communication strategies-over 52 weeks. Simple communication strategies are insufficient for achieving optimal levels of bone health behaviors.

Evaluation of a "Just-in-Time" Nurse Consultation on Bone Health: A Pilot Randomized Controlled Trial.

Context: Evidence is inconclusive whether a nurse consultation can improve osteoporosis-related patient outcomes.

Objective: To evaluate whether a nurse consultation immediately after dual-energy x-ray absorptiometry (DXA) produced better osteoporosis-related outcomes than a simple intervention to activate adults in good bone health practices or usual care.

Design: Pilot randomized controlled trial, conducted within the larger Patient Activation After DXA Result Notification (PAADRN) trial (NCT01507662).

Patient-reported reasons for nonadherence to recommended osteoporosis pharmacotherapy.

Objectives: As many as one-half of patients recommended for osteoporosis pharmacotherapy do not take their medications. To identify intervention targets, we examined patient characteristics associated with nonadherence to recommended pharmacotherapy and their reasons for nonadherence.

Methods: Data come from the Patient Activation after DXA Result Notification (PAADRN) study, a randomized controlled trial of 7749 patients aged 50 years or older presenting for dual-energy X-ray absorptiometry (DXA) at 3 health centers in the United States.

Racial Differences and Disparities in Osteoporosis-related Bone Health: Results From the PAADRN Randomized Controlled Trial.

Background: Determining whether observed differences in health care can be called disparities requires persistence of differences after adjustment for relevant patient, provider, and health system factors. We examined whether providing dual-energy x-ray absorptiometry (DXA) test results directly to patients might reduce or eliminate racial differences in osteoporosis-related health care.

Design, Subjects, And Measures: We analyzed data from 3484 white and 1041 black women who underwent DXA testing at 2 health systems participating in the Patient Activation after DXA Result Notification (PAADRN) pragmatic clinical trial (ClinicalTrials.

Improved Automated Detection of Diabetic Retinopathy on a Publicly Available Dataset Through Integration of Deep Learning.

Purpose: To compare performance of a deep-learning enhanced algorithm for automated detection of diabetic retinopathy (DR), to the previously published performance of that algorithm, the Iowa Detection Program (IDP)-without deep learning components-on the same publicly available set of fundus images and previously reported consensus reference standard set, by three US Board certified retinal specialists.

Methods: We used the previously reported consensus reference standard of referable DR (rDR), defined as International Clinical Classification of Diabetic Retinopathy moderate, severe nonproliferative (NPDR), proliferative DR, and/or macular edema (ME). Neither Messidor-2 images, nor the three retinal specialists setting the Messidor-2 reference standard were used for training IDx-DR version X2.

Activating Patients With a Tailored Bone Density Test Results Letter and Educational Brochure: the PAADRN Randomized Controlled Trial.

In cross-sectional studies, patient activation has been associated with better health behaviors, health outcomes, and health-care experiences. Moreover, tailored interventions have led to clinically meaningful improvements in patient activation, as well as health outcomes over time. We tested whether a tailored patient-activation letter communicating bone mineral density (BMD) test results plus an educational brochure improved patient activation scores and levels at 12 and 52 wk post-baseline as the mechanism leading to enhanced bone healthcare.

A pilot study among older adults of the concordance between their self-reports to a health survey and spousal proxy reports on their behalf.

Background: Proxy respondents are frequently used in health surveys, and the proxy is most often the spouse. Longstanding concerns linger, however, about the validity of using spousal proxies, especially for older adults. The purpose of this pilot study was to evaluate the concordance between self-reports and spousal proxy reports to a standard health survey in a small convenience sample of older married couples.

Effects of a DXA result letter on satisfaction, quality of life, and osteoporosis knowledge: a randomized controlled trial.

Background: Undiagnosed, or diagnosed and untreated osteoporosis (OP) increases the likelihood that falls result in hip fractures, decreased quality of life (QOL), and significant medical expenditures among older adults. We tested whether a tailored dual energy x-ray absorptiometry (DXA) test result letter and an accompanying educational bone-health brochure affected patient satisfaction, QOL, or OP knowledge.

Methods: The Patient Activation after DXA Result Notification (PAADRN) study was a double-blinded, pragmatic, randomized trial which enrolled patients from 2012 to 2014.

Does the Relationship of the Proxy to the Target Person Affect the Concordance between Survey Reports and Medicare Claims Measures of Health Services Use?

Objectives: To compare concordance of survey reports of health service use versus claims data between self respondents and spousal and nonspousal relative proxies.

Data Sources: 1995-2010 data from the Survey on Assets and Health Dynamics among the Oldest Old and 1993-2010 Medicare claims for 3,229 individuals (13,488 person-years).

Study Design: Regression models with individual fixed effects were estimated for discordance of any hospitalizations and outpatient surgery and for the numbers of under- and over-reported physician visits.

Cognitive function and the concordance between survey reports and Medicare claims in a nationally representative cohort of older adults.

Background: While age-related cognitive decline may affect all stages in the response process--comprehension, retrieval, judgment, response selection, and response reporting--the associations between objective cognitive tests and the agreement between self-reports and Medicare claims has not been assessed. We evaluate those associations using the Survey on Assets and Health Dynamics among the Oldest Old (AHEAD).

Methods: Eight waves of reinterviews (1995-2010) were linked to Medicare claims for 3661 self-respondents yielding 12,313 person-period observations.

The concordance of survey reports and Medicare claims in a nationally representative longitudinal cohort of older adults.

Background: Concordance between survey reports and claims data is not well established. We compared them for disease histories, preventative, and other health services use in a large, nationally representative sample of older Medicare beneficiaries with special attention given to evaluating age, aging, memory, and respondent status effects.

Methods: Baseline (1993) and biennial follow-up data (through 2010) from the Survey on Assets and Health Dynamics among the Oldest-Old were linked to Medicare claims from 1991 to 2010, for 4910 participants yielding 19,556 person-periods.