Patient and site characteristics associated with pirfenidone and nintedanib use in the United States; an analysis of idiopathic pulmonary fibrosis patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry.

BACKGROUND: Pragmatic use of the anti-fibrotic medications pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) in the United States (US) has not been studied and may be different from international settings due to structural differences between health care systems. This study examined the relationship between patient- and site-level characteristics and anti-fibrotic (a) use and (b) selection. METHODS: Data from the Pulmonary Fibrosis Foundation Patient Registry was used to perform univariable and multivariable regressions with generalized linear mixed models. A random effects model examined registry site variation. RESULTS: 703 of 1218 (57.7%) patients were taking a single anti-fibrotic of which 312 (44.4%) were taking nintedanib and 391 (55.6%) were taking pirfenidone. Up to 25% of patients using an anti-fibrotic may have been excluded from clinical trial participation due to having too severe disease as measured by diffusion limitation for carbon monoxide. Age (OR = 0.974, p = 0.0086) and diffusion capacity of the lungs for carbon monoxide (per 10% increase in percent-predicted; OR = 0.896, p = 0.0007) was negatively associated with anti-fibrotic use while time (in log of days) since diagnosis (OR = 1.138, p < 0.0001), recent patient clinical trial participation (OR = 1.569, p = 0.0433) and oxygen use (OR = 1.604, p = 0.0027) was positively associated with anti-fibrotic use. Time (log of days) since diagnosis (OR = 1.075, p = 0.0477), history of coronary artery disease (OR = 1.796, p = 0.0030), presence of pulmonary hypertension (OR = 2.139, p = 0.0376), patient clinical trial participation in the prior 12 months (OR = 2.485, p = 0.0002), diffusion capacity of the lungs for carbon monoxide (per 10% increase in percent-predicted; OR = 1.138, p = 0.0184), anticoagulant use (OR = 2.507, p = 0.0028), and enrollment at a registry site in the Midwest region (OR = 1.600, p = 0.0446) were associated with pirfenidone use. Anti-fibrotic use varied by registry site. Rates of discontinuation were modest and nearly identical for the two medications with side effects being the most common reason given for discontinuation. Twenty-three percent (23%, 274) of persons with IPF were using or had recently used an immunomodulatory agent. CONCLUSIONS: This analysis provides a detailed characterization of IPF treatment patterns in the US; many users of anti-fibrotic medications may not have qualified for inclusion in clinical trials. More research is needed to understand variations in medical decision-making for use and selection of anti-fibrotic medication.

Depressive symptoms and functional decline following coronary interventions in older patients with coronary artery disease: a prospective cohort study.

BACKGROUND: Depressive symptoms are prevalent in patients with coronary artery disease (CAD). It is unclear, however, how depressive symptoms change over time and the impact of these changes on long-term functional outcomes. We examined the association between different trajectories of depressive symptoms over 1 year and change in functional status over 30 months among patients undergoing coronary angiography. METHODS: This was a prospective cohort study of 350 patients aged 60 and older undergoing non-emergent cardiac catheterization (October 2003-February 2007). A dynamic measure of significant depressive symptoms (i.e., Geriatric Depression Scale score 5+) capturing change over 12 months was derived that categorized patients into the following groups: (i) no clinically important depressive symptoms (at baseline, 6 and 12 months); (ii) baseline-only symptoms (at baseline but not at 6 and 12 months); (iii) new onset symptoms (not at baseline but present at either 6 or 12 months); and, (iv) persistent symptoms (at baseline and at either 6 or 12 month assessment). Primary outcomes were mean change in Older Americans Resources and Services (OARS) instrumental (IADL) and basic activities of daily living (BADL) scores (range 0-14 for each) across baseline (pre-procedure) and 6, 12, and 30 months post-procedure visits. RESULTS: Estimates for the symptom categories were 71 % (none), 9 % (baseline only), 8 % (new onset) and 12 % (persistent). In adjusted models, patients with persistent symptoms showed a significant decrease in mean IADL and BADL scores from baseline to 6 months (-1.32 [95 % CI -1.78 to -0.86] and -0.63 [-0.97 to -0.30], respectively) and from 12 to 30 months (-0.79 [-1.27 to -0.31] and -1.00 [-1.35 to -0.65], respectively). New onset symptoms were associated with a significant decrease in mean IADL scores at 6 months and from 6 to 12 months. Patients with no depressive symptoms showed little change in scores whereas those with baseline only symptoms showed significant improvement in mean IADL at 6 months. CONCLUSIONS: Patients with persistent depressive symptoms were at greatest risk for worse functional status 30 months following coronary interventions. Proactive screening and follow-up for depression in this population offers prognostic value and may facilitate the implementation of targeted interventions.

Induced abortion and contraception use: among immigrant and Canadian-born women in Calgary, Alta.

OBJECTIVE: To determine what proportion of women seeking induced abortion in the Calgary census metropolitan area were immigrants. DESIGN: For 2 months, eligible women were asked to complete a questionnaire. Women who refused were asked to provide their country of birth (COB) to assess for selection bias. SETTING: Two abortion clinics in Calgary, Alta. PARTICIPANTS: Women presenting at or less than 15 weeks' gestational age for induced abortion for maternal indications. MAIN OUTCOME MEASURES: The primary outcome was the proportion of women seeking induced abortion services who were immigrants. Secondary outcomes compared socioeconomic characteristics and contraception use between immigrant and Canadian-born women. RESULTS: A total of 752 women either completed a questionnaire (78.6%) or provided their COB (21.4%). Overall, 28.9% of women living in the Calgary census metropolitan area who completed the questionnaire were immigrants, less than the 31.2% background proportion of immigrant women of childbearing age. However, 46.0% of women who provided only COB were immigrants. When these data were combined, 34.2% of women presenting for induced abortion identified as immigrant, a proportion not significantly different from the background proportion (P = .127). Immigrant women presenting for induced abortion tended to be older, more educated, married with children, and have increased parity. They were similar to Canadian-born women in number of previous abortions, income status, and employment status. CONCLUSION: This study suggests that immigrant women in Calgary are not presenting for induced abortion in disproportionately higher numbers, which differs from existing European literature. This is likely owing to differing socioeconomic characteristics among the immigrant women in our study from what have been previously described in the literature (typically lower socioeconomic status). Much still needs to be explored with regard to factors influencing the use of abortion services by immigrant women.

Comparing frailty measures in their ability to predict adverse outcome among older residents of assisted living.

BACKGROUND: Few studies have directly compared the competing approaches to identifying frailty in more vulnerable older populations. We examined the ability of two versions of a frailty index (43 vs. 83 items), the Cardiovascular Health Study (CHS) frailty criteria, and the CHESS scale to accurately predict the occurrence of three outcomes among Assisted Living (AL) residents followed over one year. METHODS: The three frailty measures and the CHESS scale were derived from assessment items completed among 1,066 AL residents (aged 65+) participating in the Alberta Continuing Care Epidemiological Studies (ACCES). Adjusted risks of one-year mortality, hospitalization and long-term care placement were estimated for those categorized as frail or pre-frail compared with non-frail (or at high/intermediate vs. low risk on CHESS). The area under the ROC curve (AUC) was calculated for select models to assess the predictive accuracy of the different frailty measures and CHESS scale in relation to the three outcomes examined. RESULTS: Frail subjects defined by the three approaches and those at high risk for decline on CHESS showed a statistically significant increased risk for death and long-term care placement compared with those categorized as either not frail or at low risk for decline. The risk estimates for hospitalization associated with the frailty measures and CHESS were generally weaker with one of the frailty indices (43 items) showing no significant association. For death and long-term care placement, the addition of frailty (however derived) or CHESS significantly improved on the AUC obtained with a model including only age, sex and co-morbidity, though the magnitude of improvement was sometimes small. The different frailty/risk models did not differ significantly from each other in predicting mortality or hospitalization; however, one of the frailty indices (83 items) showed significantly better performance over the other measures in predicting long-term care placement. CONCLUSIONS: Using different approaches, varying degrees of frailty were detected within the AL population. The various approaches to defining frailty were generally more similar than dissimilar with regard to predictive accuracy with some exceptions. The clinical implications and opportunities of detecting frailty in more vulnerable older adults require further investigation.

Operationalizing frailty among older residents of assisted living facilities.

BACKGROUND: Frailty in later life is viewed as a state of heightened vulnerability to poor outcomes. The utility of frailty as a measure of vulnerability in the assisted living (AL) population remains unexplored. We examined the feasibility and predictive accuracy of two different interpretations of the Cardiovascular Health Study (CHS) frailty criteria in a population-based sample of AL residents. METHODS: CHS frailty criteria were operationalized using two different approaches in 928 AL residents from the Alberta Continuing Care Epidemiological Studies (ACCES). Risks of one-year mortality and hospitalization were estimated for those categorized as frail or pre-frail (compared with non-frail). The prognostic significance of individual criteria was explored, and the area under the ROC curve (AUC) was calculated for select models to assess the utility of frailty in predicting one-year outcomes. RESULTS: Regarding feasibility, complete CHS criteria could not be assessed for 40% of the initial 1,067 residents. Consideration of supplementary items for select criteria reduced this to 12%. Using absolute (CHS-specified) cut-points, 48% of residents were categorized as frail and were at greater risk for death (adjusted risk ratio [RR] 1.75, 95% CI 1.08-2.83) and hospitalization (adjusted RR 1.54, 95% CI 1.20-1.96). Pre-frail residents defined by absolute cut-points (48.6%) showed no increased risk for mortality or hospitalization compared with non-frail residents. Using relative cut-points (derived from AL sample), 19% were defined as frail and 55% as pre-frail and the associated risks for mortality and hospitalization varied by sex. Frail (but not pre-frail) women were more likely to die (RR 1.58 95% CI 1.02-2.44) and be hospitalized (RR 1.53 95% CI 1.25-1.87). Frail and pre-frail men showed an increased mortality risk (RR 3.21 95% CI 1.71-6.00 and RR 2.61 95% CI 1.40-4.85, respectively) while only pre-frail men had an increased risk of hospitalization (RR 1.58 95% CI 1.15-2.17). Although incorporating either frailty measure improved the performance of predictive models, the best AUCs were 0.702 for mortality and 0.633 for hospitalization. CONCLUSIONS: Application of the CHS criteria for frailty was problematic and only marginally improved the prediction of select adverse outcomes in AL residents. Development and validation of alternative approaches for detecting frailty in this population, including consideration of female/male differences, is warranted.

SMART longitudinal analysis: A tutorial for using repeated outcome measures from SMART studies to compare adaptive interventions.

In recent years, there has been increased interest in the development of adaptive interventions across various domains of health and psychological research. An adaptive intervention is a protocolized sequence of individualized treatments that seeks to address the unique and changing needs of individuals as they progress through an intervention program. The sequential, multiple assignment, randomized trial (SMART) is an experimental study design that can be used to build the empirical basis for the construction of effective adaptive interventions. A SMART involves multiple stages of randomizations; each stage of randomization is designed to address scientific questions concerning the best intervention option to employ at that point in the intervention. Several adaptive interventions are embedded in a SMART by design; many SMARTs are motivated by scientific questions that concern the comparison of these embedded adaptive interventions. Until recently, analysis methods available for the comparison of adaptive interventions were limited to end-of-study outcomes. The current article provides an accessible and comprehensive tutorial to a new methodology for using repeated outcome data from SMART studies to compare adaptive interventions. We discuss how existing methods for comparing adaptive interventions in terms of end-of-study outcome data from a SMART can be extended for use with longitudinal outcome data. We also highlight the scientific utility of using longitudinal data from a SMART to compare adaptive interventions. A SMART study aiming to develop an adaptive intervention to engage alcohol- and cocaine-dependent individuals in treatment is used to demonstrate the application of this new methodology. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

The Pulmonary Fibrosis Foundation Patient Registry. Rationale, Design, and Methods.

Detailed understanding of longitudinal behavior, response to therapy, and applicable biomarkers for interstitial lung diseases (ILDs) is lacking. There is a need for a large multicenter registry that provides researchers and clinicians access to well-characterized data not limited to patients with idiopathic pulmonary fibrosis. The Pulmonary Fibrosis Foundation Patient Registry (PFF-PR) is a database that collects baseline and longitudinal demographic and clinical information about patients with ILDs in the United States. The objective of this study is to describe the patient population, data collection process, and opportunities for retrospective and prospective research with the PFF-PR. Individuals 18 years or older who had ILD diagnosed and who were seen at PFF-PR centers who provided informed consent were eligible to participate. Baseline and longitudinal demographic, spirometric, radiographic, morbidity, and mortality data are recorded into a secure electronic data capture system. Starting in 2016, the PFF-PR has collected data on 2,003 patients at 42 clinical sites in the United States. At the time of enrollment, the mean age of participants was 68 years old. Most (62%) of participants were male, and 58% had a positive smoking history. The mean forced vital capacity was 69% predicted, and the mean diffusing capacity of the lung for carbon monoxide was 43% predicted. Forty-one percent of patients were using supplemental oxygen, and 39% were on antifibrotic therapy. Reasons for attrition were mostly death or transplant, with low rates of loss to follow-up or withdrawal. The PFF-PR is a large multicenter United States-based registry that provides researchers and clinicians access to well-characterized ILD patient data.

Frailty Trajectories After Treatment for Coronary Artery Disease in Older Patients.

BACKGROUND: Frailty is an independent risk factor for cardiovascular outcomes. However, its trajectory after coronary artery disease treatment is unknown. METHODS AND RESULTS: Three hundred seventy-four patients undergoing nonemergent cardiac catheterization followed by treatment (ie, 128 coronary artery bypass graft [CABG], 150 percutaneous coronary intervention [PCI], 96 medical therapy only) were observed for 30 months. A frailty index (FI) score was calculated at baseline (before initial treatment) and 6, 12, and 30 months after treatment. Random-effects models compared FI score trajectories by sex, age, and treatment group. Mean baseline FI scores were 0.170, 0.154, and 0.154 for CABG, PCI, and medical therapy only, respectively. FI scores decreased (improved) 6 months after initial treatment, then increased (worsened) at 12 and 30 months (P<0.001 for differences over time). Women had nonsignificantly higher FI scores than men (P=0.097) but followed the same trajectory (P=0.352 for differences over time). In patients aged ≥75 years, FI scores increased postbaseline for CABG and medical therapy only and after 6 months for PCI patients. Patients <75 years assigned to PCI and CABG experienced a sustained frailty reduction, whereas those assigned to medical therapy only showed stable frailty over the 30-month follow-up period (P value for differences over time by age and treatment group=0.041). CONCLUSIONS: With coronary artery disease treatment, frailty generally follows a U-shaped trajectory, but the pattern may differ by age and treatment. Further investigation is needed to confirm these observations and determine whether patients might benefit from consideration of frailty status.

The emergency to home project: impact of an emergency department care coordinator on hospital admission and emergency department utilization among seniors.

BACKGROUND: Seniors comprise 14% to 21% of all emergency department (ED) visits, yet are disproportionately larger users of ED and inpatient resources. ED care coordinators (EDCCs) target seniors at risk for functional decline and connect them to home care and other community services in hopes of avoiding hospitalization. The goal of this study was to measure the association between the presence of EDCCs and admission rates for seniors aged ≥ 65. Secondary outcomes included length of stay, recidivism at 30 days, and revisit resulting in admission at 30 days. METHODS: This was a matched pairs study using administrative data from eight EDs in six Alberta cities. Four of these hospitals were intervention sites, in which patients were seen by an EDCC, while the other four sites had no EDCC presence. All seniors aged ≥ 65 with a discharge diagnosis of fall or musculoskeletal pathology were included. Cases were matched by CTAS category, age, gender, mode of arrival, and home living environment. McNemar's test for matched pairs was used to compare admission and recidivism rates at EDCC and non-EDCC hospitals. A paired t-test was used to compare length of stay between groups. RESULTS: There were no statistically significant differences for baseline admission rate, revisit rate at 30 days, and readmission rate at 30 days between EDCC and non-EDCC patients. CONCLUSIONS: This study showed no reduction in senior patients' admission rates, recidivism at 30 days, or hospital length of stay when comparing seniors seen by an EDCC with those not seen by an EDCC.

A dynamic view of depressive symptoms and neurocognitive change among patients with coronary artery disease.

CONTEXT: Older patients with coronary artery disease often experience depressive symptoms and are vulnerable to developing cognitive impairment. Whether depressive symptoms increase their risk of cognitive decline is unknown. OBJECTIVES: To examine the association between the stability of depressive symptoms and cognitive decline for 30 months among patients undergoing coronary angiography and to explore whether any observed associations were modified by the presence of the apolipoprotein E (APOE) ε4 allele. DESIGN: Cohort study. SETTING: Urban tertiary care hospital serving southern Alberta. PARTICIPANTS: Three hundred fifty patients 60 years or older (73.7% male) undergoing nonemergent catheterization (October 27, 2003, through February 28, 2007) without prior revascularization. We compared a baseline measure of depressive symptoms (Geriatric Depression Scale score ≥5) with a dynamic measure capturing change from baseline to 12 months. MAIN OUTCOME MEASURES: Mean change in domain (z scores for attention/executive function, learning/memory, and verbal fluency) and global (raw Mini-Mental State Examination) cognitive scores from baseline to 6, 12, and 30 months and from 12 to 30 months. RESULTS: In adjusted models, participants with persistent depressive symptoms (at baseline and ≥1follow-up visit) showed significantly greater declines at 30 months in attention/executive function (mean z score change, -0.22), learning/memory (-0.19), verbal fluency (-0.18), and global cognition (mean Mini-Mental State Examination [MMSE] score change, -0.99) compared with participants with no or baseline-only depressive symptoms. Persistent depressive symptoms were associated with significantly greater declines in all cognitive measures from 12 to 30 months after adjusting for sociodemographic and clinical factors. For global cognition, a significantly greater decline was evident for patients with persistent depressive symptoms and the APOE ε4 allele (mean MMSE score change, -2.93 [95% CI, -4.40 to -1.45]). CONCLUSIONS: Depressive symptoms persist in some patients with coronary artery disease, placing them at a greater risk for cognitive decline. Whether this decline is additionally modified by the presence of APOE ε4 requires further investigation.

Development of a frailty index for patients with coronary artery disease.

OBJECTIVES: To construct a brief frailty index for older patients with coronary artery disease (CAD) undergoing coronary angiography that includes physical, cognitive, and psychosocial criteria and accurately predicts future disability and decline in health-related quality of life (HRQL). DESIGN: Prospective cohort. SETTING: An urban tertiary care hospital in Alberta, Canada. PARTICIPANTS: Three hundred seventy-four patients aged 60 and older (73% male) undergoing cardiac catheterization for CAD between October 2003 and May 2007. MEASUREMENTS: Potential frailty criteria examined at baseline (before the procedure) included measures of balance, gait speed, cognition, self-reported health, body mass index (BMI), depressive symptoms, and living alone. The outcomes assessed over 1 year were dependency in activities of daily living (ADLs) and HRQL. RESULTS: The five best-fitting criteria from regression analyses for ADL decline were poor balance (risk ratio (RR)=2.4, 95% confidence interval (CI)=1.4­4.0), abnormal BMI (RR=1.8, 95% CI=1.1­3.0), impaired Trail-Making Test Part B performance (RR=2.3, 95% CI=1.3­4.2), depressive symptoms (RR=1.8, 95% CI=1.1­3.1), and living alone (RR=2.2, 95% CI=1.3­3.8). Using the five criteria as separate variables or as a summary frailty index yielded identical areas under the receiver operating characteristic curve (0.76, 95% CI=0.66­0.84). Patients with three or more criteria (vs none) were at statistically significant greater risk for increased disability (RR=10.4, 95% CI=4.4­24.2) and decreased HRQL (RR=4.2, 95% CI=2.3­7.4) after 1 year. CONCLUSION: This brief frailty index including physical, cognitive, and psychosocial criteria was predictive of increased disability and decreased HRQL at 1 year in older patients with CAD undergoing angiography. This index may have applications for clinicians and researchers but requires further validation.