Development of the Lung Transplant Frailty Scale (LT-FS).

BACKGROUND: Existing measures of frailty developed in community dwelling older adults may misclassify frailty in lung transplant candidates. We aimed to develop a novel frailty scale for lung transplantation with improved performance characteristics. METHODS: We measured the short physical performance battery (SPPB), fried frailty phenotype (FFP), Body Composition, and serum Biomarkers representative of putative frailty mechanisms. We applied a 4-step established approach (identify frailty domain variable bivariate associations with the outcome of waitlist delisting or death; build models sequentially incorporating variables from each frailty domain cluster; retain variables that improved model performance ability by c-statistic or AIC) to develop 3 candidate "Lung Transplant Frailty Scale (LT-FS)" measures: 1 incorporating readily available clinical data; 1 adding muscle mass, and 1 adding muscle mass and research-grade Biomarkers. We compared construct and predictive validity of LT-FS models to the SPPB and FFP by ANOVA, ANCOVA, and Cox proportional-hazard modeling. RESULTS: In 342 lung transplant candidates, LT-FS models exhibited superior construct and predictive validity compared to the SPPB and FFP. The addition of muscle mass and Biomarkers improved model performance. Frailty by all measures was associated with waitlist disability, poorer HRQL, and waitlist delisting/death. LT-FS models exhibited stronger associations with waitlist delisting/death than SPPB or FFP (C-statistic range: 0.73-0.78 vs. 0.57 and 0.55 for SPPB and FFP, respectively). Compared to SPPB and FFP, LT-FS models were generally more strongly associated with delisting/death and improved delisting/death net reclassification, with greater improvements with increasing LT-FS model complexity (range: 0.11-0.34). For example, LT-FS-Body Composition hazard ratio for delisting/death: 6.0 (95%CI: 2.5, 14.2), SPPB HR: 2.5 (95%CI: 1.1, 5.8), FFP HR: 4.3 (95%CI: 1.8, 10.1). Pre-transplant LT-FS frailty, but not SPPB or FFP, was associated with mortality after transplant. CONCLUSIONS: The LT-FS is a disease-specific physical frailty measure with face and construct validity that has superior predictive validity over established measures.

Intraindividual Change in Cognitive Function Among Adults With Systemic Lupus Erythematosus: A Markov Analysis Over 7 Years.

OBJECTIVE: Cognitive impairment is prevalent in systemic lupus erythematosus (SLE). There remain gaps in understanding cognition and SLE longitudinally. We studied intraindividual change in cognition in SLE over time. METHODS: Data were from the University of California, San Francisco Lupus Outcome Study, which included 1281 adults with SLE. The Hopkins Verbal Learning Test-Revised (HVLT-R) and the Controlled Oral Word Association Test (COWAT) were administered annually over 7 years. A two-state Markov analysis was used to model transition intensities for probabilities of change in cognition. Logistic regression examined the association between clinical variables and cognitive change. RESULTS: Minimal transition between cognitive states was observed in the Markov analysis. Using the COWAT, higher levels of self-reported depression were associated with decreased likelihood of cognitive improvement (Relative Risk [RR]: 0.98; 95% confidence interval [CI]: 0.96-0.99), and higher self-reported disease severity was associated with cognitive decline (RR: 1.05; 95% CI: 1.02-1.09). Using the HVLT-R, increasing age (RR: 1.02; 95% CI: 1.01-1.03) and higher education level (RR: 1.82; 95% CI: 1.28-2.58) were associated with cognitive improvement, and higher self-reported disease severity (RR: 1.02; 95% CI: 1.01-1.03) and depression (RR: 1.05; 95% CI: 1.03-1.07) were associated with cognitive decline. CONCLUSION: Most individuals with SLE did not transition between states of high (Z score ≥ -1.5) or low (Z score < -1.5) cognition in a Markov analysis over a 7-year assessment period, highlighting a degree of relative stability in cognition over time. Increasing age and higher education levels were associated with greater likelihood of cognitive improvement. Greater self-reported SLE disease severity and depression were associated with cognitive decline.

Race, Ethnicity, and Disparities in the Risk of End-Organ Lupus Manifestations Following a Systemic Lupus Erythematosus Diagnosis in a Multiethnic Cohort.

OBJECTIVE: Data on the onset of lupus manifestations across multiple organ domains and in diverse populations are limited. The objective was to analyze racial and ethnic differences in the risk of end-organ lupus manifestations following systemic lupus erythematosus (SLE) diagnosis in a multiethnic cohort. METHODS: The California Lupus Epidemiology Study (CLUES) is a longitudinal study of SLE. Data on major end-organ lupus manifestations were collected and categorized by organ system: renal, hematologic, neurologic, cardiovascular, and pulmonary. Multiorgan disease was defined as manifestations in ≥2 of these distinct organ systems. Kaplan-Meier curves assessed end-organ disease-free survival, and Cox proportional hazards regression estimated the rate of end-organ disease following SLE diagnosis, adjusting for age at diagnosis, sex, and self-reported race and ethnicity (White, Hispanic, Black, and Asian). RESULTS: Of 326 participants, 89% were female; the mean age was 45 years. Self-reported race and ethnicity were 30% White, 23% Hispanic, 11% Black, and 36% Asian. Multiorgan disease occurred in 29%. Compared to White participants, Hispanic and Asian participants had higher rates, respectively, of renal (hazard ratio [HR] 2.9 [95% confidence interval (95% CI) 1.8-4.7], HR 2.9 [95% CI 1.9-4.6]); hematologic (HR 2.7 [95% CI 1.3-5.7], HR 2.1 [95% CI 1.0-4.2]); and multiorgan disease (HR 3.3 [95% CI 1.8-5.9], HR 2.5 [95% CI 1.4-4.4]) following SLE diagnosis. CONCLUSION: We found heightened risks of developing renal, hematologic, and multiorgan disease following SLE diagnosis among Hispanic and Asian patients with SLE, as well as a high burden of multiorgan disease among CLUES participants.

Longitudinal relationships between cognitive domains and depression and anxiety symptoms in systemic lupus erythematosus.

OBJECTIVES: To examine i) the relationship between neuropsychological performance and depression and anxiety over time, and ii) the overlap between classification of cognitive dysfunction, anxiety, and depression in SLE. METHODS: 301 patients with SLE were included. Cognition was measured using a modified version of the ACR neuropsychological battery; cognitive dysfunction was defined as z-scores ≤-1.5 on ≥2 domains. Depression and anxiety were measured using the Beck Depression Inventory-II and the Beck Anxiety Inventory, respectively. All measures were assessed at baseline, 6, and 12 months. Their relationships were analyzed using Multiple Factor Analysis (MFA). RESULTS: Anxiety and depression and neuropsychological performance were stable across time. Factor analysis identified two dimensions explaining 42.2% of the variance in neuropsychological performance. The first dimension (33.1% of the variance) included primarily complex cognitive tests measuring executive function; verbal, visual, and working memory; and complex processing speed. The second dimension (9.1% of the variance) included primarily measures of simple information processing speed or motor dexterity. Anxiety and depression scores were consistently related to the first cognitive dimension. There was substantial overlap in participants classified with cognitive dysfunction and anxiety and depression. CONCLUSIONS: Depression and anxiety symptoms in SLE patients are related to a cognitive dimension incorporating memory, executive function and complex processing speed in a stable manner across one year. Many patients with cognitive dysfunction exhibit clinically significant anxiety and depression. Further research should examine whether cognition improves when anxiety and depression are treated and mechanistic links between anxiety and depression and cognitive dysfunction in SLE.

Defining Minimum Clinically Important Changes for the Patient Activity Scale II.

OBJECTIVE: To define the minimum clinically important improvement (MCII) and minimum clinically important worsening (MCIW) for the Patient Activity Scale II (PAS-II; range 0-10), a recommended patient-reported outcome measuring rheumatoid arthritis disease activity. METHODS: Data were taken from Forward, The National Databank for Rheumatic Diseases, from four 6-month data collection periods. Both anchor-based and distribution-based methods were used to estimate the MCII and MCIW. Anchor-based analyses used comparisons of pain and general health to the previous 6 months. Distribution-based analyses used 0.5 and 0.35 SDs. We stratified analyses based on the PAS-II score (above/below 3.7), hypothesizing that the MCII and MCIW would depend on the baseline score. To assess construct validity, we evaluated the odds of achieving the MCII in patients receiving new therapies. RESULTS: In the overall sample, for pain and general health anchor questions, the MCIW was 0.50 and 0.55, respectively. The MCII was defined as 0.39 and 0.45, respectively, for pain and general health. The MCIW for anchor-based methods among participants with low disease activity was 1.10 (1.09/1.11 [pain/general health]), while the MCII for those with moderate-to-high disease activity was 1.09 (1.15/1.02 [pain/general health]). Distribution-based methods for 0.5 and 0.35 SD were 1.08 and 0.76, respectively, for pain and general health. There was fair-to-excellent agreement with clinically important differences in assessments of pain and disability. Patients receiving new treatments had 30% greater odds of achieving the MCII. CONCLUSION: The minimum important change in PAS-II score was approximately 0.5. Among participants with a moderate-to-high PAS-II score , the MCII was 1.1, and among participants with low disease activity, the MCIW was 1.1.

Improvement in patient-reported outcomes after lung transplantation is not impacted by the use of extracorporeal membrane oxygenation as a bridge to transplantation.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is increasingly used as a bridge to lung transplantation. The impact of preoperative ECMO on health-related quality of life (HRQL) and depressive symptoms after lung transplantation remains unknown, however. METHODS: In a single-center prospective cohort study, we assessed HRQL and depressive symptoms before and at 3, 6, and 12 months after lung transplantation using the Short Form 12 Physical and Mental Component Scores (SF12-PCS and SF12-MCS), Airway Questionnaire 20-Revised (AQ20R), EuroQol 5D (EQ5D), and Geriatric Depression Scale (GDS). Changes in HRQL were quantified by segmented linear mixed-effects models controlling for age, sex, diagnosis, preoperative forced expiratory volume in 1 second, 6-minute walk distance, and Lung Allocation Score. We compared changes in HRQL among subjects bridged with ECMO, subjects hospitalized but not on ECMO, and subjects called in for transplantation as outpatients. RESULTS: Out of 189 subjects, 17 were bridged to transplantation with ECMO. In all groups, improvements in HRQL following lung transplantation exceeded the minimally clinically important difference using the SF12-PCS, AQ20R, EQ5D, and GDS. HRQL defined by SF12-MCS did not change after transplantation. Improvements were generally similar among the groups, except for EQ5D, which showed a trend toward less benefit in the outpatients, possibly due to their better HRQL before lung transplantation. CONCLUSIONS: Subjects ill enough to require ECMO as a bridge to lung transplantation appear to achieve similar improvements in HRQL and depressive symptoms as those who do not. It is reassuring to both providers and patients that lung transplantation provides substantial improvements in HRQL, even for those patients who are critically ill in the run up to transplantation.