Search

Abstract Galactomannan (GM) is a polysaccharide cell wall component released by Aspergillus spp., and an immunoenzymatic GM assay is used for the diagnosis of invasive pulmonary aspergillosis. We evaluated the cause of strong positivity for GM in patients with no typical signs of aspergillosis. Repeat assays were performed using different instruments and reagent lots, but there were no differences in results among the assays. Patients with strongly positive GM results were investigated. Medication histories revealed that 14 of 23 patients had been administered total parenteral nutrition solution from one manufacturer and 4 patients had been administered dextrose solution from a different manufacturer before being tested. The results of GM assays conducted on samples of dextrose solution and the glucose fraction of the total parenteral nutrition solution were strongly positive, confirming the causes of the false-positive reactions. We hypothesize that a trace amount of GM was introduced into the glucose-containing solutions because glucoamylase, which is necessary for the saccharification step of glucose synthesis, was derived from Aspergillus niger. To enhance patient care and prevent unnecessary antifungal prescriptions, healthcare providers and manufacturers of healthcare products need to be aware of the possibility of false-positive reactions for GM.

Background The goal was to determine the feasibility of mapping the injured‐but‐not‐infarcted myocardium using 99mTc‐duramycin in the postischemic heart, with spatial information for its characterization as a pathophysiologically intermediate tissue, which is neither normal nor infarcted. Methods and Results Coronary occlusion was conducted in Sprague Dawley rats with preconditioning and 30‐minute ligation. In vivo single‐photon emission computed tomography was acquired after 3 hours (n=6) using 99mTc‐duramycin, a phosphatidylethanolamine‐specific radiopharmaceutical. The 99mTc‐duramycin+ areas were compared with infarct and area‐at‐risk (n=8). Cardiomyocytes and endothelial cells were isolated for gene expression profiling. Cardiac function was measured with echocardiography (n=6) at 4 weeks. In vivo imaging with 99mTc‐duramycin identified the infarct (3.9±2.4% of the left ventricle and an extensive area 23.7±2.2% of the left ventricle) with diffuse signal outside the infarct, which is pathologically between normal and infarcted (apoptosis 1.8±1.6, 8.9±4.2, 13.6±3.8%; VCAM‐1 [vascular cell adhesion molecule 1] 3.2±0.8, 9.8±4.1, 15.9±4.2/mm2; tyrosine hydroxylase 14.9±2.8, 8.6±4.4, 5.6±2.2/mm2), with heterogeneous changes including scattered micronecrosis, wavy myofibrils, hydropic change, and glycogen accumulation. The 99mTc‐duramycin+ tissue is quantitatively smaller than the area‐at‐risk (26.7% versus 34.4% of the left ventricle, P=0.008). Compared with infarct, gene expression in the 99mTc‐duramycin+–noninfarct tissue indicated a greater prosurvival ratio (BCL2/BAX [B‐cell lymphoma 2/BCL2‐associated X] 7.8 versus 5.7 [cardiomyocytes], 3.7 versus 3.2 [endothelial]), and an upregulation of ion channels in electrophysiology. There was decreased contractility at 4 weeks (regional fractional shortening −8.6%, P

Background. Hispanic patients receive disproportionately fewer kidney transplants (KT) than non-Hispanic White (NHW) patients. In this observational study, we evaluated disparities in completing evaluation steps to KT among Hispanic patients. Methods. Using medical records of Hispanic and NHW patients initiating evaluation at 4 transplant centers from January 2011 to March 2020, we performed sequential Cox models to compare Hispanic versus NHW patients reaching each step of the evaluation process until receiving a KT. Results. Among all 5197 patients (Hispanic n = 2473; NHW n = 2724) initiating evaluation, Hispanic patients had 8% lower risk to be approved by the kidney pancreas (KP) committee than NHW patients (adjusted hazard ratio [aHR], 0.92; 95% confidence intervals (CI), 0.86-0.98; P = 0.015). Among 3492 patients approved by the KP committee, Hispanic patients had 13% lower risk to be waitlisted than NHW patients (aHR, 0.87; 95% CI, 0.81-0.94; P = 0.004). Among 3382 patients who were waitlisted, Hispanic patients had 11% lower risk than NHW patients to receive KT (aHR, 0.89; 95% CI, 0.81-0.97; P = 0.011). Among all patients initiating evaluation, Hispanic patients had a 16% lower risk than NHW patients to reach KT (aHR, 0.84; 95% CI, 0.76-0.92; P = 0.0002). Conclusions. Our study found that disproportionately fewer Hispanic patients were approved by the KP committee, were waitlisted, and received a KT, particularly a living donor kidney transplant, than NHW patients. Closer oversight of the evaluation process may help patients overcome challenges in access to KT.

Rationale & Objective: Heart failure (HF) is an important cause of morbidity and mortality among individuals with chronic kidney disease (CKD). A large body of evidence from preclinical and clinical studies implicates excess levels of fibroblast growth factor 23 (FGF23) in HF pathogenesis in CKD. It remains unclear whether the relationship between elevated FGF23 levels and HF risk among individuals with CKD varies by HF subtype. Study Design: Prospective cohort study. Settings & Participants: A total of 3,502 participants were selected in the Chronic Renal Insufficiency Cohort study. Exposure: Baseline plasma FGF23. Outcomes: Incident HF by subtype and total rate of HF hospitalization. HF was categorized as HF with preserved ejection fraction (HFpEF, ejection fraction [EF] ≥ 50%), HF with reduced EF (HFrEF, EF

Abstract Study objective To describe recent practice patterns of preoperative tests and to examine their association with 90-day all-cause readmissions and length of stay. Design Retrospective cohort study using the New York Statewide Planning and Research Cooperative System (SPARCS). Setting SPARCS from March 1, 2016, to July 1, 2017. Participants Adults undergoing Total Hip Replacement (THR) or Total Knee Replacement (TKR) had a preoperative screening outpatient visit within two months before their surgery. Interventions Electrocardiogram (EKG), chest X-ray, and seven preoperative laboratory tests (RBCs antibody screen, Prothrombin time (PT) and Thromboplastin time, Metabolic Panel, Complete Blood Count (CBC), Methicillin Resistance Staphylococcus Aureus (MRSA) Nasal DNA probe, Urinalysis, Urine culture) were identified. Primary and secondary outcome measures Regression analyses were utilized to determine the association between each preoperative test and two postoperative outcomes (90-day all-cause readmission and length of stay). Regression models adjusted for hospital-level random effects, patient demographics, insurance, hospital TKR, THR surgical volume, and comorbidities. Sensitivity analysis was conducted using the subset of patients with no comorbidities. Results Fifty-five thousand ninety-nine patients (60% Female, mean age 66.1+/− 9.8 SD) were included. The most common tests were metabolic panel (74.5%), CBC (66.8%), and RBC antibody screen (58.8%). The least common tests were MRSA Nasal DNA probe (13.0%), EKG (11.7%), urine culture (10.7%), and chest X-ray (7.9%). Carrying out MRSA testing, urine culture, and EKG was associated with a lower likelihood of 90-day all-cause readmissions. The length of hospital stay was not associated with carrying out any preoperative tests. Results were similar in the subset with no comorbidities. Conclusions Wide variation exists in preoperative tests before THR and TKR. We identified three preoperative tests that may play a role in reducing readmissions. Further investigation is needed to evaluate these findings using more granular clinical data.

Introduction: Management of chronic kidney disease (CKD) entails high medical complexity and often results in high hospitalization burden. There are limited data on the associations of longitudinal hospital utilization patterns with adverse clinical outcomes in individuals with CKD. Methods: We derived cumulative all-cause hospitalization trajectory groups using latent class trajectory analysis in 3012 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study who were alive and did not reach end-stage kidney disease (ESKD) within 4 years of study entry. Cox proportional hazards models tested the associations between hospitalization trajectory groups and risks of ESKD and death prior to the onset of ESKD (ESKD-censored death). Results: Within 4 years of study entry, there were 5658 hospitalizations among 3012 participants. We identified 3 distinct subgroups of individuals with CKD based on cumulative all-cause hospitalization trajectories over 4 years: low-utilizer (n = 1066), intermediate-utilizer (n = 1802), and high-utilizer (n = 144). High-utilizers represented a patient population of lower socioeconomic status who had a greater prevalence of comorbid conditions and lower kidney function compared with intermediate- and low-utilizers. After the 4-year ascertainment period to form the trajectory subgroups, there were 544 ESKD events and 437 ESKD-censored deaths during a median follow-up time of 5.1 years. Compared with low-utilizers, intermediate-utilizers and high-utilizers were at 1.49-fold (95% confidence interval [CI] 1.22–1.84) and 1.75-fold (95% CI 1.20–2.56) higher risk of ESKD in adjusted analyses, respectively. Compared with low-utilizers, intermediate-utilizers and high-utilizers were at 1.48-fold (95% CI 1.17–1.87) and 2.58-fold (95% CI 1.74–3.83) higher risk of ESKD-censored death in adjusted analyses, respectively. Conclusions: Trajectories of cumulative all-cause hospitalization identify subgroups of individuals with CKD who are at high risk of ESKD and death.

Abstract Background Skin fibrosis is the clinical hallmark of systemic sclerosis (SSc), where collagen deposition and remodeling of the dermis occur over time. The most widely used outcome measure in SSc clinical trials is the modified Rodnan skin score (mRSS), which is a semi-quantitative assessment of skin stiffness at seventeen body sites. However, the mRSS is confounded by obesity, edema, and high inter-rater variability. In order to develop a new histopathological outcome measure for SSc, we applied a computer vision technology called a deep neural network (DNN) to stained sections of SSc skin. We tested the hypotheses that DNN analysis could reliably assess mRSS and discriminate SSc from normal skin. Methods We analyzed biopsies from two independent (primary and secondary) cohorts. One investigator performed mRSS assessments and forearm biopsies, and trichrome-stained biopsy sections were photomicrographed. We used the AlexNet DNN to generate a numerical signature of 4096 quantitative image features (QIFs) for 100 randomly selected dermal image patches/biopsy. In the primary cohort, we used principal components analysis (PCA) to summarize the QIFs into a Biopsy Score for comparison with mRSS. In the secondary cohort, using QIF signatures as the input, we fit a logistic regression model to discriminate between SSc vs. control biopsy, and a linear regression model to estimate mRSS, yielding Diagnostic Scores and Fibrosis Scores, respectively. We determined the correlation between Fibrosis Scores and the published Scleroderma Skin Severity Score (4S) and between Fibrosis Scores and longitudinal changes in mRSS on a per patient basis. Results In the primary cohort (n = 6, 26 SSc biopsies), Biopsy Scores significantly correlated with mRSS (R = 0.55, p = 0.01). In the secondary cohort (n = 60 SSc and 16 controls, 164 biopsies; divided into 70% training and 30% test sets), the Diagnostic Score was significantly associated with SSc-status (misclassification rate = 1.9% [training], 6.6% [test]), and the Fibrosis Score significantly correlated with mRSS (R = 0.70 [training], 0.55 [test]). The DNN-derived Fibrosis Score significantly correlated with 4S (R = 0.69, p = 3 × 10− 17). Conclusions DNN analysis of SSc biopsies is an unbiased, quantitative, and reproducible outcome that is associated with validated SSc outcomes.

Objective We examined the accuracy of data from an affordable personal monitor (Fitbit Flex) compared with that of data from a research‐grade accelerometer worn simultaneously for 7 days; high accuracy would support substitution with this less‐expensive personal activity monitor in future community‐based arthritis research. Methods Subjects (N = 35) with chronic knee symptoms were recruited for a pilot intervention study using Fitbits to increase physical activity in employees with chronic knee symptoms at an urban corporation. Subjects simultaneously wore for 7 days a Fitbit Flex (wrist‐worn) and ActiGraph GT3X+ (waist‐worn). Fitbit Flex data were regularly stored on a research storage service (Fitabase) by participants. Bland–Altman plots were constructed to examine the agreement between the mean daily times spent in light activity and in bouted moderate‐to‐vigorous physical activity (MVPA). Comparisons were calculated by matching Fitabase data from calendar days the Fitbit was worn with data from valid monitoring days (greater than or equal to 10 hours wear time) of the ActiGraph. Results Participants at baseline were mostly female (69%) and white (57%) and had a mean age of 52 years and body mass index of 32 kg/m2. Bland–Altman analyses indicated systematic bias overall (the Fitbit overestimated both light‐intensity activity and MVPA compared with the ActiGraph). The average error varied in magnitude and direction with changing activity amounts. Conclusion The Fitbit Flex does not appear to be an adequate substitute for research‐grade accelerometry (which represents the gold standard for objective research monitoring of all physical activity intensity levels) in this population of persons with chronic knee symptoms.

Rationale & Objective: Elevated levels of deoxycholic acid (DCA) are associated with adverse outcomes and may contribute to vascular calcification in patients with chronic kidney disease (CKD). We tested the hypothesis that elevated levels of DCA were associated with increased risks of cardiovascular disease, CKD progression, and death in patients with CKD. Study Design: Prospective observational cohort study. Setting & Participants: We included 3,147 Chronic Renal Insufficiency Cohort study participants who had fasting DCA levels. The average age was 59 ± 11 years, 45.3% were women, 40.6% were African American, and the mean estimated glomerular filtration rate was 42.5 ± 16.0 mL/min/1.73 m2. Predictor: Fasting DCA levels in Chronic Renal Insufficiency Cohort study participants. Outcomes: Risks of atherosclerotic and heart failure events, end-stage kidney disease (ESKD), and all-cause mortality. Analytical Approach: We used Tobit regression to identify predictors of DCA levels. We used Cox regression to examine the association between fasting DCA levels and clinical outcomes. Results: The strongest predictors of elevated DCA levels in adjusted models were increased age and nonuse of statins. The associations between log-transformed DCA levels and clinical outcomes were nonlinear. After adjustment, DCA levels above the median were independently associated with higher risks of ESKD (HR, 2.67; 95% CI, 1.51-4.74) and all-cause mortality (HR, 2.13; 95% CI, 1.25-3.64). DCA levels above the median were not associated with atherosclerotic and heart failure events, and DCA levels below the median were not associated with clinical outcomes. Limitations: We were unable to measure DCA longitudinally or in urinary or fecal samples, and we were unable to measure other bile acids. We also could not measure many factors that affect DCA levels. Conclusions: In 3,147 participants with CKD stages 2-4, DCA levels above the median were independently associated with ESKD and all-cause mortality.

Introduction: Although knee replacement is effective for improving pain and physical function, subsequent improvements in physical activity typically do not follow. As a result, many patients spend most of their day engaged in sedentary behavior, which may put them at higher risk of experiencing poor function and disability. Intervening on sedentary time, rather than physical activity, may be a more feasible first-step approach for modifying activity-related behaviors in adults who received knee replacement. Objective: The purpose of this study is to examine the use of a mobile health (mHealth) intervention to reduce sedentary time among adults who received a knee replacement at 3 and 6 months after surgery. Methods: Patients (n = 92) scheduled for knee replacement will be recruited and at 4 weeks after surgery, they will be randomized to either NEAT!2 or Control. NEAT!2 participants will use the NEAT!2 smartphone app, which provides a vibration and/or audible tone to interrupt prolonged bouts of sitting detected from the smartphone's internal accelerometer, until 3 months after surgery. NEAT!2 participants will receive biweekly coaching calls between 4 and 12 weeks after surgery. Control participants will receive an education control app and receive non-intervention calls to assess general surgery recovery. Both groups will receive 3 retention calls between 3 and 6 months. Data collection will occur pre-operatively and at 3 and 6 months after surgery. Discussion: The results of this study will help to determine whether an innovative remotely-delivered, mHealth sedentary reduction intervention can decrease sedentary time in adults after knee replacement.

Abstract Background A number of challenges impede our ability to consistently provide high quality care to patients hospitalized with medical conditions. Teams are large, team membership continually evolves, and physicians are often spread across multiple units and floors. Moreover, patients and family members are generally poorly informed and lack opportunities to partner in decision making. Prior studies have tested interventions to redesign aspects of the care delivery system for hospitalized medical patients, but the majority have evaluated the effect of a single intervention. We believe these interventions represent complementary and mutually reinforcing components of a redesigned clinical microsystem. Our specific objective for this study is to implement a set of evidence-based complementary interventions across a range of clinical microsystems, identify factors and strategies associated with successful implementation, and evaluate the impact on quality. Methods The RESET project uses the Advanced and Integrated MicroSystems (AIMS) interventions. The AIMS interventions consist of 1) Unit-based Physician Teams, 2) Unit Nurse-Physician Co-leadership, 3) Enhanced Interprofessional Rounds, 4) Unit-level Performance Reports, and 5) Patient Engagement Activities. Four hospital sites were chosen to receive guidance and resources as they implement the AIMS interventions. Each study site has assembled a local leadership team, consisting of a physician and nurse, and receives mentorship from a physician and nurse with experience in leading similar interventions. Primary outcomes include teamwork climate, assessed using the Safety Attitudes Questionnaire, and adverse events using the Medicare Patient Safety Monitoring System (MPSMS). RESET uses a parallel group study design and two group pretest-posttest analyses for primary outcomes. We use a multi-method approach to collect and triangulate qualitative data collected during 3 visits to study sites. We will use cross-case comparisons to consider how site-specific contextual factors interact with the variation in the intensity and fidelity of implementation to affect teamwork and patient outcomes. Discussion The RESET study provides mentorship and resources to assist hospitals as they implement complementary and mutually reinforcing components to redesign the clinical microsystems caring for medical patients. Our findings will be of interest and directly applicable to all hospitals providing care to patients with medical conditions. Trial registration NCT03745677. Retrospectively registered on November 19, 2018.

Abstract Objective Examine whether pre‐intervention physical activity (PA) level is associated with achieving a positive treatment response of pain and/or function improvement after a 12‐week exercise intervention in participants with knee osteoarthritis (OA). Methods We performed a secondary analysis of a randomized, single‐blind comparative effectiveness trial showing similar treatment effects between Tai Chi mind‐body exercise and standard physical therapy intervention for knee OA. Baseline PA was assessed by a Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire and, in a subsample, by tri‐axial accelerometers. The Outcome Measures in Rheumatoid Arthritis Clinical Trials–Osteoarthritis Research Society International (OMERACT‐OARSI) dichotomous responder criteria was used for clinically meaningful improvement at follow‐up. Associations between baseline self‐reported PA by the CHAMPS questionnaire and outcomes of responders vs. nonresponders (reference group) were assessed using logistic regressions, adjusting for demographic covariates. We compared objectively measured PA by accelerometry between responders vs. nonresponders using Wilcoxon tests. Results Our sample consisted of 166 participants with knee OA who completed both baseline and 12‐week postintervention evaluations: mean age 60.7 year (SD 10.5), body mass index 32.4 kg/m2 (6.9), 119 (72%) women, and 138 (83%) OMERACT‐OARSI responders. Neither time spent in total PA [odds ratio (OR) 1.00; 95% confidence interval (CI) 0.96, 1.03] nor time in moderate‐to‐vigorous PA (OR 1.01; 95% CI 0.93, 1.09) at pre‐intervention were associated with being a responder. Similar findings were observed in 42 accelerometry sub‐cohort participants. Conclusion Pre‐intervention PA levels (subjective report or objective measurement) were not associated with individuals achieving favorable treatment outcomes after a 12‐week exercise intervention, which suggests that regardless of pre‐intervention PA level, individuals will likely benefit from structured exercise interventions.

Introduction: Abnormalities in lipid metabolism may contribute to the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes. Fenofibrate induces early and reversible reduction in estimated glomerular filtration rate (eGFR), but it may have protective effects on microvascular complications of diabetes. We hypothesized that randomization to fenofibrate versus placebo would be associated with beneficial long-term effects on kidney outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants. Methods: We conducted a post hoc analysis in the ACCORD Lipid Trial to examine the association of randomization to fenofibrate versus placebo with change in eGFR and with time-to-development of microalbuminuria, macroalbuminuria, CKD, and kidney failure. Results: We analyzed 2636 participants in the fenofibrate arm and 2632 in the placebo arm. During a median follow-up of 4 years, treatment with fenofibrate was associated with lower rate of eGFR decline (−0.28 ml/min per 1.73 m2 per year in the fenofibrate group vs. −1.25 ml/min per 1.73 m2 per year in the placebo group, P < 0.01) and with lower incidence of microalbuminuria (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.43–0.72, P < 0.001) and macroalbuminuria (HR 0.72, 95% CI 0.57–0.91, P < 0.001). There was no difference in incidence of CKD (HR 0.92, 95% CI 0.74–1.15, P = 0.46) and/or kidney failure (HR 0.95, 95% CI 0.68–1.33, P = 0.76). Conclusion: Compared with placebo, randomization to fenofibrate was associated with lower rates of incident albuminuria and a slower eGFR decline, but no difference in incidence of CKD or kidney failure in ACCORD participants. Keywords: albuminuria, chronic kidney disease, diabetic nephropathy, fenofibrate, kidney failure

Abstract Background The shortage of organs for kidney transplantation for patients with end-stage renal disease (ESRD) is magnified in Hispanics/Latin Americans in the United States. Living donor kidney transplantation (LDKT) is the treatment of choice for ESRD. However, compared to their representation on the transplant waitlist, fewer Hispanics receive a LDKT than non-Hispanic whites. Barriers to LDKT for Hispanics include: lack of knowledge, cultural concerns, and language barriers. Few interventions have been designed to reduce LDKT disparities. This study aims to reduce Hispanic disparities in LDKT through a culturally targeted intervention. Methods/Design Using a prospective effectiveness-implementation hybrid design involving pre-post intervention evaluation with matched controls, we will implement a complex culturally targeted intervention at two transplant centers in Dallas, TX and Phoenix, AZ. The goal of the study is to evaluate the effect of Northwestern Medicine’s® Hispanic Kidney Transplant Program’s (HKTP) key culturally targeted components (outreach, communication, education) on Hispanic LDKT rates over five years. The main hypothesis is that exposure to the HKTP will reduce disparities by increasing the ratio of Hispanic to non-Hispanic white LDKTs and the number of Hispanic LDKTs. We will also examine other process and outcome measures including: dialysis patient outreach, education session attendance, marketing efforts, Hispanic patients added to the waitlist, Hispanic potential donors per potential recipient, and satisfaction with culturally competent care. We will use mixed methods based on the Promoting Action on Research Implementation in Health Services (revised PARIHS) and the Consolidated Framework for Implementation Research (CFIR) frameworks to formatively evaluate the fidelity and innovative adaptations to HKTP’s components at both study sites, to identify moderating factors that most affect implementation fidelity, and to identify adaptations that positively and negatively affect outcomes for patients. Discussion Our study will provide new knowledge about implementing culturally targeted interventions and their impact on reducing health disparities. Moreover, the study of a complex organizational-level intervention’s implementation over five years is rare in implementation science; as such, this study is poised to contribute new knowledge to the factors influencing how organizational-level interventions are sustained over time. Trial registration (ClinicalTrials.gov registration # NCT03276390, date of registration: 9–7-17, retrospectively registered)

Systemic sclerosis (SSc) is a fibrotic disease affecting multiple organs. Here the authors use patient samples plus mouse studies to show a central role for tenascin C as a TLR4 activator responsible for persistence of fibrosis in the context of SSc and SSc-like disease.

Inflammation in systemic sclerosis (SSc) is a prominent, but incompletely characterized feature in early stages of the disease. The goal of these studies was to determine the circulating levels, clinical correlates and biological effects of the acute phase protein serum amyloid A (SAA), a marker of inflammation, in patients with SSc. Circulating levels of SAA were determined by multiplex assays in serum from 129 SSc patients and 98 healthy controls. Correlations between SAA levels and clinical and laboratory features of disease were analyzed. The effects of SAA on human pulmonary fibroblasts were studied ex vivo. Elevated levels of SAA were found in 25% of SSc patients, with the highest levels in those with early-stage disease and diffuse cutaneous involvement. Significant negative correlations of SAA were found with forced vital capacity and diffusion capacity for carbon monoxide. Patients with elevated SAA had greater dyspnea and more frequent interstitial lung disease, and had worse scores on patient-reported outcome measures. Incubation with recombinant SAA induced dose-dependent stimulation of IL-6 and IL-8 in normal lung fibroblasts in culture. Serum levels of the inflammatory marker SAA are elevated in patients with early diffuse cutaneous SSc, and correlate with pulmonary involvement. In lung fibroblasts, SAA acts as a direct stimulus for increased cytokine production. These findings suggest that systemic inflammation in SSc may be linked to lung involvement and SAA could serve as a potential biomarker for this complication.

Background: Reduction in door-to-needle (DTN) times in patients with acute ischemic stroke treated with tissue-type plasminogen activator is associated with improved outcomes. We hypothesized that a learning collaborative would rapidly reduce DTN times at Chicago's primary stroke centers.Methods and Results: We analyzed data from all adult patients with out-of-hospital ischemic stroke hospitalized between January 1, 2010 and March 31, 2015 and who received tissue-type plasminogen activator in the emergency department at 15 primary stroke centers in Chicago and 15 primary stroke centers in St. Louis. We implemented a structured learning collaborative in Chicago in quarter 1 of 2013 that included (1) a quality improvement leader, (2) stroke content expert, (3) multidisciplinary teams from each site, (4) a targeted goal for the program (DTN time <60 minutes in >50% of patients treated with tissue-type plasminogen activator), and (5) face-to-face meetings with on-site visits. We used interrupted time-series analysis to compare the impact of the learning collaborative on DTN times in Chicago pre- and post implementation and also concurrently versus St. Louis. We prespecified adjustment for mode of arrival, emergency medical services prenotification, and onset-to-arrival times. P values less than 0.05 were considered significant. In adjusted analysis, the reduction in DTN time within 1 quarter of implementation was 15.5 minutes (P=0.046) at Chicago sites versus 1.17 minutes at St. Louis sites (P=0.601).Conclusions: Using a learning collaborative model at Chicago's 15 primary stroke centers, we observed major reductions in DTN times within 1 quarter of implementation. Regional collaboration and best practices sharing should be a model for rapid and sustainable system-wide quality improvement. [ABSTRACT FROM AUTHOR]

Elevated levels of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23) have been linked to greater risk of fractures in some studies, especially among individuals with chronic kidney disease (CKD). We evaluated FGF23 as a risk factor for bone loss and fractures in the Health, Aging, and Body Composition (Health ABC) study, which is a prospective biracial cohort of well-functioning adults aged 70 to 79 years recruited at two clinical centers in the United States. The sample for the bone mineral density (BMD) analyses consisted of 2234 participants who had at least two serial total hip areal BMD measures. The fracture analyses included 2786 participants, 567 of whom sustained a fracture during a median follow up of 4.95 years. Linear mixed-effects models were used for longitudinal measurements of total hip areal BMD and the proportional subdistribution hazard regression model subject to competing risks of death was used for risk of fracture. The median FGF23 was 46.7 (interquartile range [IQR] 36.7 to 60.2) pg/mL. The mean annualized percent change in total hip areal BMD did not vary significantly according to FGF23 quartile in all participants (p for trend=0.70), but the effect was modified by CKD status (adjusted p for interaction <0.001). Among participants with CKD, the unadjusted mean annualized percent change in total hip areal BMD was greater with higher levels of FGF23 (unadjusted p for trend=0.02), but the trend was attenuated with adjustment for estimated glomerular filtration rate and parathyroid hormone (adjusted p for trend=0.30). FGF23 was not significantly associated with fracture risk in crude (hazard ratio [HR] per doubling of FGF23, 0.97; 95% CI, 0.85 to 1.12) or adjusted models (HR per doubling of FGF23, 1.02; 95% CI, 0.86 to 1.22), and these findings were not modified by gender or CKD status. FGF23 levels are not associated with bone loss or fracture risk in older adults with low prevalence of CKD. [ABSTRACT FROM AUTHOR]

Background: Analytic methodology for investigating physical activity patterns over time has been limited. The aim of this study was to demonstrate the group-based trajectory analysis process for identifying developmental physical activity (PA) and television (TV) viewing trajectories and the risk factor of PA trajectories, and for examining a relationship between PA and TV viewing trajectories among adolescent girls. Methods: Secondary analysis was conducted using the National Growth and Health Study (NGHS) dataset. The NGHS administered the Habitual Activity Questionnaire and TV viewing questionnaire to White and Black girls at age 10, 12, 14, 16, 17, 18, and 19 years. Group-based trajectory analyses were conducted to identify distinct PA trajectories. Race was chosen to present an example of the risk factor analysis and was added as a predictor in the trajectory model. Dual-trajectory analysis was conducted to estimate probabilities of TV viewing trajectory groups conditional on the PA trajectory groups. Results: A total of 2,155 girls (52 % Black) were included in the data analysis. We identified four PA trajectories: substantially decreasing from high PA (PA group 1, 9.4 %), maintaining moderate PA (PA group 2, 31.6 %), maintaining high PA (PA group 3, 5.8 %), and decreasing from moderate PA (PA group 4, 53.2 %). A significantly lower proportion of Black girls had high PA levels at baseline and maintained their baseline PA than White girls. Most girls who were classified as maintaining high PA (88 %) were also classified as decreasing TV viewing. Conclusions: A group-based trajectory approach provides new insights about the patterns of maintaining moderate or high levels of PA that exist among adolescent girls. However, a lower proportion of Black girls followed the maintenance patterns than White girls. The behavioral development of PA and TV viewing may be intertwined among adolescent girls. [ABSTRACT FROM AUTHOR]

Objectives. This prospective longitudinal study investigated the association between baseline objectively measured sedentary time and 2-year onset of physical frailty. Methods. We studied 1333 Osteoarthritis Initiative participants 55 to 83 years of age who were at risk for physical frailty, as assessed via low gait speed (< 0.6 m per second) or inability to perform a single chair stand. Baseline sedentary time was assessed through accelerometer monitoring. Hazard ratios (HRs) for physical frailty onset were estimated with discrete survival methods that controlled for moderate physical activity, sociodemographic characteristics, baseline gait and chair stand functioning, and health factors. Results. The incidence of physical frailty in this high-risk group was 20.7 per 1000 person-years. Greater baseline sedentary time (adjusted HR = 1.36 per sedentary hour; 95% confidence interval [Cl] = 1.02, 1.79) was significantly related to incident physical frailty after control for time spent in moderate-intensity activities and other covariates. Conclusions. Our prospective data demonstrated a strong relationship between daily sedentary time and development of physical frailty distinct from insufficient moderate activity. Interventions that promote reductions in sedentary behaviors in addition to increases in physical activity may help decrease physical frailty onset. [ABSTRACT FROM AUTHOR]

Objectives. We examined whether objectively measured sedentary behavior is related to subsequent functional loss among community-dwelling adults with or at high risk for knee osteoarthritis. Methods. We analyzed longitudinal data (2008–2012) from 1659 Osteoarthritis Initiative participants aged 49 to 83 years in 4 cities. Baseline sedentary time was assessed by accelerometer monitoring. Functional loss (gait speed and chair stand testing) was regressed on baseline sedentary time and covariates (baseline function; socioeconomics [age, gender, race/ethnicity, income, education], health factors [obesity, depression, comorbidities, knee symptoms, knee osteoarthritis severity, prior knee injury, other lower extremity pain, smoking], and moderate-to-vigorous activity). Results. This cohort spent almost two thirds of their waking hours (average = 9.8 h) in sedentary behaviors. Sedentary time was significantly positively associated with subsequent functional loss in both gait speed (-1.66 ft/min decrease per 10% increment sedentary percentage waking hours) and chair stand rate (-0.75 repetitions/min decrease), controlling for covariates. Conclusions. Being less sedentary was related to less future decline in function, independent of time spent in moderate-to-vigorous activity. Both limiting sedentary activities and promoting physical activity in adults with knee osteoarthritis may be important in maintaining function. [ABSTRACT FROM AUTHOR]