Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF) trial: Design and rationale.

BACKGROUND: Acute decompensated heart failure (ADHF) is a leading cause of hospitalization in older persons in the United States. Reduced physical function and frailty are major determinants of adverse outcomes in older patients with hospitalized ADHF. However, these are not addressed by current heart failure (HF) management strategies and there has been little study of exercise training in older, frail HF patients with recent ADHF. HYPOTHESIS: Targeting physical frailty with a multi-domain structured physical rehabilitation intervention will improve physical function and reduce adverse outcomes among older patients experiencing a HF hospitalization. STUDY DESIGN: REHAB-HF is a multi-center clinical trial in which 360 patients ≥60 years hospitalized with ADHF will be randomized either to a novel 12-week multi-domain physical rehabilitation intervention or to attention control. The goal of the intervention is to improve balance, mobility, strength and endurance utilizing reproducible, targeted exercises administered by a multi-disciplinary team with specific milestones for progression. The primary study aim is to assess the efficacy of the REHAB-HF intervention on physical function measured by total Short Physical Performance Battery score. The secondary outcome is 6-month all-cause rehospitalization. Additional outcome measures include quality of life and costs. CONCLUSIONS: REHAB-HF is the first randomized trial of a physical function intervention in older patients with hospitalized ADHF designed to determine if addressing deficits in balance, mobility, strength and endurance improves physical function and reduces rehospitalizations. It will address key evidence gaps concerning the role of physical rehabilitation in the care of older patients, those with ADHF, frailty, and multiple comorbidities

Hemodynamic Predictors of Heart Failure Morbidity and Mortality: Fluid or Flow?

BACKGROUND: Patients with advanced heart failure may persist for prolonged times with persistent hemodynamic abnormalities; intermediate and long-term outcomes of these patients are unknown. METHODS AND RESULTS: We used ESCAPE trial data to examine characteristics and outcomes of patients with invasive hemodynamic monitoring during an acute heart failure hospitalization. Patients were stratified by final measurement of cardiac index (CI; L/min/m2) and pulmonary capillary wedge pressure (PCWP; mmHg) before catheter removal. The study groups were CI ≥ 2/PCWP <20 (n = 74), CI ≥ 2/PCWP ≥ 20 (n = 37), CI < 2/PCWP < 20 (n = 23), and CI < 2/PCWP ≥ 20 (n = 17). Final CI was not associated with the combined risk of death, cardiovascular hospitalization, and transplantation (HR:1.03, 95% CI:0.96–1.11 per 0.2 L/min/m(2) decrease, p=0.39), but final PCWP ≥ 20mmHg was associated with increased risk of these events (HR:2.03, 95% CI:1.31–3.15, p<0.01), as was higher final right atrial pressure (RAP; HR:1.09, 95% CI:1.06–1.12 per mmHg increase, p<0.01). CONCLUSION: Final PCWP and final RAP were stronger predictors of post-discharge outcomes than CI in patients with advanced heart failure. The ability to lower filling pressures appears to be more prognostically important than improving CI in the management of patients with advanced heart failure. CLINICALTRIALS.GOV IDENTIFIER: NCT0000061

Differences in health care use and outcomes by the timing of in-hospital worsening heart failure

BACKGROUND: Patients hospitalized with acute heart failure may experience worsening symptoms requiring escalation of therapy. In-hospital worsening heart failure is associated with worse in-hospital and postdischarge outcomes, but associations between the timing of worsening heart failure and outcomes are unknown. METHODS: Using data from a large clinical registry linked to Medicare claims, we examined characteristics, outcomes, and costs of patients hospitalized for acute heart failure. We defined in-hospital worsening heart failure by the use of inotropes or intravenous vasodilators or initiation of mechanical circulatory support, hemodialysis, or ventilation. The study groups were early worsening heart failure (n = 1,990), late worsening heart failure (n = 4,223), complicated presentation (n = 15,361), and uncomplicated hospital course (n = 41,334). RESULTS: Among 62,908 patients, those with late in-hospital worsening heart failure had higher in-hospital and postdischarge mortality than patients with early worsening heart failure or complicated presentation. Those with early or late worsening heart failure had more frequent all-cause and heart failure readmissions at 30 days and 1 year, with resultant higher costs, compared with patients with an uncomplicated hospital course. CONCLUSION: Although late worsening heart failure was associated with the highest mortality, both early and late worsening heart failures were associated with more frequent readmissions and higher health care costs compared to uncomplicated hospital course. Prevention of worsening heart failure may be an important focus in the care of hospitalized patients with acute heart failure

Particulate matter concentrations in residences: an intervention study evaluating stand‐alone filters and air conditioners

This study, a randomized controlled trial, evaluated the effectiveness of free‐standing air filters and window air conditioners (ACs) in 126 low‐income households of children with asthma. Households were randomized into a control group, a group receiving a free‐standing HEPA filter placed in the child’s sleeping area, and a group receiving the filter and a window‐mounted AC. Indoor air quality (IAQ) was monitored for week‐long periods over three to four seasons. High concentrations of particulate matter (PM) and carbon dioxide were frequently seen. When IAQ was monitored, filters reduced PM levels in the child’s bedroom by an average of 50%. Filter use varied greatly among households and declined over time, for example, during weeks when pollutants were monitored, filter use was initially high, averaging 84 ± 27%, but dropped to 63 ± 33% in subsequent seasons. In months when households were not visited, use averaged only 34 ± 30%. Filter effectiveness did not vary in homes with central or room ACs. The study shows that measurements over multiple seasons are needed to characterize air quality and filter performance. The effectiveness of interventions using free‐standing air filters depends on occupant behavior, and strategies to ensure filter use should be an integral part of interventions. Practical Implications Environmental tobacco smoke (ETS) increased particulate matter (PM) levels by about 14 μg/m 3 and was often detected using ETS‐specific tracers despite restrictions on smoking in the house as reported on questionnaires administered to caregivers. PM concentrations depended on season, filter usage, relative humidity, air exchange ratios, number of children, outdoor PM levels, sweeping/dusting, and presence of a central air conditioner (AC). Free‐standing air filters can be an effective intervention that provides substantial reductions in PM concentrations if the filters are used. However, filter use was variable across the study population and declined over the study duration, and thus strategies are needed to encourage and maintain use of filters. The variability in filter use suggests that exposure misclassification is a potential problem in intervention studies using filters. The installation of a room AC in the bedroom, intended to limit air exchange ratios, along with an air filter, did not lower PM levels more than the filter alone.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91183/1/j.1600-0668.2011.00761.x.pd

Optimizing Strategies to Improve Interprofessional Practice for Veterans, Part 1

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Introduction Interprofessional patient care is a well-recognized path that health care systems are striving toward. The Veteran’s Affairs (VA) system initiated interprofessional practice (IPP) models with their Geriatric Evaluation and Management (GEM) programs. GEM programs incorporate a range of specialties, including but not limited to, medicine, nursing, social work, physical therapy and pharmacy, to collaboratively evaluate veterans. Despite being a valuable resource, they are now faced with significant cut-backs, including closures. The primary goal of this project was to assess how the GEM model could be optimized at the Pittsburgh, Pennsylvania VA to allow for the sustainability of this important IPP assessment. Part 1 of the study evaluated the IPP process using program, patient, and family surveys. Part 2 examined how well the geriatrician matched patients to specialists in the GEM model. This paper describes Part 1 of our study. Methods Three strategies were used: 1) a national GEM program survey; 2) a veteran/family satisfaction survey; and 3) an absentee assessment. Results Twenty-six of 92 programs responded to the GEM IPP survey. Six strategies were shared to optimize IPP models throughout the country. Of the 34 satisfaction surveys, 80% stated the GEM clinic was beneficial, 79% stated their concerns were addressed, and 100% would recommend GEM to their friends. Of the 24 absentee assessments, the top three reasons for missing the appointments were transportation, medical illnesses, and not knowing/remembering about the appointment. Absentee rate diminished from 41% to 19% after instituting a reminder phone call policy. Discussion Maintaining the sustainability of IPP programs is crucial for the health of our veterans. This project uncovered tools to improve the GEM IPP model for our veterans that can be incorporated nationally. Despite the lengthy nature of IPP models, patients and families appreciated the thoroughness, requested transportation and food, and responded well to reminder phone calls. A keen eye on these issues and concomitant medical complexity needs to be observed when planning IPP models to ensure sustainability

Private trade and monopoly structures : the East India Companies and the commodity trade to Europe in the eighteenth century

Our research is about the trade in material goods from Asia to Europe over this period, and its impact on Europe’s consumer and industrial cultures. It entails a comparative study of Europe’s East India Companies and the private trade from Asia over the period. The commodities trade was heavily dependent on private trade. The historiography to date has left a blind spot in this area, concentrating instead on corruption and malfeasance. Taking a global history approach we investigate the trade in specific consumer goods in many qualities and varieties that linked merchant communities and stimulated information flows. We set out how private trade functioned alongside and in connection with the various European East India companies; we investigate how this changed over time, how it drew on the Company infrastructure, and how it took the risks and developed new and niche markets for specific Asian commodities that the Companies could not sustain

Screening of brazilian plants for the presence of peroxides

Extratos clorofórmicos ou diclorometânicos de 357 espécies vegetais de ocorrência no sul do Brasil foram testados quanto à presença de peróxidos, através de cromatografia em camada delgada, utilizando o reagente de detecção de Huber & Fröhlke. Das espécies testadas, 71 (20%) apresentaram resultado positivo, a maioria delas (56%) pertencentes à família Asteraceae. A maioria das espécies testadas pertencia a Asteraceae, mas outras 55 famílias foram também testadas, abrangendo um total de 77 gêneros.Chloroform or dichloromethane extracts of 357 southern Brazilian plant species were tested for the presence of peroxides by thinlayer chromatography, using the spray reagent from Huber & Fröhlke. From the species tested, 71 (20%) showed positive results and most of them (56%) are Asteraceae species. The species tested were mainly from Asteraceae, but 55 more families were screened, in a total of 77 genera surveyed

Proteomic pathways across the ejection fraction spectrum in patients with heart failure and diabetes mellitus: an EXSCEL trial substudy

Ejection fraction (EF) is a key component of heart failure (HF) classification. However, the biologic basis of HF with mildly reduced EF (HFmrEF) as a distinct biologic entity distinct from HF with preserved EF (HFpEF) and reduced EF (HFrEF) has not been well characterized. The EXSCEL trial randomized participants with type 2 diabetes (T2DM) to a once-weekly glucagon-like peptide receptor agonist (GLP-1 RA) exenatide (EQW) vs. placebo. For this study, profiling of ~ 5000 proteins using the SomaLogic SomaScan platform was performed in baseline and 12-month serum samples from N = 1199 participants with prevalent HF at baseline. Unsupervised principal component analysis (PCA) and ANOVA (FDR p 55% [HFpEF], EF 40–55% [HFmrEF], EF < 40% [HFrEF], categories as previously curated in the parent trial). Cox proportional hazards was used to assess association between baseline levels of proteins significantly different between groups, and changes in protein level between baseline and 12-month, with time-to-HF hospitalization. Mixed models were used to assess whether significant proteins changed differentially with exenatide vs. placebo therapy. Of N = 1199 EXSCEL participants with prevalent HF, 284 (24%), 704 (59%) and 211 (18%) had HFpEF, HFmrEF and HFrEF, respectively. Eight principal components analysis (PCA) protein factors differed significantly across the three EF groups, of which 270 individual proteins within those factors were significant. The majority of proteins (75%) demonstrated similar levels in HFmrEF and HFpEF with higher levels in HFrEF. Biologic pathways of epithelial-mesenchymal transition, ECM receptor interaction (tenascin C [TNC], COL28A1), complement and coagulation cascades, and epithelial apical surface and junctions demonstrated enrichment among proteins with this dominant pattern. A minority of proteins (1%) demonstrated similar levels between HFmrEF and HFrEF with lower levels in HFpEF, including MMP-9 (p < 0.0001). Baseline levels of the majority of the 270 proteins (92%) were also associated with time-to-incident HF hospitalization including domains of extracellular matrix (COL28A1, TNC), angiogenesis (VEGFa, VEGFd), myocyte stretch (NT-proBNP), and renal function (cystatin-C). Change in levels of 8% of these from baseline to 12 months (including increase in TNC) predicted incident HF hospitalization (p < 0.05). Levels of 41% of the 270 significant proteins (including TNC and NT-proBNP; p < 0.0001) were reduced differentially by EQW compared with placebo. In conclusion, we found that serum levels of the vast majority of proteins across multiple biologic domains were similar between HFmrEF and HFpEF suggesting that HFmrEF may be more biologically similar to HFpEF than HFrEF. We also identified specific biomarkers showing this pattern, most notably TNC, for which baseline and change levels predicted incident HF hospitalization and were beneficially modified by the GLP-1 RA EQW. These results may offer unique data on prognosis and pharmacotherapy modification with variability by EF

Within-trial evaluation of medical resources, costs, and quality of life among patients with type 2 diabetes participating in the exenatide study of cardiovascular event lowering (EXSCEL)

OBJECTIVE To compare medical resource use, costs, and health utilities for 14,752 patients with type 2 diabetes who were randomized to once-weekly exenatide (EQW) or placebo in addition to usual diabetes care in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL). RESEARCH DESIGN AND METHODS Medical resource use data and responses to the EuroQol 5-Dimension (EQ-5D) instrument were collected at baseline and throughout the trial. Medical resources and medications were assigned values by using U.S. Medicare payments and wholesale acquisition costs, respectively. Secondary analyses used English costs. RESULTS Patients were followed for an average of 3.3 years, during which time those randomized to EQW experienced 0.41 fewer inpatient days (7.05 vs. 7.46 days; relative rate ratio 0.91; P = 0.05). Rates of outpatient medical visits were similar, as were total inpatient and outpatient costs. Mean costs for nonstudy diabetes medications over the study period were ∼USD 1,600 lower with EQW than with placebo (P = 0.01). Total within-study costs, excluding study medication, were lower in the EQW arm than in the placebo arm (USD 28,907 vs. USD 30,914; P ≤ 0.01). When including the estimated cost of EQW, total mean costs were significantly higher in the EQW group than in the placebo group (USD 42,697 vs. USD 30,914; P < 0.01). With English costs applied, mean total costs, including exenatide costs, were £1,670 higher in the EQW group than the placebo group (£10,874 vs. £9,204; P < 0.01). There were no significant differences in EQ-5D health utilities between arms over time. CONCLUSIONS Medical costs were lower in the EQW arm than the placebo arm, but total costs were significantly higher once the cost of branded exenatide was incorporated