Reducing the Risk of Hospitalization for Nursing Home Residents: Effects and Facility Variation From OPTIMISTIC

Objectives The Optimizing Patient Transfers, Impacting Medical Quality, and Improving Symptoms: Transforming Institutional Care (OPTIMISTIC) project led to significant decreases in potentially avoidable hospitalizations of long-stay nursing facility residents in external evaluation. The purpose of this study was to quantify hospitalization risk from the start of the project and describe the heterogeneity of the enrolled facilities in order to better understand the context for successful implementation. Design Pre-post analysis design of a prospective intervention within a single group. Setting and Participants A total of 4320 residents in the 19 facilities were included from admission until time to the first hospitalization. Measures Data were extracted from Minimum Data Set assessments and linked with facility-level covariates from the LTCFocus.org data set. Kaplan-Meier and Cox proportional hazards regression were used to assess risk of hospitalization during the preintervention period (2011-2012), a “ramp-up” period (2013-2014), and an intervention period (2015-2016). Results The cohort consisted of 4230 long-stay nursing facility residents. Compared with the preintervention period, residents during the intervention period had an increased probability of having no hospitalizations within 1 year, increasing from 0.51 to 0.57, which was statistically significant ( P < .001). In adjusted Cox models, the risk of hospitalization was lower in the ramp-up period compared to the pre-period [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.75-0.95] and decreased further during the intervention period (HR 0.74, 95% CI 0.65-0.84). Conclusions and Implications As part of a large multisite demonstration project, OPTIMISTIC has successfully reduced hospitalizations. However, this study highlights the magnitude and extent to which results differ across facilities. Implementing the OPTIMISTIC program was associated with a 16% risk reduction after the first 18 months and continued to a final risk reduction of 26% after 5½ years. Although this model of care reduces hospitalizations overall, facility variation should be expected

Facility and resident characteristics associated with variation in nursing home transfers: evidence from the OPTIMISTIC demonstration project

Background: Centers for Medicare and Medicaid Services (CMS) funded demonstration project to evaluate financial incentives for nursing facilities providing care for 6 clinical conditions to reduce potentially avoidable hospitalizations (PAHs). The Optimizing Patient Transfers, Impacting Medical Quality, and Improving Symptoms: Transforming Institutional Care (OPTIMISTIC) site tested payment incentives alone and in combination with the successful nurse-led OPTIMISTIC clinical model. Our objective was to identify facility and resident characteristics associated with transfers, including financial incentives with or without the clinical model. Methods: This was a longitudinal analysis from April 2017 to June 2018 of transfers among nursing home residents in 40 nursing facilities, 17 had the full clinical + payment model (1726 residents) and 23 had payment only model (2142 residents). Using CMS claims data, the Minimum Data Set, and Nursing Home Compare, multilevel logit models estimated the likelihood of all-cause transfers and PAHs (based on CMS claims data and ICD-codes) associated with facility and resident characteristics. Results: The clinical + payment model was associated with 4.1 percentage points (pps) lower risk of all-cause transfers (95% confidence interval [CI] - 6.2 to - 2.1). Characteristics associated with lower PAH risk included residents aged 95+ years (- 2.4 pps; 95% CI - 3.8 to - 1.1), Medicare-Medicaid dual-eligibility (- 2.5 pps; 95% CI - 3.3 to - 1.7), advanced and moderate cognitive impairment (- 3.3 pps; 95% CI - 4.4 to - 2.1; - 1.2 pps; 95% CI - 2.2 to - 0.2). Changes in Health, End-stage disease and Symptoms and Signs (CHESS) score above most stable (CHESS score 4) increased the risk of PAH by 7.3 pps (95% CI 1.5 to 13.1). Conclusions: Multiple resident and facility characteristics are associated with transfers. Facilities with the clinical + payment model demonstrated lower risk of all-cause transfers compared to those with payment only, but not for PAHs

Age-specific rates of hospital transfers in long-stay nursing home residents

Introduction hospital transfers and admissions are critical events in the care of nursing home residents. We sought to determine hospital transfer rates at different ages. Methods a cohort of 1,187 long-stay nursing home residents who had participated in a Centers for Medicare and Medicaid demonstration project. We analysed the number of hospital transfers of the study participants recorded by the Minimum Data Set. Using a modern regression technique, we depicted the annual rate of hospital transfers as a smooth function of age. Results transfer rates declined with age in a nonlinear fashion. Rates were the highest among residents younger than 60 years of age (1.30-2.15 transfers per year), relatively stable between 60 and 80 (1.17-1.30 transfers per year) and lower in those older than 80 (0.77-1.17 transfers per year). Factors associated with increased risk of transfers included prior diagnoses of hip fracture (annual incidence rate ratio or IRR: 2.057, 95% confidence interval (CI): [1.240, 3.412]), dialysis (IRR: 1.717, 95% CI: [1.313, 2.246]), urinary tract infection (IRR: 1.755, 95% CI: [1.361, 2.264]), pneumonia (IRR: 1.501, 95% CI: [1.072, 2.104]), daily pain (IRR: 1.297, 95% CI: [1.055,1.594]), anaemia (IRR: 1.229, 95% CI [1.068, 1.414]) and chronic obstructive pulmonary disease (IRR: 1.168, 95% CI: [1.010,1.352]). Transfer rates were lower in residents who had orders reflecting preferences for comfort care (IRR: 0.79, 95% CI: [0.665, 0.936]). Discussion younger nursing home residents may require specialised interventions to reduce hospital transfers; declining transfer rates with the oldest age groups may reflect preferences for comfort-focused care

Randomised, open-label, phase II study of Gemcitabine with and without IMM-101 for advanced pancreatic cancer

Background: Immune Modulation and Gemcitabine Evaluation-1, a randomised, open-label, phase II, first-line, proof of concept study (NCT01303172), explored safety and tolerability of IMM-101 (heat-killed Mycobacterium obuense; NCTC 13365) with gemcitabine (GEM) in advanced pancreatic ductal adenocarcinoma. Methods: Patients were randomised (2 : 1) to IMM-101 (10 mg ml−l intradermally)+GEM (1000 mg m−2 intravenously; n=75), or GEM alone (n=35). Safety was assessed on frequency and incidence of adverse events (AEs). Overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) were collected. Results: IMM-101 was well tolerated with a similar rate of AE and serious adverse event reporting in both groups after allowance for exposure. Median OS in the intent-to-treat population was 6.7 months for IMM-101+GEM v 5.6 months for GEM; while not significant, the hazard ratio (HR) numerically favoured IMM-101+GEM (HR, 0.68 (95% CI, 0.44–1.04, P=0.074). In a pre-defined metastatic subgroup (84%), OS was significantly improved from 4.4 to 7.0 months in favour of IMM-101+GEM (HR, 0.54, 95% CI 0.33–0.87, P=0.01). Conclusions: IMM-101 with GEM was as safe and well tolerated as GEM alone, and there was a suggestion of a beneficial effect on survival in patients with metastatic disease. This warrants further evaluation in an adequately powered confirmatory study

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Localisation and Function of the Endocannabinoid System in the Human Ovary

Although anandamide (AEA) had been measured in human follicular fluid and is suggested to play a role in ovarian follicle and oocyte maturity, its exact source and role in the human ovary remains unclear.Immunohistochemical examination of normal human ovaries indicated that the endocannabinoid system was present and widely expressed in the ovarian medulla and cortex with more intense cannabinoid receptor 2 (CB2) than CB1 immunoreactivity in the granulosa cells of primordial, primary, secondary, tertiary follicles, corpus luteum and corpus albicans. The enzymes, fatty acid amide hydrolase (FAAH) and N-acyclphosphatidylethanolamine-phospholipase D (NAPE-PLD), were only found in growing secondary and tertiary follicles and corpora lutea and albicantes. The follicular fluid (FF) AEA concentrations of 260 FF samples, taken from 37 infertile women undergoing controlled ovarian hyperstimulation for in vitro fertilisation and intracytoplasmic sperm injection with embryo transfer, were correlated with ovarian follicle size (P = 0.03). Significantly higher FF AEA concentrations were also observed in mature follicles (1.43+/-0.04 nM; mean+/-SEM) compared to immature follicles (1.26+/-0.06 nM), P = 0.0142 and from follicles containing morphologically assessed mature oocytes (1.56+/-0.11 nM) compared to that containing immature oocytes (0.99+/-0.09 nM), P = 0.0011. ROC analysis indicated that a FF AEA level of 1.09 nM could discriminate between mature and immature oocytes with 72.2% sensitivity and 77.14% specificity, whilst plasma AEA levels and FF AEA levels on oocyte retrieval day were not significantly different (P = 0.23).These data suggest that AEA is produced in the ovary, is under hormonal control and plays a role in folliculogenesis, preovulatory follicle maturation, oocyte maturity and ovulation

The Genome Sequence of the Leaf-Cutter Ant Atta cephalotes Reveals Insights into Its Obligate Symbiotic Lifestyle

Leaf-cutter ants are one of the most important herbivorous insects in the Neotropics, harvesting vast quantities of fresh leaf material. The ants use leaves to cultivate a fungus that serves as the colony's primary food source. This obligate ant-fungus mutualism is one of the few occurrences of farming by non-humans and likely facilitated the formation of their massive colonies. Mature leaf-cutter ant colonies contain millions of workers ranging in size from small garden tenders to large soldiers, resulting in one of the most complex polymorphic caste systems within ants. To begin uncovering the genomic underpinnings of this system, we sequenced the genome of Atta cephalotes using 454 pyrosequencing. One prediction from this ant's lifestyle is that it has undergone genetic modifications that reflect its obligate dependence on the fungus for nutrients. Analysis of this genome sequence is consistent with this hypothesis, as we find evidence for reductions in genes related to nutrient acquisition. These include extensive reductions in serine proteases (which are likely unnecessary because proteolysis is not a primary mechanism used to process nutrients obtained from the fungus), a loss of genes involved in arginine biosynthesis (suggesting that this amino acid is obtained from the fungus), and the absence of a hexamerin (which sequesters amino acids during larval development in other insects). Following recent reports of genome sequences from other insects that engage in symbioses with beneficial microbes, the A. cephalotes genome provides new insights into the symbiotic lifestyle of this ant and advances our understanding of host–microbe symbioses

Overcoming leakage in scalable quantum error correction

Leakage of quantum information out of computational states into higher energy states represents a major challenge in the pursuit of quantum error correction (QEC). In a QEC circuit, leakage builds over time and spreads through multi-qubit interactions. This leads to correlated errors that degrade the exponential suppression of logical error with scale, challenging the feasibility of QEC as a path towards fault-tolerant quantum computation. Here, we demonstrate the execution of a distance-3 surface code and distance-21 bit-flip code on a Sycamore quantum processor where leakage is removed from all qubits in each cycle. This shortens the lifetime of leakage and curtails its ability to spread and induce correlated errors. We report a ten-fold reduction in steady-state leakage population on the data qubits encoding the logical state and an average leakage population of less than $1 \times 10^{-3}$ throughout the entire device. The leakage removal process itself efficiently returns leakage population back to the computational basis, and adding it to a code circuit prevents leakage from inducing correlated error across cycles, restoring a fundamental assumption of QEC. With this demonstration that leakage can be contained, we resolve a key challenge for practical QEC at scale.Comment: Main text: 7 pages, 5 figure