Hospice Use Among Nursing Home Patients

Objectives Among hospice patients who lived in nursing homes, we sought to: (1) report trends in hospice use over time, (2) describe factors associated with very long hospice stays (>6 months), and (3) describe hospice utilization patterns. Design, setting, and participants We conducted a retrospective study from an urban, Midwest cohort of hospice patients, aged ≥65 years, who lived in nursing homes between 1999 and 2008. Measurements Demographic data, clinical characteristics, and health care utilization were collected from Medicare claims, Medicaid claims, and Minimum Data Set assessments. Patients with overlapping nursing home and hospice stays were identified. χ2 and t tests were used to compare patients with less than or longer than a 6-month hospice stay. Logistic regression was used to model the likelihood of being on hospice longer than 6 months. Results A total of 1452 patients received hospice services while living in nursing homes. The proportion of patients with noncancer primary hospice diagnoses increased over time; the mean length of hospice stay (114 days) remained high throughout the 10-year period. More than 90% of all patients had 3 or more comorbid diagnoses. Nearly 20% of patients had hospice stays longer than 6 months. The hospice patients with stays longer than 6 months were observed to have a smaller percentage of cancer (25% vs 30%) as a primary hospice diagnosis. The two groups did not differ by mean cognitive status scores, number of comorbidities, or activities of daily living impairments. The greater than 6 months group was much more likely to disenroll before death: 33.9% compared with 13.8% (P < .0001). A variety of patterns of utilization of hospice across settings were observed; 21 % of patients spent some of their hospice stay in the community. Conclusions Any policy proposals that impact the hospice benefit in nursing homes should take into account the difficulty in predicting the clinical course of these patients, varying utilization patterns and transitions across settings, and the importance of supporting multiple approaches for delivery of palliative care in this setting

Systematic Advance Care Planning and Potentially Avoidable Hospitalizations of Nursing Facility Residents

BACKGROUND/OBJECTIVES The Optimizing Patient Transfers, Impacting Medical Quality, Improving Symptoms: Transforming Institutional Care (OPTIMISTIC) project is a successful, multicomponent demonstration project to reduce potentially avoidable hospitalizations of long‐stay nursing facility residents. Systematic advance care planning (ACP) is a core component of the intervention, based on research suggesting ACP is associated with decreased hospitalizations of nursing facility residents. The purpose of this study was to describe associations between ACP documentation resulting from the OPTIMISTIC intervention and hospitalizations. DESIGN Specially trained project nurses were embedded in 19 nursing facilities and systematically engaged in ACP as part of a larger demonstration project. PARTICIPANTS Residents (n = 1482) enrolled in the demonstration project for a minimum of 30 days between January 1, 2015, and June 30, 2016. MEASUREMENTS ACP status: (1) Physician Orders for Scope of Treatment (POST) comfort measures or do not hospitalize (DNH) orders; (2) ACP orders with no hospitalization limit (eg, code status only); and (3) no ACP (potentially avoidable and all‐cause hospitalizations per 1000 resident days). RESULTS Residents with POST comfort measures/DNH orders (33.2% or n = 493) were less likely than residents with no ACP (14.7% or n = 218) to experience a potentially avoidable hospitalization (P = .001) or all‐cause hospitalization (P = .001). These differences became statistically nonsignificant after adjusting for age, functional status, and cognitive functioning. CONCLUSION In this successful multicomponent demonstration project to reduce potentially avoidable hospitalizations, ACP outcomes were not associated with hospitalization rates of nursing facility residents after adjusting for resident characteristics. These findings highlight the challenge of measuring the contributions of individual components of complex, multicomponent interventions. Associations between lower hospitalization rates and ACP completion may be influenced by contextual factors, such as clinical expertise and resources to manage acute conditions leading to hospitalization, in addition to interventions to increase ACP

Proteogenomic analysis reveals cytoplasmic sequestration of RUNX1 by the acute myeloid leukemia-initiating CBFB::MYH11 oncofusion protein

Several canonical translocations produce oncofusion genes that can initiate acute myeloid leukemia (AML). Although each translocation is associated with unique features, the mechanisms responsible remain unclear. While proteins interacting with each oncofusion are known to be relevant for how they act, these interactions have not yet been systematically defined. To address this issue in an unbiased fashion, we fused a promiscuous biotin ligase (TurboID) in-frame with 3 favorable-risk AML oncofusion cDNAs (PML::RARA, RUNX1::RUNX1T1, and CBFB::MYH11) and identified their interacting proteins in primary murine hematopoietic cells. The PML::RARA- and RUNX1::RUNX1T1-TurboID fusion proteins labeled common and unique nuclear repressor complexes, implying their nuclear localization. However, CBFB::MYH11-TurboID-interacting proteins were largely cytoplasmic, probably because of an interaction of the MYH11 domain with several cytoplasmic myosin-related proteins. Using a variety of methods, we showed that the CBFB domain of CBFB::MYH11 sequesters RUNX1 in cytoplasmic aggregates; these findings were confirmed in primary human AML cells. Paradoxically, CBFB::MYH11 expression was associated with increased RUNX1/2 expression, suggesting the presence of a sensor for reduced functional RUNX1 protein, and a feedback loop that may attempt to compensate by increasing RUNX1/2 transcription. These findings may have broad implications for AML pathogenesis

Using routinely collected data to understand and predict adverse outcomes in opioid agonist treatment:Protocol for the Opioid Agonist Treatment Safety (OATS) Study

INTRODUCTION: North America is amid an opioid use epidemic. Opioid agonist treatment (OAT) effectively reduces extramedical opioid use and related harms. As with all pharmacological treatments, there are risks associated with OAT, including fatal overdose. There is a need to better understand risk for adverse outcomes during and after OAT, and for innovative approaches to identifying people at greatest risk of adverse outcomes. The Opioid Agonist Treatment and Safety study aims to address these questions so as to inform the expansion of OAT in the USA. METHODS AND ANALYSIS: This is a retrospective cohort study using linked, routinely collected health data for all people seeking OAT in New South Wales, Australia, between 2001 and 2017. Linked data include hospitalisation, emergency department presentation, mental health diagnoses, incarceration and mortality. We will use standard regression techniques to model the magnitude and risk factors for adverse outcomes (eg, mortality, unplanned hospitalisation and emergency department presentation, and unplanned treatment cessation) during and after OAT, and machine learning approaches to develop a risk-prediction model. ETHICS AND DISSEMINATION: This study has been approved by the Population and Health Services Research Ethics Committee (2018HRE0205). Results will be reported in accordance with the REporting of studies Conducted using Observational Routinely-collected health Data statement

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

The contradictory politics of the right to travel: mobilities, borders & tourism

The freedom of movement and right to travel are intrinsic to the growth of international tourism. Notwithstanding the inchoate nature of the right to tourism, the entitlement to travel and to pursue tourism without hindrance is firmly established in advanced capitalist societies. Moreover, the right to tourism has been recently enshrined in the 2017 United Nations World Tourism Organisation (UNWTO) Framework Convention on Tourism Ethics. Tourists’ ease of mobility contrasts starkly with the movements of less privileged forms of mobility that may be variously constrained by racism, xenophobia and restrictive border controls. This paper contends that rather than a mere reflection of accumulated political rights (citizenship), such unequal and differentiated mobilities are conditioned by a complex assemblage of discursive frameworks and structural forces that are played out in specific historical-geographic contexts. Accordingly, we argue that the rights associated with global tourism must be analysed in the context of the contradictory politics of global mobility, or indeed in terms of the ‘mobility crisis’. This ‘crisis’ is one that is rooted in and shaped by the cumulative legacy of past colonial orders, global capitalism and geopolitical realignments, in addition to multi-scalar systems of governance through which borders are constituted, managed and policed

A steric tethering approach enables palladium-catalysed C-H activation of primary amino alcohols.

Aliphatic primary amines are a class of chemical feedstock essential to the synthesis of higher-order nitrogen-containing molecules, commonly found in biologically active compounds and pharmaceutical agents. New methods for the construction of complex amines remain a continuous challenge to synthetic chemists. Here, we outline a general palladium-catalysed strategy for the functionalization of aliphatic C-H bonds within amino alcohols, an important class of small molecule. Central to this strategy is the temporary conversion of catalytically incompatible primary amino alcohols into hindered secondary amines that are capable of undergoing a sterically promoted palladium-catalysed C-H activation. Furthermore, a hydrogen bond between amine and catalyst intensifies interactions around the palladium and orients the aliphatic amine substituents in an ideal geometry for C-H activation. This catalytic method directly transforms simple, easily accessible amines into highly substituted, functionally concentrated and structurally diverse products, and can streamline the synthesis of biologically important amine-containing molecules.We are grateful to the Marie Curie Foundation (D.P. & J.C.), EPSRC (T.W.G.), the ERC (V.D.), and the ERC and EPSRC for Fellowships (M.J.G.). We are grateful to Adam Smalley for DFT calculations and Yohei Shimidzu for assistance with optimization of the C–H acetoxylation reaction. Mass spectrometry data was acquired at the EPSRC UK National Mass Spectrometry Facility at Swansea University. The authors declare no competing financial interests.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nchem.236

Genome-wide association meta-analysis of age at first cannabis use

Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identify associations with genetic variants. A twin-based heritability analysis using 8,055 twins from three cohorts was performed. We then carried-out a genome wide survival meta-analysis of age at first cannabis use in a discovery sample of 24,953 individuals from nine European, North American, and Australian cohorts, and a replication sample of 3,735 individuals. The twin-based heritability for age at first cannabis use was 38% (95% confidence interval [CI] 19-60%). Shared and unique environmental factors explained 39% (95% CI 20-56%) and 22% (95% CI 16-29%). The genome wide survival meta-analysis identified five SNPs on chromosome 16 within the Calcium-transporting ATPase gene (ATP2C2) at P 0.8) with the strongest association at the intronic variant rs1574587 (P=4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P=1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been previously associated with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant. Age at cannabis initiation appears to be moderately heritable in Western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders

Why strict drug laws work (and why they do not)

&lt;!--StartFragment--&gt; &lt;p class="MsoNormal" style="margin-bottom: .0001pt; text-align: justify; line-height: normal;"&gt;&lt;span style="font-size: 13.0pt; font-family: Garamond;"&gt;Academic and scientific arguments in favour of the de-regulation of illicit drugs are usually made on the basis of the greater harm done by the laws than by the drugs themselves. This article argues that such claims miss a key point. They forget that drug policy is made for people from wealthy countries who do not and are not likely to take drugs. As such, arguments based on failed treatment programmes or on large-scale, organised drug crime often fall on the deaf ears of those who believe that strict drug laws help to keep them, and especially their children, off drugs. Advocates of drug de-regulation must take the interests and beliefs of this voting majority seriously if they wish to persuade politicians to ease their &amp;lsquo;war on drugs&amp;rsquo;.&lt;/span&gt;&lt;/p&gt; &lt;!--EndFragment--&gt