Factors Important to Older Adults Who Disagree With a Deprescribing Recommendation.

IMPORTANCE Little is known about why older adults decline deprescribing recommendations, primarily because interventional studies rarely capture the reasons. OBJECTIVE To examine factors important to older adults who disagree with a deprescribing recommendation given by a primary care physician to a hypothetical patient experiencing polypharmacy. DESIGN, SETTING, AND PARTICIPANTS This online, vignette-based survey study was conducted from December 1, 2020, to March 31, 2021, with participants 65 years or older in the United Kingdom, the US, Australia, and the Netherlands. The primary outcome of the main study was disagreement with a deprescribing recommendation. A content analysis was subsequently conducted of the free-text reasons provided by participants who strongly disagreed or disagreed with deprescribing. Data were analyzed from August 22, 2022, to February 12, 2023. MAIN OUTCOMES AND MEASURES Attitudes, beliefs, fears, and recommended actions of older adults in response to deprescribing recommendations. RESULTS Of the 899 participants included in the analysis, the mean (SD) age was 71.5 (4.9) years; 456 participants (50.7%) were men. Attitudes, beliefs, and fears reported by participants included doubts about deprescribing (361 [40.2%]), valuing medications (139 [15.5%]), and a preference to avoid change (132 [14.7%]). Valuing medications was reported more commonly among participants who strongly disagreed compared with those who disagreed with deprescribing (48 of 205 [23.4%] vs 91 of 694 [13.1%], respectively; P < .001) or had personal experience with the same medication class as the vignette compared with no experience (93 of 517 [18.0%] vs 46 of 318 [12.1%], respectively; P = .02). Participants shared that improved communication (225 [25.0%]), alternative strategies (138 [15.4%]), and consideration of medication preferences (137 [15.2%]) may increase their agreement with deprescribing. Participants who disagreed compared with those who strongly disagreed were more interested in additional communication (196 [28.2%] vs 29 [14.2%], respectively; P < .001), alternative strategies (117 [16.9%] vs 21 [10.2%], respectively; P = .02), or consideration of medication preferences (122 [17.6%] vs 15 [7.3%], respectively; P < .001). CONCLUSIONS AND RELEVANCE In this survey study, older adults who disagreed with a deprescribing recommendation were more interested in additional communication, alternative strategies, or consideration of medication preferences compared with those who strongly disagreed. These findings suggest that identifying the degree of disagreement with deprescribing could be used to tailor patient-centered communication about deprescribing in older adults

Australia\u27s health 2006 : the tenth biennial report of the Australian Institute of Health and Welfare

The report shows that Australians generally have good health and are privileged to have a range of health care services available to them. There are stark exceptions to this that can be confronting&mdash;even if well-known already&mdash;notably the generally much poorer health status of Indigenous Australians.Health care service provider and funding arrangements are both increasingly complex and increasingly costly to both individuals and taxpayers. A continuing challenge is how to balance both the complementary and competitive perspectives of government and non-government agencies, professional groups, and small businesses. Overall, national expenditure on health was 9.7% of GDP in 2003&ndash;04; and average health expenditure per person has grown by an average 3.8% each year between 1997&ndash;98 to 2002&ndash;03. Expenditure on aids and appliances, health research and pharmaceuticals contributed more to this growth than other areas.While the ageing of the population is having a significant impact on the number and type of health care services delivered, high quality services for children continue to be a priority. Australia&rsquo;s health 2006 has a special chapter focusing on children and their health. The chapter highlights the fact that while our children are generally very healthy, there are concerns that their ongoing health could be affected by more and more of them becoming overweight or obese. Levels of diabetes are now rising among our children and it is a continuing concern that asthma and mental health problems affect so many of them.<br /

Searching for Inflow Towards Massive Starless Clump Candidates Identified in the Bolocam Galactic Plane Survey

Recent Galactic plane surveys of dust continuum emission at long wavelengths have identified a population of dense, massive clumps with no evidence for on-going star formation. These massive starless clump candidates are excellent sites to search for the initial phases of massive star formation before the feedback from massive star formation effects the clump. In this study, we search for the spectroscopic signature of inflowing gas toward starless clumps, some of which are massive enough to form a massive star. We observed 101 starless clump candidates identified in the Bolocam Galactic Plane Survey (BGPS) in HCO+ J = 1-0 using the 12m Arizona Radio Observatory telescope. We find a small blue excess of E = (Nblue - Nred)/Ntotal = 0.03 for the complete survey. We identified 6 clumps that are good candidates for inflow motion and used a radiative transfer model to calculate mass inflow rates that range from 500 - 2000 M /Myr. If the observed line profiles are indeed due to large-scale inflow motions, then these clumps will typically double their mass on a free fall time. Our survey finds that massive BGPS starless clump candidates with inflow signatures in HCO+ J = 1-0 are rare throughout our Galaxy.Comment: 14 pages, 9 figure

Australia\u27s health 2004 : the ninth biennial report of the Australian Institute of Health and Welfare

Australia\u27s Health 2004 is the ninth biennial health report of the Australian Institute of Health and Welfare. It is the nation\u27s authoritative source of information on patterns of health and illness, determinants of health, the supply and use of health services, and health services expenditure. The report also includes a special chapter on the health of older Australians. Australia\u27s Health 2004 is an essential reference and information resource for all Australians with an interest in health

Can Machines Learn Morality? The Delphi Experiment

As AI systems become increasingly powerful and pervasive, there are growing concerns about machines' morality or a lack thereof. Yet, teaching morality to machines is a formidable task, as morality remains among the most intensely debated questions in humanity, let alone for AI. Existing AI systems deployed to millions of users, however, are already making decisions loaded with moral implications, which poses a seemingly impossible challenge: teaching machines moral sense, while humanity continues to grapple with it. To explore this challenge, we introduce Delphi, an experimental framework based on deep neural networks trained directly to reason about descriptive ethical judgments, e.g., "helping a friend" is generally good, while "helping a friend spread fake news" is not. Empirical results shed novel insights on the promises and limits of machine ethics; Delphi demonstrates strong generalization capabilities in the face of novel ethical situations, while off-the-shelf neural network models exhibit markedly poor judgment including unjust biases, confirming the need for explicitly teaching machines moral sense. Yet, Delphi is not perfect, exhibiting susceptibility to pervasive biases and inconsistencies. Despite that, we demonstrate positive use cases of imperfect Delphi, including using it as a component model within other imperfect AI systems. Importantly, we interpret the operationalization of Delphi in light of prominent ethical theories, which leads us to important future research questions

Inhibition of iNOS as a Novel Effective Targeted Therapy Against Triple-Negative Breast Cancer

INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with no effective targeted therapy. Inducible nitric oxide synthase (iNOS) is associated with poor survival in patients with breast cancer by increasing tumor aggressiveness. This work aimed to investigate the potential of iNOS inhibitors as a targeted therapy for TNBC. We hypothesized that inhibition of endogenous iNOS would decrease TNBC aggressiveness by reducing tumor initiation and metastasis through modulation of epithelial-mesenchymal transition (EMT)-inducing factors. METHODS: iNOS protein levels were determined in 83 human TNBC tissues and correlated with clinical outcome. Proliferation, mammosphere-forming efficiency, migration, and EMT transcription factors were assessed in vitro after iNOS inhibition. Endogenous iNOS targeting was evaluated as a potential therapy in TNBC mouse models. RESULTS: High endogenous iNOS expression was associated with worse prognosis in patients with TNBC by gene expression as well as immunohistochemical analysis. Selective iNOS (1400 W) and pan-NOS (L-NMMA and L-NAME) inhibitors diminished cell proliferation, cancer stem cell self-renewal, and cell migration in vitro, together with inhibition of EMT transcription factors (Snail, Slug, Twist1, and Zeb1). Impairment of hypoxia-inducible factor 1α, endoplasmic reticulum stress (IRE1α/XBP1), and the crosstalk between activating transcription factor 3/activating transcription factor 4 and transforming growth factor β was observed. iNOS inhibition significantly reduced tumor growth, the number of lung metastases, tumor initiation, and self-renewal. CONCLUSIONS: Considering the effectiveness of L-NMMA in decreasing tumor growth and enhancing survival rate in TNBC, we propose a targeted therapeutic clinical trial by re-purposing the pan-NOS inhibitor L-NMMA, which has been extensively investigated for cardiogenic shock as an anti-cancer therapeutic

Allogeneic stem cell transplant in patients with acute myeloid leukemia and karnofsky performance status score less than or equal to 80% : A study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation (EBMT)

Limited data are currently available on the outcome of patients with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplantation (allo-SCT) with a reduced performance status. We herein present the results of a registry study on 2,936 AML patients undergoing allo-SCT in first remission (CR1) with a Karnofsky Performance Status (KPS) score less than or equal to 80%. Two-year leukemia-free survival (LFS), overall survival (OS) and graft-versus-host disease (GVHD)-free, and relapse-free survival (GRFS) rates were 54%, 59%, and 41%, respectively. In multivariable analysis, patients with a KPS score = 80% had lower non-relapse mortality (NRM) and superior OS in comparison to patients with a KPS scorePeer reviewe

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against &gt;100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology