Potential Quality Indicators for Seriously Ill Home Care Clients: A Cross-Sectional Analysis Using Resident Assessment Instrument for Home Care (RAI-HC) Data for Ontario

Background Currently, there are no formalized measures for the quality of home based palliative care in Ontario. This study developed a set of potential quality indicators for seriously ill home care clients using a standardized assessment. Methods Secondary analysis of Resident Assessment Instrument for Home Care data for Ontario completed between 2006 and 2013 was used to develop quality indicators (QIs) thought to be relevant to the needs of older (65+) seriously ill clients. QIs were developed through a review of the literature and consultation with subject matter experts in palliative care. Serious illness was defined as a prognosis of less than 6 months to live or the presence of severe health instability. The rates of the QIs were stratified across Ontario’s geographic regions, and across four common life-limiting illnesses to observe variation. Results Within the sample, 14,312 clients were considered to be seriously ill and were more likely to experience negative health outcomes such as cognitive performance (OR = 2.77; 95% CI: 2.66–2.89) and pain (OR = 1.59; 95% CI: 1.53–1.64). Twenty subject matter experts were consulted and a list of seven QIs was developed. Indicators with the highest overall rates were prevalence of falls (50%) prevalence of daily pain (47%), and prevalence of caregiver distress (42%). The range in QI rates was largest across regions for prevalence of caregiver distress (21.5%), the prevalence of falls (16.6%), and the prevalence of social isolation (13.7%). Those with some form of dementia were most likely to have a caregiver that was distressed (52.6%) or to experience a fall (53.3%). Conclusion Home care clients in Ontario who are seriously ill are experiencing high rates of negative health outcomes, many of which are amenable to change. The RAI-HC can be a useful tool in identifying these clients in order to better understand their needs and abilities. These results contribute significantly to the process of creating and validating a standardized set of QIs that can be generated by organizations using the RAI-HC as part of normal clinical practice

Dichotomous factor analysis of symptoms reported by UK and US veterans of the 1991 Gulf War

BACKGROUND: Factor analysis is one of the most used statistical techniques to analyze the inter-relationships among symptoms reported by Gulf War veterans. The objective of this study was to apply factor analyses to binary symptom data from the UK study of Gulf War illness and the US Air Force study of Gulf War veterans, and to compare the symptom domains derived from the distinct samples. METHODS: UK veterans of the 1991 Gulf War (n = 3,454), individuals deployed to Bosnia on U.N. peacekeeping operations (n = 1,979) and Gulf War-era servicemen (n = 2,577) who were not deployed to the Gulf were surveyed in 1997–1998, and US 1991 Gulf War veterans from four Air Force units (n = 1,163) were surveyed in 1995 to collect health characteristics including symptoms. Each sample was randomly split in half for exploratory and confirmatory dichotomous factor analyses with promax oblique rotation. RESULTS: Four correlated factors were identified in each of the samples. Three factors (Respiratory, Mood-Cognition, Peripheral Nervous) overlapped considerably across the UK cohorts. The Gastrointestinal/Urogenital factor in the UK Gulf cohort was noticeably different from the Gastrointestinal factor identified from the Bosnia and Era cohorts. Symptoms from Gulf War UK and U.S cohorts yielded similar Gastrointestinal, Respiratory and Mood-Cognition factors, despite differences in symptom inventories between the two surveys. A Musculoskeletal factor was only elicited from the US Gulf sample. CONCLUSION: Findings of this report are consistent with those from other factor analysis studies that identified similar symptom dimensions between Gulf and non-Gulf War veterans, except that the Gastrointestinal factor in Gulf veterans included other symptom types. Correlations among factors raise the question as to whether there is a general illness, even if not unique to Gulf veterans, representing the common pathway underlying the identified factors. Hierarchical factor analysis models may be useful to address this issue

Consumer acceptance of dairy products with a saturated fatty acid-reduced, monounsaturated fatty acid-enriched content

Agriculture-based reformulation initiatives, including oleic acid-rich lipid supplementation of the dairy cow diet, provide a novel means for reducing intake of saturated fatty acids (SFA) at a population level. In a blinded manner, this study evaluated the consumer acceptance of SFA-reduced, monounsaturated fatty acid-enriched (modified) milk, Cheddar cheese, and butter when compared with control and commercially available comparative samples. The effect of providing nutritional information about the modified cheese was also evaluated. Consumers (n = 115) rated samples for overall liking (appearance, flavor, and texture) using 9-point hedonic scales. Although no significant differences were found between the milk samples, the modified cheese was liked significantly less than a regular-fat commercial alternative for overall liking and liking of specific modalities and had a lower liking of texture score compared with the control cheese. The provision of health information significantly increased the overall liking of the modified cheese compared with tasting the same sample in a blinded manner. Significant differences were evident between the butter samples for overall liking and modalities of liking; all of the samples were significantly more liked than the commercial butter and sunflower oil spread. In conclusion, this study illustrated that consumer acceptance of SFA-reduced, monounsaturated fatty acid-enriched dairy products was dependent on product type. Future research should consider how optimization of the textural properties of fatty acid-modified (and fat-reduced) cheese might enhance consumer acceptance of this product

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

A cluster randomized trial of standard quality improvement versus patient-centered interventions to enhance depression care for African Americans in the primary care setting: study protocol NCT00243425

<p>Abstract</p> <p>Background</p> <p>Several studies document disparities in access to care and quality of care for depression for African Americans. Research suggests that patient attitudes and clinician communication behaviors may contribute to these disparities. Evidence links patient-centered care to improvements in mental health outcomes; therefore, quality improvement interventions that enhance this dimension of care are promising strategies to improve treatment and outcomes of depression among African Americans. This paper describes the design of the BRIDGE (Blacks Receiving Interventions for Depression and Gaining Empowerment) Study. The goal of the study is to compare the effectiveness of two interventions for African-American patients with depression--a standard quality improvement program and a patient-centered quality improvement program. The main hypothesis is that patients in the patient-centered group will have a greater reduction in their depression symptoms, higher rates of depression remission, and greater improvements in mental health functioning at six, twelve, and eighteen months than patients in the standard group. The study also examines patient ratings of care and receipt of guideline-concordant treatment for depression.</p> <p>Methods/Design</p> <p>A total of 36 primary care clinicians and 132 of their African-American patients with major depressive disorder were recruited into a cluster randomized trial. The study uses intent-to-treat analyses to compare the effectiveness of standard quality improvement interventions (academic detailing about depression guidelines for clinicians and disease-oriented care management for their patients) and patient-centered quality improvement interventions (communication skills training to enhance participatory decision-making for clinicians and care management focused on explanatory models, socio-cultural barriers, and treatment preferences for their patients) for improving outcomes over 12 months of follow-up.</p> <p>Discussion</p> <p>The BRIDGE Study includes clinicians and African-American patients in under-resourced community-based practices who have not been well-represented in clinical trials to improve depression care. The patient-centered and culturally targeted approach to depression care is a relatively new one that has not been tested in most previous studies. The study will provide evidence about whether patient-centered accommodations improve quality of care and outcomes to a greater extent than standard quality improvement strategies for African Americans with depression.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00243425</p

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types