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Introduction This study provides a comprehensive summary of the sociodemographic, psychosocial and health characteristics of a large population-based cohort of Ontario home care clients (aged 50 years and over) with dementia and examines the variation in these characteristics in those with co-existing neurological conditions. Methods Clients were assessed with the Resident Assessment Instrument-Home Care (RAI-HC) between January 2003 and December 2010. Descriptive analyses examined the distribution of these characteristics among clients with dementia relative to several comparison groups, as well as clients with other recorded neurological conditions. Results Approximately 22% of clients (n = 104 802) had a diagnosis of dementia (average age 83 years, 64% female) and about one in four within this group had a co-existing neurological condition (most commonly stroke or Parkinson disease). About 43% of those with dementia did not live with their primary caregiver. Relative to several comparison groups, clients with dementia showed considerably higher levels of cognitive and functional impairment, aggression, anxiety, wandering, hallucinations/delusions, caregiver distress and a greater risk for institutionalization. Conversely, they showed a lower prevalence of several chronic conditions and lower levels of recent health service use. Depressive symptoms were relatively common in the dementia and other neurological groups. Conclusion Clients with co-existing neurological conditions exhibited unique clinical profiles illustrating the need for tailored and flexible home care services and enhanced caregiver assistance programs.

Background aims Umbilical cord blood transplantation (CBT) is an effective treatment for benign and malignant diseases. Late effects of CBT are not well described in the literature. In the present study, we present our experience of new-onset allergies in long-term survivors after CBT. Methods After an initial patient had a severe peanut allergic reaction after CBT, all CBT patients were prospectively followed for new allergy development. Fifty patients received CBT between March 2006 and June 2011. Results The median follow-up after CBT was 447 days (range, 12–2022). At the time of analysis, 30 patients were alive, with 3-year survival of 55.5%; median follow-up of surviving patients was 910 days (range, 68–2022). The allergic syndrome developed in five patients, with the cumulative incidence of new allergies at 2 years of 18.4% (95% confidence interval, 10.8–26). The median time to onset of new allergy after transplantation was 298 days (range, 250–809). Conclusions Allergy development has been linked to a delayed maturation of the immune system in several studies. We present the first case series of patients who had new allergies after CBT. Further study of this novel complication as well as counseling of patients after CBT would be important.

The transforming growth factor-β (TGF-β) pathway has tumor-suppressor activity in many epithelial tissues. Because TGF-β is a potent inhibitor of epithelial cell proliferation, it has been widely assumed that this property underlies the tumor-suppressor effect. Here, we have used a xenograft model of breast cancer to show that endogenous TGF-β has the potential to suppress tumorigenesis through a novel mechanism, involving effects at two distinct levels in the hierarchy of cellular progeny that make up the epithelial component of the tumor. First, TGF-β reduces the size of the putative cancer stem or early progenitor cell population, and second it promotes differentiation of a more committed, but highly proliferative, progenitor cell population to an intrinsically less proliferative state. We further show that reduced expression of the type II TGF-β receptor correlates with loss of luminal differentiation in a clinical breast cancer cohort, suggesting that this mechanism may be clinically relevant. At a molecular level, the induction of differentiation by TGF-β involves down-regulation of Id1, and forced overexpression of Id1 can promote tumorigenesis despite persistence of the antiproliferative effect of TGF-β. These data suggest new roles for the TGF-β pathway in regulating tumor cell dynamics that are independent of direct effects on proliferation. [Cancer Res 2007;67(18):8643–52]

Patients with pancreatic and biliary carcinomas lack personalized treatment options, in part because biopsies are often inadequate for molecular characterization. Cell-free DNA (cfDNA) sequencing may enable a precision oncology approach in this setting. We attempted to prospectively analyze 54 genes in tumor and cfDNA for 26 patients. Tumor sequencing failed in 9 patients (35%). In the remaining 17, 90.3% (95% confidence interval, 73.1%–97.5%) of mutations detected in tumor biopsies were also detected in cfDNA. The diagnostic accuracy of cfDNA sequencing was 97.7%, with 92.3% average sensitivity and 100% specificity across five informative genes. Changes in cfDNA correlated well with tumor marker dynamics in serial sampling (r = 0.93). We demonstrate that cfDNA sequencing is feasible, accurate, and sensitive in identifying tumor-derived mutations without prior knowledge of tumor genotype or the abundance of circulating tumor DNA. cfDNA sequencing should be considered in pancreatobiliary cancer trials where tissue sampling is unsafe, infeasible, or otherwise unsuccessful. Significance: Precision medicine efforts in biliary and pancreatic cancers have been frustrated by difficulties in obtaining adequate tumor tissue for next-generation sequencing. cfDNA sequencing reliably and accurately detects tumor-derived mutations, paving the way for precision oncology approaches in these deadly diseases. Cancer Discov; 5(10); 1040–8. ©2015 AACR. This article is highlighted in the In This Issue feature, p. 1005

Little is known about the needs of older home care clients with dementia or their key quality of care issues, including their use of pharmacotherapy for Alzheimer's disease.The objectives of this study were to (1) describe the sociodemographic, psychosocial, and health characteristics of clients with dementia (relative to two control subgroups) from a population-based home care cohort; and, (2) determine the distribution and associated characteristics of cholinesterase inhibitor (ChEI) and/or memantine use among dementia clients overall and according to medication class, comorbid illness, and year of assessment.This cross-sectional study included all home care clients aged 50 years or older assessed with the Resident Assessment Instrument-Home Care (RAI-HC) in Ontario, Canada from January 2003 to December 2010. Multivariable logistic regression models were used to identify factors associated with receiving a dementia medication (a ChEI and/or memantine).There were 104,802 (21.5 %) clients with a diagnosis of dementia, 92,529 (18.9 %) cognitively impaired clients without a dementia diagnosis, and 290,929 (59.6 %) cognitively intact clients. Relative to the comparison groups, dementia clients were more likely to have reported conflicts with others, a distressed caregiver, greater levels of cognitive and functional impairment, and to exhibit wandering, aggressive behaviors, anxiety, hallucinations or delusions, and swallowing problems. Approximately half of dementia clients were taking a dementia medication, most commonly donepezil. Characteristics most strongly associated with use of ChEI monotherapy included age greater than 64 (especially 75-84), absence of economic barriers, availability of a primary caregiver, year of assessment, moderate to severe cognitive impairment, relative independence in function, health stability, no depressive symptoms or hallucinations/delusions, no recent hospitalization, use of at least 9 medications, the absence of chronic health and neurological conditions, and the use of an antipsychotic or antidepressant. For combination therapy, strong positive associations were observed for younger age, year of assessment, increasing cognitive impairment, presence of a primary caregiver, male sex, absence of economic barriers, use of at least 9 medications, and various indicators of positive health status (e.g., stability in health, absence of chronic health and neurological conditions, and no recent hospitalization). The percentage of clients receiving ChEIs increased with cognitive impairment scores but declined slightly at the highest level of impairment, whereas the percentage receiving memantine increased with cognitive impairment level. The number and percentage of dementia clients receiving any pharmacotherapy increased during the study interval.We observed a relatively high prevalence of dementia-specific pharmacotherapy among Ontario long-stay home care clients as well as significant variation in utilization patterns by select sociodemographic, functional, and clinical characteristics, and over time. While physicians generally followed recommended guidelines regarding appropriate dementia pharmacotherapy, continued efforts to monitor practice patterns are required among vulnerable older adults across care settings.