Age, Multiple Chronic Conditions, and COVID-19: A literature review

BACKGROUND: Various patient demographic and clinical characteristics have been associated with poor outcomes for individuals with coronavirus disease 2019 (COVID-19). To describe the importance of age and chronic conditions in predicting COVID-19 related outcomes. METHODS: Search strategies were conducted in PubMed/MEDLINE. Daily alerts were created. RESULTS: A total of 28 studies met our inclusion criteria. Studies varied broadly in sample size (n=21 to more than 17,000,000). Participants mean age ranged from 48 years to 80 years and the proportion of male participants ranged from 44%-82%. The most prevalent underlying conditions in patients with COVID-19 were hypertension (range: 15% - 69%), diabetes (8% - 40%), cardiovascular disease (4% - 61%), chronic pulmonary disease (1% - 33%), and chronic kidney disease (range 1% - 48%). These conditions were each associated with an increased in-hospital case fatality rate ranging from 1% to 56%. Overall, older adults have a substantially higher case fatality rate (CFR) as compared with younger individuals affected by COVID-19 (42% for those \u3c 65 vs 65% \u3e 65 years ). Only one study examined the association of chronic conditions and the risk of dying across different age groups; their findings suggested similar trends of increased risk in those \u3c 65 and those \u3e 65 years as compared to those without these conditions. CONCLUSIONS: There has been a traditional, single condition approach to consideration of how chronic conditions and advancing age relate to COVID-19 outcomes. A more complete picture of the impact of burden of multimorbidity and advancing patient age is needed

Examining provider perceptions and practices for comprehensive geriatric assessment among cancer survivors: a qualitative study with an implementation science focus

Introduction: Cancer rates increase with age, and older cancer survivors have unique medical care needs, making assessment of health status and identification of appropriate supportive resources key to delivery of optimal cancer care. Comprehensive geriatric assessments (CGAs) help determine an older person’s functional capabilities as cancer care providers plan treatment and follow-up care. Despite its proven utility, research on implementation of CGA is lacking.Methods: Guided by a qualitative description approach and through interviews with primary care providers and oncologists, our goal was to better understand barriers and facilitators of CGA use and identify training and support needs for implementation. Participants were identified through Cancer Prevention and Control Research Network partner listservs and a national cancer and aging organization. Potential interviewees, contacted via email, were provided with a description of the study purpose. Eight semi-structured interviews were conducted via Zoom, recorded, and transcribed verbatim by a professional transcription service. The interview guide explored providers’ knowledge and use of CGAs. For codebook development, three representative transcripts were independently reviewed and coded by four team members. The interpretive process involved reflecting, transcribing, coding, and searching for and identifying themes.Results: Providers shared that, while it would be ideal to administer CGAs with all new patients, they were not always able to do this. Instead, they used brief screening tools or portions of CGAs, or both. There was variability in how CGA domains were assessed; however, all considered CGAs useful and they communicated with patients about their benefits. Identified facilitators of implementation included having clinic champions, an interdisciplinary care team to assist with implementation and referrals for intervention, and institutional resources and buy-in. Barriers noted included limited staff capacity and competing demands on time, provider inexperience, and misaligned institutional priorities.Discussion: Findings can guide solutions for improving the broader and more systematic use of CGAs in the care of older cancer patients. Uptake of processes like CGA to better identify those at risk of poor outcomes and intervening early to modify treatments are critical to maximize the health of the growing population of older cancer survivors living through and beyond their disease

A Tri-Oceanic Perspective: DNA Barcoding Reveals Geographic Structure and Cryptic Diversity in Canadian Polychaetes

Although polychaetes are one of the dominant taxa in marine communities, their distributions and taxonomic diversity are poorly understood. Recent studies have shown that many species thought to have broad distributions are actually a complex of allied species. In Canada, 12% of polychaete species are thought to occur in Atlantic, Arctic, and Pacific Oceans, but the extent of gene flow among their populations has not been tested.Sequence variation in a segment of the mitochondrial cytochrome c oxidase I (COI) gene was employed to compare morphological versus molecular diversity estimates, to examine gene flow among populations of widespread species, and to explore connectivity patterns among Canada's three oceans. Analysis of 1876 specimens, representing 333 provisional species, revealed 40 times more sequence divergence between than within species (16.5% versus 0.38%). Genetic data suggest that one quarter of previously recognized species actually include two or more divergent lineages, indicating that richness in this region is currently underestimated. Few species with a tri-oceanic distribution showed genetic cohesion. Instead, large genetic breaks occur between Pacific and Atlantic-Arctic lineages, suggesting their long-term separation. High connectivity among Arctic and Atlantic regions and low connectivity with the Pacific further supports the conclusion that Canadian polychaetes are partitioned into two distinct faunas.Results of this study confirm that COI sequences are an effective tool for species identification in polychaetes, and suggest that DNA barcoding will aid the recognition of species overlooked by the current taxonomic system. The consistent geographic structuring within presumed widespread species suggests that historical range fragmentation during the Pleistocene ultimately increased Canadian polychaete diversity and that the coastal British Columbia fauna played a minor role in Arctic recolonization following deglaciation. This study highlights the value of DNA barcoding for providing rapid insights into species distributions and biogeographic patterns in understudied groups

Ethics review as a component of institutional approval for a multicentre continuous quality improvement project: the investigator's perspective

BACKGROUND: For ethical approval of a multicentre study in Canada, investigators must apply separately to individual Research Ethics Boards (REBs). In principle, the protection of human research subjects is of utmost importance. However, in practice, the process of multicentre ethics review can be time consuming and costly, requiring duplication of effort for researchers and REBs. We used our experience with ethical review of The Canadian Perinatal Network (CPN), to gain insight into the Canadian system. METHODS: The applications forms of 16 different REBs were abstracted for a list of standardized items. The application process across sites was compared. Correspondence between the REB and the investigators was documented in order to construct a timeline to approval, identify the specific issues raised by each board, and describe how they were resolved. RESULTS: Each REB had a different application form. Most (n = 9) had a two or three step application process. Overall, it took a median of 31 days (range 2-174 days) to receive an initial response from the REB. Approval took a median of 42 days (range 4-443 days). Privacy and consent were the two major issues raised. Several additional minor or administrative issues were raised which delayed approval. CONCLUSIONS: For CPN, the Canadian REB process of ethical review proved challenging. REBs acted independently and without unified application forms or submission procedures. We call for a critical examination of the ethical, privacy and institutional review processes in Canada, to determine the best way to undertake multicentre review

TDP-43 Depletion in Microglia Promotes Amyloid Clearance but Also Induces Synapse Loss

Microglia coordinate various functions in the central nervous system ranging from removing synaptic connections, to maintaining brain homeostasis by monitoring neuronal function, and clearing protein aggregates across the lifespan. Here we investigated whether increased microglial phagocytic activity that clears amyloid can also cause pathological synapse loss. We identified TDP-43, a DNA-RNA binding protein encoded by the Tardbp gene, as a strong regulator of microglial phagocytosis. Mice lacking TDP-43 in microglia exhibit reduced amyloid load in a model of Alzheimer's disease (AD) but at the same time display drastic synapse loss, even in the absence of amyloid. Clinical examination from TDP-43 pathology cases reveal a considerably reduced prevalence of AD and decreased amyloid pathology compared to age-matched healthy controls, confirming our experimental results. Overall, our data suggest that dysfunctional microglia might play a causative role in the pathogenesis of neurodegenerative disorders, critically modulating the early stages of cognitive decline

Macrophage-Secreted TNFα and TGFβ1 Influence Migration Speed and Persistence of Cancer Cells in 3D Tissue Culture via Independent Pathways

The ability of a cancer cell to migrate through the dense extracellular matrix within and surrounding the solid tumor is a critical determinant of metastasis. Macrophages enhance invasion and metastasis in the tumor microenvironment, but the basis for their effects is not fully understood. Using a microfluidic 3D cell migration assay, we found that the presence of macrophages enhanced the speed and persistence of cancer cell migration through a 3D extracellular matrix in a matrix metalloproteinases (MMP)-dependent fashion. Mechanistic investigations revealed that macrophage-released TNFα and TGFβ1 mediated the observed behaviors by two distinct pathways. These factors synergistically enhanced migration persistence through a synergistic induction of NF-κB-dependent MMP1 expression in cancer cells. In contrast, macrophage-released TGFβ1 enhanced migration speed primarily by inducing MT1-MMP expression. Taken together, our results reveal new insights into how macrophages enhance cancer cell metastasis, and they identify TNFα and TGFβ1 dual blockade as an antimetastatic strategy in solid tumors.National Institutes of Health (U.S.) (Grant U01 CA202177-01

Senior Studio Art Capstone // VAC 119

Moderator: Professor Courtney Chenett

Diabetes and health-related quality of life among American Indians: the role of psychosocial factors.

PurposeLittle is known about the association of psychosocial factors with health-related quality of life (HRQoL) among American Indians with type 2 diabetes (T2D). This study described functional social support, emotional support, coping, resilience, post-traumatic stress disorder, and HRQoL, among American Indians by diabetes status and, among those with diabetes, examined the association of these factors with HRQoL.MethodsUsing data from the Cherokee Nation Health Survey collected between 2017 and 2019, we evaluated differences in each measure of interest according to diabetes status, using t-test and Chi-squared tests of association. We used weighted multiple logistic regression to examine associations between multiple psychosocial factors and HRQoL among those with diabetes.ResultsCompared to individuals without diabetes, participants with diabetes rated their functional social support (4.62 vs. 4.56, respectively) and coping (2.65 vs. 2.61, respectively) slightly lower and were more likely to report ≥ 15 days of poor physical (14% vs. 26%, respectively) and mental health (14% vs. 17%, respectively) in the past month. Odds of reporting poor overall health increased more than sixfold for those who were dissatisfied/very dissatisfied with life (AOR = 6.70). Resilience scores reduced odds of reporting ≥ 15 days with poor physical health, while experiences of post-traumatic stress doubled these odds.ConclusionOur study yielded insights into the risk as well as protective factors associated with diabetes outcomes in a large sample of American Indians with T2D. Researchers should design pragmatic trials that deepen understanding of preventive as well as treatment leverage through greater attention to experiences that compromise HRQoL

Diabetes and health-related quality of life among American Indians: the role of psychosocial factors.

PurposeLittle is known about the association of psychosocial factors with health-related quality of life (HRQoL) among American Indians with type 2 diabetes (T2D). This study described functional social support, emotional support, coping, resilience, post-traumatic stress disorder, and HRQoL, among American Indians by diabetes status and, among those with diabetes, examined the association of these factors with HRQoL.MethodsUsing data from the Cherokee Nation Health Survey collected between 2017 and 2019, we evaluated differences in each measure of interest according to diabetes status, using t-test and Chi-squared tests of association. We used weighted multiple logistic regression to examine associations between multiple psychosocial factors and HRQoL among those with diabetes.ResultsCompared to individuals without diabetes, participants with diabetes rated their functional social support (4.62 vs. 4.56, respectively) and coping (2.65 vs. 2.61, respectively) slightly lower and were more likely to report ≥ 15 days of poor physical (14% vs. 26%, respectively) and mental health (14% vs. 17%, respectively) in the past month. Odds of reporting poor overall health increased more than sixfold for those who were dissatisfied/very dissatisfied with life (AOR = 6.70). Resilience scores reduced odds of reporting ≥ 15 days with poor physical health, while experiences of post-traumatic stress doubled these odds.ConclusionOur study yielded insights into the risk as well as protective factors associated with diabetes outcomes in a large sample of American Indians with T2D. Researchers should design pragmatic trials that deepen understanding of preventive as well as treatment leverage through greater attention to experiences that compromise HRQoL