Search

BACKGROUND Interdisciplinary team (IDT) care is central to home-based primary care (HBPC) of frail elders. Traditionally, all HBPC disciplines managed a patient (Full IDT), a costly approach to maintain. The recent PACE (Program of All-inclusive Care for the Elderly) regulation provides for a flexible approach of annual assessments from a core team with involvement of additional disciplines dependent upon patient needs (Core+). Current Department of Veterans Affairs (VA) HBPC guidance specifies Full IDTs care for medically complex and functionally impaired Veterans similar to PACE participants. We evaluated whether VA HBPC has adopted the flexible structure of the PACE regulation, aligned to Veteran needs. DESIGN Cross-sectional analysis. SETTING All 139 VA HBPC programs administered across 379 sites. PARTICIPANTS About 55,173 Veterans enrolled in HBPC during fiscal year 2018. MEASUREMENTS Patients' HBPC physician, nurse, psychologist/psychiatrist, social worker, therapist, dietitian, and pharmacist visits were grouped into interdisciplinary team types. Patient frailty was classified using VA HNHR v2 (High-Need High-Risk version 2, a measure of high, medium, and low risk of long-term institutionalization). Medical complexity was measured by clusters of impairment in the JEN frailty index (JFI). JFI clusters were validated by VA's Nosos measure to project cost and Care Assessment Need (CAN) measure of hospitalization and mortality risk. RESULTS HBPC provided Full IDT care to 21%, Core+ care to 54%, and Home Health+ (HHA+) care (skilled home health services plus additional disciplines, without primary care) to 16% of Veterans. Team type was associated with medical complexity (X2 2863.5 [66 df], p

Background Empirical evidence supports the use of structured goals of care conversations and documentation of life-sustaining treatment (LST) preferences in durable, accessible, and actionable orders to improve the care for people living with serious illness. As the largest integrated healthcare system in the USA, the Veterans Health Administration (VA) provides an excellent environment to test implementation strategies that promote this evidence-based practice. The Preferences Elicited and Respected for Seriously Ill Veterans through Enhanced Decision-Making (PERSIVED) program seeks to improve care outcomes for seriously ill Veterans by supporting efforts to conduct goals of care conversations, systematically document LST preferences, and ensure timely and accurate communication about preferences across VA and non-VA settings. Methods PERSIVED encompasses two separate but related implementation projects that support the same evidence-based practice. Project 1 will enroll 12 VA Home Based Primary Care (HBPC) programs and Project 2 will enroll six VA Community Nursing Home (CNH) programs. Both projects begin with a pre-implementation phase during which data from diverse stakeholders are gathered to identify barriers and facilitators to adoption of the LST evidence-based practice. This baseline assessment is used to tailor quality improvement activities using audit with feedback and implementation facilitation during the implementation phase. Site champions serve as the lynchpin between the PERSIVED project team and site personnel. PERSIVED teams support site champions through monthly coaching sessions. At the end of implementation, baseline site process maps are updated to reflect new steps and procedures to ensure timely conversations and documentation of treatment preferences. During the sustainability phase, intense engagement with champions ends, at which point champions work independently to maintain and improve processes and outcomes. Ongoing process evaluation, guided by the RE-AIM framework, is used to monitor Reach, Adoption, Implementation, and Maintenance outcomes. Effectiveness will be assessed using several endorsed clinical metrics for seriously ill populations. Discussion The PERSIVED program aims to prevent potentially burdensome LSTs by consistently eliciting and documenting values, goals, and treatment preferences of seriously ill Veterans. Working with clinical operational partners, we will apply our findings to HBPC and CNH programs throughout the national VA healthcare system during a future scale-out period.

Objective The objective of this study was to examine site of death and hospice use, identifying potential disparities among veterans dying in Department of Veterans Affairs (VA) Home Based Primary Care (VA-HBPC). Methods Administrative data (2008, 2012, and 2016) were compiled using the VA Residential-History-File which tracks health care service location, daily. Outcomes were site of death [home, nursing home (NH), hospital, inpatient hospice]; and hospice use on the day of death. We compared VA-HBPC rates to rates of 2 decedent benchmarks: VA patients and 5% Traditional Medicare non-veteran males. Potential age, race, urban/rural residence and living alone status disparities in rates among veterans dying in VA-HBPC in 2016 were examined by multinomial logistic regression. Results In 2016, 7796 veterans died in VA-HBPC of whom 62.1% died at home, 11.8% in NHs, 14.7% in hospitals and 11.4% in inpatient hospice. Hospice was provided to 60.9% of veterans dying at home and 63.9% of veterans dying in NH. Over the 2008-2012-2016 period, rates of VA-HBPC veterans who died at home and rates of home death with hospice increased and were higher than both benchmarks. Among VA-HBPC decedents, younger/older veterans were more/less likely to die at home and less/more likely to die with hospice. Race/ethnicity and urban/rural residence were unrelated to death at home but veterans living alone were less likely to die at home. Conclusions Results reflect VA-HBPC's primary goal of supporting its veterans at home, including at the end-of-life, surpassing other population benchmarks with some potential disparities remaining.

BACKGROUND The Department of Veterans Affairs (VA)'s home-based primary care (HBPC) program provides coordinated, interdisciplinary care to seriously ill and disabled veterans, but few evaluations have considered end-of-life (EOL) care in this population. The aim of this study was to describe veterans' use of community-based hospice services while enrolled in HBPC and their associations with bereaved families' perceptions of care. METHODS This study was a retrospective analysis of electronic medical record and bereaved family survey (BFS) data for veterans who died while enrolled in VA's HBPC program between October 2013 and September 2019. Seven regional VA networks called Veteran Integrated Service Networks participated in BFS data collection. The final sample included 3967 veterans who were receiving HBPC services at the time of death and whose next-of-kin completed a BFS. The primary outcome was the BFS global rating of care received in the last 30 days of life. Adjusted proportions for all BFS outcomes were examined and compared between those who received community-based hospice services and those who did not. RESULTS Overall, 52.6% of BFS respondents reported that the care received by HBPC-enrolled veterans in the last 30 days of life was excellent using the BFS global rating. Among families of HBPC-enrolled veterans who received community-based hospice services, the BFS global rating was roughly eight percentage points higher than those who did not (55.7 vs. 47.0%, p

Summary: Background: Historical, colonial, and racist policies continue to influence the health of Indigenous people, and they continue to have higher rates of chronic diseases and reduced life expectancy compared with non-Indigenous people. We determined factors accounting for variations in cardiovascular risk factors among First Nations communities in Canada. Methods: Men and women (n=1302) aged 18 years or older from eight First Nations communities participated in a population-based study. Questionnaires, physical measures, blood samples, MRI of preclinical vascular disease, and community audits were collected. In this cross-sectional analysis, the main outcome was the INTERHEART risk score, a measure of cardiovascular risk factor burden. A multivariable model was developed to explain the variations in INTERHEART risk score among communities. The secondary outcome was MRI-detected carotid wall volume, a measure of subclinical atherosclerosis. Findings: The mean INTERHEART risk score of all communities was 17·2 (SE 0·2), and more than 85% of individuals had a risk score in the moderate to high risk range. Subclinical atherosclerosis increased significantly across risk score categories (p

Haudenosaunee Peoples of eastern North America have a strong agricultural tradition and culture associated with maize horticulture. Traditional foodways and diet were disrupted after the people were dispossessed from traditional lands maintained prior to colonization. As a result, Haudenosaunee have been disconnected from their traditional diet and lifestyle, and chronic diseases such as diabetes and obesity are increasing. Healthy Roots was developed in Six Nations of the Grand River territory by Haudenosaunee community members. It started as a 90-day challenge, in which participants adhere to a diet of traditional foods found in Haudenosaunee territories pre-European contact. The community decided to formally evaluate the impact of the diet in a pilot pre–post intervention study of 22 participants in 2016/17. We investigated the effects of the 3-month dietary intervention on physical measurements, ectopic fat (including visceral and liver adipose tissue), serum lipids, and hemoglobin A1c among Haudenosaunee participants in Six Nations. We provided biweekly Haudenosaunee food boxes, and offered workshops, cooking classes, and individual support from a dietitian. The intervention reduced body weight, body circumferences including waist circumference, hemoglobin A1c, and MRI-detected hepatic fat fraction. There were no adverse events. Engagement in the program was high and trends favoured improved well-being. The intervention shows great potential as a mechanism for improving physical health and restoring cultural connectedness and identity. The implications for improving mental health and community cohesion are also important areas to consider in future research.

RESEARCH OBJECTIVE: Department of Veterans Affairs (VA) Home‐Based Primary Care (HBPC) employing mobile interdisciplinary teams (IDT: physician/nurse practitioner, nurse, therapist, social worker, dietician, pharmacist, and psychologist) has been reported to be effective at improving care and lowering cost for frail, high‐risk Veterans. The full IDT represents a significant investment in care for complex Veterans. Some VA Medical Centers (VAMCs) employ HBPC without providing mobile primary care but use an enhanced home health team. The Program for All Inclusive Care for the Elderly (PACE) employs a similar IDT to care for frail older adults. The updated Centers for Medicare & Medicaid Services (CMS) PACE addresses the cost of a full IDT by regulating a “core” team (primary care, nursing, social work, and therapy), with additional team members as needed. We examined the variability of IDT care by frailty of HBPC Veterans. STUDY DESIGN: Using discipline‐specific visit codes, we classified staffing patterns by IDT involvement: full IDT (all 7 members), core (primary care, nursing, social work, and therapy), core+ (core and one or more noncore disciplines), home health (nursing, social work, and therapy), home health + (home health and one or more noncore disciplines), and housecalls (mobile primary care). We clustered the 13 domains of frailty identified from diagnoses codes in the JEN Frailty Index domains (JFI=sum of domains, range 0‐13) to identify clusters of high and low frailty. Chi‐square goodness of fit tested the association of HBPC service teams with the frailty profiles among all HBPC Veterans and the subset with high frailty (JFI > 6). POPULATION STUDIED: Veterans enrolled in HBPC in fiscal year 2018 across 139 VA Medical Centers (VAMCs) (N = 55 197) of whom 35 876 (65%) were high frailty (JFI > 6). PRINCIPAL FINDINGS: Forty‐one percent of all HBPC Veterans received care from a full IDT, 22% received care from a Core IDT, 16% received care from a Core+ IDT, 4% received care from a Home Health IDT, while 16% received care from a Home Health+ IDT and 1% received housecalls. Ten clusters of teams were identified ranging from high risk to low risk and an “Other” risk formed the 11th cluster. Among high frailty Veterans, 71% were in the top 2 high‐risk clusters, among whom 62% received Full IDT or Core+ IDT. Among lower risk Veterans, 74% were in clusters 1‐10, among whom 28% were in the 3 lowest risk clusters, and 38.9% received HH/HH+ IDT. The 15 VAMCs with the greatest share of a HH or HH+ teams had between 34 and 100% of Veterans receiving mobile primary care. The chi‐square with 66 degrees of freedom (11 clusters * 6 IDT models) of the global association of care patterns and Veteran frailty was 1487 (P

Background: Historically, older adults have been disproportionately affected by disasters. In particular, homebound adults are especially at risk. As one facet of bolstering community resilience, home health agencies have been tasked with improving their patients’ disaster preparedness. However, home health practitioners often lack the information necessary to fulfill these requirements. Providing resources about disaster preparedness will allow these practitioners, often seen as trusted advisors, to better prepare their patients. Objective: This study explores the utility of implementing a checklist-style assessment tool to guide Veterans Health Administration (VHA) Home-Based Primary Care (HBPC) practitioners in disaster preparedness assessments of their patients. Methods: The HBPC Patient Assessment Tool for Disaster Planning (“Tool”) was fielded by practitioners at 10 VHA HBPC programs with all patients seen over the course of a 3-week period. Descriptive statistics and bivariate analysis of the data collected via the Tool were used to understand the baseline levels of preparedness education provided by practitioners to their patients. Data from a follow-up survey and follow-up interviews with Program Managers were analyzed, the latter using content analysis methods. Results: 754 surveys were returned for analysis. We examined how frequently practitioners reviewed the included preparedness items with their patients. Of those patients on oxygen, adherence ranged from 67 to 94% for practitioners covering a discussion about smoking materials/open flame, despite strong efforts to achieve high compliance on this measure as reported by several program managers. Of those items applicable to the general population, certain items were more frequently discussed than others. How to activate 911 services was most frequently reviewed (87%). Providing information about emergency shelter registration and specialty transport was the item least frequently reviewed (44%). Strengths about the Tool included its ease of use, flow, comprehensiveness, and that it fits on one page. Conclusion: Home-based care programs, such as the VHA HBPC program, are tasked with supporting the emergency preparedness of their patients, but often do not have the expertise to do so. This study shows that the checklist-like structure of an assessment tool can assist with this role by encouraging practitioners to cover key points with patients and their caregivers.

Objective:The aim of this study is to determine the response of home-based primary care programs to the fall 2017 Atlantic hurricane season.Methods:This study examines the experiences of 9 Veterans Health Administration (VHA) Home-Based Primary Care (HBPC) programs in their responses to Hurricanes Harvey, Irma, and Maria. Thirty-four phone interviews with HBPC leadership and staff were conducted from April to July 2018.Results:The total census of impacted HBPC programs was 3118. No program reported loss of life due to these hurricanes. Early preparedness was key to an effective program response. Response included prompt tracking of the patients. In the most affected areas, respondents noted limited resources to support basic patient needs.Conclusions:Medically complex patients served by programs such as the VHA’s HBPC program represent a subset of the population, yet they have an outsized impact on health care resources that could be exacerbated by inadequate disaster preparedness. HBPC programs serve a unique role in supporting the “older old.” They are tasked with supporting disaster preparedness activities of patients. Understanding what is involved in actualizing their requirements shows communities how to effectively engage with these programs.

Background: This is the first national indigenous cohort study in which a common, in-depth protocol with a common set of objectives has been adopted by several indigenous communities across Canada. Objectives: The overarching objective of the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort is to investigate how the community-level environment is associated with individual health behaviors and the presence and progression of chronic disease risk factors and chronic diseases such as cardiovascular disease (CVD) and cancer. Methods: CAHHM aims to recruit approximately 2,000 First Nations indigenous individuals from up to nine communities across Canada and have participants complete questionnaires, blood collection, physical measurements, cognitive assessments, and magnetic resonance imaging (MRI). Results: Through individual- and community-level data collection, we will develop an understanding of the specific role of the socioenvironmental, biological, and contextual factors have on the development of chronic disease risk factors and chronic diseases. Conclusions: Information collected in the indigenous cohort will be used to assist communities to develop local management strategies for chronic disease, and can be used collectively to understand the contextual, environmental, socioeconomic, and biological determinants of differences in health status in harmony with First Nations beliefs and reality.

Background Women play important roles in translating health knowledge, particularly around pregnancy and birth, in Indigenous societies. We investigated elder Indigenous women's perceptions around optimal perinatal health. Methods Using a methodological framework that integrated a constructivist grounded-theory approach with an Indigenous epistemology, we conducted and analyzed in-depth interviews and focus groups with women from the Six Nations community in southern Ontario who self-identified as grandmothers. Our purposive sampling strategy was guided by a Six Nations advisory group and included researcher participation in a variety of local gatherings as well as personalized invitations to specific women, either face-to-face or via telephone. Results Three focus groups and 7 individual interviews were conducted with 18 grandmothers. The participants' experiences converged on 3 primary beliefs: pregnancy is a natural phase, pregnancy is a sacred period for the woman and the unborn child, and the requirements of immunity, security (trust), comfort, social development and parental responsibility are necessary for optimal postnatal health. Participants also identified 6 communal responsibilities necessary for families to raise healthy children: access to healthy and safe food, assurance of strong social support networks for mothers, access to resources for postnatal support, increased opportunities for children to participate in physical activity, more teachings around the impact of maternal behaviours during pregnancy and more teachings around spirituality/positive thinking. We also worked with the Six Nations community on several integrated knowledge-translation elements, including collaboration with an Indigenous artist to develop a digital story (short film). Interpretation Elder women are a trusted and knowledgeable group who are able to understand and incorporate multiple sources of knowledge and deliver it in culturally meaningful ways. Thus, tailoring public health programming to include elder women's voices may improve the impact and uptake of perinatal health information for Indigenous women.

ObjectiveHealth agencies working with the homebound play a vital role in bolstering a community’s resiliency by improving the preparedness of this vulnerable population. Nevertheless, this role is one for which agencies lack training and resources, which leaves many homebound at heightened risk. This study examined the utility of an evidence-based Disaster Preparedness Toolkit in Veterans Health Administration (VHA) Home-Based Primary Care (HBPC) programs.MethodsWe conducted an online survey of all VHA HBPC program managers (N=77/146; 53% response rate).ResultsRespondents with fewer years with the HBPC program rated the toolkit as being more helpful (PPConclusionThis toolkit helps support programs as they fulfill their preparedness requirements, especially practitioners who are new to their position in HBPC. Programs that implement disaster protocols infrequently may require additional efforts to increase understanding of the toolkit’s utility. Engaging all members of the team with their diverse clinical expertise could strengthen a patient’s personal preparedness plan. (Disaster Med Public Health Preparedness. 2017;11:56–63)

IntroductionHome health agencies have been tasked to improve their patients’ disaster preparedness. Few studies have evaluated the robustness of tools to support preparedness in home health. Through evaluation of the Home-Based Primary Care (HBPC) Patient Assessment Tool, we conducted a survey to identify strengths and challenges in supporting the preparedness of patients served by home health programs such as the Veterans Health Administration’s HBPC program.MethodsPractitioners from 10 HBPC programs fielded the Patient Assessment Tool with all patients during a 3-week period. Logistic regression and bivariate analyses were used to identify patient characteristics associated with the delivery of preparedness education.ResultsA total of 754 Patient Assessment Tools were returned. The educational item most likely to be covered was how to activate 911 services (87%). The item least likely to be discussed was information on emergency shelter registration and emergency specialty transportation (44%). When compared to the low risk group, HBPC patients in the high/medium risk group were more likely to receive preparedness education materials for 6 of the 9 educational preparedness items (P values less than 0.05).DiscussionPractitioners are relaying preparedness education to their most vulnerable patients, suggesting that home health agencies can provide disaster preparedness in the home. Nonetheless, there is room for improvement. (Disaster Med Public Health Preparedness. 2019;13:547-554)

Candida albicans is a major fungal pathogen whose virulence is associated with its ability to transition from a budding yeast form to invasive hyphal filaments. The kinesin-14 family member Ca Kar3 is required for transition between these morphological states, as well as for mitotic progression and karyogamy. While kinesin-14 proteins are ubiquitous, Ca Kar3 homologs in hemiascomycete fungi are unique because they form heterodimers with noncatalytic kinesin-like proteins. Thus, Ca Kar3-based motors may represent a novel antifungal drug target. We have identified and examined the roles of a kinesin-like regulator of Ca Kar3. We show that orf19.306 (dubbed CaCIK1 ) encodes a protein that forms a heterodimer with Ca Kar3, localizes Ca Kar3 to spindle pole bodies, and can bind microtubules and influence Ca Kar3 mechanochemistry despite lacking an ATPase activity of its own. Similar to Ca Kar3 depletion, loss of Ca Cik1 results in cell cycle arrest, filamentation defects, and an inability to undergo karyogamy. Furthermore, an examination of the spindle structure in cells lacking either of these proteins shows that a large proportion have a monopolar spindle or two dissociated half-spindles, a phenotype unique to the C. albicans kinesin-14 homolog. These findings provide new insights into mitotic spindle structure and kinesin motor function in C. albicans and identify a potentially vulnerable target for antifungal drug development.

Kar3 kinesins are microtubule (MT) minus-end-directed motors with pleiotropic functions in mitotic spindle formation and nuclear movement in budding and fission yeasts. A Kar3-like kinesin is also expressed by the filamentous fungus Ashbya gossypi, which exhibits different nuclear movement challenges from its yeast relatives. Presented here is a 2.35 Å crystal structure and enzymatic analysis of the AgKar3 motor domain (AgKar3MD). Compared to the previously published Saccharomyces cerevisiae Kar3MD structure (ScKar3MD), AgKar3MD displays differences in the conformation of some of its nucleotide-binding motifs and peripheral elements. Unlike ScKar3MD, the salt bridge between Switch I and Switch II in AgKar3MD is broken. Most of the Switch I, and the adjoining region of helix α3, are also disordered instead of bending into the active site cleft as is observed in ScKar3MD. These aspects of AgKar3MD are highly reminiscent of the ScKar3 R598A mutant that disrupts the Switch I-Switch II salt bridge and impairs MT-stimulated ATPase activity of the motor. Subtle differences in the disposition of secondary structure elements in the small lobe (β1a, β1b, and β1c) at the edge of the MD are also apparent even though it contains approximately the same number of residues as ScKar3. These differences may reflect the unique enzymatic properties we measured for this motor, which include a lower MT-stimulated ATPase rate relative to ScKar3, or they could relate to its interactions with different regulatory companion proteins than its budding yeast counterpart.

Elevated plasma plasminogen activator inhibitor-1 (PAI-1) concentration is associated with cardiovascular disease risk. PAI-1 is the primary inhibitor of fibrinolysis within both the circulation and the arterial wall, playing roles in both atherosclerosis and thrombosis. To define the heritable component, subjects within the population-based SHARE (Study of Health Assessment and Risk in Ethnic groups) and SHARE-AP (Study of Health Assessment and Risk Evaluation in Aboriginal Peoples) studies, composed of Canadians of South Asian (n = 298), Chinese (n = 284), European (n = 227), and Aboriginal (n = 284) descent, were genotyped using the gene-centric Illumina HumanCVD BeadChip. After imputation, more than 150 000 single nucleotide polymorphisms (SNPs) in more than 2000 loci were tested for association with plasma PAI-1 concentration. Marginal association was observed with the PAI-1 locus itself (SERPINE1; P < .05). However, 5 loci (HABP2, HSPA1A, HYAL1, MBTPS1, TARP) were associated with PAI-1 concentration at a P < 1 × 10−5 threshold. The protein products of 2 of these loci, hyaluronan binding protein 2 (HABP2) and hyaluronoglucosaminidase 1 (HYAL1), play key roles in hyaluronan metabolism, providing genetic evidence to link these pathways.

OBJECTIVE To investigate ethnic differences in adiponectin and leptin concentration and to determine whether these adipokines and a high–glycemic index diet account for ethnic variation in insulin resistance. RESEARCH DESIGN AND METHODS In 1,176 South Asian, Chinese, Aboriginal, and European Canadians, fasting blood samples were drawn, and clinical history and dietary habits including glycemic index/glycemic load were recorded using standardized questionnaires. Insulin resistance was defined using homeostasis model assessment–insulin resistance (HOMA-IR). RESULTS Adiponectin concentrations were significantly higher in Europeans (adjusted mean 12.94 [95% CI 2.27–13.64]) and Aboriginal people (11.87 [11.19–12.59]) than in South Asians (9.35 [8.82–9.92]) and Chinese (8.52 [8.03–9.03]) (overall P < 0.001). Serum leptin was significantly higher in South Asians (11.82 [10.72–13.04]) and Aboriginal people (11.13 [10.13–12.23]) than in Europeans (9.21 [8.38–10.12]) and Chinese (8.25 [7.48–9.10]). BMI and waist circumference were inversely associated with adiponectin in every group except the South Asians (P < 0.001 for interaction). Adiponectin was inversely and leptin was positively associated with HOMA-IR (P < 0.001). The increase in HOMA-IR for each given decrease in adiponectin was larger among South Asians (P = 0.01) and Aboriginal people (P < 0.001) than among Europeans. A high glycemic index was associated with a larger decrease in adiponectin among South Asians (P = 0.03) and Aboriginal people (P < 0.001) and a larger increase in HOMA-IR among South Asians (P < 0.05) relative to that in other groups. CONCLUSIONS South Asians have the least favorable adipokine profile and, like the Aboriginal people, display a greater increase in insulin resistance with decreasing levels of adiponectin. Differences in adipokines and responses to glycemic foods parallel the ethnic differences in insulin resistance.

CONTEXT: Obesity is a major public health problem in North America, particularly in Aboriginal people. OBJECTIVE: To determine if a household-based lifestyle intervention is effective at reducing energy intake and increasing physical activity among Aboriginal families after 6 months. DESIGN, PARTICIPANTS, AND INTERVENTION: Randomized, open trial of 57 Aboriginal households recruited between May 2004 and April 2005 from the Six Nations Reserve in Ohsweken, Canada. Aboriginal Health Counsellors made regular home visits to assist families in setting dietary and physical activity goals. Additional interventions included provision of filtered water, a physical activity program for children, and educational events about healthy lifestyles. RESULTS: 57 households involving 174 individuals were randomized to intervention or usual care. Intervention households decreased consumption of fats, oils and sweets compared to usual care households (-4.9 servings per day vs. -3 servings/day, p=0.006), and this was associated with a reduction in trans fatty acids (-0.2 vs. +0.6 grams/day, p=0.02). Water consumption increased (+0.3 vs. -0.1 servings/day, p

Background Microflora-dependent trimethylamine-N-oxide (TMAO) formation, which results from intake of choline and L-carnitine-rich food, shows promise as a predictor of cardiovascular disease (CVD) risk, but these associations have not been examined in ethnically diverse populations. In a multiethnic population-based study of adults in Canada, we assessed the stability of TMAO and L-carnitine in stored serum samples and their association with intimal medial thickness, prevalent risk factors, and clinical events. Methods In a randomly sampled cross-sectional study of 1286 Canadians, fasting serum samples were collected and stored. In 292 consecutive individuals (99 CVD cases and 193 unmatched control subjects), L-carnitine and TMAO concentrations were assessed using validated analytical approaches. Results The mean (± SD) TMAO level was 1.998 ± 3.13 μM and L-carnitine was 42.29 ± 11.35 μM. The relative levels of the samples did not appreciably change after 3 freeze-thaw cycles (coefficient of variation, 5.6% and 4.7%, respectively). No significant association between L-carnitine levels and prevalent CVD was found, with adjustment for covariates (odds ratio, 1.57; 95% confidence interval, 0.58-4.26; P trend = 0.65), for highest vs lowest quintile group. TMAO levels showed a significant, graded association with prevalent CVD (odds ratio, 3.17; 95% confidence interval, 1.05-9.51; P trend = 0.02). After further adjustment for diabetes status, meat, fish, and cholesterol intake, the association remained significant. No significant association between carotid intimal medial thickness and L-carnitine ( P = 0.64) or TMAO ( P = 0.18) was found. Conclusions Serum TMAO and L-carnitine analysis on stored samples is reliable. Our findings support an association between TMAO with prevalent CVD in a multiethnic population. This finding requires replication in larger studies in which dietary intake and stored serum samples exist.

This article describes the methods taken to create an understanding of the perinatal health beliefs of elder Indigenous women of the Six Nations of the Grand River in Ontario, Canada. Our study paired constructivist grounded theory data collection and analysis methods with an Indigenous epistemological framework. We aimed to create knowledge that was specific to an Indigenous context, which was useful and resonant with both Indigenous and Western readers. The multidisciplinary research team included Indigenous and non-Indigenous members and worked with a common appreciation for multiple knowledge sources. We offer an account of our process and methodological principles to serve as an illustrative case study of bringing together diverse approaches when working with Indigenous communities.

Summary Background Little is known about the rates of cardiovascular disease (CVD), atherosclerosis, and their risk factors among Canada's Aboriginal people. To establish the relative prevalence of risk factors, atherosclerosis, and CVD, we undertook a population-based study among people of Aboriginal and European ancestry in Canada. Methods We randomly recruited 301 Aboriginal people from the Six Nations Reservation, and 326 people of European origin from Hamilton, Toronto, and Edmonton, Canada. Clinical CVD was defined by history or electrocardiographic findings, atherosclerosis was measured by B-mode carotid ultrasonography, and conventional and new CVD risk factors were measured using standardised methods. Findings Aboriginal people had significantly more carotid atherosclerosis (mean of the maximum intimal-medial thickness 0·82 (SD 0·20) mm vs 0·78 (0·20) mm, p=0·027), and had a higher frequency of CVD (18·5% vs 7·6%, p=0·00002) compared with Europeans. Aboriginal people had significantly higher rates of smoking, glucose intolerance, obesity, abdominal obesity, and substantially higher concentrations of fibrinogen, and plasminogen activator inhibitor-1. Aboriginal people had significantly higher rates of unemployment and a lower annual household income. For any given income level, Aboriginal people had higher rates of risk factors and CVD compared with the Europeans. Interpretation A significant proportion of Aboriginal people live in poverty which is associated with high rates of CVD and CVD risk factors. Improvement of the socioeconomic status of Aboriginal people might be a key to reduce CVD in this group.

Force production by kinesins has been linked to structural rearrangements of the N and C termini of their motor domain upon nucleotide binding. In recent crystal structures, the Kar3-associated protein Vik1 shows unexpected homology to these conformational states even though it lacks a nucleotide-binding site. This conservation infers a degree of commonality in the function of the N- and C-terminal regions during the mechanochemical cycle of all kinesins and kinesin-related proteins. We tested this inference by examining the functional effects on Kar3Vik1 of mutating or deleting residues in Vik1 that are involved in stabilizing the C terminus against the core and N terminus of the Vik1 motor homology domain (MHD). Point mutations at two moderately conserved residues near the Vik1 C terminus impaired microtubule gliding and microtubule-stimulated ATP turnover by Kar3Vik1. Deletion of the seven C-terminal residues inhibited Kar3Vik1 motility much more drastically. Interestingly, none of the point mutants seemed to perturb the ability of Kar3Vik1 to bind microtubules, whereas the C-terminal truncation mutant did. Molecular dynamics simulations of these C-terminal mutants showed distinct root mean square fluctuations in the N-terminal region of the Vik1 MHD that connects it to Kar3. Here, the degree of motion in the N-terminal portion of Vik1 highly correlated with that in the C terminus. These observations suggest that the N and C termini of the Vik1 MHD form a discrete folding motif that is part of a communication pathway to the nucleotide-binding site of Kar3.

Background Adiponectin, a secretagogue exclusively produced by adipocytes, has been associated with metabolic features, but its role in the development of the metabolic syndrome remains unclear. Objectives We investigated the association between serum adiponectin level and metabolic traits, using both observational and genetic epidemiologic approaches in a multiethnic population assembled in Canada. Methods Clinical data and serum adiponectin level were collected in 1,157 participants of the SHARE/SHARE-AP studies. Participants were genotyped for the functional rs266729 and rs1260326 SNPs in ADIPOQ and GCKR genes. Results Adiponectin level was positively associated with HDL cholesterol and negatively associated with body mass index, waist-to-hip ratio, triglycerides, fasting glucose, fasting insulin, systolic and diastolic pressure (all P

Background Rapid change in food intake, physical activity, and tobacco use in recent decades have contributed to the soaring rates of obesity, type 2 diabetes and cardiovascular disease (CVD) in Aboriginal populations living in Canada. The nature and influence of contextual factors on Aboriginal health behaviours are not well characterized. Methods To describe the contextual determinants of health behaviours associated with cardiovascular risk factors on the Six Nations reserve, including the built environment, access and affordability of healthy foods, and the use of tobacco. In this cross-sectional study, 63 adults from the Six Nations Reserve completed the modified Neighbourhood Environment Walkability Scale (NEWS), questionnaire assessing food access and availability, tobacco pricing and availability, and the Environmental Profile of Community Health (EPOCH) tool. Results The structured environment of Six Nations Reserve scored low for walkability, street connectivity, aesthetics, safety, and access to walking and cycling facilities. All participants purchased groceries off-reserve, although fresh fruits and vegetables were reported to be available and affordable both on and off-reserve. On average $151/week is spent on groceries per family. Ninety percent of individuals report tobacco use is a problem in the community. Tobacco is easily accessible for children and youth, and only three percent of community members would accept increased tobacco taxation as a strategy to reduce tobacco access. Conclusions The built environment, access and affordability of healthy food and tobacco on the Six Nations Reserve are not perceived favourably. Modification of these contextual factors described here may reduce adverse health behaviours in the community.

Kar3Vik1 is a heterodimeric kinesin with one catalytic subunit (Kar3) and one noncatalytic subunit (Vik1).Vik1 experiences conformational changes in regions analogous to the force-producing elements in catalytic kinesins.A molecular mechanism by which Kar3 could trigger Vik1's release from microtubules was revealed.These findings will serve as the prototype for understanding the motile mechanism of kinesin-14 motors in general. It is widely accepted that movement of kinesin motor proteins is accomplished by coupling ATP binding, hydrolysis, and product release to conformational changes in the microtubule-binding and force-generating elements of their motor domain. Therefore, understanding how the Saccharomyces cerevisiae proteins Cik1 and Vik1 are able to function as direct participants in movement of Kar3Cik1 and Kar3Vik1 kinesin complexes presents an interesting challenge given that their motor homology domain (MHD) cannot bind ATP. Our crystal structures of the Vik1 ortholog from Candida glabrata may provide insight into this mechanism by showing that its neck and neck mimic-like element can adopt several different conformations reminiscent of those observed in catalytic kinesins. We found that when the neck is α-helical and interacting with the MHD core, the C terminus of CgVik1 docks onto the central β-sheet similarly to the ATP-bound form of Ncd. Alternatively, when neck-core interactions are broken, the C terminus is disordered. Mutations designed to impair neck rotation, or some of the neck-MHD interactions, decreased microtubule gliding velocity and steady state ATPase rate of CgKar3Vik1 complexes significantly. These results strongly suggest that neck rotation and neck mimic docking in Vik1 and Cik1 may be a structural mechanism for communication with Kar3.

Background Germline mutations of BRCA1/2 are associated with hereditary breast and ovarian cancer. Recent data suggests excess mortality in mutation carriers beyond that conferred by neoplasia, and recent in vivo and in vitro studies suggest a modulatory role for BRCA proteins in endothelial and cardiomyocyte function. We therefore tested the association of BRCA2 variants with clinical cardiovascular disease (CVD). Methods Using data from 1,170 individuals included in two multi-ethnic population-based studies (SHARE and SHARE-AP), the association between BRCA2 variants and CVD was evaluated. 15 SNPs in BRCA2 with minor allele frequencies (MAF) > 0.01 had been previously genotyped using the cardiovascular gene-centric 50 k SNP array. 115 individuals (9.8%) reported a CVD event, defined as myocardial infarction (MI), angina, silent MI, stroke, and angioplasty or coronary artery bypass surgery. Analyses were adjusted for age and sex. The SNPs rs11571836 and rs1799943 were subsequently genotyped using the MassARRAY platform in 1,045 cases of incident MI and 1,135 controls from the South Asian subset of an international case-control study of acute MI (INTERHEART), and rs11571836 was imputed in 4,686 cases and 4500 controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS). Results Two BRCA2 SNPs, rs11571836 and rs1799943, both located in untranslated regions, were associated with lower risk of CVD (OR 0.47 p = 0.01 and OR 0.56 p = 0.03 respectively) in the SHARE studies. Analysis by specific ethnicities demonstrated an association with CVD for both SNPs in Aboriginal People, and for rs11571836 only in South Asians. No association was observed in the European and Chinese subgroups. A non-significant trend towards an association between rs11571836 and lower risk of MI was observed in South Asians from INTERHEART [OR = 0.87 (95% CI: 0.75-1.01) p = 0.068], but was not evident in PROMIS [OR = 0.96 (95% CI: 0.90-1.03) p = 0.230]. Meta-analysis of both case-control studies resulted in a combined OR of 0.94 (95% CI: 0.89-1.004, p = 0.06). Conclusions Although there was an association between two SNPs in BRCA2 and CVD in a multi-ethnic population, these results were not replicated in two South Asian case-control studies of incident MI. Future studies exploring the association between BRCA variants and cardiovascular disorders are needed to clarify the role, if any, for BRCA variants in CVD pathogenesis.

Background Social disadvantage is defined by adverse socio-economic characteristics and is distributed unequally by age, sex, and ethnicity. We studied the relationship between social disadvantage, cardiovascular risk factors, and cardiovascular disease (CVD) among men and women from diverse ethno-racial backgrounds. Methods A total of 1227 men and women of South Asian, Chinese, Aboriginal, and European ancestry were randomly selected from four communities in Canada to undergo a health assessment. Socio-economic factors, conventional and novel CV risk factors, atherosclerosis, and CVD were measured. A social disadvantage index was generated and included employment status, income, and marital status. Social disadvantage was examined in relation to risk factors for CVD, atherosclerosis, and prevalent CVD. Results Social disadvantage was higher among older people, women, and non-white ethnic groups. Cigarette smoking, glucose, overweight, abdominal obesity, and CRP were higher among individuals with higher social disadvantage, whereas systolic blood pressure, lipids, norepinephrine, and atherosclerosis were not. Social disadvantage is an independent predictor of CVD after adjustment for conventional and novel risk markers for CVD (OR for 1 point increase = 1.25; 95% CI 1.06-1.47). Conclusion The social disadvantage index combines social and economic exposures into a single continuous measure. Significant variation in social disadvantage by age, sex, and ethnic group exists. Increased social disadvantage is associated with an increased burden of some CV risk factors, and is an independently associated with CVD.

OBJECTIVE: To study how clinical preceptors select patients for medical student teaching in ambulatory care and to explore key factors they consider in the selection process. DESIGN: Qualitative analysis of transcribed interviews. SETTING: Harvard Medical School, Boston, Mass. PARTICIPANTS: Nineteen physicians (14 general internists and 5 general pediatricians) who serve as clinical preceptors. MEASUREMENTS: Responses to in-depth open-ended interview regarding selection of patients for participation in medical student teaching. MAIN RESULTS: Preceptors consider the competing needs of the patient, the student, and the practice the most important factors in selecting patients for medical student teaching. Three dominant themes emerged: time and efficiency, educational value, and the influence of teaching on the doctor-patient relationship. These physicians consciously attempt to select patients whose participation in medical student teaching maximizes the efficiency of the clinical practice and optimizes the students’ educational experiences, while minimizing any potential for harming the relationship between preceptor and patient. CONCLUSIONS: These findings may help validate the frustration preceptors frequently feel in their efforts to teach in the outpatient setting. Becoming more cognizant of the competing interests—the needs of the patient, the student, and the practice—may help physicians to select patients to enhance the educational experience without compromising efficiency or the doctor-patient relationship. For educators, this study suggests an opportunity for faculty development programs to assist the clinical preceptor both in selecting patients for medical student teaching and in finding ways to maximize the efficiency and educational quality of the outpatient teaching environment.

Background: The goals of antihypertensive therapy are to achieve and maintain blood pressure control by the least intrusive means possible to prevent future cardiovascular and renal events. To achieve these goals, pharmacologic agents must be chosen so as to minimize drug-related adverse events, increase patient adherence to treatment regimens, and minimize the negative impact on health-related quality of life (HRQL). Although the effects of antihypertensive therapy on HRQL have been extensively investigated, there is little synthesis of the research findings. Objective: This review was undertaken to provide a synthesis of the available data on the impact of antihypertensive therapy on HRQL and to provide recommendations for future research. Methods: A MEDLINE literature search was conducted to identify English-language articles published from 1990 to 2000 that included random assignment to antihypertensive treatment and HRQL as an outcome. In addition, reference lists of published reviews and other trials were reviewed to identify other studies of HRQL and antihypertensive therapy. Results: A total of 48 articles were included in the review. Results among studies were frequently inconsistent, which is likely due to the wide variety of dimensions studied and instruments used as well as a number of methodological weaknesses, including small sample sizes, short-term assessments, and failure to account for missing data. Conclusion: A standardized approach to the assessment of HRQL in hypertensive patients is needed so that research in this area can be of value to clinical practice and to hypertensive patients and their families.

Recommendations resulting from a JCAHO survey can be a true blessing as they force nursing departments to assess critically their professional practice and documentation systems. Systematic preparation, begun at least two years prior to the survey, includes Nursing Administration, a Nursing Documentation Task Force and all staff nurses. Educational consultants assigned to each unit bring nurses up-to-date on nursing process and nursing diagnosis. Mock surveys and cross-training in chart review prepare staff nurses for confident participation in the accreditation process.

The spatial arrangement of a cell's contents, and its ability to redistribute them, is fundamental to its survival. In all animal and plant cells, kinesins fill a large part of this need, hauling chromosomes and vital cargo-containing sacks to their required destinations. Many kinesins operate as a homodimer in which the two subunits coordinate their movement along microtubules and perform a single cellular function. However, a few kinesins in certain species mix-and-match different molecules in ways that allow the motor to perform multiple functions. Certain types of pathogenic fungi harbor an unusual group of kinesins that form heterodimeric complexes with one or more non-catalytic kinesin-like proteins that regulate the function and cellular localization of their catalytic partner. A challenge in the motor protein field is to provide a mechanistic view of how these asymmetric motors move using this unconventional form of motor subunit arrangement. Our recent determination of the X-ray crystal structures of the motor domain region of both the catalytic and non-catalytic subunits of a heterodimeric kinesin from Candida glabrata revealed that certain regions of the latter subunit are highly dynamic. Specifically, our crystals of CgVik1 (the non-catalytic subunit) exhibit three very different conformations of an alpha-helical segment that is analogous to the force-producing ‘neck’ element of kinesins. The intramolecular interactions of the CgVik1 neck and its motor core differ in each conformation and are accompanied by movements in elements that are analogous to the nucleotide binding ‘P-loop’ and part of the microtubule binding surface of catalytic kinesins. This suggests a functional link between CgVik1 neck orientation and microtubule interactions and motility of the motor complex, and sheds light on how this kinesin works at the atomic level as an asymmetric motor complex.