Comparison of Clinical, Genetic, and Pathologic Features of Limbic and Diffuse Transactive Response DNA-Binding Protein 43 Pathology in Alzheimer's Disease Neuropathologic Spectrum.

BACKGROUND: Increasing evidence suggests that TAR DNA-binding protein 43 (TDP-43) pathology in Alzheimer's disease (AD), or AD-TDP, can be diffuse or limbic-predominant. Understanding whether diffuse AD-TDP has genetic, clinical, and pathological features that differ from limbic AD-TDP could have clinical and research implications. OBJECTIVE: To better characterize the clinical and pathologic features of diffuse AD-TDP and differentiate it from limbic AD-TDP. METHODS: 363 participants from the Mayo Clinic Study of Aging, Alzheimer's Disease Research Center, and Neurodegenerative Research Group with autopsy confirmed AD and TDP-43 pathology were included. All underwent genetic, clinical, neuropsychologic, and neuropathologic evaluations. AD-TDP pathology distribution was assessed using the Josephs 6-stage scale. Stages 1-3 were classified as Limbic, those 4-6 as Diffuse. Multivariable logistic regression was used to identify clinicopathologic features that independently predicted diffuse pathology. RESULTS: The cohort was 61% female and old at onset (median: 76 years [IQR:70-82]) and death (median: 88 years [IQR:82-92]). Fifty-four percent were Limbic and 46% Diffuse. Clinically, ∼10-20% increases in odds of being Diffuse associated with 5-year increments in age at onset (p = 0.04), 1-year longer disease duration (p = 0.02), and higher Neuropsychiatric Inventory scores (p = 0.03), while 15-second longer Trailmaking Test-B times (p = 0.02) and higher Block Design Test scores (p = 0.02) independently decreased the odds by ~ 10-15%. There was evidence for association of APOEɛ4 allele with limbic AD-TDP and of TMEM106B rs3173615 C allele with diffuse AD-TDP. Pathologically, widespread amyloid-ß plaques (Thal phases: 3-5) decreased the odds of diffuse TDP-43 pathology by 80-90%, while hippocampal sclerosis increased it sixfold (p < 0.001). CONCLUSION: Diffuse AD-TDP shows clinicopathologic and genetic features different from limbic AD-TDP.

Examining Psychological and Knowledge Barriers to Colorectal Cancer Screening in Rural Appalachian Kentucky.

While recent rates of colorectal cancer (CRC) screening have improved in Appalachian Kentucky due to public health efforts, they remain lower compared to both KY as a whole, and the USA. Suboptimal screening rates represent a missed opportunity to engage in early detection and prevention. The purpose of this study is to determine the impact that lack of knowledge has on psychological barriers (e.g., fear and embarrassment) to CRC screening as well as the potential effect of a psychosocial intervention to reduce these barriers. Participants were recruited through faith-based organizations and other community sites. After randomizing participants to either an early or delayed group, a faith-based group education and motivational interviewing intervention was administered. Existing and pilot tested instruments were used to assess knowledge and potential psychological barriers. Data were analyzed using paired t tests and linear regression. We hypothesized that (1) psychological barriers are associated with inadequate knowledge and (2) the intervention, by improving knowledge, could reduce these barriers and increase screening rates. There was a small but significant reduction in psychological barriers (-0.11, p value = 0.015) and moderate increases in CRC knowledge scores (+0.17, p value = 0.06). There was no evidence that the intervention affected these measures (+0.10, p value = 0.58). The relationship between lower barrier scores and increased knowledge was significant at follow up (-0.05, 95% CI (-0.09, -0.00)). An increase in CRC knowledge was correlated with a small but significant decrease in psychological barriers, although there was no evidence that these changes were associated with one another. Future cognitive-based interventions may be effective in increasing CRC knowledge and reducing barriers, but new intervention approaches should be considered.

Expression of select mRNA in Thoroughbreds with catastrophic racing injuries.

BACKGROUND: The ability to identify horses at risk for catastrophic injuries continues to be a pressing issue for the racing industry, especially given recent events in North America. OBJECTIVES: Since most catastrophic injuries occur in areas of existing pathology and this pathology is likely to elicit an inflammatory response, it was hypothesised that analysis of messenger RNA (mRNA) expression would detect significant changes in select genes in horses at risk for a catastrophic injury. STUDY DESIGN: Prospective cohort study. METHODS: Five racing jurisdictions across the United States participated in this study. A total of 686 Tempus® RNA Blood Tube samples were collected for mRNA analysis from 107 catastrophically injured horses, as well as from noninjured horses sampled either prerace (n = 374) or postrace (n = 205). A subset of horses (n = 37) were sampled both prerace and postrace for analysis of expression changes during the postrace period. RESULTS: Of 21 genes analysed via RT-qPCR, the expression of 12 genes (ALOX5AP, CD14, IL-10, IL-1ß, IL-6, IL-8, MMP1, PTGS2, TLR4, TNFα, TNFSF13B and VEGFA) changed significantly within 45 minutes after a race and were excluded. Of the remaining nine genes (BMP-2, IGF-1, IL1RN, MMP2, MMP9, Osteoprotegrin, RANKL, SAA1 and TGFß), three genes (IGF-1, IL1RN and MMP2) were found to be significantly different between catastrophically injured and noninjured horses using multiple logistic regression modelling. Receiver operating characteristic analysis of models, which included mRNA expression, demonstrated sensitivities from 76%-82% (95% CI: 67%-93%) and specificities from 84%-88% (95% CI: 71%-94%) at the Youden Index. MAIN LIMITATIONS: Samples were collected as soon as possible postinjury (within 30 minutes). CONCLUSIONS: Analysis of mRNA expression of specific genes in the future may be considered as an economical, accessible and noninvasive means by which horses at risk for catastrophic injury can be identified.

The mediating/moderating role of cultural context factors on self-care practices among those living with diabetes in rural Appalachia.

BACKGROUND: The aim of this study was to examine whether cultural factors, such as religiosity and social support, mediate/moderate the relationship between personal/psychosocial factors and T2DM self-care in a rural Appalachian community. METHODS: Regression models were utilized to assess for mediation and moderation. Multilevel linear mixed effects models and GEE-type logistic regression models were fit for continuous (social support, self-care) and binary (religiosity) outcomes, respectively. RESULTS: The results indicated that cultural context factors (religiosity and social support) can mediate/moderate the relationship between psychosocial factors and T2DM self-care. Specifically, after adjusting for demographic variables, the findings suggested that social support may moderate the effect of depressive symptoms and stress on self-care. Religiosity may moderate the effect of distress on self-care, and empowerment was a predictor of self-care but was not mediated/moderated by the assessed cultural context factors. When considering health status, religiosity was a moderately significant predictor of self-care and may mediate the relationship between perceived health status and T2DM self-care. CONCLUSIONS: This study represents the first known research to examine cultural assets and diabetes self-care practices among a community-based sample of Appalachian adults. We echo calls to increase the evidence on social support and religiosity and other contextual factors among this highly affected population. TRIAL REGISTRATION: US National Library of Science identifier NCT03474731. Registered March 23, 2018, www.clinicaltrials.gov .

Rural Residents' Perspectives on an mHealth or Personalized Health Coaching Intervention: Qualitative Study With Focus Groups and Key Informant Interviews.

BACKGROUND: Compared with national averages, rural Appalachians experience extremely elevated rates of premature morbidity and mortality. New opportunities, including approaches incorporating personal technology, may help improve lifestyles and overcome health inequities. OBJECTIVE: This study aims to gather perspectives on whether a healthy lifestyle intervention, specifically an app originally designed for urban users, may be feasible and acceptable to rural residents. In addition to a smartphone app, this program-Make Better Choices 2-consists of personalized health coaching, accelerometer use, and financial incentives. METHODS: We convened 4 focus groups and 16 key informant interviews with diverse community stakeholders to assess perspectives on this novel, evidence-based diet and physical activity intervention. Participants were shown a slide presentation and asked open-ended follow-up questions. The focus group and key informant interview sessions were audiotaped, transcribed, and subjected to thematic analysis. RESULTS: We identified 3 main themes regarding Appalachian residents' perspectives on this mobile health (mHealth) intervention: personal technology is feasible and desirable; challenges persist in implementing mHealth lifestyle interventions in Appalachian communities; and successful mHealth interventions should include personal connections, local coaches, and educational opportunities. Although viewed as feasible and acceptable overall, lack of healthy lifestyle awareness, habitual behavior, and financial constraints may challenge the success of mHealth lifestyle interventions in Appalachia. Finally, participants described several minor elements that require modification, including expanding the upper age inclusion, providing extra coaching on technology use, emphasizing personal and supportive connections, employing local coaches, and ensuring adequate educational content for the program. CONCLUSIONS: Blending new technologies, health coaching, and other features is not only acceptable but may be essential to reach vulnerable rural residents.

The effect of analyst training on fecal egg counting variability.

Fecal egg counts (FECs) are essential for veterinary parasite control programs. Recent advances led to the creation of an automated FEC system that performs with increased precision and reduces the need for training of analysts. However, the variability contributed by analysts has not been quantified for FEC methods, nor has the impact of training on analyst performance been quantified. In this study, three untrained analysts performed FECs on the same slides using the modified McMaster (MM), modified Wisconsin (MW), and the automated system with two different algorithms: particle shape analysis (PSA) and machine learning (ML). Samples were screened and separated into negative (no strongylid eggs seen), 1-200 eggs per gram of feces (EPG), 201-500 EPG, 501-1000 EPG, and 1001+ EPG levels, and ten repeated counts were performed for each level and method. Analysts were then formally trained and repeated the study protocol. Between analyst variability (BV), analyst precision (AP), and the proportion of variance contributed by analysts were calculated. Total BV was significantly lower for MM post-training (p = 0.0105). Additionally, AP variability and analyst variance both tended to decrease for the manual MM and MW methods. Overall, MM had the lowest BV both pre- and post-training, although PSA and ML were minimally affected by analyst training. This research illustrates not only how the automated methods could be useful when formal training is unavailable but also how impactful formal training is for traditional manual FEC methods.

Diagnostic performance of McMaster, Wisconsin, and automated egg counting techniques for enumeration of equine strongyle eggs in fecal samples.

Fecal egg counts are the cornerstone of equine parasite control programs. Previous work led to the development of an automated, image-analysis-based parasite egg counting system. The system has been further developed to include an automated reagent dispenser unit and a custom camera (CC) unit that generates higher resolution images, as well as a particle shape analysis (PSA) algorithm and machine learning (ML) algorithm. The first aim of this study was to conduct a comprehensive comparison of method precision between the original smartphone (SP) unit with the PSA algorithm, CC/PSA, CC/ML, and the traditional McMaster (MM) and Wisconsin (MW) manual techniques. Additionally, a Bayesian analysis was performed to estimate and compare sensitivity and specificity of all five methods. Feces were collected from horses, screened with triplicate Mini-FLOTAC counts, and placed into five categories: negative (no eggs seen), > 0 - ≤ 200 eggs per gram (EPG), > 200 - ≤ 500 EPG, > 500 - ≤ 1000 EPG, and > 1000 EPG. Ten replicates per horse were analyzed for each technique. Technical variability for samples > 200 EPG was significantly higher for MM than CC/PSA and CC/ML (p <  0.0001). Biological variability for samples> 0 was numerically highest for CC/PSA, but with samples > 200 EPG, MM had a significantly lower CV than MW (p =  0.001), MW had a significantly lower CV than CC/PSA (p <  0.0001), CC/ML had a significantly lower CV than both MW and SP/PSA (p <  0.0001, p =  0.0003), and CC/PSA had a significantly lower CV than CC/SP (p =  0.0115). Sensitivity was> 98 % for all five methods with no significant differences. Specificity, however, was significantly the highest for CC/PSA, followed numerically by SP/PSA, MM, CC/ML, and finally MW. Overall, the automated counting system is a promising new development in equine parasitology. Continued refinement to the counting algorithms will help improve precision and specificity, while additional research in areas such as egg loss, analyst variability at the counting step, and accuracy will help create a complete picture of its impact as a new fecal egg count method.

Evaluating the Feasibility and Acceptability of Internet-Based Cognitive Behavioral Therapy for Insomnia in Rural Women.

Background: Insomnia, one of the most common sleep disorders among women in midlife, is associated with multiple negative health outcomes. Rural Appalachian women are disproportionately affected by insufficient sleep, but their barriers to care (e.g., health care shortages, cultural norms) may prevent intervention. This study assessed the feasibility and acceptability of Sleep Healthy Using the Internet (SHUTi) an Internet-based version of cognitive behavioral therapy for insomnia in Appalachian women ages 45+ years. Materials and Methods: We used mixed methods to assess feasibility (through summaries of recruitment and retention data) and acceptability (quantitatively through online survey scales and qualitatively through interviews). Subject-level responses for satisfaction, adherence, and helpfulness scales were averaged over the multiple response domains and reported as percentages. Interviews were transcribed and coded using a multistage coding process. Results: Forty-six women (average age 55 years) enrolled; 38 completed the SHUTi program (retention = 82.6%). The majority of participants (61%) indicated that SHUTi made things "somewhat better" or "a lot better." Seventy-six percent reported that they followed the SHUTi protocol "most of the time" or "consistently." Most participants (84%) ranked SHUTi as "moderately" or "very" helpful. Participants expressed enthusiasm about SHUTi and offered minor suggestions for improvement. Conclusions: This study was the first to asses SHUTi in the health disparity population of Appalachian women. Rich insights gained through quantitative and qualitative data suggest that SHUTi was feasible and acceptable for middle-aged Appalachian women. Given rural Appalachian women's documented barriers to utilizing technology, these results hold promise for SHUTi's utility in other rural populations. Future research should incorporate a randomized case-control design within a larger sample and consider participants' suggestions for improvement.

Bevacizumab and Temozolomide Plus Radiation Regimen for Glioblastoma Multiforme.

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net.

Irinotecan and Carboplatin (IC) Regimen for Small-Cell Lung Cancer and Non-Small-Cell Lung Cancer.

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net.

Carboplatin (renally dosed) and Etoposide regimen for small-cell lung cancer.

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc, 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net.

Maintenance of activity and eating change after a clinical trial of tailored newsletters with older rural women.

BACKGROUND: In the Wellness for Women Project, a randomized-by-site 1-year controlled clinical trial, the efficacy of generic newsletters and newsletters tailored on Health Promotion Model behavior-specific cognitions, eating behavior, and activity behavior were compared among 225 women aged 50 to 69 years. OBJECTIVES: The purpose of this study was to compare the maintenance of change in healthy eating and physical activity over the 12 months following the tailored versus generic mailed newsletter intervention. METHODS: Outcomes at 18 and 24 months included behavioral markers and biomarkers of physical activity and eating. Data were analyzed using the multivariate approach to repeated measures analysis of variance and generalized estimating equations (alpha <.05). RESULTS: At 18 months, the tailored group maintained levels of all eating and activity behaviors, whereas the generic group maintained levels of fruit and vegetable servings, a moderate or greater activity, stretching exercise, lower body strength and flexibility but increased saturated fat intake and declined in weekly strength exercise and cardiorespiratory fitness. At 24 months, both groups maintained or returned to 12-month levels of all eating behaviors,moderate or greater activity, stretching exercise, and flexibility but declined in cardiorespiratory fitness; the tailored group maintained levels of strength exercise and lower body strength, whereas the generic group decreased in both. A greater proportion of women who received tailored newsletters continued to achieve most Healthy People 2010 criteria for eating and activity. DISCUSSION: Mailed tailored print newsletters were more efficacious than generic newsletters in facilitating maintenance of change in eating and activity for 6 months postintervention. Both tailored and generic newsletters facilitated the maintenance of change in eating behaviors and in moderate or greater physical activity and stretching exercise, whereas tailored newsletters were more efficacious in maintaining change in strength exercise for 12 months postintervention.

Clinical trial of tailored activity and eating newsletters with older rural women.

BACKGROUND: Unhealthy diet and lack of physical activity increase rural midlife and older women's risk of chronic diseases and premature death, and they are behind urban residents in meeting Healthy People 2010 objectives. OBJECTIVES: The objective of this study was to compare a tailored intervention based on the Health Promotion Model with a generic intervention to increase physical activity and healthy eating among rural women. METHODS: In a randomized-by-site, community-based, controlled, clinical trial, Wellness for Women, 225 women aged 50 to 69 years were recruited in two similar rural areas. Over 12 months, women received by mail either 18 generic newsletters or 18 newsletters computer tailored on Health Promotion Model behavior-specific cognitions (benefits, barriers, self-efficacy, and interpersonal support), activity, and eating. Outcomes at 6 and 12 months included behavioral markers and biomarkers of physical activity and eating. Data were analyzed by repeated-measures analysis of variance and chi-square tests (alpha < .05). RESULTS: Both groups significantly increased stretching and strengthening exercise and fruit and vegetable servings and decreased percentage of calories from fat, whereas only the tailored group increased moderate or greater intensity activity and decreased percentage of calories from saturated fat from baseline to 6 months. Both groups increased stretching and strengthening exercise, whereas only the tailored group increased moderate or greater intensity activity and fruit and vegetable servings and decreased percentage of calories from fat from baseline to 12 months. Both groups had several changes in biomarkers over the study. A higher proportion of women receiving tailored newsletters met Healthy People 2010 criteria for moderate or greater intensity activity, fruit and vegetable servings, and percentage of calories from fat at 12 months. DISCUSSION: Mailed computer-tailored and generic print newsletters facilitated the adoption of change in both activity and eating over 6 months. Tailored newsletters were more efficacious in facilitating change over 12 months.

Hispanics and health insurance coverage: the rising disparity.

BACKGROUND: Many reports have focused attention on the rising percentage of adults in the United States without health insurance. This hides the fact that the uninsured rate for non-Hispanic nonelderly adults has held fairly steady since 1983, while the rate for Hispanics has increased. OBJECTIVES: To document the trends in the coverage rate by source of coverage for different population groups between 1983 and 2003 and suggest how changes in the composition of these groups have contributed to these trends. RESEARCH DESIGN: We stack panels of the Survey of Income and Program Participation to create a nationally representative 20-year pooled cross-section of nonelderly adults. We calculate actual trends in insurance coverage as well as 2 hypothetical time series that disentangle the effect of the decreasing coverage rate for Hispanics from the growth of the Hispanic adult population. RESULTS: Although the increase in uninsured rate is largest for Hispanic noncitizens, US-born Hispanics also have a significant upward trend, primarily driven by a decrease in private coverage, with little change in public coverage. Although the increase in the Hispanic population contributed to the increase in the number of uninsured adults, the widening coverage disparity was more important. CONCLUSIONS: Hispanic nonelderly adults, both US-born and immigrants, have fallen behind non-Hispanic nonelderly adults in insurance coverage. Although combinations of economic growth and private and public insurance policy changes have maintained, and in some cases improved, overall coverage rates for non-Hispanics, these changes have not helped Hispanic adults, leading to increased disparities in coverage.

Higher income and uninsured: common or rare?

Massachusetts plans to penalize those who do not have health insurance, targeting higher-income people. Are higher-income Americans a small or substantial share of the uninsured? The U.S. Census Bureau reports that one in three Americans without health insurance lived in a household with income greater than $50,000 in 2005. Many of these higher-income uninsured people do not fit the profile of free-riders who have the money but are unwilling to buy coverage. A majority have lower incomes but live with others; only together are they higher income. For others, higher income or lack of insurance is transient.