Protocol for the Brain Health Support Program Study of the Canadian Therapeutic Platform Trial for Multidomain Interventions to Prevent Dementia (CAN-THUMBS UP): A Prospective 12-Month Intervention Study.

BACKGROUND/OBJECTIVES: CAN-THUMBS UP is designed as a comprehensive and innovative fully remote program to 1) develop an interactive and compelling online Brain Health Support Program intervention, with potential to positively influence dementia literacy, self-efficacy and lifestyle risk factors; 2) enroll and retain a community-dwelling Platform Trial Cohort of individuals at risk of dementia who will participate in the intervention; 3) support an open platform trial to test a variety of multidomain interventions that might further benefit individuals at risk of dementia. This manuscript presents the Brain Health Support Program Study protocol. DESIGN/SETTING: Twelve-month prospective multi-center longitudinal study to evaluate a fully remote web-based educational intervention. Participants will subsequently be part of a Platform Trial Cohort and may be eligible to participate in further dementia prevention clinical trials. PARTICIPANTS: Three hundred fifty older adults who are cognitively unimpaired or have mild cognitive impairment, with at least 1 well established dementia risk factor. INTERVENTION: Participants engage in the Brain Health Support Program intervention for 45-weeks and complete pre/post intervention measures. This intervention is designed to convey best available evidence for dementia prevention, consists of 181 chapters within 8 modules that are progressively delivered, and is available online in English and French. The program has been developed as a collaborative effort by investigators with recognized expertise in the program's content areas, along with input from older-adult citizen advisors. MEASUREMENTS: This study utilizes adapted remote assessments with accessible technologies (e.g. videoconferencing, cognitive testing via computer and mobile phone, wearable devices to track physical activity and sleep, self-administered saliva sample collection). The primary outcome is change in dementia literacy, as measured by the Alzheimer's Disease Knowledge Scale. Secondary outcomes include change in self-efficacy; engagement using the online program; user satisfaction ratings; and evaluation of usability and acceptance. Exploratory outcomes include changes in attitudes toward dementia, modifiable risk factors, performance on the Neuropsychological Test Battery, performance on self-administered online cognitive assessments, and levels of physical activity and sleep; success of the national recruitment plan; and the distribution of age adjusted polygenic hazard scores. CONCLUSIONS: This fully remote study provides an accessible approach to research with all study activities being completed in the participants' home environment. This approach may reduce barriers to participation, provide an easier and less demanding participant experience, and reach a broader geography with recruitment from all regions of Canada. CAN-THUMBS UP represents a Canadian contribution to the global World-Wide FINGERS program (alz.org/wwfingers).

A systematic review of viral exposures as a risk for rheumatoid arthritis.

OBJECTIVE: Different viral exposures have been implicated in the etiology of rheumatoid arthritis (RA). Evidence relating to the association between putative viral exposures and the development of RA was reviewed. METHODS: A systematic literature search was conducted using MEDLINE-OVID, EMBASE-OVID, PUBMED and Cochrane library databases. Articles were included if they were case-controls, cross-sectional or cohort studies and were published in English. Case-series were included if there was a lack of other study designs. RESULTS: Of 6724 citations, 48 were included in meta-analysis. Studies had poor quality. PBV19 infection was increased in RA compared to controls [N = 12, odds ratio (OR) 1.77 (95% CI: 1.11; 2.80) p = 0.02 for PVB19 IgG]. IgG anti-EBNA antibodies were not increased in RA (N = 17, p = 0.75), but anti-VCA [N = 18, OR 1.5 (95% CI: 1.07; 2.10), p = 0.02] and anti-EA antibodies [N = 11, OR 2.74 (95% CI: 1.27; 5.94), p = 0.01] were increased in RA. CMV was not associated with RA (N = 13, p = 0.42), nor was HBV (N = 5, p = 0.09). HCV was associated with RA in 7 case-control studies [OR 2.82 (95% CI: 1.35; 5.90), p = 0.006] and one cohort study [hazard ratio (HR) 2.03 (95% CI: 1.27, 3.22), p < 0.01]. Persistent arthritis was increased after Chikungunya fever [N = 2, OR 90 (95% CI: 15.2, 134.3), p = 0.047]. CONCLUSIONS: Studies of RA after viral exposures have poor quality. There is a risk of RA after Parvo B19, HCV and possibly EBV infection. CMV and HBV infections are not associated with RA. CHIKV is associated with the persistent inflammatory arthritis.

Accepting kidneys from older living donors: impact on transplant recipient outcomes.

Older living kidney donors are regularly accepted. Better knowledge of recipient outcomes is needed to inform this practice. This retrospective cohort study observed kidney allograft recipients from Ontario, Canada between January 2000 and March 2008. Donors to these recipients were older living (≥ 60 years), younger living, or standard criteria deceased (SCD). Review of medical records and electronic healthcare data were used to perform survival analysis. Recipients received 73 older living, 1187 younger living and 1400 SCD kidneys. Recipients of older living kidneys were older than recipients of younger living kidneys. Baseline glomerular filtration rate (eGFR) of older kidneys was 13 mL/min per 1.73 m² lower than younger kidneys. Median follow-up time was 4 years. The primary outcome of total graft loss was not significantly different between older and younger living kidney recipients [adjusted hazard ratio, HR (95%CI): 1.56 (0.98-2.49)]. This hazard ratio was not proportional and increased with time. Associations were not modified by recipient age or donor eGFR. There was no significant difference in total graft loss comparing older living to SCD kidney recipients [HR: 1.29 (0.80-2.08)]. In light of an observed trend towards potential differences beyond 4 years, uncertainty remains, and extended follow-up of this and other cohorts is warranted.

A genome-wide linkage scan for iron phenotype quantitative trait loci: the HEIRS Family Study.

Iron overload phenotypes in persons with and without hemochromatosis are variable. To investigate this further, probands with hemochromatosis or evidence of elevated iron stores and their family members were recruited for a genome-wide linkage scan to identify potential quantitative trait loci (QTL) that contribute to variation in transferrin saturation (TS), unsaturated iron-binding capacity (UIBC), and serum ferritin (SF). Genotyping utilized 402 microsatellite markers with average spacing of 9 cM. A total of 943 individuals, 64% Caucasian, were evaluated from 174 families. After adjusting for age, gender, and race/ethnicity, there was evidence for linkage of UIBC to chromosome 4q logarithm of the odds (LOD) = 2.08, p = 0.001) and of UIBC (LOD = 9.52), TS (LOD = 4.78), and SF (LOD = 2.75) to the chromosome 6p region containing HFE (each p < 0.0001). After adjustments for HFE genotype and other covariates, there was evidence of linkage of SF to chromosome 16p (LOD = 2.63, p = 0.0007) and of UIBC to chromosome 5q (LOD = 2.12, p = 0.002) and to chromosome 17q (LOD = 2.19, p = 0.002). We conclude that these regions should be considered for fine mapping studies to identify QTL that contribute to variation in SF and UIBC.

Initial screening transferrin saturation values, serum ferritin concentrations, and HFE genotypes in Native Americans and whites in the Hemochromatosis and Iron Overload Screening Study.

We compared initial screening transferrin saturation (TfSat) and serum ferritin (SF) phenotypes and HFE C282Y and H63D genotypes of 645 Native American and 43,453 white Hemochromatosis and Iron Overload Screening Study participants who did not report a previous diagnosis of hemochromatosis or iron overload. Elevated measurements were defined as TfSat >50% in men and >45% in women and SF >300 ng/ml in men and >200 ng/ml in women. Mean TfSat was 31% in Native American men and 32% in white men (p = 0.0337) and 25% in Native American women and 27% in white women (p < 0.0001). Mean SF was 153 microg/l in Native American and 151 microg/l in white men (p = 0.8256); mean SF was 55 microg/l in Native American women and 63 microg/l in white women (p = 0.0015). The C282Y allele frequency was 0.0340 in Native Americans and 0.0683 in whites (p < 0.0001). The H63D allele frequency was 0.1150 in Native Americans and 0.1532 in whites (p = 0.0001). We conclude that the screening TfSat and SF phenotypes of Native Americans are similar to those of whites. The allele frequencies of HFE C282Y and H63D are significantly lower in Native Americans than in whites.

A critical view of the rationale for routine, initial and periodic radiographic surveys.

Most dentists and dental faculties use an initial radiographic survey for the comprehensive-care patient rather than selective radiography, as recommended by professional organizations and radiation protection agencies. Survey or screening radiography has been justified in the belief that it is an essential health service designed to disclose serious occult disease and that failure to use such films might expose the dentist to successful malpractice litigation. However, incidence data indicate the chance of disclosing tumors, non-inflammatory cysts or other serious bone disease in the asymptomatic patient by screening jaw films is infinitesimal. On this basis, the practice is not justifiable as a public health measure, nor is the dentist who follows published national guidelines for prescription radiography vulnerable to successful litigation.