isrctn.org Identifier: ISRCTN42520374.

The vitamin D binding protein (DBP) is the major plasma carrier for vitamin D and its metabolites, but it is also an actin scavenger, and is the precursor to the immunomodulatory protein, Gc-MAF. Two missense variants of the DBP gene – rs7041 encoding Asp432Glu and rs4588 encoding Thr436Lys – change the amino acid sequence and alter the protein function. They are common enough to generate population-wide constitutive differences in vitamin D status, based on assay of the serum metabolite, 25-hydroxyvitamin D (25OHD). Whether these variants also influence the role of vitamin D in an immunologic milieu is not known. However, the issue is relevant, given the immunomodulatory effects of DBP and the role of protracted innate immune-related inflammation in response to tissue injury or repeated infection. Indeed, DBP and vitamin D may jointly or independently contribute to a variety of adverse health outcomes unrelated to classical notions of their function in bone and mineral metabolism. This review summarizes the reports to date of associations between DBP variants, and various chronic and infectious diseases. The available information leads us to conclude that DBP variants are a significant and common genetic factor in some common disorders, and therefore, are worthy of closer attention. In view of the heightened interest in vitamin D as a public health target, well-designed studies that look simultaneously at vitamin D and its carrier in relation to genotypes and adverse health outcome should be encouraged.

The last decade has witnessed important advances in our understanding of the genetics of pigmentation in European populations, but very little is known about the genes involved in skin pigmentation variation in East Asian populations. Here, we present the results of a study evaluating the association of 10 Single Nucleotide Polymorphisms (SNPs) located within 5 pigmentation candidate genes (OCA2, DCT, ADAM17, ADAMTS20, and TYRP1) with skin pigmentation measured quantitatively in a sample of individuals of East Asian ancestry living in Canada. We show that the non-synonymous polymorphism rs1800414 (His615Arg) located within the OCA2 gene is significantly associated with skin pigmentation in this sample. We replicated this result in an independent sample of Chinese individuals of Han ancestry. This polymorphism is characterized by a derived allele that is present at a high frequency in East Asian populations, but is absent in other population groups. In both samples, individuals with the derived G allele, which codes for the amino acid arginine, show lower melanin levels than those with the ancestral A allele, which codes for the amino acid histidine. An analysis of this non-synonymous polymorphism using several programs to predict potential functional effects provides additional support for the role of this SNP in skin pigmentation variation in East Asian populations. Our results are consistent with previous research indicating that evolution to lightly-pigmented skin occurred, at least in part, independently in Europe and East Asia.

BackgroundThe At Home/Chez Soi (AH/CS) Project is a randomized controlled trial of a Housing First intervention to meet the needs of homeless individuals with mental illness in five cities across Canada. The objectives of this paper are to examine the approach to participant recruitment and community engagement at the Toronto site of the AH/CS Project, and to describe the baseline demographics of participants in Toronto.MethodsHomeless individuals (n = 575) with either high needs (n = 197) or moderate needs (n = 378) for mental health support were recruited through service providers in the city of Toronto. Participants were randomized to Housing First interventions or Treatment as Usual (control) groups. Housing First interventions were offered at two different mental health service delivery levels: Assertive Community Treatment for high needs participants and Intensive Case Management for moderate needs participants. Demographic data were collected via quantitative questionnaires at baseline interviews.ResultsThe effectiveness of the recruitment strategy was influenced by a carefully designed referral system, targeted recruitment of specific groups, and an extensive network of pre-existing services. Community members, potential participants, service providers, and other stakeholders were engaged through active outreach and information sessions. Challenges related to the need for different sectors to work together were resolved through team building strategies. Randomization produced similar demographic, mental health, cognitive and functional impairment characteristics in the intervention and control groups for both the high needs and moderate needs groups. The majority of participants were male (69%), aged >40 years (53%), single/never married (69%), without dependent children (71%), born in Canada (54%), and non-white (64%). Many participants had substance dependence (38%), psychotic disorder (37%), major depressive episode (36%), alcohol dependence (29%), post-traumatic stress disorder (PTSD) (23%), and mood disorder with psychotic features (21%). More than two-thirds of the participants (65%) indicated some level of suicidality.ConclusionsRecruitment at the Toronto site of AH/CS project produced a sample of participants that reflects the diverse demographics of the target population. This study will provide much needed data on how to best address the issue of homelessness and mental illness in Canada.

BackgroundHousing First has become a popular treatment model for homeless adults with mental illness, yet little is known about program participants’ early experiences or trajectories. This study used a mixed methods design to examine participant changes in selected domains 6 months after enrolment in a Canadian field trial of Housing First.MethodsThe study sample included 301 participants receiving the Housing First intervention at the Toronto site of the At Home/Chez Soi project. This study used a pre-post design to compare quantitative 6-month outcome data to baseline values in key domains and multivariate regression to identify baseline demographic, clinical or service use variables associated with observed changes in these domains. In addition, qualitative data exploring participant and service provider perspectives and experiences was collected via stakeholder interviews and focus groups, and analyzed using thematic analysis.ResultsThe majority (60 to 72%) of participants followed the expected trajectory of improvement, with the remaining experiencing difficulties in community integration, mental health symptom severity, substance use, community functioning and quality of life 6 months after program enrolment. Diagnosis of psychotic disorder was associated with a reduction in quality of life from baseline to 6-months, while substance use disorders were associated with reduced mental illness symptoms and substance use related problems and an improvement in quality of life. Participants housed in independent housing at 6-months had greater improvements in community integration and quality of life, and greater reduction in mental illness symptoms, compared to those not independently housed. The quality of the working alliance was positively associated with improvements in physical and psychological community integration and quality of life. Qualitative data provided a unique window into the loneliness and isolation experienced by Housing First participants, as well as problems related to substance use and a need for life skills training and support.ConclusionsAdditional strategies can help support Housing First participants in the early stages of program participation and address potential causes of early difficulties, including lack of life skills and social isolation. This study highlights the importance of early and ongoing evaluation, monitoring and program adaptations to address consumer support needs.Trial registrationCurrent Controlled Trials ISRCTN42520374

Housing First (HF) is being widely disseminated in efforts to end homelessness among homeless adults with psychiatric disabilities. This study evaluates the effectiveness of HF with Intensive Case Management (ICM) among ethnically diverse homeless adults in an urban setting. 378 participants were randomized to HF with ICM or treatment-as-usual (TAU) in Toronto (Canada), and followed for 24 months. Measures of effectiveness included housing stability, physical (EQ5D-VAS) and mental (CSI, GAIN-SS) health, social functioning (MCAS), quality of life (QoLI20), and health service use. Two-thirds of the sample (63%) was from racialized groups and half (50%) were born outside Canada. Over the 24 months of follow-up, HF participants spent a significantly greater percentage of time in stable residences compared to TAU participants (75.1% 95% CI 70.5 to 79.7 vs. 39.3% 95% CI 34.3 to 44.2, respectively). Similarly, community functioning (MCAS) improved significantly from baseline in HF compared to TAU participants (change in mean difference = +1.67 95% CI 0.04 to 3.30). There was a significant reduction in the number of days spent experiencing alcohol problems among the HF compared to TAU participants at 24 months (ratio of rate ratios = 0.47 95% CI 0.22 to 0.99) relative to baseline, a reduction of 53%. Although the number of emergency department visits and days in hospital over 24 months did not differ significantly between HF and TAU participants, fewer HF participants compared to TAU participants had 1 or more hospitalizations during this period (70.4% vs. 81.1%, respectively; P=0.044). Compared to non-racialized HF participants, racialized HF participants saw an increase in the amount of money spent on alcohol (change in mean difference = $112.90 95% CI 5.84 to 219.96) and a reduction in physical community integration (ratio of rate ratios = 0.67 95% CI 0.47 to 0.96) from baseline to 24 months. Secondary analyses found a significant reduction in the number of days experiencing problems due to alcohol use among foreign-born (vs. Canadian-born) HF participants at 24 months (ratio of rate ratios = 0.19 95% 0.04 to 0.88), relative to baseline. Compared to usual care, HF with ICM can improve housing stability and community functioning and reduce the days of alcohol related problems in an ethnically diverse sample of homeless adults with mental illness within 2-years.Trial RegistrationControlled-Trials.com ISRCTN42520374.

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