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This study used administrative data to compare the socio-demographics, health conditions, and health service use of autistic adults with adults with and without other developmental disabilities, after matching for age and sex. Autistic women and men were more likely to have a wide range of physical and mental health conditions compared to adults without developmental disabilities. Rates of co-occurring health conditions were similar or lower among autistic adults compared to adults with other developmental disabilities, except for a higher prevalence of psychiatric conditions among autistic adults. Notably increased psychiatric service use was evident among autistic women and men compared to the other groups. Among age-matched autistic women and men, significant differences were found for physical (i.e. Crohn's disease/colitis, rheumatoid arthritis) and psychiatric conditions (i.e. psychotic disorders, non-psychotic disorders), as well as service use (i.e. emergency department visits, hospitalizations, family doctor and neurologist visits). These findings suggest autistic adults have high health care needs, as do adults with other developmental disabilities. Mental health support is especially critical for autistic adults and research examining sex and gender effects will assist in tailoring health promotion and intervention efforts.

Background: Rates of death and avoidable deaths are reportedly higher among people with intellectual and developmental disabilities. This study contributes to our understanding of how mortality and intellectual and development disabilities are associated. Method: General population and intellectual and developmental disabilities adult cohorts were defined using linked administrative data. All-cause and amenable deaths between 2010 and 2015 were reported for these cohorts and subcohorts with and without Down syndrome. Cox proportional hazards models evaluated the impact of potential contributors to amenable deaths. Results: Adults with intellectual and developmental disabilities had higher all-cause (6.1 vs. 1.6%) and amenable death percentages (21.4 vs. 14.1%) than general population comparators. Within intellectual and developmental disabilities, those with Down syndrome had higher all-cause (12.0 vs. 6.0%) but lower amenable death percentages (19.2 vs. 21.8%) than those without. Conclusions: Results suggest that interventions to reduce amenable deaths target provider-care-recipient interactions and coordination across care and support sectors.

Background: To address the growing concerns over poor mental health experienced by adults with intellectual disabilities due to the COVID-19 pandemic, a national virtual mental health course was delivered and evaluated. Methods: This mixed methods study utilized both qualitative and quantitative assessments. Participants were 27 adults with intellectual disabilities who participated in the 6-week course. Participants completed measures of self-efficacy and well-being at three time points and qualitative satisfaction measures at post and follow-up. Results: Attendance was high and the course was feasible and acceptable to participants. Positive changes related to mental health self-efficacy were detected (p = 0.01), though mental well-being did not improve. Conclusion: The study provided evidence for the feasibility and value of the course for this population. Future research should examine how virtual courses could support the population in terms of pandemic recovery and how courses may work for individuals who are less independent.

BackgroundThe safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known.MethodsIn this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru.ResultsA total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P

Background: There is little research with people who experience intellectual/developmental disabilities and imprisonment. Methods: The study linked health and correctional data to examine prevalence of intellectual/developmental disabilities and health and correctional characteristics among adults experiencing their first federal incarceration between 1 January 2002 and 31 December 2011 (n = 9278) and two non-incarcerated groups (n = 10,086,802). Results: The prevalence of intellectual/developmental disabilities was 2.1% in the incarcerated group and 0.9% in the non-incarcerated group. Before incarceration, those with, versus without, intellectual/developmental disabilities were at greater risk of traumatic brain injury, mental illness, and substance use disorders. While incarcerated, those with intellectual/developmental disabilities were more likely to incur serious institutional disciplinary charges. Post-incarceration, persons with intellectual/developmental disabilities were at greater risk of emergency department visits, and psychiatric and acute hospitalizations, than the non-incarcerated groups. Conclusions: People with intellectual/developmental disabilities are overrepresented in Canadian federal correctional institutions. The authors offer strategies to support people prior to, during, and post-incarceration.

BACKGROUND. Disease due to dengue viruses is a growing global health threat, causing 100-400 million cases annually. An ideal dengue vaccine should demonstrate durable protection against all 4 serotypes in phase III efficacy trials, however the lack of circulating serotypes may lead to incomplete efficacy data. Controlled human infection models help downselect vaccine candidates and supply critical data to supplement efficacy trials. We evaluated the efficacy of a leading live-attenuated tetravalent dengue vaccine candidate, TV005, against infection with a newly established dengue serotype 3 or an established serotype 2 challenge virus. METHODS. Two randomized, controlled clinical trials were performed. In study 1, a total of 42 participants received TV005 or placebo (n = 21 each), and 6 months later, all were challenged with dengue 2 virus (rDEN2[DELTA]30) at a dose of 103 PFU. In study 2, a total of 23 participants received TV005 and 20 received placebo, and 6 months later, all were challenged with 104 PFU dengue 3 virus (rDEN3[DELTA]30). The study participants were closely monitored for safety, viremia, and immunologic responses. Infection, measured by post-challenge viremia, and the occurrence of rash and neutropenia were the primary endpoints. Secondary endpoints included safety, immunologic, and virologic profiles following vaccination with TV005 and subsequent challenge with the rDEN2[DELTA]30 or rDEN3[DELTA]30 strain. RESULTS. TV005 was well tolerated and protected all vaccinated volunteers from viremia with DENV2 or DENV3 (none infected in either group). Placebo recipients had post-challenge viremia (100% in study 1, 85% in study 2), and all experienced rash following challenge with either serotype. CONCLUSIONS. TV005 is a leading tetravalent dengue vaccine candidate that fully protected against infection with DENV2 and DENV3 in an established controlled human infection model. TRIAL REGISTRATION. ClinicalTrials.gov NCT02317900 and NCT02873260. FUNDING. Intramural Research Program, NIH (contract HHSN272200900010C)., Introduction Dengue viruses are estimated to cause 100-400 million symptomatic illnesses each year, with a significant and expanding burden of severe disease and mortality in both endemic populations and travelers [...]

Background: This study examines newcomers with intellectual and developmental disabilities compared to other adults with intellectual and developmental disabilities in Ontario, Canada. Methods: This population-based retrospective cohort study used linked health and social services administrative data to identify adults with intellectual and developmental disabilities as newcomers, or non-newcomers, and compared their health status and health service outcomes. Results: Among those with intellectual and developmental disabilities, compared to non-newcomers, newcomers generally had lower or similar rates of health issues, except for higher rates of psychosis. Newcomers also had slightly greater use of community-based health services, but less hospital use. Conclusion: Trends among those with the intellectual and developmental disabilities were consistent with general population trends; newcomers had lower rates of many health issues and lower hospital use. It also underscores the value of understanding drivers of heterogeneity within newcomers, such as the circumstances of admission and settlement in their new country.

Zika virus (ZIKV) constitutes an increasing public health problem. Previous studies have shown that CD8+ T cells play an important role in ZIKV-specific protective immunity. We have previously defined antigenic targets of the ZIKV-specific CD8+ T cell response in humans. In this study, we characterized the quality and phenotypes of these responses by a combined use of flow cytometry and transcriptomic methods, using PBMCs from donors deriving from different geographical locations collected in the convalescent phase of infection. We show that ZIKV-specific CD8+ T cells are characterized by a polyfunctional IFN-γ signature with upregulation of TNF-α, TNF receptors, and related activation markers, such as CD69, as well as a cytotoxic signature characterized by strong upregulation of GZMB and CRTAM. The signature is stable and not influenced by previous dengue virus exposure, geographical location, or time of sample collection postinfection. To our knowledge, this work elucidates the first in-depth characterization of human CD8+ T cells responding to ZIKV infection.

Background: Adults with intellectual and developmental disabilities (IDD) have high rates of homelessness. This observational study evaluates Bridges to Housing, a cross-sector intervention offering immediate access to housing and supports to this population in Toronto, Canada. Methods: Twenty-six participants, enrolled between April 2016 and December 2017, were assessed at baseline, six and 12 months post-enrolment. Descriptive statistics and generalized linear modelling evaluated quality of life (QOL) and service needs outcomes. Twenty-one service users and providers participated in semi-structured interviews between August 2017 and June 2018 to elicit their experiences of the intervention, which were analysed thematically. Results: Twelve months post-enrolment, 24 participants were successfully housed and reported increased QOL scores (F(2,43) = 13.73, p = <0.001) and decreased perceived unmet service needs (Wald X[superscript 2](2) = 12.93, p = 0.002). Individual-, intervention- and system-level characteristics facilitated housing stability in this population. Conclusions: Cross-sector approaches can improve outcomes for homeless adults with IDD and may have an important role in supporting this marginalized population.

Background: Data on the prevalence of developmental disabilities in people who experience imprisonment and on their characteristics are lacking. Methods: The present authors identified adults with developmental disabilities who were released from Ontario provincial prisons in 2010 and a general population comparator group using administrative data. The present authors examined demographic characteristics, morbidity and healthcare use. Results: The prevalence of developmental disabilities was 2.2% in the prison group (N = 52,302) and 0.7% in the general population (N = 10,466,847). The prevalence of psychotic illness, substance-related disorder and self-harm was higher among people in the prison group with developmental disabilities. People with developmental disabilities were more likely to have emergency department visits and hospitalizations in prison and in the year after release. Conclusions: People with developmental disabilities are overrepresented in provincial prisons and have a high burden of disease. Strategies are indicated to prevent incarceration and to improve health.

The gold-standard method for quantifying neutralizing antibody responses to many viruses, including dengue virus (DENV), is the plaque reduction neutralization test (PRNT, also called the immunofocus reduction neutralization test). The PRNT conducted on 96-well plates is high-throughput and requires a smaller volume of antiserum than on 6- or 24-well plates, but manual plaque counting is challenging and existing automated plaque counters are expensive or difficult to optimize. We have developed Viridot (Viridot package), a program for R with a user interface in shiny, that counts viral plaques of a variety of phenotypes, estimates neutralizing antibody titers, and performs other calculations of use to virologists. The Viridot plaque counter includes an automatic parameter identification mode (misses

While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here, we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether preexisting dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with tetravalent dengue attenuated vaccines (TDLAV) recognize ZIKV-derived peptides. This cross-reactivity is explained by the sequence similarity of the two viruses, as the ZIKV peptides recognized by DENV-elicited memory T cells are identical or highly conserved in DENV and ZIKV. DENV exposure prior to ZIKV infection also influences the timing and magnitude of the T cell response. ZIKV-reactive T cells in the acute phase of infection are detected earlier and in greater magnitude in DENV-immune patients. Conversely, the frequency of ZIKV-reactive T cells continues to rise in the convalescent phase in DENV-naive donors but declines in DENV-preexposed donors, compatible with more efficient control of ZIKV replication and/or clearance of ZIKV antigen. The quality of responses is also influenced by previous DENV exposure, and ZIKV-specific CD8 T cells from DENV-preexposed donors selectively upregulated granzyme B and PD1, unlike DENV-naive donors. Finally, we discovered that ZIKV structural proteins (E, prM, and C) are major targets of both the CD4 and CD8 T cell responses, whereas DENV T cell epitopes are found primarily in nonstructural proteins.IMPORTANCE The issue of potential ZIKV and DENV cross-reactivity and how preexisting DENV T cell immunity modulates Zika T cell responses is of great relevance, as the two viruses often cocirculate and Zika virus has been spreading in geographical regions where DENV is endemic or hyperendemic. Our data show that memory T cell responses elicited by prior infection with DENV recognize ZIKV-derived peptides and that DENV exposure prior to ZIKV infection influences the timing, magnitude, and quality of the T cell response. Additionally, we show that ZIKV-specific responses target different proteins than DENV-specific responses, pointing toward important implications for vaccine design against this global threat.

Dengue viruses (DENV1-4) are mosquito-borne flaviviruses estimated to cause up to ∼400 million infections and ∼100 million dengue cases each year. Factors that contribute to protection from and risk of dengue and severe dengue disease have been studied extensively but are still not fully understood. Results from Phase 3 vaccine efficacy trials have recently become available for one vaccine candidate, now licensed for use in several countries, and more Phase 2 and 3 studies of additional vaccine candidates are ongoing, making these issues all the more urgent and timely. At the "Summit on Dengue Immune Correlates of Protection", held in Annecy, France, on March 8-9, 2016, dengue experts from diverse fields came together to discuss the current understanding of the immune response to and protection from DENV infection and disease, identify key unanswered questions, discuss data on immune correlates and plans for comparison of results across assays/consortia, and propose a research agenda for investigation of dengue immune correlates, all in the context of both natural infection studies and vaccine trials.

BACKGROUND: Dengue is a major public health problem worldwide. Assessment of adaptive immunity is important to understanding immunopathology and to define correlates of protection against dengue virus (DENV). To enable global assessment of CD4+ T cell responses, we mapped HLA-DRB1-restricted DENV-specific CD4+ T cell epitopes in individuals previously exposed to DENV in the general population of the dengue-endemic region of Managua, Nicaragua. METHODS: HLA class II epitopes in the population of Managua were identified by an in vitro IFNγ ELISPOT assay. CD4+ T cells purified by magnetic bead negative selection were stimulated with HLA-matched epitope pools in the presence of autologous antigen-presenting cells, followed by pool deconvolution to identify specific epitopes. The epitopes identified in this study were combined with those previously identified in the DENV endemic region of Sri Lanka, to generate a megapool (MP) consisting of 180 peptides specifically designed to achieve balanced HLA and DENV serotype coverage. The DENV CD4MP180 was validated by intracellular cytokine staining assays. RESULTS: We detected responses directed against a total of 431 epitopes, representing all 4 DENV serotypes, restricted by 15 different HLA-DRB1 alleles. The responses were associated with a similar pattern of protein immunodominance, overall higher magnitude of responses, as compared to what was observed previously in the Sri Lanka region. Based on these epitope mapping studies, we designed a DENV CD4 MP180 with higher and more consistent coverage, which allowed the detection of CD4+ T cell DENV responses ex vivo in various cohorts of DENV exposed donors worldwide, including donors from Nicaragua, Brazil, Singapore, Sri Lanka, and U.S. domestic flavivirus-naïve subjects immunized with Tetravalent Dengue Live-Attenuated Vaccine (TV005). This broad reactivity reflects that the 21 HLA-DRB1 alleles analyzed in this and previous studies account for more than 80% of alleles present with a phenotypic frequency ≥5% worldwide, corresponding to 92% phenotypic coverage of the general population (i.e., 92% of individuals express at least one of these alleles). CONCLUSION: The DENV CD4 MP180 can be utilized to measure ex vivo responses to DENV irrespective of geographical location.

Background: HIV among individuals with intellectual and developmental disabilities (IDD) is rarely studied. This scoping review examined the HIV prevalence, health service use, prevention and risk behaviours among individuals with IDD. Method: Journal articles, book chapters and theses written in English and published from 1991 to 2017 in four academic databases (PubMed, PsycINFO, CINAHL and Web of Science) were eligible for inclusion. Results: From 1636 unique records, 32 documents were included in this review. They contained limited information on HIV prevalence and health service use by individuals with IDD and HIV. Most studies identified a poor understanding of HIV and high-risk behaviours, such as inconsistent condom use, among individuals with IDD. While HIV education programs were effective for this population, no studies identified educational interventions for their service providers. Conclusion: There is a need for educational programs and policies on HIV for both service providers and individuals with IDD.

Arthropod-borne viruses represent a crucial public health threat. Current arboviral serology assays are either labor intensive or incapable of distinguishing closely related viruses, and many zoonotic arboviruses that may transition to humans lack any serologic assays. In this study, we present a programmable phage display platform, ArboScan, that evaluates antibody binding to overlapping peptides that represent the proteomes of 691 human and zoonotic arboviruses. We confirm that ArboScan provides detailed antibody binding information from animal sera, human sera, and an arthropod blood meal. ArboScan identifies distinguishing features of antibody responses based on exposure history in a Colombian cohort of Zika patients. Finally, ArboScan details epitope level information that rapidly identifies candidate epitopes with potential protective significance. ArboScan thus represents a resource for characterizing human and animal arbovirus antibody responses at cohort scale. Arboviruses are transmitted by arthropods and include a number of critical human and zoonotic pathogens. Here the authors report a phage display library, ArboScan, for evaluating antibody binding to the peptidome of 691 human and zoonotic arthropod borne viruses, and use it to profile anti-arbovirus antibodies from diverse samples. [ABSTRACT FROM AUTHOR]

Beyond the challenges of diagnosis, complexity measurement in clients with mental illness is an important but under-recognized area. Accurate and appropriate psychiatric diagnoses are essential, and further complexity measurements could contribute to improving patient understanding, referral, and service matching and coordination, outcome evaluation, and system-level care planning. Myriad conceptualizations, frameworks, and definitions of patient complexity exist, which are operationalized by a variety of complexity measuring tools. A limited number of these tools are developed for people with mental illness, and they differ in the extent to which they capture clinical, psychosocial, economic, and environmental domains. Guided by the PRISMA Extension for Scoping Reviews, this review evaluates the tools best suited for different mental health settings. The search found 5345 articles published until November 2023 and screened 14 qualified papers and corresponding tools. For each of these, detailed data on their use of psychiatric diagnostic categories, definition of complexity, primary aim and purpose, context of use and settings for their validation, best target populations, historical references, extent of biopsychosocial information inclusion, database and input technology required, and performance assessments were extracted, analyzed, and presented for comparisons. Two tools—the INTERMED, a clinician-scored and multiple healthcare data-sourced tool, and the VCAT, a computer-based instrument that utilizes healthcare databases to generate a comprehensive picture of complexity—are exemplary among the tools reviewed. Information on these limited but suitable tools related to their unique characteristics and utilities, and specialized recommendations for their use in mental health settings could contribute to improved patient care. [ABSTRACT FROM AUTHOR]

This population-based cohort study examined the relationship between level of continuity of primary care and subsequent emergency department (ED) visits for adults with (n = 66,484) and without intellectual and developmental disabilities (IDD)(n = 2,760,670). Individuals with IDD were more likely than individuals with no IDD to visit the ED (33.96% versus 20.28%, p < 0.0001). For both groups receiving greater continuity of primary care was associated with less ED use, but this relationship was more marked for adults with IDD. While continuity of primary care can reduce ED use for populations with and without IDD, it is a higher priority for individuals with IDD whose cognitive and adaptive impairments may complicate help-seeking, diagnosis, and treatment. Improving primary care can have far-reaching implications for this complex population.