Universal access to genetic counseling for women with epithelial ovarian cancer in Nova Scotia: Evaluating a new collaborative care model.

Women with pathogenic variants in BRCA1/2 have a significantly increased lifetime risk of breast and ovarian cancers. The availability of genetic testing to identify BRCA1/2 carriers is imperative to disease prevention and treatment. We evaluated the effectiveness of a new collaborative care model in Nova Scotia, involving the integration of genetic counselors into tumor board rounds, reduction in time allotted for initial genetic counseling appointments from 60 to 45 min, and a standardized dictation template, to increase referral rate for genetic counseling. We also assessed the study cohorts' preferences on timing for genetic testing. A retrospective chart review was performed on all women diagnosed with epithelial ovarian cancer (EOC) from 2012 to 2017 (N = 386). Pertinent clinical outcomes were categorized and wait times to different nodes of the clinical pathway assessed. A questionnaire was sent to this same cohort of women to identify preference for the timing of genetic testing (n = 103). The chi-square and Wilcoxon's rank-sum tests were used to compare demographic and clinical variables pre- and post-care model implementation. We identified a 48.2% (95% CI: 39.4-56.7, p < .001) increase in referral for genetic counseling following implementation of the new care model. Median time from diagnosis to referral decreased by 74.0 days (p < .001) and median time from referral to first appointment by 54.0 days (p < .001). 56.3% of women desired referral at the time of diagnosis. This care model for women newly diagnosed with EOC in Nova Scotia was successful in increasing referral rates for genetic counseling. Majority of women pursued genetic testing following and favored that referral for genetic counseling be made at the time of diagnosis, highlighting the importance for timely access.

LINE- and Alu-containing genomic instability hotspot at 16q24.1 associated with recurrent and nonrecurrent CNV deletions causative for ACDMPV.

Transposable elements modify human genome by inserting into new loci or by mediating homology-, microhomology-, or homeology-driven DNA recombination or repair, resulting in genomic structural variation. Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal neonatal developmental lung disorder caused by point mutations or copy-number variant (CNV) deletions of FOXF1 or its distant tissue-specific enhancer. Eighty-five percent of 45 ACDMPV-causative CNV deletions, of which junctions have been sequenced, had at least one of their two breakpoints located in a retrotransposon, with more than half of them being Alu elements. We describe a novel ∼35 kb-large genomic instability hotspot at 16q24.1, involving two evolutionarily young LINE-1 (L1) elements, L1PA2 and L1PA3, flanking AluY, two AluSx, AluSx1, and AluJr elements. The occurrence of L1s at this location coincided with the branching out of the Homo-Pan-Gorilla clade, and was preceded by the insertion of AluSx, AluSx1, and AluJr. Our data show that, in addition to mediating recurrent CNVs, L1 and Alu retrotransposons can predispose the human genome to formation of variably sized CNVs, both of clinical and evolutionary relevance. Nonetheless, epigenetic or other genomic features of this locus might also contribute to its increased instability.

Continuity of Care among People Experiencing Homelessness and Mental Illness: Does Community Follow-up Reduce Rehospitalization?

OBJECTIVE: To examine whether timely outpatient follow-up after hospital discharge reduces the risk of subsequent rehospitalization among people experiencing homelessness and mental illness. DATA SOURCES: Comprehensive linked administrative data including hospital admissions, laboratory services, and community medical services. STUDY DESIGN: Participants were recruited to the Vancouver At Home study based on a-priori criteria for homelessness and mental illness (n = 497). Logistic regression analysis was used to assess the relationship between outpatient care within 7 days postdischarge and subsequent rehospitalization over a 1-year period. DATA EXTRACTION: Data were extracted for a consenting subsample of participants (n = 433) spanning 5 years prior to study enrollment. PRINCIPAL FINDINGS: More than half of the eligible sample (53 percent; n = 128) were rehospitalized within 1 year following an index hospital discharge. Neither outpatient medical services nor laboratory services within 7 days following discharge were associated with a significantly reduced likelihood of rehospitalization within 2 months (AOR = 1.17 [CI = 0.94, 1.46]), 6 months (AOR = 1.00 [CI = 0.82, 1.23]) or 12 months (AOR = 1.24 [CI = 1.02, 1.52]). CONCLUSIONS: In contrast to evidence from nonhomeless samples, we found no association between timely outpatient follow-up and the likelihood of rehospitalization in our homeless, mentally ill cohort. Our findings indicate a need to address housing as an essential component of discharge planning alongside outpatient care.

A Randomized Trial Examining Housing First in Congregate and Scattered Site Formats.

OBJECTIVE: No previous experimental trials have investigated Housing First (HF) in both scattered site (SHF) and congregate (CHF) formats. We hypothesized that CHF and SHF would be associated with a greater percentage of time stably housed as well as superior health and psychosocial outcomes over 24 months compared to treatment as usual (TAU). METHODS: Inclusion criteria were homelessness, mental illness, and high need for support. Participants were randomised to SHF, CHF, or TAU. SHF consisted of market rental apartments with support provided by Assertive Community Treatment (ACT). CHF consisted of a single building with supports equivalent to ACT. TAU included existing services and supports. RESULTS: Of 800 people screened, 297 were randomly assigned to CHF (107), SHF (90), or TAU (100). The percentage of time in stable housing over 24 months was 26.3% in TAU (reference; 95% confidence interval (CI) = 20.5, 32.0), compared to 74.3% in CHF (95% CI = 69.3, 79.3, p<0.001) and 74.5% in SHF (95% CI = 69.2, 79.7, p<0.001). Secondary outcomes favoured CHF but not SHF compared to TAU. CONCLUSION: HF in scattered and congregate formats is capable of achieving housing stability among people experiencing major mental illness and chronic homelessness. Only CHF was associated with improvement on select secondary outcomes. REGISTRATION: Current Controlled Trials: ISRCTN57595077.

Accuracy of reported service use in a cohort of people who are chronically homeless and seriously mentally ill.

BACKGROUND: Self-reported service use is an integral feature of interventional research with people who are homeless and mentally ill. The objective of this study was to investigate the accuracy of self-reported involvement with major categories of publicly funded services (health, justice, social welfare) within this sub-population. METHODS: Measures were administered pre-randomization in two randomized controlled trials, using timeline follow back with calendar aids for Health, Social, and Justice Service Use, compared to linked administrative data. Variables examined were: psychiatric admissions (both extended stays of more than 6 months and two or more stays within 5 years); emergency department visits, general hospitalization and jail in the past 6 months; and income assistance in the past 1 month. Participants (n = 433) met criteria for homelessness and a least one mental illness. RESULTS: Prevalence adjusted and bias adjusted kappa (PABAK) values ranged between moderate and almost perfect for extended psychiatric hospital separations (PABAK: 0.77; 95 % confidence interval (CI) = 0.71, 0.83), multiple psychiatric hospitalizations (PABAK = 0.50, 95 % CI = 0.41, 0.59), emergency department visits (PABAK: 0.77; 95 % CI = 0.71, 0.83), jail (PABAK: 0.74; 95 % CI = 0.68, 0.81), and income assistance (PABAK: 0.82; 95 % CI = 0.76, 0.87). Significant differences in under versus over reporting were also found. CONCLUSIONS: People who are homeless and mentally ill reliably reported their overall use of health, justice, and income assistance services. Evidence of under-reporting and over-reporting of certain variables has implications for specific research questions. ISRCTN registry: 57595077 (Vancouver at Home Study: Housing First plus Assertive Community Treatment versus congregate housing plus supports versus treatment as usual); and 66721740 (Vancouver at Home study: Housing First plus Intensive Case management versus treatment as usual).

A 10-year retrospective analysis of hospital admissions and length of stay among a cohort of homeless adults in Vancouver, Canada.

BACKGROUND: Homelessness is associated with a very high prevalence of substance use and mental disorders and elevated levels of acute health service use. Among the homeless, little is known regarding the relative impact of specific mental disorders on healthcare utilization. The aim of the present study was to examine the association between different categories of diagnosed mental disorders with hospital admission and length of stay (LOS) in a cohort of homeless adults in Vancouver, Canada. METHODS: Participants were recruited as part of an experimental trial in which participants met criteria for both homelessness and mental illness. Administrative data were obtained (with separate consent) including comprehensive records of acute hospitalizations during the 10 years prior to recruitment and while participants where experiencing homelessness. Generalized Estimating Equations were used to estimate the associations between outcome variables (acute hospital admissions and LOS) and predictor variables (specific disorders). RESULTS: Among the eligible sample (n = 433) 80 % were hospitalized, with an average of 6.0 hospital admissions and 71.4 days per person during the 10-year observation period. Of a combined total 2601 admissions to hospital, 1982 were psychiatric and 619 were non-psychiatric. Significant (p <0.001) independent predictors of hospital admission and LOS included a diagnosis of schizophrenia or bipolar disorder, as well as high (≥32 service contacts) non-psychiatric medical service use in the community. CONCLUSIONS: Our results demonstrate that specific mental disorders alongside high non-psychiatric service use were significantly associated with hospital admission and LOS. These findings suggest the importance of screening within the homeless population to identify individuals who may be at risk for acute illness and the implementation of services to promote recovery and prevent repeated hospitalization. TRIAL REGISTRATION: ISRCTN57595077 ; ISRCTN66721740.

Exiting homelessness: perceived changes, barriers, and facilitators among formerly homeless adults with mental disorders.

OBJECTIVE: This study examines key themes from narrative interviews conducted with 43 homeless adults with mental disorders 18 months after random assignment to Housing First with intensive supports or to treatment as usual (no housing or supports through the study). METHOD: Coding and thematic analysis of semistructured interviews was based on 2 research questions from participants' perspectives: (a) What changes were perceived over time? (b) What factors facilitated or hindered change? RESULTS: The majority of participants assigned to Housing First reported positive change across multiple domains as a result of stable housing; whereas the majority of treatment as usual participants reported negative or neutral change. Key themes included feelings of security and pride; adjusting to living alone; housing as a learning process; and developing meaningful activity. The sense of security associated with stable housing was the most influential factor that supported change. Factors that helped or hindered change clustered into 4 key themes: the type and quality of services; the cumulative effects of trauma; social ties; and concurrent substance use. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Our findings provide important context to the emerging body of quantitative research on Housing First and recovery from homelessness. Participants' experiences of recovery, particularly as it relates to housing and supports, shifts in identity, and meaningful activity must be acknowledged and incorporated into the design and evaluation of public services, and policy and service reforms. (PsycINFO Database Record

Examining the relationship between health-related need and the receipt of care by participants experiencing homelessness and mental illness.

BACKGROUND: People experiencing homelessness and mental illness face multiple barriers to care. The goal of this study was to examine the association between health service use and indicators of need among individuals experiencing homelessness and mental illness in Vancouver, Canada. We hypothesized that those with more severe mental illness would access greater levels of primary and specialist health services than those with less severe mental illness. METHODS: Participants met criteria for homelessness and current mental disorder using standardized criteria (n = 497). Interviews assessed current health status and involvement with a variety of health services including specialist, general practice, and emergency services. The 80th percentile was used to differentiate 'low health service use' and 'high health service use'. Using multivariate logistic regression analysis, we analyzed associations between predisposing, enabling and need-related factors with levels of primary and specialist health service use. RESULTS: Twenty-one percent of participants had high primary care use, and 12% had high use of specialist services. Factors significantly (p ≤ 0.05) associated with high primary care use were: multiple physical illnesses [AOR 2.74 (1.12, 6.70]; poor general health [AOR 1.68 (1.01, 2.81)]; having a regular family physician [AOR 2.27 (1.27, 4.07)]; and negative social relationships [AOR 1.74 (1.01, 2.99)]. Conversely, having a more severe mental disorder (e.g. psychotic disorder) was significantly associated with lower odds of high service use [AOR 0.59 (0.35, 0.97)]. For specialist care, recent history of psychiatric hospitalization [AOR 2.53 (1.35, 4.75)] and major depressive episode [AOR 1.98 (1.11, 3.56)] were associated with high use, while having a blood borne infectious disease (i.e., HIV, HCV, HBV) was associated with lower odds of high service use. CONCLUSIONS: Contrary to our hypotheses, we found that individuals with greater assessed need, including more severe mental disorders, and blood-borne infectious diseases had significantly lower odds of being high health service users than those with lower assessed needs. Our findings reveal an important gap between levels of need and service involvement for individuals who are both homeless and mentally ill and have implications for health service reform in relation to the unmet and complex needs of a marginalized sub-population. ( TRIAL REGISTRATION: ISRCTN57595077 and ISRCTN66721740).

Vancouver At Home: pragmatic randomized trials investigating Housing First for homeless and mentally ill adults.

BACKGROUND: Individuals with mental illnesses are overrepresented among the homeless. Housing First (HF) has been shown to promote positive outcomes in this population. However, key questions remain unresolved, including: how to match support services to client needs, the benefits of housing in scattered sites versus single congregate building, and the effectiveness of HF with individuals actively using substances. The present study aimed to recruit two samples of homeless mentally ill participants who differed in the complexity of their needs. Study details, including recruitment, randomization, and follow-up, are presented. METHODS: Eligibility was based on homeless status and current mental disorder. Participants were classified as either moderate needs (MN) or high needs (HN). Those with MN were randomized to HF with Intensive Case Management (HF-ICM) or usual care. Those with HN were randomized to HF with Assertive Community Treatment (HF-ACT), congregate housing with support, or usual care. Participants were interviewed every 3 months for 2 years. Separate consent was sought to access administrative data. RESULTS: Participants met eligibility for either MN (n = 200) or HN (n = 297) and were randomized accordingly. Both samples were primarily male and white. Compared to participants designated MN, HN participants had higher rates of hospitalization for psychiatric reasons prior to randomization, were younger at the time of recruitment, younger when first homeless, more likely to meet criteria for substance dependence, and less likely to have completed high school. Across all study arms, between 92% and 100% of participants were followed over 24 months post-randomization. Minimal significant differences were found between study arms following randomization. 438 participants (88%) provided consent to access administrative data. CONCLUSION: The study successfully recruited participants meeting criteria for homelessness and current mental disorder. Both MN and HN groups had high rates of substance dependence, suicidality, and physical illness. Randomization resulted in no meaningful detectable differences between study arms. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN57595077 (Vancouver at Home study: Housing First plus Assertive Community Treatment versus congregate housing plus supports versus treatment as usual) and ISRCTN66721740 (Vancouver At Home study: Housing First plus Intensive Case Management versus treatment as usual).

Trajectories of recovery among homeless adults with mental illness who participated in a randomised controlled trial of Housing First: a longitudinal, narrative analysis.

OBJECTIVES: This study used longitudinal, narrative data to identify trajectories of recovery among homeless adults with mental illness alongside the factors that contribute to positive, negative, mixed or neutral trajectories over time. We expected that participants who received Housing First (HF) would describe more positive trajectories of recovery than those who were assigned to Treatment as Usual (TAU; no housing or support provided through the study). DESIGN: Narrative interview data were collected from participants at baseline and 18 months after random assignment to HF or TAU. SETTING: Participants were sampled from the community in Vancouver, British Columbia. PARTICIPANTS: Fifty-four participants were randomly and purposively selected from the larger trial; 52 were interviewed at baseline and 43 were reinterviewed 18 months after randomisation. METHOD: Semistructured interviews were conducted at both time points. For each participant, paired baseline and follow-up narratives were classified as positive, negative, mixed or neutral trajectories of recovery, and thematic analysis was used to identify the factors underlying different trajectories. RESULTS: Participants assigned to HF (n=28) were generally classified as positive or mixed trajectories; those assigned to TAU (n=15) were generally classified as neutral or negative trajectories. Positive trajectories were characterised by a range of benefits associated with good-quality, stable housing (eg, reduced substance use, greater social support), positive expressions of identity and the willingness to self-reflect. Negative, neutral and mixed trajectories were characterised by hopelessness ('things will never get better') related to continued hardship (eg, eviction, substance use problems), perceived failures and loss. CONCLUSIONS: HF is associated with positive trajectories of recovery among homeless adults with mental illness. Those who did not receive housing or support continued to struggle across a wide range of life domains. Findings are discussed with implications for addressing services and broader social change in order to benefit this marginalised population.

Drug treatment court of Vancouver: an empirical evaluation of recidivism.

BACKGROUND: Drug treatment courts (DTCs) have proliferated on the basis of their promise to reduce criminal recidivism among the burgeoning numbers of drug-related offenders. Empirical research on the effectiveness of DTCs indicates that they produce reductions in recidivism, primarily drawn from experiences in the US. There are no published outcome studies on Canadian DTCs. Canada's second DTC has operated in Vancouver's Downtown Eastside since 2001. We examine longitudinal changes in recidivism and characteristics of participants in the DTC in Vancouver (DTCV). METHODS: DTCV participants (n=180) were included in a longitudinal cohort design (intent-to-treat), and a comparison group was derived using the propensity score matching method. Matching variables represented the domains of health, offending, and socio-economic histories as well as demographics. Annualized rates of offending were compared for the two years prior to entering DTCV and two years following programme termination. RESULTS: Compared to the matched group of offenders, DTCV participants exhibited significantly greater reductions in offending, and a significant decrease in drug-related offences. The characteristics of DTCV participants differ significantly from those of the larger offender population in the DTES. CONCLUSION: Results provide empirical support for the DTCV in relation to the goal of reducing criminal recidivism. Participants in the DTCV are disadvantaged in diverse ways apart from their offence-related difficulties. These results have implications for the design of DTC programmes, as well as for future research.

Resistance and aerobic exercise: the influence of mode on the relationship between IL-6 and glucose tolerance in young men who are obese.

Regular exercise lowers indicators of disease risk including some inflammatory cytokines; however, the relationship between different modes of acute exercise, cytokine levels, and subsequent glucose tolerance is unclear. The purpose was to determine the effects of resistance (RES) and aerobic (AER) exercises on interleukin-6 (IL-6) and its association with glucose tolerance 24 hours after exercise. After testing for 1 repetition maximum (1RM) and VO2peak, 10 obese (body mass index > 30 kg · m(-2)), untrained men aged 18-26 years completed 3 protocols: 60 minutes of RES, AER, and a resting (CON) condition. The RES was 2 sets of 8 repetitions and a third set to fatigue at 80% 1RM of 8 lifts using all major muscle groups. The AER was 60 minutes of cycling at 70% of VO2peak. On day 1, subjects completed the 60-minute exercise or resting protocol, and on day 2, they completed an oral glucose tolerance test (OGTT). Blood was collected before and after exercise, at 2 and 7 hour postexercise, and before and every 30 minutes during the OGTT and was analyzed for IL-6, glucose and insulin. Postexercise IL-6 was greater in RES (8.01 ± 2.08 pg · mL(-1)) vs. in AER (4.26 ± 0.27 pg · mL(-1)), and both were greater than in CON (1.61 ± 0.18 pg · mL(-1)). During the OGTT, there were no differences in glucose or insulin between conditions for single time points or as area under the curve. The RES caused greater IL-6 levels immediately after exercise that may be related to the greater active muscle mass compared to AER. Neither exercise produced enhanced glucose removal compared to control; thus, despite the greater elevation in IL-6 in RES, for these exercise conditions and this population, this cytokine did not influence glucose tolerance.

Perceptions of genetic discrimination among people at risk for Huntington's disease: a cross sectional survey.

OBJECTIVE: To assess the nature and prevalence of genetic discrimination experienced by people at risk for Huntington's disease who had undergone genetic testing or remained untested. DESIGN: Cross sectional, self reported survey. SETTING: Seven genetics and movement disorders clinics servicing rural and urban communities in Canada. PARTICIPANTS: 233 genetically tested and untested asymptomatic people at risk for Huntington's disease (response rate 80%): 167 underwent testing (83 had the Huntington's disease mutation, 84 did not) and 66 chose not to be tested. MAIN OUTCOME MEASURES: Self reported experiences of genetic discrimination and related psychological distress based on family history or genetic test results. RESULTS: Discrimination was reported by 93 respondents (39.9%). Reported experiences occurred most often in insurance (29.2%), family (15.5%), and social (12.4%) settings. There were few reports of discrimination in employment (6.9%), health care (8.6%), or public sector settings (3.9%). Although respondents who were aware that they carried the Huntington's disease mutation reported the highest levels of discrimination, participation in genetic testing was not associated with increased levels of genetic discrimination. Family history of Huntington's disease, rather than the result of genetic testing, was the main reason given for experiences of genetic discrimination. Psychological distress was associated with genetic discrimination (P<0.001). CONCLUSIONS: Genetic discrimination was commonly reported by people at risk for Huntington's disease and was a source of psychological distress. Family history, and not genetic testing, was the major reason for genetic discrimination.

Estrogen receptor alpha gene polymorphisms are associated with idiopathic premature ovarian failure.

OBJECTIVE: To assess the role of hormone receptor/binding protein variants in genetic predisposition to premature ovarian failure (POF). DESIGN: Case-control study. SETTING: Academic. PATIENT(S): Fifty-five POF patients, 107 control women from the general population, and 27 control women who had proven fertility after age 37. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Allele distributions in cases and controls were assessed for genetic association. RESULT(S): Allele distributions of polymorphisms at the androgen receptor (AR) gene, estrogen receptor beta (ESR2) gene, sex hormone-binding globulin (SHBG) gene, and FSH receptor (FSHR) gene did not differ between patients and controls. At a repeat in a promoter of the estrogen receptor alpha(ESR1) gene, POF patients had fewer (<18) short repeat alleles than did controls (P=.004 vs. combined controls). Genotypes consisting of two short alleles were found in 36.4% of control women but only 5.5% of POF patients (P<.0001 vs. combined controls). The ESR1 repeat may confer risk for POF in a simple dominant manner in which carriers of a long repeat have a relative risk of 9.7 (95% CI = 2.6 - 35.6). CONCLUSION(S): Polymorphisms at the ESR1 gene are associated with POF in this patient population, while those in AR, ESR2, SHBG, and FSHR showed no association. Further studies are necessary to confirm these findings in larger patient samples and to identify the specific predisposing lesion.