Potent pollen gene regulation by DNA glycosylases in maize.

Although DNA methylation primarily represses TEs, it also represses select genes that are methylated in plant body tissues but demethylated by DNA glycosylases (DNGs) in endosperm or pollen. Activity of either one of two DNGs, MDR1 or DNG102, is essential for pollen viability in maize. Using single-pollen mRNA sequencing on pollen segregating mutations in both genes, we identified 58 candidate DNG target genes that account for 11.1% of the wild-type transcriptome but are silent or barely detectable in the plant body (sporophyte). They are unusual in their tendency to lack introns but even more so in their having TE-like methylation in their CDS. The majority have predicted functions in cell wall modification, and they likely support the rapid tip growth characteristic of pollen tubes. These results suggest a critical role for DNA methylation and demethylation in regulating maize genes with potential for extremely high expression in pollen but constitutive silencing elsewhere.

The sporophyte-to-gametophyte transition: The haploid generation comes of age.

Flowering plants alternate between two multicellular generations: the diploid sporophyte and haploid gametophyte. Despite its small size, the gametophyte has significant impacts on plant genetics, evolution, and breeding. Each male pollen grain and female embryo sac is a multicellular organism with independent gene expression, a functioning metabolism, and specialized cell types. In this review, we describe recent progress in understanding the process in which the haploid genome takes over expression from its diploid parent - the sporophyte-to-gametophyte transition. The focus is on pollen, but similar concepts may also apply to the female gametophyte. Technological advances in single-cell genomics offer the opportunity to characterize haploid gene expression in unprecedented detail, positioning the field to make rapid progress.

Association of homelessness and psychiatric hospital readmission-a retrospective cohort study 2016-2020.

BACKGROUND: A large proportion of adult psychiatric inpatients experience homelessness and are often discharged to unstable accommodation or the street. It is unclear whether homelessness impacts psychiatric hospital readmission. Our primary objective was to examine the association between homelessness and risk for 30-day and 90-day readmission following discharge from a psychiatric unit at a single urban hospital. METHODS: A retrospective cohort study involving health administrative data among individuals (n = 3907) in Vancouver, Canada with an acute psychiatric admission between January 2016 and December 2020. Participants were followed from the date of index admission until censoring (December 30, 2020). Homelessness was measured at index admission and treated as a time-varying exposure. Adjusted Hazard Ratios (aHRs) of acute readmission (30-day and 90-day) for psychiatric and substance use disorders were estimated using multivariable Cox proportional hazards regression. RESULTS: The cohort comprised 3907 individuals who were predominantly male (61.89%) with a severe mental illness (70.92%), substance use disorder (20.45%) and mean age of 40.66 (SD, 14.33). A total of 686 (17.56%) individuals were homeless at their index hospitalization averaging 19.13 (21.53) days in hospital. After adjusting for covariates, patients experiencing homelessness had a 2.04 (1.65, 2.51) increased rate of 30-day readmission and 1.65 (1.24, 2.19) increased rate of 90-day readmission during the observation period. CONCLUSIONS: Homelessness was significantly associated with increased 30-day and 90-day readmission rates in a large comprehensive sample of adults with mental illness and substance use disorders. Interventions to reduce homelessness are urgently needed. QUESTION: Is homelessness associated with risk for 30-day and 90-day psychiatric hospital readmission? FINDINGS: In this retrospective cohort study of 3907 individuals, homelessness at discharge was associated with increased 30-day and 90-day psychiatric readmission. MEANING: Housing status is an important risk factor for hospital readmission. High-quality interventions focused on housing supports have the potential to reduce psychiatric readmission.

Shelter Bans Among People Experiencing Homelessness: an Exploratory Study of Predictors in Two Large Canadian Datasets.

Emergency shelters are a core component of homeless service systems that address immediate basic needs. Service bans, which refer to temporary or permanent disallowances from a program or organization, are an underresearched phenomenon that can leave people experiencing homelessness without needed supports. This exploratory study examined the factors associated with shelter bans among people experiencing homelessness using secondary data from two Canadian studies: (1) a multisite randomized controlled trial of Housing First (At Home/Chez Soi Demonstration Project) and (2) a cross-sectional survey of youth experiencing homelessness across Canada (2019 Without a Home-National Youth Homelessness Survey). The two datasets were analyzed separately using logistic regression models with similar predictors to maximize the comparability of the results. Participants who experienced homelessness at an earlier age and had recent criminal justice system involvement were more likely to have shelter bans in both datasets. Impaired impulse control, more chronic medical conditions and living in Toronto were associated with increased likelihood of shelter bans in the At Home/Chez Soi dataset, whereas more adverse childhood experiences, physical violence victimization, engagement in survival sex behaviours and longer current episodes of homelessness were significant predictors of bans in the Without A Home dataset. Overall, the findings suggest that victimization and criminalization during homelessness may increase the risk of shelter loss from bans and further exclusion. The observed regional differences also highlight the potential limits of individual-level predictors. Further research is needed on shelter ban outcomes, as well as how capacity limits and organizational policies affect banning decisions.

Knowledge of a Drug-Related Good Samaritan Law Among People Who Use Drugs, Vancouver, Canada.

BACKGROUND: Across the United States and Canada drug-related Good Samaritan laws (GSLs) have been enacted to encourage observers of acute drug overdose events to contact emergency medical services (EMS) without fear of legal repercussions. However, little is known about the working knowledge of GSLs among people who use illicit drugs (PWUD). We sought to evaluate the prevalence and factors associated with accurate knowledge of a GSL among PWUD in Vancouver, Canada, 1 year after the GSL was enacted. METHOD: We used data from participants in three community-recruited prospective cohort studies of PWUD interviewed between June and November 2018. Multivariable logistic regression was used to identify factors associated with accurate knowledge of the GSL. RESULTS: Among 1,258 participants, including 760 males (60%), 358 (28%) had accurate knowledge of the GSL. In multivariable analyses, participants who reported ever having a negative police encounter (defined as being stopped, searched, or detained by the police) were less likely to have accurate knowledge of the GSL (adjusted odds ratio [AOR] = 0.70; 95% CI [0.54, 0.90]), while those involved in drug dealing were more likely to have accurate knowledge of the GSL (AOR = 1.50; 95% CI [1.06, 2.06]). DISCUSSION: Despite having been enacted for a full year, approximately three quarters of participants did not have accurate GSL knowledge, warranting urgent educational efforts among PWUD. Additional research is needed to understand whether GSLs can mitigate the fears of legal repercussions among those engaged in drug dealing and with past negative experiences with the police.

Multivariable modelling of factors associated with criminal convictions among people experiencing homelessness and serious mental illness: a multi-year study.

People experiencing homelessness and serious mental illness exhibit high rates of criminal justice system involvement. Researchers have debated the causes of such involvement among people experiencing serious mental illness, including what services to prioritize. Some, for example, have emphasized mental illness while others have emphasized poverty. We examined factors associated with criminal convictions among people experiencing homelessness and serious mental illness recruited to the Vancouver At Home study. Participants were recruited between October 2009 and June 2011. Comprehensive administrative data were examined over the five-year period preceding study baseline to identify risk and protective factors associated with criminal convictions among participants (n = 425). Eight variables were independently associated with criminal convictions, some of which included drug dependence (RR = 1.53; P = 0.009), psychiatric hospitalization (RR = 1.44; P = 0.030), an irregular frequency of social assistance payments (compared to regular payments; 1.75; P < 0.001), and prior conviction (RR = 3.56; P < 0.001). Collectively, findings of the present study implicate poverty, social marginalization, crises involving mental illness, and the need for long-term recovery-oriented services that address these conditions to reduce criminal convictions among people experiencing homelessness and serious mental illness.

The association between experiencing homelessness in childhood or youth and adult housing stability in Housing First.

BACKGROUND: Researchers have pointed out the paucity of research investigating long-term consequences of experiencing homelessness in childhood or youth. Limited research has indicated that the experience of homelessness in childhood or youth is associated with adverse adjustment-related consequences in adulthood. Housing First (HF) has acknowledged effectiveness in improving housing outcomes among adults experiencing homelessness and living with serious mental illness, although some HF clients struggle with maintaining housing. The current study was conducted to examine whether the experience of homelessness in childhood or youth increases the odds of poorer housing stability following entry into high-fidelity HF among adults experiencing serious mental illness and who were formerly homeless. METHODS: Data were drawn from the active intervention arms of a HF randomized controlled trial in Metro Vancouver, Canada. Participants (n = 297) were referred to the study from service agencies serving adults experiencing homelessness and mental illness between October 2009 and June 2011. The Residential Time-Line Follow-Back Inventory was used to measure housing stability. Least absolute shrinkage and selection operator was used to estimate the association between first experiencing homelessness in childhood or youth and later housing stability as an adult in HF. RESULTS: Analyses indicated that homelessness in childhood or youth was negatively associated with experiencing housing stability as an adult in HF (aOR = 0.53; 95% CI = 0.31-0.90). CONCLUSIONS: Further supports are needed within HF to increase housing stability among adult clients who have experienced homelessness in childhood or youth. Asking clients about the age they first experienced homelessness may be of clinical utility upon enrollment in HF and may help identify support needs related to developmental experiences. Results further emphasize the importance of intervening earlier in life in childhood and youth before experiencing homelessness or before it becomes chronic. Findings also contribute to a limited knowledge base regarding the adverse long-term consequences of childhood and youth homelessness. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN57595077 and ISRCTN66721740 . Registered on October 9, 2012.

Overall and Gender-specific Associations between Dimensions of Adverse Childhood Experiences and Mental Health Outcomes among Homeless Adults: Associations Générales et Sexospécifiques Entre les Dimensions des Expériences Défavorables de L'enfance et les Résultats de Santé Mentale Chez les Adultes Sans Abri.

OBJECTIVE: The associations between adverse childhood experiences (ACEs) and psychopathology have been well-established in the general population. Research on ACEs in the homeless population has been limited. This study examined whether ACE exposure is associated with specific mental health outcomes among a national sample of homeless adults with mental illness and whether this association varies according to ACE dimension and gender. METHODS: This cross-sectional study utilized data from a national sample of 2,235 homeless adults with mental illness in Canada to evaluate their sociodemographic characteristics, exposure to ACEs, and mental health outcomes. Exploratory and confirmatory factor analyses were conducted to identify and confirm ACE dimensions (maltreatment, sexual abuse, neglect, divorce, and household dysfunction) from individual ACE items. Multivariable logistic regression was used to examine the associations between total ACE score and ACE dimensions with mental illness diagnoses and psychopathology severity. RESULTS: The mean total ACE score among all study participants was 4.44 (standard deviation [SD]: 2.99). Total ACE score was positively associated with several mental illness diagnoses and psychopathology severity. Unique associations were found between specific ACE dimensions and poor mental health outcomes. The prevalence of almost all ACEs was significantly higher among women. Yet, associations between several ACE dimensions and poor mental health outcomes existed uniquely among men. CONCLUSIONS: There are unique and gender-specific associations between specific ACE dimensions and mental health outcomes among homeless adults. Better understanding of the mechanisms underlying these associations is needed to inform screening, prevention, and treatment efforts, particularly given the very high prevalence of ACEs among this vulnerable and marginalized population.

Chronic Pain among Individuals Experiencing Homelessness and Its Interdependence with Opioid and Other Substance Use and Mental Illness.

Chronic pain and substance use disorders are serious conditions that are prevalent among homeless populations. The aim of this study was to examine the association between chronic pain and substance use among individuals experiencing homelessness and mental illness. We analyzed cross-sectional data from two sites of the At Home/Chez Soi study (Vancouver and Toronto) using bivariate statistics and multivariate logistic regression. Substance use and chronic pain parameters were assessed with the Maudsley Addiction Profile and purpose-designed short instruments. The sample comprised 828 participants. Mean age was 42.4 years and 54% reported chronic pain. In bivariate analysis, chronic pain was significantly associated with use of opioids and stimulants, daily substance use, polysubstance use and injecting as route of administration. In multivariate analysis, only daily substance use (OR: 1.46, 95% CI: 1.02-2.09) and injecting (OR: 1.81, 95% CI: 1.08-3.05) remained as significant associated factors, whereas neither use of opioids nor use of stimulants specifically were significantly associated with chronic pain. Among participants with chronic pain, daily substance users (50% vs. 22%, p < 0.001) and injectors (66% vs. 24%, p < 0.001) were more likely to use non-prescribed medication for pain. Participants with daily substance use were less likely to receive professional treatment (52% vs. 64%, p = 0.017) and prescribed pain medication (42% vs. 54%, p = 0.023). Our findings suggest an association of chronic pain with patterns related to severity of substance use rather than to specific substance use in homeless persons with mental illness. Interventions aiming at prevention and treatment of chronic pain in this population should consider severity of substance use and associated risk behavior over use of specific substances.

Cost-Effectiveness of Housing First With Assertive Community Treatment: Results From the Canadian At Home/Chez Soi Trial.

OBJECTIVE: The At Home/Chez Soi trial for homeless individuals with mental illness showed scattered-site Housing First with Assertive Community Treatment (ACT) to be more effective than treatment as usual. This study evaluated the cost-effectiveness of Housing First with ACT and treatment as usual. METHODS: Between October 2009 and June 2011, a total of 950 homeless individuals with serious mental illness were recruited in five Canadian cities: Vancouver, Winnipeg, Toronto, Montreal, and Moncton. Participants were randomly assigned to Housing First (N=469) or treatment as usual (N=481) and followed up for up to 24 months. The intervention consisted of scattered-site Housing First, using rent supplements, with ACT. The treatment-as-usual group had access to all other services. The perspective of society was adopted for the cost-effectiveness analysis. Days of stable housing served as the outcome measure. Retrospective questionnaires captured service use data. RESULTS: Most (69%) of the costs of the intervention were offset by savings in other costs, such as emergency shelters, reducing the net annual cost of the intervention to about Can$6,311 per person. The incremental cost-effectiveness ratio was Can$41.73 per day of stable housing (95% confidence interval=Can$1.96-$83.70). At up to Can$60 per day, Housing First had more than an 80% chance of being cost-effective, compared with treatment as usual. Cost-effectiveness did not vary by participant characteristics. CONCLUSIONS: Housing First with ACT appeared about as cost-effective as Housing First with intensive case management for people with moderate needs. The optimal mix between the two remains to be determined.

Effectiveness of Housing First for Homeless Adults with Mental Illness Who Frequently Use Emergency Departments in a Multisite Randomized Controlled Trial.

Frequent emergency department (ED) users experiencing homelessness are associated with high costs for healthcare systems yet interventions for this group have been minimally investigated. This study used 24-month data from a multisite randomized controlled trial of Housing First (HF) to examine how effective the intervention is in helping frequent ED users with a mental illness to achieve housing stability, improve behavioural health and functioning, and reduce their ED use. Findings showed that HF is effective in stably housing frequent ED users despite their complex health needs. Reductions in ED use and substance use problems, and improvements in mental health symptoms and community functioning were found for frequent ED users in both the HF and treatment as usual conditions.

Examining the Relationships between Cumulative Childhood Adversity and the Risk of Criminal Justice Involvement and Victimization among Homeless Adults with Mental Illnesses after Receiving Housing First Intervention.

OBJECTIVES: Exposure to adverse childhood experiences (ACEs) is associated with increased risk of criminal justice involvement and repeated victimization among homeless individuals. This study aimed to (1) examine whether the relationship between cumulative ACE score and odds of experiencing criminal justice involvement and victimization remains significant over time after receiving the Housing First (HF) intervention and (2) investigate the moderating effect of cumulative ACE score on the effectiveness of the HF intervention on the likelihood of experiencing these outcomes among homeless individuals with mental illnesses. METHODS: We used longitudinal data over the 2-year follow-up period from the At Home/Chez Soi demonstration project that provided HF versus treatment as usual (TAU) to homeless adults with mental illness in five Canadian cities (N = 1,888). RESULTS: In all 4 follow-up time points, the relationship between cumulative ACE score and both outcomes remained significant, regardless of study arm (HF vs. TAU) and other confounding factors. However, cumulative ACE score did not moderate intervention effects on odds of experiencing either outcome, suggesting that the effectiveness of HF versus TAU, with regard to the odds of being victimized or criminal justice involvement, did not differ by cumulative ACE scores over the course of study. CONCLUSIONS: Findings suggest that providing services for homeless individuals with mental illness should be trauma informed and include specialized treatment strategies targeting the experience of ACEs and trauma to improve their treatment outcomes. An intensive approach is required to directly address the problem of criminal justice involvement and victimization in these individuals.

Cost-effectiveness of Housing First Intervention With Intensive Case Management Compared With Treatment as Usual for Homeless Adults With Mental Illness: Secondary Analysis of a Randomized Clinical Trial.

Importance: In the At Home/Chez Soi trial for homeless individuals with mental illness, the scattered-site Housing First (HF) with Intensive Case Management (ICM) intervention proved more effective than treatment as usual (TAU). Objective: To evaluate the cost-effectiveness of the HF plus ICM intervention compared with TAU. Design, Setting, and Participants: This is an economic evaluation study of data from the At Home/Chez Soi randomized clinical trial. From October 2009 through July 2011, 1198 individuals were randomized to the intervention (n = 689) or TAU (n = 509) and followed up for as long as 24 months. Participants were recruited in the Canadian cities of Vancouver, Winnipeg, Toronto, and Montreal. Participants with a current mental disorder who were homeless and had a moderate level of need were included. Data were analyzed from 2013 through 2019, per protocol. Interventions: Scattered-site HF (using rent supplements) with off-site ICM services was compared with usual housing and support services in each city. Main Outcomes and Measures: The analysis was performed from the perspective of society, with days of stable housing as the outcome. Service use was ascertained using questionnaires. Unit costs were estimated in 2016 Canadian dollars. Results: Of 1198 randomized individuals, 795 (66.4%) were men and 696 (58.1%) were aged 30 to 49 years. Almost all (1160 participants, including 677 in the HF group and 483 in the TAU group) contributed data to the economic analysis. Days of stable housing were higher by 140.34 days (95% CI, 128.14-153.31 days) in the HF group. The intervention cost $14 496 per person per year; reductions in costs of other services brought the net cost down by 46% to $7868 (95% CI, $4409-$11 405). The incremental cost-effectiveness ratio was $56.08 (95% CI, $29.55-$84.78) per additional day of stable housing. In sensitivity analyses, adjusting for baseline differences using a regression-based method, without altering the discount rate, caused the largest change in the incremental cost-effectiveness ratio with an increase to $60.18 (95% CI, $35.27-$86.95). At $67 per day of stable housing, there was an 80% chance that HF was cost-effective compared with TAU. The cost-effectiveness of HF appeared to be similar for all participants, although possibly less for those with a higher number of previous psychiatric hospitalizations. Conclusions and Relevance: In this study, the cost per additional day of stable housing was similar to that of many interventions for homeless individuals. Based on these results, expanding access to HF with ICM appears to be warranted from an economic standpoint. Trial Registration: isrctn.org Identifier: ISRCTN42520374.

Gender differences among Indigenous Canadians experiencing homelessness and mental illness.

BACKGROUND: Indigenous people are over represented among homeless populations worldwide and the prevalence of Indigenous homelessness appears to be increasing in Canadian cities. Violence against Indigenous women in Canada has been widely publicized but has not informed the planning of housing interventions. Despite historical policies leading to disenfranchisement of Indigenous rights in gender-specific ways, little is known about contemporary differences in need between homeless Indigenous men and women. This study investigated mental health, substance use and service use among Indigenous people who met criteria for homelessness and mental illness, and hypothesized that, compared to men, women would have significantly higher rates of trauma, suicidality, substance dependence, and experiences of violence. METHODS: This study was conducted using baseline (pre-randomization) data from a multi-site trial. Inclusion in the current analyses was restricted to participants who self-reported Indigenous ethnicity, and combined eligible participants from Vancouver, BC and Winnipeg, MB. Logistic regression analyses were used to model the independent associations between gender and outcome variables. RESULTS: In multivariable regression models among Indigenous participants (n = 439), female gender was predictive of meeting criteria for PTSD, multiple mental disorders, current high suicidality and current substance dependence. Female gender was also significantly associated with reported physical (AOR: 1.52, 95% CI = 1.10-2.23) and sexual (AOR: 6.31, 95% CI = 2.78-14.31) violence. CONCLUSIONS: Our analyses of Indigenous men and women who are homeless illustrate the distinct legacy of colonization on the experiences of Indigenous women. Our findings are consistent with the widely documented violence against Indigenous women in Canada. Housing policies and services are urgently needed that take Indigenous historical contexts, trauma and gender into account. TRIAL REGISTRATION: This trial has been registered with the International Standard Randomized Control Trial Number Register and assigned ISRCTN42520374 ; ISRCTN57595077 ; ISRCTN66721740 .

Temporal associations between medication adherence for patients with schizophrenia and opioid dependence: A 17-year Canadian Cohort Study.

The current study investigated whether a previously reported beneficial effect of methadone maintenance therapy (MMT) on antiretroviral adherence is also present in relation to antipsychotic treatment for schizophrenia. Administrative data were linked over a 17-year period for 1996 people who were dually diagnosed with schizophrenia and opioid dependence and, as an indicator of further marginalization, experienced at least one episode of correctional supervision in British Columbia. Adherence was estimated using the medication possession ratio (MPR ≥ 0.80), calculated in each 120-day period beginning with the first date of concurrent use of MMT and antipsychotic medication. Generalized Estimating Equations were used to estimate the association between independent and dependent variables. The probability of antipsychotic adherence doubled in periods that were preceded by a period of MMT adherence (AOR: P: 2.07; 95% CI: 1.90-2.26). Subgroup and sensitivity analyses yielded results similar to those derived through the primary analysis, examining: conviction history; length of follow-up; initiation of MMT prior to antipsychotic induction; excluding participants who died during the study period; and restricted to participants who received methadone exclusively as part of a MMT program. Despite a strong temporal association between MMT and antipsychotic adherence, overall MPRs for both prescriptions remained <0.50 throughout the study period. Antipsychotic adherence was more than twice as likely following periods of adherence to MMT among dually-diagnosed patients. Research is needed to identify the conditions responsible for MMT adherence, and to further clarify the relationship between opioid agonist treatment and antipsychotic pharmacotherapy in this vulnerable and under-studied population.

Indigenous and non-Indigenous people experiencing homelessness and mental illness in two Canadian cities: A retrospective analysis and implications for culturally informed action.

OBJECTIVES: Indigenous people in Canada are not only over-represented among the homeless population but their pathways to homelessness may differ from those of non-Indigenous people. This study investigated the history and current status of Indigenous and non-Indigenous people experiencing homelessness and mental illness. We hypothesised that compared with non-Indigenous people, those who are Indigenous would demonstrate histories of displacement earlier in life, higher rates of trauma and self-medication with alcohol and other substances. DESIGN AND SETTING: Retrospective data were collected from a sample recruited through referral from diverse social and health agencies in Winnipeg and Vancouver. PARTICIPANTS: Eligibility included being 19 years or older, current mental disorder and homelessness. MEASURES: Data were collected via interviews, using questionnaires, on sociodemographics (eg, age, ethnicity, education), mental illness, substance use, physical health, service use and quality of life. Univariate and multivariable models were used to model the association between Indigenous ethnicity and dependent variables. RESULTS: A total of 1010 people met the inclusion criteria, of whom 439 self-identified as Indigenous. In adjusted models, Indigenous ethnicity was independently associated with being homeless at a younger age, having a lifetime duration of homelessness longer than 3 years, post-traumatic stress disorder, less severe mental disorder, alcohol dependence, more severe substance use in the past month and infectious disease. Indigenous participants were also nearly twice as likely as others (47% vs 25%) to have children younger than 18 years. CONCLUSIONS: Among Canadians who are homeless and mentally ill, those who are Indigenous have distinct histories and current needs that are consistent with the legacy of colonisation. Responses to Indigenous homelessness must be developed within the context of reconciliation between Indigenous and non-Indigenous Canadians, addressing trauma, substance use and family separations. TRIAL REGISTRATION NUMBER: ISRCTN42520374, ISRCTN57595077, ISRCTN66721740.

Association of Methadone Treatment With Substance-Related Hospital Admissions Among a Population in Canada With a History of Criminal Convictions.

Importance: People with criminal histories experience high rates of opioid dependence and are frequent users of acute health care services. It is unclear whether methadone adherence prevents hospitalizations. Objective: To compare hospital admissions during medicated and nonmedicated methadone periods. Design, Setting, and Participants: A retrospective cohort study involving linked population-level administrative data among individuals in British Columbia, Canada, with provincial justice contacts (n= 250 884) and who filled a methadone prescription between April 1, 2001, and March 31, 2015. Participants were followed from the date of first dispensed methadone prescription until censoring (date of death, or March 31, 2015). Data analysis was conducted from May 1 to August 31, 2018. Exposures: Methadone treatment was divided into medicated (methadone was dispensed) and nonmedicated (methadone was not dispensed) periods and analyzed as a time-varying exposure. Main Outcome and Measures: Adjusted hazard ratios (aHRs) of acute hospitalizations for any cause and cause-specific (substance use disorder [SUD], non-substance-related mental disorders [NSMDs], and medical diagnoses [MEDs]) were estimated using multivariable Cox proportional hazards regression. Results: A total of 11 401 people (mean [SD] age, 34.9 [9.4] years; 8230 [72.2%] men) met inclusion criteria and were followed up for a total of 69 279.3 person-years. During a median follow-up time of 5.5 years (interquartile range, 2.8-9.1 years), there were 19 160 acute hospital admissions. Dispensed methadone was associated with a 50% lower rate of hospitalization for any cause (aHR, 0.50; 95% CI, 0.46-0.53) during the first 2 years (≤2.0 years) following methadone initiation, demonstrating significantly lower rates of admission for SUD (aHR, 0.32; 95% CI, 0.27-0.38), NSMD (aHR, 0.41; 95% CI, 0.34-0.50), and MED (aHR, 0.57; 95% CI, 0.52-0.62). As duration of time increased (2.1 to ≤5.0 years; 5.1 to ≤10.0 years), methadone was associated with a significant but smaller magnitude of effect: SUD (aHR, 0.43; 95% CI, 0.36-0.52; aHR, 0.47; 95% CI, 0.37-0.61), NSMD (aHR, 0.51; 95% CI, 0.41-0.64; aHR, 0.60; 95% CI, 0.47-0.78), and MED (aHR, 0.71; 95% CI, 0.65-0.77; aHR, 0.85; 95% CI, 0.76-0.95). Conclusions and Relevance: In this study, methadone was associated with a lower rate of hospitalization among a large cohort of Canadian individuals with histories of convictions and prevalent concurrent health and social needs. Practices to improve methadone adherence are warranted.

Predictive Validity of the MINI Suicidality Subscale for Suicide Attempts in a Homeless Population With Mental Illness.

OBJECTIVE: Suicide is a leading cause of death, yet the accurate prediction of suicidal behavior is an elusive target for clinicians and researchers. The current paper examines the predictive validity of the Mini Neuropsychiatric Interview (MINI) Suicidality subscale for suicide attempts (SAs) for a homeless population with mental illness. METHODS: Two thousand two hundred and fifty-five homeless individuals with mental illness across five Canadian cities enrolled in the At Home/Chez Soi Housing First trial interviewed at baseline using the MINI Suicidality subscale with 2-year follow-up of self-reported SAs. RESULTS: Two thousand two hundred and twenty-one participants were included in the analysis. High rates of mood and substance use disorders were present (56.5% and 67.4%, respectively). The mean MINI Suicidality subscale score was 7.71. Among 1,700 participants with follow-up data, 11.4% reported a SA over the 2-year study period. MINI Suicidality subscale scores were predictive of SAs (AUC ≥ 0.70) among those with and without a history of SAs, even among those with missing answers. A positive predictive value of 0.20 and a negative predictive value of 0.95 were demonstrated, with a relatively low number needed to assess of 4.5-5. CONCLUSION: The MINI Suicidal subscale shows promise as an easy to use and accurate suicide risk prediction tool among homeless individuals with mental illness.

Bayesian sensitivity analysis for unmeasured confounding in causal mediation analysis.

Causal mediation analysis techniques enable investigators to examine whether the effect of the exposure on an outcome is mediated by some intermediate variable. Motivated by a data example from epidemiology, we consider estimation of natural direct and indirect effects on a survival outcome. An important concern is bias from confounders that may be unmeasured. Estimating natural direct and indirect effects requires an elaborate series of assumptions in order to identify the target quantities. The analyst must carefully measure and adjust for important predictors of the exposure, mediator and outcome. Omitting important confounders may bias the results in a way that is difficult to predict. In recent years, several methods have been proposed to explore sensitivity to unmeasured confounding in mediation analysis. However, many of these methods limit complexity by relying on a handful of sensitivity parameters that are difficult to interpret, or alternatively, by assuming that specific patterns of unmeasured confounding are absent. Instead, we propose a simple Bayesian sensitivity analysis technique that is indexed by four bias parameters. Our method has the unique advantage that it is able to simultaneously assess unmeasured confounding in the mediator-outcome, exposure-outcome and exposure-mediator relationships. It is a natural Bayesian extension of the sensitivity analysis methodologies of VanderWeele, which have been widely used in the epidemiology literature. We present simulation findings, and additionally, we illustrate the method in an epidemiological study of mortality rates in criminal offenders from British Columbia.