Spatially resolved multiomics on the neuronal effects induced by spaceflight in mice.

Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate the impact of spaceflight on the mouse brain in female mice. Our comparative analysis between ground control and spaceflight-exposed animals revealed significant alterations in essential brain processes including neurogenesis, synaptogenesis and synaptic transmission, particularly affecting the cortex, hippocampus, striatum and neuroendocrine structures. Additionally, we observed astrocyte activation and signs of immune dysfunction. At the pathway level, some spaceflight-induced changes in the brain exhibit similarities with neurodegenerative disorders, marked by oxidative stress and protein misfolding. Our integrated spatial multiomics approach serves as a stepping stone towards understanding spaceflight-induced CNS impairments at the level of individual brain regions and cell types, and provides a basis for comparison in future spaceflight studies. For broader scientific impact, all datasets from this study are available through an interactive data portal, as well as the National Aeronautics and Space Administration (NASA) Open Science Data Repository (OSDR).

Inspiration4 data access through the NASA Open Science Data Repository.

The increasing accessibility of commercial and private space travel necessitates a profound understanding of its impact on human health. The NASA Open Science Data Repository (OSDR) provides transparent and FAIR access to biological studies, notably the SpaceX Inspiration4 (I4) mission, which amassed extensive data from civilian astronauts. This dataset encompasses omics and clinical assays, facilitating comprehensive research on space-induced biological responses. These data allow for multi-modal, longitudinal assessments, bridging the gap between human and model organism studies. Crucially, community-driven data standards established by NASA's OSDR Analysis Working Groups empower artificial intelligence and machine learning to glean invaluable insights, guiding future mission planning and health risk mitigation. This article presents a concise guide to access and analyze I4 data in OSDR, including programmatic access through GLOpenAPI. This pioneering effort establishes a precedent for post-mission health monitoring programs within space agencies, propelling research in the burgeoning field of commercial space travel's impact on human physiology.

Drosophila parasitoids go to space: Unexpected effects of spaceflight on hosts and their parasitoids.

While fruit flies (Drosophila melanogaster) and humans exhibit immune system dysfunction in space, studies examining their immune systems' interactions with natural parasites in space are lacking. Drosophila parasitoid wasps modify blood cell function to suppress host immunity. In this study, naive and parasitized ground and space flies from a tumor-free control and a blood tumor-bearing mutant strain were examined. Inflammation-related genes were activated in space in both fly strains. Whereas control flies did not develop tumors, tumor burden increased in the space-returned tumor-bearing mutants. Surprisingly, control flies were more sensitive to spaceflight than mutant flies; many of their essential genes were downregulated. Parasitoids appeared more resilient than fly hosts, and spaceflight did not significantly impact wasp survival or the expression of their virulence genes. Previously undocumented mutant wasps with novel wing color and wing shape were isolated post-flight and will be invaluable for host-parasite studies on Earth.

Opioid toxicity deaths in Black persons who experienced provincial incarceration in Ontario, Canada 2015-2020: A population-based study.

OBJECTIVE: In the context of mass incarceration and the opioid toxicity crisis in North America, there is a lack of data on the burden of opioid toxicity deaths in Black persons who experience incarceration. We aimed to describe absolute and relative opioid toxicity mortality for Black persons who experienced incarceration in Ontario, Canada between 2015 and 2020. METHODS: We linked data for all persons incarcerated in provincial correctional facilities and all persons who died from opioid toxicity in Ontario between 2015 and 2020, and accessed public data on population sizes. We described the characteristics of Black persons who were incarcerated and died from opioid toxicity, and calculated absolute mortality rates, as well as age-standardized mortality rates compared with all persons in Ontario not incarcerated during this period. RESULTS: Between 2015 and 2020, 0.9% (n = 137) of 16,177 Black persons who experienced incarceration died from opioid toxicity in custody or post-release, for an opioid toxicity death rate of 0.207 per 100 person years. In the two weeks post-release, the opioid toxicity death rate was 1.34 per 100 person years. Standardized for age and compared with persons not incarcerated, the mortality ratio (SMR) was 17.8 (95%CI 16.4-23.1) for Black persons who experienced incarceration. CONCLUSIONS: We identified a large, inequitable burden of opioid toxicity death for Black persons who experience incarceration in Ontario, Canada. Work is needed to support access to culturally appropriate prevention and treatment in custody and post-release for persons who are Black, and to prevent incarceration and improve determinants of health.

The impact of COVID-19 on opioid toxicity deaths for people who experience incarceration compared to the general population in Ontario: A whole population data linkage study.

BACKGROUND: To inform preparedness and population health action, we need to understand the effects of COVID-19 on health inequities. In this study, we assess the impact of COVID-19 on opioid toxicity deaths among people who experience incarceration compared to others in the general population in Ontario, Canada. METHODS: We conducted a retrospective cohort study for the period of January 1, 2015 to December 31, 2020. We accessed and linked coronial data on all opioid toxicity deaths in Ontario with correctional data for people aged 18 years and older who were incarcerated in a provincial correctional facility. We used data from the Statistics Canada Census to calculate whole population rates. We used an interrupted time series design and segmented regression to assess for change in the level or rate of increase in deaths due to opioid toxicity coinciding with the COVID-19 pandemic. We compared the impact of COVID-19 on the opioid toxicity death rates for people exposed and not exposed to incarceration. RESULTS: Rates of opioid toxicity death increased with a linear positive slope in both persons exposed to incarceration and those not exposed over the study period. The start of COVID-19 measures coincided with a marked upward shift in the trend lines with modification of the effect of COVID-19 by both sex and exposure to incarceration. For persons exposed to incarceration, the risk ratio (RR) was 1.50 (95%CI 1.35-1.69) for males and 1.21 (95%CI 1.06-1.42) for females, and for persons not exposed to incarceration, the RR was 1.25 (95%CI 1.13-1.38) for males and not significant for females. CONCLUSIONS: COVID-19 substantially exacerbated the risk of opioid toxicity death, impacting males and females who experienced incarceration more than those who had not, with an immediate stepwise increase in risk but no change in the rate of increase of risk over time. Public health work, including pandemic preparedness, should consider the specific needs and circumstances of people who experience incarceration.

The Commit to Be Fit framework: a community case study of a multi-level, holistic school-based wellness initiative in rural Virginia.

Background: Public health interventions that target children's physical, mental, and emotional health will enhance their ability to learn and grow. Although more complex, school initiatives that address multiple ecological levels and take a holistic view may be more effective and likely to lead to lasting change. Aims: This article presents the framework of Commit to Be Fit (C2BF) as an example of how schools can integrate multi-level and holistic approaches for health. This innovative school-based intervention includes activities addressing individual, home, school, and community to create a culture of wellness. We describe the implementation of C2BF and its basis in ecological models and give examples of activities across three components: cafeteria, classroom, and community. We discuss challenges and note that leadership engagement and alignment were critical elements for C2BF's success thus far. Discussion: C2BF uses a school-based multi-level approach to creating a culture of wellness and holistic health for students, teachers, and community members. C2BF is unique compared to other school-based programming and includes activities that address all eight domains posited for program sustainability within public health. Built to be flexible and adaptive, C2BF was able to successfully pivot during the COVID pandemic and also follow new science. Conclusion: C2BF and other multi-level holistic approaches are more likely to achieve long-term change by utilizing strategies across the multiple levels of the ecological model to improve health and wellbeing.

Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins bind to host mitochondrial proteins, likely inhibiting oxidative phosphorylation (OXPHOS) and stimulating glycolysis. We analyzed mitochondrial gene expression in nasopharyngeal and autopsy tissues from patients with coronavirus disease 2019 (COVID-19). In nasopharyngeal samples with declining viral titers, the virus blocked the transcription of a subset of nuclear DNA (nDNA)-encoded mitochondrial OXPHOS genes, induced the expression of microRNA 2392, activated HIF-1α to induce glycolysis, and activated host immune defenses including the integrated stress response. In autopsy tissues from patients with COVID-19, SARS-CoV-2 was no longer present, and mitochondrial gene transcription had recovered in the lungs. However, nDNA mitochondrial gene expression remained suppressed in autopsy tissue from the heart and, to a lesser extent, kidney, and liver, whereas mitochondrial DNA transcription was induced and host-immune defense pathways were activated. During early SARS-CoV-2 infection of hamsters with peak lung viral load, mitochondrial gene expression in the lung was minimally perturbed but was down-regulated in the cerebellum and up-regulated in the striatum even though no SARS-CoV-2 was detected in the brain. During the mid-phase SARS-CoV-2 infection of mice, mitochondrial gene expression was starting to recover in mouse lungs. These data suggest that when the viral titer first peaks, there is a systemic host response followed by viral suppression of mitochondrial gene transcription and induction of glycolysis leading to the deployment of antiviral immune defenses. Even when the virus was cleared and lung mitochondrial function had recovered, mitochondrial function in the heart, kidney, liver, and lymph nodes remained impaired, potentially leading to severe COVID-19 pathology.

Burden of opioid toxicity death in the fentanyl-dominant era for people who experience incarceration in Ontario, Canada, 2015-2020: a whole population retrospective cohort study.

OBJECTIVES: To describe mortality due to opioid toxicity among people who experienced incarceration in Ontario between 2015 and 2020, during the fentanyl-dominant era. DESIGN: In this retrospective cohort study, we linked Ontario coronial data on opioid toxicity deaths between 2015 and 2020 with correctional data for adults incarcerated in Ontario provincial correctional facilities. SETTING: Ontario, Canada. PARTICIPANTS: Whole population data. MAIN OUTCOMES AND MEASURES: The primary outcome was opioid toxicity death and the exposure was any incarceration in a provincial correctional facility between 2015 and 2020. We calculated crude death rates and age-standardised mortality ratios (SMR). RESULTS: Between 2015 and 2020, 8460 people died from opioid toxicity in Ontario. Of those, 2207 (26.1%) were exposed to incarceration during the study period. Among those exposed to incarceration during the study period (n=1 29 152), 1.7% died from opioid toxicity during this period. Crude opioid toxicity death rates per 10 000 persons years were 43.6 (95% CI=41.8 to 45.5) for those exposed to incarceration and 0.95 (95% CI=0.93 to 0.97) for those not exposed. Compared with those not exposed, the SMR for people exposed to incarceration was 31.2 (95% CI=29.8 to 32.6), and differed by sex, at 28.1 (95% CI=26.7 to 29.5) for males and 77.7 (95% CI=69.6 to 85.9) for females. For those exposed to incarceration who died from opioid toxicity, 10.6% died within 14 days of release and the risk was highest between days 4 and 7 postrelease, at 288.1 per 10 000 person years (95% CI=227.8 to 348.1). CONCLUSIONS: The risk of opioid toxicity death is many times higher for people who experience incarceration compared with others in Ontario. Risk is markedly elevated in the week after release, and women who experience incarceration have a substantially higher SMR than men who experience incarceration. Initiatives to prevent deaths should consider programmes and policies in correctional facilities to address high risk on release.

Meta-analysis of the space flight and microgravity response of the Arabidopsis plant transcriptome.

Spaceflight presents a multifaceted environment for plants, combining the effects on growth of many stressors and factors including altered gravity, the influence of experiment hardware, and increased radiation exposure. To help understand the plant response to this complex suite of factors this study compared transcriptomic analysis of 15 Arabidopsis thaliana spaceflight experiments deposited in the National Aeronautics and Space Administration's GeneLab data repository. These data were reanalyzed for genes showing significant differential expression in spaceflight versus ground controls using a single common computational pipeline for either the microarray or the RNA-seq datasets. Such a standardized approach to analysis should greatly increase the robustness of comparisons made between datasets. This analysis was coupled with extensive cross-referencing to a curated matrix of metadata associated with these experiments. Our study reveals that factors such as analysis type (i.e., microarray versus RNA-seq) or environmental and hardware conditions have important confounding effects on comparisons seeking to define plant reactions to spaceflight. The metadata matrix allows selection of studies with high similarity scores, i.e., that share multiple elements of experimental design, such as plant age or flight hardware. Comparisons between these studies then helps reduce the complexity in drawing conclusions arising from comparisons made between experiments with very different designs.

Lymphomatosis as a Cause of Abdominal Pain and Distension in Two Adult Horses.

Two equine patients presented separately with severe abdominal distention, colic, lethargy, and decreased appetite. An ante-mortem diagnosis of lymphoma was reached in each case based on peritoneal fluid cytology. Due to a poor prognosis, the horses were humanely euthanized. Post-mortem examination with histology and immunohistochemistry confirmed both cases as lymphoma: alimentary B-cell lymphoma of the distal jejunum and cecum in one case, and T-cell lymphoma of the cecum in the second case. Both cases exhibited extensive metastasis with peritoneal and pleural serosae covered in small nodules and plaque like masses consistent with lymphomatosis. These cases document a unique presentation of lymphoma in equine patients presenting as peritoneal lymphomatosis with ascites.

Host transcriptional responses in nasal swabs identify potential SARS-CoV-2 infection in PCR negative patients.

We analyzed RNA sequencing data from nasal swabs used for SARS-CoV-2 testing. 13% of 317 PCR-negative samples contained over 100 reads aligned to multiple regions of the SARS-CoV-2 genome. Differential gene expression analysis compares the host gene expression in potential false-negative (FN: PCR negative, sequencing positive) samples to subjects with multiple SARS-CoV-2 viral loads. The host transcriptional response in FN samples was distinct from true negative samples (PCR & sequencing negative) and similar to low viral load samples. Gene Ontology analysis shows viral load-dependent changes in gene expression are functionally distinct; 23 common pathways include responses to viral infections and associated immune responses. GO analysis reveals FN samples had a high overlap with high viral load samples. Deconvolution of RNA-seq data shows similar cell content across viral loads. Hence, transcriptome analysis of nasal swabs provides an additional level of identifying SARS-CoV-2 infection.

Opioid agonist treatment take-home doses ('carries'): Are current guidelines resulting in low treatment coverage among high-risk populations in Canada and the USA?

Opioid agonist treatment (OAT) is the primary intervention for opioid use disorder (OUD) in Canada and the USA. Yet, a number of barriers contribute to sub-optimal treatment uptake and retention, including daily-supervised medication administration. Thus, clients are eventually granted access to take-home OAT doses (i.e., 'carries') to reduce this burden. However, this decision is based on physician discretion and whether patients can demonstrate stability in various life domains, many of which are inextricably linked to the social determinants of health (SDOH). Current Canadian and USA OAT carry guidance documents are not standardized and do not take the SDOH into consideration, resulting in the potential for inequitable access to OAT carries, which may be the case particularly among marginalized populations such as individuals with OUD who have been released from custody. This perspective article posits that current OAT guidelines contribute to inequities in access to OAT carries, and that these inequities likely result in disproportionately low coverage for OUD treatment among some high-risk groups, including individuals on release from incarceration in particular. Relevant impacts of COVID-19 and related policy changes are considered, and suggestions and recommendations to amend current OAT guidance documents are provided.

Multimorbidity and quality of primary care after release from prison: a prospective data-linkage cohort study.

BACKGROUND: The period after release from prison can be challenging, especially due to a higher risk of morbidity and mortality despite commonly increased use of healthcare services. However, little is known about the quality of the healthcare offered to this population, which limits the possibility of addressing this important health inequity. This study characterised multimorbidity and investigated the relationship between multimorbidity and quality of primary healthcare in adults within 2 years after release from prison. METHODS: This was a prospective cohort study of 1046 participants of a service brokerage intervention after release from prison between August 2008 and July 2010 in Queensland, Australia. Participants had their baseline survey and clinical data linked prospectively with their medical, correctional and death records. Multimorbidity was ascertained using the Cumulative Illness Rating Scale and classified into three categories: none, moderate (morbidity in 2-3 domains) and complex (morbidity in 4 or more domains). Outcomes were Usual Provider Continuity Index (UPCI), Continuity of Care (COC) Index, and having at least one extended primary care consultation (> 20 minutes). Descriptive statistics and logistic regression were used in the analyses. RESULTS: Multimorbidity was present for 761 (73%) participants, being more prevalent among females (85%) than males (69%), p < 0.001. Moderate multimorbidity was not associated with UPCI or COC, but was associated with having at least one long consultation (AOR = 1.64; 95% CI:1.14-2.39), after adjusting for covariates. Complex multimorbidity was positively associated with all outcomes in the adjusted models. Indigenous status was negatively associated with UPCI (AOR = 0.54; 95% CI: 0.37-0.80) and COC (AOR = 0.53; 95% CI: 0.36-0.77), and people younger than 25 years were at 36% lower odds (AOR = 0.64; 95% CI: 0.44-0.93) of having a long consultation than the middle-aged group (25-44 years) in the adjusted models. CONCLUSION: Moderate multimorbidity was associated with having at least one extended primary care consultation, but not with adequate continuity of care, for adults within 2 years of being released from prison. Nearly half of those with complex multimorbidity did not receive adequate continuity of care. The quality of primary care is inadequate for a large proportion of adults released from prison, constituting an important and actionable health inequity.

The interplay between lncRNAs, RNA-binding proteins and viral genome during SARS-CoV-2 infection reveals strong connections with regulatory events involved in RNA metabolism and immune response.

Rationale: Viral infections are complex processes based on an intricate network of molecular interactions. The infectious agent hijacks components of the cellular machinery for its profit, circumventing the natural defense mechanisms triggered by the infected cell. The successful completion of the replicative viral cycle within a cell depends on the function of viral components versus the cellular defenses. Non-coding RNAs (ncRNAs) are important cellular modulators, either promoting or preventing the progression of viral infections. Among these ncRNAs, the long non-coding RNA (lncRNA) family is especially relevant due to their intrinsic functional properties and ubiquitous biological roles. Specific lncRNAs have been recently characterized as modulators of the cellular response during infection of human host cells by single stranded RNA viruses. However, the role of host lncRNAs in the infection by human RNA coronaviruses such as SARS-CoV-2 remains uncharacterized. Methods: In the present work, we have performed a transcriptomic study of a cohort of patients with different SARS-CoV-2 viral load and analyzed the involvement of lncRNAs in supporting regulatory networks based on their interaction with RNA-binding proteins (RBPs). Results: Our results revealed the existence of a SARS-CoV-2 infection-dependent pattern of transcriptional up-regulation in which specific lncRNAs are an integral component. To determine the role of these lncRNAs, we performed a functional correlation analysis complemented with the study of the validated interactions between lncRNAs and RBPs. This combination of in silico functional association studies and experimental evidence allowed us to identify a lncRNA signature composed of six elements - NRIR, BISPR, MIR155HG, FMR1-IT1, USP30-AS1, and U62317.2 - associated with the regulation of SARS-CoV-2 infection. Conclusions: We propose a competition mechanism between the viral RNA genome and the regulatory lncRNAs in the sequestering of specific RBPs that modulates the interferon response and the regulation of RNA surveillance by nonsense-mediated decay (NMD).

Total systems failure: police officers' perspectives on the impacts of the justice, health, and social service systems on people who use drugs.

BACKGROUND: Police in Canada have become main responders to behavioural health concerns in the community-a role that disproportionately harms people who use drugs (PWUD). Recent calls to defund the police emphasize the need to shift responsibility for non-criminal health issues from police to health and social services. This study explores the role of police interactions in responding to PWUD within the broader institutional and structural contexts in which they operate. METHODS: We conducted a qualitative thematic analysis of interviews with sixteen police officers across nine jurisdictions in British Columbia, Canada. We examined police officers' everyday policing experiences interacting with PWUD, enforcing drug laws, and working alongside other service sectors. RESULTS: Officers explained that the criminal justice system is one component of a wider network of systems that collectively fail to meet the needs of PWUD. They recognized that PWUD who interact with police often experienced intersecting structural vulnerabilities such as poverty, homelessness, and intergenerational trauma. Harmful drug laws in conjunction with inadequate treatment and housing resources contributed to a funnelling of PWUD into interactions with police. They provided several recommendations for reform including specialized health and justice roles, formalized intersectoral collaboration, and poverty reduction. CONCLUSIONS: Overall, this study provides unique insights into the positioning and role of police officers within a "total systems failure" that negatively impact PWUD. Police have become responders-by-default for issues that are fundamentally related to people's health conditions and socioeconomic circumstances. Addressing failures across the health, social, and justice systems to meet the needs of PWUD will require an examination of the shortcomings across these systems, as well as substantial funding and system reforms.

System-wide transcriptome damage and tissue identity loss in COVID-19 patients.

The molecular mechanisms underlying the clinical manifestations of coronavirus disease 2019 (COVID-19), and what distinguishes them from common seasonal influenza virus and other lung injury states such as acute respiratory distress syndrome, remain poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19. We then match these data with spatial protein and expression profiling across 357 tissue sections from 16 representative patient lung samples and identify tissue-compartment-specific damage wrought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, evident as a function of varying viral loads during the clinical course of infection and tissue-type-specific expression states. Overall, our findings reveal a systemic disruption of canonical cellular and transcriptional pathways across all tissues, which can inform subsequent studies to combat the mortality of COVID-19 and to better understand the molecular dynamics of lethal SARS-CoV-2 and other respiratory infections.

TARGETED DOWN REGULATION OF CORE MITOCHONDRIAL GENES DURING SARS-COV-2 INFECTION.

Defects in mitochondrial oxidative phosphorylation (OXPHOS) have been reported in COVID-19 patients, but the timing and organs affected vary among reports. Here, we reveal the dynamics of COVID-19 through transcription profiles in nasopharyngeal and autopsy samples from patients and infected rodent models. While mitochondrial bioenergetics is repressed in the viral nasopharyngeal portal of entry, it is up regulated in autopsy lung tissues from deceased patients. In most disease stages and organs, discrete OXPHOS functions are blocked by the virus, and this is countered by the host broadly up regulating unblocked OXPHOS functions. No such rebound is seen in autopsy heart, results in severe repression of genes across all OXPHOS modules. Hence, targeted enhancement of mitochondrial gene expression may mitigate the pathogenesis of COVID-19.

Betacoronavirus-specific alternate splicing.

Viruses can subvert a number of cellular processes including splicing in order to block innate antiviral responses, and many viruses interact with cellular splicing machinery. SARS-CoV-2 infection was shown to suppress global mRNA splicing, and at least 10 SARS-CoV-2 proteins bind specifically to one or more human RNAs. Here, we investigate 17 published experimental and clinical datasets related to SARS-CoV-2 infection, datasets from the betacoronaviruses SARS-CoV and MERS, as well as Streptococcus pneumonia, HCV, Zika virus, Dengue virus, influenza H3N2, and RSV. We show that genes showing differential alternative splicing in SARS-CoV-2 have a similar functional profile to those of SARS-CoV and MERS and affect a diverse set of genes and biological functions, including many closely related to virus biology. Additionally, the differentially spliced transcripts of cells infected by coronaviruses were more likely to undergo intron-retention, contain a pseudouridine modification, and have a smaller number of exons as compared with differentially spliced transcripts in the control groups. Viral load in clinical COVID-19 samples was correlated with isoform distribution of differentially spliced genes. A significantly higher number of ribosomal genes are affected by differential alternative splicing and gene expression in betacoronavirus samples, and the betacoronavirus differentially spliced genes are depleted for binding sites of RNA-binding proteins. Our results demonstrate characteristic patterns of differential splicing in cells infected by SARS-CoV-2, SARS-CoV, and MERS. The alternative splicing changes observed in betacoronaviruses infection potentially modify a broad range of cellular functions, via changes in the functions of the products of a diverse set of genes involved in different biological processes.

Interventions to reduce suicidal thoughts and behaviours among people in contact with the criminal justice system: A global systematic review.

BACKGROUND: People who experience incarceration die by suicide at a higher rate than those who have no prior criminal justice system contact, but little is known about the effectiveness of interventions in other criminal justice settings. We aimed to synthesise evidence regarding the effectiveness of interventions to reduce suicide and suicide-related behaviours among people in contact with the criminal justice system. METHODS: We searched Embase, PsycINFO, MEDLINE, and grey literature databases for articles published between 1 January 2000 and 1 June 2021. The protocol was registered with PROSPERO (CRD42020185989). FINDINGS: Thirty-eight studies (36 primary research articles, two grey literature reports) met our inclusion criteria, 23 of which were conducted in adult custodial settings in high-income, Western countries. Four studies were randomised controlled trials. Two-thirds of studies (n=26, 68%) were assessed as medium quality, 11 (29%) were assessed as high quality, and one (3%) was assessed as low quality. Most had considerable methodological limitations and very few interventions had been rigorously evaluated; as such, drawing robust conclusions about the efficacy of interventions was difficult. INTERPRETATION: More high-quality evidence from criminal justice settings other than adult prisons, particularly from low- and middle-income countries, should be considered a priority for future research. FUNDING: This work was funded by the Australian government's National Suicide Prevention Taskforce. RB is supported by a National Health and Medical Research Council (NHMRC) Emerging Leader Investigator Grant (EL2; GNT2008073). MW is supported by a NHMRC Postgraduate Scholarship (GNT1151103). SF was funded by the NIHR HTA Programme (HTA Project:16/159/09).

Simple possession as a 'tool': Drug law enforcement practices among police officers in the context of depenalization in British Columbia, Canada.

BACKGROUND: Examining drug law enforcement practices in the context of an evolving drug policy environment is critical for informing policy reforms and practices as they unfold. In this study, we aimed to examine police officer accounts of drug law enforcement practices, including officer use of discretion in simple possession cases, within the sociolegal context in British Columbia, Canada. METHODS: Using a qualitative approach, we conducted a thematic analysis of interviews with sixteen police officers across nine jurisdictions in the province. The analysis provided insights into police officers' recent experiences enforcing drug laws. Two major themes and several subthemes are presented which relate to drug law enforcement practices within the context of depenalization. FINDINGS: Officers' experiences and views towards simple possession enforcement suggested a model of de facto depenalization in the province, although enforcement practices including police discretion were inconsistent across officers and jurisdictions. Prosecutorial discretion was a major factor that shaped officers' enforcement practices. While officers reported not pursuing simple possession offences, many used simple possession charges as a 'tool' to do investigations, pursue other charges, and to promote social order. CONCLUSION: This study provides unique insights into drug law enforcement in an evolving sociolegal context, highlighting the potential inconsistencies, inequities, and harms that may arise from relying on a model of depenalization. In the face of drug law reforms both in Canada and elsewhere, these findings have important implications regarding the design and implementation of alternatives, such as depenalization, decriminalization, and diversion programs, which may potentially rely on, remove, and/or enhance police discretion. Where drug possession is formally decriminalized, police officers may need alternative enforcement 'tools' to support their work moving forward.