Supervised consumption sites and crime: scrutinizing the methodological weaknesses and aberrant results of a government report in Alberta, Canada.

To date, peer-reviewed research has found no evidence linking supervised consumptions sites (SCSs) to increased crime. Yet, in March 2020, a government Report released in the province of Alberta, Canada, presented the results of a review that reached a different conclusion. This commentary highlights the Report's major methodological limitations with respect to its criminological components, including that crime was poorly operationalized and measured, change in crime was inadequately assessed, and the effect of SCSs on crime was not ascertained. It is argued that the magnitude of methodological flaws in the Report undermine the validity of its criminological claims and raise significant issues with the soundness of its conclusions.

Mapping of biguanide transporters in human fat cells and their impact on lipolysis.

AIM: To examine the cell membrane transporters involved in mediating the antilipolytic effect of biguanides in human fat cells. MATERIALS AND METHODS: Gene expression of biguanide transporters was mapped in human subcutaneous adipose tissue and in adipocytes before and after differentiation. Those expressed in mature fat cells were knocked down by RNA interference (RNAi) and the antilipolytic effects of metformin and two novel, highly potent biguanides, NT1014 and NT1044, were examined. RESULTS: Analysis of the transporter affinity of biguanides in HEK293 cells overexpressing individual transporters showed that NT1014 and NT1044 had >10 times higher affinity than metformin. Animal studies showed that NT1014 was >5 times more potent than metformin in lowering plasma glucose in mice. In human fat cells, the novel biguanides displayed higher AMP-activated protein kinase activation and antilipolytic efficacy than metformin. Five transporters, organic cation transporter (OCT)1 (SLC22A1), organic cation transporter novel type 1 (OCTN1; SLC22A4), OCT3 (SLC22A3), plasma membrane monoamine transporter (PMAT; SLC29A4) and multidrug and toxin extrusion transporter (MATE1; SLC47A1), were detectable in fat cells but only OCT3, PMAT and MATE1 increased during adipogenesis in vitro and were enriched in fat cells compared with other adipose cell types. Gene knockdown by RNAi showed that MATE1 and PMAT reduction attenuated the antilipolytic effect of metformin but only PMAT knockdown decreased the effect of all three biguanides. CONCLUSIONS: While human fat cells primarily express three biguanide transporters, our data suggest that PMAT is the primary target for development of fat cell-specific antilipolytic biguanides with high sensitivity and potency.

Primary Care Physicians' Views about Prescribing Methadone to Treat Opioid Use Disorder.

BACKGROUND: Methadone maintenance treatment is an effective way to reduce harms associated with opioid use disorder and, in several countries, is delivered in community-based primary care settings. Expanding methadone into primary care depends, in part, on physicians' willingness and readiness to integrate it into their practices. OBJECTIVES: This qualitative study explores factors that primary care physicians consider important when contemplating prescribing methadone to treat opioid use disorder. METHODS: In-depth interviews were conducted during 2015 with 20 primary care physicians in various sized communities throughout Nova Scotia, Canada. Participants shared their views and experiences related to prescribing methadone to treat opioid use disorder. Data were analyzed inductively using thematic analysis to identify predominant themes. RESULTS: Participants discussed an interplay of factors as they contemplated prescribing methadone to treat opioid use disorder in primary care. Physician-related factors included access to methadone expertise, support from allied professionals, suitability of skills, and personal experiences. Patient-related factors involved perceptions about methadone users as a difficult patient group with highly complex needs. Practice-related factors encompassed concerns about threats to physicians' careers, surveillance duties, unfair remuneration, safety risks, and practice disruptions. Contextual factors included knowledge deficits about substance use disorders, the generalist nature of primary care, methadone's socio-political context, and opioid prescribing patterns in primary care. CONCLUSIONS: Understanding the perspectives of physicians is vital to expanding methadone into primary care. This study identifies factors that should be addressed to attract, support, and retain primary care physicians in prescribing methadone to treat opioid use disorder.

Using social bonding theory to examine 'recovery' in a forensic mental health hospital: A qualitative study.

BACKGROUND: For people living with mental illness, recovery involves learning to overcome and manage their symptoms and striving to live fulfilling lives. The literature on achieving recovery emphasises the importance of social connections and positive role models. Hirschi's social bonding theory posits that an individual's attachment to others, belief in social norms, and their commitment and involvement in conventional activities are the major contributors to normalising social behaviour. AIMS: The aim of this study is to understand the qualities of service identified by patients in a forensic hospital as being important and meaningful to recovery. METHODS: Semi-structured interviews with 30 inpatients in a forensic mental health hospital in British Columbia, Canada, were audio recorded, and the transcriptions were analysed using thematic analysis. RESULTS: Five themes emerged: involvement in programmes, belief in rules and social norms, attachment to supportive individuals, commitment to work-related activities and concern about indeterminacy of stay. CONCLUSIONS: The first four themes map closely onto Hirschi's criminologically derived social bonding theory; however, indeterminacy of stay also arose as a common theme. In addition, the theory was too simple in its separation of elements; our data suggested the complex integration of themes. Our findings may be useful for informing evaluation of forensic mental health services.

Another time point, a different story: one year effects of a social media intervention on the attitudes of young people towards mental health issues.

PURPOSE: This study extends an evaluation of a brief, social media intervention, called In One Voice, for raising mental health awareness and improving attitudes of youth and young adults towards mental health issues. METHODS: A successive independent samples design assessed market penetration and attitudinal changes among the young people who completed an online questionnaire 1 year after (T3: n = 438) the intervention. This is compared with two samples that completed a survey either immediately before (T1: n = 403) or 2 months after (T2: n = 403) the campaign launch. RESULTS: The proportion of respondents who remembered the campaign grew from 24.8 % at T2 to 48.6 % at T3. Elevated website activity on mindcheck.ca was sustained 1 year after In One Voice had ended. Small but significant reductions in personal stigma and social distance were detected from T1 and T3, which were not observed at T2. Respondents' self-rated ability to help others with mental health issues and to engage in positive behaviors relating to mental health issues (e.g., seeking information) did not improve significantly from T1 to T3. CONCLUSIONS: Improved attitudes towards mental health issues were observed among young people 1 year following a brief social media campaign. The campaign was less effective at providing the tools young people need to feel capable of helping someone who may be experiencing mental health issues, and motivating them to engage in constructive behaviors related to mental health.

What influences perceptions of procedural justice among people with mental illness regarding their interactions with the police?

According to procedural justice theory, a central factor shaping perceptions about authority figures and dispute resolution processes is whether an individual believes they were treated justly and fairly during personal encounters with agents of authority. This paper describes findings from a community-based participatory research study examining perceptions of procedural justice among sixty people with mental illness regarding their interactions with police. The degree to which these perceptions were associated with selected individual (e.g., socio-demographic characteristics), contextual (e.g., neighborhood, past experiences), and interactional (e.g., actions of the officer) factors was explored. The results of regression analyses indicate that the behavior of police officers during the interactions appears to be the key to whether or not these interactions are perceived by people with mental illness as being procedurally just. Implications of these findings for improving interactions between the police and people with mental illness are discussed.

Evaluation of a campaign to improve awareness and attitudes of young people towards mental health issues.

PURPOSE: This study evaluated the effectiveness of the In One Voice campaign for raising mental health awareness and improving attitudes of youth and young adults towards mental health issues. The campaign featured a prominent male sports figure talking about mental health issues and used online social media. METHODS: A successive independent samples design assessed market penetration and attitudinal changes among the young people. Two samples completed an online questionnaire either immediately before (T1: n = 403) or 2 months after (T2: n = 403) the campaign launch. Website analytics determined changes in activity levels of a youth-focused mental health website (mindcheck.ca). RESULTS: One-quarter (24.8 %, n = 100) of the respondents remembered the campaign. The proportion of respondents who were aware of the website increased significantly from 6.0 % at T1 to 15.6 % at T2. Average overall scores on standardized measures of personal stigma and social distance were not significantly different between T1 and T2 respondents. Attitudes towards mental health issues were statistically similar between respondents who were or were not exposed to the campaign. Those who were exposed to the campaign were significantly more likely to talk about and seek information relating to mental health issues. CONCLUSIONS: The proximal outcomes of the campaign to increase awareness and use of the website were achieved. The distal outcome of the campaign to improve attitudes towards mental health issues was not successfully achieved. The brief social media campaign improved mental health literacy outcomes, but had limited effect on personal stigma and social distance.

Supporting recovery by improving patient engagement in a forensic mental health hospital: results from a demonstration project.

BACKGROUND: Mental health services are shifting toward approaches that promote patients' choices and acknowledge the value of their lived experiences. OBJECTIVE: To support patients' recovery and improve their experiences of care in a Canadian forensic mental health hospital, an intervention was launched to increase patient engagement by establishing a peer support program, strengthening a patient advisory committee, and creating a patient-led research team. DESIGN: The effect of the intervention on patient- and system-level outcomes was studied using a naturalistic, prospective, longitudinal approach. Quantitative and qualitative data were gathered from inpatients and service providers twice during the 19-month intervention. RESULTS: Despite succeeding in supporting patients' participation, the intervention had minimal impacts on internalized stigma, personal recovery, personal empowerment, service engagement, therapeutic milieu, and the recovery orientation of services. Peer support demonstrated positive effects on internalized stigma and personal recovery. CONCLUSIONS: Strengthening patient engagement contributes toward improving experiences of care in a forensic hospital, but it may have limited effects on outcomes.

Stressors and barriers to using mental health services among diverse groups of first-generation immigrants to the United States.

This study examined stressors and barriers to using mental health services among first-generation immigrants in San Jose, California. Focus groups for 30 immigrants from Cambodia, Eastern Europe, Iran, Iraq, Africa, and Vietnam were audio-recorded, translated and transcribed. Two researchers coded the data and identified themes pertaining to mental health stressors and barriers. Six primary stressors were identified: economic, discrimination, acculturation due to language differences, enculturation, parenting differences, and finding suitable employment. Primary barriers included: stigma, lack of a perceived norm in country of origin for using mental health services, competing cultural practices, lack of information, language barriers, and cost. A conceptual model is presented that may be used to inform the design and implementation of mental health services for this population.

'Forensic' labelling: an empirical assessment of its effects on self-stigma for people with severe mental illness.

Increasingly, specialized 'forensic' mental health services are being developed to address the criminogenic and clinical needs of people with mental illness who are involved in the criminal justice system. Theoretically, the construction of such specialized services can produce simultaneous positive benefits and negative consequences. This mixed methods study examined and compared the level of self-stigma that was experienced by people who receive compulsory community-based treatment services in the forensic (n=52) and civil (n=39) mental health systems of British Columbia, Canada. The quantitative findings indicate that 'forensic' labelling was not associated with elevated levels of self-stigma. Quantitative level of self-stigma was significantly associated with psychiatric symptom severity, history of incarceration, and history of homelessness. The qualitative findings suggest that access to high-quality, well-resourced forensic mental health services may, for some service users, come at the risk of increased exposure to social and structural stigma. Together, these findings reveal some of the strengths and weaknesses that are associated with organizing forensic mental health services using a specialized service delivery model.

The Effects of NT-1044, a Novel AMPK Activator, on Endometrial Cancer Cell Proliferation, Apoptosis, Cell Stress and In Vivo Tumor Growth.

OBJECTIVES: Anti-diabetic biguanide drugs such as metformin may have anti-tumorigenic effects by behaving as AMPK activators and mTOR inhibitors. Metformin requires organic cation transporters (OCTs) for entry into cells, and NT-1044 is an AMPK activator designed to have greater affinity for two of these transporters, OCT1 and OCT3. We sought to compare the effects of NT-1044 on cell proliferation in human endometrial cancer (EC) cell lines and on tumor growth in an endometrioid EC mouse model. METHODS: Cell proliferation was assessed in two EC cell lines, ECC-1 and Ishikawa, by MTT assay after exposure to NT-1044 for 72 hours of treatment. Apoptosis was analyzed by Annexin V-FITC and cleaved caspase 3 assays. Cell cycle progression was evaluated by Cellometer. Reactive oxygen species (ROS) were measured using DCFH-DA and JC-1 assays. For the in vivo studies, we utilized the LKB1fl/flp53fl/fl mouse model of endometrioid endometrial cancer. The mice were treated with placebo or NT-1044 or metformin following tumor onset for 4 weeks. RESULTS: NT-1044 and metformin significantly inhibited cell proliferation in a dose-dependent manner in both EC cell lines after 72 hours of exposure (IC50 218 µM for Ishikawa; 87 µM for ECC-1 cells). Treatment with NT-1044 resulted in G1 cell cycle arrest, induced apoptosis and increased ROS production in both cell lines. NT-1044 increased phosphorylation of AMPK and decreased phosphorylation of S6, a key downstream target of the mTOR pathway. Expression of the cell cycle proteins CDK4, CDK6 and cyclin D1 decreased in a dose-dependent fashion while cellular stress protein expression was induced in both cell lines. As compared to placebo, NT-1044 and metformin inhibited endometrial tumor growth in obese and lean LKB1fl/flp53fl/fl mice. CONCLUSIONS: NT-1044 suppressed EC cell growth through G1 cell cycle arrest, induction of apoptosis and cellular stress, activation of AMPK and inhibition of the mTOR pathway. In addition, NT-1044 inhibited EC tumor growth in vivo under obese and lean conditions. More work is needed to determine if this novel biguanide will be beneficial in the treatment of women with EC, a disease strongly impacted by obesity and diabetes.

Antidepressant medication use and risk of persistent pulmonary hypertension of the newborn.

PURPOSE: To determine the prevalence of persistent pulmonary hypertension of the newborn (PPHN) among infants whose mothers were exposed to antidepressants in the third trimester of pregnancy compared to the prevalence among infants whose mothers were not exposed to antidepressants in the third trimester. METHODS: A retrospective study was conducted using the automated databases of four health plans participating in the HMO Research Network Center for Education and Research on Therapeutics. Women who delivered an infant in a hospital from 1 January 1996 through 31 December 2000 were identified. The administrative databases were used to identify full-term infants whose mothers received an antidepressant during the third trimester of pregnancy and unexposed infants whose mothers did not receive an antidepressant during the third trimester. Hospitalization data were used to identify diagnoses or procedure codes potentially indicative of PPHN. RESULTS: Among 1104 infants exposed to antidepressants in the third trimester and a matched sample of 1104 unexposed infants, five infants were classified by the expert reviewers as having PPHN. Among those infants whose mothers were exposed to selective serotonin reuptake inhibitors (SSRIs) in the third trimester, the prevalence of PPHN was 2.14 per 1000 (95% confidence interval (CI) 0.26, 7.74), while the prevalence among infants whose mothers were not exposed was 2.72 per 1000 (95%CI 0.56, 7.93). CONCLUSIONS: We did not find an association between SSRI use in late pregnancy and PPHN. Limitations of the present study, including the small number of confirmed cases, suggest further research in this area may be warranted.

Use of antidepressant medications during pregnancy: a multisite study.

OBJECTIVE: This study was undertaken to provide information on the prevalence of use of antidepressant drugs among pregnant women in the United States. STUDY DESIGN: A retrospective study was conducted using the automated databases of 7 health plans. Women who delivered an infant in a hospital were identified. Antidepressant drug use was evaluated assuming a gestational duration of 270 days. RESULTS: Among the 118,935 deliveries occurring from 2001-2005, 6.6% of women were dispensed an antidepressant during pregnancy. Antidepressant drug use increased from 2.0% in 1996 to 7.6% of deliveries in 2004 and 2005. Selective serotonin reuptake inhibitor use increased from 1.5% in 1996 to 6.4% in 2004 and 6.2% in 2005. CONCLUSION: Our finding that nearly 8% of pregnant women were prescribed antidepressants drugs during the years 2004 and 2005 highlights the importance of understanding the effects of these medications on the developing fetus and on the pregnant woman.

Outpatient use of cardiovascular drugs during pregnancy.

PURPOSE: To provide information on the prevalence of use of cardiovascular drugs, some of which may have fetotoxic or teratogenic effects, in the outpatient setting among pregnant women in the United States. METHODS: A retrospective study was conducted using the automated databases of seven health plans participating in the HMO Research Network Center for Education and Research on Therapeutics (CERT). Women who delivered an infant from 1 January 2001 to 31 December 2005 were identified. Cardiovascular drug use was evaluated assuming a gestational duration of 270 days. RESULTS: During the period 2001 through 2005, 118,935 deliveries were identified that met the criteria for study; 3.1% of women (N = 3672) were dispensed an antihypertensive medication and 0.12% of women (N = 146) were dispensed an antihyperlipidemic medication at any time during pregnancy. The most common antihypertensive drugs dispensed during pregnancy were nifedipine (1219 deliveries; 1.0%), methyldopa (961 deliveries; 0.8%), atenolol (593 deliveries; 0.5%), and labetalol (576 deliveries; 0.5%). Overall, 134 women (0.11%) received an angiotensin converting enzyme (ACE) inhibitor and 7 women (0.006%) received an angiotensin II receptor blocker (ARB) during pregnancy. Statins were the most commonly dispensed antihyperlipidemic drugs (71 deliveries; 0.06%). CONCLUSIONS: The prevalence of use of cardiovascular drugs that are suspected to be fetotoxic or teratogenic (ACE inhibitors, ARBs, and statins) was low in this cohort of pregnant women. Differing patterns of use across health plans suggests that further research is needed to evaluate the potential differential effects of cardiovascular drugs to assist prescribers and patients in making informed treatment decisions.

What Does Success Look Like in the Forensic Mental Health System? Perspectives of Service Users and Service Providers.

Outcomes research in forensic mental health (FMH) has concentrated on reoffending as the principal indicator of success. Defining success in one-dimensional, negative terms can create a distorted view of the diverse objectives of the FMH system. This qualitative study examined the complexity of success from the perspectives of people in the FMH system. Interviews were conducted with 18 forensic service users and 10 forensic service providers. Data were analyzed inductively using thematic analysis to identify predominant themes. The participants conceptualized success as a dynamic process materializing across six different domains in the context of the FMH system: (a) normal life, (b) independent life, (c) compliant life, (d) healthy life, (e) meaningful life, and (f) progressing life. The results indicate that people who provide or use FMH services emphasize a broad range of processes and outcomes, apart from public safety, when they think about success.

Stigma associated with mental illness among Asian men in Vancouver, Canada.

BACKGROUND:: Due to racism, xenophobic nationalism, acculturation pressures and patriarchal social relations, Asian men in Western societies may be particularly susceptible to negative experiences and beliefs regarding mental illness and treatment services. AIMS:: We examine factors associated with stigma toward mental illness among Asian men in Canada. METHODS:: Between 2013 and 2017, 428 self-identified Asian men living in proximity to Vancouver, Canada, were recruited and completed self-administered questionnaires assessing social stigma and self-stigma. The degree to which these variables were associated with the men's sociodemographic characteristics was analyzed. RESULTS:: Multivariable regression revealed that social stigma was significantly predicted by age, immigration, employment status and experience with mental illness. Together, these variables accounted for 12.36% of variance in social stigma. Interaction terms were added to the regression models to examine whether the effects of immigration on social stigma varied by age and experience with mental illness, but none of the interaction terms were statistically significant. Among the 94 Asian men identified as living with mental illness, self-stigma was predicted by age, immigration and employment status, which together accounted for 14.97% of variance in self-stigma. CONCLUSION:: These results offer new knowledge about the factors predicting stigma toward mental illness among Asian men in Western societies.

Small-molecule ghrelin receptor antagonists improve glucose tolerance, suppress appetite, and promote weight loss.

Ghrelin, through action on its receptor, GH secretagogue receptor type 1a (GHS-R1a), exerts a variety of metabolic functions including stimulation of appetite and weight gain and suppression of insulin secretion. In the present study, we examined the effects of novel small-molecule GHS-R1a antagonists on insulin secretion, glucose tolerance, and weight loss. Ghrelin dose-dependently suppressed insulin secretion from dispersed rat islets. This effect was fully blocked by a GHS-R1a antagonist. Consistent with this observation, a single oral dose of a GHS-R1a antagonist improved glucose homeostasis in an ip glucose tolerance test in rat. Improvement in glucose tolerance was attributed to increased insulin secretion. Daily oral administration of a GHS-R1a antagonist to diet-induced obese mice led to reduced food intake and weight loss (up to 15%) due to selective loss of fat mass. Pair-feeding experiments indicated that weight loss was largely a consequence of reduced food intake. The impact of a GHS-R1a antagonist on gastric emptying was also examined. Although the GHS-R1a antagonist modestly delayed gastric emptying at the highest dose tested (10 mg/kg), delayed gastric emptying does not appear to be a requirement for weight loss because lower doses produced weight loss without an effect on gastric emptying. Consistent with the hypothesis that ghrelin regulates feeding centrally, the anorexigenic effects of potent GHS-R1a antagonists in mice appeared to correspond with their brain exposure. These observations demonstrate that GHS-R1a antagonists have the potential to improve the diabetic condition by promoting glucose-dependent insulin secretion and promoting weight loss.

Indanylacetic acid derivatives carrying 4-thiazolyl-phenoxy tail groups, a new class of potent PPAR alpha/gamma/delta pan agonists: synthesis, structure-activity relationship, and in vivo efficacy.

Compounds that simultaneously activate the three peroxisome proliferator-activated receptor (PPAR) subtypes alpha, gamma, and delta hold potential to address the adverse metabolic and cardiovascular conditions associated with diabetes and the metabolic syndrome. We recently identified the indanylacetic acid moiety as a well-tunable PPAR agonist head group. Here we report the synthesis and structure-activity relationship (SAR) studies of novel aryl tail group derivatives that led to a new class of potent PPAR pan agonists. While most of the tail group modifications imparted potent PPAR delta agonist activity, improvement of PPAR alpha and gamma activity required the introduction of new heterocyclic substituents that were not known in the PPAR literature. Systematic optimization led to the discovery of 4-thiazolyl-phenyl derivatives with potent PPAR alpha/gamma/delta pan agonistic activity. The lead candidate from this series was found to exhibit excellent ADME properties and superior therapeutic potential compared to known PPAR gamma activating agents by favorably modulating lipid levels in hApoA1 mice and hyperlipidemic hamsters, while normalizing glucose levels in diabetic rodent models.

Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity.

The peptide hormone ghrelin is the endogenous ligand for the type 1a growth hormone secretagogue receptor (GHS-R1a) and the only currently known circulating appetite stimulant. GHS-R1a antagonism has therefore been proposed as a potential approach for obesity treatment. More recently, ghrelin has been recognized to also play a role in controlling glucose-induced insulin secretion, which suggests another possible benefit for a GHS-R1a antagonist, namely, the role as an insulin secretagogue with potential value for diabetes treatment. In our laboratories, piperidine-substituted quinazolinone derivatives were identified as a new class of small-molecule GHS-R1a antagonists. Starting from an agonist with poor oral bioavailability, optimization led to potent, selective, and orally bioavailable antagonists. In vivo efficacy evaluation of selected compounds revealed suppression of food intake and body weight reduction as well as glucose-lowering effects mediated by glucose-dependent insulin secretion.

Dual-acting peptide with prolonged glucagon-like peptide-1 receptor agonist and glucagon receptor antagonist activity for the treatment of type 2 diabetes.

Type 2 diabetes is characterized by reduced insulin secretion from the pancreas and overproduction of glucose by the liver. Glucagon-like peptide-1 (GLP-1) promotes glucose-dependent insulin secretion from the pancreas, while glucagon promotes glucose output from the liver. Taking advantage of the homology between GLP-1 and glucagon, a GLP-1/glucagon hybrid peptide, dual-acting peptide for diabetes (DAPD), was identified with combined GLP-1 receptor agonist and glucagon receptor antagonist activity. To overcome its short plasma half-life DAPD was PEGylated, resulting in dramatically prolonged activity in vivo. PEGylated DAPD (PEG-DAPD) increases insulin and decreases glucose in a glucose tolerance test, evidence of GLP-1 receptor agonism. It also reduces blood glucose following a glucagon challenge and elevates fasting glucagon levels in mice, evidence of glucagon receptor antagonism. The PEG-DAPD effects on glucose tolerance are also observed in the presence of the GLP-1 antagonist peptide, exendin(9-39). An antidiabetic effect of PEG-DAPD is observed in db/db mice. Furthermore, PEGylation of DAPD eliminates the inhibition of gastrointestinal motility observed with GLP-1 and its analogues. Thus, PEG-DAPD has the potential to be developed as a novel dual-acting peptide to treat type 2 diabetes, with prolonged in vivo activity, and without the GI side-effects.