A population-based time-series analysis of opioid agonist treatment dispensed during pregnancy.

BACKGROUND AND AIMS: Identifying effective opioid treatment options during pregnancy is a high priority due to the growing prevalence of opioid use disorder across North America. We assessed the temporal impact of three population-level interventions on the use of opioid agonist treatment (OAT) during pregnancy in Ontario, Canada. DESIGN: This was a population-based time-series analysis to identify trends in the monthly prevalence of pregnant people dispensed methadone and buprenorphine. The impact of adding buprenorphine/naloxone to the public drug formulary, the release of pregnancy-specific guidance and the start of the COVID-19 pandemic were assessed. SETTING AND PARTICIPANTS: The study was conducted in Ontario, Canada between 1 July 2013 and 31 March 2022, comprising people who delivered a live or stillbirth in any Ontario hospital during the study period. MEASUREMENTS: We identified any prescription for methadone or buprenorphine dispensed between the estimated conception date and delivery date and calculated the monthly prevalence of OAT-exposed pregnancies among all pregnant people in Ontario. FINDINGS: Overall, rates of OAT during pregnancy have declined since mid-2018. Methadone-exposed pregnancies decreased from 0.46% of all pregnancies in Ontario in 2015 to a low of 0.16% in 2022. In the primary analysis, none of the interventions had a statistically significant impact on overall OAT rates; however, in the stratified analyses, there was a small increase in buprenorphine after the formulary change [0.006%, 95% confidence interval (CI) = 0.0032-0.0081, P < 0.0001] and a decrease in buprenorphine after the release of the 2017 guidelines (-0.005%, 95% CI = -0.0080 to -0.0020, P = 0.001) and the start of the COVID-19 pandemic (-0.003%, 95% CI = -0.0054 to -0.0006, P = 0.015). CONCLUSION: Despite changes in guidance and funding, opioid agonist treatment during pregnancy has been declining in Ontario, Canada since 2018.

'I don't chase drugs as much anymore, and I'm not dead': Client reported outcomes associated with safer opioid supply programs in Ontario, Canada.

INTRODUCTION: The ongoing opioid overdose crisis, which has killed over 30,000 people in Canada since 2016, is driven by the volatility of an unregulated opioid drug supply comprised primarily of fentanyl. The Canadian government has recently funded safer opioid supply (SOS) programs, which include off-label prescriptions of pharmaceutical-grade opioids to high risk individuals with the goal of reducing overdose deaths. METHODS: In 2021, we examined the implementation and adaption of four SOS programs in Ontario. These programs use a primary care model and serve communities experiencing marginalisation. We conducted semi-structured interviews with program clients. We present the results of a thematic analysis with the aim of describing clients' self-reported impact of these programs on their health and well-being. RESULTS: We interviewed 52 clients between June and October 2021 (mean age 47 years, 56% men, 17% self-identified Indigenous, 14% living with HIV). Our results indicate multifaceted pathways to improved self-reported health and well-being among clients including changes to drug use practices, fewer overdoses, reduced criminalised activity, improved trust and engagement in health care, and increased social stability (e.g., housing). DISCUSSION AND CONCLUSION: Most clients reported that the intervention saved their life because of the reduced frequency of overdoses. Findings suggest that SOS programs improved clients' health outcomes and increase opportunities for engagement in health services. Our results provide insight into the mechanisms behind some of the emergent evidence on the impact of safer supply prescribing.

Impact of safer supply programs on injection practices: client and provider experiences in Ontario, Canada.

OBJECTIVES: Fentanyl has contributed to a sharp rise in the toxicity of the unregulated drug supply and fatal overdoses in Canada. It has also changed injection practices. Injection frequency has increased as a result and so has equipment sharing and health-related risks. The aim of this analysis was to explore the impact of safer supply programs on injection practices from the perspective of clients and providers in Ontario, Canada. METHODS: The data set included qualitative interviews with 52 clients and 21 providers that were conducted between February and October 2021 across four safer supply programs. Interview excerpts discussing injection practices were extracted, screened, coded and then grouped into themes. RESULTS: We identified three themes, each theme corresponding to a change in injection practices. The first change was a decrease in the amount of fentanyl used and a decrease in injection frequency. The second change involved switching to injecting hydromorphone tablets instead of fentanyl. Finally, the third change was stopping injecting altogether and taking safer supply medications orally. CONCLUSION: Safer supply programs can contribute to reducing injection-related health risks in addition to overdose risks. More specifically, they have the potential to address disease prevention and health promotion gaps that stand-alone downstream harm reduction interventions cannot address, by working upstream and providing a safer alternative to fentanyl.

A harmonized analysis of five Canadian pregnancy cohort studies: exploring the characteristics and pregnancy outcomes associated with prenatal alcohol exposure.

BACKGROUND: As a teratogen, alcohol exposure during pregnancy can impact fetal development and result in adverse birth outcomes. Despite the clinical and social importance of prenatal alcohol use, limited routinely collected information or epidemiological data exists in Canada. The aim of this study was to pool data from multiple Canadian cohort studies to identify sociodemographic characteristics before and during pregnancy that were associated with alcohol consumption during pregnancy and to assess the impact of different patterns of alcohol use on birth outcomes. METHODS: We harmonized information collected (e.g., pregnant women's alcohol intake, infants' gestational age and birth weight) from five Canadian pregnancy cohort studies to consolidate a large sample (n = 11,448). Risk factors for any alcohol use during pregnancy, including any alcohol use prior to pregnancy recognition, and binge drinking, were estimated using binomial regressions including fixed effects of pregnancy cohort membership and multiple maternal risk factors. Impacts of alcohol use during pregnancy on birth outcomes (preterm birth and low birth weight for gestational) were also estimated using binomial regression models. RESULTS: In analyses adjusting for multiple risk factors, women's alcohol use during pregnancy, both any use and any binge drinking, was associated with drinking prior to pregnancy, smoking during pregnancy, and white ethnicity. Higher income level was associated with any drinking during pregnancy. Neither drinking during pregnancy nor binge drinking during pregnancy was significantly associated with preterm delivery or low birth weight for gestational age in our sample. CONCLUSIONS: Pooling data across pregnancy cohort studies allowed us to create a large sample of Canadian women and investigate the risk factors for alcohol consumption during pregnancy. We suggest that future pregnancy and birth cohorts should always include questions related to the frequency and amount of alcohol consumed before and during pregnancy that are prospectively harmonized to support data reusability and collaborative research.

COVID-19 and the opportunity for gender-responsive virtual and remote substance use treatment and harm reduction services.

The COVID-19 pandemic has increased the uptake of virtual and remote service delivery in the substance use field, which was previously uncommon. This swift uptake of virtual services provides an opportunity to improve service design to meet the diverse needs of women and gender-diverse people. Such services have the potential to better meet the needs of women and gender-diverse people by allowing for increased choice, control, and autonomy, enabling empowerment, facilitating greater considerations of power relations, violence, childcare responsibilities, and fostering greater inclusion of trans and non-binary people. This commentary aims to identify how virtual and remote delivery of substance use treatment and harm reduction services can be gender-responsive. We highlight the role gender transformative services play in meeting the unique needs of women and gender-diverse people who use drugs both during and after the COVID-19 pandemic. By using the unique window of opportunity COVID-19 has created to develop and deliver gender-transformative programs, we can help address the detrimental gaps in service accessibility and effectiveness that have persistently been experienced by women and gender-diverse people who use drugs.

The early impact of COVID-19 on the incidence, prevalence, and severity of alcohol use and other drugs: A systematic review.

BACKGROUND: The aim of this paper was to examine the early impact of COVID-19 on substance use to assess implications for planning substance use treatment and support systems. METHOD: A systematic review of literature published up to March 2021 was conducted to summarize changes in prevalence, incidence, and severity of substance use associated with COVID-19 and the accompanying public health measures, including lockdown, stay-at-home orders, and social distancing. RESULTS: We identified 53 papers describing changes to substance use at the population level. The majority of papers described changes related to alcohol use and most relied on self-reported measures of consumption during the COVID-19 pandemic, compared with pre-pandemic use. There was less evidence to support changes in non-alcohol substance use. In general, risky pre-pandemic alcohol use, caregiving responsibilities, stress, depression, anxiety, and current treatment for a mental disorder were found to be associated with increased substance use. CONCLUSION: This review provides preliminary data on changes in substance use, indicating that certain segments of the population increased their alcohol use early on in the COVID-19 pandemic and may be at greater risk of harm and in need of additional services. There is a need for additional population-level information on substance use to inform evidence-based rapid responses from a treatment system perspective.

Examining barriers to harm reduction and child welfare services for pregnant women and mothers who use substances using a stigma action framework.

Pregnant women and mothers who use substances often face significant barriers to accessing and engaging with substance use services. A scoping review was conducted in 2019 to understand how stigma impacts access to, retention in and outcomes of harm reduction and child welfare services for pregnant women and mothers who use substances. The forty-two (n = 42) articles were analysed using the Action Framework for Building an Inclusive Health System developed by Canada's Chief Public Health Officer to articulate the ways in which stigma and related health system barriers are experienced at the individual, interpersonal, institutional and population levels. Many articles highlighted barriers across multiple levels, 19 of which cited barriers at the individual level (i.e., fear and mistrust of child welfare services), 18 at the interpersonal level (i.e., familial and relational influence on accessing substance use treatment), 30 at the institutional level (i.e., high organisational expectations on women) and 17 at the population level (i.e., negative stereotypes and racism). Our findings highlight the interconnectedness of stigma and related barriers and the ways in which stigma at the institutional and population levels pervasively influence individual and interpersonal experiences of stigma. Despite a wealth of literature on barriers to treatment and support for pregnant women and mothers who use substances, there has been minimal focus on how systems can address these formidable barriers. This review highlights the ways in which the barriers are connected and identifies opportunities for service providers and policymakers to better support pregnant women and mothers who use substances.

Multi-service prevention programs for pregnant and parenting women with substance use and multiple vulnerabilities: Program structure and clients' perspectives on wraparound programming.

BACKGROUND: In Canada, several community-based, multi-service programs aimed at reaching vulnerable pregnant or parenting women with substance use and complex issues have emerged. These programs offer basic needs and social supports along with perinatal, primary, and mental health care, as well as substance use services. Evaluations of these 'one-stop' programs have demonstrated positive outcomes; nevertheless, few published studies have focused on how these programs are structured, on their cross-sectoral partnerships, and on clients' perceptions of their services. METHODS: The Co-Creating Evidence (CCE) project was a three-year evaluation of eight multi-service programs located in six Canadian jurisdictions. The study used a mixed-methods design involving semi-structured interviews, questionnaires, output data, and de-identified client data. This article focuses on qualitative interviews undertaken with 125 clients during the first round of site visits, supplemented by interview data with program staff and service partners. RESULTS: Each of the programs in the CCE study employs a multi-service model that both reflects a wrap-around approach to care and is intentionally geared to removing barriers to accessing services. The programs are either operated by a health authority (n = 4) or by a community-based agency (n = 4). The programs' focus on the social determinants of health, and their provision of primary, prenatal, perinatal and mental health care services is essential; similarly, on-site substance use and trauma/violence related services is pivotal. Further, programs' support in relation to women's child welfare issues promotes collaboration, common understanding of expectations, and helps to prevent child/infant removals. CONCLUSIONS: The programs involved in the Co-Creating Evidence study have impressively blended social and primary care and prenatal care. Their success in respectfully and flexibly responding to women's diverse needs, interests and readiness, within a community-based, wraparound service delivery model paves the way for others offering pre- and postnatal programming.

Multi-Service Programs for Pregnant and Parenting Women with Substance Use Concerns: Women's Perspectives on Why They Seek Help and Their Significant Changes.

Within Canada, several specialized multi-service prevention programs work with highly vulnerable pregnant and early parenting women with substance use issues. Experiences of trauma, mental health, poverty, and other factors associated with the social determinants of health complete the picture. Program evaluations have demonstrated their value, but less has been said as to women's reasons for choosing to seek help from these programs, what they were hoping to gain, or what difference they believe has occurred as a result. The Co-creating Evidence project is a multi-year (2017-2020) national evaluation of holistic programs serving women at high risk of having an infant with prenatal alcohol or substance exposure. The evaluation uses a mixed methods design involving quarterly program output and "snapshot" client data, as well as in-person, semi-structured interviews and questionnaires with clients, program staff, and program partners. This article presents findings from interviews with women regarding why they sought help, how they used the services, and what they perceived to be the most significant change in their lives as a result. Obtaining help with substance use was the top theme for what women hoped to get from their participation in their program; however, women's reasons were often intertwined. Additional motivations included wanting information, support or assistance with: child welfare; pregnancy; housing; getting connected to health care or prenatal care; and opportunities for peer support. With respect to the most significant life change, themes included: reduced substance use; improved housing; stronger mother-child connection; and improved wellness and social connections. Findings demonstrated that vulnerable, marginalized pregnant and parenting women who are using substances will seek help when health and social care services are configured in such a way as to take into consideration and address their unique roles, responsibilities, and realities.

The Potential for Fetal Alcohol Spectrum Disorder Prevention of a Harmonized Approach to Data Collection about Alcohol Use in Pregnancy Cohort Studies.

Prenatal alcohol exposure is a leading cause of disability, and a major public health concern in Canada. There are well-documented barriers for women and for service providers related to asking about alcohol use in pregnancy. Confidential research is important for learning about alcohol use before, during and after pregnancy, in order to inform fetal alcohol spectrum disorder (FASD) prevention strategies. The Research Advancement through Cohort Cataloguing and Harmonization (ReACH) initiative provides a unique opportunity to leverage the integration of the Canadian pregnancy and birth cohort information regarding women's drinking during pregnancy. In this paper, we identify: The data that can be collected using formal validated alcohol screening tools; the data currently collected through Canadian provincial/territorial perinatal surveillance efforts; and the data currently collected in the research context from 12 pregnancy cohorts in the ReACH Catalogue. We use these findings to make recommendations for data collection about women's alcohol use by future pregnancy cohorts, related to the frequency and quantity of alcohol consumed, the number of drinks consumed on an occasion, any alcohol consumption before pregnancy, changes in use since pregnancy recognition, and the quit date. Leveraging the development of a Canadian standard to measure alcohol consumption is essential to facilitate harmonization and co-analysis of data across cohorts, to obtain more accurate data on women's alcohol use and also to inform FASD prevention strategies.

Hair and stress: A pilot study of hair and cytokine balance alteration in healthy young women under major exam stress.

Mouse models show that experimental stress mimicking prolonged life-stress exposure enhances neurogenic inflammation, induces adaptive immunity cytokine-imbalance characterized by a shift to Type 1 T-helper cell cytokines and increases apoptosis of epithelial cells. This affects hair growth in otherwise healthy animals. In this study, we investigate whether a prolonged naturalistic life-stress exposure affects cytokine balance and hair parameters in healthy humans. 33 (18 exam, 15 comparison) female medical students with comparable sociobiological status were analyzed during a stressful final examination period, at three points in time (T) 12 weeks apart. T1 was before start of the learning period, T2 between the three-day written exam and an oral examination, and T3 after a 12 week rest and recovery from the stress of the examination period. Assessments included: self-reported distress and coping strategies (Perceived Stress Questionnaire [PSQ], Trier Inventory for the Assessment of Chronic Stress [TICS]), COPE), cytokines in supernatants of stimulated peripheral blood mononucleocytes (PBMCs), and trichogram (hair cycle and pigmentation analysis). Comparison between students participating in the final medical exam at T2 and non-exam students, revealed significantly higher stress perception in exam students. Time-wise comparison revealed that stress level, TH1/TH2 cytokine balance and hair parameters changed significantly from T1 to T2 in the exam group, but not the control. However, no group differences were found for cytokine balance or hair parameters at T2. The study concludes that in humans, naturalistic stress, as perceived during participation in a major medical exam, has the potential to shift the immune response to TH1 and transiently hamper hair growth, but these changes stay within a physiological range. Findings are instructive for patients suffering from hair loss in times of high stress. Replication in larger and more diverse sample populations is required, to assess suitability of trichogram analysis as biological outcome for stress studies.

Misuse of Prescription Opioid Medication among Women: A Scoping Review.

Background. National data from Canada and the United States identify women to be at greater risk than men for the misuse of prescription opioid medications. Various sex- and gender-based factors and patient and physician practices may affect women's use and misuse of prescription opioid drugs. Objectives. To explore the particular risks, issues, and treatment considerations for prescription opioid misuse among women who experience chronic noncancer pain and trauma. Methods. A scoping review for articles published between January 1990 and May 2014 was conducted on sex- and gender-based risks and treatment considerations among women who experience chronic noncancer pain and trauma. Results. A total of 57 articles were identified. The present narrative review summarizes the specific risks for the misuse of prescription opioid medication among women who have experienced violence and trauma, Aboriginal women, adolescents and young women, older women, pregnant women, women of a sexual minority, and transwomen. Discussion. The majority of the literature is descriptive, with few studies that evaluate approaches and interventions to respond to the issue of chronic pain, trauma, and misuse of prescription opioids among women, particularly vulnerable subgroups of women. Conclusions. Trauma-informed and women-centred approaches that address women's vulnerabilities and complex needs require further attention.

Prevention of Fetal Alcohol Spectrum Disorder: Current Canadian Efforts and Analysis of Gaps.

Effective prevention of risky alcohol use in pregnancy involves much more than providing information about the risk of potential birth defects and developmental disabilities in children. To categorize the breadth of possible initiatives, Canadian experts have identified a four-part framework for fetal alcohol spectrum disorder (FASD) prevention: Level 1, public awareness and broad health promotion; Level 2, conversations about alcohol with women of childbearing age and their partners; Level 3, specialized support for pregnant women; and Level 4, postpartum support for new mothers. In order to describe the level of services across Canada, 50 Canadian service providers, civil servants, and researchers working in the area of FASD prevention were involved in an online Delphi survey process to create a snapshot of current FASD prevention efforts, identify gaps, and provide ideas on how to close these gaps to improve FASD prevention. Promising Canadian practices and key areas for future action are described. Overall, Canadian FASD prevention programming reflects evidence-based practices; however, there are many opportunities to improve scope and availability of these initiatives.

Trajectories of women's homelessness in Canada's 3 northern territories.

BACKGROUND: Repairing the Holes in the Net was a 2-year, multilevel action research project designed to inform the development of culturally appropriate and gender-specific services for northern women who are homeless or marginally housed and who face mental health and substance use concerns. The study was designed to learn about the barriers and supports experienced by homeless women in the North when accessing mental health care, shelter, housing and other services; and to inform the work of northern service providers and policy advocates in a position to implement adjustments in their praxis. METHODS: This article describes the trajectories of women's service access and their ideas for service improvement from 61 qualitative, semi-structured interviews conducted with homeless women in Whitehorse, Yukon (YT), Yellowknife, Northwest Territories (NT), and Iqualit, Nunavut (NU). RESULTS: Unresolved trauma, poverty and social exclusion, inability to find and maintain housing and ineffective services emerged as interconnected and multifaceted challenges related to women's service engagement. In the face of these challenges, women displayed significant resilience and resistance, and offered important ideas for service improvement. CONCLUSIONS: The 4 interconnected systemic challenges identified in the research, coupled with specific ideas for change cited by the resilient homeless women interviewed, offer points of entry to improve service policy and delivery. Implementing trauma-informed approaches emerged as a key example of how access to, and quality of, services could be improved for homeless women in the North.

Glutathione-conjugated sulfanylalkanols are substrates for ABCC11 and γ-glutamyl transferase 1: a potential new pathway for the formation of odorant precursors in the apocrine sweat gland.

We have previously shown that precursors of odorous components characteristic of axillary sweat are hardly detectable or undetectable in individuals carrying the 538G > A SNP in the ABCC11 transporter gene. However, it is unclear, whether ABCC11 is directly involved in the transport of these compounds. To approach this question, transport of peptide-conjugated potential precursors of 3-methyl-3-sulfanylhexanol (3M3SH), a key determinant of axillary malodour, was measured using membrane vesicles of Sf9 insect cells overexpressing human ABCC11. Whilst no ABCC11-mediated transport was detected for the dipeptide precursor Cys-Gly-3M3SH, the glutathione conjugate of 3M3SH (SG-3M3SH) was robustly taken up by ABCC11 at a transport rate of 0.47 pmol/mg/min. Collectively, these results illuminate SG-3M3SH as a putative precursor of 3M3SH, which then may undergo intra-vesicular maturation to generate Cys-Gly-3M3SH. Critically, the apocrine sweat gland was demonstrated to express γ-glutamyl transferase 1 (GGT1) protein, which is known to catalyse the deglutamylation of glutathionyl conjugates. Additionally, we provide evidence that recombinant and isolated hepatic human GGT1 is capable of transforming SG-3M3SH to Cys-Gly-3M3SH in vitro. To sum up, we demonstrate that the functionality of ABCC11 is likely to play an important role in the generation of axillary malodour. Furthermore, we identify GGT1 as a key enzyme involved in the biosynthesis of Cys-Gly-3M3SH.

Efficient sweat reduction of three different antiperspirant application forms during stress-induced sweating.

OBJECTIVES: Stress sweating can occur in everyday situations independently of thermally-induced perspiration. It is triggered by emotionally challenging situations and leads to underarm wetness and a characteristic unpleasant malodor. In this study, we aimed to determine the long-term efficacy of three unperfumed antiperspirant (AP) formulas for different application forms (roll-on, stick, aerosol) against stress-induced sweating and malodor formation. METHODS: We utilized the widely accepted Trier Social Stress Test (TSST) to induce psychosocial stress in female and male volunteers (18 - 40 years) and determined physiological stress parameters. To additionally assess the efficacy of the test AP roll-on against thermally-induced sweating, a hot room study was performed. RESULTS: Increasing heart rates and an augmentation of saliva cortisol levels during the TSST indicated a substantial stress reaction which was paralleled by a pronounced sweat production in the untreated axillae of both males and females. Forty-eight hours after application, all three test APs significantly decreased the amount of sweat in the treated axillae independent of gender. With respect to AP effects on malodor production, trained sniffers assessed sweat samples collected during the TSST from the untreated axillae as significantly more malodorous than comparable samples from the AP-treated axillae. Also, independent of gender the test AP roll-on significantly decreased the thermally-induced sweat in the AP-treated axilla. CONCLUSION: We show for the first time a highly effective reduction of emotionally-induced axillary sweating and malodor production for three different application forms 48 h after the last product use. The specially developed roll-on, stick, and aerosol AP provide long-term protection against stress-induced sweat which is of high relevance in everyday life.

Topically applied L-carnitine effectively reduces sebum secretion in human skin.

BACKGROUND: Oily skin condition is caused by an excessive sebaceous gland activity, resulting in an overproduction of sebum, giving the skin an undesired shiny, oily appearance. AIMS: To identify an active substance that reduces sebum production in human sebaceous glands by regulating fat metabolism in a natural way. PATIENTS/METHODS: The effects of L-carnitine on ß-oxidation and intracellular lipid content were investigated in vitro using the human sebaceous cell line SZ95. Penetration experiments utilizing pig skin as a model system were performed with a cosmetic formulation containing radioactively labeled L-carnitine. To determine the in vivo effects, a vehicle-controlled, randomized study was carried out using a cosmetic formulation containing 2%l-carnitine for 3 weeks. Sebum production was investigated utilizing the lipid-absorbent Sebutape(®). RESULTS: SZ95 cells treated with 0.5% or 1% L-carnitine demonstrated a significant concentration-dependent increase in ß-oxidation compared to control cells. Following the treatment with L-carnitine, intracellular lipid concentrations decreased significantly in a dose-dependent manner compared with untreated control cells. In skin penetration experiments, topically applied L-carnitine reached the dermis. In addition, topical in vivo application of a formulation containing 2% L-carnitine for 3 weeks significantly decreased the sebum secretion rate compared to the treatment with vehicle. CONCLUSIONS: Our results show that the treatment of human sebocytes with L-carnitine significantly augments ß-oxidation and significantly decreases intracellular lipid content in human sebocytes. Topically applied L-carnitine is bioavailable and leads to a significant sebum reduction in vivo. In conclusion, L-carnitine represents a valuable compound, produced naturally within the body, for the topical treatment of oily skin in humans.