Pre-Pandemic and Recent Oral and Medical Health Care Utilization among Young American Indian Children and Their Caregivers.

Children from diverse ethnic groups are at significantly increased risk for dental caries. In particular, American Indian (AI) children have the highest incidence of detal caries of any ethnic group. The COVID-19 pandemic dramatically restricted health care access, including preventive oral health care. Given this context, it is unclear whether or not preventive oral health care for AI children has resumed since lockdown. To address this question, we surveyed adult AI caregivers (N = 152) of children aged 0-5 years, assessing recent (12-month) and pre-COVID (for caregivers of children aged 3-5 years) preventive oral and medical health services. We also examined medical health care access and utilization among caregivers. Among children aged 3-5 years old, both pre-pandemic and past year medical care utilization were generally high (80 and 90%, respectively) as was any oral health care utilization (64 & 78%, respectively). Oral health check-ups were more common over the last year (62%) compared to pre-COVID (44%). Recent health care utilization among children 1-5 years old in this sample were generally comparable to national estimates, except for higher reported preventive medical care (99% vs. 87.6%, respectively) and higher preventive oral care (96% vs. 59.6%, respectively). More caregivers reported delaying or foregoing needed health care due to COVID (28-38%) versus due to cost (8-17%). In this survey of AI caregivers, recent child preventive health care utilization was high, and changes in utilization following the lockdown phases of the pandemic were comparable for oral and medical health care.

Group B Streptococcus Infection and Obstetric Hemorrhage Risk.

OBJECTIVE: To elucidate the association between GBS infection and maternal risk for obstetric hemorrhage (OBH) and OBH-related morbidities (OBH-M). METHODS: This was a retrospective cohort study of all deliveries with a documented GBS status at a single large academic medical center from 2018 to 2019. GBS status was determined by either urine culture or rectovaginal culture collected during the antepartum period. The primary outcomes were quantitative blood loss (QBL), OBH, and a composite of OBH-M. Secondary outcomes were individual components of the OBH-M composite and frequency of hemorrhage-related interventions utilized intrapartum and postpartum. A stratified analysis was conducted examining only patients who were diagnosed intrapartum with an intrapartum intraamniotic infection (III). RESULTS: Of 4679 pregnant individuals who delivered a live infant between January 1, 2018 and January 1,2019 with a documented GBS status, 1,487 were identified as GBS positive (+) and 3192 were identified as GBS negative (-). The GBS + group did not have significantly higher QBL (p = 0.29) or rate of OBH (p = 0.35). There were no significant differences by GBS status in OBH morbidity (p = 0.79) or its individual components or frequency of individual pharmacologic or non-pharmacologic OBHrelated interventions. There were also no significant differences by GBS status among patients with an III. CONCLUSIONS FOR PRACTICE: GBS infection at the time of delivery was not associated with increased risk for OBH or OBH-M. Further research is needed to further explore the relationship between peripartum infections and OBH risk.

Assessing Time to Removal of Tunneled Dialysis Catheters after Arteriovenous Access Creation.

BACKGROUND: Tunneled dialysis catheters (TDCs) are a temporary bridge until definitive arteriovenous (AV) access is established. Our objective was to evaluate the time to TDC removal in patients who underwent AV access creations with TDCs already in place. METHODS: A single-center analysis of all AV access creations in patients with TDCs was performed (2014-2020). Primary outcome was time to TDC removal after access creation. RESULTS: There were 364 AV access creations with TDCs in place. The average age was 58 years, 44% of patients were female, and 64% were Black. The median time to TDC removal was 113 days (range, 22-931 days) with 71.4% having a TDC >90 days after access creation. Patients with TDC >90 days were often older (60 vs. 54.7), had hypertension (98.1% vs. 93.3%), were diabetic (65.4% vs. 47.1%), and had longer average time to maturation (107.1 vs. 55.4 days, P < 0.001) and first access (114 vs. 59.4 days, P < 0.001). Multivariable analysis showed that older age was associated with prolonged TDC placement (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05, P = 0.005) and prosthetic graft use was associated with shorter TDC indwelling time (OR 0.09, 95% CI 0.04-0.23, P ≤ 0.001). Kaplan-Meier analysis showed that 87% of TDCs were removed at 1 year. CONCLUSIONS: The majority of patients with TDCs who underwent AV access creation had prolonged TDC placement. Prosthetic graft use was associated with shorter catheter times. Close follow-up after access placement, improving maturation times, and access type selection should be considered to shortened TDC times.

Breast Cancer Screening and BI-RADS Scoring Trends Before and During the COVID-19 Pandemic in an Academic Safety-Net Hospital.

BACKGROUND: Little is known about how the COVID-19 pandemic affected screening mammography rates and Breast Imaging Reporting and Data Systems (BI-RADS) categorizations within populations facing social and economic inequities. Our study seeks to compare trends in breast cancer screening and BI-RADS assessments in an academic safety-net patient population before and during the COVID-19 pandemic. PATIENTS AND METHODS: Our single-center retrospective study evaluated women ≥ 18 years old with no known breast cancer diagnosis who received breast cancer screening from March 2019-September 2020. The screening BI-RADS score, completion of recommended diagnostic imaging, and diagnostic BI-RADS scores were compared between the pre-COVID-19 era (from 1 March 2019 to 19 March 2020) and COVID-19 era (from 20 March 2020 to 30 September 2020). RESULTS: Among the 11,798 patients identified, screened patients were younger (median age 57 versus 59 years, p < 0.001) and more likely covered by private insurance (35.9% versus 32.3%, p < 0.001) during the COVID-19 era compared with the pre-COVID-19 era. During the pandemic, there was an increase in screening mammograms categorized as BI-RADS 0 compared with the pre-COVID-19 era (20% versus 14.5%, p < 0.0001). There was no statistically significant difference in rates of completion of diagnostic imaging (81.6% versus 85.4%, p = 0.764) or assignment of suspicious BI-RADS scores (BI-RADS 4-5; 79.9% versus 80.8%, p = 0.762) between the two eras. CONCLUSIONS: Although more patients were recommended to undergo diagnostic imaging during the pandemic, there were no significant differences in race, completion of diagnostic imaging, or proportions of mammograms categorized as suspicious between the two time periods. These findings likely reflect efforts to maintain equitable care among diverse racial groups served by our safety-net hospital.

Association between duration of intrapartum oxytocin exposure and obstetric hemorrhage.

PURPOSE: Prolonged duration of intrapartum oxytocin exposure is included as a risk factor within widely adopted obstetric hemorrhage risk stratification tools. However, the duration of exposure that confers increased risk is poorly understood. This study aimed to assess the association between duration of intrapartum oxytocin exposure and obstetric blood loss, as measured by quantitative blood loss, and hemorrhage-related maternal morbidity. METHODS: This was a retrospective cohort study of all deliveries from 2018 to 2019 at a single medical center. We included patients who had received any intrapartum oxytocin, and we categorized them into 1 of 5 groups: > 0-2, ≥ 2-4, ≥ 4-6, ≥ 6-12, and ≥ 12 h of intrapartum oxytocin exposure. The primary outcomes were mean quantitative blood loss, proportion with obstetric hemorrhage (defined as quantitative blood loss ≥ 1000 mL), and proportion with obstetric hemorrhage-related morbidity, a composite of hemorrhage-related morbidity outcomes. Secondary outcomes were hemorrhage-related pharmacologic and procedural interventions. A stratified analysis was also conducted to examine primary and secondary outcomes by delivery mode. RESULTS: Of 5332 deliveries between January 1, 2018 and December 31, 2019 at our institution, 2232 (41.9%) utilized oxytocin for induction or augmentation. 326 (14.6%) had exposure of > 0-2 h, 295 (13.2%) ≥ 2-4 h, 298 (13.4%) ≥ 4-6 h, 562 (25.2%) ≥ 6-12 h, and 751 (33.6%) ≥ 12 h. Across all deliveries, there was higher mean quantitative blood loss (p < 0.01) as well as increased odds of obstetric hemorrhage (adjusted odds ratio [aOR] 1.52, 95% confidence interval [CI] 1.21-1.91) for those with ≥ 12 h of oxytocin compared to all groups between > 0-12 h of exposure. In our stratified analysis, ≥ 12 h of oxytocin exposure was associated with higher mean quantitative blood loss (p = 0.04) and odds of obstetric hemorrhage in vaginal deliveries (aOR 1.47, 95% CI: 1.03-2.11), though not in cesarean deliveries (aOR 1.16, 95% CI 0.82-1.62). There were no differences in proportion with obstetric hemorrhage-related morbidity across all deliveries (p = 0.40) or in the stratified analysis. CONCLUSION: Intrapartum oxytocin exposure of ≥ 12 h was associated with increased quantitative blood loss and odds of obstetric hemorrhage in vaginal, but not cesarean, deliveries.

Factors associated with uptake of guideline-recommended cardiovascular implantable electronic device management: a nationwide, retrospective cohort study.

Clinical guidelines recommend device removal for cardiovascular implantable electronic device (CIED) infection management. In this retrospective, nationwide cohort, 60.8% of CIED infections received guideline-concordant care. One-year mortality was higher among those without procedural management (25% vs 16%). Factors associated with receipt of device procedures included pocket infections and positive microbiology.

Hospital-based opioid treatment: Expanding and sustaining the model in Texas.

This Brief Report includes follow-up data about the sustainability and expansion of the Buprenorphine Team (B-Team), a hospital-based opioid treatment (HBOT) program. Between September 2018 and January 2023, the B-Team started 398 patients with opioid-use disorder (OUD) on buprenorphine therapy and coordinated outpatient care for 353 patients before discharge. Two-hundred and forty-nine of these patients were scheduled for follow-up at our partner addiction treatment clinic. Retention rates at our partner clinic remain relatively high: 73 patients (36% of eligible patients) continued to attend appointments between 6 and 12 months, and 40 of 180 patients (22%) who have been discharged from the hospital for at least 1 year continued to attend appointments. This model has been adopted at three additional Texas hospitals, resulting in rapid growth: 1037 patients were started on buprenorphine across these four sites during 2021-2022. Our longitudinal results support HBOT as an effective model for treating patients with OUD.

SGLT2 inhibitor ertugliflozin decreases elevated intracellular sodium, and improves energetics and contractile function in diabetic cardiomyopathy.

BACKGROUND: Elevated myocardial intracellular sodium ([Na+]i) was shown to decrease mitochondrial calcium ([Ca2+]MITO) via mitochondrial sodium/calcium exchanger (NCXMITO), resulting in decreased mitochondrial ATP synthesis. The sodium-glucose co-transporter 2 inhibitor (SGLT2i) ertugliflozin (ERTU) improved energetic deficit and contractile dysfunction in a mouse model of high fat, high sucrose (HFHS) diet-induced diabetic cardiomyopathy (DCMP). As SGLT2is were shown to lower [Na+]i in isolated cardiomyocytes, we hypothesized that energetic improvement in DCMP is at least partially mediated by a decrease in abnormally elevated myocardial [Na+]i. METHODS: Forty-two eight-week-old male C57BL/6J mice were fed a control or HFHS diet for six months. In the last month, a subgroup of HFHS-fed mice was treated with ERTU. At the end of the study, left ventricular contractile function and energetics were measured simultaneously in isolated beating hearts by 31P NMR (Nuclear Magnetic Resonance) spectroscopy. A subset of untreated HFHS hearts was perfused with vehicle vs. CGP 37157, an NCXMITO inhibitor. Myocardial [Na+]i was measured by 23Na NMR spectroscopy. RESULTS: HFHS hearts showed diastolic dysfunction, decreased contractile reserve, and impaired energetics as reflected by decreased phosphocreatine (PCr) and PCr/ATP ratio. Myocardial [Na+]i was elevated > 2-fold in HFHS (vs. control diet). ERTU reversed the impairments in HFHS hearts to levels similar to or better than control diet and decreased myocardial [Na+]i to control levels. CGP 37157 normalized the PCr/ATP ratio in HFHS hearts. CONCLUSIONS: Elevated myocardial [Na+]i contributes to mitochondrial and contractile dysfunction in DCMP. Targeting myocardial [Na+]i and/or NCXMITO may be an effective strategy in DCMP and other forms of heart disease associated with elevated myocardial [Na+]i.

Intrapartum Risk Factors and Prediction of Obstetric Hemorrhage-Related Morbidity.

OBJECTIVE: The aim of this study was to assess whether inclusion of intrapartum risk factors improves our obstetric hemorrhage risk stratification tool in predicting obstetric hemorrhage, transfusion, and related severe morbidity. STUDY DESIGN: This is a retrospective cohort study using all live deliveries at a single institution over a 2-year period (n = 5,332). Obstetric hemorrhage risk factors, hemorrhage burden, and severe maternal morbidity index outcomes were assessed through chart abstraction. Hemorrhage risk was assessed at (1) "time of admission" through chart abstraction and (2) "predelivery" by calculation after inclusion of all abstracted intrapartum risk factors. Admission high risk was compared with predelivery high risk for sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio in predicting obstetric hemorrhage, obstetric hemorrhage requiring transfusion, and obstetric hemorrhage-related severe morbidity. Significance levels were calculated using descriptive statistical methods including chi-squared tests and McNemar's tests. RESULTS: The sensitivities of the risk assessment tool using admission risk classification for high-risk patients is 25% for obstetric hemorrhage, 37% for obstetric hemorrhage requiring transfusion, and 22% for obstetric hemorrhage-related severe morbidity. After intrapartum factor inclusion, the sensitivities increase to 55% for obstetric hemorrhage, 59% for obstetric hemorrhage requiring transfusion, and 47% for obstetric hemorrhage-related severe morbidity. This "predelivery" risk assessment is significantly more sensitive across all three end points (p < 0.001 for all three outcomes). While the positive likelihood ratios for obstetric hemorrhage are equal on admission and predelivery (2.10 on admission and predelivery), they increase after intrapartum factor inclusion for obstetric hemorrhage requiring transfusion and obstetric hemorrhage-related severe morbidity (on admission, 2.74 and 1.6, respectively, and predelivery: 4.57 and 3.58, respectively). CONCLUSION: Inclusion of intrapartum risk factors increases the accuracy of this obstetric hemorrhage risk stratification tool in predicting patients requiring hemorrhage management with transfusion and obstetric hemorrhage-related severe morbidity. KEY POINTS: · There are little data to validate intrapartum hemorrhage risk reassessment.. · Including intrapartum factors improves risk stratification for transfusion and related morbidity.. · Future research should clinically validate risk reassessment in the intrapartum period..

Intrapartum magnesium sulfate exposure and obstetric hemorrhage risk.

BACKGROUND: The gold standard intrapartum treatment for preeclampsia with severe features is magnesium sulfate in order to provide prophylaxis against eclampsia. However, though magnesium sulfate is known to have a relaxant effect on uterine muscle, there have been variable reports in the literature in regard to the association between magnesium and obstetric hemorrhage (OBH). OBJECTIVE: We aim to compare OBH incidence in patients with hypertensive disease of pregnancy (HDP) with or without exposure to intrapartum magnesium sulfate. METHODS: We performed a retrospective cohort study of all deliveries at our institution associated with a diagnosis of hypertensive disease of pregnancy (HDP) (e.g. chronic and gestational hypertension, preeclampsia with or without severe features, eclampsia, or HELLP) from January 1, 2018 to December 31, 2019. The category of HDP diagnosis was determined by a detailed chart review by trained chart abstractors. The primary outcome was total quantitative blood loss (QBL) and the rate of obstetric hemorrhage. Secondary outcomes included a composite of obstetric hemorrhage-related maternal morbidity outcomes (OBH-M), the individual composite components and the incidence of additional hemorrhage-related interventions (e.g. uterotonics and surgical interventions). We also examined the same primary and secondary outcomes in a stratified analysis based on delivery mode (i.e. vaginal deliveries only and cesarean deliveries only). RESULTS: Of 791 patients with a diagnosis of HDP, 411 patients received magnesium sulfate for eclampsia prophylaxis and 380 patients did not receive magnesium sulfate. For all delivery modes, there was a significantly higher QBL (p < .01), increased rate of OBH (p = .04) and increased OBH-M (p < .01) in deliveries associated with intrapartum exposure to magnesium compared to those without. However, our stratified analysis by delivery mode demonstrated that magnesium-related hemorrhage risk only persisted for vaginal deliveries (QBL p < .01; OBH aOR 1.47, 95% CI: 0.75-2.85; OBH-M aOR 1.47, 95% CI 1.00-7.55) with no significant hemorrhage-related differences among cesareans with or without magnesium exposure (QBL p = .51; OBH aOR 1.45, 95% CI: 0.85-2.47; OBH-M 1.50 95% CI: 0.70-3.23). CONCLUSION: Intrapartum exposure to magnesium sulfate use was associated with an increase in QBL and risk of OBH-M in vaginal deliveries, but not associated with any hemorrhage-related outcome differences in cesarean deliveries. More research is needed to explore the effects of hypertensive disease, magnesium exposure, and delivery mode on obstetric hemorrhage risk.

Community based participatory research approaches to combat oral health inequities among American Indian and Alaska Native populations.

American Indian and Alaska Native (AI/AN) communities have experienced a history of systemic racism and still face significant oral health disparities. These disparities extend to the youngest community members in the form of early childhood caries (ECC). Although behavior and biology contribute to ECC, the conditions where people live, grow, and work, and the systems and political and economic forces that shape individual health outcomes, are thought to greatly impact ECC among AI/AN populations. To address ECC in AI/AN communities, we used a community based participatory approach that incorporated social determinants of health. We found that implementing culturally-tailored, culturally-centered, and AI/AN-created materials for ECC interventions is viewed favorably by community members and tribal leaders. Because of the complexity of ECC in AI/AN communities we adopted a bundled approach of best practices to reduce ECC including: (1) incorporating locally, contextually, and culturally relevant strategies to present recommended ECC prevention approaches; (2) employing AI/AN community members as educators; (3) utilizing motivational interviewing with expectant mothers; and (4) providing fluoride varnish. Our work underscores the importance of developing trusting partnerships with each other and with our communities, drawing upon the insights of community advisory board members, and eliciting formative assessment data from tribal members to gain a more holistic understanding of our participants' lived experience to design relevant intervention materials. Incorporating local knowledge and situating Western oral health prevention approaches within culturally aligned frameworks can enhance partnerships and create sustainable materials for community work.

Motivations for concurrent use of uppers and downers among people who access harm reduction services in British Columbia, Canada: findings from the 2019 Harm Reduction Client Survey.

INTRODUCTION: An increase in crystal methamphetamine (methamphetamine) use during the overdose epidemic is being observed in British Columbia (BC), Canada, and across North America. Concurrent use (ie, using uppers and downers one after the other or together) can increase the risk of fatal and non-fatal opioid overdose. OBJECTIVES: We investigated motivations for concurrent use of uppers and downers, specifically how (eg, in what order) and why people use concurrently, to identify potential interventions to prevent overdose and other harms. SETTING AND PARTICIPANTS: The 2019 Harm Reduction Client Survey was administered across 22 harm reduction supply distribution sites in BC (n=621). This thematic analysis examined 307 responses by people who affirmed concurrent use to classify order and reasons for using uppers and downers concurrently. RESULTS: Of the 307 people who responded 'yes' to concurrent use, 179 (58.3%) used downers then uppers, 76 (24.8%) used uppers then downers and 184 (59.9%) mixed uppers and downers together. Four main reasons for concurrent use emerged: self-medication, availability and preference, drug effects/properties, and financial and life situation. People who mixed drugs together predominantly wanted to achieve desired drug effects/properties, such as a specific high or balancing stimulating and sedating effects. CONCLUSIONS: The ongoing rise in overdoses in BC is multifactorial, and the recent parallel increases in methamphetamine use and concurrent use with opioids may contribute. Qualitative interviews may further elucidate reasons for concurrent use. Addressing reasons for concurrent use identified in this study through harm reduction strategies and education may affect the rates of overdose morbidity and mortality.

Cardiovascular Complications of Acetylcholinesterase Inhibitors in Patients with Alzheimer's Disease: A Narrative Review.

While acetylcholinesterase inhibitors are used to treat a wide range of patients with Alzheimer's disease, acetylcholinesterase inhibitor use has also been associated with a variety of cardiovascular complications, including bradycardia and syncope. Herein, we review the pathophysiology and clinical evidence for cardiovascular complications caused by acetylcholinesterase inhibitors in patients being treated for dementia and discuss options for their management.

A case of premature ventricular contractions-related cardiomyopathy.

Premature ventricular contractions (PVCs) are heart beats initiated in the ventricles instead of in the sinoatrial node. A high burden of PVCs can lead to a cardiomyopathy, characterised by reduced left ventricular (LV) systolic dysfunction. We present a case of PVC-related cardiomyopathy where the 65-year-old male was initially seen by his primary care provider for recent onset chest pain and dizziness. His transthoracic echocardiogram showed mild concentric LV hypertrophy and mildly reduced systolic function (LV ejection fraction 43%). There was also mild right ventricular (RV) systolic dysfunction. He was started on a beta-blocker and an angiotensin-converting enzyme inhibitor. A 24-hour Holter monitor showed a very high burden of PVCs (32% of all beats). He continued to have frequent PVCs and his echocardiogram did not improve. He was eventually referred for a PVC ablation. Following the ablation, a repeat Holter monitor showed a marked reduction in PVC burden (<1% of beats) and his echocardiogram had normalised.

Increasing fatty acid oxidation elicits a sex-dependent response in failing mouse hearts.

BACKGROUND: Reduced fatty acid oxidation (FAO) is a hallmark of metabolic remodeling in heart failure. Enhancing mitochondrial long-chain fatty acid uptake by Acetyl-CoA carboxylase 2 (ACC2) deletion increases FAO and prevents cardiac dysfunction during chronic stresses, but therapeutic efficacy of this approach has not been determined. METHODS: Male and female ACC2 f/f-MCM (ACC2KO) and their respective littermate controls were subjected to chronic pressure overload by TAC surgery. Tamoxifen injection 3 weeks after TAC induced ACC2 deletion and increased FAO in ACC2KO mice with pathological hypertrophy. RESULTS: ACC2 deletion in mice with pre-existing cardiac pathology promoted FAO in female and male hearts, but improved cardiac function only in female mice. In males, pressure overload caused a downregulation in the mitochondrial oxidative function. Stimulating FAO by ACC2 deletion caused unproductive acyl-carnitine accumulation, which failed to improve cardiac energetics. In contrast, mitochondrial oxidative capacity was sustained in female pressure overloaded hearts and ACC2 deletion improved myocardial energetics. Mechanistically, we revealed a sex-dependent regulation of PPARα signaling pathway in heart failure, which accounted for the differential response to ACC2 deletion. CONCLUSION: Metabolic remodeling in the failing heart is sex-dependent which could determine the response to metabolic intervention. The findings suggest that both mitochondrial oxidative capacity and substrate preference should be considered for metabolic therapy of heart failure.

Our Relationship to Water and Experience of Water Insecurity among Apsáalooke (Crow Indian) People, Montana.

Affordable access to safe drinking water is essential to community health, yet there is limited understanding of water insecurity among Native Americans. Therefore, the focus of this paper is to describe Apsáalooke (Crow Indian) tribal members' experiences with water insecurity. For Apsáalooke people, local rivers and springs are still vitally important for traditional cultural activities. We interviewed 30 Native American adults living on the Crow Reservation in Southeastern Montana. Participants answered six open-ended interview questions about their water access, costs of obtaining water and changes in their domestic and traditional water uses. Participants emphasized how the use of water has changed over time and described the complex challenges associated with addressing water insecurity in their community, including the importance of considering the spiritual and cultural impacts of water insecurity on health. Water insecurity is a growing global problem and more attention and efforts are needed to find appropriate and affordable solutions.

Convenience and comfort: reasons reported for using drugs alone among clients of harm reduction sites in British Columbia, Canada.

BACKGROUND: North American communities are severely impacted by the overdose crisis, particularly in British Columbia (BC), which has the highest toxic drug overdose death rate in Canada. Most fatal overdoses in BC occurred among individuals using alone and in private residences. This study aimed to assess prevalence and reasons for using drugs alone among people accessing harm reduction services in BC. METHODS: We recruited harm reduction supply distribution site clients from 22 communities across BC. Descriptive statistics and multivariable logistic regression were used to describe factors associated with using alone. Thematic analysis of free-text responses providing reasons for using alone were grouped with survey data and additional themes identified. RESULTS: Overall, 75.8% (n = 314) of the study sample (N = 414) reported using drugs alone within the last week. Those that reported using alone did not differ from those that did not by gender, age, urbanicity, or preferred drug use method. Among those that used alone, 73.2% (n = 230) used opioids, 76.8% (n = 241) used crystal meth, 41.4% (n = 130) used crack/cocaine, and 44.6% (n = 140) used alcohol in the past week. Polysubstance use involving stimulants, opioids, and/or benzodiazepines was reported by 68.5% (n = 215) of those that used alone. Additionally, 22.9% (n = 72) of those that used alone had experienced an opioid and/or stimulant overdose in the past 6 months. In a multivariable logistic regression model, having no regular housing and past week crack/cocaine use were associated with using alone (adjusted odds ratio (AOR): 2.27; 95% CI 1.20-4.27 and AOR: 2.10; 95% CI 1.15-3.82, respectively). The most common reason reported for using alone was convenience and comfort of using alone (44.3%). Additional reasons included: stigma/hiding drug use (14.0%); having no one around (11.7%); safety (9.6%); and not wanting to share drugs with others (8.6%). CONCLUSIONS: Using drugs alone, particularly for convenience and comfort, is ubiquitous among people accessing harm reduction services. Overdose prevention measures that go beyond individual behaviour changes, including providing a safer supply of drugs and eliminating stigma, are paramount to mitigate harms. These interventions are especially necessary as emergence of coronavirus disease may further exacerbate unpredictability of illicit drug content and overdose risk.

Known fentanyl use among clients of harm reduction sites in British Columbia, Canada.

BACKGROUND: North America is in the midst of an opioid overdose epidemic and it is commonly suggested that exposure to fentanyl is unknown. Using a provincial survey of harm reduction site clients, we aimed to characterize known and unknown fentanyl use and their correlates among people who use drugs in British Columbia, Canada. METHODS: We recruited 486 clients who were >18 years old and 316 agreed to provide a urine sample for substance use testing. Reported known fentanyl use was defined as a three-level categorical variable assessing recent (i.e., in the previous three days) fentanyl exposure: (i) known exposure; (ii) unknown exposure; and (iii) no exposure. We also assessed any exposure to fentanyl (Yes vs. No) confirmed by urinalysis. Survey data were summarized using descriptive statistics. Multinomial logistic regression and modified Poisson regression models were built to examine different correlates of exposure to fentanyl. RESULTS: Median age of the participants was 40 (IQR: 32-49). Out of the 303 eligible participants, 38.7% (117) reported known fentanyl use, 21.7% (66) had unknown fentanyl use, and 39.6% (120) had no recent fentanyl use. In the adjusted multinomial logistic regression model and in comparison with unknown fentanyl use, recent known fentanyl use was significantly associated with self-report of methadone use (aRRR = 3.18), heroin/morphine use (aRRR = 4.40), and crystal meth use (aRRR = 2.95). Moreover, any recent exposure to fentanyl (i.e., positive urine test for fentanyl) was significantly associated with living in urban settings (aPR = 1.49), and self-reporting recent cannabis use (aPR = 0.73), crystal meth (aPR = 1.45), and heroin/morphine use (aPR = 2.48). CONCLUSION: The landscape of illicit opioid use is changing in BC and more people are using fentanyl knowingly. The increasing prevalence of known fentanyl use is concerning and calls for further investments in public awareness and public policy efforts regarding fentanyl exposure and risks.

Metabolic Remodeling Promotes Cardiac Hypertrophy by Directing Glucose to Aspartate Biosynthesis.

RATIONALE: Hypertrophied hearts switch from mainly using fatty acids (FAs) to an increased reliance on glucose for energy production. It has been shown that preserving FA oxidation (FAO) prevents the pathological shift of substrate preference, preserves cardiac function and energetics, and reduces cardiomyocyte hypertrophy during cardiac stresses. However, it remains elusive whether substrate metabolism regulates cardiomyocyte hypertrophy directly or via a secondary effect of improving cardiac energetics. OBJECTIVE: The goal of this study was to determine the mechanisms of how preservation of FAO prevents the hypertrophic growth of cardiomyocytes. METHODS AND RESULTS: We cultured adult rat cardiomyocytes in a medium containing glucose and mixed-chain FAs and induced pathological hypertrophy by phenylephrine. Phenylephrine-induced hypertrophy was associated with increased glucose consumption and higher intracellular aspartate levels, resulting in increased synthesis of nucleotides, RNA, and proteins. These changes could be prevented by increasing FAO via deletion of ACC2 (acetyl-CoA-carboxylase 2) in phenylephrine-stimulated cardiomyocytes and in pressure overload-induced cardiac hypertrophy in vivo. Furthermore, aspartate supplementation was sufficient to reverse the antihypertrophic effect of ACC2 deletion demonstrating a causal role of elevated aspartate level in cardiomyocyte hypertrophy. 15N and 13C stable isotope tracing revealed that glucose but not glutamine contributed to increased biosynthesis of aspartate, which supplied nitrogen for nucleotide synthesis during cardiomyocyte hypertrophy. CONCLUSIONS: Our data show that increased glucose consumption is required to support aspartate synthesis that drives the increase of biomass during cardiac hypertrophy. Preservation of FAO prevents the shift of metabolic flux into the anabolic pathway and maintains catabolic metabolism for energy production, thus preventing cardiac hypertrophy and improving myocardial energetics.