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JACC. Advances Oct 2023Substance use and cardiovascular (CV) events are increasing among pregnant women in the United States, but association between substance use in pregnancy and CV events...
BACKGROUND
Substance use and cardiovascular (CV) events are increasing among pregnant women in the United States, but association between substance use in pregnancy and CV events remains unknown.
OBJECTIVES
The purpose of this study was to examine the association between substance use and acute CV events in pregnancy.
METHODS
We identified all women with a delivery hospitalization between 2004 and 2018 in the Nationwide Inpatient Sample, stratified on the presence or absence of substance use. The primary outcome was any acute CV event, defined as the presence of: acute myocardial infarction, stroke, arrhythmia, endocarditis, acute cardiomyopathy or heart failure, or cardiac arrest. Secondary outcomes were individual acute CV events, major adverse cardiac events, and maternal mortality. The association between substance use and outcomes were examined using multivariable logistical regression.
RESULTS
A total of 60,014,368 delivery hospitalizations occurred from 2004 to 2018, with substance use complicating 955,531 (1.6%) deliveries. Substance use was independently associated with CV events (adjusted odds ratio [aOR]: 1.61; 95% CI: 1.53-1.70; < 0.001), major adverse cardiac events (aOR: 1.53; 95% CI: 1.46-1.61; < 0.001), and maternal mortality (aOR: 2.65; 95% CI: 2.15-3.25; < 0.001) during delivery hospitalization. All individual substances had an increased association with CV events; however, amphetamine/methamphetamine had the strongest association (aOR: 2.71; 95% CI: 2.35-3.12; < 0.001). All substances other than cocaine and cannabis had a significant association with maternal death.
CONCLUSIONS
Substance use has a strong association with acute CV events and maternal mortality during hospitalization for delivery and women with substance use warrant increased surveillance for CV events during this time.
PubMed: 38938361
DOI: 10.1016/j.jacadv.2023.100619 -
Addiction Neuroscience Jun 2024Relapse is a major challenge in treating drug addiction, and drug seeking progressively increases after abstinence, a phenomenon termed "incubation of drug craving"....
The estrous cycle has no effect on incubation of methamphetamine craving and associated Fos expression in dorsomedial striatum and anterior intralaminar nucleus of thalamus.
Relapse is a major challenge in treating drug addiction, and drug seeking progressively increases after abstinence, a phenomenon termed "incubation of drug craving". Previous studies demonstrated both sex differences and an effect of estrous cycle in female rats in incubation of cocaine craving. In contrast, while incubation of methamphetamine craving is similar across sexes, whether estrous cycle plays a role in this incubation has yet to be fully addressed. Moreover, whether neural mechanisms underlying incubation of methamphetamine craving differ across estrous cycles is largely unknown. To address these gaps, we first compared methamphetamine self-administration, and methamphetamine seeking on both abstinence days 1 and 28 between male rats and female rats across the estrous cycle. Next, we examined neuronal activation associated with incubated methamphetamine seeking in dorsomedial striatum (DMS) and lateral portion of the anterior intralaminar nucleus of thalamus (AIT-L), two brain areas previously implicated in incubation of methamphetamine craving. We found no effect of sex or estrous cycle on methamphetamine self-administration and methamphetamine seeking on abstinence days 1 and 28. We also found no effect of sex or estrous cycle on the number of Fos-expressing cells in DMS or AIT-L following methamphetamine seeking test. Taken together, our results showed that methamphetamine self-administration and incubation of methamphetamine craving was not dependent on sex or estrous cycles under our experimental condition, and the role of DMS and AIT-L in incubation of methamphetamine craving may be similar across sexes and across estrous cycles in female rats.
PubMed: 38938268
DOI: 10.1016/j.addicn.2024.100158 -
Journal of Analytical Toxicology Jun 2024Brain can a useful specimen for toxicology testing as it is a protected and isolated organ with lower metabolic activity than other tissues, but there is currently no...
Brain can a useful specimen for toxicology testing as it is a protected and isolated organ with lower metabolic activity than other tissues, but there is currently no published data supporting the stability of stimulant drugs in prepared brain homogenates. Brain homogenates were evaluated to determine the stability of the following stimulant drugs: amphetamine, benzoylecgonine, bupropion, cocaethylene, cocaine, ephedrine, methylenedioxyamphetamine, methylenedioxymethamphetamine, methamphetamine, and phentermine. Four different homogenates were prepared at a 1:4 dilution with deionized water and fortified at 500 ng/mL of: cocaine without sodium fluoride, cocaine with 1% sodium fluoride, stimulant drugs other than cocaine without sodium fluoride, and stimulant drugs other than cocaine with 1% sodium fluoride. The fortified homogenates were aliquoted into 13x100 mm screw cap tubes and stored at room temperature (~20 °C), refrigerated (2-8 °C), or frozen (< -5 °C) and analyzed in triplicate on Days 0, 1, 3, 7, 14, 30, 60, and 90. Analytes were considered stable as long as the difference in analyte/internal standard response ratio from Day 0 was less than 20% and the peaks met qualitative acceptance criteria. All analytes were stable for up to 90 days when stored frozen with or without sodium fluoride and had variable stability at all other evaluated conditions.
PubMed: 38937871
DOI: 10.1093/jat/bkae058 -
Brain Research Jun 2024Drug addiction may result in sleep problems. Importantly, sleep deprivation (SD) is known as an important risk factor for relapse to drug abuse as SD mimics the effects...
Drug addiction may result in sleep problems. Importantly, sleep deprivation (SD) is known as an important risk factor for relapse to drug abuse as SD mimics the effects of psychostimulants on dopamine system of the brain. Moreover, aging may affect sleep and drug addiction. This study, therefore, set out to assess the effects of methamphetamine (METH) and REM sleep deprivation (RSD) on locomotor activity, anxiety-like behavior and spatial memory in adult and adolescent rats. Adult and adolescent male Wistar rats received a neurotoxic METH regimen; four subcutaneous injections of 6 mg/kg, at 2 h intervals. Five days later, the animals underwent a 48-h RSD episode using the multiple platforms method. They were then examined using the open field (OF), elevated plus maze (EPM) and Y-maze tasks. We found that the METH and RSD paradigms showed synergistic effects to increase locomotion and risk-taking behavior in both adult and adolescent animals, while only adolescent rats revealed RSD-induced anxiety-like behavior. Moreover, adolescent animals revealed greater sensitization for vertical activity following METH plus RSD episode. In addition, METH and RSD paradigms revealed synergistic effects to impair spatial working memory, but neither METH nor RSD alone affected performance of animals in the Y-maze task. Our findings may indicate that there are important relationships between METH and RSD to induce hyperlocomotion, risk-taking behavior and spatial memory impairment, particularly in adolescent animals. Moreover, it seems that adolescent rats may be more susceptible to anxiety-like behavior and hyperlocomotion than adults.
PubMed: 38936532
DOI: 10.1016/j.brainres.2024.149096 -
Endocrine Jun 2024We recently demonstrated an additional oxytocin (OT) deficiency in patients with arginine vasopressin (AVP) deficiency (central diabetes insipidus) by using...
PURPOSE
We recently demonstrated an additional oxytocin (OT) deficiency in patients with arginine vasopressin (AVP) deficiency (central diabetes insipidus) by using 3,4-methylenedioxy-methamphetamine (MDMA) as a novel provocation test. However, the implication of the MDMA provocation test in clinical practice might be challenging. Glucagon effectively stimulates vasopressinergic neurons with a strong increase in plasma copeptin. We therefore hypothesized that this provocation test might also stimulate OT.
METHODS
This is a predefined secondary analysis of a prospective double-blind, randomised, placebo-controlled cross-over trial involving ten patients with AVP deficiency and ten sex- and body-mass index-matched healthy participants at the University Hospital Basel, Switzerland. Each participant underwent the glucagon test (s.c. injection of 1 mg glucagon) and placebo test (s.c. injection of 0.9% normal saline). Plasma OT levels were measured at baseline, 60, 120 and 180 min after injection. The primary objective was to determine whether glucagon stimulates OT and whether OT levels differ between patients with AVP deficiency and healthy participants. The primary outcome (maximum change in OT within 180 min) was compared between groups and conditions using a linear mixed effects model.
RESULTS
In healthy participants, the median OT at baseline was 82.7 pg/ml [62.3-94.3] and slightly increased to a maximum of 93.3 pg/ml [87.2-121.1] after injection of glucagon, resulting in a change increase of 24.9 pg/ml [5.1-27.8]. Similarly, in patients with AVP deficiency, the median OT at baseline was 73.9 pg/ml [65.3-81.6] and slightly increased after glucagon injection to 114.9 pg/ml [70.9-140.9], resulting in a change increase of 36.8 pg/ml [-2.2 to 51.2]. The results from the mixed model showed no effect between glucagon compared to placebo on OT (difference: -0.5 pg/ml; 95%-CI [-25, 24]; p = 0.97) and no significant treatment-by-group interaction effect between patients compared to healthy participants (interaction: 28 pg/ml; 95%-CI [-7, 62]; p = 0.13).
CONCLUSION
We found no effect of glucagon on plasma OT levels and no difference between patients with AVP deficiency and healthy participants.
PubMed: 38935296
DOI: 10.1007/s12020-024-03920-2 -
Frontiers in Public Health 2024Injecting methamphetamine poses significant health risks, but little is known about how methamphetamine injectors filter their injection preparations and experience...
INTRODUCTION
Injecting methamphetamine poses significant health risks, but little is known about how methamphetamine injectors filter their injection preparations and experience related health concerns.
METHODS
A chain-referral sample of Indigenous people who inject methamphetamine ( = 30) was recruited and semistructured interviews were conducted to collect information on filtration practices and health concerns.
RESULTS
Filtration of the injection preparation was described by 53% of injectors. Elevated levels of concern for kidney disease, cancer and heart disease were observed among those who filtered their preparations (ranging from 50 to 56.3%). Concern about liver disease was the most frequent concern among those who filtered their preparations (62.5%) and was elevated in comparison to those who did not use filters (7.1%). Grouped logistic regression revealed a positive association between filtration of the injection preparation and overall health concerns expressed by injectors, after adjusting for gender and age. The marginal posterior distribution of the adjusted odds ratio for filtration of the injection preparation had a posterior median = 35.7, and 95% HPD interval = (5.1, 512.4).
DISCUSSION
Results illustrate a positive relationship between filtration of the injection preparation and health concerns among Indigenous people who inject methamphetamine. This likely reflects the use of filtration to reduce harms, and further research is needed to understand the full scope of prevention that may be associated with filtration of methamphetamine injection preparations.
Topics: Humans; Methamphetamine; Male; Female; Adult; Substance Abuse, Intravenous; Filtration; Middle Aged; Indigenous Peoples; Young Adult; Interviews as Topic
PubMed: 38932776
DOI: 10.3389/fpubh.2024.1390210 -
Life (Basel, Switzerland) Jun 2024Methamphetamine (METH) exposure increases locomotor sensitization. However, no study has explored the occurrence of cardiovascular sensitization. The present study,...
Methamphetamine (METH) exposure increases locomotor sensitization. However, no study has explored the occurrence of cardiovascular sensitization. The present study, carried out in mice, analyzed the following: (i) METH sensitization extending to systolic blood pressure (SBP); (ii) a potential correlation between ambulatory and cardiovascular sensitization; and (iii) morphological alterations within meso-striatal, meso-limbic and pontine catecholamine systems including c-fos expression. Locomotor activity, SBP and occurrence of morphological alterations of catecholaminergic neurons were assessed in mice following daily i.p. injections of either saline or METH (1, 2 or 5 mg/kg) for 5 consecutive days and following 6 days of withdrawal. Reiterated exposure to the lower doses of METH (1 mg/kg and 2 mg/kg) produced in mice locomotor sensitization without altering SBP. In contrast, repeated treatment with the highest dose of METH (5 mg/kg) produced sensitization of SBP in the absence of locomotor sensitization. No morphological alterations but increases in c-fos expression within neurons of locus coeruleus and nucleus accumbens were detected. The present data suggest that METH produces plastic changes that extend beyond the motor systems to alter autonomic regulation. This cardiovascular sensitization occurs independently of locomotor sensitization. The persistency of increased blood pressure may underlie specific mechanisms operating in producing hypertension.
PubMed: 38929706
DOI: 10.3390/life14060723 -
Neuropsychopharmacology : Official... Jun 2024Converging evidence indicates that both dopamine and glutamate neurotransmission within the nucleus accumbens (NAc) play a role in psychostimulant self-administration...
Converging evidence indicates that both dopamine and glutamate neurotransmission within the nucleus accumbens (NAc) play a role in psychostimulant self-administration and relapse in rodent models. Increased NAc dopamine release from ventral tegmental area (VTA) inputs is critical to psychostimulant self-administration and NAc glutamate release from prelimbic prefrontal cortex (PFC) inputs synapsing on medium spiny neurons (MSNs) is critical to reinstatement of psychostimulant-seeking after extinction. The regulation of the activity of MSNs by VTA dopamine inputs has been extensively studied, and recent findings have demonstrated that VTA glutamate neurons target the NAc medial shell. Here, we determined whether the mesoaccumbal glutamatergic pathway plays a role in psychostimulant conditioned place preference and self-administration in mice. We used optogenetics to induce NAc release of glutamate from VTA inputs during the acquisition, expression, and reinstatement phases of cocaine- or methamphetamine-induced conditioned place preference (CPP), and during priming-induced reinstatement of cocaine-seeking behavior. We found that NAc medial shell release of glutamate resulting from the activation of VTA glutamatergic fibers did not affect the acquisition of cocaine-induced CPP, but it blocked the expression, stress- and priming-induced reinstatement of cocaine- and methamphetamine CPP, as well as it blocked the priming-induced reinstatement of cocaine-seeking behavior after extinction. These findings indicate that in contrast to the well-recognized mesoaccumbal dopamine system that is critical to psychostimulant reward and relapse, there is a parallel mesoaccumbal glutamatergic system that suppresses reward and psychostimulant-seeking behavior.
PubMed: 38926603
DOI: 10.1038/s41386-024-01905-3 -
Drug and Alcohol Dependence Jun 2024
Corrigendum to "Co-administration of naloxone and dexmedetomidine to simultaneously reverse acute effects of fentanyl and methamphetamine in rats" [Drug Alcohol Depend. 259 (2024) 111301].
PubMed: 38926030
DOI: 10.1016/j.drugalcdep.2024.111380 -
Journal of the International AIDS... Jun 2024Community-based cohort studies of HIV seroconversion can identify important avenues for enhancing HIV prevention efforts in the era of pre-exposure prophylaxis (PrEP)....
INTRODUCTION
Community-based cohort studies of HIV seroconversion can identify important avenues for enhancing HIV prevention efforts in the era of pre-exposure prophylaxis (PrEP). Within individuals, one can assess exposure and outcome variables repeatedly and with increased certainty regarding temporal ordering. This cohort study examined the association of several risk factors with subsequent HIV seroconversion.
METHODS
We report data from a 4-year study (2017-2022) of 6059 HIV seronegative sexual and gender minority individuals who have sex with men who had indications for-, but were not using-, PrEP at enrolment. Participants completed repeat exposure assessments and self-collection of biospecimens for HIV testing. We examined the roles of race and ethnicity, socio-economic status, methamphetamine use and PrEP uptake over the course of follow-up in relation to HIV seroconversion.
RESULTS
Over 4 years, 303 of the participants seroconverted across 18,421 person-years (incidence rate = 1.64 [95% CI: 1.59-1.70] per 100 person-years). In multivariable discrete-time survival analysis, factors independently associated with elevated HIV seroconversion risk included being Black/African American (adjusted risk ratio [aRR]: 2.44, 1.79-3.28), Hispanic/Latinx (1.53, 1.19-1.96), housing instability (1.58, 1.22-2.05) and past year methamphetamine use (3.82, 2.74-5.33). Conversely, time since study enrolment (24 vs. 12 months, 0.67, 0.51-0.87; 36 months, 0.60, 0.45-0.80; 48 months, 0.48, 0.35-0.66) and higher education (master's degree or higher vs. less than or equal to high school, 0.36, 0.17-0.66) were associated with reduced seroconversion risk. Compared to non-PrEP users in the past 2 years without a current clinical indication, those who started PrEP but then discontinued had higher seroconversion risk, irrespective of clinical indication (3.23, 1.74-6.46) or lack thereof (4.30, 1.85-9.88). However, those who initiated PrEP in the past year (0.14, 0.04-0.39) or persistently used PrEP in the past 2 years (0.33, 0.14-0.74) had a lower risk of seroconversion. Of all HIV seroconversions observed during follow-up assessments (12, 24, 36 and 48 months), methamphetamine was reported in the 12 months prior 128 (42.2%) times (overall).
CONCLUSIONS
Interventions that acknowledge race and ethnicity, economic variables such as education and housing instability, and methamphetamine use are critically needed. Not only are interventions to engage individuals in PrEP care needed, but those that retain them, and re-engage those who may fall out of care are essential, given the exceptionally high risk of seroconversion in these groups.
Topics: Humans; Male; Adult; Sexual and Gender Minorities; Pre-Exposure Prophylaxis; Homosexuality, Male; HIV Seropositivity; United States; Cohort Studies; Young Adult; HIV Infections; Risk Factors; Middle Aged; Female; Adolescent; Seroconversion
PubMed: 38924359
DOI: 10.1002/jia2.26312