Cryptococcal Meningitis in an Immunocompetent Patient With Underlying Risk Factors.

Cryptococcal meningitis, a severe fungal infection of the central nervous system, is usually found in immunocompromised patients, especially those with human immunodeficiency virus/acquired immunodeficiency syndrome. Its occurrence in immunocompetent individuals is rare and the presentation can be nonspecific. We present a case of cryptococcal meningitis in a young, immunocompetent male with a known history of intravenous drug abuse who was also found to have hepatitis C during admission. Induction therapy with amphotericin B and flucytosine was completed for 14 days. This shorter duration was considered as he had a good clinical response with rapid improvement in mental status and intracranial pressure with an extraventricular drain and negative repeat cerebrospinal fluid (CSF) culture. However, during the consolidation phase with fluconazole, the patient developed new neurologic symptoms and the induction phase had to be re-initiated for a total of 28 days. The patient likewise required the re-placement of an extraventricular drain and the creation of a ventriculoperitoneal shunt due to persistent CSF accumulation and increased intracranial pressure. He was eventually discharged on fluconazole for a planned consolidation phase of eight weeks, followed by a prolonged maintenance phase, but the patient was lost to follow-up.

Nor-LAAM loaded PLGA microparticles for treating opioid use disorder.

The treatment landscape for opioid use disorder (OUD) faces challenges stemming from the limited efficacy of existing medications, poor adherence to prescribed regimens, and a heightened risk of fatal overdose post-treatment cessation. Therefore, there is a pressing need for innovative therapeutic strategies that enhance the effectiveness of interventions and the overall well-being of individuals with OUD. This study explored the therapeutic potential of nor-Levo-α-acetylmethadol (nor-LAAM) to treat OUD. We developed sustained release nor-LAAM-loaded poly (lactic-co-glycolic acid) (PLGA) microparticles (MP) using a hydrophobic ion pairing (HIP) approach. The nor-LAAM-MP prepared using HIP with pamoic acid had high drug loading and exhibited minimal initial burst release and sustained release. The nor-LAAM-MP was further optimized for desirable particle size, drug loading, and release kinetics. The lead nor-LAAM-MP (F4) had a relatively high drug loading (11 wt%) and an average diameter (19 µm) and maintained a sustained drug release for 4 weeks. A single subcutaneous injection of nor-LAAM-MP (F4) provided detectable nor-LAAM levels in rabbit plasma for at least 15 days. We further evaluated the therapeutic efficacy of nor-LAAM-MP (F4) in a well-established fentanyl-addiction rat model, and revealed a marked reduction in fentanyl choice and withdrawal symptoms in fentanyl-dependent rats. These findings provide insights into further developing long-acting nor-LAAM-MP for treating OUD. It has the potential to offer a new effective medication to the existing sparse armamentarium of products available to treat OUD.

Psychometric properties of the modified Drug Abuse Screening Test Sinhala version (DAST-SL): evaluation of reliability and validity in Sri Lanka.

BACKGROUND: Psychoactive drug use is an important public health issue in Sri Lanka as it causes substantial health, social and economic burden to the country. Screening for substance use disorders in people who use drugs is vital in preventive health care, as it can help to identify problematic use early. Screening can aid in referring those in need, for the most appropriate treatment and care. Thus, preventing them from developing severe substance use disorders with complications. The Drug Abuse Screening Test (DAST-10) is an evidence-based tool widely used to assess the severity of psychoactive drug use. This study aimed to culturally adapt and evaluate the validity and reliability of the Drug Abuse Screening Test (DAST-10) in Sri Lanka. METHODS: The DAST-10 was culturally adapted, and the nine-item Sinhala version (DAST-SL) was validated using exploratory and confirmatory factor analysis. The validation study was conducted in the Kandy district among people who use drugs, recruited using respondent-driven sampling. Criterion validity of the questionnaire was assessed by taking the diagnosis by a psychiatrist as the gold standard. Cut-off values for the modified questionnaire were developed by constructing Receiver Operating Characteristic (ROC) curves. The reliability of the DAST-SL was assessed by measuring its internal consistency and test re-test reliability. RESULTS: The validated DAST-SL demonstrated a one-factor model. A cut-off value of ≥ 2 demonstrated the presence of substance use disorder and had a sensitivity of 98.7%, specificity of 91.7%, a positive predictive value of 98.8% and a negative predictive value of 91.3%. The area under the curve of the ROC curve was 0.98. A cut-off score of ≤ 1 was considered a low level of problems associated with drug use. The DAST-SL score of 2-3 demonstrated a moderate level of problem severity, a score of 4-6 demonstrated a substantial level of problems, and a score of ≥ 7 demonstrated a severe level of drug-related problems. The questionnaire demonstrated high reliability with an internal consistency of 0.80 determined by Kuder-Richardson Formula-20 and an inter-class correlation coefficient of 0.97 for test re-test reliability. CONCLUSION: The DAST-SL questionnaire is a valid and reliable tool to screen for drug use problem severity in people who use drugs in Sri Lanka.

Wastewater-based epidemiology to monitor 68 NPS/conventional drug use in Taipei metropolitan area in Taiwan during and after COVID-19 pandemic.

Amidst far-reaching COVID-19 effects and social constraints, this study leveraged wastewater-based epidemiology to track 38 conventional drugs and 30 new psychoactive substances (NPS) in northern Taiwan. Analyzing daily samples from four Taipei wastewater plants between September 2021 and January 2024-encompassing club reopenings, holidays, Lunar New Year, an outbreak, and regular periods-thirty-one drugs were detected, including 5 NPS. Tramadol, zolpidem tartrate, CMA, and MDPV were newly detected in Taiwanese sewage with frequency of 1.4 %- 89.0 %. Conventional drug use typically increased post-pandemic, aside from benzodiazepines and methadone. Methamphetamine showed 100 % frequency, indicating ongoing daily consumption despite COVID-19 measures. Methamphetamine and morphine's consumption dipped then rose around club reopening, hinting at limited access. The consumption trend of methadone appeared to compensate for the use of morphine. Ketamine and NPS demonstrated similar patterns throughout the entire period. NPS as party drugs seemed influenced by an unstable supply chain and complexities in implementation. Benzodiazepines, commonly abused alongside synthetic cathinones in Taiwan exhibited an opposing trend to NPS while aligned with acetaminophen, suggesting elevated stress and anxiety levels during the pandemic. No significant differences were observed in drug consumption between weekdays and weekends, potentially indicating that COVID-19 measures blurred the traditional distinctions between these timeframes. ENVIRONMENTAL IMPLICATION: New psychoactive substances refer to chemically modified variants of controlled drugs designed to mimic the effects of the original drugs while evading modern detection methods, categorizing them as hazardous materials. The study presents a sewage monitoring project conducted from 2021 to 2024, collecting samples from four WWTPs to analyze NPS and conventional drug trends during and after the COVID-19 pandemic. The findings uncovered connections between drug consumption patterns and pandemic-related policies. In light of the persistent drug abuse and their environmental presence, the results bear critical importance for both environmental and public health. We provide a thorough assessment of these relationships and prioritize areas for future research.

An Observational Study of a Digital Substance Use and Recovery Program.

OBJECTIVE: Digital substance use treatment programs present an opportunity to provide nonresidential care for people with problematic substance use. In June 2021, the provincial government in Ontario provided free access to Breaking Free Online (BFO), a digital behavioral change program for people with substance use disorders. METHODS: An observational study was conducted with retrospective data to characterize clients' use and engagement patterns in BFO and examine changes in self-reported outcomes. RESULTS: In total, 6,370 individuals registered for BFO between June 2021 and October 2022, of whom 3,650 completed the intake assessment. Most of these clients were self-referred (64%), with 37% having been referred by health service providers. More than one-half of the clients (52%) resided in Ontario West or East regions. Support for addressing problematic alcohol use was the most requested program (40%). By October 2022, about 44% of the clients had completed between one and four of 12 program strategies. Analysis revealed significant changes in pre-post scores across four validated scales (p<0.001), indicating a decrease in anxiety and depression, an increase in quality of life, an improvement in recovery progression, and a decrease in severity of symptoms associated with substance use disorders. CONCLUSIONS: BFO clients with higher completion rates had the most improvement across the scales used; however, clients with lower and medium completion rates also had improvements. Because of the shame and stigma associated with substance use, digital supports with low barriers to entry can help support the autonomy, privacy, and preferences of individuals seeking help for problematic substance use.

Development of a Real-Time Dashboard for Overdose Touchpoints: User-Centered Design Approach.

BACKGROUND: Overdose Fatality Review (OFR) is an important public health tool for shaping overdose prevention strategies in communities. However, OFR teams review only a few cases at a time, which typically represent a small fraction of the total fatalities in their jurisdiction. Such limited review could result in a partial understanding of local overdose patterns, leading to policy recommendations that do not fully address the broader community needs. OBJECTIVE: This study explored the potential to enhance conventional OFRs with a data dashboard, incorporating visualizations of touchpoints-events that precede overdoses-to highlight prevention opportunities. METHODS: We conducted 2 focus groups and a survey of OFR experts to characterize their information needs and design a real-time dashboard that tracks and measures decedents' past interactions with services in Indiana. Experts (N=27) were engaged, yielding insights on essential data features to incorporate and providing feedback to guide the development of visualizations. RESULTS: The findings highlighted the importance of showing decedents' interactions with health services (emergency medical services) and the justice system (incarcerations). Emphasis was also placed on maintaining decedent anonymity, particularly in small communities, and the need for training OFR members in data interpretation. The developed dashboard summarizes key touchpoint metrics, including prevalence, interaction frequency, and time intervals between touchpoints and overdoses, with data viewable at the county and state levels. In an initial evaluation, the dashboard was well received for its comprehensive data coverage and its potential for enhancing OFR recommendations and case selection. CONCLUSIONS: The Indiana touchpoints dashboard is the first to display real-time visualizations that link administrative and overdose mortality data across the state. This resource equips local health officials and OFRs with timely, quantitative, and spatiotemporal insights into overdose risk factors in their communities, facilitating data-driven interventions and policy changes. However, fully integrating the dashboard into OFR practices will likely require training teams in data interpretation and decision-making.

Do Substances Used in Adolescence Predict the Persistence of Substance Use Disorders in Adulthood? A 15-Year Study of Youth After Detention.

PURPOSE: Investigate if the type of substance use disorder (SUD) in adolescence predicts SUDs in adulthood and examine sex and racial/ethnic differences in the persistence of SUDs. METHODS: Data are from the Northwestern Juvenile Project, a 15-year longitudinal study of 1829 youth randomly sampled from detention in Chicago, IL (1995-1998). Interviewers assessed SUDs using structured diagnostic interviews. RESULTS: Compared with females without an SUD at detention, females with cannabis alone, comorbid alcohol and cannabis, or SUDs other than alcohol and cannabis at detention had higher odds of having an SUD 5 years later (25%, 32%, and 36% vs. 15%, adjusted odds ratio [AOR] = 1.94, 95% confidence interval [CI] 1.11-3.40; AOR = 2.76, 95% CI 1.58-4.83; AOR = 3.46, 95% CI 1.56-7.66, respectively). Males and females with SUDs other than alcohol and cannabis at detention had greater odds of having an SUD 15 years later, compared with those without an SUD at detention (males: 36% vs. 14%, AOR = 2.98, 95% CI 1.14-7.83; females: 29% vs. 8%, AOR = 4.77, 95% CI 1.85-12.30). Among youth with an SUD at detention, males were more likely than females to have an SUD 15 years later (AOR = 1.84, 95% CI 1.03-3.29); non-Hispanic White and Hispanic males were more likely to persist than Black males (AOR = 3.32, 95% CI 1.50-7.35; AOR = 2.32, 95% CI 1.04-5.18, respectively). DISCUSSION: The type of SUD during adolescence matters. Youth with SUDs such as cocaine and opioids fared the worst. Healthcare providers must collaborate with correctional officials to increase service provision.

Oxygen fluctuations in the brain and periphery induced by intravenous fentanyl: effects of dose and drug experience.

Fentanyl is the leading contributor to drug overdose deaths in the US. Its potency, rapid onset of action, and lack of effective reversal treatment make the drug more lethal than other opioids. Although it is understood that fentanyl is dangerous at higher doses, literature surrounding fentanyl's physiological effects remains contradictory at lower doses. To explore this discrepancy, we designed a study incorporating electrochemical assessment of oxygen in the brain (nucleus accumbens; NAc) and subcutaneous (SC) space, multi-site thermorecording (brain, skin, muscle), and locomotor activity at varying doses of fentanyl (1.0, 3.0, 10, 30, 90 µg/kg) in rats. In the NAc, lower doses of fentanyl (3.0, 10 µg/kg) led to an increase in oxygen levels while higher doses (30, 90 µg/kg) led to a biphasic pattern, with initial dose-dependent decrease followed by increase. In the SC space, oxygen decreases started to appear at relatively lower doses (>3 µg/kg), had shorter onset latencies, and were stronger and prolonged. In the temperature experiment, lower doses of fentanyl (1.0, 3.0, 10 µg/kg) led to an increase in brain, skin, and muscle temperatures, while higher doses (30 and 90 µg/kg) resulted in a dose-dependent biphasic temperature change, with an increase followed by a prolonged decrease. We also compared oxygen and temperature responses induced by fentanyl over six consecutive days and found no evidence of tolerance in both parameters. In conclusion, we report that fentanyl's effects are highly dose-dependent, drawing attention to the importance of better characterization to adequately respond in emergent cases of fentanyl misuse.

An Unusual Case of Cryoglobulinemic Vasculitis and Acute Disseminating Encephalomyelitis in a 21-Year-Old Caucasian Male.

Cryoglobulinemic vasculitis and acute disseminated encephalomyelitis (ADEM) are characterized by damage to either blood vessels or grey matter. For both diseases, infections can be an etiology. In cryoglobulinemic vasculitis, the initial insult causes damage to the glomerulus, and in the case of ADEM, damage leads to a central nervous system demyelinating disorder. Infective endocarditis can be associated with both diseases and can be challenging to diagnose. Individuals on antibiotics may present with negative blood cultures, making underlying infective endocarditis difficult to diagnose. In this report, we describe a 21-year-old male who presented to the hospital after an assault with splenic laceration and was subsequently found to have infective endocarditis associated with cryoglobulinemic vasculitis and ADEM.

Substance use-related problems in mild intellectual disability: A Swedish nationwide population-based cohort study with sibling comparison.

Background: Evidence for substance use-related problems in individuals with mild intellectual disability is sparse and mainly limited to selected psychiatric populations. We evaluated the risk of substance use-related problems in individuals with mild intellectual disability compared to the general population. Additionally, we have performed secondary sibling comparison analyses to account for familial confounding. Methods: We conducted a population-based cohort study of individuals born in Sweden between 1973 and 2003. A total of 18,307 individuals with mild intellectual disability were compared to 915,350 reference individuals from the general population and 18,996 full siblings of individuals with mild intellectual disability. Information on mild intellectual disability and substance use-related problems was obtained from several Swedish national and regional school and healthcare registers. Substance use-related problems were measured via corresponding diagnostic and legal codes and included alcohol use disorder, drug use disorder, alcohol-related somatic disease, conviction for a substance-related crime, and substance-related death. Results: Individuals with mild intellectual disability had a higher risk of any substance use-related problem compared to the general population (HR, 1.81; 95% CI, 1.72-1.91), both in males (HR, 1.76; 95% CI, 1.65-1.89) and females (HR, 1.89; 95% CI, 1.74-2.05). The risks of substance use-related problems were particularly elevated among individuals with mild intellectual disability and psychiatric comorbidities (HR, 2.21-8.24). The associations were attenuated in the sibling comparison models. Conclusions: Individuals with mild intellectual disability, especially those with psychiatric comorbidity, are at an elevated risk of substance use-related problems. Familial factors shared by full siblings contribute considerably to the association between mild intellectual disability and substance use-related problems.

Neuronal biomarkers as potential therapeutic targets for drug addiction related to sex differences in the brain: Opportunities for personalized treatment approaches.

Biological sex disparities manifest at various stages of drug addiction, including craving, substance abuse, abstinence, and relapse. These discrepancies are underpinned by notable distinctions in neurobiological substrates, encompassing brain structures, functions, and neurotransmitter systems implicated in drug addiction. Neuronal biomarkers, such as neurotransmitters, signaling proteins, and genes may be associated with the diagnosis, prognosis, and treatment outcomes in both biological sexes afflicted by drug abuse. Sex differences in the neural reward system, mainly through dopaminergic transmission during drug abuse, can be attributed to modifications in neurotransmitter systems and signaling pathways. This results in distinct patterns of neural activation and responsiveness to addictive substances in males and females. Sex hormones, the estrus/menstrual cycle, and cerebral neurochemistry contribute to the progression of psychological and physiological dependence in both male and female individuals grappling with addiction. Moreover, the alteration of sex hormone balance and neurotransmitter release plays a pivotal role in substance use disorders, subsequently modulating cognitive functions pertinent to reward, including memory formation, decision-making, and locomotor activity. Comparative investigations reveal distinctions in brain region volume, gene expression, neuronal firing, and circuitry in substance use disorders affecting individuals of both biological sexes. This review examines prevalent substance use disorders to elucidate the impact of sex hormones as therapeutic biomarkers on the mesocorticolimbic neurotransmitter systems via diverse mechanisms within the addicted brain. We underscore the imperative necessity of considering these variations to gain a deeper comprehension of addiction mechanisms and potentially discern sex-specific neuronal biomarkers for tailored therapeutic interventions.

Investigating the Interrelationships Among Mental Health, Substance Use Disorders, and Suicidal Ideation Among Lesbian, Gay, and Bisexual Adults in the United States: Population-Based Statewide Survey Study.

BACKGROUND: Mental health disparities have been documented among lesbian, gay, and bisexual (LGB) adults in the United States. Substance use disorders and suicidal ideation have been identified as important health concerns for this population. However, the interrelationships among these factors are not well understood. OBJECTIVE: This study aims to investigate the interrelationships among mental health, substance use disorders, and suicidal ideation among LGB adults in the United States using a population-based statewide survey. METHODS: Our study was an observational cross-sectional analysis, and the data for this study were collected from a sample of LGB adults who participated in the statewide survey. The survey collected information on mental health, substance use disorders, and suicidal ideation using validated measures. Descriptive statistics and inferential data analysis were conducted to explore the interrelationships among these factors. RESULTS: The results showed that LGB adults who reported higher levels of depression and drug abuse and dependence also reported higher levels of suicidal tendency and mental illness. Inferential data analysis using χ2 tests revealed significant differences in depression score (χ22=458.241; P<.001), drug abuse and dependence score (χ22=226.946; P<.001), suicidal tendency score (χ22=67.795; P<.001), and mental illness score (χ22=363.722; P<.001) among the 3 sexual identity groups. Inferential data analysis showed significant associations between sexual identity and mental health outcomes, with bisexual individuals reporting the highest levels of depression, drug abuse and dependence, suicidal tendency, and mental illness. CONCLUSIONS: This study provides important insights into the interrelationships among mental health, substance use disorders, and suicidal ideation among LGB adults in the United States. The findings underscore the need for targeted interventions and research aimed at addressing the mental health needs of sexual minority populations. Future research should aim to better understand the underlying mechanisms driving these disparities and develop culturally sensitive and tailored interventions that meet the unique needs of LGB individuals. Reducing stigma and discrimination against sexual minority populations is also crucial to improving their mental health outcomes.

The Association of Broadband Internet Use With Drug Overdose Mortality Rates in the United States: Cross-Sectional Analysis.

BACKGROUND: The availability and use of broadband internet play an increasingly important role in health care and public health. OBJECTIVE: This study examined the associations between broadband internet availability and use with drug overdose deaths in the United States. METHODS: We linked 2019 county-level drug overdose death data in restricted-access multiple causes of death files from the National Vital Statistics System at the US Centers for Disease Control and Prevention with the 2019 county-level broadband internet rollout data from the Federal Communications Commission and the 2019 county-level broadband usage data available from Microsoft's Airband Initiative. Cross-sectional analysis was performed with the fixed-effects regression method to assess the association of broadband internet availability and usage with opioid overdose deaths. Our model also controlled for county-level socioeconomic characteristics and county-level health policy variables. RESULTS: Overall, a 1% increase in broadband internet use was linked with a 1.2% increase in overall drug overdose deaths. No significant association was observed for broadband internet availability. Although similar positive associations were found for both male and female populations, the association varied across different age subgroups. The positive association on overall drug overdose deaths was the greatest among Hispanic and Non-Hispanic White populations. CONCLUSIONS: Broadband internet use was positively associated with increased drug overdose deaths among the overall US population and some subpopulations, even after controlling for broadband availability, sociodemographic characteristics, unemployment, and median household income.

Association between history of cannabis use and outcomes after total hip or knee arthroplasty: a systematic review and meta-analysis.

Background: Cannabis use may be increasing as countries legalize it and it becomes socially acceptable. A history of cannabis use may increase risk of complications after various kinds of surgery and compromise functional recovery. Here we systematically reviewed and meta-analyzed available evidence on how history of cannabis use affects recovery after hip or knee arthroplasty (THA/TKA). Methods: The PubMed, EMBASE, and Web of Science databases were comprehensively searched and studies were selected and analyzed in accordance with the PRISMA guidelines. The methodological quality of included studies was assessed based on the Newcastle-Ottawa Scale, while quality of evidence was evaluated according to the "Grading of recommendations assessment, development, and evaluation" system. Data on various outcomes were pooled when appropriate and meta-analyzed. Results: The systematic review included 16 cohort studies involving 5.91 million patients. Meta-analysis linked history of cannabis use to higher risk of the following outcomes: revision (RR 1.68, 95% CI 1.31-2.16), mechanical loosening (RR 1.77, 95% CI 1.52-2.07), periprosthetic fracture (RR 1.85, 95% CI 1.38-2.48), dislocation (RR 2.10, 95% CI 1.18-3.73), cardiovascular events (RR 2.49, 95% CI 1.22-5.08), cerebrovascular events (RR 3.15, 95% CI 2.54-3.91), pneumonia (RR 3.97, 95% CI 3.49-4.51), respiratory failure (RR 4.10, 95% CI 3.38-4.97), urinary tract infection (RR 2.46, 95% CI 1.84-3.28), acute kidney injury (RR 3.25, 95% CI 2.94-3.60), venous thromboembolism (RR 1.48, 95% CI 1.34-1.63), and deep vein thrombosis (RR 1.42, 95% CI 1.19-1.70). In addition, cannabis use was associated with significantly greater risk of postoperative transfusion (RR 2.23, 95% CI 1.83-2.71) as well as higher hospitalization costs. Conclusion: History of cannabis use significantly increases the risk of numerous complications and transfusion after THA or TKA, leading to greater healthcare costs. Clinicians should consider these factors when treating cannabis users, and pre-surgical protocols should give special consideration to patients with history of cannbis use.

A Statewide Consultation Helpline for Rapid Linkage to Services for Youths With Opioid Use Disorder and Other Substance Use.

OBJECTIVE: The authors examined the initial implementation of the Indiana Adolescent Addiction Access (AAA) program, modeled on the widely disseminated Child Psychiatry Access Program framework. The AAA program developed a statewide consultation helpline to connect health care providers with adolescent addiction specialists. METHODS: The AAA line was staffed by a coordinator, who fielded initial questions, and on-call clinical specialists (social workers, nurse practitioners, psychiatrists, and psychologists), who were paged to complete telephone consultations and provide care recommendations. When necessary, AAA providers offered urgent clinical assessments and initiated treatment. Descriptive analyses were performed for key variables over the first 21 months of AAA operations. RESULTS: From July 2021 to March 2023, a total of 125 consultations were completed. Most callers were health care providers (71%) or parents (27%). Calls pertained to youths ages 10-18 years (mean±SD age=16.4±1.3; 62% of callers were male, 84% White, and 11% Black), with concerns around cannabis (63%), opioids (38%), and other substances. About 26% of calls related to an overdose, and 41% of cases were rated as severe. Recommendations included starting new medications (17%) or outpatient therapy (86%), and 17% of consultations resulted in urgent evaluations. CONCLUSIONS: The Indiana AAA program helps overcome key barriers to adolescent substance use treatment. Increasing the capacity to initiate medication for opioid use disorder and other treatment rapidly through consultation and direct care is a promising, scalable approach for preventing overdose deaths among youths.

LC-MS/MS quantification of olanzapine in hair after alkaline digestion.

Olanzapine (OLZ), a second-generation antipsychotic drug, is effective in the treatment of acute psychosis, schizophrenia, agitation, bipolar mania, and other psychiatric problems. Antipsychotics are prescribed drugs, which lead the drug abuser to illegal methods of access. This behavior also demonstrates the association of OLZ with criminal involvement, commonly observed at forensic crime scenes. The acute toxicity and even death resulting from OLZ exposure have been highlighted in numerous studies. Therefore, developing analytical techniques to detect OLZ is essential for forensic toxicology. This study aimed to develop a specific and reliable LC-MS/MS method for OLZ detection and quantification in hair samples. The method was validated in terms of selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), trueness, precision, and uncertainty. The range of linearity was between 0.1-100 ng/mg, with LOD and LOQ values established at 0.036 ng/mg and 0.1 ng/mg, respectively. All validation results are within acceptable parameters. The validated method has been applied to authentic hair samples. The variation of OLZ concentrations in 12 hair segments (2 from Case 1 and 10 from Case 2) from two drug-positive patients, ranging from 0.131 to 0.460 ng/mg, is presented in this study. Although several studies have been conducted to determine OLZ in hair samples using segmental analysis via hair solubilization, this study is the first to determine OLZ in hair samples after "digestion" with comparative parameters prior to chromatographic analysis.

Comprehensive glycomic and proteomic analysis of mouse striatum and lateral hypothalamus following repeated exposures to cocaine or methamphetamine.

Substance use disorder is a major concern, with few therapeutic options. Heparan sulfate (HS) and chondroitin sulfate (CS) interact with a plethora of growth factors and their receptors and have profound effects on cellular signaling. Thus, targeting these dynamic interactions might represent a potential novel therapeutic modality. In the present study, we performed mass spectrometry-based glycomic and proteomic analysis to understand the effects of cocaine and methamphetamine (METH) on HS, CS, and the proteome of two brain regions critically involved in drug addiction: the lateral hypothalamus (LH) and the striatum (ST). We observed that cocaine and METH significantly alter HS and CS abundances as well as sulfate contents and composition. In particular, repeated METH or cocaine treatments reduced CS 4-O-sulfation and increased CS 6-O-sulfation. Since C4S and C6S exercise differential effects on axon growth, regeneration and plasticity, these changes likely contribute to drug-induced neural plasticity in these brain regions. Notably, we observed that restoring these alterations by increasing CS 4-0 levels in the LH by adeno-associated virus (AAV) delivery of an shRNA to Arylsulfatase B (N-acetylgalactosamine-4-sulfatase, ARSB) ameliorated anxiety and prevented the expression of preference for cocaine in a novelty induced conditioned place preference test during cocaine withdrawal. Finally, proteomics analyses revealed a number of aberrant proteins in METH- and cocaine-treated vs. saline-treated mice, including MYPR, KCC2A, SYN2, TENR, CALX, ANXA7, HDGF, NCAN, and CSPG5, and oxidative phosphorylation among the top perturbed pathway. Taken together, these data support the role of HS, CS, and associated proteins in stimulants abuse and suggest that manipulation of HSPGs can represent a novel therapeutic strategy.

Association of Cigarette Smoking History With Drug Abuse History and Arterial Carboxyhemoglobin in Trauma Activation Patients: A Retrospective Study.

Introduction The relationship between cigarette smoking and arterial carboxyhemoglobin (CoHb) in trauma activation patients has not been investigated. The aim was to determine if cigarette smoking is associated with drug abuse history and arterial CoHb levels. Methodology This is a retrospective review of level I trauma center activations aged 18-60 during 2018-2020. A medical record audit was performed to assess each patient's cigarette smoking and drug abuse history and admission arterial CoHb level. The CoHb levels and smoking history for each patient were used to construct a receiver operating characteristic curve. Results Of the 742 trauma activations aged 18-60, 737 (99.3%) had a documented cigarette smoking history. Smoking history was positive in 49.7% (366) and negative in 50.3% (371). The positive smoking proportion was greater in patients with a drug abuse history (63.9% (234/366)) than those with a negative history (31.0% (115/371); p<0.0001; odds ratio=4.0). In 717 patients with a CoHb value, the CoHb was higher in smokers (3.9±2.2%) than in non-smokers (0.5±0.4%; p<0.0001; Cohen d=2.2). A CoHb >1.5% was higher in smokers (93.3% (333/357)) than non-smokers (1.7% (6/360); p<0.0001; odds ratio=818.6). The receiver operating characteristic curve for the relationship between CoHb and cigarette smoking history showed an area under the curve of 0.980 (p<0.0001). Using an arterial CoHb level >1.5% to predict a positive smoking history and a CoHb level ≤1.5% to predict a non-smoking history, sensitivity was 93.3% (333/357), specificity was 98.3% (354/360), and accuracy was 95.8% (687/717). Conclusion Cigarette smoking in trauma activations aged 18-60 is associated with drug abuse history and increased arterial CoHb levels on trauma center arrival.

A case report of superior vena cava/right coronary artery fistula secondary to chronic endocarditis.

Background: Coronary arteriovenous fistulas present an abnormal connection between the coronary arteries and an adjacent systemic or pulmonary vessel. They are rare, representing 0.002% of the general population. The majority is congenital but may additionally occur related to trauma or interventional cardiac procedures. Case summary: We present the case of a 48-year-old male with a history of untreated bacterial endocarditis developing a right coronary/superior vena cava fistula. We detail the imaging findings of this rare phenomenon to arrive at this diagnosis. We describe his clinical course and the interventions considered, including surgical extraction. Unfortunately, this patient left against medical advice before completing recommended treatment. Discussion: We present the first documentation of a right coronary/superior vena cava fistula secondary to chronic untreated bacterial endocarditis. Clinicians should be aware of this rare complication.