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BMC Public Health Jun 2024Drug use disorders (DUDs) have emerged as one of the most significant public health crises, exerting a substantial influence on both community health and socio-economic...
BACKGROUND
Drug use disorders (DUDs) have emerged as one of the most significant public health crises, exerting a substantial influence on both community health and socio-economic progress. The United States (US) also suffers a heavy burden, it is necessary to figure out the situation from multiple perspectives and take effective measures to deal with it. Therefore, using the data from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2021, we evaluated this topic.
METHODS
Annual data on DUDs-related burden were collected from the GBD study 2021. We calculated the indicator of estimated annual percentage change (EAPC) to evaluate the changing trend of burden. The Bayesian model for age-period-cohort was introduced to forecast the burden.
RESULTS
In 2021, the number and age-standardized rate of prevalence were particularly prominent, with 12,146.95 thousand and 3821.43 per 100,000, respectively. Higher burden was also observed in males, 15-45 years old populations, and opioid use disorders subtype. From 1990 to 2021, the DUDs-related burden increased in the US and all states, especially in West Virginia; and the national death-related burden with the highest increase (EAPC = 7.96). Other significant inverse associations were seen between EAPC, age-standardized rates, and socio-demographic index (SDI). Moreover, in the next 14 years, the projected DUDs burden remains exigent.
CONCLUSIONS
The burden of DUDs in the US is heavy and has been enlarging. This study proposes that greater attention should be paid to the strategies in males, the younger population, opioid use disorders, and low-SDI states implemented by decision-makers to achieve goals such as reducing burden.
Topics: Humans; United States; Male; Middle Aged; Adult; Female; Adolescent; Young Adult; Substance-Related Disorders; Bayes Theorem; Aged; Cost of Illness; Global Burden of Disease; Forecasting; Prevalence
PubMed: 38898398
DOI: 10.1186/s12889-024-19142-0 -
Nature Communications Jun 2024Methaqualone, a quinazolinone marketed commercially as Quaalude, is a central nervous system depressant that was used clinically as a sedative-hypnotic, then became a...
Methaqualone, a quinazolinone marketed commercially as Quaalude, is a central nervous system depressant that was used clinically as a sedative-hypnotic, then became a notorious recreational drug in the 1960s-80s. Due to its high abuse potential, medical use of methaqualone was eventually prohibited, yet it persists as a globally abused substance. Methaqualone principally targets GABA receptors, which are the major inhibitory neurotransmitter-gated ion channels in the brain. The restricted status and limited accessibility of methaqualone have contributed to its pharmacology being understudied. Here, we use cryo-EM to localize the GABA receptor binding sites of methaqualone and its more potent derivative, PPTQ, to the same intersubunit transmembrane sites targeted by the general anesthetics propofol and etomidate. Both methaqualone and PPTQ insert more deeply into subunit interfaces than the previously-characterized modulators. Binding of quinazolinones to this site results in widening of the extracellular half of the ion-conducting pore, following a trend among positive allosteric modulators in destabilizing the hydrophobic activation gate in the pore as a mechanism for receptor potentiation. These insights shed light on the underexplored pharmacology of quinazolinones and further elucidate the molecular mechanisms of allosteric GABA receptor modulation through transmembrane binding sites.
Topics: Receptors, GABA-A; Binding Sites; Cryoelectron Microscopy; Humans; Animals; Etomidate; Propofol; Quinazolinones; Allosteric Regulation; HEK293 Cells; Hypnotics and Sedatives
PubMed: 38898000
DOI: 10.1038/s41467-024-49471-y -
Translational Psychiatry Jun 2024Functional inhibition is known to improve treatment outcomes in substance use disorder (SUD), potentially through craving management enabled by underlying cerebral...
Functional inhibition is known to improve treatment outcomes in substance use disorder (SUD), potentially through craving management enabled by underlying cerebral integrity. Whereas treatment is challenged by a multitude of substances that patients often use, no study has yet unraveled if inhibition and related cerebral integrity could prevent relapse from multiples substances, that is, one's primary drug of choice and secondary ones. Individuals with primary alcohol, cannabis, or tobacco use disorders completed intensive Ecological Momentary Assessment (EMA) coupled with resting-state functional MRI (rs-fMRI) to characterize the extent to which inhibition and cerebral substrates interact with craving and use of primary and any substances. Participants were 64 patients with SUD and 35 healthy controls who completed one week EMA using Smartphones to report 5 times daily their craving intensity and substance use and to complete Stroop inhibition testing twice daily. Subsamples of 40 patients with SUD and 34 control individuals underwent rs-fMRI. Mixed Model Analysis revealed that reported use of any substance by SUD individuals predicted later use of any and primary substance, whereas use of the primary substance only predicted higher use of that same substances. Craving and inhibition level independently predicted later use but did not significantly interact. Preserved inhibition performance additionally influenced use indirectly by mediating the link between subsequent uses and by being linked to rs-fMRI connectivity strength in fronto-frontal and cerebello-occipital connections. As hypothesized, preserved inhibition performance, reinforced by the integrity of inhibitory neurofunctional substrates, may partake in breaking an unhealthy substance use pattern for a primary substance but may not generalize to non-target substances or to craving management.
Topics: Humans; Magnetic Resonance Imaging; Female; Male; Adult; Ecological Momentary Assessment; Substance-Related Disorders; Craving; Inhibition, Psychological; Middle Aged; Brain; Young Adult
PubMed: 38897999
DOI: 10.1038/s41398-024-02949-1 -
Ciencia & Saude Coletiva Jun 2024The rise in the study of sexualised drug use among gay, bisexual and other men who have sex with men (MSM), known as chemsex, has generated a multiplicity of data that...
The rise in the study of sexualised drug use among gay, bisexual and other men who have sex with men (MSM), known as chemsex, has generated a multiplicity of data that contribute to its problematisation as a public health issue through the link with HIV and addictions. The study of these practices, from a biomedical paradigm, has focused on risk and has contributed to its reduction as a unique and quantifiable phenomenon. This study aims to explore the experience of risk in the course of the practices, to find out what management strategies they employ in the face of risk and how they are generated. Semi-structured interviews were conducted with five chemsex practitioners in the Metropolitan Area of Barcelona and, subsequently, a thematic analysis was applied. The findings show how these men detect, assume and confront the risks present in these practices, where the type of relationships that take place and the social circle available to them are relevant. This study also highlights the creation of strategies based on experience and how the transmission of this knowledge among participants facilitates decision-making and risk management.
Topics: Humans; Male; Substance-Related Disorders; Homosexuality, Male; Interviews as Topic; Risk Management; Sexual and Gender Minorities; Qualitative Research; HIV Infections; Risk-Taking; Adult; Spain; Decision Making; Sexual Behavior; Middle Aged
PubMed: 38896677
DOI: 10.1590/1413-81232024296.10752023 -
JMIR Mental Health Jun 2024Internet-based cognitive behavioral interventions (iCBTs) are efficacious treatments for depression and anxiety. However, it is unknown whether adding human guidance is... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Internet-based cognitive behavioral interventions (iCBTs) are efficacious treatments for depression and anxiety. However, it is unknown whether adding human guidance is feasible and beneficial within a large educational setting.
OBJECTIVE
This study aims to potentially demonstrate the superiority of 2 variants of a transdiagnostic iCBT program (human-guided and computer-guided iCBT) over care as usual (CAU) in a large sample of university students and the superiority of human-guided iCBT over computer-guided iCBT.
METHODS
A total of 801 students with elevated levels of anxiety, depression, or both from a large university in the Netherlands were recruited as participants and randomized to 1 of 3 conditions: human-guided iCBT, computer-guided iCBT, and CAU. The primary outcome measures were depression (Patient Health Questionnaire) and anxiety (Generalized Anxiety Disorder scale). Secondary outcomes included substance use-related problems (Alcohol Use Disorder Identification Test and Drug Abuse Screening Test-10 items). Linear mixed models were used to estimate the effects of time, treatment group, and their interactions (slopes). The primary research question was whether the 3 conditions differed in improvement over 3 time points (baseline, midtreatment, and after treatment) in terms of depression and anxiety symptoms. Results were analyzed according to the intention-to-treat principle using multiple imputation. Patients were followed exploratively from baseline to 6 and 12 months.
RESULTS
In both short-term and long-term analyses, the slopes for the 3 conditions did not differ significantly in terms of depression and anxiety, although both web-based interventions were marginally more efficacious than CAU over 6 months (P values between .02 and .03). All groups showed significant improvement over time (P<.001). For the secondary outcomes, only significant improvements over time (across and not between groups) were found for drug use (P<.001). Significant differences were found in terms of adherence, indicating that participants in the human-guided condition did more sessions than those in the computer-guided condition (P=.002).
CONCLUSIONS
The transdiagnostic iCBT program offers a practical, feasible, and efficacious alternative to usual care to tackle mental health problems in a large university setting. There is no indication that human guidance should be preferred over technological guidance. The potential preference of human support also depends on the scale of implementation and cost-effectiveness, which need to be addressed in future trials.
TRIAL REGISTRATION
International Clinical Trials Registry Platform NL7328/NTR7544; https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON26795.
Topics: Humans; Cognitive Behavioral Therapy; Male; Female; Students; Universities; Young Adult; Adult; Therapy, Computer-Assisted; Internet-Based Intervention; Depression; Anxiety; Netherlands; Internet; Adolescent; Treatment Outcome
PubMed: 38896474
DOI: 10.2196/50503 -
Hepatology Communications Jul 2024The recent increase in the incidence of alcohol-associated hepatitis (AH) coincides with the obesity epidemic in the United States. However, current mouse models do not...
BACKGROUND
The recent increase in the incidence of alcohol-associated hepatitis (AH) coincides with the obesity epidemic in the United States. However, current mouse models do not fully replicate the combined insults of obesity, metabolic dysfunction-associated steatohepatitis, and alcohol. The aim of this study was to develop a new mouse model that recapitulates the robust inflammatory and fibrotic phenotype characteristic of human MetALD.
METHODS
Eight- to 10-week-old male C57BL/6 mice were fed chow or high fat-cholesterol-sugar diet (metabolic dysfunction-associated steatohepatitis diet) and in each group, some received alcohol in drinking water (ad libitum) and weekly alcohol binges (EtOH) for 3 months. The liver was assessed for features of AH.
RESULTS
MetALD mice displayed increased liver damage indicated by highly elevated ALT and bilirubin levels compared to all other groups. Liver steatosis was significantly greater in the MetALD mice compared to all other experimental groups. The inflammatory phenotype of MetALD was also recapitulated, including increased IL-6 and IL-1β protein levels as well as increased CD68+ macrophages and Ly6G+ neutrophils in the liver. Sirius red staining and expression of collagen 1, alpha-smooth muscle actin indicated advanced fibrosis in the livers of MetALD mice. In addition, indicators of epithelial-to-mesenchymal transition markers were increased in MetALD mice compared to all other groups. Furthermore, we found increased ductular reaction, dysregulated hedgehog signaling, and decreased liver synthetic functions, consistent with severe AH.
CONCLUSIONS
Alcohol administration in mice combined with metabolic dysfunction-associated steatohepatitis diet recapitulates key characteristics of human AH including liver damage, steatosis, robust systemic inflammation, and liver immune cell infiltration. This model results in advanced liver fibrosis, ductular reaction, decreased synthetic function, and hepatocyte dedifferentiation, suggesting a robust model of MetALD in mice.
Topics: Animals; Male; Mice; Disease Models, Animal; Mice, Inbred C57BL; Hepatitis, Alcoholic; Diet, High-Fat; Liver; Ethanol
PubMed: 38896082
DOI: 10.1097/HC9.0000000000000450 -
Hepatology Communications Jul 2024Alcohol (AC) and nonalcohol-associated cirrhosis (NAC) epidemiology studies are limited by available case definitions. We compared the diagnostic accuracy of previous...
BACKGROUND
Alcohol (AC) and nonalcohol-associated cirrhosis (NAC) epidemiology studies are limited by available case definitions. We compared the diagnostic accuracy of previous and newly developed case definitions to identify AC and NAC hospitalizations.
METHODS
We randomly selected 700 hospitalizations from the 2008 to 2022 Canadian Discharge Abstract Database with alcohol-associated and cirrhosis-related International Classification of Diseases 10th revision codes. We compared standard approaches for AC (ie, AC code alone and alcohol use disorder and nonspecific cirrhosis codes together) and NAC (ie, NAC codes alone) case identification to newly developed approaches that combine standard approaches with new code combinations. Using electronic medical record review as the reference standard, we calculated case definition positive and negative predictive values, sensitivity, specificity, and AUROC.
RESULTS
Electronic medical records were available for 671 admissions; 252 had confirmed AC and 195 NAC. Compared to previous AC definitions, the newly developed algorithm selecting for the AC code, alcohol-associated hepatic failure code, or alcohol use disorder code with a decompensated cirrhosis-related condition or NAC code provided the best overall positive predictive value (91%, 95% CI: 87-95), negative predictive value (89%, CI: 86-92), sensitivity (81%, CI: 76-86), specificity (96%, CI: 93-97), and AUROC (0.88, CI: 0.85-0.91). Comparing all evaluated NAC definitions, high sensitivity (92%, CI: 87-95), specificity (82%, CI: 79-86), negative predictive value (96%, CI: 94-98), AUROC (0.87, CI: 0.84-0.90), but relatively low positive predictive value (68%, CI: 62-74) were obtained by excluding alcohol use disorder codes and using either a NAC code in any diagnostic position or a primary diagnostic code for HCC, unspecified/chronic hepatic failure, esophageal varices without bleeding, or hepatorenal syndrome.
CONCLUSIONS
New case definitions show enhanced accuracy for identifying hospitalizations for AC and NAC compared to previously used approaches.
Topics: Humans; Hospitalization; Male; Liver Cirrhosis; Female; Algorithms; Middle Aged; Databases, Factual; Canada; Electronic Health Records; Liver Cirrhosis, Alcoholic; International Classification of Diseases; Aged; Clinical Coding; Sensitivity and Specificity; Adult
PubMed: 38896072
DOI: 10.1097/HC9.0000000000000469 -
Frontiers in Public Health 2024Habitual substance use, i. e., alcohol, tobacco and betel nut, has been found with an increased risk of metabolic syndrome (MetS) in the general population, whereas the...
BACKGROUNDS
Habitual substance use, i. e., alcohol, tobacco and betel nut, has been found with an increased risk of metabolic syndrome (MetS) in the general population, whereas the association remains unclear in physically fit military personnel. This study aimed to investigate the combination of these substances use and their associations with new-onset MetS in the military.
METHODS
A total of 2,890 military men and women, aged 18-39 years, without MetS were obtained from the cardiorespiratory fitness and health in eastern armed forces study (CHIEF) in Taiwan and followed for incident MetS from baseline (2014) through the end of 2020. Incident MetS event was defined by the International Diabetes Federation guideline and confirmed in the annual health examinations. A self-report was used to assess the alcohol, tobacco and betel nut use status (active vs. former/never). Multivariable Cox regression model was performed to determine the association with adjustments for sex, age, body mass index and physical activity at baseline.
RESULTS
At baseline, there were 279 active betel nut chewers (9.7%), 991 active smokers (34.3%) and 1,159 active alcohol consumers (40.1%). During a mean follow-up of 6.0 years, 673 incident MetS (23.3%) were observed. As compared to no substance users, only one substance, and two and three substances users had a greater risk of incident MetS [hazard ratios (HRs) and 95% confidence intervals: 1.27 (1.06-1.54), 1.38 (1.12-1.69) and 1.78 (1.37-2.32), respectively]. In subgroup analyses, the risk of incident MetS in two and three substances users was significantly greater in those free of baseline low high-density lipoprotein [HRs: 1.54 (1.21-1.95) and 2.57 (1.92-3.46), respectively], as compared to their counterparts (both p for interactions <0.05).
CONCLUSION
A dose-response association of more substances use for new-onset MetS was noted in military personnel. This finding suggests that the combined alcohol, tobacco and betel nut use may play a role in the development of MetS. Further study is required to establish causation and to investigate the potential benefits of substance use cessation in reducing the risk of MetS.
Topics: Humans; Male; Female; Adult; Military Personnel; Metabolic Syndrome; Taiwan; Incidence; Young Adult; Adolescent; Alcohol Drinking; Substance-Related Disorders; Risk Factors; Areca; Cohort Studies
PubMed: 38894993
DOI: 10.3389/fpubh.2024.1406524 -
Cureus May 2024Factitious disorder imposed on another (FDIA), formerly known as Munchausen syndrome by proxy (MSBP), constitutes a form of child abuse wherein a caregiver fabricates or...
Factitious disorder imposed on another (FDIA), formerly known as Munchausen syndrome by proxy (MSBP), constitutes a form of child abuse wherein a caregiver fabricates or induces illness in a person under their care or supervision. Here, we present a case of a two-year-old girl with signs and symptoms suggestive of undifferentiated connective tissue disease (UCTD) and probable autoinflammatory disease, which was a manifestation of FDIA. The patient manifested recurrent febrile episodes and presented with hepatosplenomegaly, elevated inflammatory markers, and mesangial proliferative glomerulonephritis. Regardless of extensive medical interventions, including corticosteroids and immunosuppressive therapy, the patient's condition failed to improve until the caregiver was isolated from the patient. Upon questioning, the caregiver admitted to having administered pyrogenal, an immunomodulator, to induce symptoms. This case highlights the challenges and difficulties of diagnosing and managing FDIA-associated illnesses, drawing attention to the importance of considering this diagnosis in cases of unexplained or recurrent fever in children.
PubMed: 38894791
DOI: 10.7759/cureus.60607 -
Nutrients May 2024Children and youths diagnosed with FASD may experience a range of adverse health and social outcomes. This cross-sectional study investigated the characteristics and...
Children and youths diagnosed with FASD may experience a range of adverse health and social outcomes. This cross-sectional study investigated the characteristics and outcomes of children and youths diagnosed with FASD between 2015 and 2018 at the Sunny Hill Centre in British Columbia, Canada and examined the relationships between prenatal substance exposures, FASD diagnostic categories, and adverse health and social outcomes. Patient chart data were obtained for 1187 children and youths diagnosed with FASD and analyzed. The patients (mean age: 9.7 years; range: 2-19) had up to 6 physical and 11 mental health disorders. Prenatal exposure to other substances (in addition to alcohol) significantly increased the severity of FASD diagnosis (OR: 1.18): the odds of FASD with sentinel facial features (SFF) were 41% higher with prenatal cigarette/nicotine/tobacco exposure; 75% higher with exposure to cocaine/crack; and two times higher with exposure to opioids. Maternal mental health issues and poor nutrition also increase the severity of FASD diagnosis (60% and 6%, respectively). Prenatal exposure to other substances in addition to alcohol significantly predicts involvement in the child welfare system (OR: 1.52) and current substance use when adjusted for age (aOR: 1.51). Diagnosis of FASD with SFF is associated with an increased number of physical (R = 0.071, F (3,1183) = 30.51, = 0.000) and mental health comorbidities (R = 0.023, F (3,1185) = 9.51, = 0.000) as compared to FASD without SFF adjusted for age and the number of prenatal substances. Screening of pregnant women for alcohol and other substance use, mental health status, and nutrition is extremely important.
Topics: Humans; Female; Pregnancy; Fetal Alcohol Spectrum Disorders; Prenatal Exposure Delayed Effects; Child; Male; Adolescent; Cross-Sectional Studies; Child, Preschool; Young Adult; British Columbia; Substance-Related Disorders; Mental Disorders
PubMed: 38892588
DOI: 10.3390/nu16111655