Risk Of Addiction Research Articles

Synergistic Epistasis and Systems Biology Approaches to Uncover a Pharmacogenomic Map Linked to Pain, Anti-Inflammatory and Immunomodulating Agents (PAIma) in a Healthy Cohort.

The global public health addiction crisis has been stark, with over 932,400deaths in the USA and Canada from opioid overdose since 1999-2020, surpassing the mortality rates at the top of the HIV/AIDS epidemic. Both nations exhibit opioid consumption rates significantly above the norm for developed countries. Analgesic type of opioids present both therapeutic benefits and substantial health risks, necessitating balanced drug regulation, careful prescribing, and dedicated opioid stewardship. The role of the cytochrome P450 2D6 (CYP2D6) system (Enzymatic functions) in metabolizing opioids highlights the potential of genotype-guided analgesia. By integrating Pharmacogenomics (PGx), this approach aims to optimize pain management, enhance safety, and reduce addiction risks. This understanding prompted the utilization of multifactor dimensionality reduction (MDR) to explore a range of phenotypes including PGx and gene-gene interactions (GGI) in a healthy cohort, thereby personalizing pain management strategies. The study sampled 100 unrelated healthy Western Iranians and 100 individuals from the 1000 Genome Project. Pre-testing involved searching for PGx annotations (variants associated with drug-gene-diseases) related to pain sensitivity and inflammation using the PharmGKB database, which identified 128 relevant genes. A questionnaire helped select 100 participants who had never used potent opioids but also other psychoactive agents (e.g., nicotine, amphetamines, etc.) and disease-related drugs. Whole-exome sequencing (WES) was then employed to analyze these genes in an Iranian cohort. Further analyses included MDR for identifying synergistic gene annotations and GGI for exploring complex gene interactions through the Visualization of Statistical Epistasis Networks (ViSEN). The study identified a Pain, Anti-Inflammatory, and Immunomodulating agents (PAIma) panel from the 128 genes, resulting in 55,590 annotations across 21 curated pathways. After filtering, 54 significant structural or regulatory variants were identified. This research also highlighted novel gene relationships involving the CYP3A5 gene, hsa-miR-355-5p, Paliperidone, and CYP2D6, which warrant further investigation. This study offers a novel pharmacogenetic framework that could potentially transform opioid prescribing practices to mitigate misuse and enhance personalized pain management. Further validation of these findings from multi countries and ethnic groups could guide clinicians in implementing DNA-based opioid prescribing, aligning treatment more closely with individual genetic profiles.

Fentanyl Initiation Rate Following the Requirement for Specialist Approval.

Healthcare organizations attempt to address unwarranted fentanyl use, which often leads to increased risk of addiction and overdose. To assess the impact of a requirement for a specialist's approval on fentanyl initiation for non-oncological pain. A retrospective cohort study based on observational data. All 4.4 million non-oncological members of Clalit Health Services were included, from July 20, 2021, to July 19, 2023. The rate of fentanyl initiation was assessed before and after the implementation of the requirement for specialist's approval, which was introduced on July 2022, and expanded 6months later for continued use. A sub-group analysis by age group was performed, and patient characteristics and indications were assessed. We also compared total opioid dispensation in the 6th and 12th months after the implementation with the predicted rate based on pre-implementation rates. Fentanyl initiation rate in the year before the requirement was 711 per million capita, which decreased following the requirement by - 81% (95% CI: - 77%; - 85%). The decrease attenuated with age. The prevalence of diagnosis with substance abuse disorders at the time of fentanyl initiation decreased from 6 to 3%. In the 6th and 12th months after the requirement was implemented, the morphine milligram equivalent (MME) from dispensation of total opioids was lower than predicted based on pre-implementation rates by 7% and 26%, respectively. Requiring specialist approval for fentanyl initiation for non-oncological chronic pain was associated with a decrease in fentanyl prescription initiations, especially among non-elderly patients. A decrease also occurred gradually in total opioid dispensations, further decreasing following the extension of the requirement to continuous fentanyl. The requirement for specialist approval upon fentanyl initiation and continuous fentanyl may present an effective tool for limiting the use of fentanyl and total opioids in healthcare systems.

The Role of Pain Medications in Modulating Peripheral Nerve Injury Recovery.

Peripheral nerve injuries (PNIs) are common, costly, and cause significant pain. Effective management of PNIs involves tailoring medications to the injury type as well as understanding the pharmacokinetics/pharmacodynamics to support nerve regeneration and reduce pain. Opioids act on opioid receptors to significantly reduce pain for many patients, but there are significant addiction risks and side effects. In addition, opioids may exacerbate pain sensitivity and affect nerve regeneration. Non-steroidal anti-inflammatory drugs or acetaminophen act on cyclooxygenase enzymes and are commonly used for nerve pain, with 34.7% of people using them for neuropathic pain. While effective for mild pain, they are often combined with opioids, gamma-aminobutyric acid (GABA) analogs, lidocaine, or corticosteroids for more severe pain. Corticosteroids, mimicking adrenal hormones like cortisol, treat PNI-related inflammation and pain. Their pharmacokinetics are complex, often requiring local injections in order to minimize systemic risks while effectively treating PNIs. Lidocaine, a common local anesthetic, blocks ion channels in the central nervous system (CNS) and peripheral nerves, providing strong analgesic and anti-inflammatory effects. If used improperly, lidocaine can cause neuronal toxicity instead of anesthetic effect. GABA acts as an inhibitory neurotransmitter in the CNS and its drug analogs like pregabalin and gabapentin can alleviate neuropathic pain by binding to voltage-gated Ca2+ channels, inhibiting neurotransmitter release. These pain medications are commonly prescribed for PNIs despite a limited guidance on their effects on nerve regeneration. This review will discuss these drug's mechanisms of action, pharmacokinetics/pharmacodynamics, and their clinical application to highlight their effect on the PNI recovery.

Vaping and smoking cue reactivity in young adult non-smoking electronic cigarette users: A functional neuroimaging study.

The rapid growth in the use of electronic cigarettes (e-cigarettes) among non-smoking young adults is concerning, as it raises the potential for chronic vaping and nicotine addiction. A key characteristic of drug addiction is the elevated neural response to conditioned drug-related cues (i.e., cue reactivity). Generalized reactivity to both vaping and smoking cues may signify an increased risk for smoking initiation in non-smoking vapers. In this study, we used functional magnetic resonance imaging (fMRI) to evaluate brain responses to vaping and smoking cues in young adult non-smoking vapers. Sixty-six young adult non-smoking vapers underwent functional MRI while viewing visual cues pertaining to vaping, smoking, and nicotine-unrelated unconditioned reward (i.e., food). A priori region-of-interest analysis combined with exploratory whole-brain analysis was performed to characterize neural reactivity to vaping and smoking cues in comparison to food cues. The medial prefrontal cortex and the posterior cingulate cortex, regions that play a key role in drug cue reactivity, showed significantly increased neural response to vaping cues compared to food cues. The posterior cingulate cortex additionally showed increased neural responses to smoking cues compared to food cues. Despite not currently smoking combustible cigarettes, young adult vapers exhibited heightened neural susceptibility to both vaping and smoking cues within brain systems associated with cue reactivity. The findings shed light on the mechanisms underlying nicotine addiction and smoking initiation risk in this critical population and may contribute to the development of science-based interventions and regulatory measures in the future. The escalating vaping prevalence among US non-smoking young adults is alarming, due to its potential ramifications for nicotine addiction development. Nicotine addiction is characterized by elevated neural response to conditioned nicotine-related cues. Using functional neuroimaging, we showed that young adult non-smoking vapers exhibited heightened neural susceptibility to both vaping and smoking cues within brain systems previously associated with cue reactivity. Such cross-reactivity to both types of nicotine cues may serve as the mechanism underlying nicotine addiction and smoking initiation risk in this population. Our findings may contribute to the development of science-based interventions and regulatory measures addressing the vaping epidemic.

What makes Chinese adolescents glued to their smartphones? Using network analysis and three-wave longitudinal analysis to assess how adverse childhood experiences influence smartphone addiction

Research has identified a robust connection between adverse childhood experiences and smartphone addiction. However, few studies have explored the close links between various smartphone application addictions and their co-occurrence. To bridge this gap, the current study used one pilot study and two formal studies to explore the co-occurrence of different smartphone application addictions, as well as their potential risk factors and internal mechanisms. In the pilot study (N = 118), adolescents with smartphone addictions were interviewed to determine their regularly-used applications and content type. In Study 1 (N = 1962), network analysis was used to assess six application preferences within the broader umbrella of smartphone addiction, and the potential relationship effect between adverse childhood experiences and smartphone addiction. In Study 2 (N = 835), the causal relationship was further verified through a longitudinal study which also found that alexithymia and social sensitivity played mediating roles in smartphone application addition. The application addiction with the highest centrality was for short videos, followed by games and then social media applications. In addition, a range of social experiences associated with violence (e.g., neglect and bullying) were found to be key determinants of smartphone addiction, in that these experiences hinder adolescents' socialization by increasing their alexithymia and social sensitivity, leading them to become glued to their smartphones. The findings of this study contribute to a better understanding of how adverse childhood experiences increase adolescents’ risk of smartphone addiction, while also providing new insights into the co-occurrence of addictions to various common smartphone applications.

Kontribusi Social Support terhadap Problematic Internet Use pada Mahasiswa Universitas Negeri Padang

The development of information and communication technology, particularly the internet, has significantly benefited Indonesian society, with internet users reaching 95% by 2024. Although the internet facilitates communication and access to information, excessive use can lead to mental health issues, especially among students, with 15% experiencing problematic internet use. Students often rely on the internet for social interaction and emotional management, which can increase the risk of addiction. This study aims to investigate the contribution of social support to problematic internet use among students at Universitas Negeri Padang. The research adopts a quantitative approach with statistical analysis. The population measured in this study consists of students at Universitas Negeri Padang. The sample was taken using a proportionate stratified random sampling technique, appropriate for populations with non-homogeneous and stratified members. A total of 395 students participated in the study. The instruments used were the GPIUS2 scale and the MSPSS scale, developed using the Likert model. The data obtained were analyzed using multiple regression analysis. The results show a coefficient of determination (R²) of 0.220, indicating that the social support variable contributes 22% to the problematic internet use variable.

The Role of the Church in Teaching Effective Parenting Methods to Protect the Alpha Generation from the Dangers of Gadget Addiction

This research explores the church's role in supporting parents of Generation Alpha and implementing effective parenting methods to prevent gadget addiction. This research collected and analyzed secondary data from relevant scientific journals, books, and news articles through a literature study approach. The results show that churches are important in providing education and resources for parents to face parenting challenges in the digital age. The research suggests that the integration of spiritual values and faith-based parenting guidelines can help parents in guiding their children to face the risks of device addiction. Furthermore, the study identified the need for educational programs specifically designed to equip parents with practical strategies in regulating their children's use of technology. The results of this study contribute to the understanding of the importance of synergy between church and family in educating children in the digital age.

Pengaruh Financial Tecnology terhadap Manajemen Keuangan Generasi Z

This research discusses the influence of financial technology (Fintech) on the financial management of Generation Z, a generation that is familiar with digitalization and has a consumptive lifestyle. Generation Z, which accounts for around 27.94% of Indonesia's population, exhibits financial behaviors that tend to be more concerned with wants than needs. Through a literature review, this research explores how Fintech affects Generation Z's financial behavior, including the challenges that arise, such as shopping addiction and debt risk. Fintech offers easy access to financial services, such as digital payments, investments and online lending, allowing Generation Z to manage their finances more flexibly. However, their low financial literacy may result in suboptimal financial management. This study highlights the importance of financial literacy as a key factor to help Generation Z achieve sustainable financial well-being and respond to the challenges of Fintech development in the digital era

Multivariate Bayesian variable selection for multi-trait genetic fine mapping

Abstract Genome-wide association studies (GWAS) have identified thousands of single-nucleotide polymorphisms (SNPs) associated with complex traits, but determining the underlying causal variants remains challenging. Fine mapping aims to pinpoint the potentially causal variants from a large number of correlated SNPs possibly with group structure in GWAS-enriched genomic regions using variable selection approaches. In multi-trait fine mapping, we are interested in identifying the causal variants for multiple related traits. Existing multivariate variable selection methods for fine mapping select variables for all responses without considering the possible heterogeneity across different responses. Here, we develop a novel multivariate Bayesian variable selection method for multi-trait fine mapping to select causal variants from a large number of grouped SNPs that target at multiple correlated and possibly heterogeneous traits. Our new method is featured by its selection at multiple levels, incorporation of prior biological knowledge to guide selection and identification of best subset of traits the variants target at. We showed the advantage of our method over existing methods via comprehensive simulations that mimic typical fine-mapping settings and a real-world fine-mapping example in UK Biobank, where we identified critical causal variants potentially targeting at different subsets of addictive behaviours and risk factors.

Exercise Addiction Inventory-3 (EAI-3): Psychometric properties of the Hungarian version

Background and aims: The Exercise Addiction Inventory (EAI), based on the components model addictions, is a 6-item instrument used to assess the risk of exercise addiction (REA). Its revised version (EAI-R) was published in 2019 but only differed from the original scale in the response rating range (using a 6-point rather than 5-point Likert scale). In 2023, the EAI-3 was released with two new items (guilt when missing training and exercising despite injury). We aimed to test the validity and reliability of the Hungarian EAI-3 (EAI-3-HU). Methods: We tested 507 regular exercisers (Mage = 38.7 years, SD age = 10.63 years, range age: 18–78 years; 62.7% females) who completed the EAI-3-HU, the obsessive passion subscale of the Passion Scale, and exercise habits questions on the online Qualtrics research platform during autumn/winter 2023–2024. Results: Confirmatory factor analysis resulted in a good model fit for the two factor EAI-3-HU (CFI = .96; TLI = .94; RMSEA = .07; SRMR = .04). However, the covariance between the latent factors was .97, indicating that they measure an identical concept. Thus, a single-factor solution was appropriate (CFI = .96; TLI = .94; RMSEA = .07; SRMR = .04). Testing measurement invariance revealed the partial scalar invariance across genders. The internal reliability of the scale was good (Cronbach’s α = .81). The scale had good convergent validity with obsessive passion (r = .72), and discriminant validity based on exercise frequency as well as exercise intensity (p < .001). Conclusion: The 8-item single factor EAI-3-HU adequately assesses the Hungarian samples’ REA. Nevertheless, it should be kept in perspective that the revised tool, like its predecessors, only assesses a level of ‘risk’, which does not imply morbidity, thus it has no clinical diagnostic value.

A systematic review of lithium biology and pharmacology and toxicological evaluation of new organic lithium salts

Objective: to systematize scientific data on biomedical studies investigating trace element lithium over the past 70 years; evaluate toxic properties of lithium ascorbate (LiAsc) as an important promising candidate molecule.Material and methods. An analysis of 49,959 publications on lithium biomedical research retrieved from PubMed/MEDLINE database was carried out using modern data mining methods developed within the framework of topological approach to recognizing (Yu.I. Zhuravlev scientific school). Publications found by experts and not indexed in PubMed/MEDLINE were used in discussing the results of a systematic analysis of publications array retrieved from PubMed/MEDLINE. An experimental study of chronic 180 day-long LiAsc (at doses of 5, 50 and 150 mg/kg) toxicity was performed on 36 “Soviet chinchilla” rabbits by assessing local irritant action. Intoxication clinical picture, body weight dynamics, water and food intake as well as physiological, hematological and biochemical parameters were analyzed.Results. Classification and systematization of all currently available publications on lithium biology and medicine were performed. It was shown that pharmacological applications of lithium salts in mental disorders as well as lithium effects on simple sugars metabolism, lipid metabolism, blood pressure regulation, hematopoiesis, inflammation and tumor growth inhibition, neurotransmitter homeostasis, neurotrophic and neuroprotective molecular mechanisms as well as homeostasis of other electrolytes comprised promising fields of lithium drug research. The prospects for using organic lithium salts, particularly LiAsc, for various therapeutic goals were also discussed. 180-day-long oral administration of LiAsc at doses of 5, 50, 150 mg/kg resulted in no macroscopic signs of local inflammatory reaction while examining its local irritant effect.Conclusion. The lithium-ion effect on neurotransmitters promotes neuroprotection and reduces a risk of addiction. The antihypertensive, antiatherosclerotic, antidiabetic, antitumor and neurotrophic effects related to organic lithium salts may be beneficial in various therapeutic applications.

Gidazepam – daytime tranquilizer for the treatment of anxiety

Gidazepam is a benzodiazepine tranquilizer with several characteristic pharmacodynamic properties: lower affinity to GABAА-receptors than classical benzodiazepines, partial agonism and modulation of GABAА-receptors by stimulation of neurosteroid synthesis through binding to the TranSlocator PrOtein (TSPO), influence on the activity of the serotonergic, dopaminergic and noradrenergic systems. Clinically, Gidazepam is characterized by rapid and sustained anxiolytic, antiasthenic, vegetotropic and procognitive effects. In the lower range of therapeutic doses (20–50 mg/day), the drug has antiasthenic and procognitive properties without subsequent exhaustion; the effects of the upper dose range (from 100–150 mg/day) are closer to the effects of classic benzodiazepine tranquilizers. The drug is well tolerated, it is not characterized by sedation and muscle relaxation, and the risk of addiction or dependence is extremely low.

Scrolling through adolescence: a systematic review of the impact of TikTok on adolescent mental health.

Amidst rising concerns about mental health in adolescents, the role of social media (SM), particularly highly visual platforms such as TikTok, has become a growing focus of investigation. In the extant literature, conclusive evidence is limited by the aggregate analysis of very heterogeneous SM platforms. This systematic scoping review examines the relationship between TikTok and mental health in adolescents. Additionally, it aims to highlight potential interactions between typical developmental processes and the unique aspects of TikTok, exploring their relevance to mental health within this demographic. Following PRISMA guidelines, a systematic search across PubMed, Scopus, Web of Knowledge, and PsychINFO yielded 20 studies that met the inclusion criteria, encompassing a total of 17,336 subjects from 10 countries. The retrieved studies analyzed four main topics related to TikTok use, i.e., the overall impact on adolescents' mental health, risk of problematic use and behavioral addiction, consequences on body image and self-esteem, and possible spreading of mental illness behaviors. While TikTok offers creative opportunities for self-expression and peer connection, the literature raises concerns about its potential negative effects on teens, such as lower life satisfaction, increased risk of "contagion" of certain psychiatric symptoms, and problematic usage patterns. Significant variations in study methodologies and outcome measures were observed. In the current era of evolving SM landscapes, a comprehensive approach informed by developmentally grounded research is critically needed to further understand the interplay between SM and adolescent mental health, providing insights for health authorities and policymakers.

A pH-sensitive opioid does not exhibit analgesic tolerance in a mouse model of colonic inflammation.

Tolerance to the analgesic effects of opioids and resultant dose escalation is associated with worsening of side effects and greater addiction risk. Here, we compare the development of tolerance to the conventional opioid fentanyl with a novel pH-sensitive μ-opioid receptor (MOR) agonist, (±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide (NFEPP) that is active only in acidic inflammatory microenvironments. An opioid tolerance model was developed in male C57BL/6 mice, with and without dextran sulphate sodium colitis, using increasing doses of either fentanyl or NFEPP over 5 days. Visceral nociception was assessed in vivo by measuring visceromotor responses (VMRs) to noxious colorectal distensions and in vitro measuring colonic afferent nerve activity of mesenteric nerves and performing patch-clamp recordings from isolated dorsal root ganglia neurons. Somatic thermal nociception was tested using a tail immersion assay. Cardiorespiratory effects were analysed by pulse oximeter experiments. VMRs and tail immersion tests demonstrated tolerance to fentanyl, but not to NFEPP in colitis mice. Cross-tolerance also occurred to fentanyl, but not to NFEPP. The MOR agonist DAMGO inhibited colonic afferent nerve activity in colitis mice exposed to chronic NFEPP, but not those from fentanyl-treated mice. Similarly, in patch-clamp recordings from isolated dorsal root ganglia neurons, DAMGO inhibited neurons from NFEPP-, but not fentanyl-treated mice. NFEPP did not exhibit tolerance in an inflammatory pain model, unlike fentanyl. Consequently, dose escalation to maintain analgesia during an evolving inflammation could be avoided, mitigating the potential risk of side effects.

Antioxidant activity of extracts of oregano and marsh cinquefoil, growing in the Altai region, in connection with their content of favonoids

Drugs based on medicinal plants have such advantages over synthetic analogues as low toxicity, better tolerability and reduced risk of addiction. Antioxidant agents in medicinal plants include substances from the flavonoid group, due to their ability to inactivate free radical processes, due to the mechanism of electron transfer between reaction components to neutralize free radicals. Among the medicinal plants of Western Siberia and the Altai Territory, oregano and marsh cinquefoil have a high content of flavonoids. The purpose of the study was to evaluate the antioxidant activity of alcohol-free extracts of oregano and marsh cinquefoil growing in the Altai region in connection with the content of flavonoids (flavonols and proanthocyanidins). To conduct the study, alcohol-free extracts of the studied plants were prepared using patented technology. The content of flavonols and proanthocyanidins was studied by arbitration techniques using spectrophotometry. The antioxidant activity of the extracts was measured using cathodic voltammetry method. The results showed that the average flavonol content in oregano extract was 866.5 μg/ml, while only traces were found in the extract of cinquefoil (60.0 μg/ ml). The average content of proanthocyanidins in the extract of cinquefoil was 4.05%, in the extract of oregano content of proanthocyanidins was 0.43%. The average coefficient of antioxidant activity for cinquefoil extract was 11.63 mmol/l×min and 3.81 mmol/l×min for oregano extract. From the results obtained, we can conclude that it is advisable to use extracts of marsh cinquefoil and oregano, growing in the Altai Territory, in the composition of biologically active antioxidant additives.

Smartphone Addiction among Adolescents in Southern Italy and Correlation with Other Risky Behaviors.

Addiction to smartphone is defined as the disability to cease using the device despite the physical, psychological, or social consequences. The diagnosis of this disorder is increasing exponentially among teenagers, even more so after Corona Virus Disease 2019 (COVID-19) pandemic. This study aims to analyze the risk of mobile phone addiction among teenagers in Italy and its relationship with other risk behaviors, such as drug consumption and emotional well-being, following the COVID-19 pandemic. A cross-sectional observational study was conducted in Catania, Sicily, during 2022. The study sample comprised 342 students from a secondary education center that answered to a validated Italian version of the Smartphone Addiction Scale Short Version (SAS-SV) accessing through computers and mobile devices. Subjective Wellbeing was measured with the Personal Wellbeing Index-School Children (PWI-SC). Also, they completed the NIAAA Brief Alcohol Use Screener. Our results showed that 30.1% of students who participated in the survey were classified with a smartphone addiction. Besides, most of the participants used the Smartphone for social networks (86.0%). Regarding the other aspects measured, the mean self-perceived well-being score measured with the PWI-SC was 55.5, and 36.2% of participants were categorized as "high risk" for depression. Finally, four out of ten participants were at "moderate or high risk" of an alcohol use disorder. Our results suggest that the use of mobile phones is increasing in adolescents, an age group also exposed to social and health problems.

The Influence of Childhood Emotional Abuse and Neglect on Love Addiction: The Indirect Effect of Vulnerable Narcissism Among Female and Male Emerging Adults.

Childhood maltreatment is a key precursor to vulnerable narcissism since it likely lead to a narcissistic injury that triggers defenses against rage and abandonment. In later life, this pattern may contribute to a maladaptive model of love relationships. The present study explored the association between different types of childhood maltreatment (i.e., emotional, physical, and sexual abuse; physical and emotional neglect) and love addiction via vulnerable narcissism in a community sample of 505 cisgender emerging adults (M = 24.90, SD = 2.67; 76.6% assigned female at birth (AFAB); 68.5% heterosexual) residing in Italy. Data collection relied on self-report questionnaires administered online through the Qualtrics platform, and study hypotheses were tested using structural equation modeling. The results showed that childhood emotional abuse and emotional neglect directly influenced love addiction, while physical and sexual abuse, as well as physical neglect, showed no significant effects. Greater childhood emotional abuse and neglect were associated with increased vulnerable narcissism, leading to higher levels of love addiction. Gender differences emerged, with the indirect effect of vulnerable narcissism on the relationship between emotional neglect and love addiction significant only for AFAB. The findings emphasize the risk of love addiction in emerging adults with a history of childhood emotional abuse and neglect, highlighting the importance of addressing childhood emotional maltreatment and vulnerable narcissistic personality traits in interventions to treat this condition.

B-274 Determining Novel Biomarker Candidates Associated With Heroin and Cocaine Exposure Using Urine Metabolomics

Abstract Background Substance abuse poses an escalating health risk in the United States. While acute drug exposure can be tracked using drugs and their metabolites as biomarkers in clinical settings, there is a notable absence of biomarkers for chronic drug exposure or addiction. The development and availability of such biomarkers could significantly enhance clinicians’ ability to identify patients at high risk of addiction, and more accurately predict disease progression and treatment responses. Methods Our study aimed to discover novel biomarkers associated with substance abuse by analyzing raw mass spectrometry (MS) data from urine comprehensive drug screening (UCDS) conducted at the University of Pittsburgh Medical Center (UPMC). The MS data, acquired through untargeted data collection using LC-qToF-MS at the UPMC Clinical Toxicology Laboratory, was initially preprocessed (including peak identification, alignment, and putative annotation) using MS-DIAL to generate a data matrix. This matrix, consisting of objects (cases) and features (m/z and retention time), was further normalized and analyzed using MetaboAnalyst. A combination of statistical methods, including point biserial correlation analysis, volcano plot, significance analysis of microarrays and metabolites (SAM), empirical Bayesian analysis of microarrays and metabolites (EBAM), partial least squares discriminant analysis (PLS-DA), and random forest (RF), were employed to select features significantly associated with the EIA-results. These features were subsequently evaluated for analyte identification using MS-FINDER. Results Our analysis identified nine significant features associated with 6MAM-EIA for heroin abuse, including 6-monoacetylmorphine itself and norfentanyl. For features associated with cocaine metabolite-EIA, 37 significant features were selected, including multiple cocaine metabolites, nicotine metabolites, and norfentanyl. Some of these selected features are likely products of in-source fragmentation or endogenous metabolites. Conclusions Our study has identified a set of potential biomarker candidates for illicit drug exposure. Notably, norfentanyl was found to be significantly associated with both 6MAM-EIA and cocaine metabolite-EIA, reflecting current trends in illicit drug use. Further chemical identification of these biomarkers is planned for future work.

B-123 Prediction of Opioid Use Duration in Post-Surgical Orthopedic Patients Using CYP2D6 Inhibitor Index and Routine Laboratory Markers

Abstract Background Hydrocodone, the most commonly prescribed opioid in the U.S., is typically used for pain management following surgery and is a known potential drug of abuse with non-negligible risk of addiction. Significant variability in patients’ response to hydrocodone therapy have been reported, owing to both iatrogenic and endogenous sources. The objective of this study is to evaluate the feasibility of predicting post-discharge hydrocodone use in patients who have undergone orthopedic surgery using patient demographics, genotyping, concurrently prescribed medications, and routinely collected laboratory test results. Methods Targeted genotyping was performed on each patient with genes known to affect hydrocodone pharmacokinetics or pharmacodynamics, including CYP2D6, CYP3A4, CYP3A5, CYP2B6, COMT, OPRM1, and ABCB1. An inhibition index for CYP2D6 was calculated by ranking concurrently prescribed medications as weak, moderate, or strong inhibitors of enzyme activity. Pain index, average hydrocodone dose per day during hospital stay, and CYP2D6 estimated activity scores based on allele functionality were included as predictors. In addition, a retrospective chart review of electronic hospital records was performed where basic metabolic panel and complete blood count results were screened within 10 days of each patient's surgery date. Two types of classification and decision tree algorithms were tuned and validated as prediction models using 5-fold cross validation, including a ‘Fast and Frugal Decision Tree’ (FFTree) and an extreme gradient boosting machine (xgBoost). Clinical predictive features were ranked according to the Shapley Additive Explanations (SHAP) values using the xgBoost model. Results Out of 79 total patients with hydrocodone use duration information, 25 were categorized as “Short” and 54 categorized as “Long” using a 1-week threshold. FFTree model selected the top three features of CYP2D6 inhibition index, blood sodium level, and blood creatinine level and obtained a sensitivity and specificity of 0.80 and 0.76, respectively. The xgBoost model, using the same three features, achieved a sensitivity and specificity of 0.872 and 0.628, respectively, an AUROC of 0.814, PRAUC of 0.912, net benefit of 0.359, and was well-calibrated with a Brier score of 0.161. Consistent with previously published results, the predictive capacity of all genotypes analyzed were unremarkable and consistently ranked as the least important features by the xgBoost model SHAP values, due to their low predictive value. Conclusions Both the FFTree and xgBoost models were able to adequately classify the patients according to a 1-week stratification criteria with good to excellent classification performance. Patients with larger CYP2D6 inhibition index were more likely to be classified as “Long” duration. Sodium and creatinine level, which may reflect hydration status and renal function, and therefore hydromorphone elimination rate, were key predictors of post-discharge hydrocodone use duration when combined with the CYP2D6 inhibition index. Further refinement of the proposed models and validation of model robustness and stability using external cohorts is necessary. These results may have implications for providers when prescribing hydrocodone for pain management, where the ability to risk-stratify patients according to their predicted probability of developing opioid use disorder is of clinical importance.

Exploring internet addiction during Covid-19 pandemic: a comparative study considering psychological, social, familial and individual aspects in University students.

Internet addiction causes a variety of social, interpersonal, psychological, and physical issues. We are confronting a worldwide crisis about internet addiction and its effects. Utilizing five questionnaires to survey university students during the COVID-19 epidemic, the current study sought to evaluate internet addiction and associated risk variables. At the University of Medical Sciences in North Iran, a cross-sectional analytical investigation was carried out. The sample was done among 318 students, selected through the random cluster sampling method. Data collection was done during August and September 2021. Based on our findings, the prevalence of internet addiction was 28.9% (92/318). Our results revealed that women are at twice the twice the risk of internet addiction as men (p = 0.028). Students in the medicinal field (p = 0.043; students with a positive history of mental illness in the family) p = 0.001 (and students with a fear of COVID-19) p = 0.002 (recognized in the risk of Internet addiction, thus depression) p < 0.001 (anxiety) p < 0.001 (somatization) p = 0.001 (and psychological distress) p < 0.001 are risk factors for internet addiction. Age, marital status, place of living, total social support, and use of Alcohol/cigarettes are not risk factors for internet addiction. The findings suggest that university students with a fear of COVID-19, depression, anxiety, somatization, psychological distress and a positive history of mental illness in the family, particularly medicinal field students, are at significant risk for Internet addiction.