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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 -
International Journal of Molecular... May 2024Yeast expression of human G-protein-coupled receptors (GPCRs) can be used as a biosensor platform for the detection of pharmaceuticals. Cannabinoid receptor type 1...
Yeast expression of human G-protein-coupled receptors (GPCRs) can be used as a biosensor platform for the detection of pharmaceuticals. Cannabinoid receptor type 1 (CB1R) is of particular interest, given the cornucopia of natural and synthetic cannabinoids being explored as therapeutics. We show for the first time that engineering the N-terminus of CB1R allows for efficient signal transduction in yeast, and that engineering the sterol composition of the yeast membrane modulates its performance. Using an engineered cannabinoid biosensor, we demonstrate that large libraries of synthetic cannabinoids and terpenes can be quickly screened to elucidate known and novel structure-activity relationships. The biosensor strains offer a ready platform for evaluating the activity of new synthetic cannabinoids, monitoring drugs of abuse, and developing therapeutic molecules.
Topics: Biosensing Techniques; Humans; Cannabinoids; Receptor, Cannabinoid, CB1; Saccharomyces cerevisiae; Structure-Activity Relationship; Signal Transduction
PubMed: 38892247
DOI: 10.3390/ijms25116060 -
International Journal of Molecular... May 2024This review emphasises the importance of opioid monitoring in clinical practice and advocates for a personalised approach based on pharmacogenetics. Beyond effectively... (Review)
Review
This review emphasises the importance of opioid monitoring in clinical practice and advocates for a personalised approach based on pharmacogenetics. Beyond effectively managing pain, meticulous oversight is required to address concerns about side effects, specially due to opioid-crisis-related abuse and dependence. Various monitoring techniques, along with pharmacogenetic considerations, are critical for personalising treatment and optimising pain relief while reducing misuse and addiction risks. Future perspectives reveal both opportunities and challenges, with advances in analytical technologies holding promise for increasing monitoring efficiency. The integration of pharmacogenetics has the potential to transform pain management by allowing for a precise prediction of drug responses. Nevertheless, challenges such as prominent pharmacogenetic testing and guideline standardisation persist. Collaborative efforts are critical for transforming scientific advances into tangible improvements in patient care. Standardised protocols and interdisciplinary collaboration are required to ensure consistent and evidence-based opioid monitoring. Future research should look into the long-term effects of opioid therapy, as well as the impact of genetic factors on individual responses, to help guide personalised treatment plans and reduce adverse events. Lastly, embracing innovation and collaboration can improve the standard of care in chronic pain management by striking a balance between pain relief and patient safety.
Topics: Humans; Analgesics, Opioid; Precision Medicine; Pain Management; Drug Monitoring; Chronic Pain; Pharmacogenetics; Opioid-Related Disorders
PubMed: 38892112
DOI: 10.3390/ijms25115925 -
International Journal of Molecular... May 2024This study reports the first application of in silico methods to assess the toxicity of 4-chloromethcathinone (4-CMC), a novel psychoactive substance (NPS). Employing...
Toxicity of the New Psychoactive Substance (NPS) Clephedrone (4-Chloromethcathinone, 4-CMC): Prediction of Toxicity Using In Silico Methods for Clinical and Forensic Purposes.
This study reports the first application of in silico methods to assess the toxicity of 4-chloromethcathinone (4-CMC), a novel psychoactive substance (NPS). Employing advanced toxicology in silico tools, it was possible to predict crucial aspects of the toxicological profile of 4-CMC, including acute toxicity (LD), genotoxicity, cardiotoxicity, and its potential for endocrine disruption. The obtained results indicate significant acute toxicity with species-specific variability, moderate genotoxic potential suggesting the risk of DNA damage, and a notable cardiotoxicity risk associated with hERG channel inhibition. Endocrine disruption assessment revealed a low probability of 4-CMC interacting with estrogen receptor alpha (ER-α), suggesting minimal estrogenic activity. These insights, derived from in silico studies, are critical in advancing the understanding of 4-CMC properties in forensic and clinical toxicology. These initial toxicological findings provide a foundation for future research and aid in the formulation of risk assessment and management strategies in the context of the use and abuse of NPSs.
Topics: Psychotropic Drugs; Humans; Computer Simulation; Animals; Cardiotoxicity; Propiophenones; Estrogen Receptor alpha; Endocrine Disruptors; DNA Damage
PubMed: 38892053
DOI: 10.3390/ijms25115867 -
International Journal of Molecular... May 2024Fetal alcohol spectrum disorders (FASDs) are leading causes of neurodevelopmental disability but cannot be diagnosed early in utero. Because several microRNAs (miRNAs)...
Fetal alcohol spectrum disorders (FASDs) are leading causes of neurodevelopmental disability but cannot be diagnosed early in utero. Because several microRNAs (miRNAs) are implicated in other neurological and neurodevelopmental disorders, the effects of EtOH exposure on the expression of these miRNAs and their target genes and pathways were assessed. In women who drank alcohol (EtOH) during pregnancy and non-drinking controls, matched individually for fetal sex and gestational age, the levels of miRNAs in fetal brain-derived exosomes (FB-Es) isolated from the mothers' serum correlated well with the contents of the corresponding fetal brain tissues obtained after voluntary pregnancy termination. In six EtOH-exposed cases and six matched controls, the levels of fetal brain and maternal serum miRNAs were quantified on the array by qRT-PCR. In FB-Es from 10 EtOH-exposed cases and 10 controls, selected miRNAs were quantified by ddPCR. Protein levels were quantified by ELISA. There were significant EtOH-associated reductions in the expression of several miRNAs, including miR-9 and its downstream neuronal targets BDNF, REST, Synapsin, and Sonic hedgehog. In 20 paired cases, reductions in FB-E miR-9 levels correlated strongly with reductions in fetal eye diameter, a prominent feature of FASDs. Thus, FB-E miR-9 levels might serve as a biomarker to predict FASDs in at-risk fetuses.
Topics: Humans; Fetal Alcohol Spectrum Disorders; Female; Exosomes; Pregnancy; Biomarkers; MicroRNAs; Brain; Adult; Fetus; Case-Control Studies; Ethanol; Male
PubMed: 38892014
DOI: 10.3390/ijms25115826 -
Healthcare (Basel, Switzerland) May 2024This study describes and explores the application of no-restraint policies in General Hospital Psychiatric Units (GHPUs) in Italy, a country pioneering in...
This study describes and explores the application of no-restraint policies in General Hospital Psychiatric Units (GHPUs) in Italy, a country pioneering in deinstitutionalization and psychiatric reform. The research aims to assess the organizational characteristics and effectiveness of no-restraint practices, contributing to the global discourse on humane psychiatric care. Following a purposive sampling approach, a nationwide descriptive study was conducted involving a detailed online survey distributed to 24 GHPUs actively engaged in or aspiring toward no-restraint practices. The survey, comprising 60 items across seven sections, gathered comprehensive data on the structural, organizational, and operational dimensions of the units, along with the prevalence and management of restraint episodes. Results reveal a significant commitment to no-restraint policies, with 14 GHPUs reporting zero restraint incidents in 2022. Despite variations in infrastructure and staffing, a common thread was the implementation of systematic procedures and risk management training aimed at reducing coercive practices. The study identified a correlation between the use of exclusive garden spaces and an increased incidence of restraints, suggesting nuanced factors influencing restraint practices. The findings underscore the viability and ethical alignment of no-restraint practices within psychiatric care, highlighting the crucial role of organizational protocols and training. This research adds empirical weight to the advocacy for restraint-free environments in mental health settings, signaling a paradigm shift toward more humane and rights-respecting psychiatric care.
PubMed: 38891179
DOI: 10.3390/healthcare12111104 -
Cells Jun 2024Binge drinking in obese patients positively correlates with accelerated liver damage and liver-related death. However, the underlying mechanism and the effect of alcohol...
Binge drinking in obese patients positively correlates with accelerated liver damage and liver-related death. However, the underlying mechanism and the effect of alcohol use on the progression of metabolic-dysfunction-associated steatotic liver disease (MASLD) remain unexplored. Here, we show that short-term feeding of a metabolic-dysfunction-associated steatohepatitis (MASH) diet plus daily acute alcohol binges for three days induce liver injury and activation of the NLRP3 inflammasome. We identify that a MASH diet plus acute alcohol binges promote liver inflammation via increased infiltration of monocyte-derived macrophages, neutrophil recruitment, and NET release in the liver. Our results suggest that both monocyte-derived macrophages and neutrophils are activated via NLRP3, while the administration of MCC950, an NLRP3 inhibitor, dampens these effects.In this study, we reveal important intercellular communication between hepatocytes and neutrophils. We discover that the MASH diet plus alcohol induces IL-1β via NLRP3 activation and that IL-1β acts on hepatocytes and promotes the production of CXCL1 and LCN2. In turn, the increase in these neutrophils recruits chemokines and causes further infiltration and activation of neutrophils in the liver. In vivo administration of the NLRP3 inhibitor, MCC950, improves the early phase of MetALD by preventing liver damage, steatosis, inflammation, and immune cells recruitment.
Topics: NLR Family, Pyrin Domain-Containing 3 Protein; Animals; Liver; Interleukin-1beta; Neutrophil Infiltration; Male; Neutrophils; Mice, Inbred C57BL; Mice; Inflammasomes; Binge Drinking; Hepatocytes; Cell Communication; Sulfones; Sulfonamides; Macrophages; Furans; Humans; Indenes; Diet; Signal Transduction; Extracellular Traps; Fatty Liver; Sulfoxides
PubMed: 38891092
DOI: 10.3390/cells13110960