Methamphetamine Use and Its Correlates among Individuals with Opioid Use Disorder in a Midwestern U.S. City.

Background: U.S. is experiencing a surging trend of methamphetamine use among individuals who use opioids. More research is needed to characterize this emerging "twin epidemic." Objectives: The study aims to identify social and behavioral characteristics associated with methamphetamine use among individuals with opioid use disorder (OUD) in the Dayton, Ohio, area, an epicenter of the opioid crisis and an emerging frontier of methamphetamine epidemic. Methods: 357 adult individuals with current OUD were recruited using targeted and respondent-driven sampling. Structured interviews collected information on social and drug use characteristics. Multivariable Logistic Regression was used to identify characteristics associated with the past 6-month use of methamphetamine. Results: 49.7% were female, and 88.8% were non-Hispanic whites. 55.6% used methamphetamine in the past 6-months, and 84.9% reported first use of methamphetamine after initiation of illicit opioids. Methamphetamine use was associated with homelessness (aOR = 2.46, p = .0001), lifetime history of diverted pharmaceutical stimulant use (aOR = 2.97, p < .001), injection route of heroin/fentanyl use (aOR = 1.89, p = .03), preference for fentanyl over heroin (aOR = 1.82, p = .048), lifetime history of extended-release injectable naltrexone (Vivitrol)-based treatment (aOR = 2.89, p = .003), and more frequent marijuana use (aOR = 1.26, p = .04). Discussion: The findings point to the complexity of motivational and behavioral pathways associated with methamphetamine and opioid co-use, ranging from self-treatment and substitution behaviors, attempts to endure homelessness, and greater risk taking to experience euphoria. More research is needed to understand the causal relationships and the association between methamphetamine and Vivitrol use. Public health responses to the opioid crisis need to be urgently expanded to address the growing epidemic of methamphetamine use.

Patterns of non-prescribed buprenorphine and other opioid use among individuals with opioid use disorder: A latent class analysis.

AIM: Non-prescribed buprenorphine (NPB) use increased in the US. This study aims to characterize heterogeneity in patterns of NPB and other opioid use among individuals with current opioid use disorder. METHODS: The study recruited 356 participants in Dayton (Montgomery County), Ohio, area in 2017-2018 using targeted and Respondent Driven Sampling. Participants met the following criteria: 1) 18 years or older, 2) current moderate/severe opioid use disorder (DSM-5), 3) past 6-month NPB use. Latent class analysis (LCA) was conducted to identify subgroups based on past 6-month (days of NPB and heroin/fentanyl use; use of NPB to get high; use of non-prescribed and prescribed pharmaceutical opioids; participation in formal treatment) and lifetime (years since first NPB and other illicit opioid use) characteristics. Selected auxiliary variables were compared across classes using Asparouhov and Muthén's 3-step approach. RESULTS: 49.7% were female, and 88.8% were non-Hispanic whites. 89% used NPB to self-treat withdrawal. LCA resulted in three classes: "Heavy Heroin/Fentanyl Use" (61%), "More Formal Treatment Use" (29%) and "Intense NPB Use" (10%). After adjusting for multiple testing, the following past 6-month variables differed significantly between classes: injection as a primary route of heroin/fentanyl administration (p < 0.001), cocaine use (p = 0.044), unintentional drug overdose (p = 0.023), and homelessness (p = 0.044), with the "Intense NPB Use" class having the lowest prevalences. CONCLUSION: Predominance of self-treatment goals and the association between more intense NPB use and lower risks of adverse consequences suggest potential harm minimization benefits of NPB use. More research is needed to understand consequences of NPB use over time.

Non-invasive prediction of NAFLD severity: a comprehensive, independent validation of previously postulated serum microRNA biomarkers.

Liver biopsy is currently the only reliable method to establish nonalcoholic fatty liver disease (NAFLD) severity. However, this technique is invasive and occasionally associated with severe complications. Thus, non-invasive diagnostic markers for NAFLD are needed. Former studies have postulated 18 different serum microRNA biomarkers with altered levels in NAFLD patients. In the present study, we have re-examined the predictive value of these serum microRNAs and found that 9 of them (miR-34a, -192, -27b, -122, -22, -21, -197, -30c and -16) associated to NAFLD severity in our independent cohort. Moreover, miR-192, -27b, -22, -197 and -30c appeared specific for NAFLD, when compared with patients with drug-induced liver injury. Preliminary serum RNAseq analysis allowed identifying novel potential miRNA biomarkers for nonalcoholic steatohepatitis (NASH). The classification performance of validated miRNAs (and their ratios) for NASH was better than that reached by AST, whereas for advanced fibrosis prediction miRNAs did not perform better than the FIB-4 algorithm. Cross-validated models combining both clinical and miRNA variables showed enhanced predictivity. In conclusion, the circulating microRNAs validated demonstrate a better diagnostic potential than conventional serum markers to identify NASH patients and could complement and improve current fibrosis prediction algorithms. The research in this field is still open.

New microRNA Biomarkers for Drug-Induced Steatosis and Their Potential to Predict the Contribution of Drugs to Non-alcoholic Fatty Liver Disease.

Background and Aims: Drug-induced steatosis is a major reason for drug failure in clinical trials and post-marketing withdrawal; and therefore, predictive biomarkers are essential. These could be particularly relevant in non-alcoholic fatty liver disease (NAFLD), where most patients show features of the metabolic syndrome and are prescribed with combined chronic therapies, which can contribute to fatty liver. However, specific biomarkers to assess the contribution of drugs to NAFLD are lacking. We aimed to find microRNAs (miRNAs) responsive to steatotic drugs and to investigate if they could become circulating biomarkers for drug-induced steatosis. Methods: Human HepG2 cells were treated with drugs and changes in miRNA levels were measured by microarray and qRT-PCR. Drug-induced fat accumulation in HepG2 was analyzed by high-content screening and enzymatic methods. miRNA biomarkers were also analyzed in the sera of 44 biopsy-proven NAFLD patients and in 10 controls. Results: We found a set of 10 miRNAs [miR-22-5p, -3929, -24-2-5p, -663a, -29a-3p, -21 (5p and 3p), -27a-5p, -1260 and -202-3p] that were induced in human HepG2 cells and secreted to the culture medium upon incubation with model steatotic drugs (valproate, doxycycline, cyclosporin A and tamoxifen). Moreover, cell exposure to 17 common drugs for NAFLD patients showed that some of them (e.g., irbesartan, fenofibrate, and omeprazole) also induced these miRNAs and increased intracellular triglycerides, particularly in combinations. Finally, we found that most of these miRNAs (60%) were detected in human serum, and that NAFLD patients under fibrates showed both induction of these miRNAs and a more severe steatosis grade. Conclusion: Steatotic drugs induce a common set of hepatic miRNAs that could be used in drug screening during preclinical development. Moreover, most of these miRNAs are serum circulating biomarkers that could become useful in the diagnosis of iatrogenic steatosis.

In vitro/in vivo screening of oxidative homeostasis and damage to DNA, protein, and lipids using UPLC/MS-MS.

Multiple analytical methods are required to comprehensively assess oxidative homeostasis and specific damage to macromolecules. Our aim was to develop a straightforward strategy for the fast assessment of global oxidative status and specific damage to DNA, proteins, and lipids. To this end, an analytical method, based on ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS/MS), was developed and validated for the quantification of 16 oxidative stress (OS) biomarkers. Some of these markers were unstable; thus, an easy sample treatment procedure, including fractionation and derivatization, was set up. The method was validated according to Food and Drug Administration (FDA) guidelines, and it provided good results in terms of intra- and inter-day precision (≤17.2 and 16 %, respectively), accuracy (relative error measurement between -16.6 and 19.8 %), and linearity (R (2) > 0.994). The approach was applied to determine the oxidative insult provoked to cultured rat hepatocytes by cumene hydroperoxide and to analyze the liver and serum samples from patients diagnosed with nonalcoholic steatohepatitis. In both studies, significant differences were found if compared to the corresponding control groups; interestingly, ophthalmic acid was shown as an OS biomarker in both models for the first time. A key advantage of the novel approach in comparison with former multi-method approaches is that now a single method is applied to assess the 16 OS biomarkers. Its comprehensive capacity to profile oxidative homeostasis and damage in both in vitro and clinical samples has been illustrated, which indicates that the proposed approach is a good choice to evaluate whether OS is involved in physiological signals, diseases, or toxic events and to what extent.

Prognostic factors in gastrointestinal bleeding due to peptic ulcer: construction of a predictive model.

OBJECTIVES: The identification of prognostic factors of easy application in clinical practice can improve the diagnostic and therapeutic decision making process in upper gastrointestinal bleeding (UGB). The present study estimates the capacity to predict an unfavorable clinical course (mortality, unstable bleeding, and/or interventional therapy) on the basis of the preendoscopic and endoscopic clinical analytical findings in patients with UGB owing to peptic ulcer. METHOD: A retrospective cohort study was made of 473 adult patients seen in the Emergency Service of a District Hospital, and diagnosed with UGB secondary to gastroduodenal ulcer. Logistic regression analysis was used to construct different models, with the evaluation of their predictive capacity based on calculation of the area under the receiver operating curve (ROC). The final model was used to calculate the probabilities of an unfavorable clinical course for different profiles, with the purpose of constructing an algorithm of help in the decision making process applied to patients initially considered to be at low risk (Forrest classification IIb and III). RESULTS: The model with the Forrest variable showed a high predictive capacity: ROCa=0.81 (95% confidence interval, 0.76-0.85). Incorporation to the model of clinical and preendoscopic factors (type of UGB, hematocrit, kidney failure, and liver disease) significantly increased its predictive capacity: ROCa=0.87 (95% confidence interval, 0.83-0.91). This model allows the differentiation of different complication risk levels in patients initially at low risk according to the Forrest classification (IIb and III). CONCLUSIONS: The Forrest classification is the principal predictive factor for an unfavorable course in patients with gastrointestinal bleeding owing to peptic ulcer, though clinical factors are also important and should complement the decision taking process.