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Objectives: This study aimed to examine outcomes of a pilot program designed to increase inpatient medications for opioid use disorder (MOUD) induction and to support MOUD adherence after discharge., Methods: This retrospective cohort analysis examined Medicaid adults diagnosed with opioid use disorder discharged from 2 freestanding inpatient withdrawal management facilities between October 1, 2018, and December 31, 2019. Participants had ≥90 days of continuous Medicaid enrollment before and after admission. Odds ratios (ORs) examined associations of inpatient MOUD induction with discharge against medical advice, 7- and 30-day all-cause hospital readmission, and postdischarge MOUD adherence. Mixed-effect models examined changes associated with MOUD induction and postdischarge MOUD adherence in acute service utilization and opioid overdose in the 90-day postdischarge period., Results: Of the 2332 patients discharged, 493 started MOUD inpatient care (21.1%), with most initiating buprenorphine (76.5%). Induction of MOUD was associated with a lower likelihood of discharge against medical advice (OR, 0.49; 95% confidence interval [CI], 0.37-0.64), 30-day all-cause hospital readmission (OR, 0.61; 95% CI, 0.47-0.80), and higher odds of postdischarge MOUD adherence (OR, 3.83; 95% CI, 3.06-4.81). In the 90 days after discharge, MOUD adherent patients had significant reductions in emergency department visits for behavioral health, inpatient days, withdrawal management episodes, and opioid overdoses compared with the 90-day preadmission period., Conclusions: Inpatient MOUD induction is associated with a higher likelihood of short-term MOUD adherence after discharge, which in turn is associated with significant reductions in short-term service utilization and opioid overdose after discharge., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

Columnar metaplasia of the esophagus is the main risk factor for esophageal adenocarcinoma. There is a lack of evidence to demonstrate that esophageal progenitors can be the source of columnar metaplasia. In this study, using transgenic mouse models, lineage tracing, single-cell RNA sequencing, and transcriptomic and epigenetic profiling, we found that the activation of the Hedgehog pathway in esophageal cells modifies their differentiation status in vivo. This process involves an initial step of dedifferentiation into embryonic-like esophageal progenitors. Moreover, a subset of these cells undergoes full squamous-to-columnar conversion and expresses selected intestinal markers. These modifications of cell fate are associated with remodeling of the chromatin and the appearance of Sox9. Using a conditional knockout mouse, we show that Sox9 is required for columnar conversion but not for the step of dedifferentiation. These results provide insight into the mechanisms by which esophageal cells might initiate columnar metaplasia., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Food intake and use of drugs of abuse like cocaine share common central and peripheral physiological pathways. Appetitive hormones play a major role in regulating food intake; however, little is known about the effects of acute cocaine administration on the blood concentrations of these hormones in cocaine users., Methods: We evaluated serum concentrations of six appetitive hormones: ghrelin (total and acyl-ghrelin), amylin, glucagon-like peptide-1 (GLP-1), insulin, leptin and peptide YY (PYY), as well as acute cardiorespiratory and subjective responses of 8 experienced cocaine users who received 25mg intravenous (IV) cocaine., Results: Serum concentrations of GLP-1 (p=0.014) and PYY (p=0.036) were significantly decreased one hour following IV cocaine administration; there was a trend towards a decrease for insulin (p=0.055) and amylin (p=0.063) concentrations, while no significant IV cocaine effect was observed for ghrelin (total or acyl-ghrelin) or leptin concentrations (p's≫>0.5). We also observed associations between hormone concentrations acutely affected by IV cocaine (GLP-1, PYY, insulin, amylin) and some cocaine-related cardiorespiratory and subjective responses (e.g., increased heart and respiratory rates; feeling high and anxious)., Discussion: These findings show a significant effect of acute IV cocaine administration on some appetitive hormones and suggest potential associations between these hormones and cocaine-related cardiorespiratory and subjective responses. Additional research is needed to further investigate the potential mechanisms underlining these associations., (Published by Elsevier B.V.)

Background: No controlled cocaine administration data describe cocaine and metabolite disposition in oral fluid (OF) collected with commercially-available collection devices, OF-plasma ratios, and pharmacodynamic relationships with plasma and OF cocaine and metabolite concentrations., Methods: Eleven healthy, cocaine-using adults received 25mg intravenous cocaine. Physiological and subjective effects (visual analogue scales), and plasma were collected one hour prior, and up to 21h post-dose. OF was collected with the Quantisal™ device up to 69h post-dose. Cocaine, benzoylecgonine (BE) and ecgonine methyl ester were quantified in plasma by liquid chromatography-tandem mass spectrometry; cocaine and BE were quantified in OF by two dimensional-gas chromatography-mass spectrometry., Results: Increases in heart rate, blood pressure and positive subjective effects occurred within the first 15min, persisting up to 1h ("Rush"), with clockwise hysteresis observed for plasma and OF concentrations and some subjective measures. Peak subjective effects ("Rush," "Good drug effect" and "Bad drug effect") occurred prior to peak OF cocaine concentration, whereas observed peak plasma concentrations and subjective measures occurred simultaneously, most likely due to significantly earlier plasma Tmax compared to OF Tmax.Tlast was generally longer in OF (12.5h cocaine; 33.0h BE) than plasma (9.5h cocaine; >21h BE, cutoffs 1μg/L); 8 and 10μg/L OF cocaine confirmatory cutoffs yielded detection times similar to cocaine's impairing effects, suggesting usefulness for DUID testing., Conclusions: OF offers advantages as an alternative matrix to blood and plasma for identifying cocaine intake, defining pharmacokinetic parameters at different confirmation cutoffs, and aiding different drug testing programs to best achieve their monitoring goals., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Limited oral fluid (OF) pharmacokinetic data collected with commercially available collection devices after controlled cocaine administration hinder OF result interpretations. Ten cocaine-using adults provided OF, collected with Oral-Eze(®) (OE) and StatSure Saliva Sampler™ (SS) devices, an hour prior to and up to 69 h after 25mg intravenous (IV) cocaine administration. Cocaine and benzoylecgonine (BE) were quantified by a validated 2D-GC-MS method. Large inter-subject variability was observed. Cocaine was detected in OF in the first 0.17 h sample after IV administration, with much more rapid elimination than BE. OE observed Cmax median (range) concentrations were 932 (394-1574)μg/L for cocaine and 248 (96.9-953)μg/L for BE. SS observed cocaine and BE Cmax median (range) concentrations trended lower at 732 (83.3-1892)μg/L and 360 (77.2-836)μg/L, respectively. OE and SS cocaine OF detection times were 12.5 and 6.5h and for BE 30.5 and 28.0 h, respectively at 1 μg/L. There were no significant pharmacokinetic differences between OE and SS OF collection devices, except cocaine half-life was significantly shorter in SS OF specimens. This difference could be attributed to differences in stabilizing buffers present in OF collection devices, which may affect cocaine stability in OF specimens, or decreased recovery from collection pads. Both OE and SS OF collection devices were effective in monitoring cocaine and metabolite concentrations with similar detection windows. Furthermore, we demonstrated that different confirmatory OF cutoffs can be selected to produce shorter or longer cocaine and metabolite detection windows to address specific needs of clinical and forensic drug testing programs., (Published by Elsevier Ireland Ltd.)

Accurate on-site devices to screen for drug intake are critical for establishing whether an individual is driving under the influence of drugs (DUID); however, on-site oral fluid (OF) cocaine device performance is variable. We evaluated the performance of a newly developed benzoylecgonine (BE) test-strip for the Draeger® DrugTest 5000 device (20 µg/L cut-off) with equivalent cross reactivity for cocaine and BE. Ten cocaine users provided OF, collected with the Draeger cassette and Oral-Eze® and StatSure Saliva Sampler(TM) devices, up to 69 h following 25 mg intravenous cocaine administration. All screening results were confirmed by a validated two-dimensional-gas chromatography-mass spectrometry (2D-GC-MS) method for cocaine and/or BE. Cocaine test-strip median Tlast for screening only results was 6.5 h, and 6.5 h with Oral-Eze® and 4 h for StatSure OF confirmation for cocaine and/or BE at 1, 8, and 10 µg/L; sensitivity, specificity, and efficiency ranged from 85.5 to 100% and 83.3 to 100% for cocaine only confirmation at 8 and 10 µg/L. For the BE test-strip, median Tlast was 12.5 h for screening only and confirmation for cocaine and/or BE at all three cut-offs; sensitivity, specificity, and efficiency ranged from 85.5 to 97.5% and 78.4 to 97.4% with cocaine and/or BE confirmation at 8 and 10 µg/L cut-offs, respectively. The Draeger cocaine test-strip with cocaine only confirmation offers a useful option for monitoring the acute intoxication phase of DUID; additionally the BE test-strip with cocaine and/or BE confirmation increases the length of detection of cocaine intake for workplace drug testing, drug court, parole, pain management, drug treatment programs and both the acute cocaine intoxication and cocaine crash/fatigue phase of DUID. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Introduction: Many nursing home residents have cognitive impairment that affects their decision making. In order to identify potential markers of impaired decision making, we investigated the association between a range of nursing home resident characteristics and impaired decision making in a population-based sample., Methods: Participants were 13,013 residents in the 2004 National Nursing Home Survey. We used logistic regression to determine the association between resident characteristics (ie, gender, age, race, mood, recent pain, falls, fractures, or hospitalizations, length of stay, number of activities of daily living (ADL) requiring help, and diagnoses of dementia, anxiety disorders, and depression) and impaired (vs independent) decision making., Results: After controlling for depression and anxiety diagnoses, as well as gender, age, race, and recent hospitalization or pain, characteristics associated with impaired decision making included depressed, sad, or anxious mood ["mild" odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.23-1.58; "severe" OR = 2.69, 95% CI = 2.27-3.20); diagnosed dementia or living on a dementia hall (OR = 5.07, 95% CI = 4.52-5.67); number of ADL requiring assistance (with 5 ADL, OR = 10.69, 95% CI = 6.82-16.75); length of nursing home stay [101-365 days (OR = 1.60, 95% CI = 1.36-1.89); 366 days-2 years (OR = 1.60, 95% CI = 1.34-1.90); >2 years (OR = 2.25, 95% CI = 1.92-2.63)]; and history of falls or fractures in the last 6 months (OR = 1.19, 95% CI = 1.07-1.32)]. Residents reporting pain in the last week were less likely to have impaired decision making (OR = 0.58, 95% CI = 0.52-0.66)., Conclusions: We found several independent markers of impaired decision making in nursing home residents, including depressed, sad, or anxious mood (independent of depression or anxiety diagnosis); dementia; and greater need for ADL assistance. Some of these factors, in particular mood, are modifiable and addressing them may help improve decision making. These markers should be explored further to help identify residents with impaired decision making., (Copyright © 2015 AMDA - The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: DBS are an increasingly common clinical matrix., Methods & Results: Sensitive and specific methods for DBS and venous blood cocaine and metabolite detection by LC-HRMS and 2D GC-MS, respectively, were validated to examine correlation between concentrations following controlled intravenous cocaine administration. Linear ranges from 1 to 200 µg/l were achieved, with acceptable bias and imprecision. Authentic matched specimens' (392 DBS, 97 venous blood) cocaine and benzoylecgonine concentrations were qualitatively similar, but DBS had much greater variability (21.4-105.9 %CV) and were lower than in blood., Conclusion: DBS offer advantages for monitoring cocaine intake; however, differences between capillary and venous blood and DBS concentration variability must be addressed., Competing Interests: Financial & competing interests disclosure This work was supported by the Intramural Research Program (IRP), National Institute on Drug Abuse (NIDA), NIH. JL da Costa received a postdoctoral fellowship from Brazilian National Counsel of Technological and Scientific Development (CNPq) to conduct this research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Background: Synthetic cannabinoids (SC) are a heterogeneous group of compounds developed to probe the endogenous cannabinoid system or as potential therapeutics. Clandestine laboratories subsequently utilized published data to develop SC variations marketed as abusable designer drugs. In the early 2000s, SC became popular as "legal highs" under brand names such as Spice and K2, in part due to their ability to escape detection by standard cannabinoid screening tests. The majority of SC detected in herbal products have greater binding affinity to the cannabinoid CB1 receptor than does Δ(9)-tetrahydrocannabinol (THC), the primary psychoactive compound in the cannabis plant, and greater affinity at the CB1 than the CB2 receptor. In vitro and animal in vivo studies show SC pharmacological effects 2-100 times more potent than THC, including analgesic, anti-seizure, weight-loss, anti-inflammatory, and anti-cancer growth effects. SC produce physiological and psychoactive effects similar to THC, but with greater intensity, resulting in medical and psychiatric emergencies. Human adverse effects include nausea and vomiting, shortness of breath or depressed breathing, hypertension, tachycardia, chest pain, muscle twitches, acute renal failure, anxiety, agitation, psychosis, suicidal ideation, and cognitive impairment. Long-term or residual effects are unknown. Due to these public health consequences, many SC are classified as controlled substances. However, frequent structural modification by clandestine laboratories results in a stream of novel SC that may not be legally controlled or detectable by routine laboratory tests., Methods: We present here a comprehensive review, based on a systematic electronic literature search, of SC epidemiology and pharmacology and their clinical implications., (Published by Elsevier Ireland Ltd.)

Breath has been investigated as an alternative matrix for detecting recent cocaine intake; however, there are no controlled cocaine administration studies that investigated the drug's disposition into breath. Breath was collected from 10 healthy adult cocaine users by asking them to breathe into a SensAbues device for 3 min before and up to 22 h following 25 mg intravenous (IV) cocaine dosing on days 1, 5, and 10, and assayed with a validated liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method to quantify breath cocaine, benzoylecgonine (BE), ecgonine methyl ester (EME), and norcocaine. The assay was linear from 25 to 1,000 pg/filter, extraction efficiencies were 83.6-126%, intra- and inter-assay imprecision was <10.6%, and bias was between -8.5 and 16.8%. No endogenous or exogenous interferences were observed for more than 75 tested. Analytes were generally stable under short-term storage conditions. Ion suppression was less than 46%. Of breath specimens collected after controlled cocaine administration, 2.6% were positive for cocaine (26.1-66 pg/filter, 1-9.5 h), 0.72% BE (83.3-151 pg/filter, 6.5-12.5 h), and 0.72% EME (50-69.1 pg/filter, 6.5-12.5 h); norcocaine was not detected. Methanolic extraction of the devices themselves, after filters were removed, yielded 19.2% positive cocaine tests (25.2-36.4 pg/device, 10 min-22 h) and 4.3% positive BE tests (26.4-93.7 pg/device, 10 min-22 h), explaining differences between the two extraction techniques. These results suggest that the device reflects the drug in oral fluid as well as lung microparticles, while the filter reflects only drug-laden microparticles. A sensitive and specific method for cocaine, BE, EME, and norcocaine quantification in breath was developed and validated. Cocaine in breath identifies recent cocaine ingestion, but its absence does not preclude recent use.

Purpose: : Mismatched placement, according to the American Society of Addiction Medicine's (ASAM) Patient Placement Criteria (PPC), promotes no-shows to treatment; however, little is known about the impact on patients with psychiatrically comorbid substance use disorder., Methods: : In a multisite trial, public-sector treatment-seeking adults (N = 700), following a computer-assisted ASAM PPC-1 structured interview, were blindly scored and randomly assigned to Level-of-Care (LOC)-II (intensive outpatient) or LOC-III (residential) settings. Patients scored as needing LOC-II but assigned to LOC-III were, by definition, "overmatched.", Results: : Among 143 overmatched patients, no-shows were significantly higher in comorbids versus noncomorbids (54% versus 28%; P < 0.01). Among overmatched comorbids, patients who no-showed compared with patients who showed were more likely to be females (70.4% versus 34.8%; P < 0.05), to have anxiety (63% versus 17.4%; P < 0.01), or have supportive family/social environments (81.5% versus 34.8%; P < 0.01)., Conclusions: : The data support the validity of the PPC for matching comorbid patients. Mismatching increases no-show rates in general with undermatching, but it does so in particular with overmatching in patients with comorbid psychiatric symptomatology. Comorbidity interacts with gender, overmatched status, presence of anxiety, and supportive environment as predictors of treatment no-shows (odds ratios = 2.69, P < 0.05; 3.27, P < 0.05; 5.32, P < 0.001; and 3.12, P < 0.05, respectively).

More than half of substance abusers entering addiction treatment report a history of physical or sexual abuse. It is unclear if such a history impacts treatment outcomes. This one-year follow-up study of 700 substance abusers sought to clarify the relationship between lifetime physical and/or sexual abuse and addiction treatment outcome to help address the specific needs of this population. To achieve this goal, baseline characteristics, no-show for treatment status, post-treatment clinical outcomes, and treatment history were studied for subjects with lifetime history of abuse (47.3%) versus without. Abused subjects, predominantly women, were significantly more impaired at baseline on clinical dimensions including family/social severity and psychiatric severity as measured by the Addiction Severity Index (ASI), and general level of functioning. The two groups endorsed different drugs as primary, with the abused group less frequently endorsing heroin and cocaine in favor of alcohol and polydrug use. Abused subjects reported more prior medical and psychiatric treatments. Abuse history was not a predictor of no-show for treatment. Over the 1-year follow-up, lifetime physical and/or sexual abuse was significantly associated with worse psychiatric status and more psychiatric hospitalizations and outpatient treatment despite receiving similar intensive addiction treatment.

In the current context of significant increase of health care costs over the last decades, and in a system of global budget for health care, the concept of cost-effectiveness is one of the leading elements in the political decision making process for a given strategy. Therefore, it is important for the physician to be able to understand and critically interpret cost-effectiveness and cost-utility analyses. This article tries to illustrate comprehensively some of their key concepts. The perspective and the time horizon of the study should be clearly specified. The cost-effectiveness ratio is a synthetic summary based on a micro-costing approach in order to determine the true costs (numerator), and on an effectiveness (utility) assessment which should take into account the preferences of the community (denominator) in order to allow comparisons between interventions of different natures. Advances in the development of decision analysis softwares and in the standardization of the methodology of these studies have yielded considerable improvement in the reliability of their results. Several persisting methodological problems are the scope of current research, such as the discounting rate and the calculation of the minimal sample size required to reach a statistically significant threshold.

Decision analysis is a technique which allows to clarify in an explicit, probabilistic and quantitative way the possible answers to a problem and to help the decision making process. The creation of algorithms, graphically displayed as decision trees in most cases, requires the introduction of quantitative information of two types: probabilities of the events that result from answering to the initial question, and utilities of the possible outcomes of these events. The choice of the optimal solution is based on the calculation of combinations of these data. Although the construction of models can be complex and time-consuming, their practical use has been simplified by the ease and user-friendliness of available softwares. To date, the applications of decision analysis in medicine have focused on cost-effectiveness studies and on the simulation of randomized trials. At the individual level, clinical applications of decision analysis could provide in a near future an interesting tool for the clinician involved in patient management. Even when doubts remain regarding the reliability of the data entered into the model, further sensitivity analysis provide a convenient way to test the validity of the drawn conclusions. This article hopefully offers a simplified and practical approach to basic decision analysis.

The RC2 antibody is frequently used to label mouse radial glial cells in all parts of the nervous system where neuronal migration occurs during embryonic and early postnatal life. The antigen recognized by this antibody still needs to be identified. We have characterized further its localization in vivo, its expression and subcellular localization in vitro, as well as its molecular nature. Histologic investigations of whole mouse embryos reveal an equally intense expression of RC2 immunostaining in radial glial cells in brain and spinal cord and in skeletal muscle. In glial cells cultures, the RC2 antibody recognizes an epitope located on the glial cytoskeleton and identified as an intermediate filament associated protein (IFAP) at the ultrastructural level. RC2 immunostaining in those cells is strongly dependent on the presence of a serum-derived activity. Serum-removal causes a decrease of the staining while adding serum back to the cells induces reexpression of RC2 immunoreactivity. By Western blotting, we find that in intermediate filament (IF) preparations obtained from cultured cerebellar glia, the RC2 antibody recognizes a 295-kDa protein whose expression is also dependent on the presence of serum in culture medium. In developing muscle cells, RC2 immunostaining is observed from the myoblast stage and disappears after complete myotube fusion. Both in vivo and in vitro, staining is first seen as a loose capping around myoblasts nuclei and progressively concentrates into Z-disks in association with the muscle IF protein desmin. The RC2 antibody also recognizes a 295-kDa protein band in muscle tissue protein extracts. Thus, the RC2 antibody recognizes a developmentally regulated cytoskeletal protein that is expressed, like other previously identified IFAPs, by cells of the glial and myogenic lineages and whose expression in vitro seems to be controlled by a signaling mechanism known to modulate astroglial morphology., (Copyright 2000 Wiley-Liss, Inc.)

The polypyrimidine tract-binding protein-associated splicing factor (PSF), which plays an essential role in mammalian spliceosomes, has been found to be expressed by differentiating neurons in developing mouse brain. The sequence of a fragment of mouse PSF was found to be remarkably similar to that of human PSF. Both the expression of PSF mRNA in cortex and cerebellum and PSF immunoreactivity in all brain areas were high during embryonic and early postnatal life and almost disappeared in adult tissue, except in the hippocampus and olfactory bulb where various neuronal populations remained PSF-immunopositive. Double-labeling experiments with anti-PSF antibody and anti-neurofilaments or anti-glial fibrillary acidic protein antibodies on sections of cortex, hippocampus, and cerebellum indicate that PSF is expressed by differentiating neurons but not by astrocytic cells. In vitro, mouse PSF was found to be expressed by differentiating cortical and cerebellar neurons. Radial glia or astrocyte nuclei were not immunopositive; however, oligodendrocytes differentiating in vitro were found to express PSF. The restricted expression of PSF suggests that this splicing factor could be involved in the control of neuronal-specific splicing events occurring at particular stages of neuronal differentiation and maturation.