Heroin Use Onset Among Nonmedical Prescription Opioid Users in the Club Scene

Background—Nonmedical prescription opioid use (NMPOU) is well documented among participants in the club scene, yet prior studies have not examined transition to heroin use. We prospectively examined heroin initiation among a sample of young adults with drug involvement associated with participation in the club scene, to understand factors that influence transition from NMPOU to heroin and to identify opportunities for intervention. Methods—Data were drawn from a randomized trial that enrolled 750 Miami-based club and prescription drug users through respondent driven sampling, and tested the efficacy of assessment interventions in reducing risk. Participants reported current substance use at baseline, 3, 6, and 12 month follow-ups. We examined predictors of heroin initiation among participants reporting NMPOU at baseline, with no lifetime history of heroin use (N=323). Results—The mean age was 25.0 years; 67.5% met DSM-IV criteria for substance dependence. About 1 in 13 participants (7.7%) initiated heroin use at follow-up. In univariable comparisons, frequent LSD use, history of drug overdose, high frequency NMPOU, using oral tampering methods, and endorsing a primary medical source for prescription opioids were associated with greater likelihood of heroin initiation. LSD use, oral tampering, and primary medical source were significant predictors in a Cox regression model. Conclusions—Heroin initiation of 7.7% suggests a high level of vulnerability for transition among young adult NMPO users in the club scene. The importance of oral tampering methods in the trajectory of NMPOU may indicate a need to further examine the role of abuse deterrent formulations in prevention efforts

Sustained Reduction of Diversion and Abuse after Introduction of an Abuse Deterrent Formulation of Extended Release Oxycodone

Background: The development of abuse deterrent formulations is one strategy for reducing prescription opioid misuse and abuse. A putative abuse deterrent formulation of oxycodone extended release (OxyContin®) was introduced in 2010. Early reports demonstrated reduced abuse and diversion, however, an analysis of social media found 32 feasible methods to circumventthe abuse deterrent mechanism. We measured trends of diversion, abuse and street price of OxyContin to assess the durability ofthe initial reduction in abuse. Methods: Data from the Poison Center Program, Drug Diversion Program, Opioid Treatment Program, Survey of Key Informant Patients Program and StreetRx program of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS®) System were used. The average quarterly rates of abuse and diversion for OxyContin were compared from before reformulation to the rate in second quarter 2015. Rates were adjusted for population using US Census data and drug availability. Results: OxyContin abuse and diversion declined significantly each quarter after reformulation and persisted for 5 years. The rate of abuse of other opioid analgesics increased initially and then decreased, but to lesser extent than OxyContin. Abuse through both oral and non-oral routes of self-administration declined following the reformulation. The geometric mean difference in the street price of reformulated OxyContin was 36% lower than the reformulated product in the year after reformulation. Discussion: Despite methods to circumvent the abuse deterrent mechanism, abuse and diversion of OxyContin decreased promptly following the introduction of a crush- and solubility- resistant formulation and continued to decrease over the subsequent 5 years

Systemic pro-inflammatory cytokine status following therapeutic hypothermia in a piglet hypoxia-ischemia model

BACKGROUND: Inflammatory cytokines are implicated in the pathogenesis of perinatal hypoxia-ischemia (HI). The influence of hypothermia (HT) on cytokines after HI is unclear. Our aim was to assess in a piglet asphyxia model, under normothermic (NT) and HT conditions: (i) the evolution of serum cytokines over 48 h and (ii) cerebrospinal fluid (CSF) cytokine levels at 48 h; (iii) serum pro/anti-inflammatory cytokine profile over 48 h and (iv) relation between brain injury measured by magnetic resonance spectroscopy (MRS) and brain TUNEL positive cells with serum cytokines, serum pro/anti-inflammatory cytokines and CSF cytokines. METHODS: Newborn piglets were randomized to NT (n = 5) or HT (n = 6) lasting 2-26 h after HI. Serum samples were obtained 4-6 h before, during and at 6-12 h intervals after HI; CSF was obtained at 48 h. Concentrations of interleukin (IL)-1beta, -4, -6, -8, -10 and TNF-alpha were measured and pro/anti-inflammatory status compared between groups. White matter and thalamic voxel lactate/N-acetyl aspartate (Lac/NAA) (a measure of both oxidative metabolism and neuronal loss) were acquired at baseline, after HI and at 24 and 36 h. RESULTS: Lac/NAA was reduced at 36 h with HT compared to NT (p = 0.013 basal ganglia and p = 0.033 white matter). HT showed lower serum TNF-alpha from baseline to 12 h (p < 0.05). Time-matched (acquired within 5 h of each other) serum cytokine and MRS showed correlations between Lac/NAA and serum IL-1beta and IL-10 (all p < 0.01). The pro/anti-inflammatory ratios IL-1beta/IL-10, IL-6/IL-10, IL-4/IL-10 and IL-8/IL-10 were similar in NT and HT groups until 36 h (24 h for IL-6/IL-10); after this, 36 h pro/anti-inflammatory cytokine ratios in the serum were higher in HT compared to NT (p < 0.05), indicating a pro-inflammatory cytokine surge after rewarming in the HT group. In the CSF at 48 h, IL-8 was lower in the HT group (p < 0.05). At 48 h, CSF TNF-alpha correlated with Lac/NAA (p = 0.02) and CSF IL-8 correlated with white matter TUNEL positive cell death (p = 0.04). CONCLUSIONS: Following cerebral HI, there was a systemic pro-inflammatory surge after rewarming in the HT group, which is counterintuitive to the putative neuroprotective effects of HT. While serum cytokines were variable, elevations in CSF inflammatory cytokines at 48 h were associated with MRS Lac/NAA and white matter cell death

New explanation of the GAMS results on the f0(980)f_0(980) production in the reaction π−p→π0π0n\pi^-p\to \pi^0\pi^0n

The observed alteration of the S-wave $\pi^0\pi^0$ mass spectrum in the reaction $\pi^-p\to\pi^0\pi^0n$ with increasing $-t$, i.e., the disappearance of a dip and the appearance of a peak in the region of the $f_0(980)$ resonance as $-t$ increases, is explained by the contribution of the $\pi^-p\to f_0(980)n$ reaction amplitude with the quantum numbers of the $a_1$ Regge pole in the $t$ channel. It is very interesting that nontrivial evidence for the $a_1$ exchange mechanism in the reaction $\pi^-p\to \pi^0\pi^0n$ follows for the first time from the experiment on an unpolarized target. The explanation of the GAMS results suggested by us is compared with that reported previously. Two ways of experimentally testing these explanations are pointed out.Comment: 20 pages (RevTex), 5 figures (PS), minor typos corrected (in particular in Fig. 4), replaced to match the version accepted in Phys. Rev.

Clinical approach for the classification of congenital uterine malformations

A more objective, accurate and non-invasive estimation of uterine morphology is nowadays feasible based on the use of modern imaging techniques. The validity of the current classification systems in effective categorization of the female genital malformations has been already challenged. A new clinical approach for the classification of uterine anomalies is proposed. Deviation from normal uterine anatomy is the basic characteristic used in analogy to the American Fertility Society classification. The embryological origin of the anomalies is used as a secondary parameter. Uterine anomalies are classified into the following classes: 0, normal uterus; I, dysmorphic uterus; II, septate uterus (absorption defect); III, dysfused uterus (fusion defect); IV, unilateral formed uterus (formation defect); V, aplastic or dysplastic uterus (formation defect); VI, for still unclassified cases. A subdivision of these main classes to further anatomical varieties with clinical significance is also presented. The new proposal has been designed taking into account the experience gained from the use of the currently available classification systems and intending to be as simple as possible, clear enough and accurate as well as open for further development. This proposal could be used as a starting point for a working group of experts in the field

Behavior and Cortisol Levels of Dogs in a Public Animal Shelter, and an Exploration of the Ability of These Measures to Predict Problem Behavior After Adoption

Behavior and plasma cortisol levels were examined in puppies and juvenile/adult dogs admitted to a public animal shelter. A behavioral test was developed to assess the responses of the dogs to novel or threatening conditions. Factor analysis of the behavioral responses of 166 dogs on day 3 in the shelter yielded six factors (locomotor activity, flight, sociability, timidity, solicitation, and wariness) that accounted for 68% of the total variance. Among those dogs remaining in the shelter for 9 days, plasma cortisol levels declined from day 2 to 9. Cortisol levels were weakly related to factor scores. In order to explore the relation of measures in the shelter to later behavior, questionnaires assessing problem behaviors were mailed to new owners of dogs 2 weeks and 6 months following adoption. Among puppies, wariness scores were negatively correlated with behavior problems at 2 weeks and cortisol levels were negatively correlated with behavior problems at 6 months. These results suggest how measures of behavior and endocrine activity obtained in shelters might prove useful for screening dogs for adoption or targeting dogs for behavioral intervention

Behavior and Cortisol Levels of Dogs in a Public Animal Shelter, and an Exploration of the Ability of These Measures to Predict Problem Behavior After Adoption

Behavior and plasma cortisol levels were examined in puppies and juvenile/adult dogs admitted to a public animal shelter. A behavioral test was developed to assess the responses of the dogs to novel or threatening conditions. Factor analysis of the behavioral responses of 166 dogs on day 3 in the shelter yielded six factors (locomotor activity, flight, sociability, timidity, solicitation, and wariness) that accounted for 68% of the total variance. Among those dogs remaining in the shelter for 9 days, plasma cortisol levels declined from day 2 to 9. Cortisol levels were weakly related to factor scores. In order to explore the relation of measures in the shelter to later behavior, questionnaires assessing problem behaviors were mailed to new owners of dogs 2 weeks and 6 months following adoption. Among puppies, wariness scores were negatively correlated with behavior problems at 2 weeks and cortisol levels were negatively correlated with behavior problems at 6 months. These results suggest how measures of behavior and endocrine activity obtained in shelters might prove useful for screening dogs for adoption or targeting dogs for behavioral intervention