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Byline: Hans J. Roethig, MD, PhD, FCP, FFPM (Philip Morris USA, Richmond, Virginia, hans-juergen.roethig@pmusa.com); Shixia Feng, PhD (Philip Morris USA, Richmond, Virginia); Qiwei Liang, PhD (Philip Morris USA, Richmond, Virginia); [...]

This randomized, controlled, forced-switching, open-label, parallel-group study in 100 adult male and female smokers of conventional cigarettes evaluated 8 biomarkers of tobacco smoke exposure. After baseline exposure determinations, adult smokers [...]

Abstract Background High-throughput DNA methylation arrays are likely to accelerate the pace of methylation biomarker discovery for a wide variety of diseases. A potential problem with a standard set of probes measuring the methylation status of CpG sites across the whole genome is that many sites may not show inter-individual methylation variation among the biosamples for the disease outcome being studied. Inclusion of these so-called "non-variable sites" will increase the risk of false discoveries and reduce statistical power to detect biologically relevant methylation markers. Results We propose a method to estimate the proportion of non-variable CpG sites and eliminate those sites from further analyses. Our method is illustrated using data obtained by hybridizing DNA extracted from the peripheral blood mononuclear cells of 311 samples to an array assaying 1505 CpG sites. Results showed that a large proportion of the CpG sites did not show inter-individual variation in methylation. Conclusions Our method resulted in a substantial improvement in association signals between methylation sites and outcome variables while controlling the false discovery rate at the same level.

Purpose A standardized definition for serious opioid overdose has not been clearly established for disease surveillance or assessing the impact of risk mitigation strategies. The purpose of this study was to use medical chart review to clinically validate a claims‐based algorithm to identify serious opioid overdose events. Methods: The algorithm for serious opioid overdose required an opioid poisoning or external cause ICD‐9‐CM code occurring within 1 day of (a) an adverse effect code for serious central nervous system or respiratory depression or (b) a mechanical ventilation or critical care CPT code. The claims coding algorithm identified a sample of 145 individuals 18 years or older among patients that presented to the emergency department of two large hospitals in metropolitan Atlanta, Georgia from January 2014 to August 2015. Claims‐defined cases were evaluated against rigorous clinical definitions for serious opioid overdose using (a) literature‐based criteria for typical clinical manifestations of opioid overdose and/or (b) clinical response to the opioid‐specific reversal agent naloxone. The positive predictive value (PPV) for a serious opioid overdose was calculated as the percentage of clinically confirmed cases (definite or probable). Results: Among 140 evaluable claims‐defined cases, 107 fulfilled clinical criteria for a serious opioid overdose [95 definite and 12 probable; PPV of 76.4% (95% CI 69.4%, 83.5%)]. Among 30 nonconfirmed cases, 20 were polyintoxications involving one or more nonopioid psychoactive agents. Conclusions: An administrative claims coding algorithm for serious opioid overdose had high clinical predictive performance in a medical chart review. [ABSTRACT FROM AUTHOR]

Aims To assess the safety of buprenorphine compared with methadone to treat pregnant women with opioid use disorder. Methods We searched PubMed, Embase and the Cochrane Library from inception to February 2015 for randomized controlled trials (RCT) and observational cohort studies (OBS) that compared buprenorphine with methadone for treating opioid-dependent pregnant women. Two reviewers assessed independently the titles and abstracts of all search results and full texts of potentially eligible studies reporting original data for maternal/fetal/infant death, preterm birth, fetal growth outcomes, fetal/congenital anomalies, fetal/child neurodevelopment and/or maternal adverse events. We ascertained each study's risk of bias using validated instruments and assessed the strength of evidence for each outcome using established methods. We computed effect sizes using random-effects models for each outcome with two or more studies. Results Three RCTs ( n = 223) and 15 cohort OBSs ( n = 1923) met inclusion criteria. In meta-analyses using unadjusted data and methadone as comparator, buprenorphine was associated with lower risk of preterm birth [RCT risk ratio (RR) = 0.40, 95% confidence interval (CI) = 0.18, 0.91; OBS RR = 0.67, 95% CI = 0.50, 0.90], greater birth weight [RCT weighted mean difference (WMD) = 277 g, 95% CI = 104, 450; OBS WMD = 265 g, 95% CI = 196, 335] and larger head circumference [RCT WMD = 0.90 cm, 95% CI = 0.14, 1.66; OBS WMD = 0.68 cm, 95% CI = 0.41, 0.94]. No treatment differences were observed for spontaneous fetal death, fetal/congenital anomalies and other fetal growth measures, although the power to detect such differences may be inadequate due to small sample sizes. Conclusions Moderately strong evidence indicates lower risk of preterm birth, greater birth weight and larger head circumference with buprenorphine treatment of maternal opioid use disorder during pregnancy compared with methadone treatment, and no greater harms. [ABSTRACT FROM AUTHOR]

BACKGROUND: Untreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy. OBJECTIVE: The aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden. METHODS: Pregnant women and their corresponding births during 2005-2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher's exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population. RESULTS: A total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine (N = 176) or methadone (N = 52), no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby's father. CONCLUSIONS: An increased frequency of the selected adverse birth outcomes was not observed with buprenorphine treatment during pregnancy. Twofold increased frequency of preterm birth [2.21 (1.11, 4,41)] and congenital malformations [2.05 (1.08, 3.87)] was observed in the methadone group, which may be partly explained by older average maternal age and differences in other measured and unmeasured confounders. [ABSTRACT FROM AUTHOR]

Background: The Total Exposure Study was a stratified, multi-center, cross-sectional study designed to estimate levels of biomarkers of tobacco-specific and non-specific exposure and of potential harm in U.S. adult current cigarette smokers (≥one manufactured cigarette per day over the last year) and tobacco product non-users (no smoking or use of any nicotine containing products over the last 5 years). The study was designed and sponsored by a tobacco company and implemented by contract research organizations in 2002-2003. Multiple analyses of smoking behavior, demographics, and biomarkers were performed. Study data and banked biospecimens were transferred from the sponsor to the Virginia Tobacco and Health Research Repository in 2010, and then to SRI International in 2012, for independent analysis and dissemination. Methods: We analyzed biomarker distributions overall, and by biospecimen availability, for comparison with existing studies, and to evaluate generalizability to the entire sample. We calculated genome-wide statistical power for a priori hypotheses. We performed clinical chemistries, nucleic acid extractions and genotyping, and report correlation and quality control metrics. Results: Vital signs, clinical chemistries, and laboratory measures of tobacco specific and non-specific toxicants are available from 3585 current cigarette smokers, and 1077 non-users. Peripheral blood mononuclear cells, red blood cells, plasma and 24-h urine biospecimens are available from 3073 participants (2355 smokers and 719 non-users). In multivariate analysis, participants with banked biospecimens were significantly more likely to self-identify as White, to be older, to have increased total nicotine equivalents per cigarette, decreased serum cotinine, and increased forced vital capacity, compared to participants without. Effect sizes were small (Cohen's d-values ≤ 0.11). Power for a priori hypotheses was 57 % in non-Hispanic Black (N = 340), and 96 % in non-Hispanic White (N = 1840), smokers. All DNA samples had genotype completion rates ≥97.5 %; 68 % of RNA samples yielded RIN scores ≥6.0. Conclusions: Total Exposure Study clinical and laboratory assessments and biospecimens comprise a unique resource for cigarette smoke health effects research. The Total Exposure Study Analysis Consortium seeks to perform molecular studies in multiple domains and will share data and analytic results in public repositories and the peer-reviewed literature. Data and banked biospecimens are available for independent or collaborative research. [ABSTRACT FROM AUTHOR]

Copyright of Archiv für Kriminologie is the property of Schmidt-Roemhild Verlag and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archiv für Kriminologie is the property of Schmidt-Roemhild Verlag and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archiv für Kriminologie is the property of Schmidt-Roemhild Verlag and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archiv für Kriminologie is the property of Schmidt-Roemhild Verlag and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease with associated systemic effects. Objective: To use gene expression microarrays in peripheral blood leukocytes of current and former cigarette smokers to identify differences associated with COPD. Materials and methods: Random forest modelling and a split-sample case-control approach were used to identify candidate predictors. Results: We identified 1013 genes and one smoking exposure variable that differentiated current and former smokers with or without COPD. This predictor set was reduced to a nine-gene classifier ( IL6R, CCR2, PPP2CB, RASSF2, WTAP, DNTTIP2, GDAP1, LIPE and RPL14). Conclusion: These gene expression profiles represent potential biomarkers for COPD and may help increase mechanistic understanding of the disease. [ABSTRACT FROM AUTHOR]

Although cigarette smoking is recognized as the most important cause of chronic obstructive pulmonary disease (COPD), the pathophysiological mechanisms underlying the lung function decline are not well understood. Using off-line strong cation exchange fractionation with RP-LC-ESI-MS/MS and robust database searching, 1758 tryptic peptides were identified in plasma samples from cigarette smokers. Using two statistical approaches, 30 peptides were identified to be associated with the annualized rate of lung function decline over 5 years among smokers with COPD characterized as having rapid ( n = 18) or slow ( n = 18) decline and 18 smokers without COPD. The identified peptides belong to proteins that are involved in the complement or coagulation systems or have antiprotease or metabolic functions. This research demonstrates the utility of proteomic profiling to improve the understanding of molecular mechanisms involved in cigarette smoking-related COPD by identifying plasma proteins that correlate with decline in lung function. [ABSTRACT FROM AUTHOR]

Background: High-throughput DNA methylation arrays are likely to accelerate the pace of methylation biomarker discovery for a wide variety of diseases. A potential problem with a standard set of probes measuring the methylation status of CpG sites across the whole genome is that many sites may not show inter-individual methylation variation among the biosamples for the disease outcome being studied. Inclusion of these so-called "non-variable sites" will increase the risk of false discoveries and reduce statistical power to detect biologically relevant methylation markers. Results: We propose a method to estimate the proportion of non-variable CpG sites and eliminate those sites from further analyses. Our method is illustrated using data obtained by hybridizing DNA extracted from the peripheral blood mononuclear cells of 311 samples to an array assaying 1505 CpG sites. Results showed that a large proportion of the CpG sites did not show inter-individual variation in methylation. Conclusions: Our method resulted in a substantial improvement in association signals between methylation sites and outcome variables while controlling the false discovery rate at the same level. [ABSTRACT FROM AUTHOR]

The authors discuss a review article on whether irreversible loss of brain function (ILBF) is a reliable sign of death. They believe that describing ILBF as the biological end of the life of a human being does not tally with the thanatological definition of biological death as the death of the last cell. Several definitions of death from a scientific-medical viewpoint are mentioned.

Non-natural deaths associated with sexual activity may occur either with or without the involvement of other persons. The present study provides an overview of cases of non-natural death related to sexual activities as well as recommendations of how to handle these cases and to identify potentially dangerous pleasure-enhancing techniques. This medicolegal, postmortem, retrospective, and prospective study is based on data of autopsies performed at the Institute of Legal Medicine at University Hospital, Goethe University, Frankfurt, Germany. Identification of circumstances, sexual practices, and gender distribution of cases of non-natural death in this context. Between 1993 and 2017 (25 years), 16,437 medicolegal autopsies were performed, of which 74 cases (43 males, 31 females) of non-natural death were found to relate to sexual activities (0.45%). One female and 21 males had died in the course of autoerotic practices (group I, n = 22). Nine males and 14 females had performed sexual practices with mutual consent (group II, n = 23), and 13 males and 16 females without mutual consent (group III, n = 29). The average age in group I was 45.4 years; in group II, 40.6 years; and in group III, 39.2 years. Most of the deceased were found in their own apartments. Forms of stimulation included vaginal, anal, and oral intercourse; insertion of foreign bodies; use of chemical substances; and tools for respiratory depression/hypoxia. Three cases of death occurred during sexual activities involving bondage and discipline, sadism, and masochism (BDSM). Death due to strangulation was the main cause in group I, whereas intoxications were predominant in group II. Sharp force (eg, knife) was mainly responsible for death in group III. Anogenital injuries were documented in all groups in approximately equal percentages. The cases presented show a high variety of circumstances in which non-natural death connected to sexual activity may occur. This study presents a large postmortem collection of non-natural death cases with associated sexual activity. As the main limiting factor, it must be stated that mutual consent for a sexual practice or consumption of substances was presumed based on the information provided and a lack of evidence against this assumption. In cases of death associated with sexual activity, medical staff should perform thorough unbiased examinations and documentations. Strangulation and the consumption of stimulants should be classified as life-threatening, pleasure-enhancing techniques. Patients and young people should be informed about these risks. Bunzel L, Koelzer SC, Zedler B, et al. Non-Natural Death Associated with Sexual Activity: Results of a 25-Year Medicolegal Postmortem Study. J Sex Med 2019;16:1547–1556. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The potential of dual energy computed tomography (DECT) for the analysis of gallstone compounds was investigated. The main goal was to find parameters, that can reliably define high percentage (>70%) cholesterol stones without calcium components. Materials and methods: 35 gallstones were analyzed with DECT using a phantom model. Stone samples were put into specimen containers filled with formalin. Containers were put into a water-filled cylindrical acrylic glass phantom. DECT scans were performed using a tube voltage/current of 140kV/83mAs (tube A) and 80kV/340mAs (tube B). ROI-measurements to determine CT attenuation of each sector of the stones that had different appearance on the CT images were performed. Finally, semi-quantitative infrared spectroscopy (FTIR) of these sectors was performed for chemical analysis. Results: ROI-measurements were performed in 45 different sectors in 35 gallstones. Sectors containing >70% of cholesterol and no calcium component (n =20) on FTIR could be identified with 95% sensitivity and 100% specificity on DECT. These sectors showed typical attenuation of −8±4HU at 80kV and +22±3HU at 140kV. Even the presence of a small calcium component (<10%) hindered the reliable identification of cholesterol components as such. Conclusion: Dual energy CT allows for reliable identification of gallstones containing a high percentage of cholesterol and no calcium component in this pre-clinical phantom model. Results from in vivo or anthropomorphic phantom trials will have to confirm these results. This may enable the identification of patients eligible for non-surgical treatment options in the future. [Copyright &y& Elsevier]