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Alternative matrices, especially exhaled breath (EB), have gained increasing attention for a few years. To interpret toxicological findings, knowledge on the toxicokinetic (TK) properties of a substance in EB is indispensable. While such data are already accessible for various drugs (e.g. Δ9-tetrahydrocannabinol), they are still not available for new psychoactive substances, particularly synthetic cannabinoids (SCs). As SCs raise a high public health concern, the aim of this study was to assess these data in future TK studies in pigs. For this purpose, an in vitro sampling technique of EB was initially developed, which is prospectively applied to anesthetized and ventilated pigs for the detection of SCs in a controlled and reproducible manner as exemplified by cumyl-5F-P7AICA. Furthermore, a method for the qualitative and quantitative detection of cumyl-5F-P7AICA in EB using glass fiber filters (GFFs) was established and fully validated. Therefore, cumyl-5F-P7AICA (0.5 mg/mL in ethanol absolute) was initially nebulized using a ventilation machine and a breathing tube, as they are also used in surgeries. The aerosol was delivered into a simulated pig lung. To collect EB, a pump was connected to that part of the breathing tube, which contains EB (expiratory limb), and sampling was performed repeatedly (n = 6) for 15 min (2 l EB/min) each using GFF. For extraction of the substance, the GFFs were macerated with acetone and the remaining experimental components were rinsed with ethanol. After sample preparation, the extracts were analyzed by liquid chromatography tandem mass spectrometry. In the complete experimental setup, about 40% of the initially nebulized cumyl-5F-P7AICA dose was found, with 3.6 ± 1.3% being detected in the GFF. Regarding the comparably high loss of substance, the open ventilation system and a conceivable adsorption of the SC in the ventilator have to be considered. However, the herein introduced approach is promising to determine the TK properties of cumyl-5F-P7AICA in EB., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Electronic cigarette liquids (e-liquids) can contain a variety of chemicals to impart flavors, smells and pharmacological effects. Surveillance studies have identified hundreds of chemicals used in e-liquids that have known health and safety implications. Ethyl acetate has been identified as a common constituent of e-liquids. Ethyl acetate is rapidly hydrolyzed to ethanol in vivo. Animal studies have demonstrated that inhaling >2,000 mg/L ethyl acetate can lead to the accumulation of ethanol in the blood at concentrations >1,000 mg/L, or 0.10%. A "Heisenberg" e-liquid was submitted to the Laboratory for Forensic Toxicology Research for analysis after a random workplace drug test resulted in a breath test result of 0.019% for a safety-sensitive position employee. Analysis of this sample resulted in the detection of 1,488 ± 6 mg/L ethyl acetate. The evaluation of purchased "Heisenberg" e-liquids determined that these products contain ethyl acetate. The identification of ethyl acetate in e-liquids demonstrates poor regulatory oversight and enforcement that potentially has consequences for breath ethanol testing and interpretations. The accumulation of ethanol in the breath from the ingestion/inhalation of ethyl acetate from an e-liquid used prior to a breath test may contribute to the detection of ethanol., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Legal professionals and others have suggested that vaping electronic cigarettes (e-cigs) prior to or during ethanol breath testing may produce false positives. Preliminary breath tests (PBTs) and evidentiary breath tests (EBTs) measure ethanol in exhaled breath and standardized field sobriety tests (SFSTs) are used to assess impairment. Ethanol has been identified in e-cig liquids (e-liquids). Presented are a series of experiments designed to determine the mechanics of vaping ethanol using an e-cig and the effects of vaping ethanol on the SFSTs and breath tests used by law enforcement officers (LEO). Twelve participants (five females, age: 21-32 and seven males, age: 21-55), vaped either one or ten puffs of an e-liquid (0% or 20% ethanol). LEOs assessed impairment using SFSTs (12 and 42 min), PBTs (<1, 27, 32, 37 and 57 min) and EBTs (2, 29, 34, 39 and 59 min) post-vaping. A self-assessment test was administered post-vaping (22 and 52 min). Baseline responses for all measures were collected prior to vaping. Results demonstrated that ethanol in the e-liquids was aerosolized by e-cigs and produced particles that could reach the deep lung tissue based on mean-mass diameter. Ethanol was detected by PBT <3 min after participants vaped one (0.007-0.030 g/210 L) or ten puffs (013-0.074 g/210 L) of a 20% ethanol e-liquid. Ethanol was not detected by PBT at any subsequent time point. Ethanol was not detected by the EBT under any condition. Impairment was not indicated by the SFST. Some subjective effects were reported, but few statistically significant differences between conditions were indicated. A wait period prior to ethanol breath testing is not always mandated, depending on jurisdiction, or observed in all applications, such as workplace testing. The results demonstrate that a wait period must be employed to prevent vaping-related false-positive breath ethanol results., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: COVID-19 is a highly contagious respiratory disease that can be transmitted through human exhaled breath. It has caused immense loss and has challenged the healthcare sector. It has affected the economy of countries and thereby affected numerous sectors. Analysis of human breath samples is an attractive strategy for rapid diagnosis of COVID-19 by monitoring breath biomarkers., Content: Breath collection is a noninvasive process. Various technologies are employed for detection of breath biomarkers like mass spectrometry, biosensors, artificial learning, and machine learning. These tools have low turnaround time, robustness, and provide onsite results. Also, MS-based approaches are promising tools with high speed, specificity, sensitivity, reproducibility, and broader coverage, as well as its coupling with various chromatographic separation techniques providing better clinical and biochemical understanding of COVID-19 using breath samples., Summary: Herein, we have tried to review the MS-based approaches as well as other techniques used for the analysis of breath samples for COVID-19 diagnosis. We have also highlighted the different breath analyzers being developed for COVID-19 detection., Competing Interests: Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. The authors declare no conflict of interest. Disclosures and/or potential conflicts of interest: Employment or Leadership: None declared. Consultant or Advisory Role: None declared. Stock Ownership: None declared. Honoraria: None declared. Research Funding: This work was supported by University Grants Commission, New Delhi, Fellowship no. 582/(CSIR-UGC NET JUNE 2018). Expert Testimony: None declared. Patents: None declared., (© American Association for Clinical Chemistry 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In this work, 114 volunteers were dosed with 80-proof liquor to produce peak blood-alcohol concentration (BAC) or breath-alcohol concentration (BrAC) of 0.040-0.080 g/100 mL blood or g/210 L breath. This was followed by a 30 minute deprivation period before simultaneous blood and breath samples were collected and the alcohol concentration quantified. BAC was determined by gas chromatography with flame ionization detection and BrAC by a dual-sensor Intox EC/IR II instrument. Paired Student t-tests showed that differences between paired blood- and breath-alcohol results differed significantly. Results from these two measurement methods are highly correlated and, on average, measured BAC was 11.3% greater than BrAC. There were 10 instances of BrAC being greater than the corresponding BAC, and the average difference between these two values was 0.0059 g/100 mL. Agreement plots of coupled BAC and BrAC revealed a mean bias of 0.00754 g/100 mL and 95% limits of agreement (LOA) at -0.00705 and 0.0221 g/100 mL. Once BrAC values were truncated to the hundredths place as required by Wisconsin state statute, only three participants had greater BrAC than corresponding BAC, with an average difference between these values of 0.008 g/100 mL. Agreement plots with truncated BrAC values gave a mean bias of 0.0120 g/100 mL and 95% LOA at -0.00344 and 0.0275 g/100 mL. Data showed that typically, blood samples had greater alcohol concentrations than corresponding breath values. Differences were exacerbated by Wisconsin's statutory requirement that reported breath alcohol measurements be truncated to the hundredths place, whereas blood has no corresponding mandate., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Caenorhabditis elegans contains two pathways for propionate metabolism, the vitamin B12-dependent and shunt pathways, which are similar to those in humans. In this study, we monitored the changes in propionate metabolism in the whole body of C. elegans using novel 13CO2 gas analysis. We measured the increase in 13CO2 excreted in the air after administering [1-13C]-labeled propionate ([13C]propionate) to the worms. The 13CO2 generated from [13C]propionate in C. elegans increased in a dose-dependent manner, reaching a maximum at 48 h. Enhanced expression of propionate metabolism-related genes was observed after administration of propionate. Knockdown of mmcm-1, which encodes the rate-limiting enzyme of the propionate metabolism, using RNAi reduced 13CO2 excretion. Thus, 13CO2 gas analysis could be confirmed 13CO2 excretion associated with changes in the metabolism of [13C]propionate in nematodes. This analysis can contribute to further understanding of the physiological effects of short-chain fatty acids., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Background: Starkly highlighted by the current COVID-19 pandemic, infectious diseases continue to have an outsized impact on human health worldwide. Diagnostic testing for infection can be challenging due to resource limitations, time constraints, or shortcomings in the accuracy of existing diagnostics. Rapid, simple diagnostics are highly desirable. There is increasing interest in the development of diagnostics that use exhaled breath analysis as a convenient and safe diagnostic method, as breath sampling is noninvasive, secure, and easy to perform. Volatile organic compounds (VOCs) present in exhaled breath reflect the fingerprint of the underlying metabolic and biophysical processes during disease., Content: In this review, we overview the major biomarkers present in exhaled breath in infectious diseases. We outline the promising recent advances in breath-based diagnosis of respiratory infections, including those caused by influenza virus, SARS-CoV-2, Mycobacterium tuberculosis, Pseudomonas aeruginosa, and Aspergillus fumigatus. In addition, we review the current landscape of diagnosis of 2 other globally important infections: Helicobacter pylori gastrointestinal infection and malaria., Summary: Characteristic and reproducible breath VOCs are associated with several infectious diseases, suggesting breath analysis as a promising strategy for diagnostic development. Ongoing challenges include poor standardization of breath collection and analysis and lack of validation studies. Further research is required to expand the applicability of breath analysis to clinical settings., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Study Objectives: The role of the circadian clock in regulating blood/breath alcohol levels after consuming alcohol is uncertain. Our goal was to evaluate the degree to which the circadian system regulates breath alcohol concentration (BrAC) pharmacokinetic parameters., Methods: Twenty healthy adults aged 21-30 years took part in a 4-day laboratory study. A 40-h constant routine procedure was used to assess circadian rhythms. Every 4 h, participants were given a fixed oral dose of alcohol with breathalyzer measurements taken every 5 min to construct BrAC curves. Sinusoidal models were used to test for circadian variation of the peak BrAC, the time to reach peak BrAC, the absorption rate, the elimination rate, and the time for BrAC to return to zero after alcohol was ingested., Results: A significant circadian rhythm was detected for group-averaged peak BrAC values and the time for BrAC to return to zero, but not other BrAC variables. Peak BrAC values were lowest in the evening near the peak of the core body temperature rhythm and nadir of the salivary cortisol rhythm. Peak BrAC values increased during the night and reached their highest levels in the morning and afternoon. The time needed for BrAC to return to zero was also longest in the late morning and afternoon., Conclusion: The circadian system modulates some BrAC pharmacokinetic parameters. In normally entrained individuals, taking the same oral dose of alcohol at different times of day can result in different BrAC responses. These findings have potential implications for alcohol-related accidents and alcohol toxicity., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Cyclic nigerosylnigerose (CNN) is a cyclic tetrasaccharide with properties distinct from those of other conventional cyclodextrins. We investigated the relative available energy of CNN in healthy humans. CNN digestibility was determined using brush border membrane vesicles from the small intestines of rats. CNN was not hydrolyzed by rat intestinal enzymes. To investigate breath hydrogen excretion, 13 human subjects were included in a double-blind cross-over, randomized, placebo-controlled study. The effects of CNN on hydrogen excretion were compared with those of a typical nondigestible, fermentable fructooligosaccharide (FOS). In the study participants, hydrogen excretion hardly increased upon CNN and was remarkably lower than for FOS. The available energy value was determined using the fermentability based on breath hydrogen excretion and was evaluated as 0 kcal/g for CNN. CNN was hardly metabolized and hence may be used as a low-energy dietary fiber., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Background: In recent decades there has been growing interest in the use of volatile organic compounds (VOCs) in exhaled breath as biomarkers for the diagnosis of multiple variants of cancer. This review aimed to evaluate the diagnostic accuracy and current status of VOC analysis in exhaled breath for the detection of cancer in the digestive tract., Methods: PubMed and the Cochrane Library database were searched for VOC analysis studies, in which exhaled air was used to detect gastro-oesophageal, liver, pancreatic, and intestinal cancer in humans, Quality assessment was performed using the QUADAS-2 criteria. Data on diagnostic performance, VOCs with discriminative power, and methodological information were extracted from the included articles., Results: Twenty-three articles were included (gastro-oesophageal cancer n = 14, liver cancer n = 1, pancreatic cancer n = 2, colorectal cancer n = 6). Methodological issues included different modalities of patient preparation and sampling and platform used. The sensitivity and specificity of VOC analysis ranged from 66.7 to 100 per cent and from 48.1 to 97.9 per cent respectively. Owing to heterogeneity of the studies, no pooling of the results could be performed. Of the VOCs found, 32 were identified in more than one study. Nineteen were reported as cancer type-specific, whereas 13 were found in different cancer types. Overall, decanal, nonanal, and acetone were the most frequently identified., Conclusion: The literature on VOC analysis has documented a lack of standardization in study designs. Heterogeneity between the studies and insufficient validation of the results make interpretation of the outcomes challenging. To reach clinical applicability, future studies on breath analysis should provide an accurate description of the methodology and validate their findings., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Introduction: Helicobacter pylori (H. pylori) infection affects about half of the world's population and can lead to multiple complications if left untreated. Testing for H. pylori infection in appropriate patients with prompt treatment followed by the testing of eradication is the standard of care in the United States. Active Duty Service members (ADSMs) in the U.S. military are a unique patient population that may be at higher risk for acquiring H. pylori infection given frequent deployments to developing countries. Noninvasive diagnostic strategies include the urea breath test, the stool antigen test, and serologic testing, which include H. pylori immunoglobulin M (IgM), immunoglobulin A (IgA), and immunoglobulin G (IgG) antibodies. Among noninvasive methods, the least sensitive is serology, and although there is clinical utility in testing for H. pylori IgG antibodies, H. pylori IgA or IgM antibodies have limited clinical utility. Despite this, H. pylori IgA and IgM antibodies are still widely ordered across the Military Health System., Materials and Methods: In order to determine how frequently this testing is being ordered and the associated cost, we conducted a retrospective cross-sectional study of H. pylori serologic testing utilization in the MHS from October 2015 to September 2018 in adult patients using the MHS Data Repository. All H. pylori IgM, IgA, and IgG antibodies, H. pylori stool antigen tests, and H. pylori urea breath tests were queried during this time period across all ADSMs, retirees, and ADSM dependents for all adults. Cost information was obtained from LabCorp, and the institutional price used for cost analysis was the same throughout all military treatment facilities in the Department of Defense (DOD)., Results: We discovered that over a 3-yr period, 1,916 H. pylori IgA and 2,492 IgM antibodies were ordered. In total, the DOD spent close to $400,000 on antibody-based testing for H. pylori not accounting for indirect associated costs like personnel, supplies, repeat testing, as well as the costs of delayed diagnosis and associated complications., Conclusion: H. pylori IgM and IgA have limited clinical utility, are inaccurate, and are costly to maintain, especially when more accurate alternative tests are available. Based on our analysis, we strongly recommend the removal of the H. pylori IgA and IgM serologic tests throughout the DOD in order to improve the efficiency and quality of care for patients suspected of having an H. pylori infection. Further research is needed to determine how these tests are ordered, how providers are responding to the results of the serologic tests, and if noninvasive testing is being ordered appropriately., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2020. This work is written by US Government employees and is in the public domain in the US.)

Objectives: To assess the concordance and performance characteristics of Helicobacter pylori laboratory tests compared with histopathology and to propose algorithms for the diagnosis of H pylori that minimize diagnostic error., Methods: H pylori diagnostics were reviewed from a 12-year period within a health system (2,560 cases). Analyses were performed to adjust diagnostic performance based on treatment and consensus histopathologic diagnoses among pathologists. Markers of access to care, including test cancellation frequency and turnaround time, were assessed. Costs and performance of candidate noninvasive testing algorithms were modeled as a function of disease prevalence., Results: Serum H pylori IgG demonstrated a higher sensitivity (0.94) than urea breath and stool antigen tests (0.64 and 0.61, respectively). Evidence of an advantage in access to care for serology included a lower cancellation rate. Interobserver variability was higher (κ = 0.34) among pathologists for cases with a discordant laboratory test than concordant cases (κ = 0.56). A model testing algorithm utilizing serology for first-time diagnoses minimizes diagnostic error., Conclusions: Although H pylori serology has modestly lower specificity than other noninvasive tests, the superior sensitivity and negative predictive value in our population support its use as a noninvasive test to rule out H pylori infection. Reflexive testing with positive serology followed by either stool antigen or urea breath test may optimize diagnostic accuracy in low-prevalence populations., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The DETECT algorithm has been developed to identify SSc patients at risk for pulmonary arterial hypertension (PAH) yielding high sensitivity but low specificity, and positive predictive value. We tested whether cardiopulmonary exercise testing (CPET) could improve the performance of the DETECT screening strategy., Methods: Consecutive SSc patients over a 30-month period were screened with the DETECT algorithm and positive subjects were referred for CPET before the execution of right-heart catheterization. The predictive performance of CPET on top of DETECT was evaluated and internally validated via bootstrap replicates., Results: Out of 314 patients, 96 satisfied the DETECT application criteria and 54 were positive. PAH was ascertained in 17 (31.5%) and pre-capillary pulmonary hypertension in 23 (42.6%) patients. Within CPET variables, the slope of the minute ventilation to carbon dioxide production relationship (VE/VCO2 slope) had the best performance to predict PAH at right-heart catheterization [median (interquartile range) of specificity 0.778 (0.714-0.846), positive predictive value 0.636 (0.556-0.750)]; exploratory analysis on pre-capillary yielded a specificity of 0.714 (0.636-0.8) and positive predictive value of 0.714 (0.636-0.8)., Conclusion: In association with the DETECT algorithm, CPET may be considered as a useful tool in the workup of SSc-related pulmonary hypertension. The sequential determination of the VE/VCO2 slope in DETECT-positive subjects may reduce the number of unnecessary invasive procedures without any loss in the capability to capture PAH. This strategy had also a remarkable performance in highlighting the presence of pre-capillary pulmonary hypertension., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Cannabinoid analyses generally included, until recently, the primary psychoactive cannabis compound, Δ9-tetrahydrocannabinol (THC), and/or its inactive metabolite, 11-nor-9-carboxy-THC, in blood, plasma, and urine. Technological advances revolutionized the analyses of major and minor phytocannabinoids in diverse biological fluids and tissues. An extensive literature search was conducted in PubMed for articles on cannabinoid analyses from 2000 through 2019. References in acquired manuscripts were also searched for additional articles., Content: This article summarizes analytical methodologies for identification and quantification of multiple phytocannabinoids (including THC, cannabidiol, cannabigerol, and cannabichromene) and their precursors and/or metabolites in blood, plasma, serum, urine, oral fluid, hair, breath, sweat, dried blood spots, postmortem matrices, breast milk, meconium, and umbilical cord since the year 2000. Tables of nearly 200 studies outline parameters including analytes, specimen volume, instrumentation, and limits of quantification. Important diagnostic and interpretative challenges of cannabinoid analyses are also described. Medicalization and legalization of cannabis and the 2018 Agricultural Improvement Act increased demand for cannabinoid analyses for therapeutic drug monitoring, emergency toxicology, workplace and pain-management drug testing programs, and clinical and forensic toxicology applications. This demand is expected to intensify in the near future, with advances in instrumentation performance, increasing LC-MS/MS availability in clinical and forensic toxicology laboratories, and the ever-expanding knowledge of the potential therapeutic use and toxicity of phytocannabinoids., Summary: Cannabinoid analyses and data interpretation are complex; however, major and minor phytocannabinoid detection windows and expected concentration ranges in diverse biological matrices improve the interpretation of cannabinoid test results., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: To evaluate the efficacy and monitoring capabilities of a breathalyser-based eHealth system for patients with alcohol use disorder (AUD) and to investigate the quality and validity of timeline follow-back (TLFB) as outcome measure in clinical trials and treatment., Methods: Patients (n = 115) were recruited to clinical trials from a 12-step aftercare programme (12S-ABS) and from hospital care with abstinence (HC-ABS) or controlled drinking (HC-CDR) as goal and randomly divided into an eHealth and a control group. The effect of the eHealth system was analysed with TLFB-derived primary outcomes-change in number of abstinent days (AbsDay) and heavy drinking days (HDDs) compared to baseline-and phosphatidyl ethanol (PEth) measurements. Validity and quality of TLFB were evaluated by comparison with breath alcohol content (BrAC) and eHealth digital biomarkers (DBs): Addiction Monitoring Index (AMI) and Maximum Time Between Tests (MTBT). TLFB reports were compared to eHealth data regarding reported abstinence., Results: The primary outcome (TLFB) showed no significant difference between eHealth and control groups, but PEth did show a significant difference especially at months 2 and 3. Self-reported daily abstinence suffered from severe quality issues: of the 28-day TLFB reports showing full abstinence eHealth data falsified 34% (BrAC measurements), 39% (MTBT), 54% (AMI) and 68% (BrAC/MTBT/AMI). 12S-ABS and HC-ABS patients showed severe under-reporting., Conclusions: No effect of the eHealth system was measured with TLFB, but a small positive effect was measured with PEth. The eHealth system revealed severe quality problems with TLFB, especially regarding abstinence-should measurement-based eHealth data replace TLFB as outcome measure for AUD?, (© The Author(s) 2020. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background: Cannabis use results in impaired driving and an increased risk of motor vehicle crashes. Cannabinoid concentrations in blood and other matrices can remain high long after use, prohibiting the differentiation between acute and chronic exposure. Exhaled breath has been proposed as an alternative matrix in which concentrations may more closely correspond to the window of impairment; however, efficient capture and analytically sensitive detection methods are required for measurement., Methods: Timed blood and breath samples were collected from 20 volunteers before and after controlled administration of smoked cannabis. Cannabinoid concentrations were measured using LC-MS/MS to determine release kinetics and correlation between the 2 matrices., Results: Δ9-Tetrahydrocannabinol (THC) was detected in exhaled breath for all individuals at baseline through 3 h after cannabis use. THC concentrations in breath were highest at the 15-min timepoint (median = 17.8 pg/L) and declined to <5% of this concentration in all participants 3 h after smoking. The decay curve kinetics observed for blood and breath were highly correlated within individuals and across the population., Conclusions: THC can be reliably detected throughout the presumed 3-h impairment window following controlled administration of smoked cannabis. The findings support breath THC concentrations as representing a physiological process and are correlated to blood concentrations, albeit with a shorter window of detection., (© 2019 American Association for Clinical Chemistry.)

Introduction: "Dual use" refers to the concurrent use of tobacco cigarettes (smoking) and electronic cigarettes (e-cigarettes; vaping). Although dual use is common among e-cigarette users, there is little evidence regarding biomarkers of exposure among dual users and how these change under different conditions of product use., Methods: A nonblinded within-subjects crossover experiment was conducted with adult daily dual users (n = 48) in Ontario, Canada. Participants completed three consecutive 7-day periods in which the use of tobacco cigarettes and e-cigarettes was experimentally manipulated, resulting in four study conditions: Dual use, Tobacco cigarette use, E-cigarette use, and No product use. Repeated measures models were used to examine changes in product use and biomarkers of exposure., Results: Compared to dual use, cotinine remained stable when participants exclusively smoked (p = .524), but significantly decreased when they exclusively vaped (p = .027), despite significant increases in e-cigarette consumption (p = .001). Levels of biomarkers of exposure to toxicants, including carbon monoxide (CO), 1-hydroxypyrene (1-HOP), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), were significantly lower when participants exclusively vaped than when they engaged in dual use (CO = -41%, p < .001; 1-HOP = -31%, p = .025; NNAL = -30%, p = .017). Similar findings were observed among participants abstaining from both products as compared to dual use (CO: -26%, p < .001; 1-HOP = -14% [ns]; NNAL = -35%, p = .016). In contrast, levels of biomarkers of exposure increased when participants exclusively smoked as compared to dual use (CO = +21%, p = .029; 1-HOP = +23%, p = .048; NNAL = +8% [ns])., Conclusions: Although dual use may reduce exposure to tobacco smoke constituents to some extent, abstaining from smoking is the most effective way to reduce such exposure., Implications: Public health authorities should clearly communicate the relative risk of e-cigarettes and tobacco cigarettes to the general public, focusing on two salient points: (1) e-cigarettes are not harmless, but they are less harmful than tobacco cigarettes; and (2) using e-cigarettes while smoking may not necessarily reduce health risks; therefore, consumers should stop smoking completely to maximize potential health benefits., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We aimed to evaluate in an Algerian pediatric population the diagnostic performances of the IDEIA HpStAR noninvasive stool antigen test (Oxoid, Cambridge, UK) to detect Helicobacter pylori infection before and after eradication therapy. A prospective study including 158 symptomatic Algerian children was conducted. Patients were initially diagnosed with invasive (culture, histology, and rapid urease test) and noninvasive tests (urea breath test and IDEIA HpStAR test). Infected patients were treated, and 101 were controlled after treatment with two invasive (culture and histology) and two noninvasive tests (urea breath test and IDEIA HpStAR test). In Algerian children, the IDEIA HpStAR test showed good performances for initial detection of H. pylori infection and also for subsequent control of eradication treatment. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of IDEIA HpStAR test before treatment were 93.6%, 100%, 100%, 87.3%, and 96%, respectively, and those after treatment were 100, 92.8, 78.6, 100, and 94.2%, respectively., (© The Author(s) [2018]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: Alcohol consumption is a modifiable and plausible risk factor for age-related cognitive decline but more longitudinal studies investigating the association are needed. Our aims were to estimate associations of adult-life alcohol consumption and consumption patterns with age-related cognitive decline., Methods: We investigated the associations of self-reported adult-life weekly alcohol consumption and weekly extreme binge drinking (≥10 units on the same occasion) with changes in test scores on an identical validated test of intelligence completed in early adulthood and late midlife in 2498 Danish men from the Lifestyle and Cognition Follow-up study 2015. Analyses were adjusted for year of birth, retest interval, baseline IQ, education and smoking., Results: Men with adult-life alcohol consumption of more than 28 units/week had a larger decline in IQ scores from early adulthood to late midlife than men consuming 1-14 units/week (B29-35units/week = -3.6; P < 0.001). Likewise, a 1-year increase in weekly extreme binge drinking was associated with a 0.12-point decline in IQ scores (P < 0.001). Weekly extreme binge drinking explained more variance in IQ changes than average weekly consumption. In analyses including mutual adjustment of weekly extreme binge drinking and average weekly alcohol consumption, the estimated IQ decline associated with extreme binge drinking was largely unaffected, whereas the association with weekly alcohol consumption became non-significant., Conclusions: Adult-life heavy alcohol consumption and extreme binge drinking appear to be associated with larger cognitive decline in men. Moreover, extreme binge drinking may be more important than weekly alcohol consumption in relation to cognitive decline., (© The Author(s) 2019. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Aims: The study documented elimination characteristics of three phosphatidylethanol (PEth) homologs in serially collected blood samples from 47 heavy drinkers during ~2 weeks of alcohol detoxification at hospital., Methods: Venous whole blood and urine samples were collected every 1-2 days during treatment. Concentrations of PEth, and of urinary ethyl glucuronide (EtG) and ethyl sulfate (EtS) to detect relapse drinking, were measured using liquid chromatography-tandem mass spectrometry., Results: When included in the study, negative or decreasing breath ethanol concentrations demonstrated that the patients were in the elimination phase. The EtG and EtS measurements further confirmed alcohol abstinence during the study, with three exceptions. On admission, all patients tested positive for PEth, the total concentration ranging 0.82-11.7 (mean 6.35, median 5.88) μmol/l. PEth 16:0/18:1, 16:0/18:2 and 16:0/20:4 accounted for on average ~42%, ~26% and ~9%, respectively, of total PEth in these samples. There were good correlations between total PEth and individual homologs (P < 0.0001). There was no significant difference in PEth values between male and female subjects. During abstinence, the elimination half-life values ranged 3.5-9.8 days for total PEth, 3.7-10.4 days for PEth 16:0/18:1, 2.7-8.5 days for PEth 16:0/18:2 and 2.3-8.4 days for PEth 16:0/20:4., Conclusions: The results demonstrated a very high sensitivity (100%) of PEth as alcohol biomarker for recent heavy drinking, but considerable differences in the elimination rates between individuals and between different PEth forms. This indicates that it is possible to make only approximate estimates of the quantity and recency of alcohol intake based on a single PEth value., (© The Author(s) 2019. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background Reductions in exercise capacity associated with exercise intolerance augment cardiovascular disease risk and predict mortality in chronic kidney disease. This study utilized cardiopulmonary exercise testing to (a) investigate mechanisms of exercise intolerance; (b) unmask subclinical abnormalities that may precede cardiovascular disease in chronic kidney disease. Design The design of this study was cross-sectional. Methods Cardiopulmonary exercise testing was carried out in 31 Stage 3-4 chronic kidney disease patients (60 ± 11 years; estimated glomerular filtration rate 43 ± 13 ml/min/1.73 m 2 ) and 21 matched healthy individuals (healthy controls; 56 ± 5 years; estimated glomerular filtration rate>90 ml/min/1.73 m 2 ) on a cycle ergometer with workload increased by 15 W every minute until volitional fatigue. Breath-by-breath respiratory gas analysis was performed with an automated gas analyzer and averaged over 10 s intervals. Results Peak oxygen uptake was reduced in chronic kidney disease compared to healthy controls (17.43 ± 1.03 vs 28 ± 2.05 ml/kg/min; p < 0.01), as was oxygen uptake at the ventilatory threshold (9.44 ± 0.53 vs15.55 ± 1.34 ml/kg/min; p < 0.01). A steeper minute ventilation rate/carbon dioxide production slope (32 ± 0.8 vs 28 ± 1; p < 0.01) and a lower expired carbon dioxide pressure in chronic kidney disease (27 ± 0.6 vs 31 ± 0.9 vs 0.9; p < 0.01) indicated ventilation perfusion mismatching in these patients. The ventilatory cost of oxygen uptake was higher in chronic kidney disease (37 ± 0.8 vs 33 ± 1; p < 0.01). Maximum heart rate (134 ± 5 vs 159 ± 3 bpm) and one-minute heart rate recovery (15 ± 1 vs 20 ± 2 bpm) were reduced in chronic kidney disease ( p < 0.01). Conclusion This study suggests that both central and peripheral limitations likely contribute to reduced exercise capacity in non-dialysis chronic kidney disease. Additionally, cardiopulmonary exercise testing revealed subclinical cardiopulmonary abnormalities in these patients in the absence of overt cardiovascular disease. Cardiopulmonary exercise testing could potentially be a tool for unmasking cardiopulmonary abnormalities preceding cardiovascular disease in chronic kidney disease.

Background: Pancreatic cancer has a very poor prognosis as most patients are diagnosed at an advanced stage when curative treatments are not possible. Breath volatile organic compounds (VOCs) have shown potential as novel biomarkers to detect cancer. The aim of the study was to quantify differences in exhaled breath VOCs of patients with pancreatic cancers compared with cohorts without cancer., Methods: Patients were recruited to an initial development cohort and a second validation cohort. The cancer group included patients with localized and metastatic cancers, whereas the control group included patients with benign pancreatic disease or normal pancreas. The reference test for comparison was radiological imaging using abdominal CT, ultrasound imaging or endoscopic ultrasonography, confirmed by histopathological examination as appropriate. Breath was collected from the development cohort with steel bags, and from the validation cohort using the ReCIVA™ system. Analysis was performed using gas chromatography-mass spectrometry., Results: A total of 68 patients were recruited to the development cohort (25 with cancer, 43 no cancer) and 64 to the validation cohort (32 with cancer, 32 no cancer). Of 66 VOCs identified, 12 were significantly different between groups in the development cohort on univariable analysis. Receiver operating characteristic (ROC) curve analysis using significant volatile compounds and the validation cohort produced an area under the curve of 0·736 (sensitivity 81 per cent, specificity 58 per cent) for differentiating cancer from no cancer, and 0·744 (sensitivity 70 per cent, specificity 74 per cent) for differentiating adenocarcinoma from no cancer., Conclusion: Breath VOCs may distinguish patients with pancreatic cancer from those without cancer., (© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Introduction: Arabic male adolescents have a high smoking prevalence. Introduction of "Class smoke-free" pledges have been successful amongst European adolescents but have not been evaluated using objective valid measures. We tested the impact of adding a smoke free pledge strategy to a proven peer-led asthma and smoking prevention program on breath carbon monoxide level (BCO) in male high-school students in Jordan., Methods: We enrolled male students from four high-schools in Irbid, Jordan. Schools were randomly assigned to receive either TAJ (Triple A in Jordan, n = 218) or TAJ-Plus (with added class smoke-free pledge, n = 215). We hypothesized that students receiving TAJ-Plus would have greater reduction in BCO levels than those only receiving the TAJ intervention. Asthma and smoking status were assessed by self-administered questionnaires. Smoking outcomes were collected using a BCO Monitor., Results: Both groups had significant reductions in BCO levels post-intervention (p < .0001), however, decreases were greater in TAJ-Plus group (3.9 ± 0.2 vs. 4.8 ± 0.2, p < .0001). Intervention effects on BCO over time did not vary by smoking status (p = .085), asthma status (p = .602), or a combination of the two (p = .702)., Conclusions: An added smoke-free pledge strategy to a proven peer-led asthma education program appears to be a promising approach to motivate adolescents to abstain from smoking in Jordan. Future research is required to determine if these results can be extended to Jordanian adolescent females., Implications: A commitment by students via a "class smoke-free" pledge can be an added incentive to motivate adolescents in Arabic-speaking countries to abstain from smoking. Social influence approaches in schools can be useful in countering the aggressive tobacco marketing campaigns targeting Jordanian and other Arabic-speaking youth. The combination of "class smoke-free" pledges and an evidence-based peer-led asthma and smoking education can be implemented in schools to influence adolescents with asthma to abstain from smoking.

Volatile organic compounds (VOCs) in exhaled breath may identify the presence of invasive pulmonary aspergillosis. We aimed to detect VOC profiles emitted by in vitro cultured, clinical Aspergillus isolates using gas chromatography-mass spectrometry (GC-MS). Three clinical Aspergillus isolates and a reference strain were cultured while conidiation was prevented. Headspace samples were analyzed using a standardized method. Breath samples of patients from which the cultures were obtained were checked for the presence of the VOCs found in vitro. Each Aspergillus isolate produced a distinct VOC profile. These profiles could not be confirmed in exhaled breath in vivo., (© The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Modified-risk tobacco products are expected to reduce exposure to harmful and potentially harmful constituents of cigarette smoke, and ultimately reduce the health burden of smoking-related diseases. Clinically relevant risk markers of smoking-related diseases inform about the risk profile of new tobacco products in the absence of in-market epidemiological data. The menthol Tobacco Heating System 2.2 (mTHS) is a modified-risk tobacco product in development as an alternative to cigarettes (conventional cigarettes [CCs])., Methods: In this parallel-group study, Japanese adult smokers (23-65 years; ≥10 mCCs/day) were randomized to mTHS, menthol CCs (mCC), or smoking abstinence (SA) for 5 days in confinement and 85 days in ambulatory settings. Endpoints included biomarkers of exposure to harmful and potentially harmful constituents and clinically relevant risk markers of smoking-related diseases., Results: One-hundred and sixty participants were randomized to the mTHS (n = 78), mCC (n = 42), and SA (n = 40) groups. Switching to the mTHS was associated with reductions in biomarkers of exposure compared with continuing mCCs. Reductions in 8-epi-prostaglandin F2α (biomarker of oxidative stress), 11-dehydro-thromboxane B2 (biomarker of platelet activation), soluble intracellular adhesion molecule-1 (biomarker of endothelial function), and an increase in high-density lipoprotein cholesterol (biomarker of lipid metabolism) and forced expiratory volume in 1 second (biomarker of lung function) occurred in the mTHS group compared with the mCC group. The changes in the mTHS group approached those in the SA group., Conclusions: Switching from mCCs to mTHS was associated with improvements in clinically relevant risk markers linked to mechanistic pathways involved in smoking-related diseases., Implications: In this three-way randomized study, switching from menthol cigarettes to mTHS for 5 days in confinement and 85 days in ambulatory settings was associated with reductions in biomarkers of exposure to cigarette smoke, and changes were observed in clinically relevant biomarkers of oxidative stress (8-epi-prostaglandin F2α), platelet activity (11-dehydro-thromboxane B2), endothelial function (soluble intracellular adhesion molecule-1), lipid metabolism (high-density lipoprotein cholesterol) and lung function (forced expiratory volume in 1 second), similar to the SA group. The results suggest that switching to the mTHS has the potential to reduce the adverse health effects of conventional cigarettes., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Introduction: The menthol Tobacco Heating System 2.2 (mTHS) is a newly developed candidate modified-risk tobacco product intended to reduce exposure to the harmful and potentially harmful constituents (HPHCs) of conventional cigarette (CC) smoke. This study examined the impact of switching to mTHS on biomarkers of exposure to HPHCs relative to menthol CCs (mCCs) and smoking abstinence (SA)., Methods: In this three-arm, parallel-group study, 160 Japanese adult smokers (23-65 years; smoking ≥10 mCCs per day) were randomized to mTHS (n = 78), mCC (n = 42), or SA (n = 40) for 5 days in confinement and 85 days in ambulatory settings. Endpoints included biomarkers of exposure to HPHCs, human puffing topography, safety, and subjective effects of smoking measures., Results: After 5 days of product use, the concentrations of carboxyhemoglobin, 3-hydroxypropylmercapturic acid, monohydroxybutenyl mercapturic acid, and S-phenylmercapturic acid were 55%, 49%, 87%, and 89% lower (p < .001), respectively, in the mTHS group than in the mCC group. Other biomarkers of exposure (measured as secondary endpoints) were 50%-94% lower in the mTHS group than in the mCC group on day 5. These reductions in the mTHS group were maintained at day 90, similar to the SA group. Switching to mTHS was associated with changes in human puffing topography (shorter puff intervals and more frequent puffs). The urge-to-smoke and smoking satisfaction levels on day 90 were similar in the mTHS and the mCC groups., Conclusion: Switching from mCCs to mTHS significantly reduced exposure to HPHCs relative to continuing smoking mCCs with concentrations similar to those observed following SA in Japanese adult smokers., Implications: This randomized study compared the impact of switching to a modified-risk tobacco product candidate mTHS on biomarkers of exposure to HPHCs of cigarette smoke relative to continuing smoking cigarettes or abstaining from smoking in sequential confinement and ambulatory settings. The study showed that switching to mTHS was associated with significant biomarker reductions within 5 days in confinement, these reductions being maintained throughout the ambulatory setting up to day 90. The results provide evidence that switching to mTHS reduces real-life exposure to HPHCs in adult smokers., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Background: Like other complex psychosocial interventions, mindfulness-based treatments comprise various modality-specific components as well as nonspecific therapeutic ingredients that collectively contribute to efficacy. Consequently, the isolated effects of mindfulness strategies per se remain unclear., Methods: Using a randomized double-blind design, we compared the isolated effects of 11-minutes of "supervised" mindfulness instruction against a closely matched active control (relaxation) on subjective, physiological, and behavioral indices of maladaptive alcohol responding in drinkers at risk of harm from alcohol use (n = 68). Simple follow-up instructions on strategy use were provided, but practice was unsupervised and not formally monitored., Results: Both groups showed acute reductions in craving after training, although a trend group x time interaction (P = .056) suggested that this reduction was greater in the relaxation group (d = 0.722 P < .001) compared with the mindfulness group (d = 0.317, P = .004). Furthermore, upregulation of parasympathetic activity was found after relaxation (d = 0.562; P < .001) but not mindfulness instructions (d = 0.08; P > .1; group x time interaction: P = .009). By contrast, only the mindfulness group showed a reduction in past-week alcohol consumption at 7-day follow-up (-9.31 units, d = 0.593, P < .001), whereas no significant reduction was seen in the relaxation group (-3.00 units, d = 0.268, P > .1; group x time interaction: P = .026)., Conclusion: Very brief mindfulness practice can significantly reduce alcohol consumption among at-risk drinkers, even with minimal encouragement to use this strategy outside of the experimental context. The effects on consumption may therefore represent a lower bound of efficacy of "ultra-brief" mindfulness instructions in hazardous drinkers, at least at short follow-up intervals., (© The Author 2017. Published by Oxford University Press on behalf of CINP.)

Introduction: Daily visits to biochemically verify continuous smoking abstinence via expired-air carbon monoxide (CO) may deter participation in cessation trials. One way to reduce need for daily visits while continuing to monitor abstinence success may be use of a recent procedure to verify abstinence from daily CO values via the Internet. This method requires participants submit to study staff video recordings of themselves correctly using a CO monitor. However, it has not been clearly demonstrated that those classified quit via Internet-submitted videos of CO would be reliably classified quit when assessed in lab., Methods: Our study examined agreement in quit status from Internet-submitted CO values with quit status via CO collected in later same-day lab visits. Participants (n = 23) were from a short-term cessation study who agreed to record and submit videos of offsite CO testing, in addition to attending daily lab visits. All CO values were obtained via Bedfont pico+ Smokerlyzer monitors, with CO < 8 ppm indicating quit. During two 4-day practice quit attempts, a video was submitted before daily lab visits, up to eight videos each., Results: Of the total of 150 videos submitted, 97 videos indicated "not quit" and 53 "quit." Cohen's Kappa indicated substantial agreement in quit status between assessments, 0.70, p < .001, as 85% of the videos indicating "quit" CO were also "quit" CO in lab., Conclusions: To our knowledge, these results are the first validation of daily Internet-submitted CO values to confirm daily quit status, supporting the utility of this approach for close monitoring of continuous abstinence., Implications: This study compared consistency between quit status from CO values submitted over the Internet and quit status via CO collected in later same-day lab visits. Findings indicate substantial agreement in quit status between these two methods of CO assessment. Our results validate the use of Internet-submitted CO values to verify daily quit status. This method can be used in future cessation trials as a means to biochemically validate continuous abstinence without the burden of daily lab visits or relying on self-report of recent smoking lapses., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Alcohol is a risk factor for cardiac arrhythmias. Retrospective analyses suggest supraventricular arrhythmias consecutive to acute alcohol consumption, but prospective data are limited. We intended to prospectively associate acute alcohol consumption with cardiac arrhythmias., Methods and Results: At the 2015 Munich Octoberfest, we enrolled 3028 voluntary participants who received a smartphone-based ECG and breath alcohol concentration (BAC) measurements. ECGs were analysed for cardiac arrhythmias (sinus tachycardia, sinus arrhythmia, premature atrial/ventricular complexes, atrial fibrillation/flutter) and respiratory sinus arrhythmia. By multivariable adjusted logistic regression we associated BACs with cardiac arrhythmias. Similarly, we analysed 4131 participants of the community-based KORA S4 Study (Co-operative Health Research in the Region of Augsburg) and associated cardiac arrhythmias with chronic alcohol consumption. In our acute alcohol cohort (mean age 34.4 ± 13.3 years, 29% women), mean BAC was 0.85 ± 0.54 g/kg. Cardiac arrhythmias occurred in 30.5% (sinus tachycardia 25.9%; other arrhythmia subtypes 5.4%). Breath alcohol concentration was significantly associated with cardiac arrhythmias overall (odds ratio (OR) per 1-unit change 1.75, 95% confidence interval (CI) 1.50-2.05; P < 0.001) and sinus tachycardia in particular (OR 1.96, 95%CI 1.66-2.31; P < 0.001). Respiratory sinus arrhythmia measuring autonomic tone was significantly reduced under the influence of alcohol. In KORA S4, chronic alcohol consumption was associated with sinus tachycardia (OR 1.03, 95%CI 1.01-1.06; P = 0.006)., Conclusions: Acute alcohol consumption is associated with cardiac arrhythmias and sinus tachycardia in particular. This partly reflects autonomic imbalance as assessed by significantly reduced respiratory sinus arrhythmia. Such imbalance might lead to sympathetically triggered atrial fibrillation resembling the holiday heart syndrome., Clinicaltrials.org Accession Number: NCT02550340., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Evidence indicates that feeding-related peptides, such as ghrelin, have a role in the rewarding properties of addictive substances like alcohol. Oral alcohol administration significantly suppresses ghrelin. This study was designed to evaluate the effects of two doses of alcohol on ghrelin and examine if ghrelin levels predict the subjective effects of alcohol., Methods: Healthy social drinkers (N = 20) participated in three, randomly assigned, and counterbalanced laboratory sessions. During each session they received a continuous IV infusion of either placebo (saline), low dose (40 mg%) or high dose (100 mg%) of alcohol. Participants were given a standardized, light breakfast 90 min before the start of the infusion. Ghrelin levels [acyl ghrelin (AG) and total ghrelin (TG)] were collected at four time points before, during and after the infusion. Subjective effects of alcohol, using the BAES, were evaluated before, during and after alcohol infusion., Results: IV alcohol significantly reduced AG but not TG levels with no difference between the two doses of alcohol. The percent change (%∆) in AG suppression was substantial in both high dose (43.4%∆), and low dose (39.5%∆) of alcohol. Also, fasting AG and TG levels were significant predictors of alcohol stimulant and sedative effects. Higher fasting ghrelin levels were associated with longer and more intense subjective effects., Conclusions: The results provide evidence that IV alcohol suppresses ghrelin levels similarly to oral alcohol. This study is the first to show that ghrelin predicts subjective effects of alcohol, suggesting that ghrelin may have a role in the rewarding mechanisms for alcohol., Short Summary: Intravenous alcohol infusion (low dose and high dose of alcohol) when compared to placebo (saline) significantly suppresses ghrelin in healthy social drinkers. Fasting ghrelin levels also predict subjective behavioral effects of alcohol. Those with higher fasting ghrelin levels tend to experience alcohol effects longer and more intensely., (© The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Introduction: Smoking rates among women in Poland are high, and access to specialized smoking cessation services in rural areas are limited. The aim of this study was to assess factors related to quitting among pregnant women who smoke in rural areas of Poland., Methods: Data were collected during interviews conducted by midwives among 4512 women at various stages of their pregnancy. The interviews took place in small towns with populations having less than 8000 residents, located within 12 out of 16 voivodships (provinces). We used exhaled carbon monoxide to verify self-reported smoking status., Results: Overall, 38% of women interviewed (n = 1578) smoked before they found out they were pregnant. Among these women, 33% quit just after they had become aware of their pregnancy. The main predictors of early quitting were: higher educational attainment among pregnant women (adjusted odds ratio [AOR] 3.21; 95% confidence interval [CI] = 1.81-5.68), secondary educational attainment among their partners (AOR 1.63; 95% CI = 1.06-2.48), and not having children (AOR 1.71; 95% CI = 1.31-2.24). The main barriers to early quitting were: living with at least one current smoker (AOR 0.55, 95% CI = 0.39-0.76), being single (AOR 0.45; 95% CI = 0.29-0.71), and having both parents smoke cigarettes (AOR 0.67; 95% CI = 0.46-0.97)., Conclusions: A modest proportion of women included in this study quit after they became aware of their pregnancy. However, women faced multiple barriers to quitting, including the smoking status of their family members. The factors identified in the study can inform the design of tailored interventions for pregnant women in rural areas., Implications: Smoking rates among women in Poland are high, and access to specialized smoking cessation services in rural areas are limited. This study found that women were motivated to quit smoking, and many quit after they had become aware of their pregnancy. However, women faced multiple barriers to quitting, including the smoking status of their family members. The factors identified in the study can inform the design of tailored interventions for pregnant women in rural areas., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Pulmonary hypertension (PH) is an important cause of morbidity and mortality in patients with SSc. The submaximal heart and pulmonary evaluation (step test) is a non-invasive, submaximal stress test that could be used to identify SSc patients with PH. Our aims were to determine whether change in end tidal carbon dioxide ([Formula: see text]) from rest to end-exercise, and the minute ventilation to carbon dioxide production ratio ([Formula: see text]), both as measured by the step test, differ between SSc patients with and without PH. We also examined differences in validated self-report questionnaires and potential PH biomarkers between SSc patients with and without PH., Methods: We performed a cross-sectional study of 27 patients with limited or dcSSc who underwent a right heart catheterization within 24 months prior to study entry. The study visit consisted of questionnaire completion; history; physical examination; step test performance; and phlebotomy. [Formula: see text], [Formula: see text], self-report data and biomarkers were compared between patients with and without PH., Results: SSc patients with PH had a statistically significantly lower median (interquartile range) [Formula: see text] than SSc patients without PH [-2.1 (-5.1 to 0.7) vs 1.2 (-0.7 to 5.4) mmHg, P = 0.035], and a statistically significantly higher median (interquartile range) [Formula: see text] [53.4 (39-64.1) vs 36.4 (31.9-41.1), P = 0.035]. There were no statistically significant differences in self-report data or biomarkers between groups., Conclusion: [Formula: see text] and [Formula: see text] as measured by the step test are statistically significantly different between SSc patients with and without PH. [Formula: see text] and [Formula: see text] may be useful screening tools for PH in the SSc population., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Amino acids are frequently determined in clinical chemistry. However, current analysis methods are time-consuming, invasive, and suffer from artifacts during sampling, sample handling, and sample preparation. We hypothesized in this proof-of-principle study that plasma concentrations of amino acids can be estimated by measuring their concentrations in exhaled breath. A novel breath analysis technique described here allows such measurements to be carried out in real-time and noninvasively, which should facilitate efficient diagnostics and give insights into human physiology., Methods: The amino acid profiles in 37 individuals were determined by ion-exchange HPLC in blood plasma and simultaneously in breath by secondary electrospray ionization coupled to high-resolution mass spectrometry. Participants were split into training and test sets to validate the analytical accuracy. Longitudinal profiles in 3 individuals were additionally obtained over a 12-h period., Results: Concentrations of 8 slightly volatile amino acids (A, V, I, G, P, K, F, Orn) could be determined in exhaled breath with a CV of <10%. Exhalome validation studies yielded high accuracies for each of these amino acids, on average only 3% less compared to plasma concentrations (95% CI ±13%). Higher variations were found only for amino acids with a low plasma concentration., Conclusions: This study demonstrates for the first time that amino acids can be quantified in the human breath and that their concentrations correlate with plasma concentrations. Although this noninvasive technique needs further investigation, exhalome analysis may provide significant benefits over traditional, offline analytical methods., (© 2016 American Association for Clinical Chemistry.)

Background: Extraintestinal manifestations are common among patients with inflammatory bowel disease (IBD), whereas pulmonary involvement is considered rare. However, chronic lung diseases begin with subclinical changes of the small airways and often originate in childhood. Pulmonary involvement, particularly of the small airways, can be assessed using novel inert gas washout tests., Methods: In this prospective, single-center study, 30 children and adolescents (mean age, 14 years; SD, ±2.6; 13 boys) with IBD (mean disease duration, 3.2 years; SD, ±2.8), and 32 healthy age-matched controls, performed nitrogen multiple-breath washout, double-tracer gas single-breath washout, and diffusion capacity for carbon monoxide. Patients with IBD additionally performed spirometry, plethysmography, and measurement of exhaled nitric oxide., Results: Patients with IBD demonstrated no abnormalities in classical lung function tests. There was no difference between active disease and remission. The lung clearance index, a very sensitive indicator for small airway function, did not differ between patients with IBD and healthy controls (mean difference [95% confidence interval] -0.01 [-0.28 to 0.25]). Specific markers for peripheral lung ventilation (Sacin and Scond) were also within the normal range (0.002 [-0.003 to 0.008] and -0.002 [-0.020 to 0.015], respectively). No association was found between measures of lung function and IBD subtype, clinical disease activity scores, laboratory values, treatment modalities, or disease duration., Conclusions: In our cohort of pediatric and adolescent patients with IBD without respiratory symptoms, there was no evidence of significant lung disease on extensive screening testing. General screening of asymptomatic patients therefore appears unnecessary and is not recommended in this population.

Objectives: We evaluate the efficacy of concomitant therapy for Helicobacter pylori infection and the associated factors that influence it in China, where it has not previously been investigated., Methods: In this prospective study, 374 consecutive patients with H. pylori infection were randomly assigned to 10 day regimens of concomitant therapy with different proton pump inhibitors: esomeprazole (20 mg)/omeprazole (20 mg), amoxicillin (1000 mg), clarithromycin (500 mg) and metronidazole (400 mg). All drugs were administered twice daily. A [(13)C]urea breath test was performed at least 4 weeks after the completion of treatment. Gene polymorphisms and antimicrobial susceptibility were determined., Results: A total of 374 patients with active, uncomplicated duodenal ulcer disease were enrolled in the study (187 cases in each group). The overall eradication rate resulting from concomitant therapy was 90.7% (PP) and 86.1% (ITT) and the eradication rate was significantly higher in the group that received an esomeprazole-based regimen compared with the group that received an omeprazole-based regimen [95.4% versus 86.0%, respectively, P = 0.003 (PP) and 89.8% versus 82.4%, P = 0.036 (ITT), respectively]. Moreover, the omeprazole-based regimen was an independent risk factor for treatment failure (P = 0.039), as were CYP2C19 extensive metabolizer (P = 0.005), clarithromycin (P = 0.000) and metronidazole resistance (P = 0.000). In addition, CYP2C19 polymorphisms and antibiotic resistance had a synergistic effect on eradication rates. The majority of side effects were mild and none was serious., Conclusions: The 10 day concomitant therapy yielded an eradication rate of nearly 90%. Antibiotic resistance, CYP2C19 polymorphisms and their interactions were closely associated with regimen efficacy., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Although expired-air carbon monoxide (CO) is a well characterized biomarker of cigarette smoking, limited research has assessed whether the standard clinical CO cutoffs need to be altered for postpartum women and whether these cutoffs remain constant across the postpartum year. Accordingly, the present study evaluated the effectiveness of using CO as a method to confirm smoking status relative to salivary cotinine among postpartum women and assessed optimal CO criteria to confirm smoking status across the postpartum year. Differences in optimal CO criteria to confirm smoking status also were examined between black and white postpartum women., Methods: Women (N = 208) for the present study had quit smoking for their current pregnancy and were enrolled in a larger postpartum relapse prevention intervention. Smoking status was assessed at 12, 24, and 52 weeks postpartum using both expired-air CO and salivary cotinine., Results: Receiver-operating characteristic analyses indicated that CO provided moderately high diagnostic accuracy to distinguish between women who were and were not smoking when using salivary cotinine as the reference criterion to confirm smoking status. CO cutoffs of 2 and 3 parts per million (ppm) had the highest overall efficiency and combined sensitivity and specificity across the postpartum year. Results were consistent for black and white women., Conclusions: These findings indicate that optimal CO criteria to confirm smoking status remains stable throughout the postpartum year and support a need to utilize CO cutoffs much lower than the standard clinical CO criterion of 8 ppm to confirm abstinence among postpartum women., Implications: Findings from the present study confirm the value of CO as a biomarker of smoking status among postpartum women. Results indicate that CO cutoffs of 2 and 3 ppm were optimal for confirming smoking status across the entire postpartum year in both black and white women. These findings offer a replication and extension of previous work and indicate that optimal CO criteria to confirm smoking status remain stable throughout the postpartum period and further support a need to utilize CO cutoffs much lower than the standard clinical criterion of 8 ppm to confirm smoking status among postpartum women., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The objective of this study was to assess the outcome of antimicrobial susceptibility-guided therapies in Helicobacter pylori-infected individuals who had undergone unsuccessful prior eradication treatments., Methods: From October 2004 to December 2013, 481 H. pylori-positive patients with prior unsuccessful eradication treatments were administered susceptibility-guided salvage eradication treatments. Six months on, treatment outcome was assessed by urea breath test, stool antigen ELISA, Helicobacter urease test or microbiology and/or histopathology., Results: Resistance to metronidazole and clarithromycin was high in patients with prior unsuccessful eradication treatments and was dependent on the number of treatment failures. Susceptibility-guided salvage eradication treatments achieved eradication rates of nearly 70% in these patients. No particular regimen was significantly better than another., Conclusions: Antimicrobial susceptibility testing prevents prescription of inefficient antimicrobials and enables individualized and promising salvage treatments in patients with prior unsuccessful eradication treatments., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)