Exposure to polycyclic aromatic hydrocarbons, volatile organic compounds, and tobacco-specific nitrosamines and incidence of esophageal cancer.

BACKGROUND: Studying carcinogens in tobacco and nontobacco sources may be key to understanding the pathogenesis and geographic distribution of esophageal cancer. METHODS: The Golestan Cohort Study has been conducted since 2004 in a region with high rates of esophageal squamous cell carcinoma. For this nested study, the cases comprised of all incident cases by January 1, 2018; controls were matched to the case by age, sex, residence, time in cohort, and tobacco use. We measured urinary concentrations of 33 exposure biomarkers of nicotine, polycyclic aromatic hydrocarbons, volatile organic compounds, and tobacco-specific nitrosamines. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals for associations between the 90th vs the 10th percentiles of the biomarker concentrations and incident esophageal squamous cell carcinoma. RESULTS: Among individuals who did not currently use tobacco (148 cases and 163 controls), 2 acrolein metabolites, 2 acrylonitrile metabolites, 1 propylene oxide metabolite, and one 1,3-butadiene metabolite were significantly associated with incident esophageal squamous cell carcinoma (adjusted odds ratios between 1.8 and 4.3). Among tobacco users (57 cases and 63 controls), metabolites of 2 other volatile organic compounds (styrene and xylene) were associated with esophageal squamous cell carcinoma (OR = 6.2 and 9.0, respectively). In tobacco users, 2 tobacco-specific nitrosamines (NNN and N'-Nitrosoanatabine) were also associated with esophageal squamous cell carcinoma. Suggestive associations were seen with some polycyclic aromatic hydrocarbons (especially 2-hydroxynaphthalene) in nonusers of tobacco products and other tobacco-specific nitrosamines in tobacco users. CONCLUSION: These novel associations based on individual-level data and samples collected many years before cancer diagnosis, from a population without occupational exposure, have important public health implications.

Smoke exposure associated with higher urinary benzene biomarker muconic acid (MUCA) in Golestan Cohort Study participants.

Background. Benzene is a known human carcinogen. Human exposure to benzene can be assessed by measuring trans, trans-muconic acid (MUCA) in urine. Golestan Province in northeastern Iran has been reported to have high incidence of esophageal cancer linked to the use of tobacco products. This manuscript evaluates the urinary MUCA concentrations among the participants of the Golestan Cohort Study (GCS).Methods. We analyzed MUCA concentration in 177 GCS participants' urine samples and performed nonparametric pairwise multiple comparisons to determine statistically significant difference among six different product use groups. Mixed effects model was fitted on 22 participants who exclusively smoked cigarette and 51 participants who were classified as nonusers. The urinary MUCA data were collected at the baseline and approximately five years later, and intraclass correlation coefficient (ICC) was calculated from the model.Results. Compared with nonusers, tobacco smoking was associated with higher urinary MUCA concentrations. Based on the nonparametric test of pairwise multiple comparisons, MUCA concentrations among participants who smoked combusted tobacco products were statistically significantly higher compared to nonusers. Urinary MUCA collected five years apart from the same individuals showed moderate reliability (ICC = 0.41), which was expected given the relatively short half-life (∼6 h) of MUCA.Conclusion. Our study revealed that tobacco smoke was positively associated with increased levels of urinary MUCA concentration, indicating that it is a significant source of benzene exposure among GCS participants.

Tobacco Use and Incidence of Adverse Oral Health Outcomes Among US Adults in the Population Assessment of Tobacco and Health Study.

Importance: Evolving tobacco use patterns, including increasing electronic nicotine delivery systems (ENDS) use, warrant re-examination of the associations between tobacco use and oral health. Objective: To examine associations between tobacco product use and incidence of adverse oral health outcomes. Design, Setting, and Participants: This cohort study used nationally representative data from wave (W) 1 to W5 (2013-2019) of the Population Assessment of Tobacco and Health Study. Recruitment used a stratified address-based, area-probability household sample of the noninstitutionalized US civilian population. The W1 cohort included respondents aged 18 years and older without lifetime history of oral health outcomes at W1 or W3, depending on when the outcome was first assessed. Data analysis was performed from October 2021 to September 2022. Exposures: Current (every day or someday use) established (lifetime use of at least 100 cigarettes or "fairly regular" use of other products) use of cigarettes, ENDS, cigars, pipes, hookah, snus, and smokeless tobacco, excluding snus at W1 to W4. Main Outcomes and Measures: The primary outcomes were past 12-month self-reported diagnosis of gum disease and precancerous oral lesions (W2-W5) and bone loss around teeth, bleeding after brushing or flossing, loose teeth, and 1 or more teeth removed (W4-W5). Results: Sample sizes varied across the 6 oral health outcomes (13 149 respondents for the gum disease sample, 14 993 respondents for the precancerous oral lesions sample, 16 312 respondents for the bone loss around teeth sample, 10 286 respondents for the bleeding after brushing or flossing sample, 15 686 respondents for the loose teeth sample, and 12 061 respondents for the 1 or more teeth removed sample). Slightly more than half of adults (52%-54% across the 6 samples) were women, and the majority were of non-Hispanic White race and ethnicity. Cox proportional hazards models were developed with covariates that included time-dependent tobacco use variables mutually adjusted for each other. Cigarette smoking was positively associated with incidence of gum disease diagnosis (adjusted hazard ratio [AHR], 1.33; 95% CI, 1.11-1.60), loose teeth (AHR, 1.35; 95% CI, 1.05-1.75), and 1 or more teeth removed (AHR, 1.43; 95% CI, 1.18-1.74). Cigar smoking was positively associated with incidence of precancerous oral lesions (AHR, 2.18; 95% CI, 1.38-3.43). In addition, hookah smoking was positively associated with incidence of gum disease diagnosis (AHR, 1.78; 95% CI, 1.20-2.63), and ENDS use was positively associated with incidence of bleeding after brushing or flossing (AHR, 1.27; 95% CI, 1.04-1.54). No associations were observed between snus and smokeless tobacco excluding snus and incidence of oral health outcomes. Conclusions and Relevance: The observed associations of combustible tobacco use with incidence of several adverse oral health outcomes and ENDS use with incidence of bleeding after brushing or flossing highlight the importance of longitudinal studies and emphasize the continued importance of tobacco cessation counseling and resources in clinical practice.

Awareness and Use of Heated Tobacco Products Among Middle School and High School Students, United States, 2019-2020.

PURPOSE: Heated tobacco products (HTP) heat-processed tobacco leaf into an aerosol inhaled by the user. This study assessed prevalence and correlates of HTP awareness, ever use, and current use among US middle and high school students. METHODS: Data came from the 2019 and 2020 National Youth Tobacco Survey, a cross-sectional survey of US public and private, middle and high school students. HTP awareness, ever use, and current (past 30-day) use were assessed. Weighted prevalence estimates and adjusted prevalence ratios (aPR) were assessed overall and by sex, school level, race/ethnicity, and current other tobacco product use. RESULTS: In 2019, 12.8% (3.44 million) of all students reported HTP awareness, increasing to 19.3% (5.29 million) in 2020 (p < .01). Ever [2019: 2.6% (630 000); 2020: 2.4% (620 000)] and current [2019: 1.6% (420 000); 2020: 1.4% (370 000)] HTP use did not significantly change from 2019 to 2020. Current e-cigarette users were more likely to report ever (2020 aPR = 1.79, 95% CI:1.23, 2.62) or current HTP use (2019 aPR = 5.16, 95% CI: 3.48, 7.67; 2020 aPR = 3.39, 95% CI: 2.10, 5.47) than nonusers. In both years, ever and current HTP use was more likely among current combustible (aPR range = 3.59-8.17) and smokeless tobacco product (aPR range = 2.99-4.09) users than nonusers. CONCLUSIONS: HTP awareness increased 51% among US students during 2019-2020; however, HTP use did not significantly change during this period. Students who used other tobacco products were more likely to currently use HTPs. Estimates of HTP awareness and use provided serve as a baseline as future monitoring of these products is warranted. IMPLICATIONS: Awareness of heated tobacco products (HTPs) increased among US youth from 2019 to 2020; however, HTP use did not change. These estimates of HTP awareness and use serve as a baseline for future surveillance of these products as their availability in the US increases.

Patient-Reported Opioid Analgesic Use After Discharge from Surgical Procedures: A Systematic Review.

OBJECTIVE: This systematic review synthesizes evidence on patient-reported outpatient opioid analgesic use after surgery. METHODS: We searched PubMed (February 2019) and Web of Science and Embase (June 2019) for U.S. studies describing patient-reported outpatient opioid analgesic use. Two reviewers extracted data on opioid analgesic use, standardized the data on use , and performed independent quality appraisals based on the Cochrane Risk of Bias Tool and an adapted Newcastle-Ottawa scale. RESULTS: Ninety-six studies met the eligibility criteria; 56 had sufficient information to standardize use in oxycodone 5-mg tablets. Patient-reported opioid analgesic use varied widely by procedure type; knee and hip arthroplasty had the highest postoperative opioid use, and use after many procedures was reported as <5 tablets. In studies that examined excess tablets, 25-98% of the total tablets prescribed were reported to be excess, with most studies reporting that 50-70% of tablets went unused. Factors commonly associated with higher opioid analgesic use included preoperative opioid analgesic use, higher inpatient opioid analgesic use, higher postoperative pain scores, and chronic medical conditions, among others. Estimates also varied across studies because of heterogeneity in study design, including length of follow-up and inclusion/exclusion criteria. CONCLUSION: Self-reported postsurgery outpatient opioid analgesic use varies widely both across procedures and within a given procedure type. Contributors to within-procedure variation included patient characteristics, prior opioid use, intraoperative and perioperative factors, and differences in the timing of opioid use data collection. We provide recommendations to help minimize variation caused by study design factors and maximize interpretability of forthcoming studies for use in clinical guidelines and decision-making.

Association between opioid analgesic therapy and initiation of buprenorphine management: An analysis of prescription drug monitoring program data.

BACKGROUND: In the US, medication assisted treatment, particularly with office-based buprenorphine, has been an important component of opioid dependence treatment among patients with iatrogenic addiction to opioid analgesics. The predictors of initiating buprenorphine for addiction among opioid analgesic patients have not been well-described. METHODS: We conducted a time-to-event analysis using data from the North Carolina (NC) Prescription Drug Monitoring Program (PDMP). Our outcome of interest was time-to-initiation of sublingual buprenorphine. Our study population was a prospective cohort of all state residents receiving a full-agonist opioid analgesic between 2011 and 2015. Predictors of initiation of sublingual buprenorphine examined included: age, gender, cumulative pharmacies and prescribers utilized, cumulative opioid intensity (defined as cumulative opioid exposure divided by duration of opioid exposure), and benzodiazepine dispensing. FINDINGS: Of 4.3 million patients receiving opioid analgesics in NC between 2011 and 2015 (accumulated 8.30 million person-years of follow-up), and a total of 28,904 patients initiated buprenorphine formulations intended for addiction treatment (overall rate 3.48 per 1,000 person-years). In adjusted multivariate models, the utilization of 3 or more pharmacies (HR: 2.93; 95% CI: 2.82, 3.05) or 6 or more controlled substance prescribers (HR: 12.09; 95% CI: 10.76, 13.57) was associated with buprenorphine initiation. A dose-response relationship was observed for cumulative opioid intensity (HR in highest decile relative to lowest decile: 5.05; 95% CI: 4.70, 5.42). Benzodiazepine dispensing was negatively associated with buprenorphine initiation (HR: 0.63; 95% CI: 0.61, 0.65). CONCLUSIONS: Opioid analgesic patients utilizing multiple prescribers or pharmacies are more likely to initiate sublingual buprenorphine. This finding suggests that patients with multiple healthcare interactions are more likely to be treated for high-risk opioid use, or may be more likely to be identified and treated for addiction. Future research should utilize prescription monitoring program data linked to electronic health records to include diagnosis information in analytic models.

Associations between implementation of Project Lazarus and opioid analgesic dispensing and buprenorphine utilization in North Carolina, 2009-2014.

BACKGROUND: Project Lazarus (PL) is a seven-strategy, community-coalition-based intervention designed to reduce opioid overdose and dependence. The seven strategies include: community education, provider education, hospital emergency department policy change, diversion control, support programs for patients with pain, naloxone policies, and addiction treatment expansion. PL was originally developed in Wilkes County, NC. It was made available to all counties in North Carolina starting in March 2013 with funding of up to $34,400 per county per year. We examined the association between PL implementation and 1) overall dispensing rate of opioid analgesics, and 2) utilization of buprenorphine. Buprenorphine is often used in connection with medication assisted treatment (MAT) for opioid dependence. METHODS: Observational interrupted time series analysis of 100 counties over 2009-2014 (n = 7200 county-months) in North Carolina. The intervention period was March 2013-December 2014. 74 of 100 counties implemented the intervention. Exposure data sources comprised process surveys, training records, Prescription Drug Monitoring Program (PDMP) data, and methadone treatment program quality data. Outcomes were PDMP-derived counts of opioid prescriptions and buprenorphine patients. Incidence Rate Ratios were estimated with adjusted GEE Poisson regression models of all seven PL strategies. RESULTS: In adjusted models, diversion control efforts were positively associated with increased dispensing of opioid analgesics (IRR: 1.06; 95% CI: 1.03, 1.09). None of the other PL strategies were associated with reduced prescribing of opioid analgesics. Support programs for patients with pain were associated with a non-significant decrease in buprenorphine utilization (IRR: 0.93; 95% CI: 0.85, 1.02), but addiction treatment expansion efforts were associated with no change in buprenorphine utilization (IRR: 0.98; 95% CI: 0.91, 1.06). CONCLUSIONS: Implementation of PL strategies did not appreciably reduce opioid dispensing and did not increase buprenorphine utilization. These results are consistent with previous findings of limited impact of PL strategies on overdose morbidity and mortality. Future studies should analyze the uptake of MAT using a more expansive view of institutional barriers, treating community coalition activity around MAT as an effect modifier.

Opioid Overdose Mortality Among Former North Carolina Inmates: 2000-2015.

OBJECTIVES: To examine differences in rates of opioid overdose death (OOD) between former North Carolina (NC) inmates and NC residents and evaluate factors associated with postrelease OOD. METHODS: We linked NC inmate release data to NC death records, calculated OOD standardized mortality ratios to compare former inmates with NC residents, and calculated hazard ratios to identify predictors of time to OOD. RESULTS: Of the 229 274 former inmates released during 2000 to 2015, 1329 died from OOD after release. At 2-weeks, 1-year, and complete follow-up after release, the respective OOD risk among former inmates was 40 (95% confidence interval [CI] = 30, 51), 11 (95% CI = 9.5, 12), and 8.3 (95% CI = 7.8, 8.7) times as high as general NC residents; the corresponding heroin overdose death risk among former inmates was 74 (95% CI = 43, 106), 18 (95% CI = 15, 21), and 14 (95% CI = 13, 16) times as high as general NC residents, respectively. Former inmates at greatest OOD risk were those within the first 2 weeks after release, aged 26 to 50 years, male, White, with more than 2 previous prison terms, and who received in-prison mental health and substance abuse treatment. CONCLUSIONS: Former inmates are highly vulnerable to opioids and need urgent prevention measures.

Community Readiness to Prevent Opioid Overdose.

Effective community-based actions are urgently needed to combat the ongoing epidemic of opioid overdose. Community readiness (CR) has been linked to communities' support for collective action, which in turn has been associated with the success of community-wide prevention strategies and resulting behavior change. Our study, conducted in North Carolina, assessed the relationship between CR and two indices of opioid overdose. County-level data included a survey of health directors that assessed CR to address drug overdose prevention programs, surveillance measures of opioid overdose collected from death records and emergency departments, and two indicators of general health-related status. We found that counties' rates of CR were positively associated with their opioid-related mortality (but not morbidity) and that this relationship persisted when we controlled for health status. North Carolina counties with the highest opioid misuse problems appear to be the most prepared to respond to them.

A statewide evaluation of seven strategies to reduce opioid overdose in North Carolina.

BACKGROUND: In response to increasing opioid overdoses, US prevention efforts have focused on prescriber education and supply, demand and harm reduction strategies. Limited evidence informs which interventions are effective. We evaluated Project Lazarus, a centralised statewide intervention designed to prevent opioid overdose. METHODS: Observational intervention study of seven strategies. 74 of 100 North Carolina counties implemented the intervention. Dichotomous variables were constructed for each strategy by county-month. Exposure data were: process logs, surveys, addiction treatment interviews, prescription drug monitoring data. Outcomes were: unintentional and undetermined opioid overdose deaths, overdose-related emergency department (ED) visits. Interrupted time-series Poisson regression was used to estimate rates during preintervention (2009-2012) and intervention periods (2013-2014). Adjusted IRR controlled for prescriptions, county health status and time trends. Time-lagged regression models considered delayed impact (0-6 months). RESULTS: In adjusted immediate-impact models, provider education was associated with lower overdose mortality (IRR 0.91; 95% CI 0.81 to 1.02) but little change in overdose-related ED visits. Policies to limit ED opioid dispensing were associated with lower mortality (IRR 0.97; 95% CI 0.87 to 1.07), but higher ED visits (IRR 1.06; 95% CI 1.01 to 1.12). Expansions of medication-assisted treatment (MAT) were associated with increased mortality (IRR 1.22; 95% CI 1.08 to 1.37) but lower ED visits in time-lagged models. CONCLUSIONS: Provider education related to pain management and addiction treatment, and ED policies limiting opioid dispensing showed modest immediate reductions in mortality. MAT expansions showed beneficial effects in reducing ED-related overdose visits in time-lagged models, despite an unexpected adverse association with mortality.

North Carolina's Operation Medicine Drop: Results From One of the Nation's Largest Drug Disposal Programs.

INTRODUCTION: In 2013, a total of 1,085 North Carolina residents died due to unintentional poisoning; 91% of these deaths were attributed to medications or drugs (over-the-counter, prescription, or illicit). Proper disposal of unused, unneeded, and/or expired medications is an essential part of preventing these unintentional deaths, as well as averting the other adverse consequences of these drugs on the environment and population health. METHODS: Operation Medicine Drop is a medication take-back program coordinated by Safe Kids North Carolina, a county-level, coalition-based injury prevention organization. The Operation Medicine Drop program and event registration system were used to review and validate the number of events, the counties where the events were held, and the number of unit doses (pills) collected from March 2010 to June 2014. SAS version 9.4 was used to generate basic counts and frequencies of events and doses, and ArcGIS version 10.0 was used to create the map. RESULTS: From March 2010 to June 2014, Operation Medicine Drop held 1,395 events with 245 different participating law enforcement agencies in 91 counties in North Carolina, and it collected 69.6 million unit doses of medication. More than 60 local Safe Kids North Carolina community coalitions had participated as of June 2014. Every year, Operation Medicine Drop has witnessed increases in events, participating agencies, participating counties, and the number of doses collected. CONCLUSION: Operation Medicine Drop is an excellent example of a successful and ongoing collaboration to improve public health. Medication take-back programs may play an important role in preventing future overdose deaths in North Carolina.

The effects of North Carolina's prescription drug monitoring program on the prescribing behaviors of the state's providers.

State-level prescription drug monitoring programs (PDMPs) show promise as a key strategy to respond to the epidemic of the misuse and abuse of controlled substances (CS), particularly opioid analgesics, in the United States. Undocumented concerns have been expressed that these PDMPs may have a "chilling effect" on providers' willingness to prescribe these substances to their patients. Using data from North Carolina's PDMP for the 3-year period from 2009 through 2011, we examined whether rapid increases in (1) the number of providers who queried the system, and (2) the number of days on which they queried it, would be related to their prescribing practices in regards to CS. We hypothesized that neither marker of PDMP utilization would be associated with a decrease in either patients receiving CS prescriptions or CS prescriptions filled. We found no association between either of these variables and the number of patients who filled prescriptions for CS or the number of prescriptions for CS filled. However, we did find a slight positive relationship between the growth in the utilization of the PDMP and the number of prescriptions filled for opioid analgesics. Concerns that PDMPs may constrain prescribing behavior with regards to CS are not supported.