Patient characteristics associated with definitive diagnosis of metastatic pancreatic cancer in those initially diagnosed with cancer of unknown primary.

Cancer of unknown primary (CUP) and pancreatic cancer (PC) are malignancies associated with poor prognosis. CUP is the fourth most common cause of cancer mortality in the US, and median survival time is 3-4 months. PC is the third most common cause of cancer mortality in the US, and median survival time for patients with stage 3 or 4 PC is 2-3 months. The present study aimed to understand the patient characteristics of those initially misdiagnosed with CUP who ultimately received a diagnosis of PC. The present study used 2010-2015 Surveillance, Epidemiology, and End Results-Medicare data, a US population-based cancer registry linked to Medicare health insurance claims. Odds ratios (ORs) and 95% confidence intervals were calculated using two binary logistic regression models to compare the characteristics of patients who received definitive diagnosis between the CUP-PC group (those with an initial diagnosis of CUP who eventually received a stage 3 or 4 PC diagnosis) and the PC group (those diagnosed with stage 3 or 4 PC only). Approximately 26% of patients who received a definitive diagnosis of metastatic PC started with an initial diagnosis of CUP (n=17,565). The odds of definitive PC diagnosis in patients with CUP were lower for those with a comorbidity score of 0 [OR, 0.85 (95% CI: 0.79, 0.91)] and epithelial/unspecified histology [OR, 0.76 (95% CI: 0.71, 0.82)]. The odds of definitive PC diagnosis in patients with CUP were higher for patients of other race [OR, 1.27 (95% CI: 1.13, 1.43)] compared with white patients. Definitive diagnosis of PC in patients with CUP was lower in patients who were older with fewer or no comorbidities and unspecified histology. The complexity of CUP diagnosis and patient performance status may influence delays in diagnosis to a known primary site.

Adverse childhood experiences, antenatal stressful life events, and marijuana use during pregnancy: A population-based study.

Cumulative exposure to adverse childhood experiences (ACEs) and antenatal stressful life events (ASLEs) are independently associated with marijuana use during pregnancy. However, research has not explored how both exposures may influence marijuana use jointly. Assessing the joint associations of ACEs and recent ASLEs on marijuana use can identify people who may benefit from early intervention. Data come from the Nevada Pregnancy Risk Assessment Monitoring System, 2017-2020 (N = 2483). We assessed eight measures of ACEs before age 18 and fourteen measures of ASLEs twelve months before giving birth. Generalized estimating equations estimated the direct and joint associations (additive and multiplicative interaction) of ACEs and ASLEs on marijuana use during pregnancy. 9.8% used marijuana during the most recent pregnancy. Compared to people who reported no ACEs, those reporting 1 ACE (adjusted prevalence ratio[aPR] = 1.96, 95% confidence interval [CI] = 1.30-2.94), 3 ACEs (aPR = 3.58, 95%CI = 2.69-4.77), and 4+ ACEs (aPR = 3.67, 95%CI = 2.36-5.72) were more likely to use marijuana. Compared to people reporting no ASLEs, those reporting 4+ ASLEs (aPR = 3.12, 95% CI = 1.64-5.92) were more likely to use marijuana. There was evidence of interaction for high ACE and ASLE exposure on an additive scale. ACEs and ASLEs were independently associated with marijuana use during pregnancy, and there was evidence of additive interaction. Screening for ACEs and ASLEs during pregnancy, referrals to appropriate behavioral health services, and trauma-informed approaches are important to address marijuana use during pregnancy.

Protective Environmental Factors and Opioid Use Among Sexual Minority Youth.

Objectives: Nonmedical use of prescription opioids (NMUPO) is a pressing public health concern and affects sexual minority youth (SMY) at greater rates than heterosexual youth. We investigated whether protective environmental factors-(1) Human Rights Campaign's state equality index (SEI) and (2) supportive school environments for LGBTQ youth, influenced NMUPO among SMY and non-SMY students. Methods: We combined data from the 2017-2019 Youth Risk Behavior Survey, 2016-2018 School Health Profiles, state-level socio-demographic and SEI data across 24 states (N=156,149). Generalized linear mixed models examined associations between (1) SEI and (2) supportive school environments for LGBTQ youth, with NMUPO, accounting for clustering at the school-and state-level. Results: Before adjustment, we found that youth in states with higher SEI were significantly less likely to engage in NMUPO compared to students in states with lower SEI, a relationship that became non-significant after adjustment. After adjusting for individual-and state-level indicators, SMY in states with supportive school environments for LGBTQ youth were less likely to engage in NMUPO. Conclusions: Supportive school environments for LGBTQ youth may play an important role in the health of SMY. Establishing more inclusive policies and supportive environments within schools may reduce NMUPO among SMY.

Patient Characteristics Associated with Definitive Diagnosis of Metastatic Pancreatic Cancer in Those Initially Diagnosed with Cancer of Unknown Primary.

Purpose: Cancer of unknown primary (CUP) is the fourth most common cause of cancer mortality in the U.S. Median survival after CUP diagnosis is 3-4 months. As CUP and metastatic pancreatic cancer (PC) are comparable in prevalence and survival, PC diagnosis is a useful endpoint to assess patient characteristics associated with definitive diagnosis in older patients who initially present with CUP. Methods: This study used 2010-2015 SEER-Medicare data. Logistic regression models compared patient characteristics who received definitive diagnosis in two subsets: CUP-PC and PC only. Results: Approximately 26% of patients who received a definitive diagnosis of metastatic pancreatic cancer started with an initial diagnosis of CUP (n=17,565). The odds of definitive diagnosis in CUP-PC were lower for those with a comorbidity score of 0 (OR 0.85 [0.79, 0.91]) and epithelial/unspecified histology (OR 0.76 [0.71, 0.82]). The odds of definitive diagnosis in CUP-PC were higher for patients of Other race (OR 1.27 [1.13, 1.43]) compared to White patients. Conclusion: Definitive diagnosis of CUP-PC was favorable in patients in the Other race category with fewer or no comorbidities. Unfavorable characteristics included older patients and those with epithelial/unspecified histology. Future studies will focus on patterns of care and survival in patients with CUP-PC.

Associations between Circumstances Surrounding Overdose and Underlying Classes of Polysubstance Overdose Deaths.

BACKGROUND: The overdose crisis is worsening, with polysubstance overdose deaths involving psychostimulants increasing in the U.S. Substance-specific prevention and intervention activities may not be as effective for polysubstance use, so we sought to classify substances used among overdose decedents to identify unique factors related to these classes. METHODS: We used data from the Nevada State Unintentional Drug Overdose Reporting System, Jan 2019-Jun 2021, which comes from death certificates, coroner/medical examiner reports, and postmortem toxicology. Latent class analysis, multinomial logistic regression, and Chi-squared tests determined underlying drug use classes, differences in characteristics and circumstances surrounding overdose, and assessed relationships between circumstances and drug use classes. RESULTS: We identified four latent classes: (1) prescription drugs (19.1%), (2) predominately methamphetamine (31.4%), (3) multi-drug (28.9%), and (4) opioid and stimulant (20.6%). Compared to other classes, the prescription drug class had a higher percentage of female decedents, from rural counties, with mental health diagnoses, who died at home. The predominately methamphetamine class had a higher percentage of decedents experiencing homelessness. The multi-drug use class had higher percentage of younger and Hispanic decedents. Those in the opioid and stimulant class had higher odds of being recently released from an institutional setting, compared to the multi drug class. CONCLUSIONS: These underlying classes were associated with several characteristics and circumstances that can prove useful for prevention, treatment, and harm reduction agencies when designing programs and interventions to target specific groups of people at-risk for drug overdose.

Semiparametric zero-inflated Bernoulli regression with applications.

When the observed proportion of zeros in a data set consisting of binary outcome data is larger than expected under a regular logistic regression model, it is frequently suggested to use a zero-inflated Bernoulli (ZIB) regression model. A spline-based ZIB regression model is proposed to describe the potentially nonlinear effect of a continuous covariate. A spline is used to approximate the unknown smooth function. Under the smoothness condition, the spline estimator of the unknown smooth function is uniformly consistent, and the regression parameter estimators are asymptotically normally distributed. We propose an easily implemented and consistent estimation method for the variances of the regression parameter estimators. Extensive simulations are conducted to investigate the finite-sample performance of the proposed method. A real-life data set is used to illustrate the practical use of the proposed methodology. The real-life data analysis indicates that the prediction performance of the proposed semiparametric ZIB regression model is better compared to the parametric ZIB regression model.

Who Can I Ask? Who Would I Tell? An Egocentric Network Analysis Among a Sample of Women At-Risk to Explore Anticipated Advice Seeking and Disclosure Around Pre-exposure Prophylaxis (PrEP).

Pre-Exposure Prophylaxis (PrEP) health campaigns invite women to talk with their provider, partner, and peers about PrEP, though they do not offer specific guidance about who and how to engage. This study uses egocentric network methods in a sample of women at risk for HIV to understand what characteristics of women (egos), their networks, and network members (alters) were associated with anticipated PrEP advice-seeking and anticipated PrEP disclosure. Multivariable generalized linear mixed models revealed that women often consider close, supportive, and trusted network members as PrEP discussants while ego-level, network-level, and cross-level interactions depict the complexity of anticipated network activation. Findings highlight the importance of considering women at risk for HIV in a broader social context. Anticipated advice-seeking and disclosure related to PrEP were associated but distinct forms of network activation, which highlights the need to develop specific recommendations about who and how women should engage with their networks around PrEP.

An efficient penalized estimation approach for semiparametric linear transformation models with interval-censored data.

We consider efficient estimation of flexible transformation models with interval-censored data. To reduce the dimension of semiparametric models, the unknown monotone function is approximated via a monotone B-spline. A penalization technique is used to provide computationally efficient estimation of all parameters. To accomplish model fitting and inference, an easy to implement nested iterative expectation-maximization (EM) algorithm is developed for estimation, and a simple variance-covariance estimation approach is proposed which makes large-sample inference for the regression parameters possible. Theoretically, we show that the estimator of the unknown monotone increasing function achieves the optimal rate of convergence, and the estimators of the regression parameters are asymptotically normal and efficient under the appropriate selection of the order of the smoothing parameter and the knots of the spline space. The proposed penalized procedure is assessed through extensive numerical experiments and implemented in R package PenIC. The proposed methodology is further illustrated via a signal tandmobiel study.

Sources of Information and Communication About HPV Among Chinese Students Attending U.S. Colleges: Implications for Culturally Appropriate Strategies.

INTRODUCTION: Little is known about human papillomavirus (HPV) information sources and communication among Chinese students attending U.S. colleges. We assessed information sources and communication about HPV and HPV vaccines among this population. METHODOLOGY: A cross-sectional design with 449 participants was conducted by using a questionnaire and snowball sampling. Summary statistics and multiple logistic regression were used. RESULTS: The most common sources of HPV information included the internet and friends. Communication about HPV occurred most frequently among friends, family, and health professionals. Those who had better HPV knowledge and attitudes and were vaccinated against HPV were more likely to use internet, friends, family, and health professionals as their information sources. DISCUSSION: Because the internet, friends, and families are likely sources for HPV information and communication, future internet-based culturally appropriate education should offer information not only to Chinese students but also to their social circles. Cultural beliefs may affect HPV prevention and should be examined.

The mobile emergency recovery intervention trial (MERIT): Protocol for a 3-year mixed methods observational study of mobile recovery outreach teams in Nevada's emergency departments.

BACKGROUND: The Substance Abuse and Mental Health Administration awarded State Targeted Response grants to support states' efforts to address the opioid epidemic. In Nevada, one component of this grant was mobile recovery outreach teams (MROTs) that utilized peer recovery support specialists to provide care for qualifying patients in emergency departments (EDs). The Mobile Emergency Recovery Intervention Trial (MERIT) is a mixed methods study to assess the feasibility/acceptability and effectiveness of the MROT intervention. This protocol mainly describes the R33 research activities and outcomes. The full protocol can be found protocols.io. METHODS: Data will be derived from state-level data sets containing de-identified emergency department visits, substance use disorder treatment records, and mortality files; in-person mixed methods interviews; participant observation; and self-report process evaluation forms. Primary outcomes include Medication Assisted Treatment (MAT) initiation and non-fatal overdose; secondary outcomes include MAT retention and fatal overdose. Quantitative hypotheses will be tested using generalized linear mixed effects models, Bayesian hierarchical models, and marginal Cox models. Qualitative interview data will be analyzed using an inductive thematic analysis procedure. DISCUSSION: It is impossible to conduct a randomized controlled trial of the effectiveness of the MROTs, given the ethical and logistical considerations of this intervention.This study's innovative design employs a mixed methods formative phase to examine feasibility and acceptability, and a quasi-experimental outcomes evaluation phase employing advanced statistical methods to mitigate bias and suggest causal inference regarding the effectiveness of the MROTs.Innovative interventions have been deployed in many states; evidence regarding their effectiveness is lacking, but critical to informing an effective public health response to the opioid epidemic.

Reasons and influential recommendations associated with HPV vaccination among Chinese college students in the USA.

OBJECTIVES: To evaluate (a) reasons for not receiving recommended doses of the human papillomavirus (HPV) vaccine, (b) the most influential recommending source in getting the HPV vaccine, and (c) associated factors among Chinese college students in the United States. METHODS: A cross-sectional design utilizing a structured self-report questionnaire was used. PARTICIPANTS: A network sample of 449 participants aged 18 or older completed the survey between March and May of 2018. RESULTS: Only 172 participants (38.3%) had received the HPV vaccine. The most common reason was that participants had never received recommendations from healthcare providers regarding HPV vaccines. Recommendations from doctors were the most cited source in deciding HPV vaccine uptake. Factors associated with reasons and recommendation sources included attitudes toward HPV, gender, school year, age, major, and health insurance. CONCLUSIONS: Healthcare providers play an important role in promoting HPV vaccination among Chinese college students. More research is needed for this understudied population.

A longitudinal study of the protective influence of youth assets on juvenile arrest.

BACKGROUND: The objective of this study was to determine the separate and cumulative influence of individual, family and community assets on juvenile arrest rates in a cohort of youth. METHODS: Five waves of data were collected from 1111 youth and their parents living in randomly sampled census tracts in a Midwestern state. Computer-assisted, in-person data collection methods were used to measure assets within individual (six assets), family (four assets) and community (six assets) domains. Extended Cox models were used to assess the relationship between the number of assets and time to first juvenile arrest, while controlling for known confounders. RESULTS: Nine of 16 assets across individual, family and community domains were prospectively associated with a reduction in arrest rates. There was a relationship between the number of assets youth possess within individual, family and community domains and rates of arrest. For example, compared to youth with zero to one community assets, those with three [adjusted hazard ratio (AHR): 0.52; 95% confidence interval (CI): 0.30-0.88], four [AHR: 0.57; 95% CI: 0.34-0.97] or five to six [AHR: 0.45; 95% CI: 0.25-0.82] community assets had lower risk of arrest. CONCLUSIONS: Public health efforts focused on developing policies and programs to promote asset building across multiple domains of influence are warranted.

Adverse Childhood Experiences and Suicidal Behaviors Among Youth: The Buffering Influence of Family Communication and School Connectedness.

PURPOSE: The main objectives of this study were to determine (1) whether family communication and school connectedness offer protection against suicidal behaviors in the presence of adverse childhood experiences (ACEs; direct protective effect) and (2) whether family communication or school connectedness buffer the association between ACEs and suicidal behaviors (interacting protective effect) on the multiplicative and additive scales. METHODS: Data were obtained from a western state's 2019 Youth Risk Behavior Survey that included 5,341 middle school and 4,980 high school participants. Generalized linear models were used to estimate whether family communication and school connectedness offered direct protection against suicidal behaviors or buffered the association between ACEs and suicidal behaviors using adjusted prevalence ratios and corresponding 95% confidence intervals. RESULTS: Family communication and school connectedness offered direct protection against suicidal behaviors in the presence of ACEs (a 1-unit higher score was associated with a 32%-42% lower prevalence of suicidal behaviors for middle school youth and a 27%-39% lower prevalence of suicidal behaviors for high school youth). There was evidence that family communication and school connectedness buffered the association between ACEs and suicidal behaviors on the multiplicative scale. CONCLUSIONS: The findings provide support for the development and implementation of interventions that build family communication and school connectedness to reduce suicidal behaviors. Furthermore, screening for trauma and suicidal behaviors is warranted.

Healthcare Utilization, Unmet Service Needs, and Medication Adherence Among People Living with HIV/AIDS.

BACKGROUND: Comorbidity rates and service needs are high among people living with HIV/AIDS (PLWHA). The effects of service utilization and unmet service needs on antiretroviral therapy (ART) adherence are not well understood. The purpose of this study was to investigate associations among PLWHA's service utilization, unmet service needs, and ART adherence. METHODS: PLWHA (N=162) 18 years or older were recruited from a Nevada statewide needs assessment project in 2016. Participants completed a self-administered questionnaire on paper or online. The independent variables were service utilization and unmet service needs. The outcome variable was ART adherence. Multivariable logistic regression analyses were conducted to examine associations between the amount of utilized services and unmet service needs with ART adherence. RESULTS: Only 12 (7.5%) participants reported they received all the needed services. The ART nonadherence group showed significantly higher unmet medical service needs compared to the ART adherence group (p=0.007). Unmet medical service needs (Adjusted Odds Ratio (AOR) 0.69, CI 0.53-0.90) and unmet support service needs (AOR 0.68, CI 0.48-0.97) were negatively associated with ART adherence. However, utilizing medical services (AOR 1.06, CI 0.87-1.30) and support services (AOR 0.88, CI 0.74-1.04) in the current year were not significantly associated with ART adherence. CONCLUSION: The results of this study indicate that health promotion programming should focus not only on introducing new services at the community level, but also work to optimize the availability and awareness of current services. Furthermore, health promotion programs should focus on filling service coverage gaps and improving the facilitation of services.

Knowledge, attitudes, and practices related to human papillomavirus vaccination among college students in a state university: Implications for nurse practitioners.

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States and disproportionately affects adolescents and young adults. Although a safe and efficacious vaccine is available, many college students are unimmunized against HPV. Most students presenting to college health centers are within the age range for catch-up immunization, giving nurse practitioners (NPs) in this setting an opportunity to increase vaccination rates. More information is needed about college students' HPV knowledge, attitudes, and vaccination uptake so that NPs can make effective vaccine recommendations to this population. PURPOSE: To examine (a) Knowledge and attitudes about HPV and its vaccine; (b) HPV immunization practices; and (c) factors associated with HPV knowledge, attitudes, and vaccination among college students in a US university. METHODS: This cross-sectional quantitative study collected data from participants in a state university student health center. Data collected included knowledge, attitudes, and practices about HPV and its vaccine from 627 students. RESULTS: Participants had a moderately low HPV knowledge but positive attitudes toward HPV and its vaccine. Participants with a higher level of HPV knowledge were US born, health-related majors, married or divorced, and had positive attitudes. Higher HPV knowledge, vaccine uptake, and a family history of cervical cancer were associated with positive attitudes. Predictors for vaccine uptake include being a health-related major and positive vaccine attitudes. IMPLICATIONS FOR PRACTICE: The results of this study help NPs, registered nurses, and other health care providers make effective HPV vaccine recommendations to college students. Students with positive HPV attitudes can serve as peer educators to increase HPV vaccination awareness in this population.

Prospective relationships between youth assets, negative life events, and binge drinking in a longitudinal cohort of the youth.

PURPOSE: The purpose of this study was to investigate whether individual, family, and community assets can 1) protect youth from binge drinking in the face of negative life events and 2) modify the relationship between negative life events and binge drinking. METHODS: Data from waves 2-5 of the Youth Asset Study were analyzed. Generalized estimating equations were used to assess the relationship between negative life events, assets, and binge drinking. Multiplicative and additive interaction between negative life events and assets was evaluated. RESULTS: When included in the same model as negative life events, individual, family, and community assets had a graded, protective relationship with binge drinking, with strongest protection for those with the greatest number of assets. For example, youth with 3 [adjusted odds ratio (AOR):0.78, 95% confidence interval (CI): 0.65-0.93], 4 [AOR: 0.60, 95% CI: 0.49-0.73], 5 [AOR: 0.53, 95% CI: 0.41-0.69], and 6 [AOR: 0.42, 95% CI: 0.28-0.63] assets within the community domain had a significantly lower odds of binge drinking than youth with 0-2 community assets. No significant interactions were observed. CONCLUSIONS: The findings suggest that while youth who are exposed to negative life events are at risk for binge drinking, building assets across individual, family, and community domains can have a protective influence.

Efficient estimation of a linear transformation model for current status data via penalized splines.

We propose a flexible and computationally efficient penalized estimation method for a semi-parametric linear transformation model with current status data. To facilitate model fitting, the unknown monotone function is approximated by monotone B-splines, and a computationally efficient hybrid algorithm involving the Fisher scoring algorithm and the isotonic regression is developed. A goodness-of-fit test and model diagnostics are also considered. The asymptotic properties of the penalized estimators are established, including the optimal rate of convergence for the function estimator and the semi-parametric efficiency for the regression parameter estimators. An extensive numerical experiment is conducted to evaluate the finite-sample properties of the penalized estimators, and the methodology is further illustrated with two real studies.

"Another tool for the tool box? I'll take it!": Feasibility and acceptability of mobile recovery outreach teams (MROT) for opioid overdose patients in the emergency room.

Drug poisoning deaths involving opioids have increased exponentially in the United States. Post-overdose outreach to patients in the emergency room (ER) is a promising strategy for increasing uptake of medication assisted treatment and reducing subsequent overdose. We conducted a mixed methods study to investigate the feasibility and acceptability of a mobile recovery outreach team (MROT) program for opioid overdose patients presenting in Nevada's ERs, which was funded by the SAMHSA Opioid State Targeted Response (STR) grant. We interviewed 25 ER staff using quantitative questions informed by Diffusion of Innovation (DOI) theory and qualitative questions regarding their experiences caring for overdose patients, perceived benefits, and concerns about the MROT program. Respondents expressed strong support and enthusiasm for the program, identified advantages of the program relative to standard of care, highlighted logistical issues that must be addressed prior to implementation, and illustrated how the MROT program is compatible with their personal and professional values. Our results suggest that the STR-funded MROT program could reduce burden and stress among ER staff and improve patient outcomes, but must be informed by formative research that addresses issues of logistical complexity and cultural compatibility.

Real-World Vehicle Emissions Characterization for the Shing Mun Tunnel in Hong Kong and Fort McHenry Tunnel in the United States.

INTRODUCTION: Motor vehicle exhaust is an important source of air pollutants and greenhouse gases. Concerns over the health and climate effects of mobile-source emissions have prompted worldwide efforts to reduce vehicle emissions. Implementation of more stringent emission standards have driven advances in vehicle, engine, and exhaust after-treatment technologies as well as fuel formulations. On the other hand, vehicle numbers and travel distances have been increasing because of population and economic growth and changes in land use. These factors have resulted in changes to the amount and chemical composition of vehicle emissions.Roadway tunnel studies are a practical way to characterize real-world emissions from the on-road vehicle fleet in an environment isolated from other combustion pollution sources. Measurements in the same tunnel over time allow evaluation of vehicle emission changes and the effectiveness of emission reduction measures. Tunnel studies estimate the impacts of vehicle emissions on air quality and traffic-related exposures, generate source profile inputs for receptor-oriented source apportionment models, provide data to evaluate emission models, and serve as a baseline for future comparisons.The present study characterized motor vehicle emission factors and compositions in two roadway tunnels that were first studied over a decade ago. The specific aims were to (1) quantify current fleet air pollutant emission factors, (2) evaluate emission change over time, (3) establish source profiles for volatile organic compounds (VOCs) and particulate matter ≤2.5 µm in aerodynamic diameter (PM2.5), (4) estimate contributions of fleet components and non-tailpipe emissions to VOCs and PM2.5, and (5) evaluate the performance of the latest versions of mobile-source emission models (i.e., the EMission FACtors vehicle emission model used in Hong Kong [EMFAC-HK] and the MOtor Vehicle Emission Simulator used in the United States [MOVES]). METHODS: Measurements were conducted in the Shing Mun Tunnel (SMT) in Hong Kong and the Fort McHenry Tunnel (FMT) in Baltimore, Maryland, in the United States, representing the different fleet compositions, emission controls, fuels, and near-road exposure levels found in Hong Kong and the United States. These tunnels have extensive databases acquired in 2003-2004 for the SMT and 1992 for the FMT. The SMT sampling was conducted during the period from 1/19/2015 to 3/31/2015, and the FMT sampling occurred during the periods from 2/8/2015 to 2/15/2015 (winter) and 7/31/2015 to 8/7/2015 (summer). Concentrations of criteria pollutants (e.g., carbon monoxide [CO], nitrogen oxides [NOx], and particulate matter [PM]) were measured in real time, and integrated samples of VOCs, carbonyls, polycyclic aromatic hydrocarbons (PAHs), and PM2.5 were collected in canisters and sampling media for off-line analyses. Emission factors were calculated from the tunnel measurements and compared with previous studies to evaluate emission changes over time. Emission contributions by different vehicle types were assessed by source apportionment modeling or linear regression. Vehicle emissions were modeled by EMFAC-HK version 3.3 and MOVES version 2014a for the SMT and the FMT, respectively, and compared with measured values. The influences of vehicle fleet composition and environmental parameters (i.e., temperature and relative humidity) on emissions were evaluated. RESULTS: In the SMT, emissions of PM2.5, sulfur dioxide (SO2), and total non-methane hydrocarbons (NMHCs) markedly decreased from 2003-2004 to 2015: SO2 and PM2.5 were reduced by ~80%, and total NMHCs was reduced by ~44%. Emission factors of ethene and propene, key tracers for diesel vehicle (DV) emissions, decreased by ~65%. These reductions demonstrate the effectiveness of control measures, such as the implementation of low-sulfur fuel regulations and the phasing out of older DVs. However, the emission factors of isobutane and n-butane, markers for liquefied petroleum gas (LPG), increased by 32% and 17% between 2003-2004 and 2015, respectively, because the number of LPG vehicles increased. Nitrogen dioxide (NO2) to NOx volume ratios increased between 2003-2004 and 2015, indicating an increased NO2 fraction in primary exhaust emissions. Although geological mineral concentrations were similar between the 2003-2004 and 2015 studies, the contribution of geological materials to PM2.5 increased from 2% in 2003-2004 to 5% in 2015, signifying the continuing importance of non-tailpipe PM emissions as tailpipe emissions decrease. Emissions of CO, ammonia (NH3), nitric oxide (NO), NO2, and NOx, as well as carbonyls and PAHs in the SMT did not show statistically significant (at P < 0.05 based on Student's t-test) decreases from 2003-2004 to 2015. The reason for this is not clear and requires further investigation.A steady decrease in emissions of all measured pollutants during the past 23 years has been observed from tunnel studies in the United States, reflecting the effect of emission standards and new technologies that were introduced during this period. Emission reductions were more pronounced for the light-duty (LD) fleet than for the heavy-duty (HD) fleet. In comparison with the 1992 FMT study, the 2015 FMT study demonstrated marked reductions in LD emissions for all pollutants: emission factors for naphthalene were reduced the most, by 98%; benzene, toluene, ethylbenzene, and xylene (BTEX), by 94%; CO, NMHCs, and NOx, by 87%; and aldehydes by about 71%. Smaller reductions were observed for HD emission factors: naphthalene emissions were reduced by 95%, carbonyl emissions decreased by about 75%, BTEX by 60%, and NOx 58%.The 2015 fleet-average emission factors were higher in the SMT for CO, NOx, and summer PM2.5 than those in the FMT. The higher CO emissions in the SMT were possibly attributable to a larger fraction of motorcycles and LPG vehicles in the Hong Kong fleet. DVs in Hong Kong and the United States had similar emission factors for NOx. However, the non-diesel vehicles (NDVs), particularly LPG vehicles, had higher emission factors than those of gasoline cars, contributing to higher NOx emissions in the SMT. The higher PM2.5 emission factors in the SMT were probably attributable to there being more double-deck buses in Hong Kong.In both tunnels, PAHs were predominantly in the gas phase, with larger (four and more aromatic rings) PAHs mostly in the particulate phase. Formaldehyde, acetaldehyde, crotonaldehyde, and acetone were the most abundant carbonyl compounds in the SMT. In the FMT, the most abundant carbonyls were formaldehyde, acetone, acetaldehyde, and propionaldehyde. HD vehicles emitted about threefold more carbonyl compounds than LD vehicles did. In the SMT, the NMHC species were enriched with marker species for LPG (e.g., n-butane, isobutane, and propane) and gasoline fuel vapor (e.g., toluene, isopentane, and m/p-xylene), indicating evaporative losses. Source contributions to SMT PM2.5 mass were diesel exhaust (51.5 ± 1.8%), gasoline exhaust (10.0 ± 0.8%), LPG exhaust (5.0 ± 0.5%), secondary sulfate (19.9 ± 1.0%), secondary nitrate (6.3 ± 0.9%), and road dust (7.3 ± 1.3%). In the FMT, total NMHC emissions were 14% and 8% higher in winter than in summer for LD and HD vehicles, respectively. Elemental carbon (EC) and organic carbon (OC) were the major constituents of tunnel PM2.5. De-icing salt contributions to PM2.5 were observed in the FMT in winter.Emission estimates by the EMFAC-HK agreed with SMT measurements for CO2; the modeled emission factors for CO, NOx, and NMHCs were 1.5, 1.6, and 2.2 times the measurements, respectively; and the modeled emission factor for PM2.5 was 61% of the measured value in 2003. The EMFAC-HK estimates and SMT measurements for 2015 differed by less than 35%. The MOVES2014a model generally overestimated emissions of most of the pollutants measured in the FMT. No pollutants were significantly underestimated. The largest overestimation was observed for emissions measured during HD-rich driving conditions in winter. CONCLUSIONS: Significant reductions in SO2 and PM2.5 emissions between 2003 and 2015 were observed in the SMT, indicating the effectiveness of control measures on these two pollutants. The total NMHC emissions in the SMT were reduced by 44%, although isobutane and n-butane emissions increased because of the increase in the size of the LPG fleet. No significant reductions were observed for CO and NOx, results that differed from those for roadside ambient concentrations, emission inventory estimates, and EMFAC-HK estimates. In contrast, there was a steady decrease in emissions of most pollutants in the tunnels in the United States.

Association of Angiotensin-Converting Enzyme Inhibitors with Increased Mortality Among Patients with Isolated Severe Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is associated with one-third of all deaths from trauma. Preinjury exposure to cardiovascular drugs may affect TBI outcomes. Angiotensin-converting enzyme inhibitors (ACEIs) exacerbate brain cell damage and worsen functional outcomes in the laboratory setting. ß-blockers (BBs), however, appear to be associated with reduced mortality among patients with isolated TBI. OBJECTIVE: Examine the association between preinjury ACEI and BB use and clinical outcome among patients with isolated TBI. METHODS: A retrospective cohort study of patients age ≥ 40 years admitted to an academic level 1 trauma center with isolated TBI between January 2010 and December 2014 was performed. Isolated TBI was defined as a head Abbreviated Injury Scale (AIS) score ≥ 3, with chest, abdomen, and extremity AIS scores ≤ 2. Preinjury medication use was determined through chart review. All patients with concurrent BB use were initially excluded. In-hospital mortality was the primary measured outcome. RESULTS: Over the 5-year study period, 600 patients were identified with isolated TBI who were naive to BB use. There was significantly higher mortality (P = .04) among patients who received ACEI before injury (10 of 96; 10%) than among those who did not (25 of 504; 5%). A multivariate stepwise logistic regression analysis revealed a threefold increased risk of mortality in the ACEI cohort (P < .001), which was even greater than the twofold increased risk of mortality associated with an Injury Severity Score ≥ 16. A second analysis that included patients who received preinjury BBs (n = 98) demonstrated slightly reduced mortality in the ACEI cohort with only a twofold increased risk in multivariate analysis (P = .05). CONCLUSIONS: Preinjury exposure to ACEIs is associated with an increase in mortality among patients with isolated TBI. This effect is ameliorated in patients who receive BBs, which provides evidence that this class of medications may provide a protective benefit.