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IntroductionLesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) individuals use tobacco at disproportionately high rates but are as likely as straight tobacco users to want to quit and to use quitlines. Little is known about the demographics and geographic distribution of LGBTQ quitline participants, their engagement with services, or their long-term outcomes.Aims and methodsCalifornians (N = 333 429) who enrolled in a statewide quitline 2010-2022 were asked about their sexual and gender minority (SGM) status and other baseline characteristics. All were offered telephone counseling. A subset (n = 19 431) was followed up at seven months. Data were analyzed in 2023 by SGM status (LGBTQ vs. straight) and county type (rural vs. urban).ResultsOverall, 7.0% of participants were LGBTQ, including 7.4% and 5.4% of urban and rural participants, respectively. LGBTQ participants were younger than straight participants but had similar cigarette consumption. Fewer LGBTQ participants reported a physical health condition (42.1% vs. 48.4%) but more reported a behavioral health condition (71.1% vs. 54.5%; both p's < .001). Among both LGBTQ and straight participants, nearly 9 in 10 chose counseling and both groups completed nearly three sessions on average. The groups had equivalent 30-day abstinence rates (24.5% vs. 23.2%; p = .263). Similar patterns were seen in urban and rural subgroups.ConclusionsLGBTQ tobacco users engaged with and appeared to benefit from a statewide quitline even though it was not LGBTQ community-based. A quitline with staff trained in LGBTQ cultural competence can help address the high prevalence of tobacco use in the LGBTQ community and reach members wherever they live.ImplicationsThis study describes how participants of a statewide tobacco quitline broke down by sexual orientation and gender. It compares participants both by SGM status and by type of county to provide a more complete picture of quitline participation both in urban areas where LGBTQ community-based cessation programs may exist and in rural areas where they generally do not. To our knowledge, it is the first study to compare LGBTQ and straight participants on their use of quitline services and quitting aids, satisfaction with services received, and rates of attempting quitting and achieving prolonged abstinence from smoking.

BackgroundFamily meals are associated with adolescent health outcomes. Studies have reported that girls are less likely than boys to have dinner with their families.PurposeThis study examined gender differences in family meal frequency and the relationship between meal frequency and other health measures, using a large and representative sample of California middle and high school students.MethodsThis study analyzed data from the 2019-2020 California Student Tobacco Survey (159,904 students in grades 8, 10, and 12). Dinner with the family 5-7 times per week was defined as high frequency. Students reported substance use (of tobacco, marijuana, and alcohol) and rated their mental health and happiness in their home life. All analyses were weighted to reflect the California student population.ResultsFewer than half (44.7%) of students reported a high frequency of family meals, with boys more likely than girls and those who identified their gender in another way the least likely to do so (48.3%, 42.2%, 34.0%, respectively). Gender differences persisted across demographics and the quality of family relationships, and were evident as early as eighth grade. Less frequent family meals were associated with poorer mental health (OR = 1.34, 95% CI: 1.29-1.40) and substance use (OR = 1.27, 95% CI: 1.21-1.32), controlling for the effects of demographics and family dynamics.ConclusionGender differences in family meal frequency emerge early in adolescence and persist across demographics and family relationships. Given that family meals play a protective role in an adolescent's life, these gender differences are concerning.

IntroductionThe objective of this study was to examine access, engagement, and quitting behaviors of American Indian/Alaska Native (AIAN) callers to the California Smokers' Helpline. Telephone counseling is the primary function of the quitline. The overarching theoretical framework for California's quitline is social cognitive theory, although it also utilizes motivational interviewing and cognitive-behavioral strategies.Aims and methodsAIAN (n = 16 089) and White (n = 173 425) California quitline callers from 2009 to 2018 were compared on their characteristics, engagement, and quitting behaviors. Quitline callers responded to a telephone survey at intake. A random selection was called for evaluation 7 months later (White n = 8194, AIAN n = 764). Data from the 2009 to 2017 California Health Interview Survey (CHIS) were used as a reference point for AIANs (AIAN n = 1373).ResultsThe quitline and CHIS had similar proportions of AIANs (4.6% vs. 4.3%, respectively). AIAN smokers were more likely than White smokers to report physical (53.6% vs. 44.9%) and mental (65.7% vs. 57.8%) health conditions at intake. AIANs were more likely to participate in counseling than White callers (67.1% vs. 65.7%). Among those who received counseling, AIANs had greater odds than White smokers of making a quit attempt (adjusted odds ratio = 1.39 [1.06, 1.81]) and similar odds of quitting for 180 days (adjusted odds ratio = 0.95 [0.69, 1.31]).ConclusionsRates of access, engagement, and quitting suggest that individualized quitline counseling was as effective with AIANs as it was with White smokers. Increasing efforts to refer AIANs to existing state quitlines can help more smokers quit.ImplicationsThis study showed that AIAN smokers were well represented among California quitline callers, even without a targeted campaign. It also found that AIAN smokers engaged in quitline services and were as able to quit as their White counterparts were, even after adjusting for other baseline characteristics. One implication is that public health programs can promote quitlines using broad-based campaigns knowing that they will still motivate AIAN smokers to seek help. Another implication is that a standard, individualized counseling protocol delivered by culturally competent quitline staff can effectively help AIAN smokers to quit.

Genetics researchers and clinical professionals rely on diversity measures such as race, ethnicity, and ancestry (REA) to stratify study participants and patients for a variety of applications in research and precision medicine. However, there are no comprehensive, widely accepted standards or guidelines for collecting and using such data in clinical genetics practice. Two NIH-funded research consortia, the Clinical Genome Resource (ClinGen) and Clinical Sequencing Evidence-generating Research (CSER), have partnered to address this issue and report how REA are currently collected, conceptualized, and used. Surveying clinical genetics professionals and researchers (n = 448), we found heterogeneity in the way REA are perceived, defined, and measured, with variation in the perceived importance of REA in both clinical and research settings. The majority of respondents (>55%) felt that REA are at least somewhat important for clinical variant interpretation, ordering genetic tests, and communicating results to patients. However, there was no consensus on the relevance of REA, including how each of these measures should be used in different scenarios and what information they can convey in the context of human genetics. A lack of common definitions and applications of REA across the precision medicine pipeline may contribute to inconsistencies in data collection, missing or inaccurate classifications, and misleading or inconclusive results. Thus, our findings support the need for standardization and harmonization of REA data collection and use in clinical genetics and precision health research.

BackgroundWe examined the nicotine metabolite ratio's (NMR) relationship with smoking intensity, nicotine dependence, and a broad array of biomarkers of exposure and biological effect in commercial cigarette smokers.MethodsSecondary analysis was conducted on two cross-sectional samples of adult, daily smokers from Wave 1 (2013-2014) of the Population Assessment of Tobacco Use and Health (PATH) Study and baseline data from a 2014-2017 randomized clinical trial. Data were restricted to participants of non-Hispanic, white race. The lowest quartile of NMR (

BackgroundEarly hospital readmission for patients with cirrhosis continues to challenge the healthcare system. Risk stratification may help tailor resources, but existing models were designed using small, single-institution cohorts or had modest performance.AimsWe leveraged a large clinical database from the Department of Veterans Affairs (VA) to design a readmission risk model for patients hospitalized with cirrhosis. Additionally, we analyzed potentially modifiable or unexplored readmission risk factors.MethodsA national VA retrospective cohort of patients with a history of cirrhosis hospitalized for any reason from January 1, 2006, to November 30, 2013, was developed from 123 centers. Using 174 candidate variables within demographics, laboratory results, vital signs, medications, diagnoses and procedures, and healthcare utilization, we built a 47-variable penalized logistic regression model with the outcome of all-cause 30-day readmission. We excluded patients who left against medical advice, transferred to a non-VA facility, or if the hospital length of stay was greater than 30 days. We evaluated calibration and discrimination across variable volume and compared the performance to recalibrated preexisting risk models for readmission.ResultsWe analyzed 67,749 patients and 179,298 index hospitalizations. The 30-day readmission rate was 23%. Ascites was the most common cirrhosis-related cause of index hospitalization and readmission. The AUC of the model was 0.670 compared to existing models (0.649, 0.566, 0.577). The Brier score of 0.165 showed good calibration.ConclusionOur model achieved better discrimination and calibration compared to existing models, even after local recalibration. Assessment of calibration by variable parsimony revealed performance improvements for increasing variable inclusion well beyond those detectable for discrimination.

BackgroundA mandated reduction in the nicotine content of cigarettes could reduce smoking rate and prevalence. However, one concern is that smokers may compensate by increasing the intensity with which they smoke each cigarette to obtain more nicotine. This study assessed whether smokers engage in compensatory smoking by estimating the mouth-level nicotine intake of low nicotine cigarettes smoked during a clinical trial.MethodsSmokers were randomly assigned to receive cigarettes with one of five nicotine contents for 6 weeks. An additional group received a cigarette with the lowest nicotine content, but an increased tar yield. The obtained mouth-level nicotine intake from discarded cigarette butts for a subset of participants (51-70/group) was estimated using solanesol as described previously. A compensation index was calculated for each group to estimate the proportion of nicotine per cigarette recovered through changes in smoking intensity.ResultsThere was no significant increase in smoking intensity for any of the reduced nicotine cigarettes as measured by the compensation index (an estimated 0.4% of the nicotine lost was recovered in the lowest nicotine group; 95% confidence interval, -0.1 to 1.2). There was a significant decrease in smoking intensity for very low nicotine content cigarettes with increased tar yield.ConclusionsReductions in nicotine content did not result in compensatory changes in how intensively participants smoked research cigarettes.ImpactCombined with data from clinical trials showing a reduction in cigarettes smoked per day, these data suggest that a reduction in nicotine content is unlikely to result in increased smoke exposure.

Receiving offers of cigarettes or e-cigarettes can contribute to the progression from intention to actual use. However, there is a lack of data about the prevalence or characteristics of youth being offered cigarettes or e-cigarettes. A random sample of 91 high schools in the state of California (with 40,137 students) participated in the 2015⁻16 California Student Tobacco Survey. Offers of cigarettes and e-cigarettes in the last 30 days were assessed. Separate multilevel logistical regression models identified student characteristics associated with being offered cigarettes and e-cigarettes. On average, 11.1% and 16.1% of all students reported being offered cigarettes and e-cigarettes in the last 30 days, respectively. Among those who received offers of cigarettes, 45.5% were never smokers. Among those who received offers of e-cigarettes, 29.6% were never vapers. Male students were more likely to report being offered an e-cigarette than female students (Adjusted Odds Ratio (AOR) 1.13), as were students with friends that used e-cigarettes (AOR 5.14⁻23.31) and those with high sensation seeking tendencies (AOR 1.33). Similar characteristics were associated with offers of cigarettes. Including measures of offers of cigarettes and e-cigarettes in surveillance systems could help identify those at risk of future cigarette and e-cigarette use.

The urinary metabolites cyanoethyl mercapturic acid (CEMA) and 3-hydroxypropyl mercapturic acid (3-HPMA) have been widely used as biomarkers of exposure to acrylonitrile and acrolein, respectively, but there are no published data on their consistency over time in the urine of cigarette smokers. We provided, free of charge over a 20 week period, Spectrum NRC600/601 research cigarettes to cigarette smokers in the control arm of a randomized clinical trial of the reduced nicotine cigarette. Urine samples were collected at weeks 4, 8, 12, 16, and 20 and analyzed for CEMA and 3-HPMA, and total nicotine equivalents (TNE) using validated methods. Creatinine-corrected intra-class correlation coefficients for CEMA, 3-HPMA, and TNE were 0.67, 0.46, and 0.68, respectively, indicating good longitudinal consistency for CEMA, while that of 3-HPMA was fair. A strong correlation between CEMA and TNE values was observed. These data support the use of CEMA as a reliable biomarker of tobacco smoke exposure. This is the first report of the longitudinal stability of the biomarkers of acrylonitrile and acrolein exposure in smokers. The data indicate that CEMA, the biomarker of acrylonitrile exposure, is consistent over time in cigarette smokers, supporting its use. While 3-HPMA levels were less stable over time, this biomarker is nevertheless a useful monitor of human acrolein exposure because of its specificity to this toxicant.

The urinary metabolites (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8-iso-PGF2α), an F2-isoprostane and biomarker of oxidative damage, and "prostaglandin E2 metabolite" (PGE-M), a biomarker of inflammation, are elevated in cigarette smokers. However, there is little information in the literature on the longitudinal stability of these widely used biomarkers. In a large clinical trial involving 10 institutional sites, smokers were given, free of charge over a period of 20 weeks, Spectrum NRC600/601 research cigarettes containing 15.5 mg nicotine/g tobacco. All participants were instructed to smoke these cigarettes for the duration of the study. At weeks 4, 8, 12, 16, and 20, first morning urine voids were collected and analyzed for 8-iso-PGF2α and PGE-M using validated liquid chromatography-electrospray ionization-tandem mass spectrometry methods. The mean level of 8-iso-PGF2α at Week 4 was 1.34 ± 1.08 (S.D.) pmol/mg creatinine (N = 226) while that of PGE-M was 73.7 ± 113 (S.D.) pmol/mg creatinine (N = 232). The corresponding levels at Week 20 were 1.35 ± 0.93 (S.D.) pmol/mg creatinine (N = 209) for 8-iso-PGF2α and 74.2 ± 142 (S.D.) pmol/mg creatinine (N = 210) for PGE-M. There was variation in these values in the intervening weeks. The intra-class correlation coefficients (ICC) were 0.51 (95% CI, 0.45, 0.57) and 0.36 (0.30, 0.43), for 8-iso-PGF2α and PGE-M, respectively, indicating fair longitudinal stability for 8-iso-PGF2α and poorer longitudinal stability for PGE-M in cigarette smokers. Males had higher ICC values than females for both 8-iso-PGF2α and PGE-M. These results indicate that, in addition to cigarette smoking, endogenous processes of oxidative damage and inflammation influence the levels of these biomarkers over time among current smokers.

The BRCA Challenge is a long-term data-sharing project initiated within the Global Alliance for Genomics and Health (GA4GH) to aggregate BRCA1 and BRCA2 data to support highly collaborative research activities. Its goal is to generate an informed and current understanding of the impact of genetic variation on cancer risk across the iconic cancer predisposition genes, BRCA1 and BRCA2. Initially, reported variants in BRCA1 and BRCA2 available from public databases were integrated into a single, newly created site, www.brcaexchange.org. The purpose of the BRCA Exchange is to provide the community with a reliable and easily accessible record of variants interpreted for a high-penetrance phenotype. More than 20,000 variants have been aggregated, three times the number found in the next-largest public database at the project's outset, of which approximately 7,250 have expert classifications. The data set is based on shared information from existing clinical databases-Breast Cancer Information Core (BIC), ClinVar, and the Leiden Open Variation Database (LOVD)-as well as population databases, all linked to a single point of access. The BRCA Challenge has brought together the existing international Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium expert panel, along with expert clinicians, diagnosticians, researchers, and database providers, all with a common goal of advancing our understanding of BRCA1 and BRCA2 variation. Ongoing work includes direct contact with national centers with access to BRCA1 and BRCA2 diagnostic data to encourage data sharing, development of methods suitable for extraction of genetic variation at the level of individual laboratory reports, and engagement with participant communities to enable a more comprehensive understanding of the clinical significance of genetic variation in BRCA1 and BRCA2.

IntroductionMost successful trials of financial incentives for smoking cessation have offered large rewards contingent on outcomes. This study examines whether more modest incentives to encourage engagement, non-contingent on outcomes, also increase cessation; whether sending medications directly to participants boosts quitting; and whether these strategies are effective in Medicaid.Study designThree-group RCT of usual care (UC); nicotine patch (NP); and NP and financial incentive (NP+FI).Setting/participantsMedicaid beneficiaries calling the California Smokers' Helpline, 2012-2013 (N=3,816). Data were analyzed in 2017.InterventionAll participants enrolled in evidence-based, multisession telephone counseling. All received proof of enrollment with which they could obtain free quitting aids at their pharmacy. NP and NP+FI also received nicotine patches sent to their homes. NP+FI received up to $60 for completing counseling calls.Main outcome measuresQuit attempt rate, 7-day and 30-day abstinence at 2 and 7 months, and 6-month prolonged abstinence (primary outcome).ResultsIn both complete-case and intention-to-treat analyses, outcomes trended upward from UC to NP to NP+FI. Differences between NP and UC were generally nonsignificant. By contrast, the NP+FI group significantly outperformed the other groups on all measures. In intention-to-treat analysis, compared with UC, NP+FI was more likely to make a quit attempt (68.4% vs 54.3%, p

An RCT designed to increase Medicaid smokers' quitting success was conducted in California during 2012-2013. In the trial, alternative cessation treatment strategies were embedded in the state's ongoing quitline services. It found that modest financial incentives of up to $60 per participant and sending nicotine patches induced significantly higher cessation rates compared with usual care alone and usual care plus nicotine patches. Building upon that study, this study assessed potential population-level costs and benefits of integrating financial incentives and nicotine patches in a quitline setting for Medicaid smokers. A cost-benefit analysis was undertaken from the Medicaid program's perspective. The Cardiovascular Disease Policy Model was used to simulate future healthcare expenditures over a 10-year horizon for each treatment strategy for a study cohort of California Medicaid enrollees who were aged 35-64 years in 2014 (n=2,452,000). To simulate potential population-level benefits under each treatment strategy, each treatment was applied to all active smokers in the study cohort (n=478,300). Sensitivity analyses were conducted by varying key parameters, such as cessation costs, discount rate, relapse rates, and time horizon. Adding both financial incentives and nicotine patches to usual quitline care would result in $15 million net savings over 10 years, with a benefit-cost ratio of 1.30 compared with the usual care plus nicotine patches strategy. It would yield $44 million net savings, with a benefit-cost ratio of 1.90 compared with usual care alone. The strategy of providing financial incentives and mailing nicotine patches directly to Medicaid smokers who call the quitline is cost saving. SUPPLEMENT INFORMATION: This article is part of a supplement entitled Advancing Smoking Cessation in California's Medicaid Population, which is sponsored by the California Department of Public Health.

ImportanceThe optimal temporal approach for reducing nicotine to minimally or nonaddictive levels in all cigarettes sold in the United States has not been determined.ObjectivesTo determine the effects of immediate vs gradual reduction in nicotine content to very low levels and as compared with usual nicotine level cigarettes on biomarkers of toxicant exposure.Design, setting, and participantsA double-blind, randomized, parallel-design study with 2 weeks of baseline smoking and 20 weeks of intervention was conducted at 10 US sites. A volunteer sample of daily smokers with no intention to quit within 30 days was recruited between July 2014 and September 2016, with the last follow-up completed in March 2017.Interventions(1) Immediate reduction to 0.4 mg of nicotine per gram of tobacco cigarettes; (2) gradual reduction from 15.5 mg to 0.4 mg of nicotine per gram of tobacco cigarettes with 5 monthly dose changes; or (3) maintenance on 15.5 mg of nicotine per gram of tobacco cigarettes.Main outcomes and measuresBetween-group differences in 3 co-primary biomarkers of smoke toxicant exposure: breath carbon monoxide (CO), urine 3-hydroxypropylmercapturic acid (3-HPMA, metabolite of acrolein), and urine phenanthrene tetraol (PheT, indicator of polycyclic aromatic hydrocarbons) calculated as area under the concentration-time curve over the 20 weeks of intervention.ResultsAmong 1250 randomized participants (mean age, 45 years; 549 women [44%]; 958 [77%] completed the trial), significantly lower levels of exposure were observed in the immediate vs gradual reduction group for CO (mean difference, -4.06 parts per million [ppm] [95% CI, -4.89 to -3.23]; P

PurposeWe aimed to examine the availability of medical marijuana dispensaries, price of medical marijuana products, and variety of medical marijuana products in school neighborhoods and their associations with adolescents' use of marijuana and susceptibility to use marijuana in the future.MethodsA representative sample of 8th, 10th, and 12th graders (N = 46,646) from 117 randomly selected schools in California participated in the cross-sectional 2015-2016 California Student Tobacco Survey (CSTS). Characteristics of medical marijuana dispensaries in California were collected and combined with school locations to compute availability, price, and product variety of medical marijuana in school neighborhoods. Multilevel logistic regressions with random intercepts at school level were conducted to test the associations, accounting for individual and school socioeconomic characteristics.ResultsThe distance from school to the nearest medical marijuana dispensary (within 0- to 1-mi and 1- to 3-mi bands) was not associated with adolescents' use of marijuana in the past month or susceptibility to use marijuana in the future, nor was the weighted count of medical marijuana dispensaries within the 3-mi band of school. Neither the product price nor the product variety in the dispensary nearest to school was associated with marijuana use or susceptibility to use. The results were robust to different specifications of medical marijuana measures.ConclusionsThere was no evidence supporting the associations of medical marijuana availability, price, or product variety around school with adolescents' marijuana use and susceptibility to use.

OBJECTIVE:Hepatorenal Syndrome (HRS) is a devastating form of acute kidney injury (AKI) in advanced liver disease patients with high morbidity and mortality, but phenotyping algorithms have not yet been developed using large electronic health record (EHR) databases. We evaluated and compared multiple phenotyping methods to achieve an accurate algorithm for HRS identification. MATERIALS AND METHODS:A national retrospective cohort of patients with cirrhosis and AKI admitted to 124 Veterans Affairs hospitals was assembled from electronic health record data collected from 2005 to 2013. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. Five hundred and four hospitalizations were selected for manual chart review and served as the gold standard. Electronic Health Record based predictors were identified using structured and free text clinical data, subjected through NLP from the clinical Text Analysis Knowledge Extraction System. We explored several dimension reduction techniques for the NLP data, including newer high-throughput phenotyping and word embedding methods, and ascertained their effectiveness in identifying the phenotype without structured predictor variables. With the combined structured and NLP variables, we analyzed five phenotyping algorithms: penalized logistic regression, naïve Bayes, support vector machines, random forest, and gradient boosting. Calibration and discrimination metrics were calculated using 100 bootstrap iterations. In the final model, we report odds ratios and 95% confidence intervals. RESULTS:The area under the receiver operating characteristic curve (AUC) for the different models ranged from 0.73 to 0.93; with penalized logistic regression having the best discriminatory performance. Calibration for logistic regression was modest, but gradient boosting and support vector machines were superior. NLP identified 6985 variables; a priori variable selection performed similarly to dimensionality reduction using high-throughput phenotyping and semantic similarity informed clustering (AUC of 0.81 - 0.82). CONCLUSION:This study demonstrated improved phenotyping of a challenging AKI etiology, HRS, over ICD-9 coding. We also compared performance among multiple approaches to EHR-derived phenotyping, and found similar results between methods. Lastly, we showed that automated NLP dimension reduction is viable for acute illness.

Background and aimsThe California Tobacco-Use Prevention Education (TUPE) program promotes the use of evidence-based tobacco-specific prevention and cessation programs for adolescents within the school setting. Through a competitive grant process, schools are funded to provide programs for grades 6-12. This research evaluates the association between TUPE funding and tobacco prevention activities and tobacco use prevalence.MethodsThis study utilized two data sources: (1) 2016 California Educator Tobacco Survey (CETS), and (2) 2015-2016 California Student Tobacco Survey (CSTS). The CETS collected data from educators about school prevention efforts, priority of tobacco prevention, and confidence in addressing tobacco issues with students. A total of 3,564 educators from 590 schools participated in CETS. The CSTS collected data from 8th, 10th, and 12th graders in California on their exposure to, attitudes about, and utilization of tobacco products. A total of 47,981 students from 117 schools participated in CSTS.ResultsThis study found that TUPE-funded schools were more likely to provide tobacco-specific health education programs, to place a priority on tobacco-prevention efforts, and to prepare educators to address tobacco use than non-TUPE schools. Educators at both types of schools felt better prepared to talk with students about traditional tobacco products than about emerging products such as e-cigarettes. Overall, students at TUPE-funded schools were more likely to report receiving anti-tobacco messages from school-based programs than those at non-TUPE schools. The former were also less likely to use tobacco products, even when the analysis controlled for demographics and school-level characteristics (OR = 0.82 [95% CI = 0.70-0.96]).ConclusionsTUPE funding was associated with an increase in schools' tobacco-specific prevention activities and these enhanced activities were associated with lower tobacco use among students. This study also found that education and prevention efforts regarding emerging tobacco products need to be strengthened across all schools.

AimsTo estimate the prevalence and predictors of failed biochemical verification of self-reported abstinence among participants enrolled in trials of hospital-initiated smoking cessation interventions.DesignComparison of characteristics between participants who verified and those who failed to verify self-reported abstinence.SettingsMulti-site randomized clinical trials conducted between 2010 and 2014 in hospitals throughout the United States.ParticipantsRecently hospitalized smokers who reported tobacco abstinence 6 months post-randomization and provided a saliva sample for verification purposes (n = 822).MeasurementsOutcomes were salivary cotinine-verified smoking abstinence at 10 and 15 ng/ml cut-points. Predictors and correlates included participant demographics and tobacco use; hospital diagnoses and treatment; and study characteristics collected via surveys and electronic medical records.FindingsUsable samples were returned by 69.8% of the 1178 eligible trial participants who reported 7-day point prevalence abstinence. The proportion of participants verified as quit was 57.8% [95% confidence interval (CI) = 54.4, 61.2; 10 ng/ml cut-off] or 60.6% (95% CI = 57.2, 63.9; 15 ng/ml). Factors associated independently with verification at 10 ng/ml were education beyond high school education [odds ratio (OR) = 1.51; 95% CI = 1.07, 2.11], continuous abstinence since hospitalization (OR = 2.82; 95% CI = 2.02, 3.94), mailed versus in-person sample (OR = 3.20; 95% CI = 1.96, 5.21) and race. African American participants were less likely to verify abstinence than white participants (OR = 0.64; 95% CI = 0.44, 0.93). Findings were similar for verification at 15 ng/ml. Verification rates did not differ by treatment group.ConclusionsIn the United States, high rates (40%) of recently hospitalized smokers enrolled in smoking cessation trials fail biochemical verification of their self-reported abstinence.

Objective To examine whether the increase in use of electronic cigarettes in the USA, which became noticeable around 2010 and increased dramatically by 2014, was associated with a change in overall smoking cessation rate at the population level.Design Population surveys with nationally representative samples.Setting Five of the US Current Population Survey-Tobacco Use Supplement (CPS-TUS) in 2001-02, 2003, 2006-07, 2010-11, and 2014-15.Participants Data on e-cigarette use were obtained from the total sample of the 2014-15 CPS-TUS (n=161 054). Smoking cessation rates were obtained from those who reported smoking cigarettes 12 months before the survey (n=23 270). Rates from 2014-15 CPS-TUS were then compared with those from 2010-11 CPS-TUS (n=27 280) and those from three other previous surveys.Main outcome measures Rate of attempt to quit cigarette smoking and the rate of successfully quitting smoking, defined as having quit smoking for at least three months.Results Of 161 054 respondents to the 2014-15 survey, 22 548 were current smokers and 2136 recent quitters. Among them, 38.2% of current smokers and 49.3% of recent quitters had tried e-cigarettes, and 11.5% and 19.0% used them currently (every day or some days). E-cigarette users were more likely than non-users to attempt to quit smoking, 65.1% v 40.1% (change=25.0%, 95% confidence interval 23.2% to 26.9%), and more likely to succeed in quitting, 8.2% v 4.8% (3.5%, 2.5% to 4.5%). The overall population cessation rate for 2014-15 was significantly higher than that for 2010-11, 5.6% v 4.5% (1.1%, 0.6% to 1.5%), and higher than those for all other survey years (range 4.3-4.5%).Conclusion The substantial increase in e-cigarette use among US adult smokers was associated with a statistically significant increase in the smoking cessation rate at the population level. These findings need to be weighed carefully in regulatory policy making regarding e-cigarettes and in planning tobacco control interventions.

BackgroundAlthough most US states prohibit cigarette smoking in public places and worksites, fewer jurisdictions regulate indoor use of electronic cigarettes (e-cigarettes). Given the dramatic increase in e-cigarette use and concern about its impact on non-users, there is a need to examine the use of e-cigarettes in smoke-free environments and related attitudes and perceptions.MethodsRecruited from a nationally representative adult panel (GfK's KnowledgePanel), 952 current users of e-cigarettes completed a cross-sectional online survey in 2014. Multivariate logistic regressions were conducted to examine the factors associated with ever using e-cigarettes in smoke-free environments.ResultsOverall, 59.5% of e-cigarette users had vaped where cigarette smoking was not allowed. Young adults (18-29 years) were most likely to do so, 74.2%. The places of first-time use most often mentioned were service venues (bar, restaurant, lounge and club), 30.7%, followed by worksites, 23.5%. Daily e-cigarette users were more likely to have vaped in smoke-free environments than non-daily users (OR=2.08, p=0.012). Only 2.5% of those who used e-cigarettes in smoke-free environments reported negative reactions from other people. Most e-cigarette users did not think e-cigarettes are harmful to themselves or to by-standers, and thus should not be banned where smoking is; those who had used e-cigarettes where smoking is banned were even more likely to hold these views.ConclusionsE-cigarette use in smoke-free environments was common, suggesting that most e-cigarette users do not consider smoke-free laws to apply to e-cigarettes. Explicit laws should be considered if jurisdictions want to prohibit e-cigarette use in public places.

IntroductionSocial and behavioral factors are known to affect health but are not routinely assessed in medical practice. To date, no studies have assessed a parsimonious panel of measures of social and behavioral determinants of health (SBDs). This study evaluated the panel of SBD measures recommended by the Institute of Medicine and examined the effect of question order.MethodsAdults, aged ≥18 years, were recruited using ResearchMatch.org for this randomized, parallel design study conducted in 2015 (data analyzed in 2015-2016). Three versions of the SBD measures, sharing the same items but in different orders of presentation (Versions 1-3), were developed. Randomized to six groups, participants completed each version at least 1 week apart (Weeks 1-3). Version order was counterbalanced across each administration and randomization was stratified by gender, race, and age. Main outcomes were effect of question order, completion time, and non-response rates.ResultsOf 781 participants, 624 (80%) completed the Week 1 questionnaire; median completion time for answering all SBD questions was 5 minutes, 583/624 participants answered all items, and no statistically significant differences associated with question order were observed when comparing responses across all versions. No significant differences in responses within assignment groups over time were found, with the exception of the stress measure for Group 5 (p=0.036).ConclusionQuestion order did not significantly impact participant responses. Time to complete the questionnaire was brief, and non-response rate was low. Findings support the feasibility of using the Institute of Medicine-recommended questionnaire to capture SBDs.

While smoking is the primary cause of lung cancer, only 11-24% of smokers develop the malignancy over their lifetime. The primary addictive agent in tobacco smoke is nicotine and variation in nicotine metabolism may influence the smoking levels of an individual. Therefore, inter-individual variation in lung cancer risk among smokers may be due in part to differences in the activity of enzymes involved in nicotine metabolism. In most smokers, cytochrome P450 2A6 (CYP2A6)-catalyzed C-oxidation accounts for >75% of nicotine metabolism, and the activity of this enzyme has been shown to correlate with the amount of nicotine and carcinogens drawn from cigarettes. We prospectively evaluated the association of urinary biomarkers of nicotine uptake (total nicotine equivalents [TNE]) and CYP2A6 activity (ratio of urinary total trans-3'-hydroxycotinine to cotinine) with lung cancer risk among 2,309 Multiethnic Cohort Study participants who were current smokers at time of urine collection; 92 cases were diagnosed during a mean follow-up of 9.5 years. We found that higher CYP2A6 activity and TNE was associated with increased lung cancer risk after adjusting for age, sex, race/ethnicity, body mass index, smoking duration, and urinary creatinine (p's = 0.002). The association for CYP2A6 activity remained even after adjusting for self-reported cigarettes per day (CPD) (Hazard Ratio [HR] per unit increase in log-CYP2A6 activity = 1.52; p = 0.005) and after adjusting for TNE (HR = 1.46; p = 0.01). In contrast, the association between TNE and lung cancer risk was of borderline statistical significance when adjusted for CPD (HR = 1.53; p = 0.06) and not statistically significant when further adjusted for CYP2A6 activity (HR = 1.30; p = 0.22). These findings suggest that CYP2A6 activity provides information on lung cancer risk that is not captured by smoking history or a (short-term) biomarker of dose. CYP2A6 activity should be further studied as a risk biomarker for smoking-related lung cancer.

Background and aimsClinical trials on the impact and safety of reduced nicotine content cigarettes (RNCs) are ongoing, and an important methodological concern is participant compliance with smoking only RNCs. Our aims were to measure non-compliance biochemically with urine cotinine (COT) and total nicotine equivalents (TNEs), compare with self-reported non-compliance and identify associated covariates.DesignSecondary analysis of a double-blind, parallel, randomized clinical trial.SettingResearch centers from the United States, enrolling participants from June 2013 to July 2014.ParticipantsVolunteer sample of 242 participants (55% Caucasian), average age of 41.2 years, smoking at least five cigarettes per day (CPD).InterventionSmoking very low nicotine cigarettes (VLNCs; 0.4 mg nicotine/g tobacco) for 6 weeks.MeasurementsThe primary outcome was biochemically verified non-compliance, measured as thresholds of COT/CPD and TNE/CPD ratios, considering changes in nicotine content from conventional levels to VLNCs, and as an absolute threshold of week 6 TNEs. Self-reported non-compliance was measured via daily phone calls. Key predictors included age, sex, race, menthol preference, nicotine metabolite ratio, time to first cigarette, dependence, CPD, TNEs, tar level and cigarette evaluation.FindingsEstimates of non-compliance with smoking the VLNCs exclusively include: the biochemical ratios (both 78%), the week 6 TNE threshold (76%) and self-report (39%). Of the key covariates, age, dependence and cigarette evaluations of satisfaction were significant; for age, younger participants more likely to be non-compliant [P = 0.01; odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.96-0.99]. Dependence was associated significantly with self-reported non-compliance (P = 0.01; OR = 1.28, 95% CI = 1.06-1.55). Cigarette evaluations of satisfaction were associated significantly with non-compliance (P = 0.001; OR = 0.71, 95% CI = 0.61-0.82).ConclusionsAmong smokers volunteering to smoke only very low nicotine cigarettes for 6 weeks, non-compliance was common and biochemical assessments detected more cases of non-compliance than self-report. Despite high levels of non-compliance, smokers reduced their intake of nicotine by an average of 60%.

IntroductionMost smokers abstain from smoking during hospitalization but relapse upon discharge. This study tests the effectiveness of two proven treatments (i.e., nicotine patches and telephone counseling) in helping these patients stay quit after discharge from the hospital, and assesses a model of hospital-quitline partnership.Study designThis study had a 2×2 factorial design in which participants were stratified by recruitment site and smoking rate and randomly assigned to usual care, nicotine patches only, counseling only, or patches plus counseling. They were evaluated at 2 and 6 months post-randomization.Setting/participantsA total of 1,270 hospitalized adult smokers were recruited from August 2011 to November 2013 from five hospitals within three healthcare systems.InterventionParticipants in the patch condition were provided 8 weeks of nicotine patches at discharge (or were mailed them post-discharge). Quitline staff started proactively calling participants in the counseling condition 3 days post-discharge to provide standard quitline counseling.Main outcome measuresThe primary outcome measure was self-reported 30-day abstinence at 6 months using an intention-to-treat analysis. Data were analyzed from September 2015 to May 2016.ResultsThe 30-day abstinence rate at 6 months was 22.8% for the nicotine patch condition and 18.3% for the no-patch condition (p=0.051). Nearly all participants (99%) in the patch condition were provided nicotine patches, although 36% were sent post-discharge. The abstinence rates were 20.0% and 21.1% for counseling and no counseling conditions, respectively (p=0.651). Fewer than half of the participants in the counseling condition (47%) received counseling (mean follow-up sessions, 3.6).ConclusionsProvision of nicotine patches proved feasible, although their effectiveness in helping discharged patients stay quit was not significant. Telephone counseling was not effective, in large part because of low rates of engagement. Future interventions will need to be more immediate to be effective.Trial registrationThis study is registered at www.clinicaltrials.gov NCT01289275.

BackgroundE-cigarettes have grown popular. The most common pattern is dual use with conventional cigarettes. Dual use has raised concerns that it might delay quitting of cigarette smoking. This study examined the relationship between long-term use of e-cigarettes and smoking cessation in a 2-year period.MethodsA nationally representative sample of 2028 US smokers were surveyed in 2012 and 2014. Long-term e-cigarette use was defined as using e-cigarettes at baseline and follow-up. Use of e-cigarettes only at baseline or at follow-up was defined as short-term use. Non-users did not use e-cigarettes at either survey. Quit attempt rates and cessation rates (abstinent for 3 months or longer) were compared across the three groups.ResultsAt 2-year follow-up, 43.7% of baseline dual users were still using e-cigarettes. Long-term e-cigarette users had a higher quit attempt rate than short-term or non-users (72.6% vs 53.8% and 45.5%, respectively), and a higher cessation rate (42.4% vs 14.2% and 15.6%, respectively). The difference in cessation rate between long-term users and non-users remained significant after adjusting for baseline variables, OR=4.1 (95% CI 1.5 to 11.4) as did the difference between long-term users and short-term users, OR=4.8 (95% CI 1.6 to 13.9). The difference in cessation rate between short-term users and non-users was not significant, OR=0.9 (95% CI 0.5 to 1.4). Among those making a quit attempt, use of e-cigarettes as a cessation aid surpassed that of FDA-approved pharmacotherapy.ConclusionsShort-term e-cigarette use was not associated with a lower rate of smoking cessation. Long-term use of e-cigarettes was associated with a higher rate of quitting smoking.

The number of children and adolescents seen in emergency departments (EDs) and primary care settings for mental health problems has skyrocketed in recent years, with up to 23% of patients in both settings having diagnosable mental health conditions. 1 -4 Even when a mental health problem is not the focus of an ED or primary care visit, mental health conditions, both known and occult, may challenge the treating clinician and complicate the patient's care.4 Although the American Academy of Pediatrics (AAP) has published a policy statement on mental health competencies and a Mental Health Toolkit for pediatric primary care providers, no such guidelines or resources exist for clinicians who care for pediatric mental health emergencies. 5, 6 Many ED and primary care physicians report paucity of training and lack of confidence in caring for pediatric psychiatry patients. The 2 clinical reports support the 2006 joint policy statement of the AAP and the American College of Emergency Physicians on pediatric mental health emergencies, 7 with the goal of addressing the knowledge gaps in this area. Although written primarily from the perspective of ED clinicians, it is intended for all clinicians who care for children and adolescents with acute mental health and behavioral problems. They are organized around the common clinical challenges pediatric caregivers face, both when a child or adolescent presents with a psychiatric chief complaint or emergency (part I) and when a mental health condition may be an unclear or complicating factor in a non-mental health ED presentation (part II). Part I of the clinical reports includes discussions of Medical Clearance of Pediatric Psychiatric Patients, Suicide and Suicidal Ideation, Restraint of the Agitated Patient Including Verbal, Chemical, and Physical Restraint, and Coordination of Care With the Medical Home, and it can be accessed online at www.pediatrics.org/cgi/doi/10.1542/peds. 2016-1570. This executive summary is an overview of part II of the clinical reports. Full text of the following topics can be accessed online at www.pediatrics.org/cgi/doi/10.1542/peds. 2016-1573.

The number of children and adolescents seen in emergency departments (EDs) and primary care settings for mental health problems has skyrocketed in recent years, with up to 23% of patients in both settings having diagnosable mental health conditions. 1 -4 Even when a mental health problem is not the focus of an ED or primary care visit, mental health conditions, both known and occult, may challenge the treating clinician and complicate the patient's care.4 Although the American Academy of Pediatrics has published a policy statement on mental health competencies and a Mental Health Toolkit for pediatric primary care providers, no such guidelines or resources exist for clinicians who care for pediatric mental health emergencies. 5, 6 Many ED and primary care physicians report a paucity of training and lack of confidence in caring for pediatric psychiatry patients. The 2 clinical reports (www.pediatrics.org/cgi/doi/10.1542/peds. 2016-1570 and www.pediatrics.org/cgi/doi/10.1542/peds. 2016-1573) support the 2006 joint policy statement of the American Academy of Pediatrics and the American College of Emergency Physicians on pediatric mental health emergencies, 7 with the goal of addressing the knowledge gaps in this area. Although written primarily from the perspective of ED clinicians, they are intended for all clinicians who care for children and adolescents with acute mental health and behavioral problems. The clinical reports are organized around the common clinical challenges pediatric caregivers face, both when a child or adolescent presents with a psychiatric chief complaint or emergency (part I) and also when a mental health condition may be an unclear or complicating factor in a non-mental health clinical presentation (part II). Part II of the clinical reports (www.pediatrics.org/cgi/doi/10.1542/peds. 2016-1573) includes discussions of somatic symptom and related disorders, adverse effects of psychiatric medications including neuroleptic malignant syndrome and serotonin syndrome, caring for children with special needs such as autism and developmental disorders, and mental health screening. This executive summary is an overview of part I of the clinical reports. The full text of the below topics can be accessed online at (www.pediatrics.org/cgi/doi/10.1542/peds. 2016-1570). Key considerations are shown in the following sections.

BackgroundVarenicline is known to have greater efficacy than other pharmacotherapy for treating nicotine dependence and has gained popularity since its introduction in 2006. This study examines if adding varenicline to existing pharmacotherapies increased the population cessation rate.MethodsData are from two cross-sectional US Current Population Surveys-Tobacco Use Supplements (2003 and 2010-2011). Smokers and recent quitters 18 or older (N=34 869 in 2003, N=27 751 in 2010-2011) were asked if they had used varenicline, bupropion or nicotine replacement therapies (NRT) in their most recent quit attempt. The annual cessation rate, as well as the per cent of smokers who had quit for ≥3 months, was compared between surveys.ResultsVarenicline use increased from 0% in 2003 to 10.9% in 2010-2011, while use of bupropion decreased from 9.1% to 3.5%, and NRT from 24.5% to 22.4%. Use of any pharmacotherapy increased by 2.4 percentage points. Varenicline users stayed on cessation aids longer and were less likely to relapse than users of other pharmacotherapies in the first 3 months of a quit attempt, after which the difference was no longer significant. The change in annual cessation rate was negligible, from 4.5% in 2003 to 4.7% in 2010-2011 (p=0.36).ConclusionsAddition of varenicline to the list of approved cessation aids has mainly led to displacement of other therapies. As a result, there was no meaningful change in population cessation rate despite a remarkable increase in varenicline use. The population impact of a new therapy is a function of more than efficacy or reach of the therapy.

Neonatal cholestasis is a potentially life-threatening condition requiring prompt diagnosis. Mutations in several different genes can cause progressive familial intrahepatic cholestasis, but known genes cannot account for all familial cases. Here we report four individuals from two unrelated families with neonatal cholestasis and mutations in NR1H4, which encodes the farnesoid X receptor (FXR), a bile acid-activated nuclear hormone receptor that regulates bile acid metabolism. Clinical features of severe, persistent NR1H4-related cholestasis include neonatal onset with rapid progression to end-stage liver disease, vitamin K-independent coagulopathy, low-to-normal serum gamma-glutamyl transferase activity, elevated serum alpha-fetoprotein and undetectable liver bile salt export pump (ABCB11) expression. Our findings demonstrate a pivotal function for FXR in bile acid homeostasis and liver protection.

BackgroundPeople with mental health conditions (MHC) smoke at high rates and many die prematurely from smoking-related illnesses. Smoking cessation programs, however, generally do not screen for MHC. This study examined the utility of MHC screening in a large tobacco quitline to determine whether self-reported MHC predicts service utilization and quitting behaviors.Methods & findingsA brief set of question on MHC was embedded in the routine intake of a state quitline, and 125,261 smokers calling from June 2012 to September 2015 were asked the questions. Quit attempt rate and 6-month success rate were analyzed for a random subset of participants. Overall, 52.2% of smokers reported at least one MHC. Demographic patterns like gender or ethnic difference in self-reported MHC were similar to that in the general population. Depression disorder was reported most often (38.6%), followed by anxiety disorder (33.8%), bipolar disorder (17.0%), drug/alcohol abuse (11.9%), and schizophrenia (7.9%). Among those reporting any MHC, about two-thirds reported more than 1 MHC. Smokers with MHC received more counseling than smokers with no MHC. Quit attempt rates were high for all three groups (>70%). The probability of relapse was greater for those with more than one MHC than for those with one MHC (p

BackgroundComplex wounds present a substantial economic burden on healthcare systems, costing billions of dollars annually in North America alone. The prevalence of complex wounds is a significant patient and societal healthcare concern and cost-effective wound care management remains unclear. This article summarizes the cost-effectiveness of interventions for complex wound care through a systematic review of the evidence base.MethodsWe searched multiple databases (MEDLINE, EMBASE, Cochrane Library) for cost-effectiveness studies that examined adults treated for complex wounds. Two reviewers independently screened the literature, abstracted data from full-text articles, and assessed methodological quality using the Drummond 10-item methodological quality tool. Incremental cost-effectiveness ratios were reported, or, if not reported, calculated and converted to United States Dollars for the year 2013.ResultsOverall, 59 cost-effectiveness analyses were included; 71% (42 out of 59) of the included studies scored 8 or more points on the Drummond 10-item checklist tool. Based on these, 22 interventions were found to be more effective and less costly (i.e., dominant) compared to the study comparators: 9 for diabetic ulcers, 8 for venous ulcers, 3 for pressure ulcers, 1 for mixed venous and venous/arterial ulcers, and 1 for mixed complex wound types.ConclusionsOur results can be used by decision-makers in maximizing the deployment of clinically effective and resource efficient wound care interventions. Our analysis also highlights specific treatments that are not cost-effective, thereby indicating areas of resource savings. Please see related article: http://dx.doi.org/10.1186/s12916-015-0288-5.

ObjectivesWe conducted a dissemination and implementation study to translate an intervention protocol for Asian-language smokers from an efficacy trial into an effective and sustainable multistate service.MethodsThree state tobacco programs (in California, Colorado, and Hawaii) promoted a multistate cessation quitline to 3 Asian-language-speaking communities: Chinese, Korean, and Vietnamese. The California quitline provided counseling centrally to facilitate implementation. Three more states joined the program during the study period (January 2010-July 2012). We assessed the provision of counseling, quitting outcomes, and dissemination of the program.ResultsA total of 2004 smokers called for the service, with 88.3% opting for counseling. Among those opting for counseling, the 6-month abstinence rate (18.8%) was similar to results of the earlier efficacy trial (16.4%).ConclusionsThe intervention protocol, based on an efficacy trial, was successfully translated into a multistate service and further disseminated. This project paved the way for the establishment of a national quitline for Asian-language speakers, which serves as an important strategy to address disparities in access to care.

BackgroundDespite the paramount importance of patient-reported outcomes, little is known about the evolution of patient-reported urinary and sexual function over time.ObjectiveTo evaluate differences in pretreatment urinary and sexual function in two population-based cohorts of men with prostate cancer enrolled nearly 20 yr apart.Design, setting, and participantsPatients were enrolled in the Prostate Cancer Outcomes Study (PCOS) or the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study, two population-based cohorts that enrolled patients with incident prostate cancer from 1994 to 1995 and from 2011 to 2012, respectively. Participants completed surveys at baseline and various time points thereafter.Outcome measurements and statistical analysisWe performed multivariable logistic and linear regression analysis to investigate differences in pretreatment function between studies.Results and limitationsThe study comprised 5469 men of whom 2334 (43%) were enrolled in PCOS and 3135 (57%) were enrolled in CEASAR. Self-reported urinary incontinence was higher in CEASAR compared with PCOS (7.7% vs 4.7%; adjusted odds ratio [OR]: 1.83; 95% confidence interval [CI], 1.39-2.43). Similarly, self-reported erectile dysfunction was more common among CEASAR participants (44.7% vs 24.0%) with an adjusted OR of 3.12 (95% CI, 2.68-3.64). Multivariable linear regression models revealed less favorable self-reported baseline function among CEASAR participants in the urinary incontinence and sexual function domains. The study is limited by its observational design and possibility of unmeasured confounding.ConclusionsReporting of pretreatment urinary incontinence and erectile dysfunction has increased over the past two decades. These findings may reflect sociological changes including heightened media attention and direct-to-consumer marketing, among other potential explanations.Patient summaryPatient reporting of urinary and sexual function has evolved and is likely contingent on continually changing societal norms. Recognizing the evolving nature of patient reporting is essential in efforts to conduct high-quality, impactful comparative effectiveness research.

Epidemiologic studies have shown sex differences in ischemic stroke. The four core genotype (FCG) mouse model, in which the testes determining gene, Sry, has been moved from Y chromosome to an autosome, was used to dissociate the effects of sex hormones from sex chromosome in ischemic stroke outcome. Middle cerebral artery occlusion (MCAO) in gonad intact FCG mice revealed that gonadal males (XXM and XYM) had significantly higher infarct volumes as compared with gonadal females (XXF and XYF). Serum testosterone levels were equivalent in adult XXM and XYM, as was serum estrogen in XXF and XYF mice. To remove the effects of gonadal hormones, gonadectomized FCG mice were subjected to MCAO. Gonadectomy significantly increased infarct volumes in females, while no change was seen in gonadectomized males, indicating that estrogen loss increases ischemic sensitivity. Estradiol supplementation in gonadectomized FCG mice rescued this phenotype. Interestingly, FCG male mice were less sensitive to effects of hormones. This may be due to enhanced expression of the transgene Sry in brains of FCG male mice. Sex differences in ischemic stroke sensitivity appear to be shaped by organizational and activational effects of sex hormones, rather than sex chromosomal complement.

BackgroundIndividuals with mental health conditions (MHC) have disproportionately high tobacco-related morbidity and mortality due to high smoking prevalence rates. As high consumers of cigarettes, smokers with MHC may consider using e-cigarettes as an alternative form of nicotine delivery.ObjectiveExamination of the susceptibility to use e-cigarettes by individuals with MHC.MethodsA U.S. population survey with a national probability sample (n=10,041) was used to assess ever use and current use of regular cigarettes, e-cigarettes, and U.S. Food and Drug Administration-approved pharmacotherapy for smoking cessation. Survey respondents provided information about whether they had been diagnosed with an anxiety disorder, depression, or other MHC.ResultsIndividuals with MHC were more likely to have tried e-cigarettes (14.8%) and to be current users of e-cigarettes (3.1%) than those without MHC (6.6% and 1.1%, respectively; p

BackgroundThe authors investigated the prevalence of pretreatment urinary, sexual, hormonal, and bowel dysfunction in a contemporary, population-based prostate cancer cohort. They also explored the associations between baseline function and age, comorbidity, and timing of baseline survey completion with respect to treatment.MethodsThe Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a population-based, prospective cohort study that enrolled 3691 men with incident prostate cancer during 2011 and 2012. Pretreatment function was ascertained using the Expanded Prostate Cancer Index-26 (EPIC-26). Data were stratified by age, comorbidity, and timing of baseline survey completion with respect to treatment. Unadjusted and multivariable linear regression analyses were performed to evaluate the relations between exposures and pretreatment function.ResultsAfter applying exclusion criteria, the study cohort comprised 3072 men. A strikingly high proportion of men reported inability to obtain erections satisfactory for intercourse (45%) and some degree of urinary incontinence (17%) at baseline. Sexual function was particularly age-sensitive, with patients aged ≤60 years reporting summary scores in excess of 30 points higher than patients aged ≥75 years (P < .001). Compared with the healthiest men, highly comorbid patients reported less favorable function in each domain, including urinary incontinence (summary score, 89.5 vs 74.1; P < .001) and sexual function (summary score, 70.8 vs 32.9; P < .001). Although statistically significant differences in summary scores were identified between patients who completed the baseline questionnaire before treatment (52%) versus after treatment (48%), the absolute differences were small (range, 1-3 points).ConclusionsPatients with newly diagnosed prostate cancer exhibit a wide distribution of pretreatment function. The current data may be used to redefine the population "at risk" for treatment-related harms.

PurposeTo explore the mentor-mentee relationship with a focus on determining the characteristics of effective mentors and mentees and understanding the factors influencing successful and failed mentoring relationships.MethodThe authors completed a qualitative study through the Departments of Medicine at the University of Toronto Faculty of Medicine and the University of California, San Francisco, School of Medicine between March 2010 and January 2011. They conducted individual, semistructured interviews with faculty members from different career streams and ranks and analyzed transcripts of the interviews, drawing on grounded theory.ResultsThe authors completed interviews with 54 faculty members and identified a number of themes, including the characteristics of effective mentors and mentees, actions of effective mentors, characteristics of successful and failed mentoring relationships, and tactics for successful mentoring relationships. Successful mentoring relationships were characterized by reciprocity, mutual respect, clear expectations, personal connection, and shared values. Failed mentoring relationships were characterized by poor communication, lack of commitment, personality differences, perceived (or real) competition, conflicts of interest, and the mentor's lack of experience.ConclusionsSuccessful mentorship is vital to career success and satisfaction for both mentors and mentees. Yet challenges continue to inhibit faculty members from receiving effective mentorship. Given the importance of mentorship on faculty members' careers, future studies must address the association between a failed mentoring relationship and a faculty member's career success, how to assess different approaches to mediating failed mentoring relationships, and how to evaluate strategies for effective mentorship throughout a faculty member's career.

IntroductionMetabolic syndrome (MetS) is increasing among young people. We compared the use of homeostasis model assessment of insulin resistance (HOMA-IR) with the use of fasting blood glucose to identify MetS in African American children.MethodsWe performed a cross-sectional analysis of data from a sample of 105 children (45 boys, 60 girls) aged 9 to 13 years with body mass indexes at or above the 85th percentile for age and sex. Waist circumference, blood pressure, and fasting levels of blood glucose, insulin, triglycerides, and high-density lipoprotein cholesterol were measured.ResultsWe found that HOMA-IR is a stronger indicator of MetS in children than blood glucose. Using HOMA-IR as 1 of the 5 components, we found a 38% prevalence of MetS in this sample of African American children and the proportion of false negatives decreased from 94% with blood glucose alone to 13% with HOMA-IR. The prevalence of MetS was higher in obese than overweight children and higher among girls than boys.ConclusionUsing HOMA-IR was preferred to fasting blood glucose because insulin resistance was more significantly interrelated with the other 4 MetS components.

Expansion of the cerebral ventricles may occur at an accelerated rate in subjects with dementia, but the time course of expansion during transitions between normal cognitive function, mild cognitive impairment (MCI), and dementia is not well understood. Furthermore, the effects of cardiovascular risk factors on rate of ventricular expansion are unclear. We used a fully automated segmentation technique to measure change rate in lateral ventricle-to-brain ratio (VBR) on 145 longitudinal pairs of magnetic resonance images of subjects in the Cardiovascular Health Study Cognition Study from the Pittsburgh Center. A multivariate model analyzed VBR change rate, accounting for dementia statuses at both imaging times (normal, MCI, or dementia), age, sex, education, race, magnetic resonance-defined infarcts, Center for Epidemiology Studies Depression Scale, baseline ventricular volume, and cardiovascular risk factors. VBR change was faster in subjects who were demented or transitioned from MCI to dementia, compared with subjects normal at both images and subjects who transitioned from normal to MCI or dementia. Patients with diabetes had faster VBR change. Ventricular expansion may accelerate late in the progression from normal cognitive function to dementia, and may be modulated by diabetes.