Low Diastolic Blood Pressure and Mortality in Older Women. Results From the Women's Health Initiative Long Life Study.

BACKGROUND: Recommended systolic blood pressure targets often do not consider the relationship of low diastolic blood pressure (DBP) levels with cardiovascular disease (CVD) and all-cause mortality risk, which is especially relevant for older people with concurrent comorbidities. We examined the relationship of DBP levels to CVD and all-cause mortality in older women in the Women's Health Initiative Long Life Study (WHI-LLS). METHODS: The study sample included 7,875 women (mean age: 79 years) who underwent a blood pressure measurement at an in-person home visit conducted in 2012-2013. CVD and all-cause mortality were centrally adjudicated. Hazard ratios (HRs) were obtained from adjusted Cox proportional hazards models. RESULTS: After 5 years follow-up, all-cause mortality occurred in 18.4% of women. Compared with a DBP of 80 mm Hg, the fully adjusted HR for mortality was 1.33 (95% confidence interval [CI]: 1.04-1.71) for a DBP of 50 mm Hg and 1.67 (95% CI: 1.29-2.16) for a DBP of 100 mm Hg. The HRs for CVD were 1.14 (95% CI: 0.78-1.67) for a DBP of 50 mm Hg and HR 1.50 (95% CI: 1.03-2.17) for a DBP of 100 mm Hg. The nadir DBP associated with lowest mortality risk was 72 mm Hg overall. CONCLUSIONS: In older women, consideration should be given to the potential adverse effects of low and high DBP. Low DBP may serve as a risk marker. DBP target levels between 68 and 75 mm Hg may avoid higher mortality risk.

Survival analysis of patients with advanced hypopharyngeal cancer comparing patients who received primary surgery to those who received chemoradiation: An analysis of the NCDB.

INTRODUCTION: The objective of this study was to use the American College of Surgeons' National Cancer Database (NCDB) to examine the association between primary treatment and overall survival (OS) among patients with locoregionally advanced hypopharyngeal cancer. METHODS: 6,055 adult patients diagnosed between 2004 and 2015 with stage III or IV, M0, hypopharyngeal squamous cell carcinoma were identified within the NCDB. Patients who received primary chemoradiation (CRT) were compared to those that received surgery with adjuvant radiation or chemoradiation (S + Adj). OS was compared between treatment groups using Kaplan-Meier analyses, propensity score adjustment, and Cox regression analyses. RESULTS: The median survival was 22.7 months (IQR 11.0-49.0). The S + Adj group had a significantly higher comorbidity score, higher grade disease, and more advanced stage disease than the CRT group. S + Adj was associated with significantly improved survival when compared to CRT (p < 0.0001). A propensity score adjusting for facility type, facility location, care at multiple facilities, histology, and T stage was developed. S + Adj was associated with longer survival (HR: 0.72, 95% CI: 0.64-0.80) when compared to CRT in a multivariable Cox regression analysis (adjusting for age, race and ethnicity, insurance status, a comorbidity index, diagnosis year, treatment delay, N stage, and the propensity score). S + Adj was associated with significantly improved survival among those with T2 disease (p = 0.02), T3 disease (p = 0.02), and T4 disease (p < 0.0001) in sensitivity analyses examining these subcohorts independently. CONCLUSIONS: Among patients with advanced hypopharyngeal cancer reported in NCDB, treatment with S + Adj was associated with longer survival compared to those treated with primary CRT.

Acceptability of a Tenofovir Disoproxil Fumarate Intravaginal Ring for HIV Pre-Exposure Prophylaxis Among Sexually Active Women.

INTRODUCTION: Vaginal ring delivery of antiretroviral drugs may provide protection against acquisition of HIV-1 when used as Pre-Exposure prophylaxis. As part of a randomized placebo-controlled safety trial of a tenofovir disoproxil fumarate (TDF) intravaginal ring (IVR), we assessed product acceptability through surveys of women after continuous ring use. METHODS: Sexually active, HIV-negative women were enrolled to investigate the safety and pharmacokinetics of 3 months of continuous TDF IVR use. The study was designed to include 40 US participants randomly assigned (3:1) to a TDF or placebo IVR. Twelve were randomized to TDF and 5 to the placebo group before the study was electively discontinued because of the development of vaginal ulcerations in 8 women in the TDF group. Acceptability data were gathered via self-administered, computer-based questionnaires. RESULTS: The average age of the 17 participants was 31 years (range, 18-42 years). Sixteen participants (94%) completed all questions at 2 study visits. When asked about ring likeability after 1 month of ring use, 12 (75%) of 16 reported overall liking the ring, including 6 (75%) of 8 who developed ulcerations. In addition, 10 (83%) of 12 who had their menses during the first month of ring use were not bothered by the ring, and 11 (69%) of 16 stated that the ring was not bothersome with use during sex. CONCLUSIONS: Despite unanticipated ulcers, TDF and placebo IVRs were acceptable to some women, even when used with menses and during sex, which is promising for continued development of IVRs for HIV prevention.

Treatment sequence and survival in locoregionally advanced hypopharyngeal cancer: A surveillance, epidemiology, and end results-based study.

OBJECTIVES/HYPOTHESIS: The objective of this study was to examine the association between modality of primary treatment and survival among patients with locoregionally advanced hypopharyngeal cancer. STUDY DESIGN: Retrospective cohort. METHODS: There were 2,328 adult patients diagnosed with stage III or IV, M0, hypopharyngeal squamous cell carcinoma identified within the Surveillance, Epidemiology and End Results (SEER) registry (years 2004-2015). Patients who received primary chemoradiation (CRT) were compared to those who received surgery with either adjuvant radiation therapy (S + RT), or surgery with adjuvant CRT (S + CRT). The latter primary surgery group (S + Adj) was also analyzed collectively. Overall survival (OS) and disease-specific survival (DSS) were assessed using Kaplan-Meier analyses and Cox regression models using a propensity score to adjust for factors associated with treatment allocation. RESULTS: Median survival was 20 months (interquartile range [IQR] = 10-45) with CRT and 25 months (IQR = 10-47) with S + Adj (P < .001). S + Adj had higher-grade cancers and more advanced T staging (P < .001). S + CRT was associated with longer OS (hazard ratio [HR] = 0.70, 95% confidence interval [CI]: 0.59-0.84) and DSS (HR = 0.66, 95% CI: 0.54-0.82) after adjusting for age, gender, race, subsite, grade, and stage. S + RT was associated with longer DSS than CRT (HR = 0.75, 95% CI: 0.57-0.99) but not OS (HR = 0.82, 95% CI: 0.66-1.04). S + Adj was associated with longer DSS in T1/T2 disease (P = .04) and T4 disease (P = .0003), but did not reach significance among patients with T3 disease (P = .06). CONCLUSIONS: Among patients with advanced hypopharyngeal cancer reported in the SEER database, treatment with S + Adj was associated with longer DSS and OS compared to those treated with primary CRT. LEVEL OF EVIDENCE: 2b Laryngoscope, 130:2611-2621, 2020.

Tenofovir disoproxil fumarate intravaginal ring for HIV pre-exposure prophylaxis in sexually active women: a phase 1, single-blind, randomised, controlled trial.

BACKGROUND: An intravaginal ring that releases the tenofovir prodrug, tenofovir disoproxil fumarate, provided 100% protection in macaques against simian HIV and was safe in a 14-day clinical trial in sexually abstinent women. We aimed to assess the safety and pharmacokinetics of this intravaginal ring over 90 days in sexually active women. METHODS: We did a phase 1, single-blind, randomised, placebo-controlled trial to assess safety, pharmacokinetics, and acceptability of a tenofovir disoproxil fumarate intravaginal ring used continuously with monthly ring changes for 3 months. Sexually active women who were HIV negative were randomly assigned (3:1) to a tenofovir disoproxil fumarate ring or placebo ring. Primary safety endpoint was the proportion of women who had grade 2 or higher genitourinary adverse events judged related to study product and any grade 2 or higher adverse event as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. We quantified tenofovir disoproxil fumarate and tenofovir concentrations in cervicovaginal fluid, tenofovir in plasma, and tenofovir diphosphate, the active metabolite, in cervical tissue and dried blood spots 1 month after each ring insertion. We compared changes over time in cervicovaginal fluid cytokine and chemokine concentrations and vaginal microbiota. The study was electively stopped early and is registered with ClinicalTrials.gov, number NCT02762617. FINDINGS: Between Feb 24 and July 20, 2017, 17 women were enrolled before study termination. 12 were assigned to receive the tenofovir disoproxil fumarate ring and five were assigned to receive the placebo ring. Two participants in the tenofovir disoproxil fumarate ring group completed 3 months of continuous ring use; eight were asked to discontinue ring use early because of ulcerations (grade 1) near the ring; in the remaining two women, rings were electively removed by study staff on day 20 and day 23. Ulcers were detected a mean of 32 days after ring use (range 23-56). Four of eight participants with ulcers were symptomatic with vaginal discharge; four had ulcers identified when examined; three had two ulcers; all ulcers resolved after ring removal. No participants in the placebo group developed ulcers. No grade 2 product-related adverse events were reported in either group and four non-product-related grade 2 adverse events were reported in the tenofovir disoproxil fumarate ring group. Cervicovaginal fluid tenofovir concentrations did not differ at day 14 (p=0·14) comparing the eight patients who did (median 1·0 × 105 ng/mL [IQR 9·1 × 104-1·1 × 105]) with the four who did not (6·0 × 104 ng/mL [5·6 × 104-1·1 × 105]) develop ulcers. No significant changes in vaginal microbiota were detected in either group. Concentrations of multiple inflammatory cytokines and chemokines were significantly higher at days 14 and 28 compared with baseline in the tenofovir disoproxil fumarate ring group but not the placebo group. INTERPRETATION: Future studies are needed to establish whether the unanticipated finding of ulcerations is specific to this tenofovir disoproxil fumarate ring or generalisable to other sustained topical release formulations of tenofovir or its prodrugs. FUNDING: National Institutes of Health.

Home Environment Factors and Health Behaviors of Low-income, Overweight, and Obese Youth.

Objectives: Home environment may influence children's health behaviors associated with obesity. In this study, we examined home environment factors associated with diet and physical activity behaviors of overweight or obese youth. Methods: We analyzed baseline data from child and parent/caregiver dyads enrolled in an urban family weight management program. Multivariable logistic regression examined how home environment (parenting practices, family meal habits, and home availability of fruits/vegetables, sugar-sweetened beverages (SSBs), screen media, and physical activity resources) are related to children's intake of fruit, vegetables, and SSBs, and moderate-vigorous physical activity and sedentary time (ST) after adjusting for potential confounders. Results: Children were more likely to consume fruit if their families frequently ate meals together and infrequently watched TV during meals, and more likely to consume vegetables with high fruit/vegetable availability and low SSB availability. Children were more likely to engage in ST if parents practiced monitoring and frequently watched TV during meals. Conclusions: Overweight or obese children appear to have healthier habits if their families eat meals together without watching TV and if healthy food choices are available in the home. Encouraging parents to focus these practices may promote healthier body weight in children.

Characterization of Risk Factors and Timing of Venous Thromboembolism in Patients With Uterine Serous Carcinoma.

OBJECTIVE: To characterize risk factors and timing of venous thromboembolism in women with uterine serous carcinoma. METHODS: A retrospective cohort study was performed including all women diagnosed with uterine serous carcinoma from 1999 to 2016 at our institution. Clinicopathologic data and information regarding timing of venous thromboembolism were abstracted from the medical record. Logistic regression and Cox proportional hazards modeling were used to examine the association between covariates and risk and timing of venous thromboembolism. RESULTS: Seventy of the 413 included patients (17%) developed venous thromboembolism, with a median time from presentation to venous thromboembolism of 7.2 months (interquartile range 1.0-24.8) and from surgery to venous thromboembolism of 13.2 months (interquartile range 3.5-33.6). Fifty-nine of the 70 patients (84%) who developed venous thromboembolism were diagnosed either before surgery or greater than 6 weeks postoperatively. Twenty-two of the 70 patients (31%) who developed clots were on chemotherapy at the time of diagnosis. Venous thromboembolism was highly associated with cancer stage and presence of hypertension (P<.01). Cox proportional hazards modeling revealed that only cancer stages III and IV (hazard ratio [HR] 3.20, 95% CI 1.54-6.64 and HR 8.68, 95% CI 4.50-16.73, respectively) and hypertensive or cardiovascular diseases (HR 2.29, 95% CI 1.08-4.85 and HR 1.82, 95% CI 1.05-3.13) were associated with time to venous thromboembolism. CONCLUSION: Patients with uterine serous carcinoma are at high risk of developing venous thromboembolism even many months after their cancer diagnosis. This study generates the hypothesis that venous thromboembolism prophylaxis may be beneficial in patients with uterine serous carcinoma during other time points along the continuum of disease rather than only in the postoperative period, especially for those with advanced cancer.

Exploring Preconception Care: Insurance Status, Race/Ethnicity, and Health in the Pre-pregnancy Period.

Objective To measure the association of preconception health insurance status with preconception health among women in New York City, and examine whether this association is modified by race/ethnicity. Methods Using data from the New York City Pregnancy Risk Assessment Monitoring System 2009-2011 (n = 3929), we created a "Preconception Health Score" (PHS) capturing modifiable behaviors, healthcare services utilization, pregnancy intention, and timely entry into prenatal care. We then built multivariable logistic regression models to measure the association of PHS with health insurance status and race/ethnicity. Results We found PHS to be higher among women with private insurance (7.3 ± 0.07) or public insurance (6.3 ± 0.08) before pregnancy than no insurance (5.9 ± 0.09) (p < .001). However, when stratified by race/ethnicity, the positive association of PHS with insurance was absent in the non-white population. Conclusions for Practice Having health insurance during the pre-pregnancy period is associated with greater health among white women, but not among black or Hispanic women in NYC.

Progressive kidney disease may not alter the association of hyponatremia with mortality.

BACKGROUND: Hyponatremia is a common electrolyte disorder and a prognostic marker for mortality. We hypothesize that in advanced chronic or acute kidney disease, hyponatremia is not independently associated with mortality because of the contribution of kidney failure to its pathophysiology. METHODS: Clinical Looking Glass, Montefiore's clinical database, was used to build a cohort of all patients hospitalized between January of 2009 and December of 2011. A chronic kidney disease (CKD) group and an acute kidney injury (AKI) group were defined based on GFR measurements during and before index hospitalization. Cox regression models assessed the hazard for death for those with community acquired hyponatremia as compared to those without hyponatremia, stratified by stage of kidney disease within each cohort. RESULTS: Forty-four thousand four hundred and seventy-six patients were studied. Forty six percent (46.2%) of subjects were in the CKD cohort and 53.8% were in the AKI cohort. Hyponatremic patients were older, and had a higher prevalence of CKD and AKI. A total of 7,934 subjects died (17.8%) during 22 months of follow-up. In CKD and AKI cohorts, hyponatremia, age, race, illness severity and Charlson score were associated with mortality. Hyponatremia had similar hazard ratios (HR) across kidney disease stages despite loss of statistical significance in later stages due to smaller sample size. CONCLUSIONS: The association between community acquired hyponatremia and mortality showed consistent HRs across progressive stages of CKD and AKI suggesting that the contribution of tubular dysfunction to hyponatremia in advanced kidney disease does not alter this association.

The Associations of Atrial Fibrillation With the Risks of Incident Invasive Breast and Colorectal Cancer.

Atrial fibrillation (AF) is a common arrhythmia that poses a significant risk of stroke. Cross-sectional and case-control studies have shown evidence of associations between AF and breast or colorectal cancer, but there have been no longitudinal studies in which this has been assessed. We prospectively examined a cohort of 93,676 postmenopausal women enrolled in the Women's Health Initiative from 1994 to 1998 to determine whether there are relationships between baseline AF and the development of invasive breast or colorectal cancer. The prevalence of self-reported physician diagnosis of AF at baseline was 5.1%. Over approximately 15 years of follow-up, the incidence of invasive breast cancer was 5.7%, and the incidence of colorectal cancer was 1.6%. Adjusted hazard ratios and 95% confidence intervals were obtained using Cox proportional hazards models. We found no significant association between AF and incident colorectal cancer, but we did see a 19% excess risk of invasive breast cancer among those with AF (adjusted hazard ratio (HR) = 1.19, 95% confidence interval (CI): 1.03, 1.38). Additional adjustment for baseline use of cardiac glycosides attenuated the association between AF and invasive breast cancer (HR = 1.01, 95% CI: 0.85, 1.20). Cardiac glycoside use was strongly associated with incident invasive breast cancer (HR = 1.68, 95% CI: 1.33, 2.12) independent of AF and other confounders. Mechanisms of the associations among breast cancer, AF, and cardiac glycosides need further investigation.

Longitudinal Assessment of Systemic and Genital Tract Inflammatory Markers and Endogenous Genital Tract E. coli Inhibitory Activity in HIV-Infected and Uninfected Women.

PROBLEM: Stability over time of systemic and mucosal immunity and their associations with bacterial vaginosis (BV) and HIV-specific parameters were assessed. METHOD OF STUDY: Immune mediators and HIV viral load in plasma and cervicovaginal lavage (CVL), E. coli inhibition, and Nugent score were measured at three semiannual visits among 94 participants in the Women's Interagency HIV Study. Mixed models identified the factors associated with immune mediators. RESULTS: There was higher E. coli inhibition and lower inflammation over time in the genital tract and systemically. BV was consistently associated with higher CVL inflammatory mediators and lower CVL E. coli inhibition. HIV-infected women with higher CD4 counts had lower systemic and genital inflammatory mediators, and genital HIV shedding was associated with higher CVL inflammatory mediators. Use of antiretroviral therapy (ART) was associated with lower plasma and CVL mediators, but higher E. coli inhibition. CONCLUSION: HIV and BV are linked to inflammation, and ART may be associated with improved vaginal health.

Mentoring in Clinical-Translational Research: A Study of Participants in Master's Degree Programs.

Research projects in translational science are increasingly complex and require interdisciplinary collaborations. In the context of training translational researchers, this suggests that multiple mentors may be needed in different content areas. This study explored mentoring structure as it relates to perceived mentoring effectiveness and other characteristics of master's-level trainees in clinical-translational research training programs. A cross-sectional online survey of recent graduates of clinical research master's program was conducted. Of 73 surveys distributed, 56.2% (n = 41) complete responses were analyzed. Trainees were overwhelmingly positive about participation in their master's programs and the impact it had on their professional development. Overall the majority (≥75%) of trainees perceived they had effective mentoring in terms of developing skills needed for conducting clinical-translational research. Fewer trainees perceived effective mentoring in career development and work-life balance. In all 15 areas of mentoring effectiveness assessed, higher rates of perceived mentor effectiveness was seen among trainees with ≥2 mentors compared to those with solo mentoring (SM). In addition, trainees with ≥2 mentors perceived having effective mentoring in more mentoring aspects (median: 14.0; IQR: 12.0-15.0) than trainees with SM (median: 10.5; IQR: 8.0-14.5). Results from this survey suggest having ≥2 mentors may be beneficial in fulfilling trainee expectations for mentoring in clinical-translational training.

Global health training in US obstetrics and gynaecology residency programmes: perspectives of students, residents and programme directors.

BACKGROUND: Benefits of exposure to global health training during medical education are well documented and residents' demand for this training is increasing. Despite this, it is offered by few US obstetrics and gynaecology (OBGYN) residency training programmes. OBJECTIVES: To evaluate interest, perceived importance, predictors of global health interest and barriers to offering global health training among prospective OBGYN residents, current OBGYN residents and US OGBYN residency directors. METHODS: We designed two questionnaires using Likert scale questions to assess perceived importance of global health training. The first was distributed to current and prospective OBGYN residents interviewing at a US residency programme during 2012-2013. The second questionnaire distributed to US OBGYN programme directors assessed for existing global health programmes and global health training barriers. A composite Global Health Interest/Importance score was tabulated from the Likert scores. Multivariable linear regression was performed to assess for predictors of Global Health Interest/Importance. RESULTS: A total of 159 trainees (77%; 129 prospective OBGYN residents and 30 residents) and 69 (28%) programme directors completed the questionnaires. Median Global Health Interest/Importance score was 7 (IQR 4-9). Prior volunteer experience was predictive of a 5-point increase in Global Health Interest/Importance score (95% CI -0.19 to 9.85; p=0.02). The most commonly cited barriers were cost and time. CONCLUSION: Interest and perceived importance of global health training in US OBGYN residency programmes is evident among trainees and programme directors; however, significant financial and time barriers prevent many programmes from offering opportunities to their trainees. Prior volunteer experience predicts global health interest.

The Role of Parenting Practices in the Home Environment among Underserved Youth.

BACKGROUND: The home environment, which includes parenting practices, is an important setting in which children develop their health behaviors. We examined the role of parenting practices in the home environment among underserved youth. METHODS: We examined baseline data of a family-focused pediatric obesity intervention. Parenting practices (monitoring, discipline, limit setting of soda/snacks [SS] and screen media [SM], pressure to eat, and reinforcement) and availability of fruits/vegetables (FV) and sugar-sweetened beverages (SSBs), family meals, television (TV) watching during meals, TVs in the home, owning active video games/sports equipment, and household food security were assessed in 301 parent/caregivers of overweight/obese children (ages 7-12 years; BMI≥85th percentile). Associations were evaluated using Spearman's rank correlation coefficients and logistic regression models adjusted for potential confounders. RESULTS: Parents/caregivers (ages 22-67 years) were largely Hispanic/Latino (74.1%), female (92.4%), and reported high levels of limit setting SS and low levels of pressure to eat. Parent age, gender, country of birth, and years living in the United States accounted for differences among several parenting practices. Adjusted logistic regression models identified several statistically significant associations, including: Monitoring was positively associated with availability FV (odds ratio [OR]=2.19; 95% confidence interval [CI], 1.25, 3.82); limit setting SS was inversely associated with availability of SSBs (OR=0.40; 95% CI, 0.21, 0.75); and limit setting SM was inversely associated with TV viewing during family meals (OR=0.51; 95% CI, 0.31, 0.85). Nearly 40% of our population was food insecure, and food insecurity was positively associated with pressure to eat (OR=1.77; 95% CI, 1.01, 3.15). CONCLUSIONS: Parenting practices play an important role in the home environment, and longitudinal studies are needed to examine these associations in the context of family-focused pediatric obesity interventions.

Differences in Cardiometabolic Risk between Insulin-Sensitive and Insulin-Resistant Overweight and Obese Children.

BACKGROUND: It is known that 15-30% overweight/obese adults do not suffer cardiometabolic consequences. There is limited literature examining factors that can be used to assess cardiometabolic health in overweight/obese children. If such factors can be identified, they would aid in differentiating those most in need for aggressive management. METHODS: Baseline data from 7- to 12-year-old, overweight, and obese children enrolled in a weight management program at an urban hospital were analyzed. Homeostatic model assessment for insulin resistance (HOMA-IR) <2.6 was used to define insulin-sensitive and HOMA-IR ≥2.6 was used to defined insulin-resistant participants. Demographics, physical activity measures, and cardiometabolic risk factors were compared between the two phenotypes. Odds ratios (ORs) examining the association between intermediate endpoints (metabolic syndrome [MetS], nonalcoholic fatty liver disease [NAFLD], systemic inflammation, and microalbuminuria) and the two metabolic phenotypes were evaluated. RESULTS: Of the 362 overweight/obese participants, 157 (43.5%) were insulin sensitive and 204 (56.5%) were insulin resistant. Compared to the insulin-sensitive group, the insulin-resistant group was older (8.6±1.6 vs. 9.9±1.7; p<0.001) and had a higher BMI z-score (1.89±0.42 vs. 2.04±0.42; p=0.001). After multivariable adjustment, compared to the insulin-sensitive group, the insulin-resistant group had higher odds of having MetS (OR, 5.47; 95% confidence interval [CI]: 1.72, 17.35; p=0.004) and NAFLD (OR, 8.66; 95% CI, 2.48, 30.31; p=0.001), but not systemic inflammation (OR, 1.06; 95% CI: 0.56, 2.03; p=0.86) or microalbuminuria (OR, 1.71; 95% CI, 0.49, 6.04; p=0.403). CONCLUSIONS: Using a HOMA-IR value of ≥2.6, clinical providers can identify prepubertal and early pubertal children most at risk. Focusing limited resources on aggressive weight interventions may lead to improvement in cardiometabolic health.

Fatal anaphylaxis in the United States, 1999-2010: temporal patterns and demographic associations.

BACKGROUND: Anaphylaxis-related deaths in the United States have not been well characterized in recent years. OBJECTIVES: We sought to define epidemiologic features and time trends of fatal anaphylaxis in the United States from 1999 to 2010. METHODS: Anaphylaxis-related deaths were identified by using the 10th clinical modification of the International Classification of Diseases system diagnostic codes on death certificates from the US National Mortality Database. Rates were calculated by using census population estimates. RESULTS: There were a total of 2458 anaphylaxis-related deaths in the United States from 1999 to 2010. Medications were the most common cause (58.8%), followed by "unspecified" (19.3%), venom (15.2%), and food (6.7%). There was a significant increase in fatal drug-induced anaphylaxis over 12 years: from 0.27 (95% CI, 0.23-0.30) per million in 1999 to 2001 to 0.51 (95% CI, 0.47-0.56) per million in 2008 to 2010 (P < .001). Fatal anaphylaxis caused by medications, food, and unspecified allergens was significantly associated with African American race and older age (P < .001). Fatal anaphylaxis to venom was significantly associated with white race, older age, and male sex (P < .001). The rates of fatal anaphylaxis to foods in male African American subjects increased from 0.06 (95% CI, 0.01-0.17) per million in 1999 to 2001 to 0.21 (95% CI, 0.11-0.37) per million in 2008 to 2010 (P < .001). The rates of unspecified fatal anaphylaxis decreased over time from 0.30 (95% CI, 0.26-0.34) per million in 1999 to 2001 to 0.09 (95% CI, 0.07-0.11) per million in 2008 to 2010 (P < .001). CONCLUSION: There are strong and disparate associations between race and specific classes of anaphylaxis-related mortality in the United States. The increase in medication-related deaths caused by anaphylaxis likely relates to increased medication and radiocontrast use, enhanced diagnosis, and coding changes.

Relationship between urine dichlorophenol levels and asthma morbidity.

BACKGROUND: Chlorinated phenols are associated with atopic conditions, but it is not known whether they are associated with wheeze or asthma and whether atopy is involved in these associations. OBJECTIVES: To test the association between urine levels of 2 dichlorophenols (2,4- and 2,5-dichlorophenols) and asthma morbidity in atopic and nonatopic wheezers and between total serum immunoglobulin E (IgE) levels. METHODS: Data from a sample of 2,125 participants at least 6 years old from the US National Health and Nutrition Examination Survey 2005 to 2006 were analyzed. Asthma morbidity data were available for those participants who reported wheezing in the past year ("wheezers"; n = 250). This subsample was categorized as atopic or nonatopic. RESULTS: Atopic wheezers with higher 2,5-dichlorophenol levels were more frequently diagnosed with asthma by a physician (odds ratio [OR] 4.7 for highest vs lowest tertile, P < .001), required more prescriptions for asthma medications (OR 2.2, P = .046), and reported more exercise-induced wheezing (OR 5.8, P = .045) than atopic wheezers with low dichlorophenol levels. Atopic wheezers with higher 2,5- or 2,4-dichloropheonol levels also were more likely to miss work or school because of wheezing (OR 10.0, P < .001; OR 11.4, P < .01, respectively). In contrast, in nonatopic wheezers, there were no significant associations between dichlorophenol levels and asthma morbidity measurements. The 2 dichlorophenol metabolites were positively associated with increased serum IgE levels in the larger study sample. CONCLUSION: These findings indicate that in patients with atopy and a history of wheezing, asthma morbidity is associated with high urinary dichlorophenol levels. Increased urine dichlorophenol levels are associated with higher total serum IgE.

Ectopic fat and adipokines in metabolically benign overweight/obese women: the Kronos Early Estrogen Prevention Study.

OBJECTIVE: It is unclear why despite a comparable cardiometabolic risk profile, "metabolically benign" overweight/obese individuals show an elevated risk of cardiovascular disease compared to normal weight individuals. DESIGN AND METHODS: In cross-sectional analyses, we compared levels of ectopic fat (epicardial, pericardial, and hepatic fat) and adipokines (leptin, soluble leptin receptor, and high molecular weight [HMW] adiponectin) among metabolically benign (MBO) and at-risk overweight/obese (ARO), and metabolically benign normal weight (MBNW) women, screened for the Kronos Early Estrogen Prevention Study. We defined "metabolically benign" with ≤ 1, and "at-risk" with ≥2 components of the metabolic syndrome. RESULTS: Compared to MBO women, ARO women had significantly elevated odds of being in the top tertile of epicardial fat (OR: 1.76, 95% CI: 1.04-2.99), hepatic fat (OR: 1.90, 95% CI:1.12-3.24) and leptin (OR: 2.15, 95% CI: 1.23-3.76), and the bottom tertile of HMW-adiponectin (OR: 2.90, 95% CI: 1.62-5.19). Compared to MBNW women, MBO women had significantly higher odds of being in the top tertile of epicardial fat (OR: 5.17, 95% CI: 3.22-8.29), pericardial fat (OR: 9.27, 95% CI: 5.52-15.56) and hepatic fat (OR: 2.72, 95% CI: 1.77-4.19) and the bottom tertile of HMW adiponectin levels (OR: 2.51, 95% CI: 1.60-3.94). CONCLUSIONS: Levels of ectopic fat and the adverse adipokine profile increase on a continuum of BMI, suggesting that the metabolically benign phenotype may be a transient state.

Associations of adult physical activity with perceived safety and police-recorded crime: the Multi-ethnic Study of Atherosclerosis.

BACKGROUND: Due to the inconsistent findings of prior studies, we explored the association of perceived safety and police-recorded crime measures with physical activity. METHODS: The study included 818 Chicago participants of the Multiethnic Study of Atherosclerosis 45 to 84 years of age. Questionnaire-assessed physical activity included a) transport walking; b) leisure walking; and c) non-walking leisure activities. Perceived safety was assessed through an interviewer-administered questionnaire. Police-recorded crime was assessed through 2-year counts of selected crimes (total and outdoor incivilities, criminal offenses, homicides) per 1000 population. Associations were examined using generalized estimating equation logistic regression models. RESULTS: Perceiving a safer neighborhood was positively associated with transport walking and perceiving lower violence was associated with leisure walking. Those in the lowest tertile of total or outdoor incivilities were more likely to report transport walking. Models with both perceived safety and police-recorded measures of crime as independent variables had superior fit for both transport walking and leisure walking outcomes. Neither perceived safety nor police-recorded measures of crime were associated with non-walking leisure activity. CONCLUSIONS: Perceived and police-recorded measures had independent associations with walking and both should be considered in assessing the impact of neighborhood crime on physical activity.