White Matter Hyperintensities as a Predictor of Aphasia Recovery.

OBJECTIVE: To examine the relation between baseline white matter hyperintensities (WMH) and change in naming, content production, and efficiency after treatment in subacute aphasia. We hypothesized that more severe baseline WMH would result in less improvement with treatment. DESIGN: Retrospective analysis of a cohort from a double-blind randomized controlled trial (RCT). SETTING: Outpatient clinical setting or participant home. PARTICIPANTS: We retrospectively reviewed imaging and behavioral data for 52 participants with subacute aphasia due to left-hemisphere ischemic stroke enrolled in the RCT. RCT inclusion criteria: English proficiency, normal/corrected-to-normal hearing/vision, and no history of neurologic conditions other than the stroke resulting aphasia. One participant with a chronic right-hemisphere lesion was retained as she presented with no residual deficits on neurologic examination. Individuals with scalp sensitivities or on medications that lower seizure threshold or any N-methyl-D-aspartate (NMDA) antagonists were excluded. Of the 52 participants, for this analysis, 2 were excluded for not having a magnetic resonance imaging, and 7 were excluded for not participating in treatment or pre/post assessment for at least 1 outcome, resulting in final sample of 43 participants (20 women sex, M [SD] age=64.4 [11.9] and M [SD] education=14.9 [3.1] years). INTERVENTIONS: Participants received 15 sessions (2-3 times/week) of computerized lexical-semantic (ie, verification) treatment with [sham/active] transcranial direct current stimulation (tDCS). Sessions were approximately 45 minutes each (tDCS for first 20 minutes). MAIN OUTCOME MEASURES: Naming accuracy, content units (CUs, a measure of semantically accurate production), and efficiency (ie, syllables/CU) on a picture description task. RESULTS: Periventricular WMH severity was independently associated with recovery in picture naming for the active tDCS group. Deep WMH severity was associated with recovery for CU production for the sham tDCS group. CONCLUSION: Baseline periventricular and deep WMH, among other factors, may be an important consideration for prognosis and treatment planning, especially when considered in conjunction with tDCS treatment.

Temporal change in aetiology and clinical characteristics of hepatocellular carcinoma in a large cohort of patients in New South Wales, Australia.

BACKGROUND: Viral hepatitis, alcohol-related liver disease (ARLD) and nonalcoholic fatty liver disease (NAFLD) are the main risk factors for hepatocellular carcinoma (HCC) in many countries. In Australia, given the access to hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy since 2016, a temporal change in HCC aetiology was hypothesized. This study evaluated the temporal change in the aetiology and characteristics of HCC in New South Wales (NSW). METHODS: Patients diagnosed with HCC, admitted to three public hospitals in NSW between 2008 and 2021, were included in the analyses. We assessed the annual frequency of each HCC aetiology and the distribution of HCC characteristics in participants. RESULTS: Among 1370 patients, the most common HCC etiologies were HCV (n = 483, 35%), ARLD (n = 452, 33%), NAFLD (n = 347, 25%) and hepatitis B virus (n = 301, 22%). The proportion of HCV-related HCC was the highest in 2011-2016 (41%) and significantly declined to 30% in 2017-2021 (odds ratio [OR], 0.53 [95% confidence interval (CI), 0.35-0.79]; P = 0.002). The proportion of HCC diagnosed at an early stage (Barcelona Clinic Liver Cancer stage O/A) increased from 41% in 2008-2009 to 56% in 2020-2021 (OR per annum, 1.05 [95% CI, 1.02-1.08]; P = 0.002), and the proportion of patients receiving potentially curative HCC management increased from 29% in 2008-2009 to 41% in 2020-2021 (OR per annum, 1.06 [95% CI, 1.03-1.10]; P < 0.001). CONCLUSION: The contribution of HCV to HCC burden has been decreasing in the DAA era, suggesting the role of HCV elimination in decreasing HCC risk. Increasing frequency of less advanced HCC at diagnosis over time suggests improved HCC surveillance.

Identification of US Counties at Elevated Risk for Congenital Syphilis Using Predictive Modeling and a Risk Scoring System.

BACKGROUND: Although preventable through timely screening and treatment, congenital syphilis (CS) rates are increasing in the United States, occurring in 5% of counties in 2015. Although individual-level factors are important predictors of CS, given the geographic focus of CS, it is also imperative to understand what county-level factors are associated with CS. METHODS: This is a secondary analysis of reported county CS cases to the National Notifiable Diseases Surveillance System during the periods 2014-2015 and 2016-2017. We developed a predictive model to identify county-level factors associated with CS and use these to predict counties at elevated risk for future CS. RESULTS: Our final model identified 973 (31.0% of all US counties) counties at elevated risk for CS (sensitivity, 88.1%; specificity, 74.0%). County factors that were predictive of CS included metropolitan area, income inequality, primary and secondary syphilis rates among women and men who have sex with men, and population proportions of those who are non-Hispanic black, Hispanic, living in urban areas, and uninsured. The predictive model using 2014-2015 CS outcome data was predictive of 2016-2017 CS cases (area under the curve value, 89.2%) CONCLUSIONS: Given the dire consequences of CS, increasing prevention efforts remains important. The ability to predict counties at most elevated risk for CS based on county factors may help target CS resources where they are needed most.

Causal inference of latent classes in complex survey data with the estimating equation framework.

Latent class analysis (LCA) has been effectively used to cluster multiple survey items. However, causal inference with an exposure variable, identified by an LCA model, is challenging because (1) the exposure variable is unobserved and harbors the uncertainty of estimating parameters in the LCA model and (2) confounding bias adjustments need to be done with the unobserved LCA-driven exposure variable. In addition to these challenges, complex survey design features and survey weights must be accounted for if they are present. Our solutions to these issues are to (1) assess point estimates with the expected estimating function approach and (2) modify the survey design weights with LCA-based propensity scores. This paper aims to introduce a statistical procedure to apply the estimating equation approach to assessing the effects of LCA-driven cause in complex survey data using an example of the National Health and Nutrition Examination Survey.

Psychological Traits, Heart Rate Variability, and Risk of Coronary Heart Disease in Healthy Aging Women-The Women's Health Initiative.

OBJECTIVE: Psychological traits such as optimism and hostility affect coronary heart disease (CHD) risk, but mechanisms for this association are unclear. We hypothesized that optimism and hostility may affect CHD risk via changes in heart rate variability (HRV). METHODS: We conducted a longitudinal analysis using data from the Women's Health Initiative Myocardial Ischemia and Migraine Study. Participants underwent 24-hour ambulatory electrocardiogram monitoring 3 years after enrollment. Optimism (Life Orientation Test-Revised), cynical hostility (Cook-Medley), demographics, and coronary risk factors were assessed at baseline. HRV measures included standard deviation of average N-N intervals (SDNN); standard deviation of average N-N intervals for 5 minutes (SDANN); and average heart rate (HR). CHD was defined as the first occurrence of myocardial infarction, angina, coronary angioplasty, and bypass grafting. Linear and Cox regression models adjusted for CHD risk factors were used to examine, respectively, associations between optimism, hostility, and HRV and between HRV and CHD risk. RESULTS: Final analyses included 2655 women. Although optimism was not associated with HRV, hostility was inversely associated with HRV 3 years later (SDANN: adjusted ß = -0.54; 95% CI = -0.97 to -0.11; SDNN: -0.49; 95% CI = -0.93 to -0.05). HRV was inversely associated with CHD risk; for each 10-millisecond increase in SDNN or SDANN, there was a decrease in CHD risk of 9% (p = .023) and 12% (p = .006), respectively. CONCLUSIONS: HRV did not play a major role in explaining why more optimistic women seem to be somewhat protected from CHD risk. Although hostility was inversely associated with HRV, its role in explaining the association between hostility and CHD risk remains to be established.

Laboratory Evaluation of a Commercially Available Rapid Syphilis Test.

Serological diagnosis of syphilis depends on assays that detect treponemal and nontreponemal antibodies. Laboratory certification and trained personnel are needed to perform most of these tests, while high costs and long turnaround time can hinder treatment initiation or linkage to care. A rapid treponemal syphilis test (RST) that is simple to perform, accessible, and inexpensive would be ideal. The Syphilis Health Check (SHC) assay is the only Food and Drug Administration (FDA)-cleared and Clinical Laboratory Improvement Amendments (CLIA)-waived RST in the United States. In this study, 1,406 archived human serum samples were tested using SHC and traditional treponemal and nontreponemal assays. Rapid test results were compared with treponemal data alone and with a laboratory test panel consensus defined as being reactive by both treponemal and nontreponemal assays for a given specimen, or nonreactive by both types of assays. The sensitivity and specificity of the SHC assay compared with treponemal tests alone were 88.7% (95% confidence interval [CI], 86.2 to 90.0%) and 93.1% (95% CI, 90.0 to 94.9%), respectively, while comparison with the laboratory test panel consensus showed 95.7% (95% CI, 93.6 to 97.2%) sensitivity and 93.2% (95% CI, 91.0 to 95.1%) specificity. The data were further stratified based on age, sex, pregnancy, and HIV status. The sensitivity and specificity of the SHC assay ranged from 66.7% (95% CI, 46.0 to 83.5%) to 91.7% (95% CI, 87.7 to 94.7%) and 88% (95% CI, 68.8 to 97.5%) to 100% (95% CI, 47.8 to 100%), respectively, across groups compared to traditional treponemal assays, generally increasing for all groups except the HIV-positive (HIV+) population when factoring in the laboratory test panel consensus. These data contribute to current knowledge of the SHC assay performance for distinct populations and may guide use in various settings.

Men Who Have Sex With Men-Identification Criteria and Characteristics From the National Health and Nutrition Examination Survey, 1999 to 2014.

OBJECTIVES: This study aimed to provide identification criteria for men who have sex with men (MSM), estimate the prevalence of MSM behavior, and compare sociodemographics and sexually transmitted disease risk behaviors between non-MSM and MSM groups using data from a nationally representative, population-based survey. METHODS: Using data from men aged 18 to 59 years who took part in the National Health and Nutrition Examination Survey (NHANES), 1999 to 2014, detailed criteria were developed to estimate MSM behavior-at least one lifetime same-sex partner (MSM-ever), at least one same-sex partner in the past 12 months (MSM-current), and at least one lifetime and zero same-sex partners in the past 12 months (MSM-past). RESULTS: The estimated prevalence of MSM-ever was 5.5%-of these, 52.4% were MSM-current and 47.1% were MSM-past. Furthermore, MSM-ever are a nonhomogenous subpopulation, for example, 70.4% of MSM-current identified as homosexual and 71.2% of MSM-past identified as heterosexual (P < 0.001). CONCLUSIONS: The prevalence of MSM behavior identified here is similar to other published estimates. This is also the first article, to our knowledge, to use National Health and Nutrition Examination Survey data to compare MSM by 2 recall periods (recent vs. lifetime) of last same-sex sexual behavior.

Exploring causality mechanism in the joint analysis of longitudinal and survival data.

In many biomedical studies, disease progress is monitored by a biomarker over time, eg, repeated measures of CD4 in AIDS and hemoglobin in end-stage renal disease patients. The endpoint of interest, eg, death or diagnosis of a specific disease, is correlated with the longitudinal biomarker. In this paper, we examine and compare different models of longitudinal and survival data to investigate causal mechanisms, specifically, those related to the role of random effects. We illustrate the methods by data from two clinical trials: an AIDS study and a liver cirrhosis study.

Assessment of sexual health services at US colleges and universities, 2001 and 2014.

Background Approximately 19million students attend post-secondary institutions in the US. With rates of sexually transmitted infections (STIs) at unprecedented highs, the college and university setting can provide the opportunity to engage young adults in their sexual health and deliver recommended services. The purpose of this study was to compare the provision of sexual health services at US college and university health centres across studies conducted in 2001 and 2014. METHODS: We compared data from nationally representative surveys administered by the Centers for Disease Control and Prevention (2001, n=736 schools; 2014, n=482 schools), assessing the provision of services, including STI diagnosis and treatment, contraception, STI education, condom distribution and availability of health insurance. RESULTS: Compared with 2001, statistically significant increases were observed in 2014, including in the provision of contraceptive services (56.1% vs 65.0%), HIV testing (81.5% vs 92.3%) and gonorrhoea testing (90.7% vs 95.8%). Significant decreases were found in the number of schools offering health plans (65.5% vs 49.4%) and specific modes of offering STI education, such as health fairs (82.3% vs 69.9%) and orientation presentations (46.5% vs 29.8%; all P<0.001). CONCLUSIONS: From 2001 to 2014, there have been some improvements in sexual health services at colleges and universities, but there are areas that require additional access to services. Schools may consider regular assessments of service provision in order to further promote sexual health services on college campuses.

An Illustration of Errors in Using the P Value to Indicate Clinical Significance or Epidemiological Importance of a Study Finding.

We conducted a simulation study to illustrate that P values can suggest but not confirm statistical significance; and they may not indicate epidemiological significance (importance). We recommend that researchers consider reporting effect sizes as P values in conjunction with confidence intervals or point estimates with standard errors to indicate precision (uncertainty).

Development of a rectal sexually transmitted infection (STI) Model in Rhesus macaques using Chlamydia trachomatis serovars E and L2.

BACKGROUND: Rectal STI coinfection models enhance the understanding of rectal HIV transmission risk factors. MATERIALS AND METHODS: Rhesus macaques (n=9) were exposed to one of three rectal Chlamydia trachomatis (CT) challenges: C. trachomatis L2 (CT-L2 ); C. trachomatis serovar E (CT-E), followed by CT-L2 ; or CT-E, treatment/clearance, then CT-L2 . Infections were monitored by PCR. Weekly blood and rectal secretion/lavage samples were collected for cytokine analyzes and/or epithelial sloughing, occult, and overt blood determinations. RESULTS: Chlamydial infections were successfully established in each animal, with varying degrees of persistence. Mucosal IL-1beta was upregulated in animals consecutively infected with CT-E then CT-L2 (P=.05). Epithelial sloughing was also significantly increased post-infection in this group (P=.0003). CONCLUSIONS: This study demonstrates successful rectal infection of rhesus macaques with CT-E and CT-L2 and describes measures of assessing rectal inflammation and pathology. Different infection strategies yield varying inflammatory and pathologic outcomes, providing well-described models for future SIV/SHIV susceptibility studies.

Invasive fungal infection after heart transplantation: A 7-year, single-center experience.

BACKGROUND: Invasive fungal infections (IFIs) are an infrequent but major complication of heart transplantation (HT). We sought to describe the epidemiology at our institution. METHODS: A prospective cohort study of 159 heart transplant recipients was performed from June 2005 to December 2012. IFIs were defined by European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. RESULTS: By univariate analysis, Hispanic ethnicity was associated with IFI (P=.01, odds ratio [OR] 7.0, 95% confidence interval [CI] 1.7-27.9). Subsequently, a multivariate logistic regression was performed adjusting for Hispanic ethnicity, age, and gender. Seventeen IFIs were identified, occurring at a median 110 days post HT (interquartile range: 32-411 days). Five IFIs (29% of IFIs and 3.1% of all HT) occurred during the HT hospitalization, with 13 IFIs during the first year (incidence 8.2%). CONCLUSIONS: The cumulative incidence was 10.7%. IFIs were associated with pre- and post-HT vancomycin-resistant Enterococcus colonization and/or infection, post-HT renal replacement therapy, anti-thymocyte globulin induction, and antibody-mediated rejection. There were no associations with diabetes mellitus, desensitization, 2R/3R cellular rejection, treatments for rejection, re-operation, neutropenia, or cytomegalovirus infection. IFIs were associated with death (P=.02, OR 3.9, 95% CI 1.3-12.1) and 1-year mortality (P<.001, OR 9.0, 95% CI 2.3-35.7), but not 3-year mortality. Associations with Hispanic ethnicity must be validated. Optimal strategies for risk reduction and prophylaxis remain undefined.

Sleep Variability Among Older Adults With Insomnia: Associations With Sleep Quality and Cardiometabolic Disease Risk.

Sleep variability has been linked to poor subjective sleep quality, but few studies have investigated effects on physical health. In this study, we evaluated cross sectional associations and change over time in objective sleep variability of adults with insomnia and short sleep duration who were participating in a non-pharmacologic intervention study. Results indicated greater variability in objective sleep measures were associated with poorer subjective sleep quality (p < 0.05). Higher sleep duration variability was associated with higher HbA1c (p < 0.01) and sleep onset time variability was associated with higher BMI (p < 0.05). Sleep efficiency and WASO variability decreased with intervention (p < 0.05). These results indicate that objective sleep variability may be an important feature for the assessment of insomnia outcomes.

Optimizing informed consent in living liver donors: Evaluation of a comprehension assessment tool.

Adult-to-adult living liver donation is associated with considerable risks with no direct medical benefit to liver donors (LDs). Ensuring that potential LDs comprehend the risks of donation is essential to medically and ethically justify the procedure. We developed and prospectively evaluated the initial psychometrics of an "Evaluation of Donor Informed Consent Tool" (EDICT) designed to assess LDs' comprehension about the living donation process. EDICT includes 49 true/false/unsure items related to LD informed consent. Consecutive LDs undergoing evaluation at 1 academic medical center from October 2012 to September 2014 were eligible for participation in pretest/posttest interviews. Medical records were reviewed for postdonation complications. Twenty-seven LDs participated (96% participation rate). EDICT demonstrated good internal consistency reliability at pretest, 2 days before donating (Cronbach's α = 0.78), and posttest, 1 week after donating (α = 0.70). EDICT scores significantly increased over time (P = 0.01) and demonstrated good test-retest reliability (r = 0.68; P < 0.001). EDICT was associated with race/ethnicity (P = 0.02) and relationship to the recipient (P = 0.01; pretest), and income (P = 0.01) and insurance (P = 0.01; posttest), but not with decisional conflict, preoperative preparedness, satisfaction, or decisional regret (pretest and posttest). Donor complications did not impact postdonation EDICT scores. In conclusion, EDICT has promising measurement properties and may be useful in the evaluation of informed consent for potential LDs.

Subgroup Identification in Personalized Treatment of Alcohol Dependence.

BACKGROUND: Identification of patient subgroups to enhance treatment effects is an important topic in personalized (or tailored) alcohol treatment. Recently, several recursive partitioning methods have been proposed to identify subgroups benefiting from treatment. These novel data mining methods help to address the limitations of traditional regression-based methods that focus on interactions. METHODS: We propose an exploratory approach, using recursive partitioning methods, for example, interaction trees (IT) and virtual twins (VT), to flexibly identify subgroups in which the treatment effect is likely to be large. We apply these tree-based methods to a pharmacogenetic trial of ondansetron. RESULTS: Our methods identified several subgroups based on patients' genetic and other prognostic covariates. Among the 251 subjects with complete genotype information, the IT method identified 118 with specific genetic and other prognostic factors, resulting in a 17.2% decrease in the percentage of heavy drinking days (PHDD). The VT method identified 88 subjects with a 21.8% decrease in PHDD. Overall, the VT subgroup achieved a good balance between the treatment effect and the group size. CONCLUSIONS: A data mining approach is proposed as a valid exploratory method to identify a sufficiently large subgroup of subjects that is likely to receive benefit from treatment in an alcohol dependence pharmacotherapy trial. Our results provide new insights into the heterogeneous nature of alcohol dependence and could help clinicians to tailor treatment to the biological profile of individual patients, thereby achieving better treatment outcomes.

A latent class analysis of cancer risk behaviors among U.S. college students.

OBJECTIVE: The purpose of this study is to understand how cancer risk behaviors cluster in U.S. college students and vary by race and ethnicity. METHODS: Using the fall 2010 wave of the National College Health Assessment (NCHA), we conducted a latent class analysis (LCA) to evaluate the clustering of cancer risk behaviors/conditions: tobacco use, physical inactivity, unhealthy diet, alcohol binge drinking, and overweight/obesity. The identified clusters were then examined separately by students' self-reported race and ethnicity. RESULTS: Among 30,093 college students surveyed, results show a high prevalence of unhealthy diet as defined by insufficient fruit and vegetable intake (>95%) and physical inactivity (>60%). The LCA identified behavioral clustering for the entire sample and distinct clustering among Black and American Indian students. CONCLUSIONS: Cancer risk behaviors/conditions appear to cluster among college students differentially by race. Understanding how risk behaviors cluster in young adults can lend insight to racial disparities in cancer through adulthood. Health behavior interventions focused on modifying multiple risk behaviors and tailored to students' racial group could potentially have a much larger effect on cancer prevention than those targeting any single behavior.

Association of depressive symptoms, trait anxiety, and perceived stress with subclinical atherosclerosis: results from the Chicago Healthy Aging Study (CHAS).

OBJECTIVE: Examine the association between multiple psychological factors (depressive symptoms, trait anxiety, perceived stress) and subclinical atherosclerosis in older age. METHOD: This cross-sectional study included 1101 adults ages 65-84 from the Chicago Healthy Aging Study (CHAS - 2007-2010). Previously validated self-report instruments were used to assess psychological factors. Non-invasive methods were used to assess subclinical atherosclerosis in two regions of the body, i.e., ankle-brachial blood pressure index (ABI) and coronary artery calcification (CAC). Multivariate logistic regression was used to examine the association between each psychological measure and subclinical atherosclerosis, after the adjustment for socio-demographic factors, sleep quality, young adulthood/early middle age and late-life CVD risk status, and psychological ill-being as appropriate. RESULTS: The burden of major cardiovascular disease risk factors did not significantly differ across tertiles of psychological factors. In multivariate adjusted models, trait anxiety was associated with calcification: those in the second tertile were significantly more likely to have CAC >0 compared to those in the lowest anxiety tertile [OR=1.68; 95% CI=1.09-2.58], but no significant difference was observed for Tertile III of trait anxiety [OR=1.31; 95% CI=0.75-2.27]. No association was seen between psychological measures and ABI. CONCLUSION: Of several psychological factors, only trait anxiety was significantly associated with CAC.

Adjuvant proton beam therapy in patients with grade 2 meningiomas.

Background: The World Health Organization (WHO) grade 2 meningiomas behave aggressively with a high proclivity toward recurrence despite maximal surgical resection. Our institution, a pioneer of proton therapy, uses exclusively proton beam radiation, and thus, we present a retrospective cohort analysis of patients with WHO grade 2 meningiomas treated with adjuvant proton beam therapy (PBT) at our institution between 2007 and 2019. The effects of adjuvant PBT were evaluated. Methods: Data collected include diagnosis, gender, histological subtype, WHO grade, the extent of surgical resection, adjuvant PBT radiation, details of the PBT radiation, recurrence, any additional PBT radiation, systemic medical therapy, and disease-specific survival. Results: Among the WHO grade 2 meningiomas (n = 50) recommended PBT, 80% and 78% of patients with gross-total resection (GTR) and subtotal resection (STR), respectively, followed through with PBT. The median radiation dose of PBT was 59.5 Gy and 59.92 Gy for patients with GTR and STR, respectively, with a median of 33 fractions delivered in 1.8 Gy doses for both groups. Combined 3-year progression-free survival (PFS) was 96%, and 5-year PFS was 92%. Combined overall survival was 95% at five years. Minimal radiation side effects were reported with no grade 3 or higher toxicities. Conclusion: Our results suggest that adjuvant PBT is well tolerated with minimal radiation toxicity. Alternative to photon radiation, PBT may be considered at least as safe and effective for adjuvant treatment of WHO grade 2 meningiomas when it is available.

Racial differences in risks for first cardiovascular events and noncardiovascular death: the Atherosclerosis Risk in Communities study, the Cardiovascular Health Study, and the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: No studies have compared first cardiovascular disease (CVD) events and non-CVD death between races in a competing risks framework, which examines risks for numerous events simultaneously. METHODS AND RESULTS: We used competing Cox models to estimate hazards for first CVD events and non-CVD death within and between races in 3 multicenter, National Heart, Lung, and Blood Institute-sponsored cohorts. Of 14 569 Atherosclerosis Risk in Communities (ARIC) study participants aged 45 to 64 years with mean follow-up of 10.5 years, 11.6% had CVD and 5.0% had non-CVD death as first events; among 4237 Cardiovascular Health Study (CHS) study participants aged 65 to 84 years and followed for 8.5 years, these figures were 43.2% and 15.7%, respectively. Middle-aged blacks were significantly more likely than whites to experience any CVD as a first event; this disparity disappeared by older adulthood and after adjustment for CVD risk factors. The pattern of results was similar for Multi-Ethnic Study of Atherosclerosis (MESA) participants. Traditional Cox and competing risks models yielded different results for coronary heart disease risk. Black men appeared somewhat more likely than white men to experience coronary heart disease with use of a standard Cox model (hazard ratio 1.06; 95% CI 0.90, 1.26), whereas they appeared less likely than white men to have a first coronary heart disease event with use of a competing risks model (hazard ratio, 0.77; 95% CI, 0.60, 1.00). CONCLUSIONS: CVD affects blacks at an earlier age than whites; this may be attributable in part to elevated CVD risk factor levels among blacks. Racial disparities in first CVD incidence disappear by older adulthood. Competing risks analyses may yield somewhat different results than traditional Cox models and provide a complementary approach to examining risks for first CVD events.

Association of the 4 g/5 g polymorphism of plasminogen activator inhibitor-1 gene with sudden sensorineural hearing loss. A case control study.

BACKGROUND: The 5 G/5 G genotype of PAI-1 polymorphism is linked to decreased plasminogen activator inhibitor-1 (PAI-1) levels and it has been suggested that lower PAI-1 levels may provide protective effects on inflammation, local microcirculatory disturbance, and fibrotic changes, which are likely associated with development of sudden sensorineural hearing loss (SSNHL). METHODS: The association of the 4 G/5 G PAI-1 polymorphism with the development and clinical outcome of SSNHL is evaluated via a case control study. 103 patients with SSNHL and 113 age and sex-matched controls were enrolled at University of Ferrara, Italy and hearing loss outcome was measured at least 3 months after the onset of hearing loss. DNA was isolated from peripheral blood using the QIAamp kit and the 4 G/5 G polymorphism in the -675 promoter region was genotyped with an allele-specific PCR. Genotype distribution was tested in patients and compared to controls by chi-square and odd-ratio analysis. The codominant and recessive models were used for the multiple logistic regression analyses of the PAI-1 gene allele. RESULTS: In this population, 5 G/5 G genotype had a two-time lower frequency in SSNHL patients compared to healthy controls (15.5% vs 30.1%) and was associated with decreased odds compared to 4 G/5 G genotype (OR 0.37, 95% CI 0.19-0.75, p = 0.005). In addition, the patients with 5 G/5 G genotype showed a trend of more than 2 times higher ratio of hearing recovery (> 20 dB) after systemic corticosteroid treatment compared to 4 G/5 G genotype (OR 2.3, 95% CI 0.32 - 16.83, p = 0.39), suggesting a better clinical outcome. CONCLUSIONS: The 5 G/5 G genotype of PAI-1 may be associated with a reduced risk of SSNHL in the Italian population.