Antimicrobial resistance and its detection in Staphylococcus saprophyticus urinary isolates.

The aim of this study was to describe the antibiotic susceptibility of clinical Staphylococcus saprophyticus isolates collected prospectively from urine specimens over a 2-month period from September to October 2022 at a single centre in Melbourne, Australia. Species identification was performed by MALDI-TOF MS. All isolates underwent phenotypic antibiotic susceptibility testing by disc diffusion using European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) guidelines and VITEK2, and mecA polymerase chain reaction. A total of 302 S. saprophyticus isolates from 298 patients were included in this study. Most specimens (91.1%) were referred by community general practitioners from non-hospitalised patients. Antimicrobial resistance to non-ß-lactam antibiotics was uncommon; trimethoprim susceptibility was 97%; trimethoprim/sulfamethoxazole, 98%; nitrofurantoin, 100%; and ciprofloxacin, 100% (100% ciprofloxacin susceptible, increased exposure by EUCAST breakpoints). Methicillin resistance (by mecA detection) was the most common form of urinary antibiotic resistance at 5.6%. VITEK2 susceptibility testing for methicillin resistance had a poor specificity of 61.8% (95% CI 55.8-67.4%) compared to mecA detection. These findings indicate that empiric antibiotic recommendations of trimethoprim, trimethoprim/sulfamethoxazole, and nitrofurantoin for treatment of urinary S. saprophyticus remain appropriate.

Perfluorooctanoic Acid Disrupts Ovarian Steroidogenesis and Folliculogenesis in Adult Mice.

Perfluorooctanoic acid (PFOA) is a synthetic fluorosurfactant used in the manufacturing of fluorotelomers. Although PFOA is no longer produced in the United States, it is environmentally persistent and found in imported food packaging, cookware, and textiles. Previous studies have identified developmental toxicity of PFOA, but little is known about the effects of PFOA on the adult ovary. Thus, this study examined the effects of PFOA on hormone levels, ovarian steroidogenic gene expression, and folliculogenesis in mice in vitro and in vivo. For the in vitro studies, antral follicles from adult female mice were cultured with vehicle control or 1, 10, or 100 µg/ml PFOA for 96 h. For the in vivo studies, adult CD-1 female mice were orally dosed with vehicle control or 1, 5, 10, or 20 mg/kg/day PFOA for 10 days. Gene expression of steroidogenic enzymes, levels of sex steroid hormones, and follicle counts were analyzed. In vitro, PFOA (100 µg/ml) significantly decreased follicle growth, estradiol and estrone levels, and gene expression of StaR, Cyp11a1, and Hsd3b1 compared with controls. In vivo, exposure to PFOA significantly decreased progesterone and pregnenolone levels (5 mg/kg), increased testosterone levels (1 mg/kg), and increased gene expression of Cyp19a1 (1 mg/kg) compared with controls. Exposure to PFOA also significantly altered follicle counts by decreasing primordial follicles and increasing preantral and antral follicles (5 and 10 mg/kg) compared with controls. Collectively, these data show that PFOA disrupts adult ovarian function in a nonmonotonic matter and may pose a risk for premature ovarian failure.

Association of triglyceride to HDL cholesterol ratio with cardiometabolic outcomes.

Electronic medical records (EMRs) offer a potential opportunity to identify patients at high risk for cardiometabolic disease, which encompasses type 2 diabetes and cardiovascular disease (CVD). The objective of this retrospective cohort study is to use information gathered from EMR to investigate the association between triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) and cardiometabolic outcomes in a general population of subjects over 50 years of age during a follow-up period of 8-9 years. TG/HDL-C was recorded for each of 1428 subjects in 2008, and diagnoses of type 2 diabetes and CVD were recorded through chart review until 2017. Cox proportional hazards models controlling for demographic characteristics and other risk factors demonstrated that high TG/HDL-C (>2.5 in women or >3.5 in men) was significantly associated with increased incidence of type 2 diabetes (HR 1.66; 95% CI 1.07 to 2.57; p=0.0230). There was also a suggested association between high TG/HDL-C and incidence of CVD (HR 1.51; 95% CI 0.98 to 2.35; p=0.0628). These findings suggest that using TG/HDL-C, which can be easily calculated from data in an EMR, should be another tool used in identifying patients at high cardiometabolic risk.

Do Behavioral Risk Factors for Prediabetes and Insulin Resistance Differ across the Socioeconomic Gradient? Results from a Community-Based Epidemiologic Survey.

To examine whether behavioral risk factors associated with diabetes (diet, BMI, waist circumference, physical activity, and sleep duration) are also related to both prediabetes and insulin resistance (IR), we used data from Boston Area Community Health (BACH) Survey (2010-2012, n = 3155). Logistic and linear regression models were used to test the association of lifestyle factors with prediabetes status, insulin resistance, and prediabetes or insulin resistance. All regression models were stratified by education and income levels (to examine whether risk factors had differential effects across socioeconomic factors) and adjusted for age, gender, race/ethnicity, family history of diabetes, and smoking status. We found that large waist circumference was consistently associated with higher levels of insulin resistance (IR) and increased odds of prediabetes. While the association between large waist circumference and IR was consistent across all levels of SES (P < 0.001), the association between large waist circumference and prediabetes was only statistically significant in the highest socioeconomic strata with odds ratios of 1.68 (95% CI 1.07-2.62) and 1.88 (95% CI 1.22-2.92) for postgraduate degree and income strata, respectively. There was no association between diet, physical activity, sleep duration, and the presence of multiple risk factors and prediabetes or IR within SES strata.

Racial ethnic differences in type 2 diabetes treatment patterns and glycaemic control in the Boston Area Community Health Survey.

OBJECTIVES: Numerous studies continue to report poorer glycaemic control, and a higher incidence of diabetes-related complications among African-Americans and Hispanic-Americans as compared with non-Hispanic Caucasians with type 2 diabetes. We examined racial/ethnic differences in receipt of hypoglycaemic medications and glycaemic control in a highly insured Massachusetts community sample of individuals with type 2 diabetes. SETTING: Community-based sample from Boston, Massachusetts, USA. PARTICIPANTS: 682 patients with physician-diagnosed diabetes from the third wave of the Boston Area Community Health Survey (2010-2012). The study included approximately equal proportions of African-Americans, Hispanics and Caucasians. METHODS: We examined racial/ethnic disparities in diabetes treatment by comparing proportions of individuals on mutually exclusive diabetes treatment regimens across racial/ethnic subgroups. Using multivariable linear and logistic regression, we also examined associations between race/ethnicity and glycaemic control in the overall population, and within treatment regimens, adjusting for age, gender, income, education, health insurance, health literacy, disease duration, diet and physical activity. RESULTS: Among those treated (82%), the most commonly prescribed antidiabetic regimens were biguanides only (31%), insulin only (23%), and biguanides and insulin (16%). No overall racial/ethnic differences in treatment or glycaemic control (per cent difference for African-Americans: 6.18, 95% CI -1.00 to 13.88; for Hispanic-Americans: 1.01, 95% CI -10.42 to 12.75) were observed. Within regimens, we did not observe poorer glycaemic control for African-Americans prescribed biguanides only, insulin only or biguanides combined with insulin/sulfonylureas. However, African-Americans prescribed miscellaneous regimens had higher risk of poorer glycaemic control (per cent difference=23.37, 95% CI 7.25 to 43.33). There were no associations between glycaemic levels and Hispanic ethnicity overall, or within treatment regimens. CONCLUSIONS: Findings suggest a lack of racial/ethnic disparities in diabetes treatment patterns and glycaemic control in this highly insured Massachusetts study population. Future studies are needed to understand impacts of increasing insurance coverage on racial/ethnic disparities in treatment patterns and related outcomes.

Extended genome sequences of penaeid shrimp infectious myonecrosis virus strains from Brazil and Indonesia.

New sequencing studies of the nonsegmented dsRNA genome of penaeid shrimp infectious myonecrosis virus (IMNV), a tentatively assigned member of the family Totiviridae, identified previously unread sequences at both genome termini in three previously analyzed IMNV strains, one from Brazil (the prototype strain of IMNV) and two from Indonesia. The new sequence determinations add >600 nt to the 5' end of the genomic plus strand of each strain, increasing the length of the 5' nontranslated region to at least 469-472 nt and the length of the upstream open reading frame (ORF1) translation product by at least 48 aa. These new findings are similar to recent ones for two other IMNV strains (GenBank KF836757.1 and KJ556923.1) and thereby corroborate important amendments to the full-length IMNV genome sequence.

Geographic variations in sleep duration: a multilevel analysis from the Boston Area Community Health (BACH) Survey.

BACKGROUND: Sleep plays an important role in health and varies by social determinants. Little is known, however, about geographic variations in sleep and the role of individual-level and neighbourhood-level factors. METHODS: We used a multilevel modelling approach to quantify neighbourhood variation in self-reported sleep duration (very short <5 h; short 5-6.9 h; normative 7-8.9 h; long ≥9 h) among 3591 participants of the Boston Area Community Health Survey. We determined whether geographic variations persisted with control for individual-level demographic, socioeconomic status (SES) and lifestyle factors. We then determined the role of neighbourhood SES (nSES) in geographic variations. Additional models considered individual health factors. RESULTS: Between neighbourhood differences accounted for a substantial portion of total variability in sleep duration. Neighbourhood variation persisted with control for demographics, SES and lifestyle factors. These characteristics accounted for a portion (6-20%) of between-neighbourhood variance in very short, short and long sleep, while nSES accounted for the majority of the remaining between-neighbourhood variances. Low and medium nSES were associated with very short and short sleep (eg, very short sleep OR=2.08; 95% CI 1.38 to 3.14 for low vs high nSES), but not long sleep. Further inclusion of health factors did not appreciably increase the amount of between-neighbourhood variance explained nor did it alter associations. CONCLUSIONS: Sleep duration varied by neighbourhood in a diverse urban setting in the northeastern USA. Individual-level demographics, SES and lifestyle factors explained some geographic variability, while nSES explained a substantial amount. Mechanisms associated with nSES should be examined in future studies to help understand and reduce geographic variations in sleep.

Traffic-related air pollution and sleep in the Boston Area Community Health Survey.

Little is known about environmental determinants of sleep. We investigated the association between black carbon (BC), a marker of traffic-related air pollution, and sleep measures among participants of the Boston Area Community Health Survey. We also sought to assess the impact of sociodemographic factors, health conditions, and season on associations. Residential 24-h BC was estimated from a validated land-use regression model for 3821 participants and averaged over 1-6 months and 1 year. Sleep measures included questionnaire-assessed sleep duration, sleep latency, and sleep apnea. Linear and logistic regression models controlling for confounders estimated the association between sleep measures and BC. Effect modification was tested with interaction terms. Main effects were not observed between BC and sleep measures. However, in stratified models, males experienced 0.23 h less sleep (95% CI: -0.42, -0.03) and those with low SES 0.25 h less sleep (95% CI: -0.48, -0.01) per IQR increase in annual BC (0.21 µg/m(3)). In blacks, sleep duration increased with annual BC (ß=0.34 per IQR; 95% CI: 0.12, 0.57). Similar findings were observed for short sleep (≤5 h). BC was not associated with sleep apnea or sleep latency, however, long-term exposure may be associated with shorter sleep duration, particularly in men and those with low SES, and longer sleep duration in blacks.

Pathways between acculturation and health behaviors among residents of low-income housing: the mediating role of social and contextual factors.

Acculturation may influence health behaviors, yet mechanisms underlying its effect are not well understood. In this study, we describe relationships between acculturation and health behaviors among low-income housing residents, and examine whether these relationships are mediated by social and contextual factors. Residents of 20 low-income housing sites in the Boston metropolitan area completed surveys that assessed acculturative characteristics, social/contextual factors, and health behaviors. A composite acculturation scale was developed using latent class analysis, resulting in four distinct acculturative groups. Path analysis was used to examine interrelationships between acculturation, health behaviors, and social/contextual factors, specifically self-reported social ties, social support, stress, material hardship, and discrimination. Of the 828 respondents, 69% were born outside of the U.S. Less acculturated groups exhibited healthier dietary practices and were less likely to smoke than more acculturated groups. Acculturation had a direct effect on diet and smoking, but not physical activity. Acculturation also showed an indirect effect on diet through its relationship with material hardship. Our finding that material hardship mediated the relationship between acculturation and diet suggests the need to explicate the significant role of financial resources in interventions seeking to promote healthy diets among low-income immigrant groups. Future research should examine these social and contextual mediators using larger, population-based samples, preferably with longitudinal data.

Long-term outcome of PCI versus CABG in insulin and non-insulin-treated diabetic patients: results from the FREEDOM trial.

BACKGROUND: The prospective, randomized FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial found coronary artery bypass graft surgery (CABG) was associated with better clinical outcomes than percutaneous coronary intervention (PCI) in patients with diabetes and multivessel disease, managed with or without insulin. OBJECTIVES: In this subgroup analysis of the FREEDOM trial, we examined the association of long-term clinical outcomes after revascularization in patients with insulin-treated diabetes mellitus (ITDM) compared with patients not treated with insulin. METHODS: A total of 1,850 FREEDOM subjects had an index revascularization procedure performed: 956 underwent PCI with drug-eluting stents (DES), and 894 underwent CABG. A total of 602 patients (32.5%) had ITDM (PCI/DES n = 325, 34%; CABG n = 277, 31%). Subjects were classified according to ITDM versus non-ITDM, with comparison of PCI/DES versus CABG for each group. Interaction analyses were performed for treatment by diabetes mellitus (DM) status alone and for treatment by DM status by coronary lesion complexity. Analyses were performed for the primary outcome composite of death/stroke/myocardial infarction (MI) using all available follow-up data. RESULTS: The overall 5-year event rate of death/stroke/MI was significantly higher in ITDM versus non-ITDM patients (28.7% vs. 19.5%, p < 0.001), which persisted even after adjustment for multiple baseline factors, angiographic complexity, and revascularization treatment group (death/stroke/MI hazard ratio [HR]: 1.35, 95% confidence interval [CI]: 1.06 to 1.73, p = 0.014). With respect to the primary composite endpoint, CABG was superior to PCI/DES in both DM types and the magnitude of treatment effect was similar (interaction p = 0.40) for ITDM (PCI vs. CABG HR: 1.21; 95% CI: 0.87 to 1.69) and non-ITDM patients (PCI vs. CABG HR: 1.46; 95% CI 1.10 to 1.94), even after adjusting for the angiographic SYNTAX score level. Based on 5-year event rates, the number needed to treat with CABG versus PCI to prevent 1 event is 12.7 in ITDM and 13.2 in non-ITDM. CONCLUSIONS: In patients with diabetes and multivessel coronary artery disease, the rate of major adverse cardiovascular events (death, MI, or stroke) is higher in patients treated with insulin than in those not treated with insulin. Furthermore, we did not detect a significant difference in the magnitude of PCI versus CABG treatment effect for patients treated with insulin and those not treated with insulin. (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes [FREEDOM]; NCT00086450).

Racial/ethnic and socioeconomic differences in bone loss among men.

As men age, they lose bone and are susceptible to fracture. Despite having lower fracture rates than women, men have worse fractures than women do. Racial/ethnic and socioeconomic status (SES) disparities in fracture rates exist, yet data on rates of bone loss by race/ethnicity and SES among men are limited. We examined annualized percentage change in bone mineral density (%ΔBMD) at the hip (N = 681), spine (N = 663), and forearm (N = 636) during 7 years of follow-up among men aged 30-79 years at baseline. Multivariable models tested whether race/ethnicity, income, or genetic ancestry predicted annualized %ΔBMD after controlling for an extensive set of covariates. Annualized %ΔBMD ranged from -0.65(0.04)% (femoral neck) to +0.26(0.03)% (1/3 distal radius), and changes were consistent across age groups with the exception of the ultradistal radius, where annualized declines increased with age. Neither self-identified race/ethnicity nor genetic ancestry were associated with annualized %ΔBMD. In contrast, income was strongly associated (dose-response) with annualized %ΔBMD at total hip (independent of confounders, self-identified race/ethnicity, and genetic ancestry). Fully adjusted least-square mean change in annualized %ΔBMD at the total hip were -0.24(0.12)% and -0.16(0.06)% steeper among men with low and moderate incomes, respectively, than among men with higher incomes (overall p = 0.0293). Results show a linear decline in bone that begins relatively early in life among men, that rates of bone loss do not vary with race/ethnicity (self-identified or "objectively" measured), and that income plays an important role in relation to bone loss at the hip. These data suggest that fracture risk in men may be driven in part by income-related differences in bone loss, but also, that the known higher fracture risk among white men is not the result of racial/ethnic differences in bone loss, but rather, early life exposures that lead to attainment of higher peak bone mass among minorities.

Differences in skeletal and non-skeletal factors in a diverse sample of men with and without type 2 diabetes mellitus.

AIMS: Patients with type 2 diabetes mellitus (T2DM) have increased fracture risk yet higher bone mineral density (BMD), but data are inconsistent in men. We compared skeletal and non-skeletal (e.g., muscle mass, strength) factors in men with/without T2DM. METHODS: Cross-sectional study of 1137 Boston men 30-79years in the Boston Area Community Health/Bone Survey. Diabetes status was self-reported, and BMD and body composition were measured by DXA, and grip strength by hand dynamometer. Physical function was assessed by walking speed and chair stands. Multivariable linear regressions examined associations of T2DM with skeletal/non-skeletal factors. RESULTS: Mean age was 48years. The population was 24.6% Black, 13.0% Hispanic, and 62.4% White. Prevalence of T2DM was 12.5%; average disease duration was 7.4years. While subjects with T2DM did not differ in skeletal factors (e.g., BMD), they had significantly lower appendicular lean mass [mean difference (MD)=-1.04kg; standard error (SE)=0.50; p=0.04], arms lean mass (MD=-0.42kg; SE=0.15; p=0.006) and grip strength (MD=-3.02kg; SE=1.25; p=0.025) after adjustment for age, race/ethnicity, and BMI. CONCLUSIONS: Men with T2DM have lower muscle mass and strength, but similar BMD, compared to their non-diabetic counterparts. These differences in non-skeletal factors might explain, at least in part, the higher incidence of falls and fractures observed in T2DM patients.

Does concern motivate behavior change? Exploring the relationship between physical activity and body mass index among low-income housing residents.

OBJECTIVE: To explore relationships between concerns and physical activity and body mass index (BMI) among a racially/ethnically diverse low-income population. METHOD: A cross-sectional survey documented behavioral risks among racially/ethnically diverse low-income residents in the Boston area (2005-2009). Multivariable logistic regressions were conducted in 2012 for each concern, using SAS version 9.2. RESULTS: Those very/moderately concerned about weight were more likely to have higher BMIs, be in the preparation/action stage, received behavioral counseling, participated in a weight management program, and be interested in participating in one in the future. Those very/moderately concerned about physical activity were more likely to have higher BMIs, received behavioral counseling, and participated in a physical activity program. CONCLUSION: Individuals with elevated BMIs or low levels of physical activity are concerned. While level of concern is important, these findings suggest that it is not likely to be a sufficient catalyst to behavior change.

Sleep related problems and urological symptoms: testing the hypothesis of bidirectionality in a longitudinal, population based study.

PURPOSE: We evaluate the bidirectional association between urological symptoms (urinary incontinence, lower urinary tract symptoms and nocturia) and sleep related variables. MATERIALS AND METHODS: Data were obtained from a prospective cohort study of 1,610 men and 2,535 women who completed baseline (2002 to 2005) and followup (2006 to 2010) phases of the BACH (Boston Area Community Health) Survey, a population based random sample survey. Sleep restriction (5 hours or less per night), restless sleep, sleep medication use and urological symptoms were assessed by self-report. Urinary incontinence was defined as weekly leakage or moderate/severe leakage, lower urinary tract symptoms (overall, obstructive, irritative) were defined by the AUA-SI (American Urological Association symptom index) and nocturia was defined as urinary frequency 2 or more times per night. RESULTS: At the 5-year followup 10.0%, 8.5% and 16.0% of subjects newly reported lower urinary tract symptoms, urinary incontinence and nocturia, respectively, and 24.2%, 13.3% and 11.6% newly reported poor sleep quality, sleep restriction and use of sleep medication, respectively. Controlling for confounders, the odds of urological symptoms developing were consistently increased for subjects who reported poor sleep quality and sleep restriction at baseline, but only baseline nocturia was positively associated with incident sleep related problems at followup. Body mass index, a potential mediator, reduced selected associations between sleep and incident urinary incontinence and irritative symptoms, but C-reactive protein did not. CONCLUSIONS: These data suggest that self-reported sleep related problems and urological symptoms are linked bidirectionally, and that body mass index may be a factor in the relationship between sleep and the development of urological symptoms.

Patterns and predictors of health behaviors among racially/ethnically diverse residents of low-income housing developments.

PURPOSE: To examine behavioral patterns and sociodemographic predictors of diet, inactivity, and tobacco use among a diverse sample of residents from low-income housing developments. DESIGN: In this cross-sectional survey study, households and residents were randomly selected using multistage cluster sampling. Setting . The study was conducted in 20 low-income housing developments in the Boston, Massachusetts, metropolitan area. SUBJECTS: Subjects were 828 residents who completed the survey (response rate = 49.3%). Forty-one percent of participants were Hispanic and 38% were non-Hispanic Black. Measures . Outcomes measured were diet, inactivity, and tobacco use. Predictors measured were age, race/ethnicity, gender, education, country in which the subject was born, language spoken, and financial hardship. Analysis . Logistic regression analyses were conducted to examine the association of three health behaviors with sociodemographic factors. RESULTS: Age, gender, language spoken, and financial hardship showed significant relationships with all three behaviors. For example, those who reported less financial hardship (odds ratio [OR] = 1.75) were more likely to eat healthier. Residents who spoke no English, or at least one language in addition to English, were significantly more likely to report healthier eating (OR = 2.78 and 3.30, respectively) than those who spoke English only. Men were significantly more likely to report less healthy eating (OR = 0.65) than were women. Similar trends emerged for inactivity and tobacco use. CONCLUSION: Effective health promotion interventions in low-income housing developments that leverage protective factors while addressing risk factors have the potential to reduce income-related health disparities in these concentrated resource-deprived neighborhoods.

Environmental conditions in low-income urban housing: clustering and associations with self-reported health.

OBJECTIVES: We explored prevalence and clustering of key environmental conditions in low-income housing and associations with self-reported health. METHODS: The Health in Common Study, conducted between 2005 and 2009, recruited participants (n = 828) from 20 low-income housing developments in the Boston area. We interviewed 1 participant per household and conducted a brief inspection of the unit (apartment). We created binary indexes and a summed index for household exposures: mold, combustion by-products, secondhand smoke, chemicals, pests, and inadequate ventilation. We used multivariable logistic regression to examine the associations between each index and household characteristics and between each index and self-reported health. RESULTS: Environmental problems were common; more than half of homes had 3 or more exposure-related problems (median summed index = 3). After adjustment for household-level demographics, we found clustering of problems in site (P < .01) for pests, combustion byproducts, mold, and ventilation. Higher summed index values were associated with higher adjusted odds of reporting fair-poor health (odds ratio = 2.7 for highest category; P < .008 for trend). CONCLUSIONS: We found evidence that indoor environmental conditions in multifamily housing cluster by site and that cumulative exposures may be associated with poor health.

Long-Term Outcome of PCI Versus CABG in Insulin and Non–Insulin-Treated Diabetic PatientsResults From the FREEDOM Trial

The prospective, randomized FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial found coronary artery bypass graft surgery (CABG) was associated with better clinical outcomes than percutaneous coronary intervention (PCI) in patients with diabetes and multivessel disease, managed with or without insulin.Objectives In this subgroup analysis of the FREEDOM trial, we examined the association of long-term clinical outcomes after revascularization in patients with insulin-treated diabetes mellitus (ITDM) compared with patients not treated with insulin.Methods A total of 1,850 FREEDOM subjects had an index revascularization procedure performed: 956 underwent PCI with drug-eluting stents (DES), and 894 underwent CABG. A total of 602 patients (32.5%) had ITDM (PCI/DES n = 325, 34%; CABG n = 277, 31%). Subjects were classified according to ITDM versus non-ITDM, with comparison of PCI/DES versus CABG for each group. Interaction analyses were performed for treatment by diabetes mellitus (DM) status alone and for treatment by DM status by coronary lesion complexity. Analyses were performed for the primary outcome composite of death/stroke/myocardial infarction (MI) using all available follow-up data.Results The overall 5-year event rate of death/stroke/MI was significantly higher in ITDM versus non-ITDM patients (28.7% vs. 19.5%, p < 0.001), which persisted even after adjustment for multiple baseline factors, angiographic complexity, and revascularization treatment group (death/stroke/MI hazard ratio [HR]: 1.35, 95% confidence interval [CI]: 1.06 to 1.73, p = 0.014). With respect to the primary composite endpoint, CABG was superior to PCI/DES in both DM types and the magnitude of treatment effect was similar...

Nonresponders, partial responders, and complete responders to PDE5 inhibitors therapy according to IIEF criteria: validation of an anchor-based treatment responder classification.

INTRODUCTION: Despite widespread use of the International Index of Erectile Function (IIEF) in erectile dysfunction (ED) research, there are no published criteria for classifying ED treatment responders in clinical trials or patient management settings. A new classification for treatment response in men with ED has been developed and validated in a large clinical trial database. AIM: The study aims to test discriminant and convergent validity of the responder classification and examine the role of covariates. METHOD: Treatment assignment was used to test discriminant validity. The diary-based Sexual Encounter Profile (SEP) question ("Did your erection last long enough for you to have successful intercourse?") and Global Assessment Question (GAQ) ("Has the treatment you have been taking over the past study interval improved your erections?") were used to evaluate convergent validity. Chi-square and Cochran-Armitage trend tests were used to examine outcome associations. Logistic regression was used to further assess the relationship of outcomes controlling for covariates. MAIN OUTCOME MEASURE: The classification measure was developed and validated in a database from 17 clinical trials in 3,252 men with ED randomized to placebo or tadalafil. The treatment responder is defined as complete (erectile function [EF] ≥ 26); partial (EF < 26; met minimal clinically important difference [MCID] criteria); or nonresponder following treatment (EF < 26; did not meet MCID). RESULTS: The new responder definition performed consistently well in all prespecified tests of validity. Eighty-nine percent of subjects classified as complete responders were in the treatment group, and the responder definition was associated with changes on the SEP and GAQ measures, respectively (SEP odds ratio [OR] = 14, 95% confidence intervals [CI] 11-17; GAQ OR = 50, 95% CI 39-88; complete vs. nonresponders). CONCLUSIONS: We developed and validated a novel method of defining an ED treatment responder based on multiple IIEF criteria and using other measures (SEP, GAQ) for validation. The results have implications for understanding results of clinical trials in ED, and in monitoring response to treatment in the clinic.

Structure of a protozoan virus from the human genitourinary parasite Trichomonas vaginalis.

The flagellated protozoan Trichomonas vaginalis is an obligate human genitourinary parasite and the most frequent cause of sexually transmitted disease worldwide. Most clinical isolates of T. vaginalis are persistently infected with one or more double-stranded RNA (dsRNA) viruses from the genus Trichomonasvirus, family Totiviridae, which appear to influence not only protozoan biology but also human disease. Here we describe the three-dimensional structure of Trichomonas vaginalis virus 1 (TVV1) virions, as determined by electron cryomicroscopy and icosahedral image reconstruction. The structure reveals a T = 1 capsid comprising 120 subunits, 60 in each of two nonequivalent positions, designated A and B, as previously observed for fungal Totiviridae family members. The putative protomer is identified as an asymmetric AB dimer consistent with either decamer or tetramer assembly intermediates. The capsid surface is notable for raised plateaus around the icosahedral 5-fold axes, with canyons connecting the 2- and 3-fold axes. Capsid-spanning channels at the 5-fold axes are unusually wide and may facilitate release of the viral genome, promoting dsRNA-dependent immunoinflammatory responses, as recently shown upon the exposure of human cervicovaginal epithelial cells to either TVV-infected T. vaginalis or purified TVV1 virions. Despite extensive sequence divergence, conservative features of the capsid reveal a helix-rich fold probably derived from an ancestor shared with fungal Totiviridae family members. Also notable are mass spectrometry results assessing the virion proteins as a complement to structure determination, which suggest that translation of the TVV1 RNA-dependent RNA polymerase in fusion with its capsid protein involves -2, and not +1, ribosomal frameshifting, an uncommonly found mechanism to date.