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Importance Determination of optimal treatment durations for common infectious diseases is an important strategy to preserve antibiotic effectiveness. Objective To determine whether 7 days of treatment is noninferior to 14 days when using ciprofloxacin or trimethoprim/sulfamethoxazole to treat urinary tract infection (UTI) in afebrile men. Design, Setting, and Participants Randomized, double-blind, placebo-controlled noninferiority trial of afebrile men with presumed symptomatic UTI treated with ciprofloxacin or trimethoprim/sulfamethoxazole at 2 US Veterans Affairs medical centers (enrollment, April 2014 through December 2019; final follow-up, January 28, 2020). Of 1058 eligible men, 272 were randomized. Interventions Participants continued the antibiotic prescribed by their treating clinician for 7 days of treatment and were randomized to receive continued antibiotic therapy (n = 136) or placebo (n = 136) for days 8 to 14 of treatment. Main Outcomes and Measures The prespecified primary outcome was resolution of UTI symptoms by 14 days after completion of active antibiotic treatment. A noninferiority margin of 10% was selected. The as-treated population (participants who took ≥26 of 28 doses and missed no more than 2 consecutive doses) was used for the primary analysis, and a secondary analysis included all patients as randomized, regardless of treatment adherence. Secondary outcomes included recurrence of UTI symptoms and/or adverse events within 28 days of stopping study medication. Results Among 272 patients (median [interquartile range] age, 69 [62-73] years) who were randomized, 100% completed the trial and 254 (93.4%) were included in the primary as-treated analysis. Symptom resolution occurred in 122/131 (93.1%) participants in the 7-day group vs 111/123 (90.2%) in the 14-day group (difference, 2.9% [1-sided 97.5% CI, –5.2% to ∞]), meeting the noninferiority criterion. In the secondary as-randomized analysis, symptom resolution occurred in 125/136 (91.9%) participants in the 7-day group vs 123/136 (90.4%) in the 14-day group (difference, 1.5% [1-sided 97.5% CI, –5.8% to ∞]) Recurrence of UTI symptoms occurred in 13/131 (9.9%) participants in the 7-day group vs 15/123 (12.9%) in the 14-day group (difference, –3.0% [95% CI, –10.8% to 6.2%];P = .70). Adverse events occurred in 28/136 (20.6%) participants in the 7-day group vs 33/136 (24.3%) in the 14-day group. Conclusions and Relevance Among afebrile men with suspected UTI, treatment with ciprofloxacin or trimethoprim/sulfamethoxazole for 7 days was noninferior to 14 days of treatment with regard to resolution of UTI symptoms by 14 days after antibiotic therapy. The findings support the use of a 7-day course of ciprofloxacin or trimethoprim/sulfamethoxazole as an alternative to a 14-day course for treatment of afebrile men with UTI. Trial Registration ClinicalTrials.gov identifier:NCT01994538

Many researchers have used the standard Iowa Gambling Task (IGT) to assess decision-making in adolescence given increased risk-taking during this developmental period. Most studies are cross-sectional and do not observe behavioral trajectories over time, limiting interpretation. This longitudinal study investigated healthy adolescents' and young adults' IGT performance across a 10-year span. A total of 189 individuals (aged 9-23 at baseline) completed a baseline session and were followed at 2-year intervals yielding 5 time-points. IGT deck contingencies were shuffled over time to reduce practice effects. IGT performance (good minus bad decisions) was measured at each assessment point and separated into 3 metrics: overall performance (all blocks), decision-making under ambiguity (blocks 1 and 2), and decision-making under risk (blocks 3, 4, and 5). Covariates included estimated intelligence and affective dispositions as measured by the Behavioral Inhibition and Activation System (BIS/BAS) Scales. A linear effect of age yielded the best fit when comparing linear and quadratic effects of age on overall IGT performance. Age and intelligence positively predicted overall performance, whereas affective approach tendencies (BAS) negatively predicted overall performance. Practice effects were observed and controlled for. Models of ambiguity and risk metrics yielded different patterns of significant predictors. Age predicted better performance and affective approach tendencies predicted worse performance for both metrics. Intelligence was a significant predictor for risk, but not ambiguity. This longitudinal study extends prior work by showing age-related improvements in reward-based decision-making and associating those improvements with cognitive and affective variables. Implications of the results for adolescent development are discussed. (PsycINFO Database Record

We surveyed resident physicians at 2 academic medical centers regarding urinary testing and treatment as they progressed through training. Demographics and self-reported confidence were compared to overall knowledge using clinical vignette-based questions. Overall knowledge was 40% in 2011 and increased to 48%, 55%, and 63% in subsequent years (PInfect Control Hosp Epidemiol 2018;39:616–618

Escherichia coli sequence type 13 (ST131), an emergent cause of multidrug-resistant extraintestinal infections, has important phylogenetic subsets, notably the H 30 and H 30Rx subclones, with distinctive resistance profiles and, possibly, clinical associations. To clarify the local prevalence of these ST131 subclones and their associations with antimicrobial resistance, ecological source, and virulence traits, we extensively characterized 233 consecutive E. coli clinical isolates (July and August 2013) from the University of Minnesota Medical Center-Fairview Infectious Diseases and Diagnostic Laboratory, Minneapolis, MN, which serves three adjacent facilities (a children's hospital and low- and high-acuity adult facilities). ST131 accounted for 26% of the study isolates (more than any other clonal group), was distributed similarly by facility, and was closely associated with ciprofloxacin resistance and extended-spectrum β-lactamase (ESBL) production. The H 30 and H 30Rx subclones accounted for most ST131 isolates and for the association of ST131 with fluoroquinolone resistance and ESBL production. Unlike ST131 per se , these subclones were distributed differentially by hospital, being most prevalent at the high-acuity adult facility and were absent from the children's hospital. The virulence gene profiles of ST131 and its subclones were distinctive and more extensive than those of other fluoroquinolone-resistant or ESBL-producing isolates. Within ST131, bla CTX-M-15 was confined to H 30Rx isolates and other bla CTX-M variants to non-Rx H 30 isolates. Pulsed-field gel electrophoresis documented a predominance of globally distributed pulsotypes and no local outbreak pattern. These findings help clarify the epidemiology, ecology, and bacterial correlates of the H 30 and H 30Rx ST131 subclones by documenting a high overall prevalence but significant segregation by facility, strong associations with fluoroquinolone resistance and specific ESBL variants, and distinctive virulence gene associations that may confer fitness advantages over other resistant E. coli .

A double-blind crossover pilot trial tested the hypothesis that botanically derived calcium could demonstrate greater influence over calcium metabolism markers compared with a nonplant-derived calcium carbonate supplement or placebo. Twelve fasting female subjects received a single oral dose of Aquamin F™ (derived from the marine algal Lithothamnion sp.), or calcium carbonate, or placebo. Blood and urine samples were collected at baseline and over 12 h to evaluate ionized and total calcium and parathyroid hormone (PTH). Subjects treated with Aquamin F demonstrated significantly greater urinary clearance of calcium after 12 h compared with placebo (P = .004). Following a meal at 90 min, subjects treated with Aquamin F demonstrated a more prolonged suppression of serum PTH concentration (significantly lower than placebo at 90, 120, and 240 min). Calcium carbonate provided an intermediate response; urinary clearance was not significantly different from placebo treatment and PTH was only significantly lower than placebo at 90 min. Aquamin F may demonstrate greater influence over these markers of calcium metabolism than calcium carbonate or placebo, as suggested by a greater calciuric response and a more prolonged suppression of serum PTH concentrations following a meal in premenopausal women.

Vancomycin dose selection is challenging in the spinal cord injury (SCI) population because of the difficulty in accurately estimating the renal function. Creatinine-based equations have been shown to be unreliable in this patient population. Adjusted equations designed for patients with SCI have not been well studied. Cystatin C is an alternative marker of renal function that is less affected by muscle mass and may offer improvement in estimating renal function leading to improved initial dose selection.To compare the accuracy of serum creatinine- and serum cystatin C-based equations used in a pharmacokinetic (PK) model to predict steady-state serum vancomycin concentration in an SCI population. The rationale for this study is the need for an improved predictive model to guide initial vancomycin dose design before the availability of a measured steady-state serum concentration.Patients with SCI receiving vancomycin with measured serum creatinine, cystatin C, and steady-state serum vancomycin concentration were identified. Serum creatinine- and cystatin C-based equations to estimate renal function were substituted into a population-based PK model to predict steady state-serum vancomycin concentration. Predictions using each equation in the model were compared with the measured steady-state serum vancomycin concentration. Predictive performances using each equation in the PK model were compared.The final study population included 37 patients with SCI. The Chronic Kidney Disease Epidemiology Collaboration cystatin C equation provided significantly less bias, greater precision, and superior accuracy when used in the PK model.In the SCI population, the use of Chronic Kidney Disease Epidemiology Collaboration cystatin C equation may improve initial vancomycin dosing. Further study into this potential is encouraged.

The objective of the study consisted of comparing lifetime prevalence rates and odds ratios of anxiety, mood, and psychotic disorders in adopted-versus-non-adopted people in a nationally representative sample. The data were drawn from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC). The main outcome measure was the prevalence of lifetime internalizing psychiatric disorders in adopted (n = 378) versus non-adopted (n = 42,503) individuals. Adoptees and non-adoptees were compared to estimate the odds of lifetime internalizing disorders using logistic regression analyses. Adoptees had higher prevalence rates of several lifetime mood and anxiety disorders compared with non-adoptees, with a 1.61-fold increase (95% CI 1.29–2.02) in the odds of any mood disorder and a 1.49-fold increase (95% CI 1.18–1.89) in the odds of any anxiety disorder compared with non-adoptees. Regarding specific mood and anxiety disorders, adoptees had increased odds of major depressive disorder, bipolar I disorder, panic disorder without agoraphobia, specific phobia, and generalized anxiety disorder. Disorders not differing between adoptees and non-adoptees included dysthymia, bipolar II disorder, panic disorder with agoraphobia, social phobia, and psychotic disorder. One adoption-specific risk factor was associated with lifetime mood disorder (i.e., Asian/Pacific Island). In conclusion, adoptees in a large sample from the general population had higher rates of mood and anxiety disorders compared to non-adoptees.

Prior studies suggest an association between stressful life events and fractures that may be mediated by BMD. In the current study, risk of accelerated hip BMD loss was higher in older men with any type of stressful life event and increased with the number of types of stressful life events.Prior studies suggest that stressful life events may increase adverse health outcomes, including falls and possibly fractures. The current study builds on these findings and examines whether stressful life events are associated with increased bone loss.Four thousand three hundred eighty-eight men aged ≥65 years in the Osteoporotic Fractures in Men study completed total hip bone mineral density (BMD) measures at baseline and visit 2, approximately 4.6 years later, and self-reported stressful life events data mid-way between baseline and visit 2, and at visit 2. We used linear regression to model the association of stressful life events with concurrent annualized total hip BMD loss, and log binomial regression or Poisson regression to model risk of concurrent accelerated BMD loss (1 SD more than mean annualized change).Men (75.3 %) reported ≥1 type of stressful life event, including 43.3 % with ≥2 types of stressful life events. Mean annualized BMD loss was -0.36 % (SD 0.88), and 13.9 % of men were categorized with accelerated BMD loss (about 5.7 % or more total loss). Rate of annualized BMD loss increased with the number of types of stressful life events after adjustment for age (p 0.001), but not after multivariable adjustment (p = 0.07). Multivariable-adjusted risk of accelerated BMD loss increased with the number of types of stressful life events (RR, 1.10 [95 % confidence interval (CI), 1.04-1.16]) per increase of one type of stressful life event). Fracture risk was not significantly different between stressful life event-accelerated bone loss subgroups (p = 0.08).In these older men, stressful life events were associated with a small, dose-related increase in risk of concurrent accelerated hip bone loss. Low frequency of fractures limited assessment of whether rapid bone loss mediates any association of stressful life events with incident fractures. Future studies are needed to confirm these findings and to investigate the mechanism that may underlie this association.

Background— Soluble ST2 (sST2), a biomarker related to inflammation, is associated with outcomes of patients with heart failure. In-depth analyses of the relationship among sST2, changes in sST2, and patient outcomes are reported. Methods and Results— sST2 was measured at baseline (n=1650), 4 months (n=1345), and 12 months (n=1094) in Valsartan Heart Failure Trial. Baseline sST2 averaged 28.7±16.2 ng/mL, significantly ( P 33.2 ng/mL. Each segment of the sST2 distribution was significantly ( P P Conclusions— In this study, baseline sST2 was nonlinearly associated with patient outcomes but did not provide substantial prognostic information when added to a clinical prediction model that included N-terminal probrain natriuretic peptide. An increase but not decrease in sST2 was independently associated with outcomes. Additional research is needed to determine whether monitoring ST2 levels can improve patient outcomes.

The rising prevalence of resistance to first-line antimicrobial agents in Escherichia coli , which has paralleled the emergence of E. coli sequence type ST131, has created a need for alternative oral options for use in treating outpatients with infections such as cystitis and chronic prostatitis. Accordingly, we determined susceptibility to six alternative oral agents (azithromycin, chloramphenicol, doxycycline, fosfomycin, minocycline, and rifampin) by Etest or disk diffusion for 120 recently obtained E. coli clinical isolates from Veterans Affairs Medical Centers across the United States. Isolates were randomly selected in three subgroups of 40 isolates each based on coresistance to fluoroquinolones with and without extended-spectrum cephalosporins (ESCs). Results were stratified according to trimethoprim-sulfamethoxazole (TMP-SMZ) phenotype. Overall, the prevalence of susceptible (or susceptible plus intermediate) isolates varied by agent, with rifampin being lowest (0%), fosfomycin highest (98 to 99%), and others in the mid-range (37 to 88%). Substantial proportions of isolates (15 to 27%) yielded intermediate results for azithromycin, chloramphenicol, doxycycline, and minocycline. Among isolates resistant (versus susceptible) to fluoroquinolones with or without ESCs, susceptibility to the above four agents declined significantly among non-ST131 isolates but not ST131 isolates. In contrast, in the presence of resistance to TMP-SMZ, susceptibility to azithromycin, doxycycline, and minocycline was significantly reduced among both ST131 and non-ST131 isolates. These findings identify potential alternative oral agents for use with E. coli isolates resistant to fluoroquinolones, ESCs, and/or TMP-SMZ and suggest that determination of ST131 status could help guide initial antimicrobial selection, pending susceptibility results.

(See the Editorial Commentary by Lautenbach on pages 1266–9.) Escherichia coli causes diverse extraintestinal infections, including urinary tract infection, bacteremia, and meningitis, resulting in considerable morbidity, mortality, and increased costs [1]. Management of such infections is complicated by the rising prevalence of resistance to preferred antimicrobial agents such as trimethoprim-sulfamethoxazole (TMP-SMZ), fluoroquinolones (FQs), and extended-spectrum cephalosporins [1–4]. Contributing to this problem is E. coli sequence type 131 (ST131), a newly emerged, disseminated lineage of multidrug-resistant E. coli [2, 5–9]. In recent surveys ST131 has accounted for up to 10%–27% of the total clinical E. coli population in various locales, and for up to 52%–67% of all extended-spectrum β-lactamase (ESBL)–producing or FQ-resistant (FQ-R) E. coli [2, 10–12]. The Department of Veterans Affairs (VA) operates the largest integrated healthcare system in the United States. [13]. Escherichia coli infections, especially urinary tract infections, are quite common among veterans [14]. Based on associations of ST131 with older age and health care contact [15], and the high prevalence of these characteristics among veterans, we hypothesized that ST131 may contribute importantly to antimicrobial resistance in E. coli among veterans. Accordingly, we assessed the prevalence, geographic distribution, and contribution to antimicrobial resistance of E. coli ST131 among US veterans during 2010–2011 at multiple VA medical centers (VAMCs) across the United States, and explored associations of ST131 with source and fitness-promoting bacterial traits.

Aims This study was conducted to determine whether galectin-3, a β-galactoside-binding lectin, plays a role in the pathogenesis of heart failure (HF). Methods and results Galectin-3 was measured at baseline (n = 1650), after 4 months (n = 1346), and after 12 months (n = 1097) in the Valsartan Heart Failure Trial (Val-HeFT). Galectin-3 levels at baseline ranged from 4.8 to 53 ng/mL. Higher levels were associated with features of worse HF. In a fully adjusted Cox regression model comprising 23 other prognostic variables, baseline galectin-3 was not associated with the risks of all-cause mortality, the composite of the first morbid event, or hospitalization for HF. However, when changes in galectin-3 over time were examined, the increases in galectin-3 between baseline and 4 months were independently and significantly associated with the risks of subsequent all-cause mortality, first morbid event, and hospitalizations for HF, even after adjusting for all baseline and concurrent changes in all variables including estimated glomerular filtration rate (eGFR) and NT-proBNP. The strongest correlate of galectin-3 levels was eGFR, which accounted for 20% of the variability in galectin-3 levels at baseline. There was a significant interaction (P = 0.03) between baseline galectin-3 and the effect of valsartan on hospitalizations for HF. Valsartan caused a significant 44% reduction in hospitalizations for HF in patients with galectin-3 levels below the median level of 16.2 ng/mL, but not in patients with levels above the median. Conclusions Galectin-3 levels are elevated in a substantial proportion of patients with HF, particularly those with more severe HF and renal dysfunction. Galectin-3 increased over time in this cohort, and the increase was independently associated with worse outcomes. Valsartan use was associated with a reduction in hospitalizations for HF in patients with low galectin-3, but not in those with higher levels of galectin-3.

Alzheimer's disease begins about two decades before the onset of symptoms or neuron death, and is believed to be caused by pathogenic amyloid-β aggregates that initiate a cascade of molecular events culminating in widespread neurodegeneration. The microtubule binding protein tau may mediate the effects of amyloid-β in this cascade. Amyloid plaques comprised of insoluble, fibrillar amyloid-β aggregates are the most characteristic feature of Alzheimer's disease. However, the correspondence between the distribution of plaques and the pattern of neurodegeneration is tenuous. This discrepancy has stimulated the investigation of other amyloid-β aggregates, including soluble amyloid-β oligomers. Different soluble amyloid-β oligomers have been studied in several mouse models, but not systematically in humans. Here, we measured three amyloid-β oligomers previously described in mouse models-amyloid-β trimers, Aβ*56 and amyloid-β dimers-in brain tissue from 75 cognitively intact individuals, ranging from young children to the elderly, and 58 impaired subjects with mild cognitive impairment or probable Alzheimer's disease. As in mouse models, where amyloid-β trimers appear to be the fundamental amyloid-β assembly unit of Aβ*56 and are present in young mice prior to memory decline, amyloid-β trimers in humans were present in children and adolescents; their levels rose gradually with age and were significantly above baseline in subjects in their 70s. Aβ*56 levels were negligible in children and young adults, rose significantly above baseline in subjects in their 40s and increased steadily thereafter. Amyloid-β dimers were undetectable until subjects were in their 60s; their levels then increased sharply and correlated with plaque load. Remarkably, in cognitively intact individuals we found strong positive correlations between Aβ*56 and two pathological forms of soluble tau (tau-CP13 and tau-Alz50), and negative correlations between Aβ*56 and two postsynaptic proteins (drebrin and fyn kinase), but none between amyloid-β dimers or amyloid-β trimers and tau or synaptic proteins. Comparing impaired with age-matched unimpaired subjects, we found the highest levels of amyloid-β dimers, but the lowest levels of Aβ*56 and amyloid-β trimers, in subjects with probable Alzheimer's disease. In conclusion, in cognitively normal adults Aβ*56 increased ahead of amyloid-β dimers or amyloid-β trimers, and pathological tau proteins and postsynaptic proteins correlated with Aβ*56, but not amyloid-β dimers or amyloid-β trimers. We propose that Aβ*56 may play a pathogenic role very early in the pathogenesis of Alzheimer's disease.

Objective.To determine the fraction of unnecessary antimicrobial use among patients with current and/or recent Clostridium difficile infection (CDI).Design.Retrospective review from January 2004 through December 2006.Setting.Minneapolis Veterans Affairs Medical Center (MVAMC).Participants.Patients with new-onset CDI diagnosed at the MVAMC without another CDI diagnosis in the prior 30 days.Methods.Pharmacy and medical records were reviewed to identify incident CDI cases, non-CDI antimicrobial use during and up to 30 days after completion of CDI treatment, and patient characteristics. Two infectious disease physicians independently assessed non-CDI antimicrobial use, which was classified as unnecessary if not fully indicated. Factors associated with only unnecessary use were identified through univariable and multivariable analysis.Results.Of 246 patients with new-onset CDI, 141 (57%) received non-CDI antimicrobials during and/or after their CDI treatment, totaling 2,147 antimicrobial days and 445 antimicrobial courses. The two reviewers agreed regarding the necessity of antimicrobials in more than 99% of antimicrobial courses (85% initially, 14% after discussion). Seventy-seven percent of patients received at least 1 unnecessary antimicrobial dose, 26% of patients received only unnecessary antimicrobials, and 45% of total non-CDI antimicrobial days included unnecessary antimicrobials. The leading indications for unnecessary antimicrobial use were putative urinary tract infection and pneumonia. Drug classes frequently used unnecessarily were fluoroquinolones and β-lactams.Conclusions.Twenty-six percent of patients with recent CDI received only unnecessary (and therefore potentially avoidable) antimicrobials. Heightened awareness and caution are needed when antimicrobial therapy is contemplated for patients with recent CDI.

Infections with Staphylococcus aureus may be more frequent in subjects with active hepatitis C virus (HCV) infection. In this retrospective dual-cohort study, we sought to determine whether persons with active HCV infection (positive HCV antibody, detectable blood HCV RNA) were at greater risk of S. aureus infection than those with spontaneously resolved HCV infection (positive HCV antibody, negative blood HCV RNA). Based on prestudy power calculation, we included 231 subjects with active HCV and 116 subjects with resolved HCV infection. The two groups were well matched at baseline, except that subjects with active HCV had a higher mean Charlson’s comorbidity index (2.2 vs. 1.3; p < 0.0001). Cohorts were followed for a mean of 3.67 years. Thirty-one of the 231 (13%) subjects with active HCV infection developed ≥1 S. aureus infection(s) as compared to 4/116 (3.4%) subjects with resolved HCV (p = 0.004), with a trend towards more recurrent S. aureus infections in subjects with active HCV infection. The S. aureus infections were mostly serious, necessitating hospitalization and intravenous antibiotics. In the logistic regression, factors that independently predicted S. aureus infection were active HCV and Charlson’s comorbidity index. Our regression models confirmed that the enhanced susceptibility to S. aureus infections was related to active HCV infection and not attributable solely to the increased number of comorbidities [adjusted odds ratio (OR) = 3.3, 95% confidence interval (CI) 1.1–9.8; p = 0.03]. This study shows that subjects with active HCV infection have a significantly higher incidence of serious S. aureus infections than those with spontaneously resolved HCV, even after adjustment for comorbidities.

Recurrent Clostridium difficile infection (R-CDI) is common and difficult to treat, potentially necessitating fecal microbiota transplantation (FMT). Although C. difficile spores persist in the hospital environment and cause infection, little is known about their potential presence or importance in the household environment. Households of R-CDI subjects in the peri-FMT period and of geographically matched and age-matched controls were analyzed for the presence of C. difficile . Household environmental surfaces and fecal samples from humans and pets in the household were examined. Households of post-FMT subjects were also examined (environmental surfaces only). Participants were surveyed regarding their personal history and household cleaning habits. Species identity and molecular characteristics of presumptive C. difficile isolates from environmental and fecal samples were determined by using the Pro kit (Remel, USA), Gram staining, PCR, toxinotyping, tcdC gene sequencing, and pulsed-field gel electrophoresis (PFGE). Environmental cultures detected C. difficile on ≥1 surface in 8/8 (100%) peri-FMT households, versus 3/8 (38%) post-FMT households and 3/8 (38%) control households ( P = 0.025). The most common C. difficile -positive sites were the vacuum (11/27; 41%), toilet (8/30; 27%), and bathroom sink (5/29; 17%). C. difficile was detected in 3/36 (8%) fecal samples (two R-CDI subjects and one household member). Nine (90%) of 10 households with multiple C. difficile -positive samples had a single genotype present each. In conclusion, C. difficile was found in the household environment of R-CDI patients, but whether it was found as a cause or consequence of R-CDI is unknown. If household contamination leads to R-CDI, effective decontamination may be protective.

Streptococcus pneumoniae is an uncommon cause of pyomyositis. It is unclear whether the clinical presentation and outcome of pneumococcal pyomyositis differ depending on the host's underlying immune status. We describe 2 patients with pneumococcal pyomyositis, review all published cases, and compare characteristics between apparently healthy hosts and at-risk hosts. A total of 35 cases of pneumococcal pyomyositis were identified, 11 in apparently healthy hosts and 24 in at-risk hosts. Two-thirds of the patients had an antecedent respiratory illness or meningitis. At-risk hosts tended to have a longer interval between the development of symptomatic muscle infection and the diagnosis of pyomyositis and a significantly higher risk of disseminated disease at presentation, as manifested by involvement of multiple noncontiguous muscles or presence of meningitis. Overall, other than 1 death, all patients recovered with antibiotics and surgical drainage, but as might be expected there was a significantly higher rate of complications among at-risk hosts.

Cognitive operations engage neural generators oscillating at different frequencies distributed in time and space. Accordingly, oscillatory activity detected by magnetoencephalography (MEG)/electroencephalography (EEG) should be analyzed along frequency, time, and spatial dimensions. MEG data were obtained from 19 healthy individuals while performing a modified Sternberg paradigm. The stimuli were letters, which constituted words or pronounceable nonwords. We applied tridimensional analysis of oscillations and also computed event-related fields (ERFs) in areas where significant changes in oscillatory activity were observed. Verbal working memory for visual verbal stimuli was associated with oscillatory interplay between the bilateral occipital lobes and the left frontoparietotemporal areas. Spatially stable occipital desynchrony was noted during information encoding, while a left hemisphere desynchronization, increasing in amplitude and spatial extent over time, was observed during information encoding and maintenance. No ERF changes were detected during information maintenance. Oscillatory activity associated with verbal working memory is consistent with the above hypothesis. These findings underscore the importance of multidimensional evaluation of oscillations. The findings also indicate that combining electrophysiological methods increase the chance of signal detection.

Escherichia coli sequence type ST131 (O25b:H4) has emerged over the past decade as a globally disseminated, multidrug-resistant pathogen. Unlike traditional antimicrobial-resistant E. coli , ST131 derives from virulence-associated phylogenetic group B2 and exhibits extraintestinal virulence factors. This, plus preliminary evidence of virulence in experimental animals, has suggested that ST131's epidemic emergence may be due to high virulence potential, compared with other E. coli types. To test this hypothesis, we compared a large number of matched ST131 and non-ST131 E. coli clinical isolates, both fluoroquinolone resistant and susceptible, plus isolates from classic extraintestinal pathogenic E. coli (ExPEC) sequence types (STs) and case report ST131 household transmission isolates, for virulence in a mouse subcutaneous sepsis model. Overall, in mice, the study isolates produced a wide range of lethality and clinical illness. However, neither ST131 status nor fluoroquinolone phenotype correlated with this diversity of illness severity, which occurred within each of the 6 study groups. In contrast, multiple known or suspected ExPEC virulence genes, including pap (P fimbriae), vat (vacuolating toxin), kpsM II (group 2 capsule), ibeA (invasion of brain endothelium), and clbB/N (colibactin synthesis), plus molecularly defined ExPEC status, were significantly associated with virulence. These findings point away from ST131 isolates as having higher virulence potential compared with other E. coli types in causing invasive extraintestinal infections and suggest instead that ST131's epidemiological success may reflect enhanced fitness for upstream steps in pathogenesis or in colonization and transmission. Additionally, the extensive within-ST virulence diversity suggests an opportunity to compare closely related strains to identify the responsible genetic determinants.

Background Foley catheter (FC) use is a modifiable risk factor for hospital-acquired urinary tract infection, the most common type of nosocomial infection. It is unknown whether sustained, hospital-wide reductions in FC use are achievable by combining interventions with demonstrated short-term effectiveness in selected units. Methods A multifaceted quality improvement project to decrease unnecessary FC use and increase order documentation was instituted throughout the Minneapolis Veterans Affairs Medical Center in March 2005, after a >2-year baseline period. Bundled interventions included multiple types of education, system redesign, rewards, and feedback (phases I and II), plus, in phase III, involvement of a dedicated FC nurse. Results The daily prevalence of FC use dropped steeply during intervention phase I (5.5 months), from a 15.2% baseline mean to a 9.3% nadir, but rebounded quickly during the subsequent hiatus phase (1.2 months). It dropped again (mean, 13.6%) during intervention phase II (27.3 months) and even further (mean, 12.0%) during intervention phase III (22.8 months) (P ≤ .001, phase II or III vs baseline). Compared with baseline, during phase III (with the dedicated FC nurse) the mean daily percentages of nonordered and nonindicated FCs dropped from 17% to 5.1% and from 15% to 1.2%, respectively. During phases II and III combined, an estimated total of 6691 FC days were avoided. Conclusions Significant hospital-wide reductions in total and inappropriate FC use and improved FC order documentation were achieved through a multicomponent campaign. The greatest and most sustained improvements accompanied the involvement of a dedicated FC nurse.

Breast cancer metastasis to bone is frequently accompanied by pain. What remains unclear is why this pain tends to become more severe and difficult to control with disease progression. Here we test the hypothesis that with disease progression, sensory nerve fibers that innervate the breast cancer bearing bone undergo a pathological sprouting and reorganization, which in other nonmalignant pathologies has been shown to generate and maintain chronic pain. Injection of human breast cancer cells (MDA-MB-231-BO) into the femoral intramedullary space of female athymic nude mice induces sprouting of calcitonin gene-related peptide (CGRP + ) sensory nerve fibers. Nearly all CGRP + nerve fibers that undergo sprouting also coexpress tropomyosin receptor kinase A (TrkA + ) and growth-associated protein-43 (GAP43 + ). This ectopic sprouting occurs in periosteal sensory nerve fibers that are in close proximity to breast cancer cells, tumor-associated stromal cells, and remodeled cortical bone. Therapeutic treatment with an antibody that sequesters nerve growth factor (NGF), administered when the pain and bone remodeling were first observed, blocks this ectopic sprouting and attenuates cancer pain. The present data suggest that the breast cancer cells and tumor-associated stromal cells express and release NGF, which drives bone pain and the pathological reorganization of nearby CGRP + /TrkA + /GAP43 + sensory nerve fibers. Perspective Therapies that block breast cancer pain by reducing the tumor-induced pathological sprouting and reorganization of sensory nerve fibers may provide insight into the evolving mechanisms that drive breast cancer pain and lead to more effective therapies for attenuating this chronic pain state.

Background Renal artery duplex ultrasonography (RA-DUS) is commonly used for the evaluation and follow-up of renal artery atherosclerotic disease. In a complete study, renal artery flow is evaluated from the vessel origin to the intraparenchymal branches. The quality of RA-DUS is in part technologist-dependent, but many factors may affect the ability to complete a diagnostic examination. This study evaluated the clinical and technical factors that predict the ability to obtain a complete RA-DUS examination. Methods A prospective evaluation of all patients undergoing RA-DUS between July 2008 and February 2009 was performed. Factors such as patient age, gender, body mass index, technologists’ years of experience, patient care setting (inpatient vs. outpatient), bedside examination, smoking before the examination, fasting status, and recent abdominal surgery were all recorded. Multivariate logistic regression analysis was performed. A p value of ≤0.05 was considered significant. Results During the study period, 250 patients underwent RA-DUS (mean age: 59.9 ± 17.8 years, 57% [143] female). A total of 87 (35%) examinations were incomplete. This included nondiagnostic examinations which did not exhibit any segment of the renal artery. Factors that were associated with an incomplete examination included technologists’ years of experience (OR = 0.92, p = 0.042), bedside examination (OR = 4.17, p = 0.016), and recent abdominal surgery (OR = 3.45, p = 0.047). Body mass index, fasting status, and smoking before the examination did not affect the ability to obtain a complete study. Conclusions One-third of the RA-DUS studies were classified as incomplete by the strict criteria used in this prospective study. An experienced ultrasound technologist is more likely to obtain a complete RA-DUS examination. Recent abdominal surgery and bedside examinations were predictive of a limited examination as well. Vascular laboratories should consider these factors when scheduling examinations so as to obtain complete RA-DUS studies, as well as improve the cost-effectiveness of resource utilization.

Background Acute kidney injury (AKI) after cardiac surgery is associated with increased morbidity and mortality. Methods We assessed whether statin treatment is associated with a lower incidence of postoperative AKI in 2,104 consecutive patients who underwent coronary artery bypass graft or valve surgery at the Minneapolis Veterans Administration Medical Center. Acute kidney injury was defined as absolute increase greater than 0.3 mg/dL or relative increase greater than 50% in serum creatinine from baseline, within 48 hours after surgery or requiring postoperative hemodialysis per AKI network. Propensity scores were utilized to adjust for the differences between the statin and the no-statin treatment groups. All statins were converted to equivalent-dose simvastatin and divided at the median to construct high-dose (≥40 mg) and low-dose ( Results Of the 2,104 patients, 1,435 (68%) were taking statins (638 high-dose) and 495 (24%) developed AKI (25% high-dose vs 40% low-dose vs 35% no-statin; p = 0.014). Estimated preoperative glomerular filtration rate ( p = 0.003), diabetes mellitus (p=0.02), valve surgery with or without coronary artery bypass graft ( p = 0.024), cardiopulmonary bypass time ( p = 0.001), and intraaortic balloon pump ( p = 0.055) were independent predictors of AKI. After propensity adjustment statin treatment was not associated with postoperative AKI (odds ratio 0.79; 95% confidence interval 0.59 to 1.06; p = 0.11 for high-dose v. no-statin). After full adjustment for all independent predictors of AKI, the results did not change. Statins also had no effect on the incidence of postoperative hemodialysis (0.8% high-dose vs 1.9% low-dose vs 1% no-statin; p = 0.15). Conclusions Statin treatment is not associated with a lower incidence of AKI after cardiac surgery.

Numerous studies have implicated frontal lobe dysfunction in anger-related impulsive violent behavior; however, few studies have looked at frontal activity during angry states in violent individuals. Using PET and a script-driven imagery paradigm, we report on autobiographical memories of angry vs. neutral memories in violent patients and psychiatric matched controls. Relative to recall of neutral memories, recall of anger-laden memories was associated with an activation of frontal regions among control subjects but not violent subjects. Violent subjects demonstrated relatively greater activations in the left amygdala, pontine, and cerebellar regions compared to control subjects.

The Cognitive Performance Test (CPT) is a standardized occupational therapy assessment that examines cognitive integration with functioning in an instrumental activities of daily living context. Conventional cognitive measures provide diagnostic utility but do not fully address the functional implications. Ninety-one veterans diagnosed with cognitive impairment were evaluated. We compared the predictive value of the CPT with the Large Allen Cognitive Level Screen (LACLS), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA) for the need to retire from driving versus ability to pass an on-road exam. Measures were also analyzed by diagnostic classification. CPT correctly classified a mild versus major neurocognitive disorder, whereas MMSE, MoCA, and LACLS did not differentiate the groups. A CPT cutoff score of

Background Alzheimer's disease (AD) is the most common dementing illness. Development of effective treatments directed at AD requires an early diagnosis. Mild cognitive impairment (MCI) often heralds AD. Thus, characterizing MCI is fundamental to the early diagnosis of AD. Methods 19 MCI patients referred from a memory loss clinic and 27 healthy subjects, all followed up for 3 years. Metabolism scans (MCI minus controls) were compared voxel-wise after anatomic normalization and were examined both visually and with a computerized classifier. Results Agreement between raters as to whether the individual scans were normal or abnormal was high. Agreement between raters of the eventual clinical diagnosis and baseline metabolic pattern was poor. A computerized classifier was unsuccessful at classifying MCI from normal; however, its performance improved when using only prototypic AD-like MCI scans, indicating the classifier worked well when shared patterns existed in the data. Outcomes on follow-up were nine of 19 AD, five of 19 remained MCI, and five of 19 developed dementias other than AD. Both MCI cases of early Lewy body dementia (LBD) showed an AD-like metabolic pattern. Conclusions Visual inspection proved reliable in determining normal from abnormal scans, but it proved unreliable at predicting diagnosis on follow-up. Computerized classification of MCI by using an AD-like metabolic template (such as derived from the averaged MCI images) showed potential to identify patients who will develop AD. However, the metabolic pattern in early LBD did not differ from that in AD.

Background Although nurses insert and care for many Foley catheters, little is known about nurses' attitudes and knowledge regarding indications for catheter use or methods to prevent catheter-associated urinary tract infection (CAUTI). Methods An Internet-based survey was sent to a random sample of registered nurses (RNs) in Minnesota. The survey contained demographic questions and 5-point Likert-scale questions regarding indications for Foley catheter placement and effectiveness of various interventions for preventing CAUTI. Results Nurses perceived early catheter removal as the most effective intervention to prevent CAUTI (mean score, 4.5; range 1-5). Compared with other RNs, those reporting additional catheter education were more likely to rate interventions to prevent CAUTI as effective, regardless of whether the interventions actually reduce the incidence of symptomatic CAUTI or asymptomatic bacteriuria/funguria. Intensive care unit RNs were significantly more likely than other RNs to endorse that a Foley catheter was indicated for any given clinical scenario and to endorse antimicrobial-coated catheters as effective in preventing CAUTI. Most respondents reported no institutional guidance regarding catheterization. Conclusion Although the surveyed Minnesota RNs demonstrated high-level awareness of the utility of early Foley catheter removal for preventing CAUTI, other aspects of their catheter-related knowledge were concerning. Improving these deficits may help improve catheter-related practice.

Among 40 Escherichia coli urine isolates from renal transplant recipients (Galveston, TX, 2003 to 2005), sequence type ST131 (O25:H4) was highly prevalent (representing 35% of isolates overall and 60% of fluoroquinolone-resistant isolates), virulent appearing, antimicrobial resistant (but extended-spectrum-cephalosporin susceptible), and associated with black race. Pulsotypes were diverse; some were linked to other locales. ST131 emerged significantly during the study period. These findings suggest that E. coli ST131 may constitute an important new multidrug-resistant threat to renal transplant recipients.

Background. The origins and virulence potential of meat product-associated Escherichia coli are undefined. Methods. Two hundred eighty-seven E. coli isolates (145 resistant and 142 susceptible to trimethoprim-sulfamethoxazole, nalidixic acid, and/or ceftiofur), recovered by the United States National Antimicrobial Monitoring System from retail beef, pork, chicken, and turkey products (from Oregon, Tennessee, Georgia, and Maryland, 2002-2004) underwent polymerase chain reaction testing for phylogenetic groupings and 59 virulence-associated genes. Results. However analyzed, resistant and susceptible isolates differed minimally according to the assessed characteristics. In contrast, the 4 meat types differed greatly for multiple individual traits and aggregate virulence scores. Poultry isolates exhibited virulence genes associated with avian pathogenic E. coli; beef isolates exhibited traits associated with E. coli from diseased cattle. Overall, 20% of isolates qualified as extraintestinal pathogenic E. coli, with poultry isolates exhibiting significantly higher virulence scores than beef and pork isolates (P

The extent to which clonal spread contributes to emerging antimicrobial resistance in Escherichia coli is incompletely defined. To address this question within a recent, nationally representative strain collection, three established drug-resistant E. coli clonal groups (i.e., clonal group A, E. coli O15:K52:H1, and sequence type 131 [ST131]) were sought among 199 E. coli urine isolates recovered from across Canada from 2002 to 2004, with stratification by resistance to trimethoprim-sulfamethoxazole (TS) and fluoroquinolones (FQs). The isolates' clonal backgrounds, virulence genotypes, and macrorestriction profiles were assessed. The three clonal groups were found to account for 37.2% of isolates overall, but accounted for 0% of TS-susceptible (TS-S) and FQ-susceptible (FQ-S) isolates, 20% of TS-resistant (TS-R) and FQ-S isolates, 60% of TS-S and FQ-R isolates, and 68% of TS-R and FQ-R isolates ( P < 0.001). E. coli ST131, the most prevalent clonal group, accounted for 23.1% of isolates overall and for 44% of the FQ-R isolates. Nearly all ST131 isolates were FQ-R (96%) but, notably, cephalosporin susceptible (98%). Although the distinctive virulence profiles of the FQ-R clonal group isolates were less extensive than those of the susceptible isolates, they were significantly more extensive than those of the other FQ-R isolates. These findings indicate that among the E. coli urine isolates studied, resistance to TS and FQs has a prominent clonal component, with the O15:K52:H1 clonal group and especially E. coli ST131 being the major contributors. These clonal groups appear to be more virulent than comparably resistant isolates, possibly contributing to their success as emerging multi-drug-resistant pathogens.

Objective: At the end of 2006, a survey was sent to members of the American Association of Geriatric Psychiatry (AAGP) to assess possible changes in prescribing Vitamin E to patients with Alzheimer disease that followed two published reports in early 2005 suggesting increased mortality and an increased incidence of heart failure with Vitamin E supplements. Method: A three-item questionnaire was mailed to all AAGP members who had prescription privileges to assess changes in prescribing Vitamin E after January, 2005. Results: A total of 572 completed surveys were returned for a response rate of 35%. Nearly 60% of respondents reported a change over the 2 years that followed the 2005 reports. The greatest change was in the group not prescribing Vitamin E, which increased from 6.6% before 2005 to 60.6% afterward. Conclusions: AAGP members significantly reduced prescribing Vitamin E to patients with Alzheimer disease after 2005. The two reports are discussed with an emphasis on their methodological limitations and the potential for additional information on Vitamin E side effects from ongoing research.

Objective: This phase 1 trial set out to examine the safety of a bacteriophage-based preparation for difficult-to-treat wounds. Method: The intention-to-treat sample comprised 42 patients with chronic venous leg ulcers (VLUs); 39 patients completed the trial. The ulcers were treated for 12 weeks with either a saline control or bacteriophages targeted against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. Follow-up continued until week 24. Results: No adverse events were attributed to the study product. No signifi cant difference (p>0.05) was determined between the test and control groups for frequency of adverse events, rate of healing, or frequency of healing. Conclusion: This study found no safety concerns with the bacteriophage treatment. Efficacy of the preparation will need to be evaluated in a phase II efficacy study. Declaration of interest: One of the authors (AS) holds an equity interest in Intralytix. The other authors do not have any interest in commercial activities.

The fecal Escherichia coli population structure may influence the occurrence and etiology of extraintestinal infection, but is poorly understood. Accordingly, fecal E. coli from 39 healthy women (30 putative colonies per subject) were characterized for clonal identity, urinary tract infection-associated virulence traits, and phylogenetic background. The 120 unique E. coli clones (mean, three per sample) were distributed by phylogenetic group as follows: A (33%), D (31%), B1 (19%), and B2 (17%). However, 36% of women carried ≥1 clone from group B2, and 87% had clones from groups B2 and/or D. Of the B2 clones, 90% were from pauciclonal fecal samples (≤4 clones), compared with 47% and 52% of A and B1 clones (P = .001 and P = .007, respectively). Group B2 and D clones more often were dominant within the source sample than group A and B1 clones (60% vs. 41%: P = .05). Dominant clones exhibited higher virulence scores than non-dominant clones (mean 4.4 vs. 3.1: P = .015). In multilevel regression models, pauciclonal sample, B2, and clonal prevalence significantly predicted virulence score. In conclusion, within the intestinal E. coli population, virulence-associated traits, clonal prevalence, and low fecal clonal diversity are related. Virulence-associated traits of group B2/D E. coli may enhance fitness within the gut, thereby increasing strains’ likelihood of causing extraintestinal infection.

Vagus nerve stimulation (VNS) is used as an adjunctive therapy for treatment-resistant depression (TRD). Its mechanism of action is not fully understood. Longitudinal measurement of changes in brain metabolism associated with VNS can provide insights into this new treatment modality. Eight severely depressed outpatients who were highly treatment-resistant underwent electrical stimulation of the left vagus nerve for approximately one year. The main outcome measures were resting regional brain glucose uptake measured with positron emission tomography (PET) and the 24-item Hamilton Depression Scale. The most significant and extensive change over one year of chronic VNS localized to the ventromedial prefrontal cortex extending from the subgenual cingulate to the frontal pole. This region continued to decline in metabolism even toward the end of the study. Clinically, this cohort showed a trend for improvement. No correlations surfaced between change in glucose uptake and depression scores. However, the sample size was small; none remitted; and the range of depression scores was limited. Chronic VNS as adjunctive therapy in patients with severe TRD produces protracted and robust declines in resting brain activity within the ventromedial prefrontal cortex, a network with dense connectivity to the amygdala and structures monitoring the internal milieu.

Objective To determine the incidence and predictors of delirium after cardiac surgery. Method A prospective, observational study of postcardiotomy surgical patients was conducted during a 5 month period at the Minneapolis, MN, VAMC. Results Of the 53 patients who completed the study, 12 patients (23%) met criteria for postoperative delirium and 18 patients (34%) met criteria for postoperative subsyndromal delirium. Significant predictors of postoperative delirium included a history of cerebrovascular disease (Charlson Index item, VA CICSP), high medical comorbidity (VA morbidity risk score, Charlson Index), increased preoperative creatinine level, and an increased preoperative pain rating. When delirium and subsyndromal delirium patients were combined, a history of cerebrovascular disease, left ventricular dysfunction, or diabetes predicted the development of delirious symptoms. Conclusions Incident delirium occurred in 23% of patients after cardiac surgery and incident delirium symptoms, in 57%. The strongest predictor of both incident delirium and delirium symptoms was a history of cerebrovascular disease.

Catheter-associated urinary tract infection (CAUTI) is a common occurrence, often clinically unapparent and with a benign course. However, in a small fraction of patients catheter-associated bacteriuria/funguria (CABF) produces overt clinical manifestations and adverse consequences, including (at the extreme end of the spectrum) urosepsis and death. Antimicrobial-coated catheters have been proposed as a method to prevent CAUTI and are in use worldwide, although their clinical efficacy is not well known. Randomized and quasi-randomized clinical trials have demonstrated that antimicrobial-coated catheters do decrease the incidence of CABF; however, evidence that such devices provide clinically meaningful benefit is lacking. Moreover, uncertainty exists as to which of the currently marketed catheters is most effective against CABF, since no published trial has directly compared different antimicrobial-coated catheters. We conducted a systematic review to summarize and evaluate existing evidence, and to address areas of uncertainty. We found consistent but variable evidence that antimicrobial-coated catheters prevent CABF during short-term catheterization; however, no study demonstrated a clinical benefit. Future efforts in this field should include randomized trials with clinically relevant end points, as well as research to develop improved mechanisms for bladder drainage, preferably without the risks and discomfort currently associated with urinary catheters.

Emerging antimicrobial resistance among uropathogens makes the management of acute uncomplicated cystitis increasingly challenging. Few prospective data are available on the risk factors for resistance to trimethoprim-sulfamethoxazole (TMP-SMX), the drug of choice in most settings. In order to evaluate this, we prospectively enrolled women 18 to 50 years of age presenting to an urban primary care practice with symptoms of cystitis. Potentially eligible women provided a urine sample for culture and completed a questionnaire regarding putative risk factors for TMP-SMX resistance. Escherichia coli isolates were tested for clonal group A (CGA) membership by a fumC -specific PCR. Of 165 women with cystitis symptoms, 103 had a positive urine culture and were eligible for participation. E. coli was the predominant uropathogen (86%). Fifteen (14.6%) women had a TMP-SMX-resistant (TMP-SMX r ) organism (all of which were E. coli ). Compared with the women who had a TMP-SMX-susceptible organism, women in the TMP-SMX r group were more likely to have traveled (odds ratio [OR], 15.4; 95% confidence interval [CI], 4.4 to 54.3; P < 0.001) and to be Asian (OR, 6.1; 95% CI, 1.0 to 36.4; P = 0.048). CGA was also independently associated with TMP-SMX resistance (OR, 105; 95% CI, 6.3 to 1,777.6; P = 0.001). No association with TMP-SMX resistance was demonstrated for the use of either TMP-SMX or another antibiotic in the past 3 months or with having a child in day care. Among these women with acute uncomplicated cystitis, Asian race and recent travel were independently associated with TMP-SMX resistance. TMP-SMX r isolates were more likely to belong to CGA. Knowledge of these risk factors for TMP-SMX resistance could facilitate the accurate selection of empirical therapy.

Among community-dwelling older men, compared to those without Parkinson's disease (PD), over approximately 5 years, those with baseline PD had a significantly greater rate of annualized total hip bone loss (-1.1% vs. 0.4%), proportion of incident non-spine fractures (14.9% vs. 7.2%) and mortality (34.8% vs. 9.5%).The objective of this study was to examine the association of Parkinson's disease (PD) with bone loss and fractures in older men.This prospective cohort study analyzed data from 5,937 community dwelling men agedor=65 years at six clinical centers of the Osteoporotic Fractures in Men (MrOS) Study. At baseline and visit two (mean interval 4.6 +/-0.4 SD years), community-diagnosed PD was ascertained by self-report and hip bone mineral density (BMD) was measured using dual energy x-ray absorptiometry (DXA). Incident fractures were self-reported. Fractures and deaths were centrally adjudicated.At baseline, 46 (0.8%) men had PD. Age-adjusted mean annualized total hip bone loss was greater in men with vs. those without PD (-1.08% vs. -0.36%, p0.001). 15.2% of men with PD and 7.2% of men without PD experienced an incident non-spine fracture (age-adjusted HR 2.4, 95%CI 1.1-5.0). 34.8% of men with PD and 9.5% of men without PD died during follow-up (age-adjusted HR 3.5, 95%CI 2.2-5.5). Associations of PD with bone loss, fractures and mortality were modestly altered by additional individual adjustment for possible confounders.In community-dwelling older men, PD was associated with increased bone loss, fractures and mortality. In addition to implementing fall prevention measures, clinicians should consider osteoporosis screening in older men with PD.

Molecular evidence is limited for the hypothesis that humans, dogs, and cats can become colonized and infected with similar virulent Escherichia coli strains. To further assess this possibility, archived E. coli O6 isolates ( n = 130) from humans ( n = 55), dogs ( n = 59), and cats ( n = 16), representing the three main H (flagellar) types within serogroup O6 (H1, H7, and H31), were analyzed, along with selected reference strains. Isolates underwent PCR-based phylotyping, multilocus sequence typing, PCR-based detection of 55 virulence-associated genes, and XbaI pulsed-field gel electrophoresis (PFGE) profiling. Three major sequence types (STs), which corresponded closely with H types, accounted for 99% of the 130 O6 isolates. Each ST included human, dog, and cat isolates; two included reference pyelonephritis isolates CFT073 (O6:K2:H1) and 536 (O6:K15:H31). Virulence genotypes overlapped considerably among host species, despite statistically significant differences between human and pet isolates. Several human and dog isolates from ST127 (O6:H31) exhibited identical virulence genotypes and highly similar PFGE profiles, consistent with cross-species exchange of specific E. coli clones. In conclusion, the close similarity in the genomic backbone and virulence genotype between certain human- and animal-source E. coli isolates within serogroup O6 supports the hypothesis of zoonotic potential.

Similarities were found between drug-resistant E. coli from humans and poultry products., The food supply, including poultry products, may transmit antimicrobial drug–resistant Escherichia coli to humans. To assess this hypothesis, 931 geographically and temporally matched E. coli isolates from human volunteers (hospital inpatients and healthy vegetarians) and commercial poultry products (conventionally raised or raised without antimicrobial drugs) were tested by PCR for phylogenetic group (A, B1, B2, D) and 60 virulence genes associated with extraintestinal pathogenic E. coli. Isolates resistant to trimethoprim-sulfamethoxazole, quinolones, and extended-spectrum cephalosporins (n = 331) were compared with drug-susceptible isolates (n = 600) stratified by source. Phylogenetic and virulence markers of drug-susceptible human isolates differed considerably from those of human and poultry isolates. In contrast, drug-resistant human isolates were similar to poultry isolates, and drug-susceptible and drug-resistant poultry isolates were largely indistinguishable. Many drug-resistant human fecal E. coli isolates may originate from poultry, whereas drug-resistant poultry-source E. coli isolates likely originate from susceptible poultry-source precursors.

Even healthy adults worry about declines in mental efficiency with aging. Subjective changes in mental flexibility, self-regulation, processing speed, and memory are often cited. We show here that focal decreases in brain activity occur with normal aging as measured with fluorodeoxyglucose and positron emission tomography. The largest declines localize to a medial network including the anterior cingulate/medial prefrontal cortex, dorsomedial thalamus, and sugenual cingulate/basal forebrain. Declining metabolism in this network correlates with declining cognitive function. The medial prefrontal metabolic changes with aging are similar in magnitude to the hypometabolism found in Mild Cognitive Impairment or Alzheimer's disease. These results converge with data from healthy elderly indicating dysfunction in the anterior attention system. The interaction of attention in the anterior cingulate cortex with memory in the medial temporal lobe may explain the global impairment that defines dementia. Despite the implications for an aging population, the neurophysiologic mechanisms of these metabolic decreases remain unknown.

How extraintestinal pathogenic Escherichia coli (ExPEC) and antimicrobial-resistant E. coli disseminate through the population is undefined. We studied public restrooms for contamination with E. coli and ExPEC in relation to source and extensively characterized the E. coli isolates. For this, we cultured 1,120 environmental samples from 56 public restrooms in 33 establishments (obtained from 10 cities in the greater Minneapolis-St. Paul, MN, metropolitan area in 2003) for E. coli and compared ecological data with culture results. Isolates underwent virulence genotyping, phylotyping, clonal typing, pulsed-field gel electrophoresis (PFGE), and disk diffusion antimicrobial susceptibility testing. Overall, 168 samples (15% from 89% of restrooms) fluoresced, indicating presumptive E. coli : 25 samples (2.2% from 32% of restrooms) yielded E. coli isolates, and 10 samples (0.9% from 16% of restrooms) contained ExPEC. Restroom category and cleanliness level significantly predicted only fluorescence, gender predicted fluorescence and E. coli , and feces-like material and toilet-associated sites predicted all three endpoints. Of the 25 E. coli isolates, 7 (28%) were from phylogenetic group B2(virulence-associated), and 8 (32%) were ExPEC. ExPEC isolates more commonly represented group B2 (50% versus 18%) and had significantly higher virulence gene scores than non-ExPEC isolates. Six isolates (24%) exhibited ≥3-class antibiotic resistance, 10 (40%) represented classic human-associated sequence types, and one closely resembled reference human clinical isolates by pulsed-field gel electrophoresis. Thus, E. coli , ExPEC, and antimicrobial-resistant E. coli sporadically contaminate public restrooms, in ways corresponding with restroom characteristics and within-restroom sites. Such restroom-source E. coli strains likely reflect human fecal contamination, may pose a health threat, and may contribute to population-wide dissemination of such strains.

The accurate and objective measurement of abnormal, involuntary movements remains highly desirable, whether the movements are secondary to pharmacotherapy or an expression of the primary illness. In a previous study, we found that the prevalence of tardive dyskinesia in a sample of 100 subjects ranged from 28% when using the Abnormal Involuntary Movement Scale (AIMS) or the Dyskinesia Identification Scale, Condensed User Version (DISCUS) to 62% using an instrumental measurement (IM) of peripheral dyskinesia. The goal of this study was to examine the relationship between various risk factors for tardive dyskinesia as predictor variables, and the AIMS, DISCUS, and IMs of dyskinesia, tremor, and velocity of motor movement as dependent variables. The sample consisted of 100, mostly patients with schizophrenia. Poor performance on the Mini-Mental State Examination (MMSE) and increasing age were the most consistent predictors of dyskinetic and parkinsonian movements. Various predictors were associated with specific abnormal movements. Head injury was related to slower speed of motor movements and the total DISCUS score. A history of smoking was associated with less IM dyskinesia. For those with coexisting parkinsonism and dyskinesia, significant associations were found with head injury, diabetes mellitus, and an AIMS score of 2 or greater in 2 body areas. Various classes of psychotropic agents seemed to have little influence on the MMSE or the development of dyskinesia and parkinsonism. Increasing age and a lower score on the MMSE seem to be particularly helpful in gauging the risk for parkinsonian and dyskinetic movements.

Although hypertrophic cardiomyopathy (HC) occurs in 1 of 500 adults, most cardiology practices treat relatively few patients with HC, suggesting that many affected patients evade clinical recognition. Determining the clinical circumstances under which HC is identified will provide clues to its under-recognition. Clinical triggers leading to diagnostic echocardiograms were analyzed in 711 consecutive patients with HC. In most (384 [54%]), HC was initially suspected only after the onset of cardiac symptoms or acute cardiac events. In a substantial minority (327 [46%]), HC was recognized while patients were asymptomatic, including 225 (32%) by routine medical evaluations, in 27 of whom (4%) HC was recognized during preparticipation examinations for competitive sports or other activities. Women, older patients (ageor =50 years), and those with outflow obstruction at rest (gradientor =30 mm Hg) were more likely suspected to have HC by virtue of cardiac symptoms or events (p0.0001). Conversely, patients with extreme hypertrophy (wall thicknessor =30 mm) and those at high risk for sudden death were more often asymptomatic and identified by routine or family screenings (p0.0001 and p = 0.004, respectively). Patients who subsequently died of heart failure or experienced embolic stroke were more often identified by virtue of symptoms or acute events (p = 0.03). In conclusion, although most patients with HC were recognized clinically only after overt disease manifestations, a substantial minority were diagnosed by routine examinations while asymptomatic, including an important subset of patients with HC recognized solely because of findings on sports preparticipation screening. These data underscore the need for heightened awareness and clinical suspicion of HC to increase the number of diagnosed patients, including many who may be at high risk for sudden death.

Background: The reported outcomes of patients who underwent total or unicompartmental knee arthroplasty for secondary and spontaneous osteonecrosis of the knee are often from studies that lack the number of subjects necessary to generate meaningful conclusions. We systematically reviewed the available literature in order to define the outcomes of patients after total knee arthroplasty for secondary osteonecrosis and after total or unicompartmental knee arthroplasty for spontaneous osteonecrosis of the knee. Methods: A literature review yielded twenty cohorts with demographic patient information and outcome scores (global knee scores, radiographic outcomes, and revision rates) for patients who had knee arthroplasty as treatment for either secondary or spontaneous osteonecrosis of the knee. The mean preoperative and postoperative global knee scores, the mean revision rate, and the categorization of the mean “poor” and mean “good” outcomes for the knees with each underlying disease were tabulated and reported. The demographic data and the reported mean global knee scores were weighted by the number of knees in each study. Results: Total knee arthroplasty was performed in 150 knees with secondary osteonecrosis and 148 knees with spontaneous osteonecrosis, and unicompartmental knee arthroplasty was performed in sixty-four knees with spontaneous osteonecrosis. Total knee arthroplasty for spontaneous osteonecrosis of the knee was associated with the best outcomes (higher “good” and postoperative global knee scores and lower revision [3%] and “poor” outcome [6%] rates compared with the other two groups). The outcomes after total knee arthroplasty in knees with secondary osteonecrosis as well as in knees with spontaneous osteonecrosis were better in the cohorts operated on during or after 1985 than in those operated on before 1985. Similarly, the outcomes after unicompartmental knee arthroplasty in knees with spontaneous osteonecrosis of the knee were also better in the cohorts operated on during or after 1985 than in those operated on before 1985. Conclusions: Total knee arthroplasty performed as treatment for either secondary osteonecrosis or spontaneous osteonecrosis and unicompartmental knee arthroplasty performed as treatment for spontaneous osteonecrosis were associated with improved outcomes in cohorts with more recent operative dates. The evidence suggests that the use of contemporary cemented implants in total knee arthroplasty and the selective use of stems and augments in patients who have development of secondary osteonecrosis after total knee arthroplasty are producing outcomes that are comparable to those seen after total knee arthroplasty for osteoarthritis. Although the outcomes of patients who have total knee arthroplasty for the treatment of spontaneous osteonecrosis of the knee have historically been favorable, such outcomes have also shown particular improvement in the studies from more recent operative periods. Although poor outcomes were seen after unicompartmental knee arthroplasty in earlier studies of patients with spontaneous osteonecrosis of the knee, it is possible that those results were secondary to inappropriate patient selection, as the authors of the most recent and, to our knowledge, the only study to follow established operative indications regarding the use of unicompartmental knee arthroplasty reported excellent results. Level of Evidence: Therapeutic Level IV. See Instructions to Authors on [jbjs.org][1] for a complete description of levels of evidence. [1]: http://jbjs.org

Background. The food supply is suspected to be a source of fluoroquinolone-resistant Escherichia coli that cause disease in humans, but supporting molecular data are lacking. Methods. We performed a molecular-epidemiological comparison, in Barcelona, Spain (1996-1998), of 117 contemporaneous, geographically matched E. coli isolates from humans (35 blood isolates and 33 fecal) or chickens (49 fecal) that were either susceptible (n = 57) or resistant (n = 60) to ciprofloxacin and analyzed them by phylogenetic group, virulence genotype, and O antigens using random amplified polymorphic DNA (RAPD) analysis and pulsed-field gel electrophoresis (PFGE). Results. When analyzed by phylogenetic distribution, virulence profiles, and O antigens, resistant human isolates were distinct from susceptible human isolates but were largely indistinguishable from chicken isolates, whereas resistant and susceptible chicken isolates were similar. Susceptible human isolates contained more virulence-associated genes and more frequently expressed virulence-associated O antigens than did resistant human or any chicken isolates. Certain resistant human isolates closely resembled chicken isolates by RAPD and PFGE analysis. Conclusions. Ciprofloxacin-resistant E. coli may arise de novo in poultry from susceptible progenitors, be transmitted to humans via the food supply, and go on to cause potentially life-threatening infections. If confirmed, these findings would mandate efforts to eliminate this reservoir of drug-resistant pathogens and/or to block their transmission to humans.

Although aerobic exercise training has been shown to lower blood pressure (BP) in older adults, its effect on BP sensitivity to dietary sodium (Na(+)) is unknown. Therefore, the present study was undertaken to examine the effect of aerobic exercise training on BP sensitivity to dietary Na(+) in older hypertensive individuals. Blood pressure was measured after 8 days of low (20 mEq) and high (200 mEq) Na(+) diets in 31 older (63+/-7 years, mean+/-standard deviation), hypertensive (152+/-11/88+/-5 mm Hg) individuals at baseline and following 6 months of aerobic exercise training (at 75% VO(2)max, 3 times/week, 40 min/session). Subjects were grouped on the basis of the difference in mean arterial BP (MAP) between diets (Na(+) sensitive: >or=5 mm Hg increase in MAP on high Na(+), n=20; Na(+) resistant

Localized non-small cell lung carcinoma (NSCLC) is best treated by complete surgical resection, commonly requiring lobectomy. The impact of lobectomy on the health status of the elderly patient is not well-characterized. The aim of this study was to compare the effect of lobectomy in elderly patients (or = 70 years of age) and younger patients (70 years of age) on their pulmonary function and functional status 1 year following surgery.One hundred forty patients underwent lobectomy for NSCLC at the Minneapolis Veterans Affairs Medical Center from January 1999 to December 2003. All patients underwent pulmonary function tests (PFTs) and functional status assessment using Karnofsky scores (KS) that were assessed preoperatively. Sixty-three of 140 lobectomy patients were available 1 year postoperatively for reevaluation by PFTs and KS.There was no statistical difference between groups in either the pulmonary function or functional status testing results at 1 year after undergoing lobectomy. FVC decreased by 14% in the elderly patient and by 9% in the younger patient group. FEV1 decreased by 19% in elderly patients and by 13% in younger patients. Functional status declined for two older patients (8%), who dropped their KS from 80 to 100% (normal activity without limitation) to 40 to 70% (unable to work, but able to care of self at home). Nine of the younger patients (24%) had KS drop from 80 to 100% to 40 to 70%. There was one perioperative death (30-day mortality rate for the study groups, 1.5%).Elderly patientsor = 70 years of age undergoing lobectomy for NSCLC had similar PFT results and functional status as younger patients70 years of age 1 year after undergoing surgery. Curative resection should not be denied based on age alone.

Background— The role of C-reactive protein (CRP) in heart failure is not well studied. We assessed the prognostic value of CRP in patients randomized in Val-HeFT (Valsartan Heart Failure Trial) and studied changes in CRP that were associated with valsartan. Methods and Results— Characteristics of patients with baseline CRP levels above and below the median value were compared. Univariable and multivariable Cox proportional hazards regression models were used to examine the relationship of CRP to mortality and morbidity. Interactions were tested to determine whether differences in CRP changes from baseline to 4 and 12 months between groups randomly assigned to valsartan or placebo depended on baseline ACE inhibitor use. Median plasma CRP was 3.23 mg/L (interquartile range 1.42 to 7.56 mg/L), which is higher than in the general population. Patients with CRP above the median had features of more severe heart failure than those with CRP levels below the median. The cumulative likelihood of death and first morbid event increased with increasing quartile of CRP. Relative to the lowest CRP quartile, the risk of mortality (hazard ratio 1.51, 95% CI 1.2 to 1.9) and first morbid event (hazard ratio 1.53, 95% CI 1.28 to 1.84) was increased in the highest CRP quartile in multivariable models. CRP added incremental prognostic information to that provided by brain natriuretic peptide alone. CRP did not change significantly over time in the placebo group; however, after 12 months, valsartan was associated with a decrease in CRP in patients not receiving ACE inhibitors but not in those receiving ACE inhibitors at 12 months. Conclusions— CRP is increased in heart failure. Higher levels are associated with features of more severe heart failure and are independently associated with mortality and morbidity. The ability of treatments to reduce CRP levels and the prognostic importance of reducing CRP require further study.

ObjectivesThe goal of this study was to assemble a profile and assess the significance of arrhythmias in a nontertiary-based hypertrophic cardiomyopathy (HCM) cohort.BackgroundHypertrophic cardiomyopathy is associated with arrhythmia-related consequences, particularly sudden death. Ventricular tachyarrhythmias on Holter electrocardiograms (ECG) have been reported as markers for sudden death in highly selected HCM populations.MethodsWe assessed the profile of ventricular and supraventricular ectopy and bradyarrhythmia on ambulatory 24-h Holter ECG and also related these findings to clinical outcome in 178 HCM patients.ResultsOf the 178 study patients, 157 (88%) had premature ventricular complexes (PVCs), including 21 (12%) with ≥500 PVCs, 74 (42%) had couplets, 67 (37%) had supraventricular tachycardia (SVT), and 56 (31%) had nonsustained ventricular tachycardia (NSVT). Mean number of PVCs was 330 ± 763 (range 1 to 5,435) and increased with age (p < 0.01); NSVT was associated with greater left ventricular hypertrophy (p = 0.01) and severe symptoms (New York Heart Association functional classes III and IV) (p = 0.04); SVT occurred more commonly in patients with outflow obstruction (p = 0.02). Over a follow-up of 5.5 ± 3.4 years, 11 (6%) patients died suddenly (annual mortality rate, 1.1%) including 5 patients with NSVT. For sudden death, NSVT on Holter ECG had negative and positive predictive values of 95% and 9%, and sensitivity and specificity of 45% and 69%, respectively.ConclusionsIn this nontertiary-based HCM cohort, ventricular and supraventricular tachyarrhythmias were particularly frequent and demonstrated a broad spectrum on ambulatory (Holter) ECG. Paradoxically, despite such a highly arrhythmogenic substrate, sudden death events proved to be relatively uncommon. Ventricular tachyarrhythmias had a low positive and relatively high negative predictive value for sudden death in this HCM population.