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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

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.

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.

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.

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.

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.

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.

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: 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.

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.

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.

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

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.

Objective This study evaluated whether a commercial weight-loss product (Lean System 7) would result in less reduction in resting metabolic rate (RMR) in overweight subjects on a calorie-restricted diet and exercise regimen than in subjects using diet and exercise alone. Methods In this randomized, double-blind, placebo-controlled study, healthy overweight adults were given three capsules of a commercial weight-loss product twice daily or an identical placebo and followed a calorie-restricted diet and an exercise program for 8 wk. RMR, body weight, body mass index, waist and hip circumferences, and body composition by dual-energy x-ray absorptiometry were measured at baseline and week 8. An intention-to-treat analysis was performed. Results Of 47 adults enrolled, 35 completed the study. Subjects taking the commercial weight-loss product had a significant ( P = 0.03) increase in RMR, 7.2% increase versus 0.7% decrease in the placebo group. Subjects taking the commercial weight-loss product also had a significant ( P = 0.04) decrease in hip circumference, 3.78 cm versus 2.07 cm in the placebo group. There were no other statistically significant differences in any other outcome variable, diet composition, exercise compliance, or adverse events. Conclusion The results of this study showed that administration of a commercial weight-loss product to overweight adults in conjunction with a calorie-restricted diet and moderate exercise program effectively reverses the decrease in RMR associated with calorie restriction within this study population. The commercial weight-loss product was well tolerated, and there were no serious adverse events over the 8 wk studied.

The major forms of vitamin E in human physiological fluids are alpha and gamma tocopherols which exhibit different biological activities under a variety of assay conditions. The goal of this study was to obtain indirect information about the transport of tocopherols across the blood/spinal fluid barrier by comparing the concentrations of alpha and gamma tocopherols in serum and cerebrospinal fluid (CSF).CSF and serum samples were obtained simultaneously from 28 human, male subjects excluding those with known pathology during the performance of spinal anesthesia procedures. The samples were centrifuged and frozen, and analyzed for tocopherols by HPLC with electrochemical detection.The concentrations of alpha and gamma tocopherols in CSF correlated significantly with their respective concentrations in serum. This would be expected since these nutrients have to be supplied by diet to serum followed by transport to the brain. The ratios of alpha to gamma tocopherols in the CSF and serum were highly correlated. High concentrations of alpha in serum tended to suppress gamma in both serum and CSF.These data suggest that the processes involved in the entry of tocopherol from blood to the CSF do not discriminate between the alpha and gamma tocopherols. In contrast, alpha tocopherol is highly preferred during the packaging of plasma lipoproteins by the liver. Our data also suggest that alpha and gamma tocopherols will be available to the human brain via transport from blood.

Recent studies have shown that quantitative instrumental measurements are more sensitive than clinical rating scales to subclinical dyskinesia and parkinsonism. We therefore hypothesized that an instrumental assessment would be more sensitive to the presence of dyskinetic and parkinsonian movements than the Abnormal Involuntary Movement Scale (AIMS), the Dyskinesia Identification Scale, Condensed User Version (DISCUS), and the Simpson-Angus Scale (SAS). We also hypothesized that the DISCUS, by virtue of its more detailed protocol, would be more sensitive than the AIMS.Using blinded raters, we compared the clinical rating scales with instrumental measurements in 100 patients referred to a movement disorders clinic. We collected demographic data, risk factors for tardive dyskinesia, current medication use, Axis I and III disorders, and an estimate of cognitive functioning using the Mini-Mental Status Examination.There was no significant difference between the AIM and the DISCUS in the identification of dyskinesia. However, an instrumental assessment revealed a significantly greater prevalence of dyskinesia. The Mini-Mental Status Examination was the most prominent predictor of both instrumental and clinical measurements of parkinsonian and dyskinetic movements.It appears that even trained raters, utilizing standard rating scales, may underestimate the prevalence of some motor abnormalities. Instrumental ratings may be helpful to both the clinician and investigator, particularly when abnormal movements are not clinically obvious. The relationship between cognitive impairment and motor abnormalities remains an important area for further research.

Although research on pathological gambling is increasing, there are few studies examining correlates of treatment retention. In the current study, 50 outpatients with a primary DSM-IV diagnosis of pathological gambling treated in a clinical practice were assessed by chart review. Standard scales were used to rate subjects at baseline and at 2-month intervals. Subjects who dropped out of treatment were contacted by telephone to determine reasons for discontinuation of treatment. The mean duration of follow-up was 360.4 ± 352.2 days. Twenty-four (48%) of the subjects discontinued treatment, including 14 (36.8%) of those subjects who were responders (defined as Clinical Global Impression [CGI] scale of “very much” or “much” improved) during at least one assessment point. Of those who discontinued treatment, 41.7% reported missing the thrill of gambling and 20.8% reported feeling certain that they could win and relieve financial burdens. Predictors of treatment continuation were responding to treatment within 8 weeks (odds ratio [OR], 6.00; 95% confidence interval [CI], 1.13 to 32.00; P = .04) and having a supportive environment (OR, 22.99; 95% CI, 5.04 to 104.76; P < .001). We conclude that a large percentage of patients with pathological gambling discontinue treatment. Predictors of treatment continuation may have clinical importance. Prospective longitudinal studies are needed to further elucidate the course of pathological gambling.

The effects of repetitive work on Alzheimer ' disease (AD) patientfunctioning were examined when nine veterans were movedfrom a work program to a traditional adult day care program. Subjects were reassessedfour months after the move with the Mini-Mental State Examination (MMSE), Cognitive Performance Test (CPT), and Geriatric Depression Scale (GDS). Individual slopes were calculatedfor seven subjects who had longitudinal scores, and expected scores were predicted based on the rate ofdecline. Observed scores at reassessment were significantly lower than expected scores. The MMSE was on average 4.9 points lower, and the CPT. 64 points lower than expected. The GDS did not change. The spouses of all nine patients reported declines in daily living activities. Compared to traditional day care activities, work activities involve sequencing skills and practice may translate to self-care activities at home.

BACKGROUND Recurrent hallux valgus is a relatively common, yet challenging, condition for both the patient and the surgeon. The literature on the treatment of recurrent hallux valgus is sparse. The purpose of this study was to evaluate prospectively the functional outcome and patient satisfaction following the Lapidus procedure for the treatment of recurrent hallux valgus deformity. METHODS Twenty-four patients with a total of twenty-six symptomatic recurrences of hallux valgus after previous procedures for treatment of the deformity were included in the study. Exclusion criteria included prior fusion procedures on the foot or ankle, a previous Keller or Mayo procedure, insulin-dependent diabetes, peripheral vascular disease, or peripheral neuropathy. A visual analog pain scale and the American Orthopaedic Foot and Ankle Society Hallux Metatarsophalangeal-Interphalangeal Scale were administered preoperatively, at six months postoperatively, and yearly thereafter. Weight-bearing radiographs were also made preoperatively; at six weeks, three months, six months, and one year postoperatively; and yearly thereafter. Patient satisfaction was assessed at the latest follow-up evaluation. RESULTS At twenty-four months, the mean score according to the American Orthopaedic Foot and Ankle Society (AOFAS) Hallux Metatarsophalangeal-Interphalangeal Scale had increased from 47.6 to 87.9 points, the mean score according to the visual analog pain scale had improved from 6.2 to 1.4, the mean hallux valgus angle had improved from 37.1 degrees to 17.1 degrees, and the mean intermetatarsal angle had improved from 18 degrees to 8.6 degrees. The patients were very satisfied after 77% of the twenty-six procedures, satisfied after 4%, and somewhat satisfied after 19%; no patient was dissatisfied. There were no cases of hallux varus. Complications included three nonunions, all of which occurred in smokers, and two superficial wound infections. CONCLUSION In appropriately selected patients, the Lapidus procedure is a reliable and effective operation after failed surgical treatment of hallux valgus. LEVEL OF EVIDENCE Therapeutic study, Level IV (case series [no, or historical, control group]). See p. 2 for complete description of levels of evidence.

Background. Deep wound infection (DWI) in total knee (TKA) and total hip (THA) arthroplasty has been shown to highly correlate with superficial surgical site infection (SSSI). Although several studies have reported hospital factors that predispose to SSSI, patient factors have not been clearly elucidated. Methods. All patients undergoing TKA (n=1181) and THA (n=1124) surgery during the period 1977–1995 at our institution were observed at the end of a 30-day post-operative period. Thirty-three patients that developed SSSI during this period constituted the study group. The control group was composed of 64 matched subjects that did not develop SSSI. A chart review was applied to abstract DWI cases during the first 18 post-operative months for the study group and for an average of 6.7 years for the control group (range 5–18.2 years). Potential risk factors for SSSI were used as predictors of SSSI in a logistic regression analysis. Results. During the 18-month observation period 19 out of the 33 study subjects (58%) developed DWI. No DWI was registered in the control group (the difference was significant, p

The goal of this epidemiological study was to investigate lifetime history and odds ratios of personality disorders in adopted and non-adopted adults using a nationally representative sample. Data, drawn from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC), were compared in adopted (n=378) versus non-adopted (n=42,503) adults to estimate the odds of seven personality disorders using logistic regression analyses. The seven personality disorders were histrionic, antisocial, avoidant, paranoid, schizoid, obsessive-compulsive, and dependent personality disorder. Adoptees had a 1.81-fold increase in the odds of any personality disorder compared with non-adoptees. Adoptees had increased odds of histrionic, antisocial, avoidant, paranoid, schizoid, and obsessive-compulsive personality disorder compared with non-adoptees. Two risk factors associated with lifetime history of a personality disorder in adoptees compared to non-adoptees were (1) being in the age cohort 18-29 years (but no difference in the age 30-44 cohort), using the age 45 or older cohort as the reference and (2) having 12 years of education (but no difference in higher education groups), using the 0-11 years of education as the reference. These findings support the higher rates of personality disorders among adoptees compared to non-adoptees.

The benefits of chronic systemic corticosteroids for patients with chronic obstructive pulmonary disease (COPD) are not well established. To determine whether chronic corticosteroid treatment can be safely withdrawn in "steroid-dependent""COPD patients, we performed a double-blind, placebo-controlled study of 38 patients with steroid-dependent COPD. Patients were randomly assigned to receive their usual maintenance prednisone dose for 6 mo (continuous group) or to be withdrawn from prednisone at a rate of 5 mg per week (demand group). The number of COPD exacerbations per patient (primary outcome) was 2.5 +/- 2.7 (mean +/- SD) in the continuous group and 2.7 +/- 2.5 in the demand group (p = 0.60, 95% confidence interval for the difference: -1.1 to 1.7). Spirometric results, dyspnea, and health-related quality of life did not differ significantly in the two groups. The average daily corticosteroid dose was 10.7 +/- 5.2 mg in the continuous group and 6.3 +/- 6.4 mg in the demand group (p = 0.003). Weight decreased in the demand group by 4.8 +/- 2.0 kg, compared with an increase in the continuous group of 0.5 +/- 3.5 kg (p = 0.007). Discontinuation of chronic systemic corticosteroid treatment in steroid-dependent COPD patients did not cause a significant increase in COPD exacerbations, but did reduce total systemic corticosteroid use and body weight. Larger studies may be warranted to establish the relative risks and benefits of chronic corticosteroid treatment of patients with COPD.

Objective : To determine the effect of different sites and locally applied pressure on vibration thresholds. Methods : Vibration thresholds were compared in 47 normal volunteers at 3 sites of the index finger (pulp, dorsum of the middle phalanx and nail) and at two sites of the great toe (dorsum of the proximal phalanx and nail). The effect of local pressure (30, 50 and 100 g/1.22 cm 2 ) were compared in 41 subjects at the dorsum of the middle phalanx of the index finger and the proximal phalanx of the great toe. Results : The hand was more sensitive than the foot for vibration. There were no significant differences in vibration thresholds at different sites of the index finger and different sites of the great toe. The pulp of the index finger yielded the least inter-individual variation. Testing under 30 and 50 g/1.22 cm 2 of pressure yielded equal vibration thresholds. Vibration threshold was higher when tested under 100 g/1.22 cm 2 at the index finger but not the great toe. This difference was small and clinically negligible. Conclusion : Testing of vibration thresholds in normal subjects can be adequately conducted at several sites of the index finger and the great toe. The test can be adequately done under low pressure of 30–50 g/1.22 cm 2 .

Objective : To determine the effect of different sites and local skin temperature on thermal thresholds. Methods : Cool and warm detection and cold and heat pain thresholds were compared in 46 normal volunteers at the thenar eminence (TE), dorsum of the hand (DH), volar surface of the wrist (VW) and dorsum of the foot (DF). Results : The hand is more sensitive than the foot for cool and warm. TE is more sensitive for warm than DH and VW but the difference is clinically negligible. DH and VW are equally sensitive to warm. TE, DH, and VW are equally sensitive to cool. Inter-individual variance is smallest at TE. Warm and cool thresholds are independent of local skin temperature (range of 27–37°C). TE is less sensitive for cold pain but otherwise the hand and the foot are equally sensitive to thermal pain. Conclusion : Testing of thermal thresholds in normal subjects can be adequately conducted at several sites at the hand, however, TE is preferred given the small inter-individual variability. TE may be preferred for evaluating hyperalgesia to cold given its higher threshold. Warming or cooling of the skin is unnecessary within the range normally encountered in routine clinical evaluation.

Background: Inclusion of obsessive–compulsive disorder (OCD) as an anxiety disorder in DSM-IV assumes that anxiety is the primary symptom of OCD; however, persuasive empirical evidence in support of this view has not been presented yet. In the present study we hypothesized that provoked anxiety symptoms respond better to intravenous diazepam than would provoked obsessions. We, therefore, reasoned that anxiety symptoms are secondary symptoms of OCD. Methods: To test the hypothesis we designed a double-blind, randomized, placebo-controlled crossover study. Patients underwent four experimental conditions in which the sequence of symptom provocation and IV injection of (placebo or diazepam) were alternated. Baseline and IV injection-induced symptom changes were assessed using visual analogs. Results: Obsessions and anxiety correlated strongly for all four experimental conditions in which the sequence of the symptom provocation and diazepam IV injections was alternated. IV diazepam injection before and after symptom provocation failed to preferentially modulate anxiety symptoms over obsessions. Unexpectedly, in the group in which IV diazepam injection preceded the symptom provocation, reduction of mean obsessions was even more pronounced. Conclusions: Strong correlations between anxiety and obsessions at baseline, during symptom provocation, and after IV diazepam infusion suggest that anxiety and obsessions are tightly coupled phenomena in OCD.

OBJECTIVE Although parental alcohol use disorder (AUD) increases risk for alcohol problems in offspring, no studies have evaluated the odds of AUD in offspring based on the number of biological parents with AUD (0, 1, or 2) in a population-based national sample. The purpose of this study was to investigate the relationship between the number of AUD parents and prevalence of AUD in offspring. METHOD This study utilized data from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions, which assessed AUD using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version (main outcome variable). We analyzed the sample (n = 40,374) to investigate the effect of the number of AUD parents on lifetime AUD in offspring. In a subgroup analysis, gender differences were examined. RESULTS 22% of adults in the United States had at least 1 biological parent with AUD. Compared with offspring of non-AUD parents, offspring of 1 AUD parent had a 2.5-fold increase (AOR = 2.51; 95% CI, 2.38-2.66) and offspring of 2 AUD parents had a 4.4-fold increase (AOR = 4.44; 95% CI, 3.93-5.02) in the odds of lifetime AUD. Each additional AUD parent increased the odds of AUD in offspring in an additive pattern. Female offspring were more vulnerable to the impact of parental AUD than male offspring (OR = 1.17 in offspring of 1 AUD parent; OR = 1.48 in offspring of 2 AUD parents). CONCLUSIONS Offspring of AUD parents had heightened odds of lifetime AUD, with an additive parental effect. Awareness of this risk can be useful for clinicians to educate individuals with AUD parents about prevention and intervention.

OBJECTIVE: To evaluate the relationship between total serum anticholinergic activity (SAA) and the presence or absence of delirium in older hospitalized persons on general medical wards. DESIGN: Case-control study and within-subjects repeated-measures in recovered delirious patients. SETTING: Minneapolis Veterans Affairs Medical Center medical wards. PARTICIPANTS: Eleven male delirious patients (DSM-III-R criteria) aged 60 or older and 11 comparably aged male nondelirious controls. MEASUREMENTS: Radioreceptor bioassay of total SAA using tritiated quinuclidinyl benzilate (QNB) binding to muscarinic receptors. Results are expressed in terms of atropine equivalents (nm). MAIN RESULTS: Mean SAA was significantly elevated in the delirious group (mean ± SD = 6.05 ± 2.97 nm atropine equivalents) compared with the controls (3.38 ± 2.49; t(20) = 2.28, P < .05). At study entry, mean SAA was significantly higher in delirious subjects whose symptoms eventually resolved completely (mean ± SD = 7.77 ± 2.37) compared with subjects whose delirious symptoms persisted (3.99 ± 2.30; t(9) = 2.68, P < .05). All six patients in whom delirium resolved completely had a decrease in serum anticholinergic activity when measured during delirium (7.77 ± 2.37) and after symptom resolution (3.92 ± 2.61; t(5) = 3.29, P < .05). CONCLUSIONS: Our findings suggest that serum anticholinergic activity may play a role in delirium in medical inpatients. The relationships between SAA and delirium in medical patients and between total SAA and medication use warrant further study.

Background— There are few sex-specific outcome data in heart failure with preserved ejection fraction. Methods and Results— We assessed sex differences in baseline characteristics and outcomes among 4128 patients with heart failure with preserved ejection fraction in the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial. Women (n=2491) with heart failure with preserved ejection fraction were ≈1 year older (72±7 years versus 71±7 years) and more likely to be obese (46% versus 35%) and have chronic kidney disease (34% versus 26%) and hypertension (91% versus 85%) than men but less likely to have an ischemic cause (19% versus 34%), atrial fibrillation (27% versus 33%), or chronic obstructive pulmonary disease (8% versus 13%) (all P Conclusions— In patients with typical heart failure with preserved ejection fraction, there were prominent sex differences in baseline characteristics and outcomes. Women had better overall prognosis, although the presence of 4 common baseline characteristics seemed to moderate this finding. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT000095238.

BACKGROUND: Prior research has shown that adoptees have a higher rate of substance use disorders (SUDs) than nonadoptees. But these findings have not been verified with a population-based sample of adult adoptees in the United States. Also, no previous adoption study has measured the prevalence of each specific substance use disorder (SUD). We aimed to compare lifetime prevalence rates and odds ratios of SUDs in adopted and nonadopted adults. METHODS AND FINDINGS: The data come from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). The main outcome measure was the prevalence of lifetime SUDs in adopted (n = 378) and nonadopted adults (n = 42503). Adoptees and nonadoptees were compared to estimate the odds of lifetime SUDs using logistic regression analysis. Adoptees had higher prevalence rates of lifetime SUDs than nonadoptees. Overall, adoptees had a 1.87-fold increase (adjusted odds ratio [AOR] 1.87, 95% CI 1.51-2.31) in the odds of any lifetime SUD compared to nonadoptees. For each SUD, adoptees had higher odds for alcohol abuse/dependence (AOR 1.84), nicotine dependence (AOR 1.78), cannabis abuse/dependence (AOR 1.77), cocaine abuse/dependence (AOR 2.54), amphetamine abuse/dependence (AOR 3.14), hallucinogen abuse/dependence (AOR 2.85), opioid abuse/dependence (AOR 2.21), and other drug abuse/dependence (AOR 2.87) compared to nonadoptees. This study also identified two adoption-specific risk factors (Hispanic, never married) associated with any lifetime SUD. CONCLUSIONS: This study demonstrated an increased risk of lifetime SUDs in adopted adults. The findings can be useful for clinicians and policy makers to provide education, prevention, and support for adoptees and their families.

When lifting heavy loads, trunk muscle contraction converts the abdominal and thoracic cavities into a nearly rigid-walled cylinder that provides increased extrinsic stability and allows partial transfer of load away from the spine. Because twisting is a common mechanism of low-back injuries, this study was undertaken to determine if trunk rotation results in a decrease in the extrinsic stability of the spine. We studied the effects of changes in trunk posture on intra-abdominal pressure generated during a maximum effort Valsalva's maneuver (IAP max) in eight healthy volunteers. IAP max during standing combined with trunk rotation was found to be significantly lower than IAP max during standing straight (p < 0.05). IAP max during forward flexion combined with trunk rotation was significantly lower than during forward flexion (p < 0.01). The results of our study indicate that trunk rotation adversely effects the ability to perform a Valsalva's maneuver. We conclude that extrinsic stability of the spine is at a biomechanical disadvantage when the trunk is rotated and thus may be a contributing factor to twisting-type back injuries.

Background Mortality and complications after percutaneous coronary intervention is higher when performed after regular duty hours due to challenging patient characteristics, inferior processes of care and limited resources. Since these challenges are also encountered during coronary artery bypass graft (CABG) surgery that is performed after regular work hours, we assessed whether hour and day of procedure influenced mortality after CABG. Methods We studied 4,714 consecutive patients who underwent CABG at the Minneapolis Veterans Administration (VA) Medical Center between 1987 and 2009. We compared postoperative (30-day) mortality rates in relation to hour and day in which the operation was performed. Results Operations performed on weekends and after 4 PM had higher risk patients (p < 0.0001) and were more likely to be emergent (p < 0.0001), require intra-aortic balloon pump support (p < 0.0001) and result in postoperative complications (p < 0.0001) compared to those at regular work hours. Mortality was significantly higher when CABG was performed on weekends compared to weekdays (9.4% versus 2.5%; odds ratio (OR) 4.1, 95% confidence interval (CI) 1.6 to 10.4, p = 0.003), and after 4 PM compared to between 7 AM-4 PM (6.2% versus 2.2%; OR 2.9, 95% CI 1 to 8, p = 0.049). In multivariable analysis, when adjusted for the urgency of the operation and the VA estimated mortality risk score, these associations were no longer statistically significant. Conclusions Mortality after CABG is higher when surgery is performed on the weekends and after 4 PM. These variations in mortality were related to higher patient risk, and urgency of the operation rather than external factors.

Background— Plasma concentrations of natriuretic peptides (NPs) are associated with morbidity and mortality in patients with systolic heart failure (HF). However, the role of NP as a prognostic marker in patients with HF and preserved ejection fraction (HFpEF) has not been studied in a large cohort of well-characterized patients. Moreover, it is unclear whether treatments have a differential effect on morbidity and mortality across the spectrum of NP levels. Methods and Results— N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured at baseline in 3480 patients in the I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction Trial). In a multivariable Cox regression model, NT-proBNP above the median of 339 pg/mL was independently associated with an increased risk of the primary end point of all-cause mortality and prespecified cardiovascular hospitalizations (adjusted hazard ratio [HR], 1.79; 95% CI, 1.56 to 2.10; P P P P =0.005), all-cause mortality ( P =0.05), and the HF composite outcome ( P P =0.003), all-cause mortality (HR, 0.75; 95% CI, 0.56 to 0.99; P =0.046), and HF composite outcome (HR, 0.57; 95% CI, 0.41 to 0.80; P =0.001) in patients with NT-proBNP below the median. Conclusions— The unexpected benefit of irbesartan in lower-risk patients with HFpEF in this post hoc analysis may indicate effects on early, but not later, high-risk stages of the disease. These findings question the strategy of using elevated plasma concentrations of NP as a patient selection criterion in HFpEF trials. More studies are needed to support or contest this practice. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00095238.

Several retrospective studies have raised concerns regarding digoxin therapy in select subgroups of heart failure patients. To assess the impact of digoxin therapy on outcomes in the current era of heart failure therapy, the authors analyzed data representing 5010 patients enrolled in the Valsartan Heart Failure Trial (Val-HeFT) to examine the relationship of baseline digoxin use and all-cause mortality, first morbid event, and heart failure hospitalizations. At baseline, 3374 patients (67%) were receiving digoxin therapy and 1636 (33%) were not. Patients receiving digoxin had features of worse heart failure with higher New York Heart Association class and lower blood pressure, ejection fraction, and β-blocker use (32.1% vs 40.8%). Digoxin use was associated with worse mortality (21.1 vs 15.0%, P.001), first morbid event (34.6 vs 21.7, P.001), and HF hospitalization rate (19.1 vs 10.1%, P.001). After adjustment for baseline group differences including medical therapy and baseline rhythm, patients receiving digoxin remained at a higher risk for all-cause mortality (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.05-1.57), first morbid event (HR, 1.35; 95% CI, 1.15-1.59), and heart failure hospitalization (HR, 1.41; 95% CI, 1.12-1.78). These results remained materially unchanged with propensity matched analysis. No benefit with digoxin use was observed in this study, underscoring the need to reassess the role of digoxin in the contemporary management of heart failure.

Background— Growth-differentiation factor-15 (GDF-15) is emerging as a prognostic biomarker in patients with coronary artery disease. Little is known about GDF-15 as a biomarker in patients with heart failure. Methods and Results— The circulating concentration of GDF-15 was measured at baseline (n=1734) and at 12 months (n=1517) in patients randomized in the Valsartan Heart Failure Trial (Val-HeFT). GDF-15 levels at baseline ranged from 259 to 25 637 ng/L and were abnormally high (>1200 ng/L) in 85% of patients. Higher levels were associated with features of worse heart failure and biomarkers of neurohormonal activation, inflammation, myocyte injury, and renal dysfunction. Baseline GDF-15 levels (per 100 ng/L) were associated with the risks of mortality (hazard ratio, 1.017; 95% confidence interval, 1.014 to 1.019; P P P =0.02) but not first morbid event. At 12 months, the GDF-15 levels had increased by a similar amount in the placebo and valsartan groups ( P =0.94). Increases in GDF-15 over 12 months were independently associated with the risks of future mortality and first morbid event also after adjustment for clinical prognostic variables, B-type natriuretic peptide, high-sensitivity C-reactive protein, and high-sensitivity troponin T and their changes. Conclusions— GDF-15 reflects information from several pathological pathways and provides independent prognostic information in heart failure. GDF-15 levels increase over time, suggesting that GDF-15 reflects a pathophysiological axis that is not completely addressed by the therapies prescribed in Val-HeFT.

This study attempts to quantify the impact of the introduction of local second-level health services on nonmedical costs (NMCs) for residents of the rural Ecuadorian county of La Maná.NMCs for patients accessing second-level health care were assessed by using a quasi-experimental pre- and postintervention study design. In 2007, before local second-level health care services existed, and then in 2008, after the introduction of second-level health care services in the form of a county hospital, 508 patients from the county who sought second-level health care were interviewed.Mean NMCs per patient per illness episode were US$ 93.58 before the county hospital opened and US$ 12.62 after it opened. This difference was largely due to reductions in transport costs (US$ 50.01 vs. US$ 4.28) and food costs (US$ 25.38 vs. US$ 7.28) (P0.001 for each category).NMCs can be decreased sevenfold with the introduction of a county hospital in a rural province previously lacking second-level health care. Introduction of rural second-level health care reduces financial barriers and thus may increase access to these health services for poorer patients in rural communities.