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The left atrial septal pouch (LASP) occurs due to incomplete fusion of septa primum and secundum at the inter-atrial septum, creating an open flap that may serve as a thromboembolic source. Prior studies have demonstrated increased prevalence of LASP in cryptogenic strokes. The aim of the current study was to validate the above findings in a separate, larger group of stroke and non-stroke patients. We examined transesophageal echocardiograms (TEEs) performed between July 2011 and December 2018. LASP prevalence was determined in TEEs referred for ischemic stroke or transient ischemic attack ("stroke") and compared with LASP prevalence in patients undergoing TEEs for other reasons ("non-stroke"). Stroke subtyping was performed using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. There were 306 TEEs from 144 non-stroke and 162 stroke patients. Mean age and sex distribution were 56 ± 1 (mean ± SE) and 65% male in the non-stroke group and 58 ± 1 and 54% male in the stroke group. The overall prevalence of LASP was 31%. The prevalence of LASP was 28% (41/144) in non-stroke patients, 25% (24/95) in non-cryptogenic stroke patients, and 43% (29/67) in cryptogenic stroke patients. LASP prevalence was significantly higher in the cryptogenic subgroup compared with the non-cryptogenic subgroup (p = 0.02). These findings demonstrate a significant association of LASP with risk of cryptogenic stroke, suggesting that LASP may serve as a thromboembolic nidus. Additional studies are needed to determine the generalizability of these findings, and their therapeutic implications, supporting LASP as a stroke risk factor.

Objective: The preventability of strokes treated by mechanical thrombectomy is unknown. The purpose of this study was to analyze stroke preventability for patients treated with mechanical thrombectomy for large vessel occlusion. Methods: We conducted retrospective analyses of 300 patients (mean ± SE age 69 ± 0.9 years, range 18-97 years; 53% male) treated with mechanical thrombectomy for large vessel occlusion from January 2008 to March 2019. We collected data including demographics, NIH Stroke Scale (NIHSS) at onset, and (beginning in 2015) classified 90-day outcome by modified Rankin Scale (mRS). Patients were evaluated using a Stroke Preventability Score (SPS, 0 to 10 points) based on how well patients had been treated given their hypertension, hyperlipidemia, atrial fibrillation, and prior stroke history. We examined the relationship of SPS with NIHSS at stroke onset and with mRS outcome at 90 days. Results: SPS was calculated for 272 of the 300 patients, with mean ± SE of 2.1 ± 0.1 (range 0-8); 89 (33%) had no preventability (score 0), 120 (44%) had low preventability (score 1-3), and 63 (23%) had high preventability (score 4 or higher). SPS was significantly correlated with age (r = 0.32, p < 0.0001), while NIHSS (n = 267) was significantly higher (p = 0.03) for patients with high stroke preventability vs. low/no preventability [18.8 ± 0.92 (n = 62) vs. 16.5 ± 0.51 (n = 205)]. Among 118 patients with mRS, outcome was significantly worse (p = 0.04) in patients with high stroke preventability vs. low/no preventability [4.7 ± 0.29 (n = 28) vs. 3.8 ± 0.21 (n = 90)]. The vast majority of patients with high stroke preventability had inadequately treated atrial fibrillation (85%, 53/62). Conclusions: Nearly one quarter of stroke patients undergoing mechanical thrombectomy had highly preventable strokes. While stroke preventability showed some relationship to stroke severity at onset and outcome after treatment, preventability had the strongest association with age. These findings emphasize the need for improved stroke prevention in the elderly.

Cerebral microbleeds (CMB) are a common MRI finding, representing underlying cerebral microhemorrhages (CMH). The etiology of CMB and microhemorrhages is obscure. We conducted a pathological investigation of CMH, combining standard and immunohistological analyses of postmortem human brains. We analyzed 5 brain regions (middle frontal gyrus, occipital pole, rostral cingulate cortex, caudal cingulate cortex, and basal ganglia) of 76 brain bank subjects (mean age ± SE 90 ± 1.4 years). Prussian blue positivity, used as an index of CMH, was subjected to quantitative analysis for all 5 brain regions. Brains from the top and bottom quartiles (n = 19 each) were compared for quantitative immunohistological findings of smooth muscle actin, claudin-5, and fibrinogen, and for Sclerosis Index (SI) (a measure of arteriolar remodeling). Brains in the top quartile (i.e. with most extensive CMH) had significantly higher SI in the 5 brain regions combined (0.379 ± 0.007 vs 0.355 ± 0.008; p

The objective of this study is to assess the effectiveness of a stroke clinic in stroke prevention and progression of cerebral microbleeds (CMB). We conducted a retrospective observational study of patients who visited a stroke clinic between January 2011 and March 2017. Susceptibility-weighted imaging (SWI) MRI studies were obtained at baseline and follow-up visits to identify new infarctions and CMB progression. Patients with CMB who also underwent brain computed tomography (CT) imaging were identified and their cerebral arterial calcification was quantified to evaluate the relationship between the extent of intracranial calcification and CMB burden. A total of 64 stroke patients (mean age 73.1 ± 11.0, 47% males) had CMB on baseline and follow-up MRI studies. During a mean follow-up period of 22.6 months, four strokes occurred (4/64, 6%; 3 ischemic, 1 hemorrhagic), producing mild neurological deficit. Progression of CMB was observed in 54% of patients with two MRIs and was significantly associated with length of follow-up. Subjects with intracranial calcification score > 300 cm3 had higher CMB count than those with scores

The objective of this study is to assess the effectiveness of a stroke clinic in stroke prevention and progression of cerebral microbleeds (CMB). We conducted a retrospective observational study of patients who visited a stroke clinic between January 2011 and March 2017. Susceptibility-weighted imaging (SWI) MRI studies were obtained at baseline and follow-up visits to identify new infarctions and CMB progression. Patients with CMB who also underwent brain computed tomography (CT) imaging were identified and their cerebral arterial calcification was quantified to evaluate the relationship between the extent of intracranial calcification and CMB burden. A total of 64 stroke patients (mean age 73.1 ± 11.0, 47% males) had CMB on baseline and follow-up MRI studies. During a mean follow-up period of 22.6 months, four strokes occurred (4/64, 6%; 3 ischemic, 1 hemorrhagic), producing mild neurological deficit. Progression of CMB was observed in 54% of patients with two MRIs and was significantly associated with length of follow-up. Subjects with intracranial calcification score > 300 cm3 had higher CMB count than those with scores

BackgroundCerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic cause of stroke. In addition to ischemic stroke, CADASIL predisposes to development of cerebral microbleeds (CMB). CMB and hypertension are known to be associated with intracerebral hemorrhage (ICH). The purpose of this study was to analyze the relationships among CMB, hypertension, and ICH in CADASIL.Materials and methodsWe enrolled 94 genetically confirmed CADASIL patients from 76 unrelated families at Jeju National University Hospital (Korea) between March 2012 and February 2015. We analyzed CMB presence, number, and distribution on susceptibility-weighted imaging MRI using the microbleed anatomical rating scale. Multiple logistic regression was used to determine factors associated with the presence of CMB and ICH.ResultsCMB were observed in 62 patients (66%), median number of CMB per patient was 4 (range 0-121). Twenty-two ICHs were found in 16 patients (17%). There was incongruence between the most common site of CMB (thalamus) and that of ICH (basal ganglia). Hypertension was independently associated with the presence of CMB (multiple regression OR, 2.71; 95% CI 1.02-7.18, p

The left atrial septal pouch (LASP) occurs due to incomplete fusion of septa primum and secundum at the inter-atrial septum, creating an open flap that may serve as a thromboembolic source. Prior studies have demonstrated increased prevalence of LASP in cryptogenic strokes. The aim of the current study was to validate the above findings in a separate, larger group of stroke and non-stroke patients. We examined transesophageal echocardiograms (TEEs) performed between July 2011 and December 2018. LASP prevalence was determined in TEEs referred for ischemic stroke or transient ischemic attack ("stroke") and compared with LASP prevalence in patients undergoing TEEs for other reasons ("non-stroke"). Stroke subtyping was performed using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. There were 306 TEEs from 144 non-stroke and 162 stroke patients. Mean age and sex distribution were 56 ± 1 (mean ± SE) and 65% male in the non-stroke group and 58 ± 1 and 54% male in the stroke group. The overall prevalence of LASP was 31%. The prevalence of LASP was 28% (41/144) in non-stroke patients, 25% (24/95) in non-cryptogenic stroke patients, and 43% (29/67) in cryptogenic stroke patients. LASP prevalence was significantly higher in the cryptogenic subgroup compared with the non-cryptogenic subgroup (p = 0.02). These findings demonstrate a significant association of LASP with risk of cryptogenic stroke, suggesting that LASP may serve as a thromboembolic nidus. Additional studies are needed to determine the generalizability of these findings, and their therapeutic implications, supporting LASP as a stroke risk factor.

ImportanceAlthough patients with acute stroke are routinely evaluated for potential treatment (ie, treatability of the stroke), preventability of the presenting stroke is generally not seriously considered.ObjectiveTo systematically analyze stroke preventability.Design, setting, and participantsWe evaluated medical records of 274 consecutive patients discharged with a diagnosis of ischemic stroke between December 2, 2010, and June 11, 2012, at the University of California Irvine Medical Center. Mean (SE) patient age was 67.2 (0.8) years. Data analysis was conducted from July 3, 2014, to August 4, 2015.ExposuresMedical records were systematically examined for demographic information, stroke risk factors, stroke severity, and acute stroke treatment.Main outcomes and measuresWe defined stroke preventability as the degree to which the patient's presenting stroke was preventable. Using variables easily determined at onset of stroke, we developed a 10-point scale (0, not preventable; 10, most preventable) to classify the degree of stroke preventability. Our focus was effectiveness of treatment of hypertension (0-2 points), hyperlipidemia (0-2 points), and atrial fibrillation (0-4 points), as well as use of antithrombotic treatment for known prior cerebrovascular and cardiovascular disease (0-2 points).ResultsTotal risk scores ranged from 0 to 8 (mean [SE], 2.2 [0.1]), with 207 patients (75.5%) exhibiting some degree of preventability (score of 1 or higher). Seventy-one patients (25.9%) had scores of 4 or higher, indicating that the stroke was highly preventable. Severity of stroke as determined by the National Institutes of Health Stroke Scale score was not related to preventability of stroke. However, 21 of 71 patients (29.6%) whose stroke was highly preventable were treated with intravenous or intra-arterial acute stroke therapy while these treatments were provided for only 13 of 67 patients (19.4%) with scores of 0 (no preventability) and 19 of 136 patients (14.0%) with scores of 1 to 3 (low preventability) (P = .03).Conclusions and relevanceMost patients with acute stroke exhibited some degree of preventability. Preventability and treatment of stroke were significantly associated, indicating that the most preventable strokes paradoxically were more likely to receive acute treatment.

OBJECTIVE To create a national policy model to evaluate the projected cost-effectiveness of multiple hospital-based strategies to prevent methicillin-resistant Staphylococcus aureus (MRSA) transmission and infection. DESIGN Cost-effectiveness analysis using a Markov microsimulation model that simulates the natural history of MRSA acquisition and infection. PATIENTS AND SETTING Hypothetical cohort of 10,000 adult patients admitted to a US intensive care unit. METHODS We compared 7 strategies to standard precautions using a hospital perspective: (1) active surveillance cultures; (2) active surveillance cultures plus selective decolonization; (3) universal contact precautions (UCP); (4) universal chlorhexidine gluconate baths; (5) universal decolonization; (6) UCP + chlorhexidine gluconate baths; and (7) UCP+decolonization. For each strategy, both efficacy and compliance were considered. Outcomes of interest were: (1) MRSA colonization averted; (2) MRSA infection averted; (3) incremental cost per colonization averted; (4) incremental cost per infection averted. RESULTS A total of 1989 cases of colonization and 544 MRSA invasive infections occurred under standard precautions per 10,000 patients. Universal decolonization was the least expensive strategy and was more effective compared with all strategies except UCP+decolonization and UCP+chlorhexidine gluconate. UCP+decolonization was more effective than universal decolonization but would cost $2469 per colonization averted and $9007 per infection averted. If MRSA colonization prevalence decreases from 12% to 5%, active surveillance cultures plus selective decolonization becomes the least expensive strategy. CONCLUSIONS Universal decolonization is cost-saving, preventing 44% of cases of MRSA colonization and 45% of cases of MRSA infection. Our model provides useful guidance for decision makers choosing between multiple available hospital-based strategies to prevent MRSA transmission.

BackgroundThe left atrial septal pouch (LASP), an anatomic variant of the interatrial septum, has uncertain clinical significance. We examined the association between LASP and ischemic stroke subtypes in patients undergoing transesophageal echocardiography (TEE).MethodsWe determined the prevalence of LASP among consecutive patients who underwent TEE at our institution. Patients identified with ischemic strokes were further evaluated for stroke subtype using standard and modified criteria from the Trial of Org 10172 in Acute Stroke Treatment (TOAST). We compared the prevalence of LASP in ischemic stroke, cryptogenic stroke, and non-stroke patients using prevalence ratios (PR).ResultsThe mean age of all 212 patients (including stroke and non-stroke patients) was 57 years. The overall prevalence of LASP was 17% (n = 35). Of the 75 patients who were worked-up for stroke at our institution during study period, we classified 31 as cryptogenic using standard TOAST criteria. The prevalence of LASP among cryptogenic stroke patients (using standard and modified TOAST criteria) was increased compared to the prevalence among other ischemic stroke patients (26 vs. 9%, p = 0.06; PR = 1.8, 95% CI = 1.1-3.1, and 30 vs. 10%, p = 0.04; PR = 2.2, 95% CI = 1.2-4.1, respectively).ConclusionIn this population of relatively young patients, prevalence of LASP was increased in cryptogenic stroke compared to stroke patients of other subtypes. These findings suggest LASP is associated with cryptogenic stroke, which should be verified by future large-scale studies.

It is essential to identify intermediate marker endpoints of carcinogenesis for the evaluation of the effectiveness of cancer-chemopreventive agents. We have observed that levels of proteolytic activities (as detected by 4 different substrates) are increased 2-3-fold (P < 0.003) in oral buccal mucosa cells of smokers and patients with oral leukoplakia or erythroplakia as compared to a nonsmoking comparison group. In addition, proteolytic activity levels in the buccal cells were increased nearly 3-fold in patients with oral trauma (P < 0.01) or diabetes (P < 0.02), as well as pregnant women (P < 0.04). Excluding these subgroups of patients in epidemiological studies increase the differences in levels of proteolytic activities between both the nonsmoking comparison group and smokers and between the comparison group and patients with oral leukoplakia or erythroplakia. Evaluation of prerandomization levels of proteolytic activities of patients in cancer chemoprevention trials will increase the statistical power by allowing stratified randomization based on levels of proteolytic activities. The observed increases in levels of proteolytic activities in tissues at higher than normal risk of cancer development suggest that levels of proteolytic activities should be used as immediate marker endpoints in human cancer prevention trials using protease inhibitors as potential anticarcinogenic agents.

On the basis of large cardiovascular clinical trials of lipid-lowering agents that showed a considerable decrease in the incidence of primary melanomas in the active agent arm, we have carried out a randomized, double-blind clinical trial examining the impact of lovastatin on various biomarkers of melanoma pathogenesis. Subjects with at least two clinically atypical nevi were randomized to receive oral lovastatin or placebo for a 6-month period. Clinical, histopathologic, and molecular biomarkers were evaluated for change in the two groups. Eighty subjects were randomized, evaluable, and included in the analyses. Lovastatin showed no benefit in comparison with placebo in the primary endpoint of decreasing the level of histopathologic atypia, nor in any of the secondary endpoints of decreasing clinical atypia, impact on nevus number, nor in showing significant changes in any of the molecular biomarkers. There were no significant differences in adverse event profiles for lovastatin compared with placebo. The lovastatin arm did show a significant and considerable decrease in total serum cholesterol and serum low-density lipoprotein (LDL) levels compared with placebo, an expected result. This finding bolsters confidence in subject compliance. Given the results of this trial, it is concluded that if lovastatin were to lower the incidence of melanoma, it would appear not to be doing so by reversing atypia of precursor atypical nevi over the 6-month time frame studied. Further research into the pathogenesis of melanoma and in other potential chemopreventive agents is needed. ©2014 AACR.

We surveyed administrators at 13 nursing homes in Orange County, CA, on their likelihood to admit methicillin-resistant Staphylococcus aureus (MRSA) carriers and assessed applicant characteristics associated with rejection. In multivariate models, denial of admission was associated with MRSA carriage (odds ratio, 2.7; P = .02) and receiving lower ratings for overall suitability for admission (odds ratio, 5.9; P < .001). Larger studies are needed to determine whether decolonization may remove barriers to accessing postdischarge care for MRSA carriers.

In a retrospective cohort study of 1,140 patients harboring methicillin-resistant Staphylococcus aureus, the nasal burden was low in 31%, category 1+ to 2+ in 54%, and category 3+ to 4+ in 15%. There was a significant trend in infection risk with increasing nasal burden (P = 0.007). In multivariate models, high nasal burden remained significantly associated with invasive infection.

Surgical site infection (SSI) surveillance is performed using a variety of methods with unclear performance characteristics. We used claims data to identify records for review following hysterectomy and colorectal surgery. Claims-enhanced screening identified SSIs missed by routine surveillance and could be used for targeted chart review to improve SSI detection.

BackgroundPublic reporting of surgical site infections (SSIs) by hospitals is largely limited to infections detected during surgical hospitalizations or readmissions to the same facility. SSI rates may be underestimated if patients with SSIs are readmitted to other hospitals. We assessed the impact of readmissions to other facilities on hospitals' SSI rates following primary total hip arthroplasty (THA) or total knee arthroplasty (TKA).MethodsThis was a retrospective cohort study of all patients who underwent primary THA or TKA at California hospitals between 1 January 2006 and 31 December 2009. SSIs were identified using ICD-9-CM diagnosis codes predictive of SSI assigned at any California hospital within 365 days of surgery using a statewide repository of hospital data that allowed tracking of patients between facilities. We used statewide data to estimate the fraction of each hospital's THA and TKA SSIs identified at the operative hospital versus other hospitals.ResultsA total of 91 121 THA and 121 640 TKA procedures were identified. Based on diagnosis codes, SSIs developed following 2214 (2.3%) THAs and 2465 (2.0%) TKAs. Seventeen percent of SSIs would have been missed by operative hospital surveillance alone. The proportion of hospitals' SSIs detected at nonoperative hospitals ranged from 0% to 100%. Including SSIs detected at nonoperative hospitals resulted in better relative ranking for 61% of THA hospitals and 61% of TKA hospitals.ConclusionsLimiting SSI surveillance to the operative hospital caused varying degrees of SSI underestimation and substantially impacted hospitals' relative rankings, suggesting that alternative methods for comprehensive postdischarge surveillance are needed for accurate benchmarking.

BackgroundMaternal exposures to traffic-related air pollution have been associated with adverse pregnancy outcomes. Exposures to traffic-related air pollutants are strongly influenced by time spent near traffic. However, little is known about women’s travel activities during pregnancy and whether questionnaire-based data can provide reliable information on travel patterns during pregnancy.ObjectivesExamine women’s in-vehicle travel behavior during pregnancy and examine the difference in travel data collected by questionnaire and global positioning system (GPS) and their potential for exposure error.MethodsWe measured work-related travel patterns in 56 pregnant women using a questionnaire and one-week GPS tracking three times during pregnancy (30 weeks of gestation). We compared self-reported activities with GPS-derived trip distance and duration, and examined potentially influential factors that may contribute to differences. We also described in-vehicle travel behavior by pregnancy periods and influences of demographic and personal factors on daily travel times. Finally, we estimated personal exposure to particle-bound polycyclic aromatic hydrocarbon (PB-PAH) and examined the magnitude of exposure misclassification using self-reported vs. GPS travel data.ResultsSubjects overestimated both trip duration and trip distance compared to the GPS data. We observed moderately high correlations between self-reported and GPS-recorded travel distance (home to work trips: r = 0.88; work to home trips: r = 0.80). Better agreement was observed between the GPS and the self-reported travel time for home to work trips (r = 0.77) than work to home trips (r = 0.64). The subjects on average spent 69 and 93 minutes traveling in vehicles daily based on the GPS and self-reported data, respectively. Longer daily travel time was observed among participants in early pregnancy, and during certain pregnancy periods in women with higher education attainment, higher income, and no children. When comparing self-reported vs. GPS data, we found that estimated personal exposure to PB-PAH did not differ remarkably at the population level, but the difference was large at an individual level.ConclusionSelf-reported home-to-work data overestimated both trip duration and trip distance compared to GPS data. Significant differences in PAH exposure estimates were observed at individual level using self-reported vs. GPS data, which has important implications in air pollution epidemiological studies.

Retinol (ROL) and its biologically active metabolite, all-trans retinoic acid (ATRA), are essential for a number of reproductive processes. However, there is a paucity of information regarding their roles in ovarian folliculogenesis, oocyte maturation, and early embryogenesis. The objectives of this study were to quantify and compare peripheral plasma (PP) and follicular fluid (FF) retinoid levels, including ATRA in women undergoing in vitro fertilization (IVF) and to investigate the relationship between retinoid levels and embryo quality. Retinoid levels were evaluated in PP and FF from 79 women undergoing IVF at the time of oocyte retrieval and corresponding embryo quality assessed on a daily basis after retrieval for 3 days until uterine transfer. Analysis compared the retinoid levels with day 3 embryo grades and between endometriosis versus control patients. Results demonstrated distinctive levels of retinoid metabolites and isomers in FF versus PP. There was a significantly larger percentage of high-quality grade I embryos derived from the largest versus smallest follicles. An increase in follicle size also correlated with a >50% increase in FF ROL and ATRA concentrations. Independent of follicle size, FF yielding grade I versus nongrade I embryos showed higher mean levels of ATRA but not ROL. In a nested case-control analysis, control participants had 50% higher mean levels of ATRA in their FF and PP than women with endometriosis. These findings strongly support the proposition that ATRA plays a fundamental role in oocyte development and quality, and that reduced ATRA synthesis may contribute to decreased fecundity of participants with endometriosis.

Background: Decreased heart rate variability (HRV) has been associated with future cardiac morbidity and mortality and is often used as a marker of altered cardiac autonomic balance in studies of health effects of airborne particulate matter. Fewer studies have evaluated associations between air pollutants and cardiac arrhythmia.Objectives: We examined relationships between cardiac arrhythmias, HRV, and exposures to airborne particulate matter.Methods: We measured HRV and arrhythmia with ambulatory electrocardiograms in a cohort panel study for up to 235 hr per participant among 50 nonsmokers with coronary artery disease who were ≥ 71 years of age and living in four retirement communities in the Los Angeles, California, Air Basin. Exposures included hourly outdoor gases, hourly traffic-related and secondary organic aerosol markers, and daily size-fractionated particle mass. We used repeated measures analyses, adjusting for actigraph-derived physical activity and heart rate, temperature, day of week, season, and community location.Results: Ventricular tachycardia was significantly increased in association with increases in markers of traffic-related particles, secondary organic carbon, and ozone. Few consistent associations were observed for supraventricular tachycardia. Particulates were significantly associated with decreased ambulatory HRV only in the 20 participants using ACE (angiotensin I–converting enzyme) inhibitors.Conclusions: Although these data support the hypothesis that particulate exposures may increase the risk of ventricular tachycardia for elderly people with coronary artery disease, HRV was not associated with exposure in most of our participants. These results are consistent with previous findings in this cohort for systemic inflammation, blood pressure, and ST segment depression.Citation: Bartell SM, Longhurst J, Tjoa T, Sioutas C, Delfino RJ. 2013. Particulate air pollution, ambulatory heart rate variability, and cardiac arrhythmia in retirement community residents with coronary artery disease. Environ Health Perspect 121:1135–1141; http://dx.doi.org/10.1289/ehp.1205914

BackgroundBoth targeted decolonization and universal decolonization of patients in intensive care units (ICUs) are candidate strategies to prevent health care-associated infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA).MethodsWe conducted a pragmatic, cluster-randomized trial. Hospitals were randomly assigned to one of three strategies, with all adult ICUs in a given hospital assigned to the same strategy. Group 1 implemented MRSA screening and isolation; group 2, targeted decolonization (i.e., screening, isolation, and decolonization of MRSA carriers); and group 3, universal decolonization (i.e., no screening, and decolonization of all patients). Proportional-hazards models were used to assess differences in infection reductions across the study groups, with clustering according to hospital.ResultsA total of 43 hospitals (including 74 ICUs and 74,256 patients during the intervention period) underwent randomization. In the intervention period versus the baseline period, modeled hazard ratios for MRSA clinical isolates were 0.92 for screening and isolation (crude rate, 3.2 vs. 3.4 isolates per 1000 days), 0.75 for targeted decolonization (3.2 vs. 4.3 isolates per 1000 days), and 0.63 for universal decolonization (2.1 vs. 3.4 isolates per 1000 days) (P=0.01 for test of all groups being equal). In the intervention versus baseline periods, hazard ratios for bloodstream infection with any pathogen in the three groups were 0.99 (crude rate, 4.1 vs. 4.2 infections per 1000 days), 0.78 (3.7 vs. 4.8 infections per 1000 days), and 0.56 (3.6 vs. 6.1 infections per 1000 days), respectively (P

ObjectiveWe sought to identify hospital characteristics associated with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) carriage among inpatients.Design Prospective cohort study.Setting Orange County, California.Participants Thirty hospitals in a single county.Methods We collected clinical MRSA isolates from inpatients in 30 of 31 hospitals in Orange County, California, from October 2008 through April 2010. We characterized isolates by spa typing to identify CA-MRSA strains. Using California's mandatory hospitalization data set, we identified hospital-level predictors of CA-MRSA isolation.Results CA-MRSA strains represented 1,033 (46%) of 2,246 of MRSA isolates. By hospital, the median percentage of CA-MRSA isolates was 46% (range, 14%-81%). In multivariate models, CA-MRSA isolation was associated with smaller hospitals (odds ratio [OR], 0.97, or 3% decreased odds of CA-MRSA isolation per 1,000 annual admissions; P < .001, hospitals with more Medicaid-insured patients (OR, 1.2; P = .002), and hospitals with more patients with low comorbidity scores (OR, 1.3; P < .001). Results were similar when restricted to isolates from patients with hospital-onset infection.Conclusions Among 30 hospitals, CA-MRSA comprised nearly half of MRSA isolates. There was substantial variability in CA-MRSA penetration across hospitals, with more CA-MRSA in smaller hospitals with healthier but socially disadvantaged patient populations. Additional research is needed to determine whether infection control strategies can be successful in targeting CA-MRSA influx.

The economic impact of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) remains unclear. We developed an economic simulation model to quantify the costs associated with CA-MRSA infection from the societal and third-party payer perspectives. A single CA-MRSA case costs third-party payers $2277-$3200 and society $7070-$20 489, depending on patient age. In the United States (US), CA-MRSA imposes an annual burden of $478 million to 2.2 billion on third-party payers and $1.4-13.8 billion on society, depending on the CA-MRSA definitions and incidences. The US jail system and Army may be experiencing annual total costs of $7-11 million ($6-10 million direct medical costs) and $15-36 million ($14-32 million direct costs), respectively. Hospitalization rates and mortality are important cost drivers. CA-MRSA confers a substantial economic burden on third-party payers and society, with CA-MRSA-attributable productivity losses being major contributors to the total societal economic burden. Although decreasing transmission and infection incidence would decrease costs, even if transmission were to continue at present levels, early identification and appropriate treatment of CA-MRSA infections before they progress could save considerable costs.

Oral premalignancy serves as an ideal model for study of chemopreventive agents. Although 13-cis-retinoic acid showed reversal of oral premalignancy, toxicity, and reversal of clinical response after cessation of therapy obviated its widespread use. A search for nontoxic agents with cancer preventive activity led us to evaluate Bowman Birk Inhibitor (BBI) formulated as BBI Concentrate (BBIC). We previously reported encouraging results in a phase IIa trial of BBIC in patients with oral leukoplakia with measurable clinical responses and favorable biomarker changes. On the basis of these results, we undertook a randomized, placebo controlled phase IIb trial with patients receiving BBIC or placebo for 6 months, with assessment of clinical response and change in lesion area as primary end point and an intent-to-treat analysis. One hundred and thirty two subjects were randomized; and 89 subjects completed six months on study drug or placebo. Both placebo and BBIC showed a statistically significant decrease in mean lesion area of 17.1% and 20.6%, respectively, and partial or greater clinical responses of 30% and 28% respectively. No significant difference between placebo and study drug arms was observed. Histologic review, review of photographs of lesions, and comparison of serum neu protein and oral mucosal cell protease activity also did not show significant differences between study arms. Probable reasons for these negative results were considered, are discussed, and include a placebo with non-BBIC clinical activity and reduced pharmacokinetic availability of the second batch of BBIC. This experience should be a strong cautionary note to those considering "Green" chemoprevention.

The polyamine-inhibitory regimen difluoromethylornithine (DFMO)+sulindac has marked efficacy in preventing metachronous colorectal adenomas. Polyamines are synthesised endogenously and obtained from dietary sources. Here we investigate dietary polyamine intake and outcomes in the DFMO+sulindac colorectal adenoma prevention trial.Dietary polyamine data were available for 188 of 267 patients completing the study. Total dietary polyamine content was derived by the sum of dietary putrescine, spermine and spermidine values and categorised into two groups: highest (>75-100%) vs the lower three quartiles (0-25, 25-50 and 50-75%). Baseline tissue polyamine concentration and ODC1 genotype were determined. Logistic regression models were used for risk estimation.A significant interaction was detected between dietary polyamine group and treatment with regard to adenoma recurrence (P=0.012). Significant metachronous adenoma risk reduction was observed after DFMO+sulindac treatment in dietary polyamine quartiles 1-3 (risk ratio (RR) 0.19; 95% confidence interval (CI) 0.08-0.42; P

Exposure to air pollution is frequently associated with reductions in birth weight but results of available studies vary widely, possibly in part because of differences in air pollution metrics. Further insight is needed to identify the air pollution metrics most strongly and consistently associated with birth weight.We used a hospital-based obstetric database of more than 70,000 births to study the relationships between air pollution and the risk of low birth weight (LBW,

BackgroundCentral line-associated bloodstream infection (CLABSI) is a national target for mandatory reporting and a Centers for Medicare and Medicaid Services target for value-based purchasing. Differences in chart review versus claims-based metrics used by national agencies and groups raise concerns about the validity of these measures.ObjectiveEvaluate consistency and reasons for discordance among chart review and claims-based CLABSI events.MethodsWe conducted 2 multicenter retrospective cohort studies within 6 academic institutions. A total of 150 consecutive patients were identified with CLABSI on the basis of National Healthcare Safety Network (NHSN) criteria (NHSN cohort), and an additional 150 consecutive patients were identified with CLABSI on the basis of claims codes (claims cohort). All events had full-text medical record reviews and were identified as concordant or discordant with the other metric.ResultsIn the NHSN cohort, there were 152 CLABSIs among 150 patients, and 73.0% of these cases were discordant with claims data. Common reasons for the lack of associated claims codes included coding omission and lack of physician documentation of bacteremia cause. In the claims cohort, there were 150 CLABSIs among 150 patients, and 65.3% of these cases were discordant with NHSN criteria. Common reasons for the lack of NHSN reporting were identification of non-CLABSI with bacteremia meeting Centers for Disease Control and Prevention (CDC) criteria for an alternative infection source.ConclusionSubstantial discordance between NHSN and claims-based CLABSI indicators persists. Compared with standardized CDC chart review criteria, claims data often had both coding omissions and misclassification of non-CLABSI infections as CLABSI. Additionally, claims did not identify any additional CLABSIs for CDC reporting. NHSN criteria are a more consistent interhospital standard for CLABSI reporting.

ObjectiveTo assess the ability of Medicare claims to identify US hospitals with high rates of surgical site infection (SSI) after hip arthroplasty.DesignRetrospective cohort study.SettingAcute care US hospitals.ParticipantsFee-for-service Medicare patients 65 years of age and older who underwent hip arthroplasty in US hospitals from 2005 through 2007.MethodsHospital rankings were derived from claims codes suggestive of SSI, adjusted for age, sex, and comorbidities, while using generalized linear mixed models to account for hospital volume. Medical records were obtained for validation of infection on a random sample of patients from hospitals ranked in the best and worst deciles of performance. We then calculated the risk-adjusted odds of developing a chart-confirmed SSI after hip arthroplasty in hospitals ranked by claims into worst- versus best-performing deciles.ResultsAmong 524,892 eligible Medicare patients who underwent hip arthroplasty at 3,296 US hospitals, a patient who underwent surgery in a hospital ranked in the worst-performing decile based on claims-based evidence of SSI had 2.9-fold higher odds of developing a chart-confirmed SSI relative to a patient with the same age, sex, and comorbidities in a hospital ranked in the best-performing decile (95% confidence interval, 2.2-3.7).ConclusionsMedicare claims successfully distinguished between hospitals with high and low SSI rates following hip arthroplasty. These claims can identify potential outlier hospitals that merit further evaluation. This strategy can also be used to validate the completeness of public reporting of SSI.

Chlorhexidine and mupirocin are used in health care facilities to eradicate methicillin-resistant Staphylococcus aureus (MRSA) carriage. The objective of this study was to assess the frequency of chlorhexidine and mupirocin resistance in isolates from nares carriers in multiple nursing homes and to examine characteristics associated with resistance. Nasal swab samples were collected from approximately 100 new admissions and 100 current residents in 26 nursing homes in Orange County, CA, from October 2008 to May 2011. MRSA isolates were tested for susceptibility by using broth microdilution, disk diffusion, and Etest; for genetic relatedness using pulsed-field gel electrophoresis; and for qac gene carriage by PCR. Characteristics of the nursing homes and their residents were collected from the Medicare Minimum Data Set and Long-Term Care Focus. A total of 829 MRSA isolates were obtained from swabbing 3,806 residents in 26 nursing homes. All isolates had a chlorhexidine MIC of ≤4 μg/ml. Five (0.6%) isolates harbored the qacA and/or qacB gene loci. Mupirocin resistance was identified in 101 (12%) isolates, with 78 (9%) isolates exhibiting high-level mupirocin resistance (HLMR). HLMR rates per facility ranged from 0 to 31%. None of the isolates with HLMR displayed qacA or qacB, while two isolates carried qacA and exhibited low-level mupirocin resistance. Detection of HLMR was associated with having a multidrug-resistant MRSA isolate (odds ratio [OR], 2.69; P = 0.004), a history of MRSA (OR, 2.34; P < 0.001), and dependency in activities of daily living (OR, 1.25; P = 0.004). In some facilities, HLMR was found in nearly one-third of MRSA isolates. These findings may have implications for the increasingly widespread practice of MRSA decolonization using intranasal mupirocin.

The purpose of this paper was to examine the longitudinal effects of psychological sense of control and control-related coping strategies on breast cancer outcomes. Utilizing the California Cancer Registry, follow-up data on cancer recurrence and all-cause mortality were obtained for 54 of 58 women originally diagnosed with breast cancer in 1992 to 1994. Relationships between cancer outcomes and psychological control and mood at 4 and 8 months post-diagnosis were examined. Results of the study showed that a greater sense of control at 8 months was associated with less cancer recurrence, while higher desire for control at both 4 and 8 months was associated with greater likelihood of recurrence. Utilization of an accepting mode of control appeared to mitigate the negative effects of desire for control on recurrence. No significant relationships were observed between mood and mortality or recurrence. These findings suggest the potential value of examining psychological control and control-related coping on cancer outcomes in future epidemiological and clinical studies.

Chemoprevention with the polyamine-inhibitory regimen difluoromethylornithine (DFMO) + sulindac markedly reduces risk of recurrent adenoma in colorectal adenoma patients. Obesity is associated with risk of colorectal adenoma and colorectal cancer. This study investigates how obesity influences risk of recurrent adenoma after prolonged treatment with DFMO + sulindac versus placebo.Our analysis included subjects enrolled in the phase III colorectal adenoma prevention clinical trial investigating DFMO + sulindac versus placebo. Patients were classified by obesity (body mass index, BMI ≥ 30 kg/m(2)) status at baseline. Pearson χ(2) statistic and Mann-Whitney U test were used to compare baseline characteristics, including rectal tissue polyamine levels. Log-binomial regression analysis was used to determine the risk ratio (RR) of recurrent adenomas, adjusted for covariates and an interaction term for obesity and treatment.The final analytic cohort was comprised of 267 patients. In separate regression models, the risk of adenoma recurrence after treatment compared to placebo was similar for obese (RR = 0.32, 95 % CI 15-71) and non-obese patients (RR = 0.27, 95 % CI 15-49). No significant interaction was detected between obesity, treatment, and risk of colorectal adenoma in the full regression model (p (interaction) = 0.91).Obesity does not substantially modify the colorectal adenoma risk reduction ascribed to DFMO + sulindac versus placebo.