Risk factors for transmission of carbapenem-resistant Enterobacterales to healthcare personnel gloves and gowns in the USA.

BACKGROUND: Hospitals are sources for acquisition of carbapenem-resistant Entero-bacterales (CRE), and it is believed that the contamination of healthcare personnel (HCP) hands and clothing play a major role in patient-to-patient transmission of antibiotic-resistant bacteria. AIM: The aim of this study was to determine which HCP types, HCP-patient interactions, and patient characteristics are associated with greater transmission of CRE to HCP gloves and gowns in the hospital. METHODS: This was a prospective observational cohort study that enrolled patients with recent surveillance or clinical cultures positive for CRE at five hospitals in four states in the USA. HCP gloves and gown were cultured after patient care. Samples were also obtained from patients' stool, perianal area, and skin of the chest and arm to assess bacterial burden. FINDINGS: Among 313 CRE-colonized patients and 3070 glove and gown cultures obtained after patient care, HCP gloves and gowns were found to be contaminated with CRE 7.9% and 4.3% of the time, respectively. Contamination of either gloves or gowns occurred in 10.0% of interactions. Contamination was highest (15.3%) among respiratory therapists (odds ratio: 3.79; 95% confidence interval: 1.61-8.94) and when any HCP touched the patient (1.52; 1.10-2.12). Associations were also found between CRE transmission to HCP gloves or gown and: being in the intensive care unit, having a positive clinical culture, and increasing bacterial burden on the patient. CONCLUSION: CRE transmission to HCP gloves and gown occurred frequently. These findings may inform evidence-based policies about what situations and for which patients contact precautions are most important.

EDTA-Modified Carbapenem Inactivation Method: a Phenotypic Method for Detecting Metallo-ß-Lactamase-Producing Enterobacteriaceae.

The increase in the prevalence and impact of infections caused by carbapenemase-producing Enterobacteriaceae is a global health concern. Therefore, rapid and accurate methods to detect these organisms in any clinical microbiology laboratory, including those in resource-limited settings, are essential to prevent and contain their spread. It is also important to differentiate between serine- and metal-dependent carbapenemases elaborated by carbapenemase-producing isolates for epidemiologic, infection control and prevention, and therapeutic purposes. Here, we describe the development and evaluation of the EDTA-modified carbapenem inactivation method (eCIM), an assay for discriminating between serine- and metal-dependent (i.e., metallo-ß-lactamases [MBLs]) carbapenemases when used in conjunction with the modified carbapenem inactivation method (mCIM). The eCIM had an overall sensitivity and specificity of 100% and was adopted by the Clinical and Laboratory Standards Institute as a method to use in combination with the mCIM to identify MBL-producing Enterobacteriaceae.

Validation of an Antimicrobial Stewardship-Driven Verigene Blood-Culture Gram-Negative Treatment Algorithm to Improve Appropriateness of Antibiotics.

Rapid diagnostic testing (RDT) allows for early adjustment of antibiotic therapy. This study examined the potential impact of a stewardship-driven antibiotic treatment algorithm, incorporating RDT into the management of Gram-negative bacteremia. The proposed algorithm would have resulted in 88.4% of cases receiving appropriate antibiotic therapy versus 78.1% by standard of care (P = .014).

Long-term efficacy and safety of adjunctive extended-release oxcarbazepine (Oxtellar XR® ) in adults with partial-onset seizures.

OBJECTIVE: To evaluate long-term outcomes of adjunctive therapy with SPN-804 (Oxtellar XR® , Supernus Pharmaceuticals), an extended-release tablet formulation of oxcarbazepine (OXC), in adults with refractory partial-onset seizures. METHODS: After completing a 16-week double-blind, placebo-controlled trial of SPN-804 at fixed dosages (1200 or 2400 mg QD), patients entering this open-label extension study were converted in blinded fashion to 1200 mg QD SPN-804 as a target starting dose for long-term treatment. Patients were followed for 1 year, during which SPN-804 dosages could be adjusted up to 2400 mg/day according to clinical response. RESULTS: Of 214 patients, 84% completed 1-year open-label treatment. Median maintenance SPN-804 dosage was 1200 mg; <10% of patients required 2400 mg. Median 28-day seizure frequency reduction from baseline was 59%; seizure frequency was reduced ≥50% in 58% of patients; 11% were seizure free ≥6 months; and 5% were seizure free ≥1 year. SPN-804 was discontinued due to adverse events in 5% (n = 10). Incidences of each of the most common adverse events (dizziness, headache, diplopia, nausea, vomiting, balance disorder, blurred vision) were ≤15% during 1-year follow-up and occurred most frequently in patients previously naïve to SPN-804. No new safety signals, no clinically significant changes in health status, and no deaths attributable to SPN-804 were observed. CONCLUSION: SPN-804 administered once daily for 1 year was effective as adjunctive therapy in improving seizure control and maintaining therapeutic response in adults with refractory partial-onset seizures. With dosage flexibility, SPN-804 was well tolerated.

Molecular epidemiology of Staphyloccocus aureus colonization in the Old Order of Amish of Lancaster County, Pennsylvania, USA.

Transmission of Staphylococcus aureus colonization in community-based populations is not well understood. We sought to describe the molecular epidemiology of S. aureus colonization in the Old Order Amish. The study was a prospective, observational study of healthy adults and their same-sex siblings who were cultured from the anterior nares twice. S. aureus isolates were characterized using spa typing. Overall, 40% (159/398) of the study population was colonized with S. aureus. There were 84 spa types with the most abundant spa types being t012 (13%) and t021 (7%). There was no clustering of spa types within sibling groups; however, there was clustering within households. There were 111 S. aureus-colonized participant pairs living within the same household. Of these, 47% had concordant spa types. The diversity of spa types across a relatively isolated, genetically homogenous population with a similar lifestyle is striking. Taken together this suggests that S. aureus transmission is a local phenomenon limited to very close contact.

Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy, tolerability, and safety of once-daily 1200 mg and 2400 mg SPN-804 (Oxtellar XR™, Supernus Pharmaceuticals), an extended-release tablet formulation of oxcarbazepine (OXC), added to 1-3 concomitant antiepileptic drugs (AEDs) in adults with refractory partial-onset seizures, with or without secondary generalization. METHODS: The Prospective, Randomized Study of OXC XR in Subjects with Partial Epilepsy Refractory (PROSPER) study was a multinational, randomized, double-blind, parallel-group Phase 3 study. The primary efficacy endpoint was median percent reduction from baseline in monthly (28-day) seizure frequency for the 16-week double-blind treatment period in the intent-to-treat (ITT) population with analyzable seizure data. Other efficacy analyses included proportion of patients with ≥ 50% seizure reduction, proportion of patients seizure free, and the relationship between clinical response and plasma concentration. RESULTS: Median percent reduction was -28.7% for placebo, -38.2% (P = 0.08 vs placebo) for once-daily SPN-804 1200 mg, and -42.9% (P = 0.003) for SPN-804 2400 mg. Responder rates were 28.1%, 36.1% (P = 0.08), and 40.7% (P = 0.02); 16-week seizure-free rates in a pragmatic ITT analysis were 3.3%, 4.9% (P = 0.59), and 11.4% (P = 0.008), respectively. When data were analyzed separately for study site clusters, a post hoc analysis demonstrated that both SPN-804 dosages were significantly superior to placebo in median percent seizure reduction (placebo: -13.3%; 1200 mg: -34.5%, P = 0.02; 2400 mg: -52.7%, P = 0.006) in the North American study site cluster. A concentration-response analysis also supported a clinically meaningful effect for 1200 mg. Adverse event types reflected the drug's established profile. Adverse event frequency was consistent with a pharmacokinetic profile in which SPN-804 produces lower peak plasma concentrations vs immediate-release OXC. Once-daily dosing was not associated with any new safety signals. CONCLUSIONS: Adjunctive once-daily SPN-804 improved seizure control in patients with inadequately controlled partial-onset seizures. Adverse event occurrence and discontinuations due to adverse events suggest improved tolerability vs previously published data with immediate-release OXC.

Methods and recommendations for evaluating and reporting a new diagnostic test.

No standardized guidelines exist for the biostatistical methods appropriate for studies evaluating diagnostic tests. Publication recommendations such as the STARD statement provide guidance for the analysis of data, but biostatistical advice is minimal and application is inconsistent. This article aims to provide a self-contained, accessible resource on the biostatistical aspects of study design and reporting for investigators. For all dichotomous diagnostic tests, estimates of sensitivity and specificity should be reported with confidence intervals. Power calculations are strongly recommended to ensure that investigators achieve desired levels of precision. In the absence of a gold standard reference test, the composite reference standard method is recommended for improving estimates of the sensitivity and specificity of the test under evaluation.

Comparison of culture media for detection of Acinetobacter baumannii in surveillance cultures of critically-ill patients.

The objective of this study was to evaluate the performance of CHROMagar Acinetobacter when compared to sheep blood agar, MacConkey agar and MacConkey agar with 6 µg/ml of imipenem for the detection of A. baumannii in surveillance cultures of hospitalized patients. We utilized peri-anal swabs and sputum samples from patients admitted to the University of Maryland Medical Center ICUs from December 7 through December 21, 2009. Samples were plated onto four media in the following order: (1) 5% sheep blood agar (SBA), (2) MacConkey agar, (3) MacConkey agar with 6 µg/ml of imipenem, and (4) CHROMagar Acinetobacter (CHROMagar). SBA was the gold standard to which all media was compared. There were 165 samples collected during the study period. SBA and CHROMagar detected 18 of 18 (100%) Acinetobacter and 11 of 11 (100%) MDR-A. baumannii. MacConkey agar detected 16 of 18 (89%) Acinetobacter and 10 of 11 (91%) MDR- A. baumannii while MacConkey agar with 6 µg/ml imipenem detected 9 of 11 (82%) MDR-A. baumannii. CHROMagar did not differentiate MDR- A. baumannii from non-MDR-A. baumannii. CHROMagar may be useful for rapid detection of patients with MDR-A. baumannii if improved upon to better select for MDR-A. baumannii.

Genome-wide association study of recurrent early-onset major depressive disorder.

A genome-wide association study was carried out in 1020 case subjects with recurrent early-onset major depressive disorder (MDD) (onset before age 31) and 1636 control subjects screened to exclude lifetime MDD. Subjects were genotyped with the Affymetrix 6.0 platform. After extensive quality control procedures, 671 424 autosomal single nucleotide polymorphisms (SNPs) and 25 068 X chromosome SNPs with minor allele frequency greater than 1% were available for analysis. An additional 1 892 186 HapMap II SNPs were analyzed based on imputed genotypic data. Single-SNP logistic regression trend tests were computed, with correction for ancestry-informative principal component scores. No genome-wide significant evidence for association was observed, assuming that nominal P<5 × 10(-8) approximates a 5% genome-wide significance threshold. The strongest evidence for association was observed on chromosome 18q22.1 (rs17077540, P=1.83 × 10(-7)) in a region that has produced some evidence for linkage to bipolar-I or -II disorder in several studies, within an mRNA detected in human brain tissue (BC053410) and approximately 75 kb upstream of DSEL. Comparing these results with those of a meta-analysis of three MDD GWAS data sets reported in a companion article, we note that among the strongest signals observed in the GenRED sample, the meta-analysis provided the greatest support (although not at a genome-wide significant level) for association of MDD to SNPs within SP4, a brain-specific transcription factor. Larger samples will be required to confirm the hypothesis of association between MDD (and particularly the recurrent early-onset subtype) and common SNPs.

Hand-off education and evaluation: piloting the observed simulated hand-off experience (OSHE).

AIM: The Observed Simulated Hand-off Experience (OSHE) was created to evaluate medical students' sign-out skills using a real-time assessment tool, the Hand-off CEX. SETTING: Thirty-two 4th year medical students participated as part of an elective course. PROGRAM DESCRIPTION: One week following an interactive workshop where students learned effective hand-off strategies, students participated in an experience in which they performed a hand-off of a mock patient using simulated history and physical examination data and a brief video. PROGRAM EVALUATION: Internal medicine residents served as standardized hand-off receivers and were trained on expectations. Students were provided feedback using a newly developed Hand-off CEX, based on the "Mini-CEX," which rates overall hand-off performance and its components on a 9-point Likert-type scale. Outcomes included performance ratings and pre- and post-student self-assessments of hand-off preparedness. Data were analyzed using Wilcoxon signed-rank tests and descriptive statistics. Resident receivers rated overall student performance with a mean score of 6.75 (range 4-9, maximum 9). Statistically significant improvement was observed in self-perceived preparedness for performing an effective hand-off (67% post- vs. 27% pre-reporting 'well-prepared,' p<0.009). DISCUSSION: This brief, standardized hand-off training exercise improved students' confidence and was rated highly by trained observers. Future work focuses on formal validation of the Hand-off CEX instrument. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11606-009-1170-y) contains supplementary material, which is available to authorized users.

Interactions between endothelial cells and electrospun methacrylic terpolymer fibers for engineered vascular replacements.

A compliant terpolymer made of hexylmethacrylate (HMA), methylmethacrylate (MMA), and methacrylic acid (MAA) intended for use in small diameter vascular graft applications has been developed. The mechanical properties and in vitro biostability of this terpolymer have been previously characterized. The goal of this investigation was to examine the interactions between endothelial cells and the new terpolymer and to evaluate endothelial cell function. Electrospinning was used to produce both oriented and random terpolymer fiber scaffolds. Smooth solution cast films and tissue culture polystyrene were used as negative and positive controls, respectively. Human blood outgrowth endothelial cells and human umbilical vein endothelial cells were incubated with the test and control samples and characterized with respect to initial cell attachment, proliferation, viability, and maintenance of the endothelial cell phenotype. It was found that the terpolymer is cytocompatible allowing endothelial cell growth, with random fibers being more effective in promoting enhanced cellular activities than oriented fibers. In addition, endothelial cells cultured on these substrates appeared to maintain their phenotype. The results from this study demonstrate that electrospun HMA:MMA:MAA terpolymer has the potential to be used successfully in fabricating small diameter blood vessel replacements.

Resident uncertainty in clinical decision making and impact on patient care: a qualitative study.

BACKGROUND: Little is known regarding how internal medicine residents manage uncertainty during decision making and subsequent effects on patient care. The aims of this study were to describe types of uncertainty faced by residents, strategies employed to manage uncertainty and effects on patient care. METHODS: Using critical incident technique, residents were asked to recall important clinical decisions during a recent call night, with probes to identify decisions made during uncertainty. They were also asked to report who they approached for advice. Three authors independently coded transcripts using the constant comparative method. RESULTS: The 42/50 (84%) interviewed residents reported 18 discrete critical incidents. Six categories emerged and mapped to the domains of the Beresford Model of Clinical Uncertainty: technical uncertainty (procedural skills, knowledge of indications); conceptual uncertainty (care transitions, diagnostic decision making and management conflict) and personal uncertainty (goals of care). In managing uncertainty, residents report a "hierarchy of assistance", using colleagues and literature for initial management, followed by senior residents, specialty fellows and, finally, the attending physician. Barriers to seeking the attending physician's input included the existence of a defined hierarchy for assistance and fears of losing autonomy, revealing knowledge gaps, and "being a bother". For 12 of the 18 cases reported, patient care was compromised: delay in procedure or escalation of care (n = 8); procedural complications (n = 2); and cardiac arrest (n = 2). CONCLUSION: Resident uncertainty results in delays of indicated care and, in some cases, patient harm. Despite the presence of a supervisory figure, residents adhere to a hierarchy when seeking advice in clinical matters.

A theoretical framework and competency-based approach to improving handoffs.

BACKGROUND: Once characterised by remarkable continuity of care by a familiar doctor, patient care today is delivered by multiple physicians with varying degrees of knowledge of the patient. Yet, few trainees learn the potential risks of these transitions and the strategies to improve patient care during handoffs. Little is known regarding the mechanisms by which handoffs affect patient care. RESULTS: Building on theoretical constructs from the social sciences and illustrated with a case study of the implementation of a night float service for the inpatient general medicine services at the University of Chicago, a conceptual framework is proposed to describe how handoffs affect both patients and physicians. CONCLUSION: Using this conceptual framework, recommendations are made for formal education based on the core competencies of communication and professionalism. Opportunities to educate trainees in acquiring these skills are described in the context of handoffs of patient care.

Rhodotorula glutinis fungemia in a liver-kidney transplant patient.

A 54-year-old man underwent simultaneous liver-kidney transplantation. During his prolonged hospitalization, he developed catheter-related fungemia with Rhodotorula glutinis and azole-resistant Candida glabrata. Management of the Rhodotorula fungemia was complicated by his renal insufficiency, hepatic insufficiency, and the concurrent fungemia with multi-azole resistant C. glabrata. He was treated with combination therapy with voriconazole and micafungin with subsequent clearance of the fungemia. Rhodotorula species are emerging as human pathogens with the increasing number of immunosuppressed patients in the last few decades. This is the first report of a R. glutinis fungemia in a solid organ transplant recipient.

Patient-to-patient transmission is important in extended-spectrum beta-lactamase-producing Klebsiella pneumoniae acquisition.

We performed a prospective cohort study to quantify the number of cases of patient-to-patient transmission of extended-spectrum beta-lactamase-producing Klebsiella species on perianal surveillance culture. Among 27 patients who acquired Klebsiella pneumoniae infection, 14 had infections (52%) that were due to patient-to-patient transmission, and 6 (22%) had a subsequent positive extended-spectrum beta-lactamase clinical culture results.

The prevalence of occult obstetric anal sphincter injury following childbirth--literature review.

OBJECTIVE: To calculate the published prevalence of ultrasound-detected occult anal sphincter damage associated with different modes of delivery. METHODS: A search of the English language literature for articles using keywords describing the prevalence of ultrasound-diagnosed anal sphincter injury following childbirth. The weighted mean prevalence of occult anal sphincter injury was calculated in the following groups: (1) primiparous women (unselected); (2) primiparous women after an unassisted normal vaginal delivery; (3) multiparous women (unselected); (4) following forceps delivery; (5) following ventouse delivery; (6) following cesarean section. RESULTS: Nineteen articles described ultrasound-diagnosed occult anal sphincter injury. The prevalence in unselected primiparous women (excluding cesarean section) was 29.2% (288/983). After unassisted vaginal delivery in primiparae the prevalence was 21.7% (74/341). The incidence in multiparous women (unselected) is 32.3% (107/331); following forceps delivery 49.1% (131/267) and with ventouse delivery it is 45.2% (66/146). Only one woman (in 173 cases) had anal sphincter injury following cesarean section. CONCLUSIONS: After a review of the literature, occult anal sphincter injury is mostly associated with the first vaginal delivery and is particularly high following instrumental deliveries. Ventouse is less traumatic than forceps. Cesarean section is protective to the anal sphincter.

Cognitive and motor assessment in autopsy-proven corticobasal degeneration.

OBJECTIVE: To investigate the clinical features of autopsy-proven corticobasal degeneration (CBD). METHODS: We evaluated symptoms, signs, and neuropsychological deficits longitudinally in 15 patients with autopsy-proven CBD and related these observations directly to the neuroanatomic distribution of disease. RESULTS: At presentation, a specific pattern of cognitive impairment was evident, whereas an extrapyramidal motor abnormality was present in less than half of the patients. Follow-up examination revealed persistent impairment of apraxia and executive functioning, worsening language performance, and preserved memory. The motor disorder emerged and worsened as the condition progressed. Statistical analysis associated cognitive deficits with tau-immunoreactive pathology that is significantly more prominent in frontal and parietal cortices and the basal ganglia than temporal neocortex and the hippocampus. CONCLUSION: The clinical diagnosis of corticobasal degeneration should depend on a specific pattern of impaired cognition as well as an extrapyramidal motor disorder, reflecting the neuroanatomic distribution of disease in frontal and parietal cortices and the basal ganglia.

The prevalence of emotional abuse in gynaecology patients and its association with gynaecological symptoms.

AIM: To determine the lifetime prevalence of emotional abuse in a population of women attending a gynaecology outpatient clinic and also to investigate whether women who reported emotional abuse were more likely to complain of certain gynaecological symptoms. SETTING: A gynaecology outpatient clinic in a North of England Hospital. METHODS: Anonymous confidential questionnaire given to women. RESULTS: Nine hundred and twenty consecutive women were included, 825 questionnaires were returned (90% response rate). The prevalence of emotional abuse was 24% (198/825). Emotional abuse is four times less common in women over 50 years old. Of the fifteen presenting symptoms reported by the women, referral for termination of pregnancy, cervical smear abnormality, worry about cancer and urinary incontinence were significantly more common in the group who reported emotional abuse. The women with emotional abuse also had significantly more consultations; however, the duration of their symptoms was not significantly different. CONCLUSION: The prevalence of emotional abuse in a group of women attending the gynaecology outpatient clinic in a North of England Hospital was 24%. Women who are subjected to emotional abuse tend to have more consultations and are more likely to complain of certain symptoms.

Distinct MRI atrophy patterns in autopsy-proven Alzheimer's disease and frontotemporal lobar degeneration.

To better define the anatomic distinctions between Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), we retrospectively applied voxel-based morphometry to the earliest magnetic resonance imaging scans of autopsy-proven AD (N = 11), FTLD (N = 18), and controls (N = 40). Compared with controls, AD patients showed gray matter reductions in posterior temporoparietal and occipital cortex; FTLD patients showed atrophy in medial prefrontal and medial temporal cortex, insula, hippocampus, and amygdala; and patients with both disorders showed atrophy in dorsolateral and orbital prefrontal cortex and lateral temporal cortex (P(FWE-corr) < .05). Compared with FTLD, AD patients had decreased gray matter in posterior parietal and occipital cortex, whereas FTLD patients had selective atrophy in anterior cingulate, frontal insula, subcallosal gyrus, and striatum (P < .001, uncorrected). These findings suggest that AD and FTLD are anatomically distinct, with degeneration of a posterior parietal network in AD and degeneration of a paralimbic fronto-insular-striatal network in FTLD.

Understanding the complexity of redesigning care around the clinical microsystem.

The microsystem is an organizing design construct in which social systems cut across traditional discipline boundaries. Because of its interdisciplinary focus, the clinical microsystem provides a conceptual and practical framework for simplifying complex organizations that deliver care. It also provides an important opportunity for organizational learning. Process mapping and microworld simulation may be especially useful for redesigning care around the microsystem concept. Process mapping, in which the core processes of the microsystem are delineated and assessed from the perspective of how the individual interacts with the system, is an important element of the continuous learning cycle of the microsystem and the healthcare organization. Microworld simulations are interactive computer based models that can be used as an experimental platform to test basic questions about decision making misperceptions, cause-effect inferences, and learning within the clinical microsystem. Together these tools offer the user and organization the ability to understand the complexity of healthcare systems and to facilitate the redesign of optimal outcomes.