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1.  Comparative Genomics of an IncA/C Multidrug Resistance Plasmid from Escherichia coli and Klebsiella Isolates from Intensive Care Unit Patients and the Utility of Whole-Genome Sequencing in Health Care Settings 
The IncA/C plasmids have been implicated for their role in the dissemination of β-lactamases, including gene variants that confer resistance to expanded-spectrum cephalosporins, which are often the treatment of last resort against multidrug-resistant, hospital-associated pathogens. A blaFOX-5 gene was detected in 14 Escherichia coli and 16 Klebsiella isolates that were cultured from perianal swabs of patients admitted to an intensive care unit (ICU) of the University of Maryland Medical Center (UMMC) in Baltimore, MD, over a span of 3 years. Four of the FOX-encoding isolates were obtained from subsequent samples of patients that were initially negative for an AmpC β-lactamase upon admission to the ICU, suggesting that the AmpC β-lactamase-encoding plasmid was acquired while the patient was in the ICU. The genomes of five E. coli isolates and six Klebsiella isolates containing blaFOX-5 were selected for sequencing based on their plasmid profiles. An ∼167-kb IncA/C plasmid encoding the FOX-5 β-lactamase, a CARB-2 β-lactamase, additional antimicrobial resistance genes, and heavy metal resistance genes was identified. Another FOX-5-encoding IncA/C plasmid that was nearly identical except for a variable region associated with the resistance genes was also identified. To our knowledge, these plasmids represent the first FOX-5-encoding plasmids sequenced. We used comparative genomics to describe the genetic diversity of a plasmid encoding a FOX-5 β-lactamase relative to the whole-genome diversity of 11 E. coli and Klebsiella isolates that carry this plasmid. Our findings demonstrate the utility of whole-genome sequencing for tracking of plasmid and antibiotic resistance gene distribution in health care settings.
PMCID: PMC4135983  PMID: 24914121
2.  How Doctors View and Use Social Media: A National Survey 
Doctors are uncertain of their ethical and legal obligations when communicating with patients online. Professional guidelines for patient-doctor interaction online have been written with limited quantitative data about doctors’ current usage and attitudes toward the medium. Further research into these trends will help to inform more focused policy and guidelines for doctors communicating with patients online.
The intent of the study was to provide the first national profile of Australian doctors’ attitudes toward and use of online social media.
The study involved a quantitative, cross-sectional online survey of Australian doctors using a random sample from a large representative database.
Of the 1500 doctors approached, 187 participated (12.47%). Most participants used social media privately, with only one-quarter not using any social media websites at all (48/187, 25.7%). One in five participants (30/155, 19.4%) had received a “friend request” from a patient. There was limited use of online communication in clinical practice: only 30.5% (57/187) had communicated with a patient through email and fewer than half (89/185, 48.1%) could offer their patients electronic forms of information if that were the patients’ preference. Three in five participants (110/181, 60.8%) reported not being uncomfortable about interacting with patients who had accessed personal information about them online, prior to the consultation. Most of the participants (119/181, 65.8%) were hesitant to immerse themselves more fully in social media and online communication due to worries about public access and legal concerns.
Doctors have different practices and views regarding whether or how to communicate appropriately with patients on the Internet, despite online and social media becoming an increasingly common feature of clinical practice. Additional training would assist doctors in protecting their personal information online, integrating online communication in patient care, and guidance on the best approach in ethically difficult online situations.
PMCID: PMC4275505  PMID: 25470407
social media; Internet; professional practice; health communication; ethics; health policy; patient-physician relations
3.  Major depressive disorder with melancholia displays robust alterations in resting state heart rate and its variability: implications for future morbidity and mortality 
Frontiers in Psychology  2014;5:1387.
Background: Major depressive disorder (MDD) is associated with increased heart rate and reductions in its variability (heart rate variability, HRV) – markers of future morbidity and mortality – yet prior studies have reported contradictory effects. We hypothesized that increases in heart rate and reductions in HRV would be more robust in melancholia relative to controls, than in patients with non-melancholia.
Methods: A total of 72 patients with a primary diagnosis of MDD (age M: 36.26, SE: 1.34; 42 females) and 94 controls (age M: 35.69, SE: 1.16; 52 females) were included in this study. Heart rate and measures of its variability (HRV) were calculated from two 2-min electrocardiogram recordings during resting state. Propensity score matching controlled imbalance on potential confounds between patients with melancholia (n = 40) and non-melancholia (n = 32) including age, gender, disorder severity, and comorbid anxiety disorders.
Results: MDD patients with melancholia displayed significantly increased heart rate and lower resting-state HRV (including the square root of the mean squared differences between successive N–N intervals, the absolute power of high frequency and standard deviation of the Poincaré plot perpendicular to the line of identity measures of HRV) relative to controls, findings associated with a moderate effect size (Cohens d’s = 0.56–0.58). Patients with melancholia also displayed an increased heart rate relative to those with non-melancholia (Cohen’s d = 0.20).
Conclusion: MDD patients with melancholia – but not non-melancholia – display robust increases in heart rate and decreases in HRV. These findings may underpin a variety of behavioral impairments in patients with melancholia including somatic symptoms, cognitive impairment, reduced responsiveness to the environment, and over the longer-term, morbidity and mortality.
PMCID: PMC4245890  PMID: 25505893
melancholia; non-melancholia; electrocardiogram; ECG; heart rate; heart rate variability; HRV; resting state
4.  Changes in Transfusion Practice Over Time in the Pediatric Intensive Care Unit 
Recent randomized clinical trials have shown the efficacy of a restrictive transfusion strategy in critically ill children. The impact of these trials on pediatric transfusion practice is unknown. Additionally, long-term trends in pediatric transfusion practice in the intensive care unit have not been described. We assessed transfusion practice over time, including the effect of clinical trial publication.
Single-center, retrospective observational study.
A 10-bed pediatric intensive care unit (PICU) in an urban academic medical center.
Critically ill, non-bleeding children between the ages of 3 days and 14 years old, admitted to the University of Maryland Medical Center PICU between January 1, 1998 and December 31, 2009, excluding those with congenital heart disease, hemolytic anemia, and hemoglobinopathies.
Measurements and Main Results
During the time period studied, 5327 patients met inclusion criteria. Of these, 335 received at least one red cell transfusion while in the PICU. The overall proportion transfused declined from 10.5% in 1998 to 6.8% in 2009 (p = 0.007). Adjusted for acuity, the likelihood of transfusion decreased by calendar year of admission. In transfused patients, the pre-transfusion hemoglobin level declined, from 10.5 g/dL to 9.3 g/dL, though these changes failed to meet statistical significance (p=0.09). Neonatal age, respiratory failure, shock, multi-organ dysfunction, and acidosis were associated with an increased likelihood of transfusion in both univariate and multivariable models.
The overall proportion of patients transfused between 1998 and 2009 decreased significantly. The magnitude of the decrease varied over time, and no additional change in transfusion practice occurred after the publication of a major pediatric clinical trial in 2007. Greater illness acuity and younger patient age were associated with an increased likelihood of transfusion.
PMCID: PMC4178535  PMID: 23962831
pediatrics; pediatric intensive care units; physicians practice patterns; erythrocyte transfusion; blood component transfusion; evidence-based practice
5.  Characterization of Klebsiella sp. Strain 10982, a Colonizer of Humans That Contains Novel Antibiotic Resistance Alleles and Exhibits Genetic Similarities to Plant and Clinical Klebsiella Isolates 
A unique Klebsiella species strain, 10982, was cultured from a perianal swab specimen obtained from a patient in the University of Maryland Medical Center intensive care unit. Klebsiella sp. 10982 possesses a large IncA/C multidrug resistance plasmid encoding a novel FOX AmpC β-lactamase designated FOX-10. A novel variant of the LEN β-lactamase was also identified. Genome sequencing and bioinformatic analysis demonstrated that this isolate contains genes associated with nitrogen fixation, allantoin metabolism, and citrate fermentation. These three gene regions are typically present in either Klebsiella pneumoniae clinical isolates or Klebsiella nitrogen-fixing endophytes but usually not in the same organism. Phylogenomic analysis of Klebsiella sp. 10982 and sequenced Klebsiella genomes demonstrated that Klebsiella sp. 10982 is present on a branch that is located intermediate between the genomes of nitrogen-fixing endophytes and K. pneumoniae clinical isolates. Metabolic features identified in the genome of Klebsiella sp. 10982 distinguish this isolate from other Klebsiella clinical isolates. These features include the nitrogen fixation (nif) gene cluster, which is typically present in endophytic Klebsiella isolates and is absent from Klebsiella clinical isolates. Additionally, the Klebsiella sp. 10982 genome contains genes associated with allantoin metabolism, which have been detected primarily in K. pneumoniae isolates from liver abscesses. Comparative genomic analysis of Klebsiella sp. 10982 demonstrated that this organism has acquired genes conferring new metabolic strategies and novel antibiotic resistance alleles, both of which may enhance its ability to colonize the human body.
PMCID: PMC4023768  PMID: 24395222
6.  Effects of Contact Precautions on Patient Perception of Care and Satisfaction: A Prospective Cohort Study 
Contact precautions decrease healthcare worker–patient contact and may impact patient satisfaction. To determine the association between contact precautions and patient satisfaction, we used a standardized interview for perceived issues with care.
Prospective cohort study of inpatients, evaluated at admission and on hospital days 3, 7, and 14 (until discharged). At each point, patients underwent a standardized interview to identify perceived problems with care. After discharge, the standardized interview and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey were administered by telephone. Responses were recorded, transcribed, and coded by 2 physician reviewers.
A total of 528 medical or surgical patients not admitted to the intensive care unit.
A total of 528 patients were included in the primary analysis, of whom 104 (20%) perceived some issue with their care. On multivariable logistic regression, contact precautions were independently associated with a greater number of perceived concerns with care (odds ratio, 2.05 [95% confidence interval, 1.31–3.21]; P < .01), including poor coordination of care (P = .02) and a lack of respect for patient needs and preferences (P = .001). Eighty-eight patients were included in the secondary analysis of HCAHPS. Patients under contact precautions did not have different HCAHPS scores than those not under contact precautions (odds ratio, 1.79 [95% confidence interval, 0.64–5.00]; P = .27).
Patients under contact precautions were more likely to perceive problems with their care, especially poor coordination of care and a lack of respect for patient preferences.
PMCID: PMC4070370  PMID: 24018926
7.  Comparison of Total Hospital-Acquired Bloodstream Infections to Central Line-Associated Bloodstream Infections and Implications for Outcome Measures in Infection Control 
Validity of the central line-associated bloodstream infection (CLABSI) measure is compromised by subjectivity. We observed significant decreases in both CLABSI and total hospital-acquired bloodstream infection (BSI) following a CLABSI prevention intervention in adult intensive care units. Total hospital-acquired BSI could be explored as an adjunct, objective CLABSI measure.
PMCID: PMC4070376  PMID: 23917916
central line infection; assessment bias; surveillance; BSI; surrogate measure
8.  A comparison of glycosaminoglycan distributions, keratan sulphate sulphation patterns and collagen fibril architecture from central to peripheral regions of the bovine cornea 
Matrix Biology  2014;38:59-68.
This study investigated changes in collagen fibril architecture and the sulphation status of keratan sulphate (KS) glycosaminoglycan (GAG) epitopes from central to peripheral corneal regions. Freshly excised adult bovine corneal tissue was examined as a function of radial position from the centre of the cornea outwards. Corneal thickness, tissue hydration, hydroxyproline content, and the total amount of sulphated GAG were all measured. High and low-sulphated epitopes of keratan sulphate were studied by immunohistochemistry and quantified by ELISA. Chondroitin sulphate (CS) and dermatan sulphate (DS) distributions were observed by immunohistochemistry following specific enzyme digestions. Electron microscopy and X-ray fibre diffraction were used to ascertain collagen fibril architecture. The bovine cornea was 1021 ± 5.42 μm thick at its outer periphery, defined as 9–12 mm from the corneal centre, compared to 844 ± 8.10 μm at the centre. The outer periphery of the cornea was marginally, but not significantly, more hydrated than the centre (H = 4.3 vs. H = 3.7), and was more abundant in hydroxyproline (0.12 vs. 0.06 mg/mg dry weight of cornea). DMMB assays indicated no change in the total amount of sulphated GAG across the cornea. Immunohistochemistry revealed the presence of both high- and low-sulphated epitopes of KS, as well as DS, throughout the cornea, and CS only in the peripheral cornea before the limbus. Quantification by ELISA, disclosed that although both high- and low-sulphated KS remained constant throughout stromal depth at different radial positions, high-sulphated epitopes remained constant from the corneal centre to outer-periphery, whereas low-sulphated epitopes increased significantly. Both small angle X-ray diffraction and TEM analysis revealed that collagen fibril diameter remained relatively constant until the outer periphery was reached, after which fibrils became more widely spaced (from small angle x-ray diffraction analysis) and of larger diameter as they approached the sclera. Depth-profiled synchrotron microbeam analyses showed that, at different radial positions from the corneal centre outwards, fibril diameter was greater superficially than in deeper stromal regions. The interfibrillar spacing was also higher at mid-depth in the stroma than it was in anterior and posterior stromal regions. Collagen fibrils in the bovine cornea exhibited a fairly consistent spacing and diameter from the corneal centre to the 12 mm radial position, after which a significant increase was seen. While the constancy of the overall sulphation levels of proteoglycans in the cornea may correlate with the fibrillar architecture, there was no correlation between the latter and the distribution of low-sulphated KS.
•Proteoglycans (KS, DS, CS) and collagen were correlated with corneal radial position.•Total sulfate levels on glycosaminoglycans remained constant across the cornea.•KS and DS were ubiquitous; CS was found towards the edge of the cornea onwards.•High-sulfated KS remained constant; low-sulfated KS increased peripherally.•There was no correlation between fibrillar architecture and sulfation levels of KS.
PMCID: PMC4199143  PMID: 25019467
Cornea; Proteoglycans; Glycosaminoglycans; Collagen structure
9.  Universal Glove and Gown Use and Acquisition of Antibiotic resistant bacteria in the ICU: A Randomized Trial 
Antibiotic-resistant bacteria are associated with increased patient morbidity and mortality. It is unknown whether wearing gloves and gowns for all patient contact in the intensive care unit (ICU) decreases acquisition of antibiotic-resistant bacteria.
To assess whether wearing gloves and gowns for all patient contact in the ICU decreases acquisition of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) compared with usual care.
Design, Setting, and Participants
Cluster-randomized trial in 20 medical and surgical ICUs in 20 US hospitals from January 4, 2012, to October 4, 2012.
In the intervention ICUs, all health care workers were required to wear gloves and gowns for all patient contact and when entering any patient room.
Main Outcomes and Measures
The primary outcome was acquisition of MRSA or VRE based on surveillance cultures collected on admission and discharge from the ICU. Secondary outcomes included individual VRE acquisition, MRSA acquisition, frequency of health care worker visits, hand hygiene compliance, health care–associated infections, and adverse events.
From the 26 180 patients included, 92 241 swabs were collected for the primary outcome. Intervention ICUs had a decrease in the primary outcome of MRSA or VRE from 21.35 acquisitions per 1000 patient-days (95% CI, 17.57 to 25.94) in the baseline period to 16.91 acquisitions per 1000 patient-days (95% CI, 14.09 to 20.28) in the study period, whereas control ICUs had a decrease in MRSA or VRE from 19.02 acquisitions per 1000 patient-days (95% CI, 14.20 to 25.49) in the baseline period to 16.29 acquisitions per 1000 patient-days (95% CI, 13.48 to 19.68) in the study period, a difference in changes that was not statistically significant (difference, −1.71 acquisitions per 1000 person-days, 95% CI, −6.15 to 2.73; P = .57). For key secondary outcomes, there was no difference in VRE acquisition with the intervention (difference, 0.89 acquisitions per 1000 person-days; 95% CI, −4.27 to 6.04, P = .70), whereas for MRSA, there were fewer acquisitions with the intervention (difference, −2.98 acquisitions per 1000 person-days; 95% CI, −5.58 to −0.38; P = .046). Universal glove and gown use also decreased health care worker room entry (4.28 vs 5.24 entries per hour, difference, −0.96; 95% CI, −1.71 to −0.21, P = .02), increased room-exit hand hygiene compliance (78.3% vs 62.9%, difference, 15.4%; 95% CI, 8.99% to 21.8%; P = .02) and had no statistically significant effect on rates of adverse events (58.7 events per 1000 patient days vs 74.4 events per 1000 patient days; difference, −15.7; 95% CI, −40.7 to 9.2, P = .24).
Conclusions and Relevance
The use of gloves and gowns for all patient contact compared with usual care among patients in medical and surgical ICUs did not result in a difference in the primary outcome of acquisition of MRSA or VRE. Although there was a lower risk of MRSA acquisition alone and no difference in adverse events, these secondary outcomes require replication before reaching definitive conclusions.
PMCID: PMC4026208  PMID: 24097234
10.  A randomized, controlled trial of enhanced cleaning to reduce contamination of healthcare worker gowns and gloves with multidrug-resistant bacteria 
To determine whether enhanced daily cleaning would reduce contamination of healthcare worker (HCW) gowns and gloves with methicillin-resistant Staphylococcus aureus (MRSA) or multidrug-resistant Acinetobacter baumannii (MDRAB).
A cluster-randomized controlled trial.
Four intensive care units (ICUs) in an urban tertiary care hospital.
ICU rooms occupied by patients colonized with MRSA or MDRAB.
Extra enhanced daily cleaning of ICU room surfaces frequently touched by HCWs.
A total of 4,444 cultures were collected from 132 rooms over 10 months. Using fluorescent dot markers at 2,199 surfaces, we found that 26% of surfaces in control rooms were cleaned and 100% of surfaces in experimental rooms were cleaned (p < 0.001). The mean proportion of contaminated HCW gowns and gloves following routine care provision and before leaving the rooms of patients with MDRAB was 16% among control rooms and 12% among experimental rooms (RR: 0.77, 95% CI: 0.28 – 2.11, p = 0.230). For MRSA, the mean proportions were 22% and 19%, respectively (RR: 0.89, 95%: 0.5 – 1.53, p = 0.158).
Intense enhanced daily cleaning of ICU rooms occupied by patients colonized with MRSA or MDRAB was associated with a nonsignificant reduction in contamination of HCW gowns and gloves after routine patient care activities. Further research is needed to determine whether intense environmental cleaning will lead to significant reductions and fewer infections.
PMCID: PMC3759983  PMID: 23571365
11.  A Systematic Review of Cost-Sharing Strategies Used within Publicly-Funded Drug Plans in Member Countries of the Organisation for Economic Co-Operation and Development 
PLoS ONE  2014;9(3):e90434.
Publicly-funded drug plans vary in strategies used and policies employed to reduce continually increasing pharmaceutical expenditures. We systematically reviewed the utilization of cost-sharing strategies and physician-directed prescribing regulations in publicly-funded formularies within member nations of the Organization of Economic Cooperation and Development (OECD).
Methods & Findings
Using the OECD nations as the sampling frame, a search for cost-sharing strategies and physician-directed prescribing regulations was done using published and grey literature. Collected data was verified by a system expert within the prescription drug insurance plan in each country, to ensure the accuracy of key data elements across plans.
Significant variation in the use of cost-sharing mechanisms was seen. Copayments were the most commonly used cost-containment measure, though their use and amount varied for those with certain conditions, most often chronic diseases (in 17 countries), and by socio-economic status (either income or employment status), or with age (in 15 countries). Caps and deductibles were only used by five systems. Drug cost-containment strategies targeting physicians were also identified in 24 countries, including guideline-based prescribing, prescription monitoring and incentive structures.
There was variable use of cost-containment strategies to limit pharmaceutical expenditures in publicly funded formularies within OECD countries. Further research is needed to determine the best approach to constrain costs while maintaining access to pharmaceutical drugs.
PMCID: PMC3949707  PMID: 24618721
12.  Epidemiology and outcome of major postoperative infections following cardiac surgery: Risk factors and impact of pathogen type 
Major postoperative infections (MPIs) are poorly understood complications of cardiac surgery. We examined the epidemiology, microbiology, and outcome of MPIs occurring after cardiac surgery.
The study cohort was drawn from the Society of Thoracic Surgeon National Cardiac Database and comprised adults who underwent cardiac surgery at 5 tertiary hospitals between 2000 and 2004. We studied the incidence, microbiology, and risk factors of MPI (bloodstream or chest wound infections within 30 days after surgery), as well as 30-day mortality. We used multivariate regression analyses to evaluate the risk of MPI and mortality.
MPI was identified in 341 of 10,522 patients (3.2%). Staphylococci were found in 52.5% of these patients, gram-negative bacilli (GNB) in 24.3%, and other pathogens in 23.2%. High body mass index, previous coronary bypass surgery, emergency surgery, renal impairment, immunosuppression, cardiac failure, and peripheral/cerebrovascular disease were associated with the development of MPI. Median postoperative duration of hospitalization (15 days vs 6 days) and mortality (8.5% vs 2.2%) were higher in patients with MPIs. Compared with uninfected individuals, odds of mortality were higher in patients with S aureus MPIs (adjusted odds ratio, 3.7) and GNB MPIs (adjusted odds ratio, 3.0).
Staphylococci accounted for the majority of MPIs after cardiac surgery. Mortality was higher in patients with Staphylococcus aureus- and GNB-related MPIs than in patients with MPIs caused by other pathogens and uninfected patients. Preventive strategies should target likely pathogens and high-risk patients undergoing cardiac surgery.
PMCID: PMC3535474  PMID: 22609237
Wound infection; Sepsis; Cardiac surgical procedures; Morbidity; Mortality
13.  Effect of Timing of Dialysis Commencement on Clinical Outcomes of Patients with Planned Initiation of Peritoneal Dialysis in the Ideal Trial 
♦ Background: Since the mid-1990s, early dialysis initiation has dramatically increased in many countries. The Initiating Dialysis Early and Late (IDEAL) study demonstrated that, compared with late initiation, planned early initiation of dialysis was associated with comparable clinical outcomes and increased health care costs. Because residual renal function is a key determinant of outcome and is better preserved with peritoneal dialysis (PD), the present pre-specified subgroup analysis of the IDEAL trial examined the effects of early-compared with late-start dialysis on clinical outcomes in patients whose planned therapy at the time of randomization was PD.
♦ Methods: Adults with an estimated glomerular filtration rate (eGFR) of 10 - 15 mL/min/1.73 m2 who planned to be treated with PD were randomly allocated to commence dialysis at an eGFR of 10 - 14 mL/min/1.73 m2 (early start) or 5 - 7 mL/min/1.73 m2 (late start). The primary outcome was all-cause mortality.
♦ Results: Of the 828 IDEAL trial participants, 466 (56%) planned to commence PD and were randomized to early start (n = 233) or late start (n = 233). The median times from randomization to dialysis initiation were, respectively, 2.03 months [interquartile range (IQR):1.67 - 2.30 months] and 7.83 months (IQR: 5.83 - 8.83 months). Death occurred in 102 early-start patients and 96 late-start patients [hazard ratio: 1.04; 95% confidence interval (CI): 0.79 - 1.37]. No differences in composite cardiovascular events, composite infectious deaths, or dialysis-associated complications were observed between the groups. Peritonitis rates were 0.73 episodes (95% CI: 0.65 - 0.82 episodes) per patient-year in the early-start group and 0.69 episodes (95% CI: 0.61 - 0.78 episodes) per patient-year in the late-start group (incidence rate ratio: 1.19; 95% CI: 0.86 - 1.65; p = 0.29). The proportion of patients planning to commence PD who actually initiated dialysis with PD was higher in the early-start group (80% vs 70%, p = 0.01).
♦ Conclusion: Early initiation of dialysis in patients with stage 5 chronic kidney disease who planned to be treated with PD was associated with clinical outcomes comparable to those seen with late dialysis initiation. Compared with early-start patients, late-start patients who had chosen PD as their planned dialysis modality were less likely to commence on PD.
PMCID: PMC3524893  PMID: 23212859
Dialysis timing; mortality; outcomes; peritonitis
14.  Serious Mental Illness and Acute Hospital Readmission in Diabetic Patientsa 
Patients with serious mental illness (SMI), particularly those with other chronic illnesses, may be vulnerable to unplanned hospital readmission. We hypothesized that SMI would be associated with increased 30-day hospital readmission in a cohort of adult patients with comorbid diabetes admitted to a tertiary-care facility from 2005–2009. SMI was defined by ICD-9 discharge diagnosis codes for schizophrenia, schizo-affective, bipolar, manic, or major depressive disorders, or other psychosis. The primary outcome was 30-day readmission to the index hospital. Among 26,878 eligible admissions, prevalence of SMI was 6% and incidence of 30-day hospital admission was 16%. Among patients aged <35 years, SMI was significantly associated with decreased odds of 30-day hospital readmission (OR 0.39, 95% CI: 0.17, 0.91). However, among patients ≥35 years, SMI was not significantly associated with 30-day hospital readmission (OR 1.11, 95%CI: 0.86, 1.42). SMI may not be associated with increased odds of 30-day hospital readmission in this population.
PMCID: PMC3677605  PMID: 22539798
15.  Does Nonpayment for Hospital-Acquired Catheter-Associated Urinary Tract Infections Lead to Overtesting and Increased Antimicrobial Prescribing? 
This retrospective cohort study of 39 US hospitals found that Centers for Medicare & Medicaid Services nonpayment for hospital-acquired catheter-associated urinary tract infections (UTIs) has not led to overtesting for UTI on admission or to increased antimicrobial prescribing.
Background. On 1 October 2008, in an effort to stimulate efforts to prevent catheter-associated urinary tract infection (CAUTI), the Centers for Medicare & Medicaid Services (CMS) implemented a policy of not reimbursing hospitals for hospital-acquired CAUTI. Since any urinary tract infection present on admission would not fall under this initiative, concerns have been raised that the policy may encourage more testing for and treatment of asymptomatic bacteriuria.
Methods. We conducted a retrospective multicenter cohort study with time series analysis of all adults admitted to the hospital 16 months before and 16 months after policy implementation among participating Society for Healthcare Epidemiology of America Research Network hospitals. Our outcomes were frequency of urine culture on admission and antimicrobial use.
Results. A total of 39 hospitals from 22 states submitted data on 2 362 742 admissions. In 35 hospitals affected by the CMS policy, the median frequency of urine culture performance did not change after CMS policy implementation (19.2% during the prepolicy period vs 19.3% during the postpolicy period). The rate of change in urine culture performance increased minimally during the prepolicy period (0.5% per month) and decreased slightly during the postpolicy period (–0.25% per month; P < .001). In the subset of 10 hospitals providing antimicrobial use data, the median frequency of fluoroquinolone antimicrobial use did not change substantially (14.6% during the prepolicy period vs 14.0% during the postpolicy period). The rate of change in fluoroquinolone use increased during the prepolicy period (1.26% per month) and decreased during the postpolicy period (–0.60% per month; P < .001).
Conclusions. We found no evidence that CMS nonpayment policy resulted in overtesting to screen for and document a diagnosis of urinary tract infection as present on admission.
PMCID: PMC3657518  PMID: 22700826
16.  Assessing the Burden of Acinetobacter baumannii in Maryland: A Statewide Cross-Sectional Period Prevalence Survey 
To determine the prevalence of Acinetobacter baumannii, an important healthcare-associated pathogen, among mechanically ventilated patients in Maryland.
The Maryland MDRO Prevention Collaborative performed a statewide cross-sectional active surveillance survey of mechanically ventilated patients residing in acute care and long-term care (LTC) facilities. Surveillance cultures (sputum and perianal) were obtained from all mechanically ventilated inpatients at participating facilities during a 2-week period.
All healthcare facilities in Maryland that provide care for mechanically ventilated patients were invited to participate.
Mechanically ventilated patients, known to be at high risk for colonization and infection with A. baumannii, were included.
Seventy percent (40/57) of all eligible healthcare facilities participated in the survey, representing both acute care (n = 30) and LTC (n = 10) facilities in all geographic regions of Maryland. Surveillance cultures were obtained from 92% (358/390) of eligible patients. A. baumannii was identified in 34% of all mechanically ventilated patients in Maryland; multidrug-resistant A. baumannii was found in 27% of all patients. A. baumannii was detected in at least 1 patient in 49% of participating facilities; 100% of LTC facilities had at least 1 patient with A. baumannii, compared with 31% of acute care facilities. A. baumannii was identified from all facilities in which 10 or more patients were sampled.
A. baumannii is common among mechanically ventilated patients in both acute care and LTC facilities throughout Maryland, with a high proportion of isolates demonstrating multidrug resistance.
PMCID: PMC3720130  PMID: 22869261
17.  Brain imaging predictors and the international study to predict optimized treatment for depression: study protocol for a randomized controlled trial 
Trials  2013;14:224.
Approximately 50% of patients with major depressive disorder (MDD) do not respond optimally to antidepressant treatments. Given this is a large proportion of the patient population, pretreatment tests that predict which patients will respond to which types of treatment could save time, money and patient burden. Brain imaging offers a means to identify treatment predictors that are grounded in the neurobiology of the treatment and the pathophysiology of MDD.
The international Study to Predict Optimized Treatment in Depression is a multi-center, parallel model, randomized clinical trial with an embedded imaging sub-study to identify such predictors. We focus on brain circuits implicated in major depressive disorder and its treatment. In the full trial, depressed participants are randomized to receive escitalopram, sertraline or venlafaxine-XR (open-label). They are assessed using standardized multiple clinical, cognitive-emotional behavioral, electroencephalographic and genetic measures at baseline and at eight weeks post-treatment. Overall, 2,016 depressed participants (18 to 65 years old) will enter the study, of whom a target of 10% will be recruited into the brain imaging sub-study (approximately 67 participants in each treatment arm) and 67 controls. The imaging sub-study is conducted at the University of Sydney and at Stanford University. Structural studies include high-resolution three-dimensional T1-weighted, diffusion tensor and T2/Proton Density scans. Functional studies include standardized functional magnetic resonance imaging (MRI) with three cognitive tasks (auditory oddball, a continuous performance task, and Go-NoGo) and two emotion tasks (unmasked conscious and masked non-conscious emotion processing tasks). After eight weeks of treatment, the functional MRI is repeated with the above tasks. We will establish the methods in the first 30 patients. Then we will identify predictors in the first half (n = 102), test the findings in the second half, and then extend the analyses to the total sample.
Trial registration
International Study to Predict Optimized Treatment - in Depression (iSPOT-D)., NCT00693849.
PMCID: PMC3729660  PMID: 23866851
Major depressive disorder; Antidepressant treatments; Imaging; Biomarker; iSPOT-D
18.  Association between Methicillin-Resistant Staphylococcus aureus Colonization and Infection May Not Differ by Age Group 
We assessed whether age modified the association between methicillin-resistant Staphylococcus aureus (MRSA) anterior nares colonization and subsequent infection. Among 7,405 patients (9,511 admissions), MRSA colonization was significantly associated with infection (adjusted odds ratio, 13.7 [95% confidence interval, 7.3–25.7]) but did not differ significantly by age group.
PMCID: PMC3677581  PMID: 23221199
19.  Healthcare-Associated Infection and Hospital Readmission 
Hospital readmissions are a current target of initiatives to reduce healthcare costs. This study quantified the association between having a clinical culture positive for 1 of 3 prevalent hospital-associated organisms and time to hospital readmission.
Retrospective cohort study.
Adults admitted to an academic, tertiary care referral center from January 1, 2001, through December 31, 2008.
The primary exposure of interest was a clinical culture positive for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), or Clostridium difficile obtained more than 48 hours after hospital admission during the index hospital stay. The primary outcome of interest was time to readmission to the index facility. Multivariable Cox proportional hazards models were used to model the adjusted association between positive clinical culture result and time to readmission and to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).
Among 136,513 index admissions, the prevalence of hospital-associated positive clinical culture result for 1 of the 3 organisms of interest was 3%, and 35% of patients were readmitted to the index facility within 1 year after discharge. Patients with a positive clinical culture obtained more than 48 hours after hospital admission had an increased hazard of readmission (HR, 1.40; 95% CI, 1.33–1.46) after adjusting for age, sex, index admission length of stay, intensive care unit stay, Charlson comorbidity index, and year of hospital admission.
Patients with healthcare-associated infections may be at increased risk of hospital readmission. These findings may be used to impact health outcomes after discharge from the hospital and to encourage better infection prevention efforts.
PMCID: PMC3677598  PMID: 22561707
20.  Comparison of the Methicillin-Resistant Staphylococcus aureus Acquisition among Rehabilitation and Nursing Home Residents 
To assess risk factors for methicillin-resistant Staphylococcus aureus (MRSA) acquisition among extended care residents focusing on level of care (residential vs rehabilitation) and room placement with an MRSA-positive resident.
Prospective cohort study.
Extended care units at 2 healthcare systems in Maryland.
Four hundred forty-three residents with no history of MRSA and negative MRSA surveillance cultures of the anterior nares and areas of skin breakdown at enrollment.
Follow-up cultures were collected every 4 weeks and/or at discharge for a period of 12 weeks. Study data were collected by a research nurse from the medical staff and the electronic medical records. Cox proportional hazards modeling was used to calculate adjusted hazards ratios (aHRs) and 95% confidence intervals (CIs).
. Residents in rehabilitation care had 4-fold higher risk of MRSA acquisition compared with residents in residential care (hazard ratio [HR], 4. [95% CI, 2.2–8.8]). Being bedbound was significantly associated with MRSA acquisition in both populations (residential care, aHR, 4.3 [95% CI, 1.5–12.2]; rehabilitation care, aHR, 4.8 [95% CI, 1.2–18.7]). Having an MRSA-positive roommate was not significantly associated with acquisition in either population (residential care, aHR, 1.4 [95% CI, 0.5–3.9]; rehabilitation care, aHR, 0.5 [95% CI, 0.1–2.2]); based on concordant spa typing, only 2 of 8 residents who acquired MRSA and had room placement with an MRSA-positive resident acquired their MRSA isolate from their roommate.
Residents in rehabilitation care appear at higher risk and have different risk factors for MRSA acquisition compared to those in residential care.
PMCID: PMC3677603  PMID: 21460509
21.  Risk of Acquiring Extended-Spectrum β-Lactamase–Producing Klebsiella Species and Escherichia coli from Prior Room Occupants in the Intensive Care Unit 
To quantify the association between admission to an intensive care unit (ICU) room most recently occupied by a patient positive for extended-spectrum β-lactamase (EBSL)–producing gram-negative bacteria and acquisition of infection or colonization with that pathogen.
Retrospective cohort study.
The study included patients admitted to medical and surgical ICUs of an academic medical center between September 1, 2001, and June 30, 2009.
Perianal surveillance cultures were obtained at admission to the ICU, weekly, and at discharge from the ICU. Patients were included if they had culture results that were negative for ESBL-producing gram-negative bacteria at ICU admission and had an ICU length of stay longer than 48 hours. Pulsed-field gel electrophoresis (PFGE) was performed on ESBL-positive isolates from patients who acquired the same bacterial species (eg, Klebsiella species or Escherichia coli) as the previous room occupant.
Among 9,371 eligible admissions (7,651 unique patients), 267 (3%) involved patients who acquired an ESBL-producing pathogen in the ICU; of these patients, 32 (12%) were hospitalized in a room in which the prior occupant had been positive for ESBL. Logistic regression results suggested that the prior occupant's ESBL status was not significantly associated with acquisition of an ESBL-producing pathogen (adjusted odds ratio, 1.39 [95% confidence interval, 0.94–2.08]) after adjusting for colonization pressure and antibiotic exposure in the ICU. PFGE results suggested that 6 (18%) of 32 patients acquired a bacterial strain that was the same as or closely related to the strain obtained from the prior occupant.
These data suggest that environmental contamination may not play a substantial role in the transmission of ESBL-producing pathogens among ICU patients. Intensifying environmental decontamination may be less effective than other interventions in preventing transmission of ESBL-producing pathogens.
PMCID: PMC3660030  PMID: 23571360
22.  Recovery of Gram-Negative Bacilli in Stored Endotracheal Aspirates 
Journal of Clinical Microbiology  2012;50(8):2791-2792.
This study assessed the recovery rates of Gram-negative bacilli from stored endotracheal aspirates frozen with and without glycerol. Samples frozen with glycerol showed a significant difference in isolate recovery, 89.7% versus 69.2% (P = 0.02). This study demonstrates that it is possible to achieve high recovery rates of potentially pathogenic organisms from endotracheal aspirates when stored with glycerol, thus broadening the scope of active surveillance cultures for both clinical and research purposes.
PMCID: PMC3421506  PMID: 22649011
23.  Association between Contact Precautions and Delirium at a Tertiary Care Center 
To investigate the relationship between contact precautions and delirium among inpatients, adjusting for other factors.
Retrospective cohort study.
A 662-bed tertiary care center.
All nonpyschiatric adult patients admitted to a tertiary care center from 2007 through 2009.
Generalized estimating equations were used to estimate the association between contact precautions and delirium in a retrospective cohort of 2 years of admissions to a tertiary care center.
During the 2-year period, 60,151 admissions occurred in 45,266 unique nonpsychiatric patients. After adjusting for comorbid conditions, age, sex, intensive care unit status, and length of hospitalization, contact precautions were significantly associated with delirium (as defined by International Classification of Diseases, Ninth Revision), medication, or restraint exposure (adjusted odds ratio [OR], 1.40 [95% confidence interval {CI}, 1.24–1.51]). The association between contact precautions and delirium was seen only in patients who were newly placed under contact precautions during the course of their stay (adjusted OR, 1.75 [95% CI, 1.60–1.92]; P < .01) and was not seen in patients who were already under contact precautions at admission (adjusted OR, 0.97 [95% CI, 0.86–1.09]; P=.60).
Although delirium was more common in patients who were newly placed under contact precautions during the course of their hospital admission, delirium was not associated with contact precautions started at hospital admission. Patients newly placed under contact precautions after admission but during hospitalization appear to be at a higher risk and may benefit from proven delirium-prevention strategies.
PMCID: PMC3544005  PMID: 22173520
24.  Transfer of multidrug-resistant bacteria to healthcare workers’ gloves and gowns after patient contact increases with environmental contamination 
Critical care medicine  2012;40(4):1045-1051.
To assess the role of environmental contamination in the transmission of multidrug-resistant bacteria to healthcare workers’ clothing.
Prospective cohort.
Six intensive care units at a tertiary care hospital.
Healthcare workers including registered nurses, patient care technicians, respiratory therapists, occupational/physical therapists, and physicians.
Measurements and Main Results
One hundred twenty of 585 (20.5%) healthcare worker/patient interactions resulted in contamination of healthcare workers’ gloves or gowns. Multidrug-resistant Acinetobacter baumannii contamination occurred most frequently, 55 of 167 observations (32.9%; 95% confidence interval [CI] 25.8% to 40.0%), followed by multidrug-resistant Pseudomonas aeruginosa, 15 of 86 (17.4%; 95% CI 9.4% to 25.4%), vancomycin-resistant Enterococcus, 25 of 180 (13.9%, 95% CI 8.9, 18.9%) and methicillin-resistant Staphylococcus aureus, 21 of 152 (13.8%; 95% CI 8.3% to 19.2%). Independent risk factors associated with healthcare worker contamination with multidrug-resistant bacteria were positive environmental cultures (odds ratio [OR] 4.2; 95% CI 2.7–6.5), duration in room for >5 mins (OR 2.0; 95% CI 1.2–3.4), performing physical examinations (OR 1.7; 95% CI 1.1–2.8), and contact with the ventilator (OR 1.8; 95% CI, 1.1–2.8). Pulsed field gel electrophoresis determined that 91% of healthcare worker isolates were related to an environmental or patient isolate.
The contamination of healthcare workers’ protective clothing during routine care of patients with multidrug- resistant organisms is most frequent with A. baumannii. Environmental contamination was the major determinant of transmission to healthcare workers’ gloves or gowns. Compliance with contact precautions and more aggressive environmental cleaning may decrease transmission.
PMCID: PMC3534819  PMID: 22202707
Acinetobacter; contact precautions; contamination; environment; MRSA; VRE
25.  Survival of Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococcus spp. for an Extended Period of Transport 
Journal of Clinical Microbiology  2012;50(7):2466-2468.
This study determined the survivability of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) for extended periods of time and temperatures using a standard swab for assessment. Our study showed that transportation in Liquid Amies medium could be performed at room temperature or 4°C for up to 14 days without a decrease in recovery of MRSA or VRE.
PMCID: PMC3405567  PMID: 22535993

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