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1.  Risk Factors for Bacteremia in Patients With Urinary Catheter-Associated Bacteriuria 
Catheter-associated bacteriuria is complicated by secondary bacteremia in 0.4% to 4.0% of cases. The directly attributable mortality rate is 12.7%
To identify risk factors for bacteremia associated with catheter-associated bacteriuria.
Data were acquired from a large electronic clinical and administrative database of consecutive adult inpatient admissions to 2 acute care hospitals during a 7-year period. Data on patients with catheter-associated bacteriuria and bacteremia were compared with data on control patients with catheter-associated bacteriuria and no bacteremia, matched for date of admission plus or minus 30 days. Urine and blood cultures positive for the same pathogen within 7 days were used to define catheter-associated bacteriuria and bacteremia. Multivariable conditional logistic regression was used to determine independent risk factors for bacteremia.
The sample consisted of 158 cases and 474 controls. Independent predictors of bacteremia were male sex (odds ratio, 2.76), treatment with immunosuppressants (odds ratio, 1.68), urinary tract procedure (odds ratio, 2.70), and catheter that remained in place after bacteriuria developed (odds ratio, 2.75). Patients with enterococcal bacteriuria were half as likely to become bacteremic as were patients with other urinary pathogens (odds ratio, 0.46). Odds of secondary bacteremia increased 2% per additional day of hospital stay (95% CI, 1.01-1.04) and decreased 1% with each additional year of age (95% CI, 0.97-0.99).
The results add new information about increased risk for bacteremia among patients with catheters remaining in place after catheter-associated bacteriuria and confirm evidence for previously identified risk factors.
PMCID: PMC5160996  PMID: 27965229
2.  The Effect of Contact Precautions on Frequency of Hospital Adverse Events 
To determine whether use of Contact Precautions on hospital ward patients is associated with patient adverse events.
Individually-matched prospective cohort study.
The University of Maryland Medical Center, a tertiary care hospital in Baltimore, Maryland.
A total of 296 medical or surgical inpatients admitted to non-intensive care unit hospital wards were enrolled at admission from January to November 2010. Patients on Contact Precautions were individually matched by hospital unit after an initial 3-day length of stay to patients not on Contact Precautions. Adverse events were detected by physician chart review and categorized as noninfectious, preventable and severe noninfectious, and infectious adverse events during the patient’s stay using the standardized Institute for Healthcare Improvement’s Global Trigger Tool.
148 patients on Contact Precautions at admission were matched to 148 patients not on Contact Precautions. Of the total 296 subjects, 104 (35.1%) experienced at least one adverse event during their hospital stay. Contact Precautions were associated with fewer noninfectious adverse events (rate ratio [RtR], 0.70; 95% confidence interval [CI], 0.51–0.95; p=0.02) and non-statistically significant fewer severe adverse events (RtR, 0.69; 95% CI, 0.46–1.03; p=0.07). Preventable adverse events (RtR, 0.85; 95% CI, 0.59–1.24; p=0.41) did not significantly differ between patients on Contact Precautions compared to unexposed patients.
Hospital ward patients on Contact Precautions were less likely to experience noninfectious adverse events during their hospital stay than patients unexposed to Contact Precautions.
PMCID: PMC4686266  PMID: 26278419
3.  A quasi-randomized feasibility pilot study of specific treatments to improve emotion recognition and mental-state reasoning impairments in schizophrenia 
BMC Psychiatry  2016;16:360.
Impaired ability to make inferences about what another person might think or feel (i.e., social cognition impairment) is recognised as a core feature of schizophrenia and a key determinant of the poor social functioning that characterizes this illness. The development of treatments to target social cognitive impairments as a causal factor of impaired functioning in schizophrenia is of high priority. In this study, we investigated the acceptability, feasibility, and limited efficacy of 2 programs targeted at specific domains of social cognition in schizophrenia: “SoCog” Mental-State Reasoning Training (SoCog-MSRT) and “SoCog” Emotion Recognition Training (SoCog-ERT).
Thirty-one participants with schizophrenia or schizoaffective disorder were allocated to either SoCog-MSRT (n = 19) or SoCog-ERT (n = 12). Treatment comprised 12 twice-weekly sessions for 6 weeks. Participants underwent assessments of social cognition, neurocognition and symptoms at baseline, post-training and 3-months after completing training.
Attendance at training sessions was high with an average of 89.29 % attendance in the SoCog-MSRT groups and 85.42 % in the SoCog-ERT groups. Participants also reported the 2 programs as enjoyable and beneficial. Both SoCog-MSRT and SoCog-ERT groups showed increased scores on a false belief reasoning task and the Reading the Mind in the Eyes test. The SoCog-MSRT group also showed reduced personalising attributional biases in a small number of participants, while the SoCog-ERT group showed improved emotion recognition.
The results are promising and support the feasibility and acceptability of the 2 SoCog programs as well as limited efficacy to improve social cognitive abilities in schizophrenia. There is also some evidence that skills for the recognition of basic facial expressions need specific training.
Trial registration
Australian New Zealand Clinical Trials Registry ACTRN12613000978763. Retrospectively registered 3/09/2013.
PMCID: PMC5078972  PMID: 27776504
Schizophrenia; Social cognition; Theory of mind; Emotion recognition; Mental state reasoning; Remediation; Social cognitive training
4.  N-acetylcysteine (NAC) in schizophrenia resistant to clozapine: a double blind randomised placebo controlled trial targeting negative symptoms 
BMC Psychiatry  2016;16:320.
Clozapine is an effective treatment for a proportion of people with schizophrenia (SZ) who are resistant to the beneficial effects of other antipsychotic drugs. However, anything from 40–60 % of people on clozapine experience residual symptoms even on adequate doses of the medication, and thus could be considered ‘clozapine resistant’. Agents that could work alongside clozapine to improve efficacy whilst not increasing the adverse effect burden are both desired and necessary to improve the lives of individuals with clozapine-resistant SZ. N-Acetylcysteine (NAC) is one such possible agent. Previous research from our research group provided promising pilot data suggesting the efficacy of NAC in this patient population. The aim of the study reported here is to expand this work by conducting a large scale clinical trial of NAC in the treatment of clozapine-resistant SZ.
This study is an investigator initiated, multi-site, randomised, placebo-controlled trial. It aims to include 168 patients with clozapine-resistant SZ, divided into an intervention group (NAC) and a control group (placebo). Participants in the intervention group will receive 2 g daily of NAC. The primary outcome measures will be the negative symptom scores of the Positive and Negative Syndrome Scale (PANSS). Secondary outcome measures will include: changes in quality of life (QoL) as measured by the Lancashire Quality of Life Profile (LQoLP) and cognitive functioning as measured by the total score on the MATRICS. Additionally we will examine peripheral and cortical glutathione (GSH) concentrations as process outcomes.
This large scale clinical trial will investigate the efficacy of NAC as an adjunctive medication to clozapine. This trial, if successful, will establish a cheap, safe and easy-to-use agent (NAC) as a ‘go to’ adjunct in patients that are only partly responsive to clozapine.
Trial registration
Australian and New Zealand Clinical Trials Registration Number: Current Randomised Controlled Trial ACTRN12615001273572. The date of registration 23 November 2015.
PMCID: PMC5024434  PMID: 27629871
N-Acetylcysteine; Clozapine; Schizophrenia; Negative Symptoms; Cognition; Biomarkers
5.  Amygdala Reactivity to Emotional Faces in the Prediction of General and Medication-Specific Responses to Antidepressant Treatment in the Randomized iSPOT-D Trial 
Neuropsychopharmacology  2015;40(10):2398-2408.
Although the cost of poor treatment outcomes of depression is staggering, we do not yet have clinically useful methods for selecting the most effective antidepressant for each depressed person. Emotional brain activation is altered in major depressive disorder (MDD) and implicated in treatment response. Identifying which aspects of emotional brain activation are predictive of general and specific responses to antidepressants may help clinicians and patients when making treatment decisions. We examined whether amygdala activation probed by emotion stimuli is a general or differential predictor of response to three commonly prescribed antidepressants, using functional magnetic resonance imaging (fMRI). A test–retest design was used to assess patients with MDD in an academic setting as part of the International Study to Predict Optimized Treatment in Depression. A total of 80 MDD outpatients were scanned prior to treatment and 8 weeks after randomization to the selective serotonin reuptake inhibitors escitalopram and sertraline and the serotonin–norepinephrine reuptake inhibitor, venlafaxine-extended release (XR). A total of 34 matched controls were scanned at the same timepoints. We quantified the blood oxygen level-dependent signal of the amygdala during subliminal and supraliminal viewing of facial expressions of emotion. Response to treatment was defined by ⩾50% symptom improvement on the 17-item Hamilton Depression Rating Scale. Pre-treatment amygdala hypo-reactivity to subliminal happy and threat was a general predictor of treatment response, regardless of medication type (Cohen's d effect size 0.63 to 0.77; classification accuracy, 75%). Responders showed hypo-reactivity compared to controls at baseline, and an increase toward ‘normalization' post-treatment. Pre-treatment amygdala reactivity to subliminal sadness was a differential moderator of non-response to venlafaxine-XR (Cohen's d effect size 1.5; classification accuracy, 81%). Non-responders to venlafaxine-XR showed pre-treatment hyper-reactivity, which progressed to hypo-reactivity rather than normalization post-treatment, and hypo-reactivity post-treatment was abnormal compared to controls. Impaired amygdala activation has not previously been highlighted in the general vs differential prediction of antidepressant outcomes. Amygdala hypo-reactivity to emotions signaling reward and threat predicts the general capacity to respond to antidepressants. Amygdala hyper-reactivity to sad emotion is involved in a specific non-response to a serotonin–norepinephrine reuptake inhibitor. The findings suggest amygdala probes may help inform the personal selection of antidepressant treatments.
PMCID: PMC4538354  PMID: 25824424
6.  Infrequent Air Contamination with Acinetobacter baumannii of Air Surrounding Known Colonized or Infected Patients 
Using a validated air sampling method we found Acinetobacter baumannii in the air surrounding only 1 of 12 patients known to be colonized or infected with A. baumannii. Patients’ closed circuit ventilator status, frequent air exchanges in patient rooms and short sampling time may have contributed to this low burden.
PMCID: PMC4686262  PMID: 25825865
7.  Accuracy of a radiofrequency identification (RFID) badge system to monitor hand hygiene behavior during routine clinical activities 
Hand hygiene (HH) is a critical part of infection prevention in healthcare settings. Hospitals around the world continuously struggle to improve healthcare personnel (HCP) HH compliance. The current gold standard for monitoring compliance is direct observation; however this method is time consuming and costly. One emerging area of interest involves automated systems for monitoring HH behavior such as radiofrequency identification (RFID) tracking systems.
To assess the accuracy of a commercially available RFID system in detecting HCP HH behavior, we compared direct observation to data collected by the RFID system in a simulated validation setting and to a real-life clinical setting over two hospitals.
A total of 1554 HH events were observed. Accuracy for identifying HH events was high in the simulated validation setting (88.5%) but relatively low in the real-life clinical setting (52.4%). This difference was significant (p<0.01). Accuracy for detecting HCP movement into and out of patient rooms was also high in the simulated setting but not in the real-life clinical setting (100% on entry and exit in simulated setting vs. 54.3% entry and 49.5% exit in real-life clinical setting, p<.01).
In this validation study of an RFID system, almost half of the HH events were missed. More research is necessary to further develop these systems and improve accuracy prior to widespread adoption.
PMCID: PMC4892498  PMID: 24355492
8.  Effect of chlorhexidine bathing and other infection control practices on the Benefits of Universal Glove and Gown (BUGG) Trial: A subgroup analysis 
We report the results of a subgroup analysis of the Benefits of Universal Glove and Gown (BUGG) trial. In 20 ICUs, the reduction in acquisition of methicillin-resistant Staphylococcus aureus observed in the BUGG trial was observed in units also using chlorhexidine bathing and in those that previously performed active surveillance.
PMCID: PMC4533903  PMID: 25707404
MRSA; VRE; contact precautions; chlorhexidine bathing; infection control; active surveillance
9.  Latest Quaternary palaeoceanographic change in the eastern North Atlantic based upon a dinoflagellate cyst event ecostratigraphy 
Heliyon  2016;2(5):e00114.
The analyses of dinoflagellate cyst records, from the latest Quaternary sediments recovered from DSDP Core 610A taken on the Feni Ridge in the southern Rockall Trough, and part of core MD01-2461 on the continental margin of the Porcupine Seabight in the eastern North Atlantic Ocean, has provided evidence for significant oceanographic change encompassing the Last Glacial Maximum (LGM) and part of the Holocene. This together with other published records has led to a regional evaluation of oceanographic change in the eastern North Atlantic over the past 68 ka, based upon a distinctive dinoflagellate event ecostratigraphy. These changes reflect changes in the surface waters of the North Atlantic Current (NAC), and perhaps the deeper thermohaline Atlantic Meridional Overturning Circulation (AMOC), driving fundamental regime changes within the phytoplanktonic communities. Three distinctive dinoflagellate cyst associations based upon both factor and cluster analyses have been recognised. Associations characterised by Bitectatodinium tepikiense (between 61.1 ± 6.2 to 13.4 ± 1.1 ka BP), Nematosphaeropsis labyrinthus (between 10.5 ± 0.3 and 11.45 ± 0.8 ka. BP), and the cyst of Protoceratium reticulatum (between 8.5 ± 0.9 and 5.2 ± 1.3 ka. BP) indicate major change within the eastern North Atlantic oceanography. The transitions between these changes occur over a relatively short time span (c.1.5 ka), given our sampling resolution, and have the potential to be incorporated into an event stratigraphy through the latest Quaternary as recommended by the INTIMATE (INTegrating Ice core, MArine and TErrestrial records) group. The inclusion of a dinoflagellate cyst event stratigraphy would highlight changes within the phytoplankton of the North Atlantic Ocean as a fully glacial world changed to our present interglacial.
PMCID: PMC4946179  PMID: 27441285
Earth science
10.  Carbapenem Therapy Is Associated With Improved Survival Compared With Piperacillin-Tazobactam for Patients With Extended-Spectrum β-Lactamase Bacteremia 
The role of piperacillin-tazobactam (PTZ) for extended spectrum β-lactamase (ESBL) bacteremia is unclear. In a propensity-score–matched study of ESBL bacteremic patients, the adjusted risk of death was 1.92 times higher for patients receiving empiric PTZ compared with empiric carbapenem therapy.
Background. The effectiveness of piperacillin-tazobactam (PTZ) for the treatment of extended-spectrum β-lactamase (ESBL) bacteremia is controversial. We compared 14-day mortality of PTZ vs carbapenems as empiric therapy in a cohort of patients with ESBL bacteremia who all received definitive therapy with a carbapenem.
Methods. Patients hospitalized between January 2007 and April 2014 with monomicrobial ESBL bacteremia were included. A decrease of >3 doubling dilutions in the minimum inhibitory concentration for third-generation cephalosporins tested in combination with 4 µg/mL of clavulanic acid was used to confirm ESBL status. The primary exposure was empiric therapy, defined as antibiotic therapy administered to a patient before ESBL status was known. Patients were excluded if they did not receive a carbapenem after ESBL production was identified. The primary outcome was time to death from the first day of bacteremia. Propensity scores using inverse probability of exposure weighting (IPW) were used to estimate the probability that a patient would receive PTZ vs carbapenems empirically. We calculated overall hazard ratios for mortality censored at 14 days using Cox proportional hazards models on an IPW-adjusted cohort.
Results. A total of 331 unique patients with ESBL bacteremia were identified. One hundred three (48%) patients received PTZ empirically and 110 (52%) received carbapenems empirically. The adjusted risk of death was 1.92 times higher for patients receiving empiric PTZ compared with empiric carbapenem therapy (95% confidence interval, 1.07–3.45).
Conclusions. PTZ appears inferior to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of invasive ESBL infections, early carbapenem therapy should be considered. Our findings should not be extended to β-lactam/β-lactamase inhibitor combinations in development, as limited clinical data are available for these agents.
PMCID: PMC4462658  PMID: 25586681
ESBL; piperacillin-tazobactam; carbapenem; gram-negative; resistance
11.  Surgical Site Infection after Renal Transplantation 
To identify factors associated with the development of surgical site infection among adult patients undergoing renal transplantation.
A retrospective cohort study
An urban tertiary care center in Baltimore, MD with a well-established renal transplantation program that performs approximately 200–250 renal transplant procedures annually.
441 adult patients underwent renal transplantation from January 1st, 2010 and December 31st, 2011. Fifteen percent (66/441) of cohort patients developed an SSI; 47% (31/66) of these were superficial-incisional and 53% (35/66) were deep-incisional or organ-space. The average BMI among cohort patients was 29.7 and 42% (184/441) were obese (BMI > 30). Patients who developed SSI had a greater mean BMI (31.7 vs 29.4, p =0.004) and were more likely to have a history of peripheral vascular disease, rheumatologic disease, and narcotic abuse. History of cerebral vascular disease was protective. Multivariate analysis showed BMI (Odds Ratio (OR) 1.06; 95% Confidence Interval (CI): 1.02 to 1.11) and past history of narcotic use/abuse (OR 4.86, 95% CI: 1.24 to 19.12) to be significantly associated with development of SSI after controlling for National Healthcare Surveillance Network (NHSN) Score and presence of cerebrovascular, peripheral vascular and rheumatologic disease.
We identified higher BMI as a risk factor for the development of SSI following renal transplantation. Of note, neither aggregate comorbidity scores nor NHSN risk index were associated with SSI in this population. Additional risk adjustment measures and research in this area is needed to compare SSIs across transplant centers.
PMCID: PMC4367121  PMID: 25782896
Surgical Site Infection; Kidney Transplant; Risk Adjustment
12.  Risk factors for Central Line-associated Bloodstream Infections: A Focus on Comorbid Conditions 
Narrative abstract
CDC risk adjustment methods for CLABSI only adjust for ICU type. This cohort study explored risk factors for CLABSI using two comorbidity classification schemes, the Charlson Comorbidity Index and the Chronic Disease Score. Our study supports the need for additional research into risk factors for CLABSI, including electronically-available comorbid conditions.
PMCID: PMC4367124  PMID: 25782906
13.  Difficulties in Demonstrating Superiority of an Antibiotic for Multidrug-Resistant Bacteria in Nonrandomized Studies 
This article describes the epidemiological challenges of randomized superiority trials and the epidemiological issues in studies aiming to demonstrate superiority of antibiotics in nonrandomized retrospective database trials.
The discovery and development of new antimicrobials is critically important, especially as multidrug-resistant bacteria continue to emerge. Little has been written about the epidemiological issues in nonrandomized trials aiming to evaluate the superiority of one antibiotic over another. In this manuscript, we outline some of the methodological difficulties in demonstrating superiority and discuss potential approaches to these problems. Many of the difficulties arise due to confounding by indication, which we define and explain. Epidemiological methods including restriction, matching, stratification, multivariable regression, propensity scores, and instrumental variables are discussed.
PMCID: PMC4271096  PMID: 24982037
antibiotics; epidemiology; nonrandomized studies; research design; superiority
14.  Is hand hygiene before putting on nonsterile gloves in the intensive care unit a waste of health care worker time?—A randomized controlled trial 
Hand hygiene (HH) is recognized as a basic effective measure in prevention of nosocomial infections. However, the importance of HH before donning nonsterile gloves is unknown, and few published studies address this issue. Despite the lack of evidence, the World Health Organization and other leading bodies recommend this practice. The aim of this study was to assess the utility of HH before donning nonsterile gloves prior to patient contact.
A prospective, randomized, controlled trial of health care workers entering Contact Isolation rooms in intensive care units was performed. Baseline finger and palm prints were made from dominant hands onto agar plates. Health care workers were then randomized to directly don nonsterile gloves or perform HH and then don nonsterile gloves. Postgloving finger and palm prints were then made from the gloved hands. Plates were incubated and colony-forming units (CFU) of bacteria were counted.
Total bacterial colony counts of gloved hands did not differ between the 2 groups (6.9 vs 8.1 CFU, respectively, P = .52). Staphylococcus aureus was identified from gloves (once in “hand hygiene prior to gloving” group, twice in “direct gloving” group). All other organisms were expected commensal flora.
HH before donning nonsterile gloves does not decrease already low bacterial counts on gloves. The utility of HH before donning nonsterile gloves may be unnecessary.
PMCID: PMC4594854  PMID: 23891455
Infection control; Handwashing; Health care-associated infection; Nosocomial infection; Alcohol hand rub
15.  Preventing the transmission of multidrug-resistant organisms (MDROs): Modeling the relative importance of hand hygiene and environmental cleaning interventions 
Hand hygiene and environmental cleaning are essential infection prevention strategies, but the relative impact of each is unknown. This information is important in assessing resource allocation.
We developed an agent-based model of patient-to-patient transmission—via the hands of transiently colonized healthcare workers (HCW) and incompletely terminally cleaned rooms—in a 20-patient intensive care unit. Nurses and physicians were modeled and had distinct hand-hygiene compliance levels on entry and exit to patient rooms. We simulated the transmission of Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci for one year using data from the literature and observed data to inform model input parameters.
We simulated 175 parameter-based scenarios and compared the effects of hand hygiene and environmental cleaning on rates of MDRO acquisition. For all organisms, increases in hand-hygiene compliance outperformed equal increases in thoroughness of terminal cleaning. From the baseline, a 2:1 improvement in terminal cleaning compared to hand hygiene was required to match an equal reduction in acquisition rates (e.g., a 20% improvement in terminal cleaning was required to match the reduction in acquisition due to a 10% improvement in hand hygiene compliance).
Hand hygiene should remain a priority for infection control programs, but environmental cleaning can have significant benefit for hospitals or individual hospital units that have either high hand hygiene compliance levels or low terminal cleaning thoroughness.
PMCID: PMC4204209  PMID: 25111924
16.  Prior colonization is associated with increased risk of antibiotic-resistant Gram-negative bacteremia in cancer patients☆,☆☆ 
We hypothesized that prior colonization with antibiotic-resistant Gram-negative bacteria is associated with increased risk of subsequent antibiotic-resistant Gram-negative bacteremia among cancer patients. We performed a matched case-control study. Cases were cancer patients with a blood culture positive for antibiotic-resistant Gram-negative bacteria. Controls were cancer patients with a blood culture not positive for antibiotic-resistant Gram-negative bacteria. Prior colonization was defined as any antibiotic-resistant Gram-negative bacteria in surveillance or non-sterile-site cultures obtained 2–365 days before the bacteremia. Thirty-two (37%) of 86 cases and 27 (8%) of 323 matched controls were previously colonized by any antibiotic-resistant Gram-negative bacteria. Prior colonization was strongly associated with antibiotic-resistant Gram-negative bacteremia (odds ratio [OR] 7.2, 95% confidence interval [CI] 3.5–14.7) after controlling for recent treatment with piperacillin-tazobactam (OR 2.5, 95% CI 1.3–4.8). In these patients with suspected bacteremia, prior cultures may predict increased risk of antibiotic-resistant Gram-negative bacteremia.
PMCID: PMC4440656  PMID: 24582582
Antimicrobial resistance; Surveillance cultures; Neutropenic fever
17.  The Evolving Landscape of Healthcare-Associated Infections: Recent Advances in Prevention and a Road Map for Research 
This white paper identifies knowledge gaps and new challenges in healthcare epidemiology research, assesses the progress made toward addressing research priorities, provides the Society for Healthcare Epidemiology of America (SHEA) Research Committee’s recommendations for high-priority research topics, and proposes a road map for making progress toward these goals. It updates the 2010 SHEA Research Committee document, “Charting the Course for the Future of Science in Healthcare Epidemiology: Results of a Survey of the Membership of SHEA,” which called for a national approach to healthcare-associated infections (HAIs) and a prioritized research agenda. This paper highlights recent studies that have advanced our understanding of HAIs, the establishment of the SHEA Research Network as a collaborative infrastructure to address research questions, prevention initiatives at state and national levels, changes in reporting and payment requirements, and new patterns in antimicrobial resistance.
PMCID: PMC4226401  PMID: 24709716
18.  Frequency of Klebsiella pneumoniae carbapenemase (KPC) and non-KPC-producing Klebsiella contamination of Healthcare workers and the environment 
We examined contamination of healthcare worker (HCW) gown and gloves after caring for patients with Klebsiella Producing Carbapenemase-producing and non-KPC-producing Klebsiella as a proxy for horizontal transmission. Contamination rate with Klebsiella is similar to MRSA and VRE, with 14% (31/220) of HCW-patient interactions resulting in contamination of gloves and gowns.
PMCID: PMC4030386  PMID: 24602950
20.  Efficacy, safety, and impact on hospitalizations of paliperidone palmitate in recent-onset schizophrenia 
To evaluate the efficacy, safety, and impact on hospitalizations of long-acting injectable paliperidone palmitate (PP) treatment, in patients with recent-onset schizophrenia who had not responded satisfactorily to oral antipsychotics.
In this 18-month, open-label, Phase-IIIb study from Asia-Pacific region, patients (18–50 years) with recent-onset (≤5 years) schizophrenia unsatisfactorily treated with previous oral antipsychotics were initiated on PP 150 mg eq on day 1, 100 mg eq on day 8, followed by flexible once monthly maintenance doses of 50–150 mg eq. The number and duration of hospitalizations were compared using a mirror analysis method between two periods: retrospective (12 months before PP initiation) and prospective (12 and 18 months after PP treatment) periods.
A total of 303 out of 521 (58%) patients (mean age, 28.7 years; 65.5% men, 92.5% Asian) completed the study. Positive and Negative Syndrome Scale (PANSS) total score improved significantly from baseline to month 18 (mean [standard deviation, SD] change: −11.3 [21.38], P<0.0001, primary endpoint). Subgroup analysis revealed greater improvements among patients with worse disease severity at baseline: PANSS ≥70 versus <70 (mean [SD] change: −23.1 [24.62] vs −4.7 [15.98], P<0.0001 each). Secondary efficacy endpoints such as Clinical Global Impression of Schizophrenia (CGI-SCH), Medication Satisfaction Questionnaire (MSQ) scores showed significant improvements (P<0.0001) from baseline; 33.3% patients achieved symptom remission. In mirror analyses set (N=474), PP significantly (P<0.0001) reduced mean number of hospitalization days/person/year (12-month: 74.3 vs 19.7; 18-month: 74.3 vs 18.9) as well as percentage of patients requiring hospitalization in past 12 months (12-month: 39.7% vs 24.6%; 18-month: 39.7% vs 25%), and PP treatment increased the proportion of patients not requiring hospitalization (12-month: 60.3% vs 75.4%; 18-month: 60.3% vs 75%) from retrospective to prospective period. Adverse events (≥15%) were extrapyramidal symptoms-related (31.3%), injection-site pain (18.6%), and insomnia (15.2%).
PP was efficacious and generally tolerable with significant reductions observed in both number of hospitalizations and days spent in hospital.
PMCID: PMC4362974  PMID: 25792835
atypical antipsychotics; long-acting injectables; open-label; paliperidone palmitate; schizophrenia
21.  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
22.  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
23.  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
24.  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
25.  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

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