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Find video protocols related to scientific articles indexed in Pubmed.
Computerized Clinical Decision Support Improves Warfarin Management and Decreases Recurrent Venous Thromboembolism.
Clin. Appl. Thromb. Hemost.
PUBLISHED: 09-18-2014
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An explicit approach to warfarin dose adjustment using computerized clinical decision support (CDS) improves warfarin management. We report metrics of quality for warfarin management before and after implementation of CDS in a large health care system.
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The use of plain radiographs in the classification of distal radius fractures.
J Orthop
PUBLISHED: 09-01-2014
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Classification systems guide surgical planning. We reviewed the accuracy of interpreting plain radiographs to classify distal radius fractures.
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Automated detection of physiologic deterioration in hospitalized patients.
J Am Med Inform Assoc
PUBLISHED: 08-27-2014
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Develop and evaluate an automated case detection and response triggering system to monitor patients every 5?min and identify early signs of physiologic deterioration.
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Proteinuria is associated with neurocognitive impairment in antiretroviral therapy treated HIV-infected individuals.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-15-2014
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Proteinuria is a marker of vascular dysfunction that predicted increased cardiovascular mortality and is associated with neurocognitive impairment (NCI) in population-based studies. We examined associations between proteinuria and HIV-associated NCI.
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Difficulties in demonstrating superiority of an antibiotic for multidrug-resistant bacteria in nonrandomized studies.
Clin. Infect. Dis.
PUBLISHED: 06-30-2014
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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.
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Major bleeding with dabigatran and rivaroxaban in patients with atrial fibrillation: a real-world setting.
Clin. Appl. Thromb. Hemost.
PUBLISHED: 05-28-2014
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Although the rate of bleeding among patients with atrial fibrillation (AF) taking novel oral anticoagulants in randomized controlled trials is described, the rate of bleeding with "real-world" use is uncertain.
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Impact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV-seropositive individuals with cognitive impairment.
J. Neurovirol.
PUBLISHED: 05-23-2014
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Elevated cerebrospinal fluid (CSF) levels of markers of oxidative stress, neuronal injury, and inflammation and decreased neurotransmitter levels have been reported in HIV-associated neurocognitive disorders (HAND). Minocycline may have a neuroprotective effect by inhibiting inducible nitric oxide synthase, which produces nitric oxide, a compound that induces oxygen free radical production. In A5235, "Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-Associated Cognitive Impairment," minocycline was not associated with cognitive improvement, but the effect on the above CSF measures was not examined previously. The objective of this study was to examine the effect of minocycline on markers of oxidative stress, neuronal injury, neurotransmitter levels, and inflammation from CSF in participants in A5235. One hundred seven HIV+ individuals received either minocycline 100 mg or placebo orally every 12 h for 24 weeks. Twenty-one HIV+ individuals received the optional lumbar punctures. Lipid and protein markers of oxidative stress (e.g., ceramides and protein carbonyls), glutamate, neurotransmitter precursors, kynurenine metabolites, neurofilament heavy chain, and inflammatory cytokines were measured in the CSF before and after treatment. The 24-week change in ceramides was larger in a beneficial direction in the minocycline group compared to the placebo group. The two groups did not differ in the 24-week changes for other markers.These results suggest that minocycline may decrease lipid markers of oxidative stress (ceramides) in individuals with HAND; however, an effect of minocycline on other CSF markers was not observed. A larger sample size is needed to further validate these results.
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Assessment of the safety and efficiency of using an age-adjusted d-dimer threshold to exclude suspected pulmonary embolism.
Chest
PUBLISHED: 05-17-2014
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D-dimer increases with age, and recent research suggests that the use of an age-adjusted d-dimer threshold may improve diagnostic efficiency without compromising safety.
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Surveillance of carbapenem-resistant Klebsiella pneumoniae: tracking molecular epidemiology and outcomes through a regional network.
Antimicrob. Agents Chemother.
PUBLISHED: 05-05-2014
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Carbapenem resistance in Gram-negative bacteria is on the rise in the United States. A regional network was established to study microbiological and genetic determinants of clinical outcomes in hospitalized patients with carbapenem-resistant (CR) Klebsiella pneumoniae in a prospective, multicenter, observational study. To this end, predefined clinical characteristics and outcomes were recorded and K. pneumoniae isolates were analyzed for strain typing and resistance mechanism determination. In a 14-month period, 251 patients were included. While most of the patients were admitted from long-term care settings, 28% of them were admitted from home. Hospitalizations were prolonged and complicated. Nonsusceptibility to colistin and tigecycline occurred in isolates from 7 and 45% of the patients, respectively. Most of the CR K. pneumoniae isolates belonged to repetitive extragenic palindromic PCR (rep-PCR) types A and B (both sequence type 258) and carried either blaKPC-2 (48%) or blaKPC-3 (51%). One isolate tested positive for blaNDM-1, a sentinel discovery in this region. Important differences between strain types were noted; rep-PCR type B strains were associated with blaKPC-3 (odds ratio [OR], 294; 95% confidence interval [CI], 58 to 2,552; P < 0.001), gentamicin nonsusceptibility (OR, 24; 95% CI, 8.39 to 79.38; P < 0.001), amikacin susceptibility (OR, 11.0; 95% CI, 3.21 to 42.42; P < 0.001), tigecycline nonsusceptibility (OR, 5.34; 95% CI, 1.30 to 36.41; P = 0.018), a shorter length of stay (OR, 0.98; 95% CI, 0.95 to 1.00; P = 0.043), and admission from a skilled-nursing facility (OR, 3.09; 95% CI, 1.26 to 8.08; P = 0.013). Our analysis shows that (i) CR K. pneumoniae is seen primarily in the elderly long-term care population and that (ii) regional monitoring of CR K. pneumoniae reveals insights into molecular characteristics. This work highlights the crucial role of ongoing surveillance of carbapenem resistance determinants.
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Tigecycline Therapy for Carbapenem-Resistant Klebsiella pneumoniae (CRKP) Bacteriuria Leads to Tigecycline Resistance.
Clin. Microbiol. Infect.
PUBLISHED: 04-23-2014
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Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an increasing global threat. Here, we describe the prevalence and impact of tigecycline use in a cohort of patients with CRKP bacteriuria nested within a multicenter, prospective study. In the 21 month study period, 260 unique patients were included. Tigecycline was given to 80 (31%) patients. The use of tigecycline during the index hospitalization was significantly associated with the subsequent development of tigecycline resistance in the same patient (OR 6.13, 95%CI 1.15-48.65, p=0.03). In conclusion, the use of tigecycline with CRKP bacteriuria is common, and is associated with the subsequent development of tigecycline resistance. This article is protected by copyright. All rights reserved.
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Genetic variation in COMT activity impacts learning and dopamine release capacity in the striatum.
Learn. Mem.
PUBLISHED: 03-19-2014
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A common genetic polymorphism that results in increased activity of the dopamine regulating enzyme COMT (the COMT Val(158) allele) has been found to associate with poorer cognitive performance and increased susceptibility to develop psychiatric disorders. It is generally assumed that this increase in COMT activity influences cognitive function and psychiatric disease risk by increasing dopamine turnover in cortical synapses, though this cannot be directly measured in humans. Here we explore a novel transgenic mouse model of increased COMT activity, equivalent to the relative increase in activity observed with the human COMT Val(158) allele. By performing an extensive battery of behavioral tests, we found that COMT overexpressing mice (COMT-OE mice) exhibit cognitive deficits selectively in the domains that are affected by the COMT Val(158) allele, stimulus-response learning and working memory, functionally validating our model of increased COMT activity. Although we detected no changes in the level of markers for dopamine synthesis and dopamine transport, we found that COMT-OE mice display an increase in dopamine release capacity in the striatum. This result suggests that increased COMT activity may not only affect dopamine signaling by enhancing synaptic clearance in the cortex, but may also cause changes in presynaptic dopamine function in the striatum. These changes may underlie the behavioral deficits observed in the mice and might also play a role in the cognitive deficits and increased psychiatric disease risk associated with genetic variation in COMT activity in humans.
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Assessing Compliance With Established Pneumonia Core Measures at a Comprehensive Cancer Center.
J Healthc Qual
PUBLISHED: 03-18-2014
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Healthcare organizations use Pneumonia Core Measures (PCMs) to ensure delivery of high-quality care. In this study, a multidisciplinary team was organized to optimize care and enhance compliance in a comprehensive cancer emergency center. We performed a four-phase study, three of which were interventional: intense education regarding PCM; microbiologic analysis of the pathogens responsible for the pneumonias; development and implementation of an institutional pneumonia algorithm and order set. In phase 4, we analyzed five PCMs. The percentage of pneumonia patients from whom blood cultures were obtained increased from 73% to 91% after intervention (p < .001); sputum cultures increased from baseline 24.6% to 51% (p = .004) post order-set implementation, and order-set utilization increased from 40% to 77%. We achieved the benchmark for only one PCM, PN 3a. More than 80% of patients met clinical and microbiological criteria for healthcare-associated pneumonia. We identified a gap between our patient population and some PCMs that relates to antibiotics selection. The treatment of cancer patients and pneumonia falls outside established guidelines for treating community-acquired pneumonia. Although the algorithm and order set implemented optimized care and minimized variation, national benchmarks for four of the PCMs were not met. Our findings provide information for policymakers considering pneumonia measurements for antibiotic selection in a cancer care setting.
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Antibacterial resistance leadership group: open for business.
Clin. Infect. Dis.
PUBLISHED: 03-06-2014
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Funded by the National Institute of Allergy and Infectious Diseases, the Antibacterial Resistance Leadership Group (ARLG) is tasked with developing a clinical research agenda and conducting clinical studies to address the growing public health threat of antibacterial resistance. The ARLG has identified 4 high-priority areas of research: infections caused by gram-negative bacteria, infections caused by gram-positive bacteria, antimicrobial stewardship and infection prevention, and diagnostics. The ARLG will be accepting proposals from the scientific community for clinical research that addresses 1 or more of these high-priority areas. These studies should have the potential to transform medical practice and be unlikely to occur without ARLG support. The purpose of this article is to make interested parties aware of clinical research opportunities made available by ARLG and to encourage submission of clinical research proposals that address the problem of antibacterial resistance.
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Predicting pneumonia mortality using CURB-65, PSI, and patient characteristics in patients presenting to the emergency department of a comprehensive cancer center.
Cancer Med
PUBLISHED: 03-03-2014
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The prognostic accuracy of the CURB-65 criteria and pneumonia severity index (PSI) in immunocompromised cancer patients with pneumonia is unknown. We sought to determine whether CURB-65 and PSI predict 28-day mortality in cancer patients with pneumonia, and identify other factors that predispose cancer patients with pneumonia to a high mortality risk. We assessed sensitivities, specificities, predictive values, and areas under the receiver operating curve area under the curve (AUC) of the CURB-65 and PSI in predicting the 28-day mortality of cancer patients presenting to our institution's emergency department with pneumonia. We used the DeLong and Clarke-Pearson approach to determine whether the addition of other risk factors improved the scales' performances. The overall and pneumonia-related 28-day mortality rates were 20.2% (n = 44) and 17.4% (n = 38), respectively. In predicting 28-day mortality, the CURB-65 score had sensitivity of 45% and specificity of 81%, and the PSI score had sensitivity of 82% and specificity of 34%. The CURB-65 and PSI discriminated poorly between fatal and nonfatal pneumonia cases (AUCs, 0.664 and 0.658, respectively; 95% confidence interval [CI], 0.57-0.75 for each). The addition of radiation therapy (RT) within 4 weeks and stem cell transplant (SCT) significantly improved the AUCs of the CURB-65 (0.75; 95% CI, 0.67-0.83) and PSI (0.73; 95% CI, 0.65-0.82). Inadequate performances of CURB-65 and PSI demonstrate that a tool for predicting pneumonia-related mortality in cancer patients and other immunocompromised populations is needed. Pneumonia patients who have undergone recent RT or (SCT) are at a high risk of dying from pneumonia and require special consideration when assessing pneumonia-related mortality risk.
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Sample size determination in group-sequential clinical trials with two co-primary endpoints.
Stat Med
PUBLISHED: 02-11-2014
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We discuss sample size determination in group-sequential designs with two endpoints as co-primary. We derive the power and sample size within two decision-making frameworks. One is to claim the test intervention's benefit relative to control when superiority is achieved for the two endpoints at the same interim timepoint of the trial. The other is when superiority is achieved for the two endpoints at any interim timepoint, not necessarily simultaneously. We evaluate the behaviors of sample size and power with varying design elements and provide a real example to illustrate the proposed sample size methods. In addition, we discuss sample size recalculation based on observed data and evaluate the impact on the power and Type I error rate.
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Synovial chondrosarcoma arising in synovial chondromatosis.
Sarcoma
PUBLISHED: 01-30-2014
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Primary synovial chondromatosis (SC) is a rare proliferative disorder that causes pain, swelling, and restriction of movement to the joints it affects. The disease frequently runs a protracted course, often requiring multiple surgical procedures to obtain some control. Few reports exist detailing the natural history of SC, although malignant transformation to synovial chondrosarcoma (CHS) is recognized to be a rare event. The aim of our study was to review a large orthopaedic oncology database in order to evaluate the incidence of CHS arising from SC. We identified 78 patients who have presented to our centre with primary synovial chondromatosis (SC). Of those patients, 5 went on to develop malignant change. This represents a 6.4% incidence of developing synovial chondrosarcoma (CHS) within preexisting primary synovial chondromatosis. The patients had a mean age of 28 years at first diagnosis with synovial chondromatosis with the median time from original diagnosis to malignant transformation being 20 years (range 2.7-39?yrs).
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Safety, tolerability, and biomarkers of the treatment of mice with aerosolized Toll-like receptor ligands.
Front Pharmacol
PUBLISHED: 01-01-2014
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We have previously discovered a synergistically therapeutic combination of two Toll-like receptor ligands, an oligodeoxynucleotide (ODN) and Pam2CSK4. Aerosolization of these ligands stimulates innate immunity within the lungs to prevent pneumonia from bacterial and viral pathogens. Here we examined the safety and tolerability of this treatment in mice, and characterized the expression of biomarkers of innate immune activation. We found that neutrophils appeared in lung lavage fluid 4 h after treatment, reached a peak at 48 h, and resolved by 7 days. The peak of neutrophil influx was accompanied by a small increase in lung permeability. Despite the abundance of neutrophils in lung lavage fluid, only rare neutrophils were visible histopathologically in the interstitium surrounding bronchi and veins and none were visible in alveolar airspaces. The cytokines interleukin 6 (IL-6), tumour necrosis factor, and Chemokine (C-X-C motif) ligand 2 rose several hundred-fold in lung lavage fluid 4 h after treatment in a dose-dependent and synergistic manner, providing useful biomarkers of lung activation. IL-6 rose fivefold in serum with delayed kinetics compared to its rise in lavage fluid, and might serve as a systemic biomarker of immune activation of the lungs. The dose-response relationship of lavage fluid cytokines was preserved in mice that underwent myeloablative treatment with cytosine arabinoside to model the treatment of hematologic malignancy. There were no overt signs of distress in mice treated with ODN/Pam2CSK4 in doses up to eightfold the therapeutic dose, and no changes in temperature, respiratory rate, or behavioral signs of sickness including sugar water preference, food disappearance, cage exploration or social interaction, though there was a small degree of transient weight loss. We conclude that treatment with aerosolized ODN/Pam2CSK4 is well tolerated in mice, and that innate immune activation of the lungs can be monitored by the measurement of inflammatory cytokines in lung lavage fluid and serum.
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A comparison of reversed locking compression-distal femoral plates and blade plates in osteotomies for young adult hip pathology.
Hip Int
PUBLISHED: 12-13-2013
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The aim of this study was to compare fixation of proximal femoral osteotomies using reverse contralateral LCP-Distal Femoral Plates (LCP-DF) with the more traditional blade plate technique. This was a retrospective review over six years of a single surgeons practice within a tertiary orthopaedic unit. Patient demographics were collected, along with indication for surgery. Radiological outcomes, fixation failures and the need for revision surgery were recorded. Forty-six patients were identified; 23 patients in the LCP-DF plate group (7 females, 16 males. Mean age 18.3 years old) and 23 patients in the blade plate group (6 females, 17 males. Mean age 19.1 years old). The patients presenting conditions were; 26 Perthes; eight hip dysplasia; 11 slipped capital femoral epiphysis; one fibrous dysplasia. Osteotomy type included; 13 Double osteotomy, 11 Imhauser; 13 pure valgus; eight valgus + rotation; There was one revision for implant failure in the LCP-DF group. In the blade plate group, there were four implant failures - three requiring revision operations (p = 0.155). In the LCP-DF group the mean neck-shaft angle difference compared to the contralateral side (if normal) or 135 degrees (if abnormal) was 0.58°. In the condylar plate group the mean difference was 4.37°. The use of a contralateral LCP-DF plate in the reverse contralateral position to stabilise proximal femoral osteotomies in our cohort confers advantages over blade plate technology. We have found that the plate is stiffer, is easier to use and provides increased screw placement options over standard proximal femoral locking plates.
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Muc5b is required for airway defence.
Nature
PUBLISHED: 10-28-2013
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Respiratory surfaces are exposed to billions of particulates and pathogens daily. A protective mucus barrier traps and eliminates them through mucociliary clearance (MCC). However, excessive mucus contributes to transient respiratory infections and to the pathogenesis of numerous respiratory diseases. MUC5AC and MUC5B are evolutionarily conserved genes that encode structurally related mucin glycoproteins, the principal macromolecules in airway mucus. Genetic variants are linked to diverse lung diseases, but specific roles for MUC5AC and MUC5B in MCC, and the lasting effects of their inhibition, are unknown. Here we show that mouse Muc5b (but not Muc5ac) is required for MCC, for controlling infections in the airways and middle ear, and for maintaining immune homeostasis in mouse lungs, whereas Muc5ac is dispensable. Muc5b deficiency caused materials to accumulate in upper and lower airways. This defect led to chronic infection by multiple bacterial species, including Staphylococcus aureus, and to inflammation that failed to resolve normally. Apoptotic macrophages accumulated, phagocytosis was impaired, and interleukin-23 (IL-23) production was reduced in Muc5b(-/-) mice. By contrast, in mice that transgenically overexpress Muc5b, macrophage functions improved. Existing dogma defines mucous phenotypes in asthma and chronic obstructive pulmonary disease (COPD) as driven by increased MUC5AC, with MUC5B levels either unaffected or increased in expectorated sputum. However, in many patients, MUC5B production at airway surfaces decreases by as much as 90%. By distinguishing a specific role for Muc5b in MCC, and by determining its impact on bacterial infections and inflammation in mice, our results provide a refined framework for designing targeted therapies to control mucin secretion and restore MCC.
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Pneumonia during remission induction chemotherapy in patients with acute leukemia.
Ann Am Thorac Soc
PUBLISHED: 08-31-2013
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Pneumonia is a major cause of death during induction chemotherapy for acute leukemia. The purpose of this study was to quantify the incidence, risk factors, and outcomes of pneumonia in patients with acute leukemia.
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Early detection of hospitalized patients with previously diagnosed obstructive sleep apnea using computer decision support alerts.
Stud Health Technol Inform
PUBLISHED: 08-08-2013
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Obstructive sleep apnea (OSA) is a worldwide problem affecting 2-14% of the general population and most patients remain undiagnosed. OSA patients are at elevated risk for hypoxemia, cardiac arrhythmias, cardiorespiratory arrest, hypoxic encephalopathy, stroke and death during hospitalization. Clinical screening questionnaires are used to identify hospitalized patients with OSA; especially before surgery. However, current screening questionnaires miss a significant number of patients and require more definitive testing before specific therapy can be started. Moreover, many patients are admitted to the hospital with a previous diagnosis of OSA that is not reported. Thus, many patients with OSA do not receive appropriate therapy during hospitalization due to the lack of information from previous inpatient and outpatient encounters. Large enterprise data warehouses provide the ability to monitor patient encounters over wide geographical areas. This study found that previously diagnosed OSA is highly prevalent and undertreated in hospitalized patients and the use of early computer alerts by respiratory therapists resulted in significantly more OSA patients receiving appropriate medical care (P < 0.002) which resulted in significantly fewer experiencing hypoxemia (P < 0.006). The impact was greater for non-surgery patients compared to surgery patients.
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Peripheral neuropathy in ART-experienced patients: prevalence and risk factors.
J. Neurovirol.
PUBLISHED: 08-05-2013
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Peripheral neuropathy (PN) is a common neurological complication of HIV infection that has debilitating effects on quality of life. While there has been a comprehensive evaluation of the prevalence of neuropathic signs/symptoms and risk factors (RFs) for PN or symptomatic PN (SPN) with initiation of combination antiretroviral therapy (cART) in ART-naïve patients, similar evaluation in ART-experienced patients is limited. This study investigated the prevalence and RFs for PN/SPN in ART-experienced patients enrolled in clinical salvage therapy studies. Between February 2000 and June 2007, 522 ART-experienced participants who experienced virologic failure with a prior regimen and started new regimens were followed longitudinally and annually screened for signs and symptoms of PN. Rates of PN/SPN at 3 years since parent study entry were 52.8 and 24.0 %, respectively. Aging, taller height, protease inhibitor use, and female sex were significant RFs for PN/SPN. The use of statin drugs was significantly associated with lower odds of SPN, and it may prevent progression from no SPN to SPN.
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Reduction of peripherally inserted central catheter-associated DVT.
Chest
PUBLISHED: 07-09-2013
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As peripherally inserted central catheter (PICC) use has increased, so has the upper extremity DVT rate. PICC diameter may pose the most modifiable risk for PICC-associated DVT.
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Molecular analysis of dermatophytes suggests spread of infection among household members.
Cutis
PUBLISHED: 06-18-2013
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Dermatophyte infection from the same strains may be an important route for transmission of dermatophytoses within a household. In this study, we used molecular methods to identify dermatophytes in members of dermatophyte-infected households and evaluated variables associated with the spread of infection. Fungal species were identified by polymerase chain reaction (PCR) using primers targeting the internal transcribed spacer (ITS) regions (ITS1 and ITS4). For strain differentiation, fungal DNA was probed with a ribosomal DNA-specific probe (containing ITS1, 5.8S ribosomal DNA, and ITS2) to detect restriction fragment length polymorphisms (RFLPs). Associations between the spread of a dermatophyte infection and fungal/host variables were determined using ?² and logistic regression analyses. Among the 50 households enrolled in this study, 18 included multiple infected members (MIMs). Trichophyton rubrum was the most commonly isolated dermatophyte species, followed by Trichophyton mentagrophyts and Epidermophyton floccosum. Sixteen T rubrum strains (TR-A to TR-P) were identified, with spread of infection detected in 8 MIM households. Factors that were significantly (P<.05) associated with the spread of infection included the presence of strains TR-B or TR-D, a history of concomitant tinea pedis and onychomycosis, and plantar scaling and/or nail discoloration. This study is unique in that it used molecular evidence to demonstrate the association of certain strains with the spread of dermatophyte infection among members of the same household.
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Follow-Up of Incidental Pulmonary Nodules and the Radiology Report.
J Am Coll Radiol
PUBLISHED: 05-14-2013
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Incidental pulmonary nodules that require follow-up are often noted on chest CT. Evidence-based guidelines regarding appropriate follow-up have been published, but the rate of adherence to guideline recommendations is unknown. Furthermore, it is unknown whether the radiology report affects the nodule follow-up rate.
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Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies.
Pain Med
PUBLISHED: 04-08-2013
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There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared with placebo.
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Deletion of the gene encoding calcitonin and calcitonin gene-related peptide ? does not affect the outcome of severe infection in mice.
Am. J. Respir. Cell Mol. Biol.
PUBLISHED: 03-26-2013
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Procalcitonin (PCT) is expressed in nonthryoidal tissues of humans during severe infections. Serum PCT levels are measured to diagnose and guide therapy, and there is some evidence that PCT may also contribute to the pathogenesis of sepsis. We tested whether disruption of the gene encoding PCT in mice affected the course of sepsis. Mice with exons 2-5 of the gene encoding calcitonin/calcitonin gene-related polypeptide ? (Calca) knocked out and congenic C57BL/6J control mice were challenged with aerosolized Streptococcus pneumoniae or Pseudomonas aeruginosa, or injected intraperitoneally with S. pneumoniae. There were no significant differences in the survival of knockout and control mice in the two pneumonia models, and no significant differences in weight loss, splenic bacterial counts, or blood leukocyte levels in the peritoneal sepsis model. To verify disruption of the Calca gene in knockout mice, the absence of calcitonin in the serum of knockout mice and its presence and inducibility in control mice were confirmed. To evaluate PCT expression in nonthyroidal tissues of control mice, transcripts were measured in multiple organs. PCT transcripts were not significantly expressed in liver or spleen of control mice challenged with aerosolized P. aeruginosa or intraperitoneal endotoxin, and were expressed in lung only at low levels, even though serum IL-6 rose 3,548-fold. We conclude that mice are not an ideal loss-of-function model to test the role of PCT in the pathogenesis of sepsis because of low nonendocrine PCT expression during infection and inflammation. Nonetheless, our studies demonstrate that nonendocrine PCT expression is not necessary for adverse outcomes from sepsis.
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Toll-like receptor-2/6 and Toll-like receptor-9 agonists suppress viral replication but not airway hyperreactivity in guinea pigs.
Am. J. Respir. Cell Mol. Biol.
PUBLISHED: 03-02-2013
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Respiratory virus infections cause airway hyperreactivity (AHR). Preventative strategies for virus-induced AHR remain limited. Toll-like receptors (TLRs) have been suggested as a therapeutic target because of their central role in triggering antiviral immune responses. Previous studies showed that concurrent treatment with TLR2/6 and TLR9 agonists reduced lethality and the microbial burden in murine models of bacterial and viral pneumonia. This study investigated the effects of TLR2/6 and TLR9 agonist pretreatment on parainfluenza virus pneumonia and virus-induced AHR in guinea pigs in vivo. Synthetic TLR2/6 lipopeptide agonist Pam?CSK? and Class C oligodeoxynucleotide TLR9 agonist ODN2395, administered in combination 24 hours before virus infection, significantly reduced viral replication in the lung. Despite a fivefold reduction in viral titers, concurrent TLR2/6 and TLR9 agonist pretreatment did not prevent virus-induced AHR or virus-induced inhibitory M2 muscarinic receptor dysfunction. Interestingly, the TLR agonists independently caused non-M2-dependent AHR. These data confirm the therapeutic antiviral potential of TLR agonists, while suggesting that virus inhibition may be insufficient to prevent virus-induced airway pathophysiology. Furthermore, TLR agonists independently cause AHR, albeit through a distinctly different mechanism from that of parainfluenza virus.
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A logrank test-based method for sizing clinical trials with two co-primary time-to-event endpoints.
Biostatistics
PUBLISHED: 01-10-2013
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We discuss sample size determination for clinical trials evaluating the joint effects of an intervention on two potentially correlated co-primary time-to-event endpoints. For illustration, we consider the most common case, a comparison of two randomized groups, and use typical copula families to model the bivariate endpoints. A correlation structure of the bivariate logrank statistic is specified to account for the correlation among the endpoints, although the between-group comparison is performed using the univariate logrank statistic. We propose methods to calculate the required sample size to compare the two groups and evaluate the performance of the methods and the behavior of required sample sizes via simulation.
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Strengthening Partnerships along the Informatics Innovation Stages and Spaces: Research and Practice Collaboration in Utah.
Online J Public Health Inform
PUBLISHED: 12-22-2011
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Collaborate, translate, and impact are key concepts describing the roles and purposes of the research Centers of Excellence (COE) in Public Health Informatics (PHI). Rocky Mountain COE integrated these concepts into a framework of PHI Innovation Space and Stage to guide their collaboration between the University of Utah, Intermountain Healthcare, and Utah Department of Health. Seven research projects are introduced that illustrate the framework and demonstrate how to effectively manage multiple innovations among multiple organizations over a five-year period. A COE is more than an aggregation of distinct research projects over a short time period. The people, partnership, shared vision, and mutual understanding and appreciation developed over a long period of time form the core and foundation for ongoing collaborative innovations and its successes.
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Evaluation of HL7 v2.5.1 electronic case reports transmitted from a healthcare enterprise to public health.
AMIA Annu Symp Proc
PUBLISHED: 10-22-2011
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Public health surveillance is necessary to prevent and control communicable and non-communicable diseases. An electronic reporting system using HL7 v2.5.1 was implemented between Intermountain Healthcare and the Utah Department of Health. We conducted prospective and retrospective studies to evaluate the timeliness, completeness of content information, and completeness of the electronic reporting process, and compared these metrics against other reporting entities. The electronic reporting system was more timely than other clinical reporting facilities and included more complete information in initial case reports. During a four month period, the electronic reporting system captured 8% of the cases not reported by the paper-based reporting system but missed 5% of the cases reported by the paper-based reporting system. We believe it would be more efficient for Infection Preventionists at hospitals to use their resources to detect cases not captured by the electronic reporting system instead of manually re-reporting cases already transmitted to public health electronically.
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Comparison of computerized surveillance and manual chart review for adverse events.
J Am Med Inform Assoc
PUBLISHED: 06-16-2011
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To understand how the source of information affects different adverse event (AE) surveillance methods.
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Derivation and validation of a simple model to identify venous thromboembolism risk in medical patients.
Am. J. Med.
PUBLISHED: 05-17-2011
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Fewer than half of eligible hospitalized medical patients receive appropriate venous thromboembolism (VTE) prophylaxis. One reason for this low rate is the complexity of existing risk assessment models. A simple set of easily identifiable risk factors that are highly predictive of VTE among hospitalized medical patients may enhance appropriate thromboprophylaxis.
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Effects of central nervous system antiretroviral penetration on cognitive functioning in the ALLRT cohort.
AIDS
PUBLISHED: 05-17-2011
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Differences in antiretroviral distribution into the central nervous system (CNS) may impact neurocognitive status. We assessed the relationship between estimates of antiretroviral therapy penetration into the CNS, using a published ranking system, and neurocognitive status in HIV-positive participants with plasma HIV-1 RNA (vRNA) suppression.
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Deriving measures of intensive care unit antimicrobial use from computerized pharmacy data: methods, validation, and overcoming barriers.
Infect Control Hosp Epidemiol
PUBLISHED: 04-26-2011
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To outline methods for deriving and validating intensive care unit (ICU) antimicrobial utilization (AU) measures from computerized data and to describe programming problems that emerged.
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Synergistic interactions of TLR2/6 and TLR9 induce a high level of resistance to lung infection in mice.
J. Immunol.
PUBLISHED: 04-11-2011
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Infectious pneumonias exact an unacceptable mortality burden worldwide. Efforts to protect populations from pneumonia have focused historically on antibiotic development and vaccine-enhanced adaptive immunity. However, we have reported recently that the lungs innate defenses can be induced therapeutically by inhalation of a bacterial lysate that protects mice against otherwise lethal pneumonia. In this study, we tested in mice the hypothesis that TLRs are required for this antimicrobial phenomenon and found that resistance could not be induced in the absence of the TLR signaling adaptor protein MyD88. We then attempted to recapitulate the protection afforded by the bacterial lysate by stimulating the lung epithelium with aerosolized synthetic TLR ligands. Although most single or combination treatments yielded no protection, simultaneous treatment with ligands for TLR2/6 and TLR9 conferred robust, synergistic protection against virulent gram-positive and gram-negative pathogens. Protection was associated with rapid pathogen killing in the lungs, and pathogen killing could be induced from lung epithelial cells in isolation. Taken together, these data demonstrate the requirement for TLRs in inducible resistance against pneumonia, reveal a remarkable, unanticipated synergistic interaction of TLR2/6 and TLR9, reinforce the emerging evidence supporting the antimicrobial capacity of the lung epithelium, and may provide the basis for a novel clinical therapeutic that can protect patients against pneumonia during periods of peak vulnerability.
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Development and evaluation of a comprehensive clinical decision support taxonomy: comparison of front-end tools in commercial and internally developed electronic health record systems.
J Am Med Inform Assoc
PUBLISHED: 03-17-2011
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Clinical decision support (CDS) is a valuable tool for improving healthcare quality and lowering costs. However, there is no comprehensive taxonomy of types of CDS and there has been limited research on the availability of various CDS tools across current electronic health record (EHR) systems.
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Multicenter evaluation of a novel surveillance paradigm for complications of mechanical ventilation.
PLoS ONE
PUBLISHED: 02-21-2011
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Ventilator-associated pneumonia (VAP) surveillance is time consuming, subjective, inaccurate, and inconsistently predicts outcomes. Shifting surveillance from pneumonia in particular to complications in general might circumvent the VAP definitions subjectivity and inaccuracy, facilitate electronic assessment, make interfacility comparisons more meaningful, and encourage broader prevention strategies. We therefore evaluated a novel surveillance paradigm for ventilator-associated complications (VAC) defined by sustained increases in patients ventilator settings after a period of stable or decreasing support.
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Peripheral neuropathy in HIV: prevalence and risk factors.
AIDS
PUBLISHED: 02-19-2011
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To estimate neuropathic sign/symptom rates with initiation of combination antiretroviral therapy (cART) in HIV-infected ART-naive patients, and to investigate risk factors for: peripheral neuropathy and symptomatic peripheral neuropathy (SPN), recovery from peripheral neuropathy/SPN after neurotoxic ART (nART) discontinuation, and the absence of peripheral neuropathy/SPN while on nART.
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Comparison of clinical knowledge management capabilities of commercially-available and leading internally-developed electronic health records.
BMC Med Inform Decis Mak
PUBLISHED: 02-17-2011
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We have carried out an extensive qualitative research program focused on the barriers and facilitators to successful adoption and use of various features of advanced, state-of-the-art electronic health records (EHRs) within large, academic, teaching facilities with long-standing EHR research and development programs. We have recently begun investigating smaller, community hospitals and out-patient clinics that rely on commercially-available EHRs. We sought to assess whether the current generation of commercially-available EHRs are capable of providing the clinical knowledge management features, functions, tools, and techniques required to deliver and maintain the clinical decision support (CDS) interventions required to support the recently defined "meaningful use" criteria.
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Inhaled innate immune ligands to prevent pneumonia.
Br. J. Pharmacol.
PUBLISHED: 01-22-2011
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Epithelial surfaces throughout the body continuously sample and respond to environmental stimuli. The accessibility of lung epithelium to inhaled therapies makes it possible to stimulate local antimicrobial defences with aerosolized innate immune ligands. This strategy has been shown to be effective in preclinical models, as delivery of innate immune ligands to the lungs of laboratory animals results in protection from subsequent challenge with microbial pathogens. Survival of the animal host in this setting correlates directly with killing of pathogens within the lungs, indicating the induction of a resistance mechanism. Resistance appears to be mediated primarily by activated epithelial cells rather than recruited leucocytes. Resistance reaches a peak within hours and persists for several days. Innate immune ligands can interact synergistically under some circumstances, and synergistic combinations of innate ligands delivered by aerosol are capable of inducing a high level of broad host resistance to bacteria, fungi and viruses. The induction of innate antimicrobial resistance within the lungs could have clinical applications in the prevention of lower respiratory tract infection in subjects transiently at high risk. These include cancer patients undergoing myeloablative chemotherapy, intubated patients being mechanically ventilated, vulnerable individuals during seasonal influenza epidemics, asthmatic subjects experiencing a respiratory viral infection, and healthy subjects exposed to virulent pathogens from a bioterror attack or emergent pandemic. In summary, stimulation of the lung epithelium to induce localized resistance to infection is a novel strategy whose clinical utility will be assessed in the near future.
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Performance of a standardized bronchoalveolar lavage protocol in a comprehensive cancer center: a prospective 2-year study.
Cancer
PUBLISHED: 01-18-2011
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Flexible bronchoscopy with bronchoalveolar lavage (BAL) is performed widely for the diagnosis of pulmonary infections in patients with cancer, but there is no consensus regarding the technical parameters of the lavage procedure in this setting.
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A multinational study of neurological performance in antiretroviral therapy-naïve HIV-1-infected persons in diverse resource-constrained settings.
J. Neurovirol.
PUBLISHED: 01-12-2011
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Little is known about how the prevalence and incidence of neurological disease in HIV-infected patients in resource-limited settings. We present an analysis of neurological and neurocognitive function in antiretroviral naïve individuals in multinational resource-limited settings. This prospective multinational cohort study, a substudy of a large international randomized antiretroviral treatment trial, was conducted in seven low- and middle-income countries in sub-Saharan Africa, South America, and Asia. Subjects were HIV-infected and met regional criteria to initiate antiretroviral therapy. Standardized neurological examination and a brief motor-based neuropsychological examination were administered. A total of 860 subjects were studied. Overall 249 (29%) had one or more abnormalities on neurological examinations, but there was a low prevalence of HIV-associated dementia (HAD) and minor neurocognitive disorder (MND). Twenty percent of subjects had evidence of peripheral neuropathy. There were significant differences across countries (p?
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Interleukin 6, but not T helper 2 cytokines, promotes lung carcinogenesis.
Cancer Prev Res (Phila)
PUBLISHED: 11-22-2010
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Several epidemiologic studies have found that smokers with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lung, have an increased risk of lung cancer compared with smokers without COPD. We have shown a causal role for COPD-like airway inflammation in lung cancer promotion in the CCSP(Cre)/LSL-K-ras(G12D) mouse model (CC-LR). In contrast, existing epidemiologic data do not suggest any definite association between allergic airway inflammation and lung cancer. To test this, CC-LR mice were sensitized to ovalbumin (OVA) and then challenged with an OVA aerosol weekly for 8 weeks. This resulted in eosinophilic lung inflammation associated with increased levels of T helper 2 cytokines and mucous metaplasia of airway epithelium, similar to what is seen in asthmatic patients. However, this type of inflammation did not result in a significant difference in lung surface tumor number (49 ± 9 in OVA vs. 52 ± 5 in control) in contrast to a 3.2-fold increase with COPD-like inflammation. Gene expression analysis of nontypeable Haemophilus influenzae (NTHi)-treated lungs showed upregulation of a different profile of inflammatory genes, including interleukin 6 (IL-6), compared with OVA-treated lungs. Therefore, to determine the causal role of cytokines that mediate COPD-like inflammation in lung carcinogenesis, we genetically ablated IL-6 in CC-LR mice. This not only inhibited intrinsic lung cancer development (1.7-fold) but also inhibited the promoting effect of extrinsic COPD-like airway inflammation (2.6-fold). We conclude that there is a clear specificity for the nature of inflammation in lung cancer promotion, and IL-6 has an essential role in lung cancer promotion.
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Computer surveillance of patients at high risk for and with venous thromboembolism.
AMIA Annu Symp Proc
PUBLISHED: 11-13-2010
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Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), may be the number one preventable cause of death associated with hospitalization. Numerous evidence-based guidelines for effective VTE prophylaxis therapy exist. However, underuse is common due to the difficulty in integrating VTE risk assessment into routine patient care. Previous studies utilizing computer decision support to identify high-risk patients report improved use of prophylaxis therapy and reduced VTE. However, those studies did not report the sensitivity, specificity or positive predictive value of their methods to identify patients at high risk. We report an evaluation of a computerized tool to identify patients at high risk for VTE that found a sensitivity of 98% and positive predictive value of 99%. Another computer program used to detect VTE had a sensitivity of 92%, specificity of 99% and a positive predictive value of 97% to identify DVT and a sensitivity of 100%, specificity of 98% and positive predictive value of 89% to identify PE. These tools were found to provide a dependable method to identify patients at high risk for and with VTE.
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Toll-deficient Drosophila are resistant to infection by Pneumocystis spp.: additional evidence of specificity to mammalian hosts.
Virulence
PUBLISHED: 11-01-2010
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Pneumocystis spp. are significant pathogens in a variety of mammals. We tried to establish a Drosophila model of pneumocystosis using either P. murina or P. carinii. Whereas the pathogens were competent in susceptible mice, no infection could be established even in corticosteroid-treated Toll-deficient flies. This further substantiates the tropism described for mammalian hosts.
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Risk of symptomatic DVT associated with peripherally inserted central catheters.
Chest
PUBLISHED: 10-07-2010
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Previous studies undertaken to identify risk factors for peripherally inserted central catheter (PICC)-associated DVT have yielded conflicting results. PICC insertion teams and other health-care providers need to understand the risk factors so that they can develop methods to prevent DVT.
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Enhanced notification of infusion pump programming errors.
Stud Health Technol Inform
PUBLISHED: 09-16-2010
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Hospitalized patients receive countless doses of medications through manually programmed infusion pumps. Many medication errors are the result of programming incorrect pump settings. When used appropriately, smart pumps have the potential to detect some programming errors. However, based on the current use of smart pumps, there are conflicting reports on their ability to prevent patient harm without additional capabilities and interfaces to electronic medical records (EMR). We developed a smart system that is connected to the EMR including medication charting that can detect and alert on potential pump programming errors. Acceptable programming limits of dose rate increases in addition to initial drug doses for 23 high-risk medications are monitored. During 22.5 months in a 24 bed ICU, 970 alerts (4% of 25,040 doses, 1.4 alerts per day) were generated for pump settings programmed outside acceptable limits of which 137 (14%) were found to have prevented potential harm. Monitoring pump programming at the system level rather than the pump provides access to additional patient data in the EMR including previous dosage levels, other concurrent medications and caloric intake, age, gender, vitals and laboratory results.
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Treatment with pravastatin and fenofibrate improves atherogenic lipid profiles but not inflammatory markers in ACTG 5087.
J Clin Lipidol
PUBLISHED: 09-09-2010
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Statins and fibrates alter lipids, apolipoproteins and inflammatory markers in persons without HIV. The objective of this study was to evaluate changes in lipoproteins, apolipoproteins and other markers of inflammation with the use of pravastatin and fenofibrate.
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Clinical, laboratory, and neuroimaging characteristics of fatigue in HIV-infected individuals.
J. Neurovirol.
PUBLISHED: 08-31-2010
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Fatigue is among the most common symptoms reported by HIV-infected individuals. Previous reports suggest that the prevalence of fatigue varies by disease status with rates close to 80% in patients with AIDS. However, most studies have not been conducted in the setting of a controlled trial and have not assessed the association of fatigue with cellular markers of brain activity. Data for this study were derived from baseline and longitudinal evaluations in ACTG A5090, a randomized, double-blind, placebo-controlled trial of the Selegiline Transdermal System for the treatment of HIV-associated cognitive impairment. Fatigue was assessed using the Fatigue Severity Scale with scores of >4 considered "fatigued". Participants in a substudy underwent brain magnetic resonance spectroscopy (MRS) imaging, an in vivo method for assessing brain metabolites associated with neuronal and glia activity. Differences between fatigued and non-fatigued participants were evaluated with respect to demographics and clinical characteristics, plasma and CSF HIV-1 RNA concentration, CD4 counts, and brain metabolites. One hundred and twenty-eight participants were enrolled (88% male, median age?=?45 years) and 82 participants (64%, 95% confidence interval 55%, 72%) were fatigued at baseline. MRS was conducted in 62 of the 128 participants. Fatigued participants were significantly younger (p?=?0.011), had lower Karnofsky scores (p?=?0.032), and had higher levels of depressive symptoms on the Center for Epidemiologic Studies Depression (CES-D) scale (p?
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Potential use of 68Ga-apo-transferrin as a PET imaging agent for detecting Staphylococcus aureus infection.
Nucl. Med. Biol.
PUBLISHED: 08-05-2010
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(67)Ga citrate has been extensively used to detect infection and inflammation since 1971. However, its clinical utility is compromised due to several limitations. The present project explored whether (68)Ga-apo-transferrin ((68)Ga-TF), when prepared in vitro, is a useful agent for positron emission tomography (PET) imaging of bacterial infection.
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Absence of NMDA receptors in dopamine neurons attenuates dopamine release but not conditioned approach during Pavlovian conditioning.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-07-2010
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During Pavlovian conditioning, phasic dopamine (DA) responses emerge to reward-predictive stimuli as the subject learns to anticipate reward delivery. This observation has led to the hypothesis that phasic dopamine signaling is important for learning. To assess the ability of mice to develop anticipatory behavior and to characterize the contribution of dopamine, we used a food-reinforced Pavlovian conditioning paradigm. As mice learned the cue-reward association, they increased their head entries to the food receptacle in a pattern that was consistent with conditioned anticipatory behavior. D1-receptor knockout (D1R-KO) mice had impaired acquisition, and systemic administration of a D1R antagonist blocked both the acquisition and expression of conditioned approach in wild-type mice. To assess the specific contribution of phasic dopamine transmission, we tested mice lacking NMDA-type glutamate receptors (NMDARs) exclusively in dopamine neurons (NR1-KO mice). Surprisingly, NR1-KO mice learned at the same rate as their littermate controls. To evaluate the contribution of NMDARs to phasic dopamine release in this paradigm, we performed fast-scan cyclic voltammetry in the nucleus accumbens of awake mice. Despite having significantly attenuated phasic dopamine release following reward delivery, KO mice developed cue-evoked dopamine release at the same rate as controls. We conclude that NMDARs in dopamine neurons enhance but are not critical for phasic dopamine release to behaviorally relevant stimuli; furthermore, their contribution to phasic dopamine signaling is not necessary for the development of cue-evoked dopamine or anticipatory activity in a D1R-dependent Pavlovian conditioning paradigm.
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Coping with Candida infections.
Proc Am Thorac Soc
PUBLISHED: 05-14-2010
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Although Candida spp. exist as normal flora on much of the human body, life-threatening invasive infections by these organisms have increased in recent decades. Candida spp. are now one of the most common causes of nosocomial blood stream infections worldwide, and patients with critical illness or malignant disease demonstrate particular susceptibility. Risk factors are identifiable for virtually all patients who develop invasive candidiasis, and clinicians must maintain vigilance for Candida infections in the appropriate clinical context, given the attributable mortality. This review addresses the clinical and molecular epidemiology of invasive Candida infections, common clinical manifestations, available diagnostic methods, and current recommendations for initial therapy.
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Memantine for AIDS dementia complex: open-label report of ACTG 301.
HIV Clin Trials
PUBLISHED: 04-20-2010
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To evaluate the long-term safety and efficacy of memantine use as treatment of HIV-associated cognitive impairment.
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Vicriviroc and peripheral neuropathy: results from AIDS Clinical Trials Group 5211.
HIV Clin Trials
PUBLISHED: 04-20-2010
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To evaluate the effect of vicriviroc (VCV) on peripheral neuropathy (PN), the most prevalent neurological complication of HIV infection in HIV-1-infected treatment- experienced population.
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Host lung gene expression patterns predict infectious etiology in a mouse model of pneumonia.
Respir. Res.
PUBLISHED: 04-08-2010
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Lower respiratory tract infections continue to exact unacceptable worldwide mortality, often because the infecting pathogen cannot be identified. The respiratory epithelia provide protection from pneumonias through organism-specific generation of antimicrobial products, offering potential insight into the identity of infecting pathogens. This study assesses the capacity of the host gene expression response to infection to predict the presence and identity of lower respiratory pathogens without reliance on culture data.
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Inducible innate resistance of lung epithelium to infection.
Annu. Rev. Physiol.
PUBLISHED: 02-13-2010
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Most studies of innate immunity have focused on leukocytes such as neutrophils, macrophages, and natural killer cells. However, epithelial cells play key roles in innate defenses that include providing a mechanical barrier to microbial entry, signaling to leukocytes, and directly killing pathogens. Importantly, all these defenses are highly inducible in response to the sensing of microbial and host products. In healthy lungs, the level of innate immune epithelial function is low at baseline. This is indicated by low levels of spontaneous microbial killing and cytokine release, reflecting low constitutive stimulation in the nearly sterile lower respiratory tract when mucociliary clearance mechanisms are functioning effectively. This contrasts with the colon, where bacteria are continuously present and epithelial cells are constitutively activated. Although the surface area of the lungs presents a large target for microbial invasion, activated lung epithelial cells that are closely apposed to deposited pathogens are ideally positioned for microbial killing.
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Common statistical concerns in clinical trials.
J Exp Stroke Transl Med
PUBLISHED: 02-02-2010
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Statistics are an integral part of clinical trials. Elements of statistics span clinical trial design, data monitoring, analyses, and reporting. A solid understanding of statistical concepts by clinicians improves the comprehension and the resulting quality of clinical trials. This manuscript outlines common statistical concerns in clinical trials that are important for clinicians to understand.
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Clinical trial structures.
J Exp Stroke Transl Med
PUBLISHED: 02-02-2010
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Most errors in clinical trials are a result of poor planning. Fancy statistical methods cannot rescue design flaws. Thus careful planning with clear foresight is crucial. The selection of a clinical trial design structure requires logic and creativity. Common structural designs are discussed.
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Development of an electronic public health case report using HL7 v2.5 to meet public health needs.
J Am Med Inform Assoc
PUBLISHED: 01-13-2010
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Clinicians are required to report selected conditions to public health authorities within a stipulated amount of time. The current reporting process is mostly paper-based and inefficient and may lead to delays in case investigation. As electronic medical records become more prevalent, electronic case reporting is becoming increasingly feasible. However, there is no existing standard for the electronic transmission of case reports from healthcare to public health entities. We identified the major requirements of electronic case reports and verified that the requirements support the work processes of the local health departments. We propose an extendable standards-based model to electronically transmit case information and associated laboratory information from healthcare to public health entities. The HL7 v2.5 message model is currently being implemented to transmit electronic case reports from Intermountain Healthcare to the Utah Department of Health.
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Long-term impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals (ACTG 5097s).
HIV Clin Trials
PUBLISHED: 12-31-2009
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Efavirenz (EFV) is an antiretroviral (ARV) drug associated with neuropsychological effects. Limited data describing the long-term impact of EFV-based regimens on neuropsychological performance over more than 3 years are available.
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Surface water quality along the Central John Muir Trail in the Sierra Nevada Mountains: coliforms and algae.
High Alt. Med. Biol.
PUBLISHED: 12-31-2009
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The John Muir Trail (JMT) in the Sierra Nevada Mountains of California is one of the most popular alpine wilderness trails in the United States, where backpackers depend on trailside water sources for more than 335 km (208 miles). This study addressed the risk of acquiring waterborne disease by analyzing prevalence and changes in coliform bacteria and Escherichia coli (E. coli) in lakes and streams adjacent to the central JMT. Chlorophyll-a levels were also measured as an indicator of high elevation eutrophication. Categories of environmental land use which might affect water quality were defined as: Pristine areas rarely traversed by humans; Backpack off-trail areas not traversed by pack or stock animals; and Multiuse areas with backpacker and animal use. We analyzed surface water at 36 different sites three separate times over an eight week period in the summer of 2008. Chlorophyll-a concentration increased significantly in Backpack and Multiuse sites over the summer months, but not in Pristine sites. Similar results were obtained for coliforms, with prevalence also increasing significantly over the summer months in Backpack and Multiuse sites. There was a much higher prevalence of E. coli in Multiuse sites compared to Pristine and Backpack sites. Our study provides evidence pack and stock animals serve as a source of microbial contamination of water along this section of trail.
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Computer surveillance of hospital-acquired infections: a 25 year update.
AMIA Annu Symp Proc
PUBLISHED: 11-14-2009
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Hospital-acquired infections (HAIs) are a significant cause of patient harm and increased healthcare cost. Many states have instituted mandatory hospital-wide reporting of HAIs which will increase the workload of infection preventionists and the Center for Medicare and Medicaid Services is no longer paying hospitals to treat certain HAIs. These competing priorities for increased reporting and prevention have many hospitals worried. Manual surveillance of HAIs cannot provide the speed, accuracy and consistency of computerized surveillance. Computer tools can also improve the speed and accuracy of HAI analysis and reporting. Computerized surveillance for HAIs was implemented at LDS Hospital in 1984, but that system required manual entry of data for analysis and reporting. This paper reports on the current functionality and status of the updated computer system for HAI surveillance, analysis and reporting used at LDS Hospital and the 21 other Intermountain Healthcare hospitals.
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Predicted Interval Plots (PIPS): A Graphical Tool for Data Monitoring of Clinical Trials.
Stat Biopharm Res
PUBLISHED: 11-01-2009
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Group sequential designs are often used in clinical trials to evaluate efficacy and/or futility. Many methods have been developed for different types of endpoints and scenarios. However, few of these methods convey information regarding effect sizes (e.g., treatment differences) and none uses prediction to convey information regarding potential effect size estimates and associated precision, with trial continuation. To address these limitations, Evans et al. (2007) proposed to use prediction and predicted intervals as a flexible and practical tool for quantitative monitoring of clinical trials. In this article, we reaffirm the importance and usefulness of this innovative approach and introduce a graphical summary, predicted interval plots (PIPS), to display the information obtained in the prediction process in a straightforward yet comprehensive manner. We outline the construction of PIPS and apply this method in two examples. The results and the interpretations of the PIPS are discussed.
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Chronic microsensors for longitudinal, subsecond dopamine detection in behaving animals.
Nat. Methods
PUBLISHED: 09-08-2009
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Neurotransmission operates on a millisecond timescale but is changed by normal experience or neuropathology over days to months. Despite the importance of long-term neurotransmitter dynamics, no technique exists to track these changes in a subject from day to day over extended periods of time. Here we describe and characterize a microsensor that can detect the neurotransmitter dopamine with subsecond temporal resolution over months in vivo in rats and mice.
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A multivariate time series approach to modeling and forecasting demand in the emergency department.
J Biomed Inform
PUBLISHED: 08-14-2009
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The goals of this investigation were to study the temporal relationships between the demands for key resources in the emergency department (ED) and the inpatient hospital, and to develop multivariate forecasting models.
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Inhaled therapeutics for prevention and treatment of pneumonia.
Expert Opin Drug Saf
PUBLISHED: 06-23-2009
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The lungs are the most common site of serious infection owing to their large surface area exposed to the external environment and minimum barrier defense. However, this architecture makes the lungs readily available for topical therapy. Therapeutic aerosols include those directed towards improving mucociliary clearance of pathogens, stimulation of innate resistance to microbial infection, cytokine stimulation of immune function and delivery of antibiotics. In our opinion inhaled antimicrobials are underused, especially in patients with difficult-to-treat lung infections. The use of inhaled antimicrobial therapy has become an important part of the treatment of airway infection with Pseudomonas aeruginosa in cystic fibrosis and the prevention of invasive fungal infection in patients undergoing heart and lung transplantation. Cytokine inhaled therapy has also been explored in the treatment of neoplastic and infectious disease. The choice of pulmonary drug delivery systems remains critical as air-jet and ultrasonic nebulizer may deliver sub-optimum drug concentration if not used properly. In future development of this field, we recommend an emphasis on the study of the use of aerosolized hypertonic saline solution to reduce pathogen burden in the airways of subjects infected with microbes of low virulence, stimulation of innate resistance to prevent pneumonia in immunocompromised subjects using cytokines or synthetic pathogen-associated molecular pattern analogues and more opportunities for the use of inhaled antimicrobials. These therapeutics are still in their infancy but show great promise.
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Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance.
AIDS
PUBLISHED: 05-09-2009
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To determine whether antiretroviral regimens with good central nervous system (CNS) penetration control HIV in cerebrospinal fluid (CSF) and improve cognition.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.