Biomedical subjects

William Shannon

Publications and source records attributed to William Shannon.

10 recordsLinked to original sources

PubMed2006

Factors influencing general practitioner referral of patients developing end-stage renal failure: a standardised case-analysis study.

BACKGROUND: To understand why treatment referral rates for ESRF are lower in Ireland than in other European countries, an investigation of factors influencing general practitioner referral of patients developing ESRF was conducted. METHOD: Randomly selected general practitioners (N = 51) were interviewed using 32 standardised written patient scenarios to elicit referral strategies. MAIN OUTCOME MEASURES: General practitioner referral levels and thresholds for patients developing end-stage renal disease; referral routes (nephrologist vs other physicians); influence of patient age, marital status and co-morbidity on referral. RESULTS: Referral levels varied widely with the full range of cases (0-32; median = 15) referred by different doctors after consideration of first laboratory results. Less than half (44%) of cases were referred to a nephrologist. Patient age (40 vs 70 years), marital status, co-morbidity (none vs rheumatoid arthritis) and general practitioner prior specialist renal training (yes or no) did not influence referral rates. Many patients were not referred to a specialist at creatinine levels of 129 micromol/l (47% not referred) or 250 micromol/l (45%). While all patients were referred at higher levels (350 and 480 micromol/l), referral to a nephrologist decreased in likelihood as scenarios became more complex; 28% at 129 micromol/l creatinine; 28% at 250 micromol/l; 18% at 350 micromol/l and 14% at 480 micromol/l. Referral levels and routes were not influenced by general practitioner age, sex or practice location. Most general practitioners had little current contact with chronic renal patients (mean number in practice = 0.7, s.d. = 1.3). CONCLUSION: The very divergent management patterns identified highlight the need for guidance to general practitioners on appropriate management of this serious condition.

Age Factors↗

PubMed2005

Predictors of hospital mortality for patients with severe sepsis treated with Drotrecogin alfa (activated).

STUDY OBJECTIVE: To identify predictors of hospital mortality among patients with severe sepsis who were treated with drotrecogin alfa (activated). DESIGN: Prospective observational cohort study. SETTING: A 1400-bed academic medical center. PATIENTS: One hundred two patients treated with drotrecogin alfa (activated) for severe sepsis. MEASUREMENTS AND MAIN RESULTS: To identify potential risk factors for hospital mortality, the main outcome evaluated, all patients who received drotrecogin alfa (activated) were segregated according to hospital survival. The following characteristics were recorded: age, sex, weight, surgical or nonsurgical, Acute Physiology and Chronic Health Evaluation (APACHE) II score, number of acquired organ-system derangements, mechanical ventilation, use of vasopressors or dobutamine, patient location 24 hours before receiving drotrecogin alfa (activated), source of infection, microbiologically positive culture, and other process-of-care variables. Of the 102 patients, 43 (42.2%) died during their hospitalization. Potential predictors of hospital mortality identified by univariate analysis included greater APACHE II scores, administration of vasopressin or dobutamine, number of acquired organ-system derangements, time to treatment with drotrecogin alfa (activated), intravenous fluid administered before receiving vasopressors or drotrecogin alfa (activated), number of red blood cell transfusions, and administration of inappropriate initial antimicrobial treatment. Multivariate analysis revealed that vasopressin administration (odds ratio [OR] 3.72, 95% confidence interval [CI] 1.95-7.10), number of acquired organ-system derangements (OR 2.30, 95% CI 1.59-3.31), and administration of inappropriate initial antimicrobial treatment (OR 15.5, 95% CI 6.78-35.6) were independently associated with hospital mortality. CONCLUSION: Number of acquired organ-system derangements, vasopressin administration, and treatment with an inappropriate initial antimicrobial regimen are independently associated with an increased risk of hospital mortality among patients treated with drotrecogin alfa (activated) for severe sepsis. These findings suggest that other specific medical interventions may increase survival in this patient population.

Gastrointestinal Diseases↗

PubMed2004

DNA microarray analysis of gene expression in human optic nerve head astrocytes in response to hydrostatic pressure.

There is clinical and experimental evidence that elevated intraocular pressure (IOP), a mechanical stress, is involved in the pathogenesis of glaucomatous optic neuropathy. The mechanism by which astrocytes in the optic nerve head (ONH) respond to changes in IOP is under study. Gene transcription by ONH astrocytes exposed either to 60 mmHg hydrostatic pressure (HP) or control ambient pressure (CP) for 6, 24, and 48 h was compared using Affymetrix GeneChip microarrays to identify HP-responsive genes. Data were normalized across arrays within each gene. A linear regression model applied to test effect of time and HP on changes in expression level identified 596 genes affected by HP over time. Using GeneSpring analysis we selected genes whose average expression level increased or decreased more than 1.5-fold at 6, 24, or 48 h. Expression of selected genes was confirmed by real-time RT-PCR; protein levels were detected by Western blot. Among the genes highly responsive to HP were those involved in signal transduction, such as Rho nucleotide exchange factors, Ras p21 protein activator, tyrosine kinases and serine threonine kinases, and genes involved in transcriptional regulation, such as c-Fos, Egr2, and Smad3. Other genes that increased expression included ATP-binding cassettes, solute carriers, and genes associated with lipid metabolism. Among the genes that decreased expression under HP were genes encoding for dual activity phosphatases, transcription factors, and enzymes involved in protein degradation. These HP-responsive genes may be important in the establishment and maintenance of the ONH astrocyte phenotype under conditions of elevated IOP in glaucoma.

Adolescent↗

PubMed2004

Detecting epistatic interactions contributing to quantitative traits.

The restricted partition method (RPM) is a partitioning algorithm for examining multi-locus genotypes as (potentially non-additive) predictors of a quantitative trait. The motivating application was to develop a robust method to examine quantitative phenotypes for epistasis (gene-gene interactions), but the method can be applied without modification to gene-environment interactions. Simulation results indicate that the method provides an efficient way to identify loci contributing epistatically to a quantitative trait, even if the loci have no single locus effects. Statistical significance can be estimated through permutation testing. An example using real data involving the metabolism of a chemotherapy drug is included for illustration. Although the examples in this article involve 2-locus interactions, the RPM is computationally feasible for the analysis of more than two loci or factors.

Algorithms↗

PubMed2004

Effect of kinetic therapy on pulmonary complications.

BACKGROUND: Optimal turning of critically ill patients is not well established. Kinetic therapy (systematic mechanical rotation of patients with 40 degree turns) may improve pulmonary function more than the improvement in function achieved via the standard of care (turning patients every 2 hours). OBJECTIVE: To determine (1) if patients receiving mechanical ventilation who tolerate kinetic therapy have better pulmonary function than do patients treated with standard turning and (2) the cost-effectiveness of kinetic therapy. METHODS: A prospective, randomized, multicenter study including 234 medical, surgical, and trauma patients (137 control patients, 97 patients receiving kinetic therapy). RESULTS: Kinetic therapy significantly decreased the occurrence of ventilator-associated pneumonia and lobar atelectasis. The risk of pneumonia developing was lower (P = .002) in patients receiving kinetic therapy than in the control patients. The risk of lobar atelectasis developing was decreased (P = .02) for the patients receiving kinetic therapy. Lengths of stay in the intensive care unit and in the hospital did not differ between the groups. Charges for intensive care were less in the kinetic therapy group (81,700 dollars) than in the control group (84,958 dollars), but not significantly less. Twenty-one patients did not tolerate kinetic therapy and were not included in the analysis. CONCLUSION: Kinetic therapy helps prevent ventilator-associated pneumonia and lobar atelectasis in critically ill patients. Costs to rent the bed may be offset by the potential cost reduction associated with kinetic therapy.

Cost-Benefit Analysis↗

PubMed2003

A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes.

In this pilot study, we used primary human acute myeloid leukemia (AML) cell genomes as templates for exonic PCR amplification, followed by high-throughput resequencing, analyzing approximately 7 million base pairs of DNA from 140 AML samples and 48 controls. We identified six previously described, and seven previously undescribed sequence changes that may be relevant for AML pathogenesis. Because the sequencing templates were generated from primary AML cells, the technique favors the detection of mutations from the most dominant clones within the tumor cell mixture. This strategy represents a viable approach for the detection of potentially relevant, nonrandom mutations in primary human cancer cell genomes.

Case-Control Studies↗

PubMed2003

The influence of infection on hospital mortality for patients requiring > 48 h of intensive care.

OBJECTIVE: To determine the influence of microbiologically confirmed infection on hospital mortality among patients requiring intensive care for > 48 h. DESIGN: Prospective cohort study. SETTING: Medical ICU of the Barnes-Jewish Hospital, an urban teaching hospital. PATIENTS: A total of 893 patients requiring intensive care for > 48 h. INTERVENTIONS: Prospective patient surveillance and data collection. MEASUREMENTS AND MAIN RESULTS: Three hundred seventy-two patients (41.7%) requiring intensive care for > 48 h had a microbiologically confirmed infection. Only six patients (0.7% [1.6% of patients with microbiologically confirmed infections]) received inadequate antimicrobial therapy during the first 24 h of treatment, and 248 patients (27.8%) died during hospitalization. Compared to hospital survivors, hospital nonsurvivors were significantly more likely to have a microbiologically confirmed infection (53.2% vs 37.2%, respectively; p < 0.001) and to develop severe sepsis (45.6% vs 28.7%, respectively; p < 0.001). Cirrhosis and the requirement for vasopressors were the only variables identified by multiple logistic regression analysis as independent risk factors for hospital mortality in all patient groupings of severity of illness. Multiple logistic regression analysis also demonstrated that underlying malignancy (adjusted odds ratio [AOR], 1.98; 95% CI, 1.55 to 2.53), chronic renal insufficiency (AOR, 1.57; 95% CI, 1.31 to 1.87), cirrhosis (AOR, 1.94; 95% CI, 1.48 to 2.53), temperature > 38.3 degrees C (AOR, 1.72; 95% CI, 1.47 to 2.02), severe sepsis (AOR, 2.78; 95% CI, 1.94 to 3.98), positive culture for vancomycin-resistant enterococci (AOR, 1.78; 95% CI, 1.51 to 2.09), and the presence of multiple infections (AOR, 1.65; 95% CI, 1.28 to 2.14) were independently associated with the requirement for therapy with vasopressors. CONCLUSIONS: Microbiologically confirmed infections are common among patients requiring medical intensive care for > 48 h. Despite the administration of adequate antimicrobial therapy, microbiologically confirmed infections appear to be an important cause of hemodynamic instability and increased hospital mortality. These data suggest that clinical efforts aimed at the prevention of infections and improvements in the medical management of patients with severe infections, especially those associated with hemodynamic instability and the need for vasopressors, are required to achieve further improvements in patient outcomes.

Adolescent↗

PubMed2003

Analyzing microarray data using cluster analysis.

As pharmacogenetics researchers gather more detailed and complex data on gene polymorphisms that effect drug metabolizing enzymes, drug target receptors and drug transporters, they will need access to advanced statistical tools to mine that data. These tools include approaches from classical biostatistics, such as logistic regression or linear discriminant analysis, and supervised learning methods from computer science, such as support vector machines and artificial neural networks. In this review, we present an overview of another class of models, cluster analysis, which will likely be less familiar to pharmacogenetics researchers. Cluster analysis is used to analyze data that is not a priori known to contain any specific subgroups. The goal is to use the data itself to identify meaningful or informative subgroups. Specifically, we will focus on demonstrating the use of distance-based methods of hierarchical clustering to analyze gene expression data.

Cluster Analysis↗

PubMed2002

Deep vein thrombosis during prolonged mechanical ventilation despite prophylaxis.

OBJECTIVE: To determine the prevalence of deep vein thrombosis (DVT) among patients requiring prolonged mechanical ventilation in the intensive care unit. DESIGN: Prospective cohort study. SETTING: Medical intensive care unit of a university-affiliated urban teaching hospital. PATIENTS: Patients requiring mechanical ventilation for >7 days. INTERVENTIONS: All patients admitted to the medical intensive care unit requiring prolonged mechanical ventilation underwent duplex ultrasonography of their lower extremities and upper extremities every 7 days. The main outcome identified was the presence of DVT. Secondary outcomes included hospital mortality, hospital and intensive care unit lengths of stay, and the occurrence of pulmonary embolism. MEASUREMENTS AND MAIN RESULTS: A total of 110 patients requiring mechanical ventilation for >7 days were enrolled. Prophylaxis against DVT was employed in 110 of the patients (100%). A total of 26 patients (23.6%) developed DVT. Patients with DVT were statistically more likely to have underlying malignancy (30.8% vs. 8.3%; p =.004) and longer durations of central venous catheterization (26.9 +/- 22.2 days vs. 14.5 +/- 12.1 days; p =.024) compared with patients without DVT. There were no statistically significant differences in hospital mortality or lengths of stay in the hospital and intensive care unit for patients with and without DVT. Patients documented to have DVT by using duplex ultrasonography had a statistically greater frequency of subsequent pulmonary embolism during their hospitalization (11.5% vs. 0.0%; p =.012). CONCLUSION: The occurrence of DVT is common among patients requiring prolonged mechanical ventilation in the intensive care unit setting despite the use of prophylaxis measures. These data suggest that alternative strategies for the prevention of DVT should be evaluated. Additionally, early detection methods should be considered to reduce the potential morbidity associated with untreated DVT in this high-risk population.

Adult↗

PubMed2002

Limb dominance as a potential etiologic factor in noncontact anterior cruciate ligament tears.

A retrospective case series analysis of 80 patients (44 males and 36 females) who presented with acute, unilateral, noncontact anterior cruciate ligament (ACL) tears was performed. The role of limb dominance as a possible etiologic factor in noncontact ACL tears was investigated and the gender-specific relationship was determined. Patients were questioned about the nature of their injury and asked to list their preferred upper and lower extremities for writing, throwing, and kicking-activities previously used to define upper and lower extremity dominance. The relationships between limb dominance, side of injury, and gender were assessed. Mean patient age was 27.8 years. The left knee was involved in 54% of patients and the right knee in 46%. Eighty-nine percent of the study group identified themselves as right-hand dominant for writing, 91% were right-hand dominant for throwing, and 89% were right-leg dominant for kicking. Overall, there was no significant correlation between the side of injury and dominant limb for writing (P=.84), throwing (P=.68), or kicking (P=.99). There also was no significant gender effect on the relationship between limb dominance and side of injury (P=.65). Limited numbers precluded an analysis of specific limb-dominant sports activities as potential risk factors. The results of this pilot study suggest limb dominance is not a significant etiologic factor for noncontact ACL tears.

Adolescent↗