PubMed Health⌕ Search

Biomedical subjects

Daniel J Sexton

Publications and source records attributed to Daniel J Sexton.

At least 19 recordsLinked to original sources
PubMed2007

Early surgery in patients with infective endocarditis: a propensity score analysis.

BACKGROUND: An accurate assessment of the predictors of long-term mortality in patients with infective endocarditis is not possible using retrospective data because of inherent treatment biases and predictable imbalances in the distribution of prognostic factors. Largely because of these limitations, the role of surgery in long-term survival has not been adequately studied. METHODS: Data were collected prospectively from 426 patients with infective endocarditis. Variables associated with surgery in patients who did not have intracardiac devices who had left-side-associated valvular infections were determined using multivariable analysis. Propensity scores were then assigned to each patient based on the likelihood of undergoing surgery. Using individual propensity scores, 51 patients who received medical and surgical treatment were matched with 51 patients who received medical treatment only. RESULTS: The following factors were statistically associated with surgical therapy: age, transfer from an outside hospital, evidence of infective endocarditis on physical examination, the presence of infection with staphylococci, congestive heart failure, intracardiac abscess, and undergoing hemodialysis without a chronic catheter. After adjusting for surgical selection bias by propensity score matching, regression analysis of the matched cohorts revealed that surgery was associated with decreased mortality (hazard ratio, 0.27; 95% confidence interval, 0.13-0.55). A history of diabetes mellitus (hazard ratio, 4.81; 95% confidence interval, 2.41-9.62), the presence of chronic intravenous catheters at the beginning of the episode (hazard ratio, 2.65; 95% confidence interval, 1.31-5.33), and paravalvular complications (hazard ratio, 2.16; 95% confidence interval, 1.06-4.44) were independently associated with increased mortality. CONCLUSIONS: Differences between clinical characteristics of patients with infective endocarditis who receive medical therapy versus patients who receive surgical and medical therapy are paramount. After controlling for inherent treatment selection bias and imbalances in prognostic factors using propensity score methodology, risk factors associated with increased long-term mortality included diabetes mellitus, the presence of a chronic catheter at the onset of infection, and paravalvular complications. In contrast, surgical therapy was associated with a significant long-term survival benefit.

Adult↗
PubMed2006

Sample preparation for MALDI mass spectrometry using an elastomeric device reversibly sealed on the MALDI target.

A new method for improving low-concentration sample recovery and reducing sample preparation steps in matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) is presented. In the conventional approach, samples are typically desalted and/or concentrated with various techniques and deposited on the MALDI target as small droplets. In this work, we describe a new approach in which an elastomeric device is reversibly sealed on the MALDI target to form a multi-well plate with the MALDI target as the base of the plate. The new format allows a larger volume (5-200 microL) of samples to be deposited on each spot and a series of sample handling processes, including desalting and concentrating, to be performed directly on the MALDI target. Several advantages have been observed: (i) multiple sample transferring steps are avoided; (ii) recovery of low-concentration peptides during sample preparation is improved using a novel desalting method that utilizes the hydrophobic surface of the elastomeric device; and (iii) sequence coverage of the peptide mass fingerprinting map is improved using a novel method in which proteins are immobilized on the hydrophobic surface of the elastomeric device for in-well trypsin digestion, followed by desalting and concentrating the digestion products in the same well.

Animals↗
PubMed2006

Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis--United States: a practical guide for physicians and other health-care and public health professionals.

Tickborne rickettsial diseases (TBRD) continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low cost, effective antimicrobial therapy. The greatest challenge to clinicians is the difficult diagnostic dilemma posed by these infections early in their clinical course, when antibiotic therapy is most effective. Early signs and symptoms of these illnesses are notoriously nonspecific or mimic benign viral illnesses, making diagnosis difficult. In October 2004, CDC's Viral and Rickettsial Zoonoses Branch, in consultation with 11 clinical and academic specialists of Rocky Mountain spotted fever, human granulocytotropic anaplasmosis, and human monocytotropic ehrlichiosis, developed guidelines to address the need for a consolidated source for the diagnosis and management of TBRD. The preparers focused on the practical aspects of epidemiology, clinical assessment, treatment, and laboratory diagnosis of TBRD. This report will assist clinicians and other health-care and public health professionals to 1) recognize epidemiologic features and clinical manifestations of TBRD, 2) develop a differential diagnosis that includes and ranks TBRD, 3) understand that the recommendations for doxycycline are the treatment of choice for both adults and children, 4) understand that early empiric antibiotic therapy can prevent severe morbidity and death, and 5) report suspect or confirmed cases of TBRD to local public health authorities to assist them with control measures and public health education efforts.

Anaplasmosis↗
PubMed2006

Favorable impact of an infection control network on nosocomial infection rates in community hospitals.

OBJECTIVE: To describe an infection control network (the Duke Infection Control Outreach Network [DICON]) and its impact on nosocomial infection rates in community hospitals. DESIGN: Prospective cohort study of rates of nosocomial infections and exposures of employees to bloodborne pathogens in hospitals during the first 3 years of their affiliation with DICON. Attributable cost and mortality estimates were obtained from published studies.Setting. Twelve community hospitals in North Carolina and Virginia. RESULTS: During the first 3 years of hospital affiliation with DICON, annual rates of nosocomial bloodstream infections at study hospitals decreased by 23% (P = .009). Annual rates of nosocomial infection and colonization due to methicillin-resistant Staphylococcus aureus decreased by 22% (P = .002), and rates of ventilator-associated pneumonia decreased by 40% (P = .001). Rates of exposure of employees to bloodborne pathogens decreased by 18% (P = .003). CONCLUSIONS: The establishment of an infection control network within a group of community hospitals was associated with substantial decreases in nosocomial infection rates. Standard surveillance methods, frequent data analysis and feedback, and interventions based on guidelines and protocols from the Centers for Disease Control and Prevention were the principal strategies used to achieve these reductions. In addition to lessening the adverse clinical outcomes due to nosocomial infections, these reductions substantially decreased the economic burden of infection: the decline in nosocomial bloodstream infections and ventilator-associated pneumonia alone yielded potential savings of 578,307 US dollars to 2,195,954 US dollars per year at the study hospitals.

Community-Acquired Infections↗
PubMed2006

High-throughput affinity ranking of antibodies using surface plasmon resonance microarrays.

A method was developed to rapidly identify high-affinity human antibodies from phage display library selection outputs. It combines high-throughput Fab fragment expression and purification with surface plasmon resonance (SPR) microarrays to determine kinetic constants (kon and koff) for 96 different Fab fragments in a single experiment. Fabs against human tissue kallikrein 1 (hK1, KLK1 gene product) were discovered by phage display, expressed in Escherichia coli in batches of 96, and purified using protein A PhyTip columns. Kinetic constants were obtained for 191 unique anti-hK1 Fabs using the Flexchip SPR microarray device. The highest affinity Fabs discovered had dissociation constants of less than 1 nM. The described SPR method was also used to categorize Fabs according to their ability to recognize an apparent active site epitope. The ability to rapidly determine the affinities of hundreds of antibodies significantly accelerates the discovery of high-affinity antibody leads.

Automation↗
PubMed2006

Rapid kinetic-based screening of human Fab fragments.

Human antibodies able to bind with high affinity and specificity to numerous targets have been successfully identified from Fab phage display libraries. A key step in the library selection screening process is the early characterization of library isolates in order to determine which of these isolates to pursue further. Here we describe a Biacore assay that allows isolated clones expressed as soluble Fab fragments in E. coli to be screened and ranked based on their affinity against the target. The assay takes advantage of our ability to measure Fab concentrations in crude bacterial extracts in Biacore using very high density Protein A chips. The procedure allows up to 100 clones per week to be screened and permits the identification of a small number of high-affinity Fabs from a large batch obtained following library selection or affinity maturation.

Antibody Affinity↗
PubMed2006

Risk factors for 1-year mortality after postoperative mediastinitis.

OBJECTIVE: Postoperative mediastinitis after median sternotomy is associated with disability and mortality. The aim of this study was to identify risk factors for mortality 1 year after postoperative mediastinitis diagnosis. METHODS: Postoperative mediastinitis was defined as an organ-space infection involving the mediastinum and necessitating debridement. A total of 183 cases of postoperative mediastinitis were prospectively identified from infection control databases. By using univariate and multivariate analysis, clinical risk factors for 1-year mortality were identified. RESULTS: Of 183 patients, 36 (19.7%) died within 3 months of the initial operation. Overall, 51 (33%) died during the study period (the median time to death from the date of diagnosis was 37 days [interquartile range, 11,139 days]). In multivariate analysis, independent predictors of 1-year mortality were a greater than 3-day delay in sternal closure after debridement (hazard ratio, 6.27; P < .001), age greater than 65 years (hazard ratio, 2.29; P = .015), serum creatinine level greater than 2 mg/dL before debridement (hazard ratio, 2.52; P = .019), stay in an intensive care unit before sternal debridement (hazard ratio, 5.56; P < .001), and postoperative mediastinitis due to methicillin-resistant Staphylococcus aureus (hazard ratio, 2.13; P = .02). Treatment with antibiotics with in vitro activity against the infecting pathogen within 7 days of initial debridement was associated with a decreased risk for mortality (hazard ratio, 0.40; P = .03). CONCLUSIONS: Our data suggest that, to improve long-term survival, patients with postoperative mediastinitis should undergo sternal closure within 72 hours after sternal debridement and should receive effective antimicrobial therapy based on operative culture results.

Aged↗
PubMed2006

Influence of diabetes mellitus on the clinical manifestations and prognosis of infective endocarditis: a report from the International Collaboration on Endocarditis-Merged Database.

The purpose of this investigation was to study the influence of diabetes mellitus (DM) on outcomes of infective endocarditis (IE). Outcomes were compared between 150 diabetic and 905 non-diabetic patients with IE from the International Collaboration on Endocarditis Merged Database. Compared to non-diabetic patients, diabetic patients were older (median age 63 vs 57 y, p<0.001), were more often female (42.0% vs 31.9%, p=0.01), more often had comorbidities (41.5% vs 26.7%, p<0.001), and were more likely to be dialysis dependent (12.7% vs 4.0%, p<0.001). S. aureus was isolated more often (30.7% vs 21.7%, p=0.02), and microorganisms from the viridans Streptococcus group less often (16.7% vs 28.2%, p = 0.001) in the diabetic group. There was no difference with respect to the presence of congestive heart failure, embolism, intra-cardiac abscess, new valvular regurgitation, or valvular vegetation. Diabetic patients underwent surgical intervention less frequently (32.0% vs 44.9%, p = 0.003), and had higher overall in-hospital mortality (30.3% vs 18.6%, p = 0.001). On multivariable analysis, DM was an independent predictor of mortality (odds ratio (OR) = 1.71, 95% confidence interval (CI) 1.08-2.70), especially in male patients, as diabetic males had higher mortality than non-diabetic males (OR 2.18, CI 1.08-4.35). DM is an independent predictor of in-hospital mortality among patients hospitalized with IE.

Aged↗
PubMed2006

Risk factors for surgical site infections in older people.

OBJECTIVES: To identify risk factors for surgical site infection (SSI) in older people and to test a priori hypotheses regarding particular variables and SSI risk. DESIGN: Case-control study. SETTING: Duke University Medical Center and seven community hospitals in North Carolina and Virginia. PARTICIPANTS: Elderly patients (> or =65) who underwent surgery between 1991 and 2002 at the study hospitals. Cases were elderly patients with SSI; controls were elderly operative patients without SSI. Infection control practitioners prospectively identified patients. MEASUREMENTS: Data were collected retrospectively. Case patients who developed SSI were compared with control patients who did not develop SSI. RESULTS: Five hundred sixty-nine SSI cases were identified, and 589 uninfected controls were selected. In multivariate analysis, independent predictors of SSI included obesity (odds ratio (OR)=1.77, 95% confidence interval (CI)=1.34-2.32), chronic obstructive pulmonary disease (COPD) (OR=1.66, 95% CI=1.17-2.34), and a wound class classified as contaminated or dirty (OR=1.65, 95% CI=1.01-2.72). Having private insurance was associated with lower risk (OR=0.29, 95% CI=0.12-0.68). CONCLUSION: This study identified several independent predictors of SSI in older people, including comorbid conditions (COPD and obesity), perioperative variables (wound class), and socioeconomic factors (private insurance, which was associated with lower risk). The results from this study can be used to design and implement interventions for SSI prevention in high-risk older people.

Age Factors↗
PubMed2005

Repeat infective endocarditis: differentiating relapse from reinfection.

Repeat infective endocarditis due to the same species can represent relapse of the initial infection or a new infection. We used time-based clinical criteria and pulsed-field gel electrophoresis-based molecular criteria to classify 13 cases of repeat infective endocarditis as either relapse or reinfection. The agreement between clinical and molecular criteria was imperfect (agreement in 10 [77%] of 13 cases).

Endocarditis, Bacterial↗
PubMed2005

The effect of increasing age on the risk of surgical site infection.

BACKGROUND: An increasing number of older persons undergo surgery, but the relationship between increasing age and risk of surgical site infection (SSI) has not been established. The objective of the present study was to determine the relationship between increasing age and risk of SSI. METHODS: The present cohort study included patients who underwent surgery between February 1991 and July 2002. Patients >17 years of age were divided randomly into derivation and validation cohorts. The study was conducted at 11 hospitals. SSIs were prospectively identified by use of Centers for Disease Control and Prevention criteria. RESULTS: The study included 144,485 consecutive surgical patients and 1684 SSIs (rate of SSI, 1.2%). There were 72,139 procedures and 873 SSIs in the derivation cohort. Adjusted analyses revealed a significant relationship between age and risk of SSI (P=.006). Risk of SSI increased by 1.1%/year between ages 17 and 65 years (P=.002). At age >/=65 years, risk of SSI decreased by 1.2% for each additional year (P=.008). There were 72,334 procedures and 811 SSIs in the validation cohort. The relationship between age and risk of SSI was similar in the validation cohort. CONCLUSIONS: Increasing age independently predicted an increased risk of SSI until age 65 years. At ages >/=65 years, increasing age independently predicted a decreased risk of SSI.

Adolescent↗
PubMed2005

Generation of high-affinity human antibodies by combining donor-derived and synthetic complementarity-determining-region diversity.

Combinatorial libraries of rearranged hypervariable V(H) and V(L) sequences from nonimmunized human donors contain antigen specificities, including anti-self reactivities, created by random pairing of V(H)s and V(L)s. Somatic hypermutation of immunoglobulin genes, however, is critical in the generation of high-affinity antibodies in vivo and occurs only after immunization. Thus, in combinatorial phage display libraries from nonimmunized donors, high-affinity antibodies are rarely found. Lengthy in vitro affinity maturation is often needed to improve antibodies from such libraries. We report the construction of human Fab libraries having a unique combination of immunoglobulin sequences captured from human donors and synthetic diversity in key antigen contact sites in heavy-chain complementarity-determining regions 1 and 2. The success of this strategy is demonstrated by identifying many monovalent Fabs against multiple therapeutic targets that show higher affinities than approved therapeutic antibodies. This very often circumvents the need for affinity maturation, accelerating discovery of antibody drug candidates.

Antibody Affinity↗
PubMed2005

Risk factors for ineffective therapy in patients with bloodstream infection.

BACKGROUND: Infections occurring among outpatients having recent contact with the health care system have been termed health care-associated infections. The objective of this study was to analyze the impact of health care-associated status on effectiveness of initial therapy in hospitalized patients with bloodstream infections. METHODS: Prospective cohort study of adults with bloodstream infections at 3 North Carolina hospitals. Bloodstream infection was defined as health care-associated if it occurred within the first 48 hours after hospitalization and if patients had 1 of the following characteristics: had received home health services, outpatient intravenous therapy, or outpatient renal dialysis in the 30 days prior to hospital admission; had been hospitalized within 90 days prior to admission; or lived in a long-term care facility. RESULTS: Of 466 bloodstream infections, 132 (28%) were community-acquired, 178 (38%) were health care-associated, and 156 (33%) were nosocomial. Multivariable logistic regression using community-acquired status as a reference identified health care-associated status (odds ratio, 3.1; 95% confidence interval, 1.6-6.1) and nosocomial status (odds ratio, 4.3; 95% confidence interval, 2.2-8.3) as independent predictors of ineffective initial antibiotic therapy. Among health care-associated characteristics, hospitalization in the 90 days prior to admission was independently associated with ineffective initial therapy (odds ratio, 2.4; 95% confidence interval, 1.4-4.2). CONCLUSIONS: Among patients treated in the hospital for bloodstream infection, health care-associated status was an independent predictor of ineffective initial antibiotic therapy. Hospitalization within 90 days prior to hospital admission was the component of health care-associated status most strongly associated with ineffective initial therapy.

Anti-Bacterial Agents↗
PubMed2005

Aortic coarctation endarteritis in an adult: case report with cardiovascular magnetic resonance imaging findings and review of the literature.

We describe a case of coarctation endarteritis in an adult and review the literature pertaining to this condition. Adult coarctation endarteritis is a rare entity but often represents the initial presentation of coarctation. Diagnosis is critically important given the risk of rupture. Cardiovascular magnetic resonance imaging can be helpful in management.

Adolescent↗