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Biomedical subjects

David Newman

Publications and source records attributed to David Newman.

At least 19 recordsLinked to original sources
PubMed2006

Psychological correlates of quality of life in atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) is associated with significant health-related quality of life (QoL) impairments. Markers of heart disease severity have explained little variance in QoL and it is unclear what other factors will better account for the observed differences in adjustment. We examined whether specific personality traits and illness management styles would help explain the severity of QoL impairments reported in this population. METHODS: Patients with AF (N = 93) completed validated questionnaires measuring disease burden (dependent variables: physical and mental QoL, symptom severity, psychological distress), personality (independent variables: anxiety sensitivity, optimism), and illness management style (mediating variable: symptom preoccupation). Hypothesized relationships were evaluated using mediation models. RESULTS: Anxiety sensitivity was associated with poorer physical and mental QoL, greater symptom severity, and higher distress. Optimism was correlated with better mental QoL and lower distress, but unrelated to physical QoL and symptom severity. Symptom preoccupation significantly mediated the relationships between anxiety sensitivity and each of the QoL measures, as well as the relationships between optimism and mental well-being. CONCLUSIONS: Personality traits and illness management styles are important to consider when assessing the impact of AF on QoL. The data support a cognitive-behavioral model that explains the direct and indirect relationships between psychological predictors and multiple indices of QoL.

Aged↗
PubMed2006

ET743: Chemical analysis of the sea squirt Ecteinascidia turbinata ecosystem.

The sea squirt Ecteinascidia turbinata produces the powerful drug ET743. In this study Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) and Matrix Assisted Laser Desorption Ionization-Mass Spectrometry (MALDI-MS) are systematically used to measure elemental and molecular species in a Florida Keys mangrove ecosystem that contains the sea squirt. ICP-AES is used to measure the concentration of 27 elements down to the parts per billion level in 16 organisms and 3 sediment samples that reside in the mangrove ecosystem including turtle grass, blue crabs, fire sponge, and lettuce slugs. MALDI-MS is used to search for ET743 in these same organisms and sediment samples. A mass spectral feature corresponding to ET743 is identified in the extract of the sea squirt, red mangrove root (Rhizophera mangle), the schoolmaster snapper (Lutjanus griseus), and a sediment sample taken from the ecosystem. We use MALDI-MS to study the impact that various environmental conditions, such as UV light, I(2), cation binding (Fe(+3), Zn(+2), Pb(+2), Cu(+2)), metal oxide nanoparticles (FeO, CuO, TiO(2), ZnO, Al(2)O(3)), a common mineral (CaCO(3)), and extremes in acidity (0.1 M HCl, 0.1 M NaOH) have on the ET743 structure. The data provide potential structures (degradation products, metal-ligand complexes, etc.) that might be present in organism or sedimentary extracts that are similar to ET743. We are studying the marine geochemistry of this ecosystem so a broth can be developed and tested for producing this marine natural product.

Animals↗
PubMed2006

Improving antimicrobial use in the hospital setting by providing usage feedback to prescribing physicians.

OBJECTIVE: To determine whether feedback on antimicrobial use improves physician compliance with local hospital guidelines on antimicrobial prescribing. DESIGN: In this time series analysis, in which a historical control period was compared with an intervention period, all orders for antimicrobials (except those for surgical prophylaxis) placed from November 1, 2002, through April 30, 2004, were prospectively evaluated by an antimicrobial management team (AMT) for compliance with local hospital guidelines. During the control period, orders were evaluated to determine compliance with hospital guidelines before and after recommendations by the AMT were provided to physicians. Feedback was given for the second 9-month period in the form of a weekly report to prescribing physicians, a monthly hospital newsletter, and a quarterly report to various hospital committees. During the intervention period, orders were evaluated to determine compliance with hospital guidelines before and after recommendations by the AMT were provided to physicians. SETTING: The Veterans Affairs Medical Center, a 110-bed facility, in Louisville, Kentucky. PARTICIPANTS: Internal medicine physicians and general surgeons. RESULTS: A total of 2,807 antimicrobial courses were evaluated. Compliance with hospital guidelines before AMT recommendations was 70% during the control period and 74% during the intervention period (P=.02). Compliance after AMT recommendations was 90% during the control period and 93% during the intervention period (P< or =.01). CONCLUSION: The use of feedback had a significantly favorable impact on physician compliance with the hospital's guidelines on antimicrobial prescribing. Use of feedback should be added to the list of interventions that promote appropriate antimicrobial use in the hospital setting.

Anti-Bacterial Agents↗
PubMed2006

Gender differences and quality of life in atrial fibrillation: the mediating role of depression.

OBJECTIVE: This study investigated gender differences, depression, and health-related quality of life (QoL) in a cross-sectional sample of patients with atrial fibrillation (AF). METHODS: This cross-sectional study involved a convenience sample of AF patients from two tertiary-care clinics in Toronto, Canada. Ninety-three AF patients completed psychometrically validated measures of generic QoL and depression. Mediation analyses evaluated the relationship between gender and QoL using depression as mediating variable. RESULTS: Relative to male patients, female patients reported lower physical, but not mental, QoL. Gender was associated with both depression and physical QoL, while depression was correlated with poorer physical QoL. Path analyses demonstrated that depression significantly mediated the relationship between gender and physical QoL. CONCLUSION: Among AF patients, female patients report lower physical QoL relative to male patients, and this relationship may be mediated by self-reported symptoms of depression. Albeit correlational, the findings underscore the need to develop a better understanding of the role of depression in physical QoL, especially when considering the burden of AF in women.

Aged↗
PubMed2006

Disparities in the circumstances of asthma deaths in Maryland.

The reasons for significant disparities in asthma mortality are unclear. Maryland vital statistics and medical examiner data were used to examine timing, location, and circumstances of asthma deaths. We found that unexplained deaths increased substantially over the past 10 years and that young, male, and black asthmatics were more likely to die before hospital admission. Factors contributing to disparities included better availability of anti-inflammatory medications among whites versus blacks, and a higher incidence of positive toxicology screens among males versus females. Disparities in asthma mortality might be reduced through efforts to optimize asthma treatment and reduce illicit drug use.

Adolescent↗
PubMed2005

Progression to chronic atrial fibrillation after the initial diagnosis of paroxysmal atrial fibrillation: results from the Canadian Registry of Atrial Fibrillation.

BACKGROUND: After its initial diagnosis, atrial fibrillation (AF) may progress from paroxysmal to chronic AF (CAF). The rate of progression and risk factors for progression are not clearly defined. METHODS: The Canadian Registry of Atrial Fibrillation (CARAF) enrolled patients from 6 Canadian cities at the time of their first electrocardiographic diagnosis of AF. Comprehensive clinical and echocardiographic data were collected and patients were followed annually, carefully documenting clinical outcomes, recurrence of paroxysmal AF, and progression to CAF. Baseline clinical, electrocardiographic, and echocardiographic variables were evaluated by univariate Cox proportionate hazards analysis. A stepwise approach was used to model the association between echocardiographic and clinical variables with progression to CAF. RESULTS: A total of 757 patients with a baseline diagnosis of paroxysmal AF were evaluated. Median follow-up was 8.0 years (range 2 days to 11.1 years). The probability of progression to CAF by 1 year was 8.6% and thereafter there was a slow but steady progression to 24.7% by 5 years. By 5 years, the probability of documented recurrence of any AF (chronic or paroxysmal) was 63.2%. Increasing age, significant aortic stenosis or mitral regurgitation, left atrial enlargement, and diagnosis of cardiomyopathy were independently associated with progression to CAF. A more rapid heart rate during AF was associated with decreased risk of progression. CONCLUSIONS: After the initial diagnosis of paroxysmal AF, there is a slow but steady progression to CAF. Baseline echocardiographic variables, age, cardiomyopathy, and heart rate were independently associated with progression to CAF.

Adolescent↗
PubMed2005

Systematic evaluation of the determinants of defibrillation efficacy.

OBJECTIVES: We studied the effect of varying shock capacitance, shock impedance, and pulse duration on defibrillation efficacy in a randomized, crossover manner for biphasic shocks. BACKGROUND: The relationship between the electrical determinants of defibrillation efficacy is incompletely understood. METHODS: Biphasic shocks were delivered to 12 dogs through epicardial patches (to vary impedance) after 15 seconds of ventricular fibrillation using one of 100- or 155-muF capacitors at each of four pulse durations (2.5, 5, 10, 20 ms), in a balanced random order. There were two impedance groups: six with higher impedance (mean 97 +/- 15 Omega, range 80-120) and six with lower impedance (mean 39 +/- 3 Omega, range 34-44). Voltage requirements were estimated as the average of three defibrillation threshold (DFT) tests. RESULTS: Shock capacitance, resistance, and pulse duration all had significant effects upon the minimum voltage DFT (P = .0065, P = .0066, and P = .0001, respectively). The tilt associated with the lowest voltage and current requirement for each of the four capacitance/resistance combinations varied widely, between 34 +/- 5% and 63 +/- 3%, depending on capacitance and impedance. The optimal pulse duration associated with minimum DFT lies between 5.11 and 5.34 ms. CONCLUSIONS: Defibrillation voltage requirements for biphasic shocks are affected by pulse duration, capacitance and impedance, but not "tilt."

Animals↗
PubMed2004

Effects of ventricular rate regularization pacing on quality of life and symptoms in patients with atrial fibrillation (Atrial fibrillation symptoms mediated by pacing to mean rates [AF SYMPTOMS study]).

The aim of this study was to investigate the effect of the Ventricular Response Pacing (VRP) algorithm, which regularizes ventricular rate during atrial fibrillation (AF), on symptoms, quality of life, and functional capacity. VRP regularizes the ventricular rate during AF without increasing the mean ventricular rate, thereby reducing the severity of AF-related symptoms in patients with persistent AF. However, VRP did not improve general quality of life (Medical Outcomes Study 36-item Short-Form General Health Survey), the performance of routine activities (Duke Activity Status Index), or functional capacity (hall walk) in patients with AF.

Aged↗
PubMed2004

Long-term comparison of the implantable cardioverter defibrillator versus amiodarone: eleven-year follow-up of a subset of patients in the Canadian Implantable Defibrillator Study (CIDS).

BACKGROUND: The implantable cardioverter defibrillator (ICD) is superior to amiodarone for secondary prophylaxis of sudden cardiac death. However, the magnitude of this benefit over long-term follow-up is not known. Thus, our objective was to evaluate the long-term consequences of using amiodarone versus an ICD as first-line monotherapy in patients with a prior history of sustained ventricular tachycardia/ventricular fibrillation or cardiac arrest. METHODS AND RESULTS: A total of 120 patients were enrolled at St Michael's Hospital in the Canadian Implantable Defibrillator Study (CIDS) and were randomly assigned to receive either amiodarone (n=60) or an ICD (n=60). The treatment strategy was not altered after the end of CIDS unless the initial assigned therapy was not effective or was associated with serious side effects. After a mean follow-up of 5.6+/-2.6 years, there were 28 deaths (47%) in the amiodarone group, compared with 16 deaths (27%) in the ICD group (P=0.0213). Total mortality was 5.5% per year in the amiodarone group versus 2.8% per year in the ICD group (hazard ratio of amiodarone: ICD, 2.011; 95% confidence interval, 1.087 to 3.721; P=0.0261). In the amiodarone group, 49 patients (82% of all patients) had side effects related to amiodarone, of which 30 patients (50% of all patients) required discontinuation or dose reduction; 19 patients crossed over to ICD because of amiodarone failure (n=7) or side effects (n=12). CONCLUSIONS: In a subset of CIDS, the benefit of the ICD over amiodarone increases with time; most amiodarone-treated patients eventually develop side effects, have arrhythmia recurrences, or die.

Aged↗
PubMed2004

Prognostic differences between atrial fibrillation and atrial flutter.

This report presents the outcome of a cohort of 94 patients with atrial fibrillation from the Canadian Registry of Atrial Fibrillation, in which we paid particular attention to the probability of stroke and death. We also evaluated warfarin use over time and compared left atrial dimensions in patients with atrial flutter with those with atrial fibrillation.

Aged↗
PubMed2004

Quality of life as an endpoint for atrial fibrillation research: pitfalls and practice.

There have been few health-related quality-of-life (HR-QOL) studies of atrial fibrillation in nontreated cohorts, even though it often is used as an endpoint in clinical trials. Nonintervention data now available are selected for those in whom novel therapies are most often offered. These data suggest that atrial fibrillation confers an HR-QOL impact commensurate with postangioplasty and significant coronary disease groups. The correlation of HR-QOL measures and formal measures of atrial fibrillation "burden" (frequency or duration) is either poor or unknown (in the case of permanent atrial fibrillation). HR-QOL tools, although relevant, may not be as precise as traditional outcome measures. As a result, a 0.5 standard deviation unit of change in scale is needed to be considered moderate. There is a need to use validated instruments that are hypothesized to be sensitive to any intervention under study. The most studied area in atrial fibrillation has been that of ablation and pacing as rate control strategy. Depending on selection bias, SF-36 full standard deviation unit changes have been observed. Less controlled studies have documented significant benefit to left atrial ablative strategies. Device- and drug-based strategies in atrial fibrillation management have not demonstrated significant HR-QOL benefits, other than one controlled evaluation of an atrial defibrillator. Further study is needed both to refine instrument precision and to translate HR-QOL data into the denominator of cost-efficacy evaluations.

Atrial Fibrillation↗
PubMed2004

Randomized controlled study of detection enhancements versus rate-only detection to prevent inappropriate therapy in a dual-chamber implantable cardioverter-defibrillator.

OBJECTIVES: The purpose of this study was to compare rate-only detection to enhanced detection in a dual-chamber implantable cardioverter-defibrillator (ICD), to discriminate ventricular tachycardia from supraventricular tachycardia. BACKGROUND: ICDs are highly effective in treating ventricular tachycardia (VT) or ventricular fibrillation (VF). However, they frequently deliver inappropriate therapy during supraventricular tachycardia (SVT). METHODS: We conducted a randomized clinical trial of detection enhancements in a dual-chamber ICD compared to control (rate-only) detection to discriminate VT from SVT. Detection enhancements included a specific standardized protocol identical for all patients for programming rate stability, sudden onset, atrial-to-ventricular relationship (sudden onset = 9% and rate stability = 10 ms; V > A "on"), and "sustained rate duration" (3 minutes). The primary endpoint was the time to first inappropriate therapy classified by a blinded events committee. RESULTS: One hundred forty-nine patients had a history of sustained VT or VF. Mean age (+/- SD) was 60 +/- 13 years; 83% were male, and mean ejection fraction was 35 +/- 15%. Control (n = 70) and "enhanced" (n = 79) groups did not differ with regard to age, sex, ejection fraction, or primary arrhythmia. The proportion of patients free of inappropriate therapy over time was significantly higher in the enhanced versus the control group (hazard ratio = 0.47, P = .011). High-energy shocks were reduced from 0.58 +/- 4.23 shocks/patient/month in the control group to 0.04 +/- 0.15 shocks/patient/month in the enhanced group (P = .0425). No patient programmed per protocol failed to receive therapy for VT detected by the ICD (422 VT episodes). CONCLUSIONS: Standardized programming in a dual-chamber ICD leads to a significant and clinically important reduction in inappropriate therapies compared to rate-only detection and does not compromise safety with respect to appropriate treatment of VT.

Age Factors↗
PubMed2004

Feasibility of implantable cardioverter defibrillator use in elderly patients: a case series of octogenarians.

This article addresses the feasibility and safety of ICD therapy in patients >80 years of age. Recent trials have expanded the indication for ICD implantation to include an increasing number and variety of patients. The feasibility of ICD implantation in elderly patients has not been adequately studied. A prospectively collected single center ICD database was analyzed to assess the safety and feasibility of ICD implantation in elderly patients. Patients were divided based on age into two groups (group 1: 70-79 years of age, n = 183; group 2: >or=80 years of age, n = 29). The two groups were similar in gender distribution, NYHA class, and indication for implantation. The actuarial survival was not significantly different between groups 1 and 2 (P > 0.05; primary endpoint), with a 1-year survival of 91% and 93% in groups 1 and 2, respectively, (P = NS). The complication rates at the time of ICD implantation were similar in groups 1 and 2 (6.6% and 13.1%, respectively, P = 0.16). Age alone may not be sufficient criteria to exclude ICD implantation. The current consensus guidelines for ICD implantation appear to be generalizable to treating octogenarians who are otherwise medically fit.

Actuarial Analysis↗
PubMed2003

Expression of ICAM-1, TNF-alpha, NF kappa B, and MAP kinase in tubers of the tuberous sclerosis complex.

Individuals affected with tuberous sclerosis complex (TSC) develop cortical tubers characterized by disorganized cytoarchitecture and morphologically abnormal cell types, such as dysplastic neurons (DNs) and giant cells (GCs). As part of ongoing cDNA array analysis to study the molecular pathogenesis of tuber formation, we detected increased expression of intercellular adhesion molecule-1 (ICAM-1) mRNA, a cell adhesion molecule (CAM) that functions in cytokine signaling, in tubers. Western and immunohistochemical analyses revealed that ICAM-1 protein was selectively expressed in tubers, but was only minimally expressed in control cortex, adjacent nontuberal cortex, or in non-TSC focal cortical dysplasia. Increased expression of ICAM-1 was found in mice in which the Tsc1 gene was conditionally inactivated in astrocytes. Expression of molecules involved in ICAM-1 activation and cytokine signaling were increased in tubers, including tumor necrosis factor alpha (TNF-alpha), mitogen activated protein kinase (MAPK), and nuclear factor kappa B (NF-kappaB). Numerous CD68-immunoreactive macrophages were observed clustered around GCs further supporting an inflammatory response in tubers. Expression of caspase 8 and Fas support cytokine activation and detection of TUNEL reactivity suggests ongoing cell death in tubers. Specific alterations in ICAM-1, TNF-alpha, NF-kappaB1, and MAPK expression coupled with the detection of numerous CD68-immunoreactive macrophages suggests activation of proinflammatory cytokine signaling pathways in tubers that may culminate in cell death.

Adult↗
PubMed2003

Is inappropriate implantable defibrillator shock therapy predictable?

OBJECTIVE: To identify implantable cardioverter defibrillator (ICD) patients who are at risk of receiving inappropriate shock. BACKGROUND: Inappropriate ICD shock, usually from atrial fibrillation (AF) or sinus tachycardia (ST), is a common problem. We hypothesized that clinical variables would predict which patients with single chamber ICDs would be more likely to receive inappropriate therapy and be candidates for more accurate discriminators such as those available in dual chamber ICDs. METHODS: The ICD registry at St. Michael's Hospital has it's clinical information and demographic data updated after each clinic visit. Inappropriate shock was considered as the outcome variable. Possible predictors considered were age, gender, ejection fraction, NYHA class, prior CABG and prior history of AF. Univariate predictors were identified using t-test for continuous variables and Chi-square test for categorical variables. Multivariate predictors were identified using stepwise logistic regression analyses. RESULTS: Of 299 patients, 261 had complete data for analysis. In this population 78% were male, mean age was 60 +/- 13 years, mean ejection fraction was 37 +/- 15% and mean follow up was 53 +/- 36 months. One hundred and sixteen of the 261 patients (44%) received one or more inappropriate therapies (73% within 2 years of receiving their device), and 140 (51%) received one or more appropriate therapies. Significant predictors of inappropriate therapy by multivariate model were prior AF (OR 2.6, 95% CI 1.5-4.5) and NYHA class 1 vs. classes 2-4 (OR 2.2, 95% CI 1.2-3.7). CONCLUSION: Clinical characteristics of ICD patients can predict those at risk for inappropriate shock and should be considered for interventions to decrease such shocks.

Aged↗
PubMed2003

Relationships between pacing mode and quality of life: evidence from randomized clinical trials.

Although mode-dependent differences in mortality are for the moment unproven, establishing a health-related quality of life difference between assigned pacing modes would be useful. Such a difference, if one exists, should be >or=0.5 standard deviation units among scales using validated instruments to have significant clinical meaning. Two large data sets, the Canadian Trial of Physiological Pacing (CTOPP) and the Mode Selection Trial (MOST) both similar in design, largely failed to clearly establish such a significant difference. Another trial the Pacemaker Selection in the Elderly (PASE) did suggest that for sinus node disease, DDD-R pacing may lead to an improvement in quality of life mainly early post implant. Two other large trials, UK-PACE and DANPACE have yet to present quality of life related results. All published data have established that restoration of chronotropic competence by pacing leads to improvements in quality of life that are significant. In CTOPP an attempt to quantify a mode-dependent difference for a pacemaker syndrome suggested that the prevalence and clinical importance of pacemaker syndrome may be exaggerated. The relative ease of crossover from VVI-R to DDD, by device upgrade in CTOPP or by programming in MOST, may explain the 2.9% vs. 31% crossover rates seen in CTOPP vs. MOST respectively. Trials to date may have had a mode dependent difference undermined by possible adverse effects from right ventricular apical sites of pacing. Future trial data; DANPACE, sinus node disease AAI-R vs. DDD-R and PAVE, post AVJ ablation VVI-R vs. VVI-CRT, will asses in more detail the role of site of pacing as a factor in determining mode dependent outcomes in pacing.

Cardiac Pacing, Artificial↗