Showing papers by "Frank E. Speizer published in 2006"

Reduction in fine particulate air pollution and mortality : Extended Follow-up of the Harvard Six Cities Study

Abstract: Rationale: A large body of epidemiologic literature has found an association of increased fine particulate air pollution (PM2.5) with acute and chronic mortality. The effect of improvements in particle exposure is less clear. Objectives: Earlier analysis of the Harvard Six Cities adult cohort study showed an association between long-term ambient PM2.5 and mortality between enrollment in the mid-1970s and follow-up until 1990. We extended mortality follow-up for 8 yr in a period of reduced air pollution concentrations. Methods: Annual city-specific PM2.5 concentrations were measured between 1979 and 1988, and estimated for later years from publicly available data. Exposure was defined as (1) city-specific mean PM2.5 during the two follow-up periods, (2) mean PM2.5 in the first period and change between these periods, (3) overall mean PM2.5 across the entire follow-up, and (4) year-specific mean PM2.5. Mortality rateratioswereestimatedwithCoxproportionalhazardsregression controlling for individual risk factors. Measurements and Main Results: We found an increase in overall mortality associated with each 10 g/m 3 increase in PM2.5 modeled either as the overall mean (rate ratio [RR], 1.16; 95% confidence interval [CI], 1.07–1.26) or as exposure in the year of death (RR, 1.14; 95% CI, 1.06–1.22). PM2.5 exposure was associated with lung cancer (RR, 1.27; 95% CI, 0.96–1.69) and cardiovascular deaths (RR, 1.28;95%CI, 1.13–1.44).Improved overallmortality wasassociated with decreased mean PM2.5 (10 g/m 3 ) between periods (RR, 0.73; 95% CI, 0.57–0.95). Conclusion: Total, cardiovascular, and lung cancer mortality were each positively associated with ambient PM2.5 concentrations. Reduced PM2.5 concentrations were associated with reduced mortality risk.

Impact of Extended-Duration Shifts on Medical Errors, Adverse Events, and Attentional Failures

Abstract: Background A recent randomized controlled trial in critical-care units revealed that the elimination of extended-duration work shifts (� 24 h) reduces the rates of significant medical errors and polysomnographically recorded attentional failures. This raised the concern that the extendedduration shifts commonly worked by interns may contribute to the risk of medical errors being made, and perhaps to the risk of adverse events more generally. Our current study assessed whether extended-duration shifts worked by interns are associated with significant medical errors, adverse events, and attentional failures in a diverse population of interns across the United States.

Extended Work Duration and the Risk of Self-reported Percutaneous Injuries in Interns

Abstract: Context In their first year of postgraduate training, interns commonly work shifts that are longer than 24 hours. Extended-duration work shifts are associated with increased risks of automobile crash, particularly during a commute from work. Interns may be at risk for other occupation-related injuries. Objective To assess the relationship between extended work duration and rates of percutaneous injuries in a diverse population of interns in the United States.

The SERPINE2 Gene Is Associated with Chronic Obstructive Pulmonary Disease

Abstract: Chronic obstructive pulmonary disease (COPD) is a complex human disease likely influenced by multiple genes, cigarette smoking, and gene-by-smoking interactions, but only severe alpha 1-antitrypsin deficiency is a proven genetic risk factor for COPD. Prior linkage analyses in the Boston Early-Onset COPD Study have demonstrated significant linkage to a key intermediate phenotype of COPD on chromosome 2q. We integrated results from murine lung development and human COPD gene–expression microarray studies with human COPD linkage results on chromosome 2q to prioritize candidate-gene selection, thus identifying SERPINE2 as a positional candidate susceptibility gene for COPD. Immunohistochemistry demonstrated expression of serpine2 protein in mouse and human adult lung tissue. In family-based association testing of 127 severe, early-onset COPD pedigrees from the Boston Early-Onset COPD Study, we observed significant association with COPD phenotypes and 18 single-nucleotide polymorphisms (SNPs) in the SERPINE2 gene. Association of five of these SNPs with COPD was replicated in a case-control analysis, with cases from the National Emphysema Treatment Trial and controls from the Normative Aging Study. Family-based and case-control haplotype analyses supported similar regions of association within the SERPINE2 gene. When significantly associated SNPs in these haplotypic regions were included as covariates in linkage models, LOD score attenuation was observed most markedly in a smokers-only linkage model (LOD 4.41, attenuated to 1.74). After the integration of murine and human microarray data to inform candidate-gene selection, we observed significant family-based association and independent replication of association in a case-control study, suggesting that SERPINE2 is a COPD-susceptibility gene and is likely influenced by gene-by-smoking interaction.

Increased risk of paroxysmal atrial fibrillation episodes associated with acute increases in ambient air pollution.

Abstract: Objectives: We reported previously that 24-hr moving average ambient air pollution concentrations were positively associated with ventricular arrhythmias detected by implantable cardioverter defibrillators (ICDs). ICDs also detect paroxysmal atrial fibrillation episodes (PAF) that result in rapid ventricular rates. In this same cohort of ICD patients, we assessed the association between ambient air pollution and episodes of PAF. Design: We performed a case–crossover study. Participants: Patients who lived in the Boston, Massachusetts, metropolitan area and who had ICDs implanted between June 1995 and December 1999 (n = 203) were followed until July 2002. Evaluations/Measurements: We used conditional logistic regression to explore the association between community air pollution and 91 electrophysiologist-confirmed episodes of PAF among 29 subjects. Results: We found a statistically significant positive association between episodes of PAF and increased ozone concentration (22 ppb) in the hour before the arrhythmia (odds ratio = 2.08; 95% confidence interval = 1.22, 3.54; p = 0.001). The risk estimate for a longer (24-hr) moving average was smaller, thus suggesting an immediate effect. Positive but not statistically significant risks were associated with fine particles, nitrogen dioxide, and black carbon. Conclusions: Increased ambient O3 pollution was associated with increased risk of episodes of rapid ventricular response due to PAF, thereby suggesting that community air pollution may be a precipitant of these events.

The SERPINE2 Gene Is Associated with Chronic Obstructive Pulmonary Disease

Abstract: Channing Laboratory and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Harvard School of Public Health, Veterans Affairs Medical Center, The Pulmonary Center and Bioinformatics Program, College of Engineering, Boston University Medical Center, and Division of Pulmonary and Critical Care, Department of Medicine, Caritas-St. Elizabeth’s Medical Center, Boston; Department of Physiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok; and Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California at San Francisco, San Francisco

A functional mutation in the terminal exon of elastin in severe, early onset chronic obstructive pulmonary disease: Am J Respir Cell Mol Biol 2005;33:355–62

Abstract: We describe a novel variant in the terminal exon of human elastin, c.2318 G > A, resulting in an amino acid substitution of glycine 773 to aspartate (G773D) in a pedigree with severe early-onset chronic obstructive pulmonary disease (COPD). Transfection studies with elastin cDNAs demonstrate that the glycine to aspartate change compromises the ability of the mutant protein to undergo normal elastin assembly. Other functional consequences of this amino acid substitution include altered proteolytic susceptibility of the C-terminal region of elastin and reduced interaction of the exon 36 sequence with matrix receptors on cells. These results suggest that the G773D variant confers structural and functional consequences relevant to the pathogenesis of COPD.

Extended work duration and the risk of self-reported percutaneous injuries in interns. Commentary

Abstract: Context In their first year of postgraduate training, interns commonly work shifts that are longer than 24 hours. Extended-duration work shifts are associated with increased risks of automobile crash, particularly during a commute from work. Interns may be at risk for other occupation-related injuries. Objective To assess the relationship between extended work duration and rates of percutaneous injuries in a diverse population of interns in the United States. Design, Setting, and Participants National prospective cohort study of 2737 of the estimated 18447 interns in US postgraduate residency programs from July 2002 through May 2003. Each month, comprehensive Web-based surveys that asked about work schedules and the occurrence of percutaneous injuries in the previous month were sent to all participants. Case-crossover within-subjects analyses were performed. Main Outcome Measures Comparisons of rates of percutaneous injuries during day work (6:30 AM to 5:30 PM) after working overnight (extended work) vs day work that was not preceded by working overnight (nonextended work). We also compared injuries during the nighttime (11:30 PM to 7:30 AM) vs the daytime (7:30 AM to 3:30 PM). Results From a total of17 003 monthly surveys, 498 percutaneous injuries were reported (0.029/intern-month). In 448 injuries, at least 1 contributing factor was reported. Lapse in concentration and fatigue were the 2 most commonly reported contributing factors (64% and 31 % of injuries, respectively). Percutaneous injuries were more frequent during extended work compared with nonextended work (1.31/1000 opportunities vs 0.76/1000 opportunities, respectively; odds ratio [OR], 1.61; 95% confidence interval [Cl], 1.46-1.78). Extended work injuries occurred after a mean of 29.1 consecutive work hours; nonextended work injuries occurred after a mean of 6.1 consecutive work hours. Injuries were more frequent during the nighttime than during the daytime (1.48/1000 opportunities vs 0.70/1000 opportunities, respectively; OR, 2.04; 95% Cl, 1.98-2.11). Conclusion Extended work duration and night work were associated with an increased risk of percutaneous injuries in this study population of physicians during their first year of clinical training.