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Laird, Nan

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Laird

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Nan

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Laird, Nan
Author's Publications: search.filters.isAuthorOfPublication.198b069a-5901-4617-b33f-1cd3655825d8

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    Effect of Computerized Physician Order Entry and a Team Intervention on Prevention of Serious Medication Errors
    (American Medical Association (AMA), 1998-10-21) Bates, David; Leape, Lucian; Cullen, David J; Laird, Nan; Petersen, Laura A; Teich, Jonathan; Burdick, Elizabeth; Hickey, Mairead; Kleefield, Sharon; Shea, Brian; Vander Vliet, Martha; Seger, Diane L
    Context: Adverse drug events (ADEs) are a significant and costly cause of injury during hospitalization. Objectives: To evaluate the efficacy of 2 interventions for preventing nonintercepted serious medication errors, defined as those that either resulted in or had potential to result in an ADE and were not intercepted before reaching the patient. Design: Before-after comparison between phase 1 (baseline) and phase 2 (after intervention was implemented) and, within phase 2, a randomized comparison between physician computer order entry (POE) and the combination of POE plus a team intervention. Setting: Large tertiary care hospital. Participants: For the comparison of phase 1 and 2, all patients admitted to a stratified random sample of 6 medical and surgical units in a tertiary care hospital over a 6-month period, and for the randomized comparison during phase 2, all patients admitted to the same units and 2 randomly selected additional units over a subsequent 9-month period. Interventions: A physician computer order entry system (POE) for all units and a team-based intervention that included changing the role of pharmacists, implemented for half the units. Main outcome measure: Nonintercepted serious medication errors. Results: Comparing identical units between phases 1 and 2, nonintercepted serious medication errors decreased 55%, from 10.7 events per 1000 patient-days to 4.86 events per 1000 (P=.01). The decline occurred for all stages of the medication-use process. Preventable ADEs declined 17% from 4.69 to 3.88 (P=.37), while nonintercepted potential ADEs declined 84% from 5.99 to 0.98 per 1000 patient-days (P=.002). When POE-only was compared with the POE plus team intervention combined, the team intervention conferred no additional benefit over POE. Conclusions: Physician computer order entry decreased the rate of nonintercepted serious medication errors by more than half, although this decrease was larger for potential ADEs than for errors that actually resulted in an ADE.
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    Exome Sequencing in Schizophrenia-Affected Parent–offspring Trios Reveals Risk Conferred by Protein-Coding De Novo Mutations
    (Springer Science and Business Media LLC, 2020-01-13) Howrigan, Daniel; Rose, Samuel A.; Samocha, Kaitlin E.; Fromer, Menachem; Cerrato, Felecia; Chen, Wei J.; Churchhouse, Claire; Chambert, Kimberly; Chandler, Sharon D.; Daly, Mark; Dumont, Ashley; Genovese, Giulio; Hwu, Hai-Gwo; Laird, Nan; Kosmicki, Jack; Moran, Jennifer L.; Singh, Tarjinder; McCarroll, Steven; Faraone, Stephen V.; Glatt, Stephen J.; Tsuang, Ming; Neale, Benjamin
    Protein-coding de novo mutations (DNMs) are significant risk factors in many neurodevelopmental disorders, whereas association with schizophrenia (SCZ) risk thus far has been modest. We analyze whole-exome sequence from 1,695 SCZ affected trios along with DNMs from 1,077 published SCZ trios to better understand their contribution to SCZ risk. Among 2,772 SCZ probands, exome-wide DNM burden remains modest. Gene set analyses reveal that SCZ DNMs are significantly concentrated in genes either highly brain expressed, under strong evolutionary constraint, and/or overlap with genes identified in other neurodevelopmental disorders. No single gene surpasses exome-wide significance, however sixteen genes are recurrently hit by protein-truncating DNMs, a 3.15-fold higher rate than the mutation model expectation (permuted 95% CI=1-10 genes, permuted p=3e-5). Overall, DNMs explain only a small fraction of SCZ risk, and larger samples are needed to identify individual risk genes, as coding variation across many genes confer risk for SCZ in the population.
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    A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry
    (BioMed Central, 2015) Lutz, Sharon M.; Cho, Michael; Young, Kendra; Hersh, Craig; Castaldi, Peter; McDonald, Merry-Lynn N; Regan, Elizabeth; Mattheisen, Manuel; Demeo, Dawn; Parker, Margaret; Foreman, Marilyn; Make, Barry J.; Jensen, Robert L.; Casaburi, Richard; Lomas, David A.; Bhatt, Surya P.; Bakke, Per; Gulsvik, Amund; Crapo, James D.; Beaty, Terri H.; Laird, Nan; Lange, Christoph; Hokanson, John E.; Silverman, Edwin
    Background: Pulmonary function decline is a major contributor to morbidity and mortality among smokers. Post bronchodilator FEV1 and FEV1/FVC ratio are considered the standard assessment of airflow obstruction. We performed a genome-wide association study (GWAS) in 9919 current and former smokers in the COPDGene study (6659 non-Hispanic Whites [NHW] and 3260 African Americans [AA]) to identify associations with spirometric measures (post-bronchodilator FEV1 and FEV1/FVC). We also conducted meta-analysis of FEV1 and FEV1/FVC GWAS in the COPDGene, ECLIPSE, and GenKOLS cohorts (total n = 13,532). Results: Among NHW in the COPDGene cohort, both measures of pulmonary function were significantly associated with SNPs at the 15q25 locus [containing CHRNA3/5, AGPHD1, IREB2, CHRNB4] (lowest p-value = 2.17 × 10−11), and FEV1/FVC was associated with a genomic region on chromosome 4 [upstream of HHIP] (lowest p-value = 5.94 × 10−10); both regions have been previously associated with COPD. For the meta-analysis, in addition to confirming associations to the regions near CHRNA3/5 and HHIP, genome-wide significant associations were identified for FEV1 on chromosome 1 [TGFB2] (p-value = 8.99 × 10−9), 9 [DBH] (p-value = 9.69 × 10−9) and 19 [CYP2A6/7] (p-value = 3.49 × 10−8) and for FEV1/FVC on chromosome 1 [TGFB2] (p-value = 8.99 × 10−9), 4 [FAM13A] (p-value = 3.88 × 10−12), 11 [MMP3/12] (p-value = 3.29 × 10−10) and 14 [RIN3] (p-value = 5.64 × 10−9). Conclusions: In a large genome-wide association study of lung function in smokers, we found genome-wide significant associations at several previously described loci with lung function or COPD. We additionally identified a novel genome-wide significant locus with FEV1 on chromosome 9 [DBH] in a meta-analysis of three study populations. Electronic supplementary material The online version of this article (doi:10.1186/s12863-015-0299-4) contains supplementary material, which is available to authorized users.
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    Analyzing networks of phenotypes in complex diseases: methodology and applications in COPD
    (BioMed Central, 2014) Chu, Jen-Hwa; Hersh, Craig; Castaldi, Peter; Cho, Michael; Raby, Benjamin; Laird, Nan; Bowler, Russell; Rennard, Stephen; Loscalzo, Joseph; Quackenbush, John; Silverman, Edwin
    Background: The investigation of complex disease heterogeneity has been challenging. Here, we introduce a network-based approach, using partial correlations, that analyzes the relationships among multiple disease-related phenotypes. Results: We applied this method to two large, well-characterized studies of chronic obstructive pulmonary disease (COPD). We also examined the associations between these COPD phenotypic networks and other factors, including case-control status, disease severity, and genetic variants. Using these phenotypic networks, we have detected novel relationships between phenotypes that would not have been observed using traditional epidemiological approaches. Conclusion: Phenotypic network analysis of complex diseases could provide novel insights into disease susceptibility, disease severity, and genetic mechanisms.
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    A comparative analysis of family-based and population-based association tests using whole genome sequence data
    (BioMed Central, 2014) Zhou, Jin J; Yip, Wai-Ki; Cho, Michael; Qiao, Dandi; McDonald, Merry-Lynn N; Laird, Nan
    The revolution in next-generation sequencing has made obtaining both common and rare high-quality sequence variants across the entire genome feasible. Because researchers are now faced with the analytical challenges of handling a massive amount of genetic variant information from sequencing studies, numerous methods have been developed to assess the impact of both common and rare variants on disease traits. In this report, whole genome sequencing data from Genetic Analysis Workshop 18 was used to compare the power of several methods, considering both family-based and population-based designs, to detect association with variants in the MAP4 gene region and on chromosome 3 with blood pressure. To prioritize variants across the genome for testing, variants were first functionally assessed using prediction algorithms and expression quantitative trait loci (eQTLs) data. Four set-based tests in the family-based association tests (FBAT) framework--FBAT-v, FBAT-lmm, FBAT-m, and FBAT-l--were used to analyze 20 pedigrees, and 2 variance component tests, sequence kernel association test (SKAT) and genome-wide complex trait analysis (GCTA), were used with 142 unrelated individuals in the sample. Both set-based and variance-component-based tests had high power and an adequate type I error rate. Of the various FBATs, FBAT-l demonstrated superior performance, indicating the potential for it to be used in rare-variant analysis. The updated FBAT package is available at: http://www.hsph.harvard.edu/fbat/.
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    Incidence of Adverse Events and Negligence in Hospitalized Patients — Results of the Harvard Medical Practice Study I
    (Massachusetts Medical Society, 1991-02-07) Brennan, Troyen; Leape, Lucian; Laird, Nan; Hebert, Liesi; Localio, A. Russell; Lawthers, Ann G.; Newhouse, Joseph; Weiler, Paul; Hiatt, Howard
    METHODS We reviewed 30,121 randomly selected records from 51 randomly selected acute care, nonpsychiatric hospitals in New York State in 1984. We then developed population estimates of injuries and computed rates according to the age and sex of the patients as well as the specialties of the physicians. RESULTS Adverse events occurred in 3.7 percent of the hospitalizations (95 percent confidence interval, 3.2 to 4.2), and 27.6 percent of the adverse events were due to negligence (95 percent confidence interval, 22.5 to 32.6). Although 70.5 percent of the adverse events gave rise to disability lasting less than six months, 2.6 percent caused permanently disabling injuries and 13.6 percent led to death. The percentage of adverse events attributable to negligence increased in the categories of more severe injuries (Wald test χ2 = 21.04, P<0.0001). Using weighted totals, we estimated that among the 2,671,863 patients discharged from New York hospitals in 1984 there were 98,609 adverse events and 27,179 adverse events involving negligence. Rates of adverse events rose with age (P<0.0001). The percentage of adverse events due to negligence was markedly higher among the elderly (P<0.01). There were significant differences in rates of adverse events among categories of clinical specialties (P<0.0001), but no differences in the percentage due to negligence. CONCLUSIONS There is a substantial amount of injury to patients from medical management, and many injuries are the result of substandard care.
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    The Nature of Adverse Events in Hospitalized Patients: Results of the Harvard Medical Practice Study II
    (Massachusetts Medical Society, 1991-02-07) Leape, Lucian; Brennan, Troyen; Laird, Nan; Lawthers, Ann G.; Localio, A. Russell; Barnes, Benjamin A.; Hebert, Liesi; Newhouse, Joseph; Weiler, Paul; Hiatt, Howard
    Background: In a sample of 30,195 randomly selected hospital records, we identified 1133 patients (3.7 percent) with disabling injuries caused by medical treatment. We report here an analysis of these adverse events and their relation to error, negligence, and disability. Methods: Two physician-reviewers independently identified the adverse events and evaluated them with respect to negligence, errors in management, and extent of disability. One of the authors classified each event according to type of injury. We tested the significance of differences in rates of negligence and disability among categories with at least 30 adverse events. Results: Drug complications were the most common type of adverse event (19 percent), followed by wound infections (14 percent) and technical complications (13 percent). Nearly half the adverse events (48 percent) were associated with an operation. Adverse events during surgery were less likely to be caused by negligence (17 percent) than nonsurgical ones (37 percent). The proportion of adverse events due to negligence was highest for diagnostic mishaps (75 percent), noninvasive therapeutic mishaps ("errors of omission") (77 percent), and events occurring in the emergency room (70 percent). Errors in management were identified for 58 percent of the adverse events, among which nearly half were attributed to negligence. Conclusions: Although the prevention of many adverse events must await improvements in medical knowledge, the high proportion that are due to management errors suggests that many others are potentially preventable now. Reducing the incidence of these events will require identifying their causes and developing methods to prevent error or reduce its effects.
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    Ozone exposure, vitamin C intake, and genetic susceptibility of asthmatic children in Mexico City: a cohort study
    (BioMed Central, 2013) Moreno-Macías, Hortensia; Dockery, Douglas; Schwartz, Joel; Gold, Diane; Laird, Nan; Sienra-Monge, Juan J; Del Río-Navarro, Blanca E; Ramírez-Aguilar, Matiana; Barraza-Villarreal, Albino; Li, Huiling; London, Stephanie J; Romieu, Isabelle
    Background: We previously reported that asthmatic children with GSTM1 null genotype may be more susceptible to the acute effect of ozone on the small airways and might benefit from antioxidant supplementation. This study aims to assess the acute effect of ozone on lung function (FEF25-75) in asthmatic children according to dietary intake of vitamin C and the number of putative risk alleles in three antioxidant genes: GSTM1, GSTP1 (rs1695), and NQO1 (rs1800566). Methods: 257 asthmatic children from two cohort studies conducted in Mexico City were included. Stratified linear mixed models with random intercepts and random slopes on ozone were used. Potential confounding by ethnicity was assessed. Analyses were conducted under single gene and genotype score approaches. Results: The change in FEF25-75 per interquartile range (60 ppb) of ozone in persistent asthmatic children with low vitamin C intake and GSTM1 null was −91.2 ml/s (p = 0.06). Persistent asthmatic children with 4 to 6 risk alleles and low vitamin C intake showed an average decrement in FEF25-75 of 97.2 ml/s per 60 ppb of ozone (p = 0.03). In contrast in children with 1 to 3 risk alleles, acute effects of ozone on FEF25-75 did not differ by vitamin C intake. Conclusions: Our results provide further evidence that asthmatic children predicted to have compromised antioxidant defense by virtue of genetic susceptibility combined with deficient antioxidant intake may be at increased risk of adverse effects of ozone on pulmonary function.
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    Identifying Rare Variants from Exome Scans: The GAW17 Experience
    (BioMed Central, 2011) Ghosh, Saurabh; Bickeböller, Heike; Bailey-Wilson, Joan E; Cantor, Rita; Culverhouse, Robert; Daw, Warwick; DeStefano, Anita L; Engelman, Corinne D; Hinrichs, Anthony; Houwing-Duistermaat, Jeanine; König, Inke R; Kent, Jack; Pankratz, Nathan; Pugh, Elizabeth; Suarez, Brian; Thomas, Alun; Tintle, Nathan; Zhu, Xiaofeng; Ziegler, Andreas; MacCluer, Jean W; Almasy, Laura; Bailey, Julia; Laird, Nan; Paterson, Andrew; Sun, Yan
    Genetic Analysis Workshop 17 (GAW17) provided a platform for evaluating existing statistical genetic methods and for developing novel methods to analyze rare variants that modulate complex traits. In this article, we present an overview of the 1000 Genomes Project exome data and simulated phenotype data that were distributed to GAW17 participants for analyses, the different issues addressed by the participants, and the process of preparation of manuscripts resulting from the discussions during the workshop.
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    Identifying Causal Rare Variants of Disease Through Family-based Analysis of Genetics Analysis Workshop 17 Data Set
    (BioMed Central, 2011) Yip, Wai-Ki; De, Gourab; Raby, Benjamin; Laird, Nan
    Linkage- and association-based methods have been proposed for mapping disease-causing rare variants. Based on the family information provided in the Genetic Analysis Workshop 17 data set, we formulate a two-pronged approach that combines both methods. Using the identity-by-descent information provided for eight extended pedigrees (n = 697) and the simulated quantitative trait Q1, we explore various traditional nonparametric linkage analysis methods; the best result is obtained by assuming between-family heterogeneity and applying the Haseman-Elston regression to each pedigree separately. We discover strong signals from two genes in two different families and weaker signals for a third gene from two other families. As an exploratory approach, we apply an association test based on a modified family-based association test statistic to all rare variants (frequency < 1% or < 3%) designated as causal for Q1. Family-based association tests correctly identified causal single-nucleotide polymorphisms for four genes (KDR, VEGFA, VEGFC, and FLT1). Our results suggest that both linkage and association tests with families show promise for identifying rare variants.