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1.  Alpha-1 antitrypsin deficiency and the risk of hepatocellular carcinoma in end-stage liver disease 
World Journal of Hepatology  2015;7(10):1427-1432.
AIM: To evaluate the association between alpha-1 antitrypsin deficiency (A1ATD) and hepatocellular carcinoma (HCC) in patients with end-stage liver disease (ESLD).
METHODS: Patients with cirrhosis and ESLD referred to the Cleveland Clinic Foundation for liver transplantation between 2003 and 2014 were included in the study (N = 675). ESLD was defined as having histological features of cirrhosis and/or radiological evidence of cirrhosis in the context of portal hypertension (ascites, variceal bleeding, thrombocytopenia, or hepatic encephalopathy). A1ATD was diagnosed using phenotype characterization (MZ or ZZ), liver biopsy detection of PAS-positive diastase-resistant (PAS+) globules, or both. Patients with other causes of liver diseases such as hepatitis C virus (HCV), alcoholic liver disease and non-alcoholic steatohepatitis (NASH) or NASH were also included in the study. HCC was diagnosed by using imaging modalities, biopsy findings, or explanted liver inspection. Follow-up time was defined as the number of years from the diagnosis of cirrhosis to the diagnosis of hepatocellular carcinoma, or from the diagnosis of cirrhosis to the last follow up visit. The rate of HCC was assessed using time-to-interval analysis for interval censored data.
RESULTS: This study included 675 patients. 7% of subjects had A1ATD (n = 47). Out of all subjects who did not have A1ATD, 46% had HCV, 17% had alcoholic liver disease, 19% had NASH and 18% had another primary diagnosis. Of the 47 subjects with A1ATD, 15 had a primary diagnosis of A1ATD (PI*ZZ phenotype and PAS+ globules), 8 had a PI*MZ phenotype alone, 14 had PAS+ alone, and 10 had both the PI*MZ phenotype and PAS+. Median follow-up time was 3.4 (25th, 75th percentiles: 1, 5.2) years. The overall rate of hepatocellular carcinoma in all subjects was 29% (n = 199). In the A1ATD group, the incidence rate of HCC was 8.5% compared to 31% in the group of patients with other causes of cirrhosis (P = 0.001). Patients with ESLD due to A1ATD had the lowest yearly cumulative rate of hepatocellular carcinoma at 0.88% per year compared to 2.7% for those with HCV cirrhosis, 1.5% in patients with NASH and 0.9% in alcohol-induced liver disease (P < 0.001).
CONCLUSION: Within this group of patients with ESLD, there was no significant association between A1ATD and increased risk of HCC.
PMCID: PMC4450206  PMID: 26052388
Hepatocellular carcinoma; Liver cirrhosis; End-stage liver disease; Hepatitis C virus; Alpha-1 antitrypsin deficiency
2.  Developing a leadership pipeline: the Cleveland Clinic experience 
The complexity of health care requires excellent leadership to address the challenges of access, quality, and cost of care. Because competencies to lead differ from clinical or research skills, there is a compelling need to develop leaders and create a talent pipeline, perhaps especially in physician-led organizations like Cleveland Clinic. In this context, we previously reported on a cohort-based physician leadership development course called Leading in Health Care and, in the current report, detail an expanded health care leadership development programme called the Cleveland Clinic Academy (CCA). CCA consists of a broad suite of offerings, including cohort-based learning and ‘a la carte’ half- or full-day courses addressing specific competencies to manage and to lead. Academy attendance is optional and is available to all physicians, nurses, and administrators with the requisite experience. Course selection is guided by competency matrices which map leadership competencies to specific courses. As of December 2012, a total of 285 course sessions have been offered to 6,050 attendees with uniformly high ratings of course quality and impact. During the past 10 years, Cleveland Clinic’s leadership and management curriculum has successfully created a pipeline of health care leaders to fill executive positions, search committees, board openings, and various other organizational leadership positions. Health care leadership can be taught and learned.
PMCID: PMC4235808  PMID: 25082312
Leadership; Development; Pipeline; Healthcare; Physician
3.  Help wanted: developing clinician leaders 
Because healthcare faces challenges, such as ensuring quality and access and controlling cost, effective leadership is needed at every level of healthcare organizations. Yet, physicians are trained in clinical and scientific skills but not in leadership competencies. Furthermore, clinicians often feel ill-prepared to assume managerial and leadership roles. To close this gap, training in leadership competencies, such as emotional intelligence, communication, teamwork, and change management, is urgently needed for physicians and clinicians of all disciplines. Leadership training should be multidisciplinary and should begin early in clinicians’ careers.
PMCID: PMC4078054  PMID: 24865886
Leadership development; Emotional intelligence; Teamwork; Curriculum
4.  The Cleveland Clinic: a distinctive model of American medicine 
The Cleveland Clinic is a large healthcare system based in Cleveland, Ohio (USA) with an extensive American (throughout Northeast Ohio; Weston, Florida; and Las Vegas, Nevada) and global presence (in Abu Dhabi, UAE; and with training alumni in >70 countries). Cleveland Clinic was founded in 1921 as a distinctive medical model with a tripartite mission of “better care of the sick, investigation of their problems, and more teaching of those who serve” which has been vibrantly maintained. Distinctive aspects of the Clinic include its being a closed staff, salaried, group practice which is physician-led and which features 1-year faculty appointments and a vigorous annual review process for all physicians and leaders. Regarding its tripartite mission, the Clinic has demonstrated longstanding clinical excellence, e.g., with consistent ranking as first in cardiovascular care in U.S. News and World Report and top-10 rankings in at least 12 other specialties. A longstanding tradition of research has contributed landmark discoveries, including performance of the first coronary revascularization procedure, the first intra-coronary angiogram, the world’s third face transplant, ongoing development of a breast cancer vaccine, etc. Regarding education, the Clinic serves many educational audiences excellently through its Education Institute. These audiences include medical students, graduate medical trainees, faculty physicians, nurses, and allied health providers (both within the Cleveland Clinic and from other institutions worldwide), and patients. The Education Institute also includes the Cleveland Clinic Academy, which offers training in leadership competencies to physicians, nurses, and healthcare administrators both within the Cleveland Clinic and to visitors from abroad (through the Executive Visitors Program and the Samson Global Leadership Academy for Healthcare Executives). The latter program is an intensive 2-week residential leadership development course for emerging healthcare leaders focusing on both personal leadership competencies and on healthcare system thinking ( Participants from 18 countries have attended to date.
PMCID: PMC4200609  PMID: 25333009
Cleveland Clinic; model of medicine; excellence; clinical care; research; education
5.  Granulomatosis with polyangiitis and associated pulmonary emphysema: Breathtaking vasculitis 
Pulmonary emphysema occasionally occurs in the absence of smoking or noxious exposures. Other than through a known association with alpha-1 antitryspin deficiency, to our knowledge, no reports implicate granulomatosis with polyangiitis (GPA) in causing airflow obstruction with small airway involvement and severe air trapping. To extend available experience, we report a 51-year-old male with biopsy-proven cytoplasmic–antineutrophilic cytoplasmic antibody proteinase 3 (ANCA PR3)-positive GPA who developed centrilobular emphysema and airflow obstruction during a phase of active vasculitis. He was a lifelong non-smoker and had a normal alpha-1 antitrypsin level and a PI*MM phenotype. Treatment with corticosteroids and cyclophosphamide caused clinical remission of his vasculitis which was associated with improvement in his respiratory symptoms. However, to date, structural changes of emphysema have persisted for over 9 years of follow-up. Clinicians should remain vigilant to the possibility of emphysema in patients with pulmonary vasculitis.
PMCID: PMC4502202  PMID: 26180387
Chronic obstructive pulmonary disease (COPD); emphysema; granulomatosis with polyangiitis (GPA)
6.  Communicating with graduate medical trainees: the Cleveland Clinic experience 
Optimizing communication with graduate medical trainees is critical, as they contribute importantly to the mission of academic medical centres. Yet, communication is challenged by their complex schedules, geographic separation, and time constraints. Few studies have examined this issue to offer valuable solutions. Because traditional approaches are suboptimal, two communication tools were implemented: (1) a web-based intranet site called [graduate medical education] GME|com, and (2) an electronic newsletter, GME|com Headlines. The goals were to: (1) build a single repository of information relevant to trainees, programme directors, and coordinators, and (2) minimize their email burdens. A post-launch survey showed that >75 % of respondents indicated they visited the site and, of those, >90 % perceived value to the site. Analysis of use over the first year showed 39,377 visits (mean 108/day) and 93,785 pageviews. Sixty percent of users visited GME|com between 9 and 201 times and 18 % >201 times. A survey of programme directors from the 25 largest training programmes in the US confirmed the challenges of communicating with trainees and suboptimal results of current solutions. GME|com and Headlines represent complementary communication tools that have been well-received and frequently used. Future opportunities include assessing the association of GME|com use with increments in quality and patient safety.
PMCID: PMC3722368
Communication; Educational technology; Health information technology; Medical education; Post-graduate education; Medical student and resident education
7.  Communicating with graduate medical trainees: the Cleveland Clinic experience 
Optimizing communication with graduate medical trainees is critical, as they contribute importantly to the mission of academic medical centres. Yet, communication is challenged by their complex schedules, geographic separation, and time constraints. Few studies have examined this issue to offer valuable solutions. Because traditional approaches are suboptimal, two communication tools were implemented: (1) a web-based intranet site called [graduate medical education] GME|com, and (2) an electronic newsletter, GME|com Headlines. The goals were to: (1) build a single repository of information relevant to trainees, programme directors, and coordinators, and (2) minimize their email burdens. A post-launch survey showed that >75 % of respondents indicated they visited the site and, of those, >90 % perceived value to the site. Analysis of use over the first year showed 39,377 visits (mean 108/day) and 93,785 pageviews. Sixty percent of users visited GME|com between 9 and 201 times and 18 % >201 times. A survey of programme directors from the 25 largest training programmes in the US confirmed the challenges of communicating with trainees and suboptimal results of current solutions. GME|com and Headlines represent complementary communication tools that have been well-received and frequently used. Future opportunities include assessing the association of GME|com use with increments in quality and patient safety.
PMCID: PMC3722368
Communication; Educational technology; Health information technology; Medical education; Post-graduate education; Medical student and resident education
8.  A Systematic Review of Physician Leadership and Emotional Intelligence 
This review evaluates the current understanding of emotional intelligence (EI) and physician leadership, exploring key themes and areas for future research.
Literature Search
We searched the literature using PubMed, Google Scholar, and Business Source Complete for articles published between 1990 and 2012. Search terms included physician and leadership, emotional intelligence, organizational behavior, and organizational development. All abstracts were reviewed. Full articles were evaluated if they addressed the connection between EI and physician leadership. Articles were included if they focused on physicians or physicians-in-training and discussed interventions or recommendations.
Appraisal and Synthesis
We assessed articles for conceptual rigor, study design, and measurement quality. A thematic analysis categorized the main themes and findings of the articles.
The search produced 3713 abstracts, of which 437 full articles were read and 144 were included in this review. Three themes were identified: (1) EI is broadly endorsed as a leadership development strategy across providers and settings; (2) models of EI and leadership development practices vary widely; and (3) EI is considered relevant throughout medical education and practice. Limitations of the literature were that most reports were expert opinion or observational and studies used several different tools for measuring EI.
EI is widely endorsed as a component of curricula for developing physician leaders. Research comparing practice models and measurement tools will critically advance understanding about how to develop and nurture EI to enhance leadership skills in physicians throughout their careers.
PMCID: PMC3963790  PMID: 24701306
9.  Toward “The Genius of the AND”: Balancing Professionalism and Duty Hour Requirements in Graduate Medical Education 
Although enhancing professionalism and ensuring compliance with duty hour regulations both represent important priorities of current graduate medical education, tension in reconciling these goals has been expressed. The term tyranny of the OR has been coined to express the assumption of dichotomous thinking, that is, that we assume we must choose between seemingly competing goals. In contrast, because there is powerful creative value in adopting a bridging mindset, an alternative state called the genius of the AND has been defined to express the benefits of reconciling perceived competing goals.
PMCID: PMC3179216  PMID: 22942952
10.  Determinants of airflow obstruction in severe alpha‐1‐antitrypsin deficiency 
Thorax  2007;62(9):806-813.
Severe α1‐antitrypsin (AAT) deficiency is an autosomal recessive genetic condition associated with an increased but variable risk for chronic obstructive pulmonary disease (COPD). A study was undertaken to assess the impact of chronic bronchitis, pneumonia, asthma and sex on the development of COPD in individuals with severe AAT deficiency.
The AAT Genetic Modifier Study is a multicentre family‐based cohort study designed to study the genetic and epidemiological determinants of COPD in AAT deficiency. 378 individuals (age range 33–80 years), confirmed to be homozygous for the SERPINA1 Z mutation, were included in the analyses. The primary outcomes of interest were a quantitative outcome, forced expiratory volume in 1 s (FEV1) percentage predicted, and a qualitative outcome, severe airflow obstruction (FEV1 <50% predicted).
In multivariate analysis of the overall cohort, cigarette smoking, sex, asthma, chronic bronchitis and pneumonia were risk factors for reduced FEV1 percentage predicted and severe airflow obstruction (p<0.01). Index cases had lower FEV1 values, higher smoking histories and more reports of adult asthma, pneumonia and asthma before age 16 than non‐index cases (p<0.01). Men had lower pre‐ and post‐bronchodilator FEV1 percentage predicted than women (p<0.0001); the lowest FEV1 values were observed in men reporting a history of childhood asthma (26.9%). This trend for more severe obstruction in men remained when index and non‐index groups were examined separately, with men representing the majority of non‐index individuals with airflow obstruction (71%). Chronic bronchitis (OR 3.8, CI 1.8 to 12.0) and a physician's report of asthma (OR 4.2, CI 1.4 to 13.1) were predictors of severe airflow obstruction in multivariate analysis of non‐index men but not women.
In individuals with severe AAT deficiency, sex, asthma, chronic bronchitis and pneumonia are risk factors for severe COPD, in addition to cigarette smoking. These results suggest that, in subjects severely deficient in AAT, men, individuals with symptoms of chronic bronchitis and/or a past diagnosis of asthma or pneumonia may benefit from closer monitoring and potentially earlier treatment.
PMCID: PMC2117297  PMID: 17389752
11.  Association of cigarette smoking and CRP levels with DNA methylation in α-1 antitrypsin deficiency 
Epigenetics  2012;7(7):720-728.
Alpha-1 antitrypsin (AAT) deficiency and tobacco smoking are confirmed risk factors for Chronic Obstructive Pulmonary Disease. We hypothesized that variable DNA methylation would be associated with smoking and inflammation, as reflected by the level of C-Reactive Protein (CRP) in AAT-deficient subjects. Methylation levels of 1,411 autosomal CpG sites from the Illumina GoldenGate Methylation Cancer Panel I were analyzed in 316 subjects. Associations of five smoking behaviors and CRP levels with individual CpG sites and average methylation levels were assessed using non-parametric testing, linear regression and linear mixed effect models, with and without adjustment for age and gender. Univariate linear regression analysis revealed that methylation levels of 16 CpG sites significantly associated with ever-smoking status. A CpG site in the TGFBI gene was the only site associated with ever-smoking after adjustment for age and gender. No highly significant associations existed between age at smoking initiation, pack-years smoked, duration of smoking, and time since quitting smoking as predictors of individual CpG site methylation levels. However, ever-smoking and younger age at smoking initiation associated with lower methylation level averaged across all sites. DNA methylation at CpG sites in the RUNX3, JAK3 and KRT1 genes associated with CRP levels. The most significantly associated CpG sites with gender and age mapped to the CASP6 and FZD9 genes, respectively. In summary, this study identified multiple potential candidate CpG sites associated with ever-smoking and CRP level in AAT-deficient subjects. Phenotypic variability in Mendelian diseases may be due to epigenetic factors.
PMCID: PMC3414392  PMID: 22617718
68kDa (TGFBI); C-Reactive Protein (CRP); Chronic Obstructive Pulmonary Disease (COPD); Illumina GoldenGate Methylation Cancer Panel I; alpha-1 antitrypsin (AAT) deficiency; beta-induced; methylation; smoking behaviors; transforming growth factor
12.  Association of IREB2 and CHRNA3 polymorphisms with airflow obstruction in severe alpha-1 antitrypsin deficiency 
Respiratory Research  2012;13(1):16.
The development of COPD in subjects with alpha-1 antitrypsin (AAT) deficiency is likely to be influenced by modifier genes. Genome-wide association studies and integrative genomics approaches in COPD have demonstrated significant associations with SNPs in the chromosome 15q region that includes CHRNA3 (cholinergic nicotine receptor alpha3) and IREB2 (iron regulatory binding protein 2).
We investigated whether SNPs in the chromosome 15q region would be modifiers for lung function and COPD in AAT deficiency.
The current analysis included 378 PIZZ subjects in the AAT Genetic Modifiers Study and a replication cohort of 458 subjects from the UK AAT Deficiency National Registry. Nine SNPs in LOC123688, CHRNA3 and IREB2 were selected for genotyping. FEV1 percent of predicted and FEV1/FVC ratio were analyzed as quantitative phenotypes. Family-based association analysis was performed in the AAT Genetic Modifiers Study. In the replication set, general linear models were used for quantitative phenotypes and logistic regression models were used for the presence/absence of emphysema or COPD.
Three SNPs (rs2568494 in IREB2, rs8034191 in LOC123688, and rs1051730 in CHRNA3) were associated with pre-bronchodilator FEV1 percent of predicted in the AAT Genetic Modifiers Study. Two SNPs (rs2568494 and rs1051730) were associated with the post-bronchodilator FEV1 percent of predicted and pre-bronchodilator FEV1/FVC ratio; SNP-by-gender interactions were observed. In the UK National Registry dataset, rs2568494 was significantly associated with emphysema in the male subgroup; significant SNP-by-smoking interactions were observed.
IREB2 and CHRNA3 are potential genetic modifiers of COPD phenotypes in individuals with severe AAT deficiency and may be sex-specific in their impact.
PMCID: PMC3306733  PMID: 22356581
CHRNA3; Chronic obstructive pulmonary disease; Genetic association analysis; Genetic modifiers; IREB2
13.  The Influence of Mentorship and Role Modeling on Developing Physician–Leaders: Views of Aspiring and Established Physician–Leaders 
Journal of General Internal Medicine  2009;24(10):1130-1134.
Although the benefits of mentoring in academic medical centers have been amply discussed, the major focus has been on conferring traditional academic skills (e.g., grantsmanship, publications, etc.). In contrast, little attention has been given to the career development of physician–leaders (e.g., communication, vision, teambuilding, etc.).
To understand the role and functions of mentoring and role-modeling in developing physician–leaders as experienced by aspiring and established physician–leaders.
Qualitative design using a stratified purposeful sample and inductive analysis.
Semi-structured interviews.
Twenty-five Cleveland Clinic faculty participated (14 established physician–leaders, 11 aspiring leaders). Three themes emerged: 1. Role modeling was differentiated as a valued experience separate from mentoring, with respondents describing the significant influence of purely observational learning and “watching leaders-in-action”. 2. Many respondents favored a series of “strategic” interactions with various individuals about specific professional issues rather than traditional, longitudinal mentoring experiences. 3. Emotional and psychological support was considered the most valued type of interventional activity.
In our small sample both established and aspiring physician leaders believed that mentorship and role modeling played a significant role in their career development. Short, focused “strategic” mentoring relationships were favored by many over the classic longitudinal experience. Our participants valued role-modeling as an experience separate from mentoring and described the impact of learning from direct observation of skilled leaders. The educational implications of these findings are summarized.
PMCID: PMC2762511  PMID: 19711134
mentorship; role modeling; physician leadership
14.  Developing Physician-Leaders: A Call to Action 
The many challenges in health care today create a special need for great leadership. However, traditional criteria for physicians’ advancement to leadership positions often regard academic and/or clinical accomplishments rather than the distinctive competencies needed to lead. Furthermore, physicians’ training can handicap their developing leadership skills. In this context, an emerging trend is for health-care institutions to offer physician-leadership programs.
Methods and Results
This paper reviews the rationale for developing physician-leaders. Factors that underscore this need include: (1) physicians may lack inclinations to collaborate and to follow, (2) health-care organizations pose challenging environments in which to lead (e.g., because of silo-based structures, etc.), (3) traditional criteria for advancement in medicine regard clinical and/or academic skills rather than leadership competencies, and (4) little attention is currently given to training physicians regarding leadership competencies.
Definition of these competencies of ideal physician-leaders will inform the curricula and format of emerging physician leadership development programs.
PMCID: PMC2695517  PMID: 19455370
leadership; physician-leader; competencies; organizational development
15.  Comorbidities, Patient Knowledge, and Disease Management in a National Sample of Patients with Chronic Obstructive Pulmonary Disease 
The American journal of medicine  2009;122(4):348-355.
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States but is often under-treated. COPD often overlaps with other conditions such as hypertension and osteoporosis, which are less morbid but which may be treated more aggressively. We evaluated the prevalence of these comorbid conditions and compared testing, patient knowledge, and management in a national sample of patients with COPD.
Methods and Methods
A survey was administered by telephone in 2006 to 1,003 COPD patients to evaluate the prevalence of comorbid conditions, diagnostic testing, knowledge, and management using standardized instruments. The completion rate was 87%.
Among 1,003 patients with COPD, 61% reported moderate or severe dyspnea and 41% a prior hospitalization for COPD. The most prevalent comorbid diagnoses were hypertension (55%), hypercholesterolemia (52%), depression (37%), cataracts (31%) and osteoporosis (28%). Only 10% of respondents knew their FEV1 (95% CI: 8, 12%) compared to 79% who knew their blood pressure (95% CI: 76%, 83%). Seventy-two percent (95% CI: 69%, 75%) reported taking any medication for COPD – usually a short-acting bronchodilator – whereas 87% (95% CI: 84%, 90%) of patients with COPD and hypertension were taking an antihypertensive medication and 72% (95% CI: 68%, 75%) of patients with COPD and hypercholesterolemia were taking a statin.
Although most of these COPD patients in this national sample were symptomatic and many had been hospitalized for COPD, COPD self-knowledge was low and COPD was undertreated compared to generally asymptomatic, less morbid conditions such as hypertension.
PMCID: PMC2692705  PMID: 19332230
chronic obstructive pulmonary disease; emphysema; chronic bronchitis; asthma; comorbidities
16.  Exploring Leadership Competencies in Established and Aspiring Physician Leaders: An Interview-based Study 
Background and Objectives
Academic health care institutions have become interested in understanding and supporting current leaders and preparing leaders for the future. We designed this exploratory study to better understand specific perceived leadership needs of physicians from the perspective of “aspiring” and “established” leaders within our institution.
A qualitative, inductive, structured interview-based design was used to examine the study questions.
A purposeful sample of current and aspiring leaders was obtained, sampling across specialties and levels of leadership.
All participants were interviewed by the same investigator (CT). Five open-ended questions were developed as prompts. Two of the investigators independently analyzed the transcripts, using an open coding method to identify themes within the narratives. Inter-observer comparisons were made and discrepancies were resolved through discussion.
Four themes emerged from analyzing the responses to our questions. Aspiring and established leaders agreed that “knowledge”, “people skills” or emotional intelligence, and “vision” were all characteristics of effective leaders and critical to the success of aspiring leaders. Established leaders in our sample added a characteristic of “organizational orientation” that extended the description of “leaders” to include an understanding of the institution as well as dedication to its success (a trait we have called “organizational altruism”).
Our findings validate others’ regarding leadership competencies while extending these findings to the specific context of health care and physicians. Important implications for curricular design include: inclusion of emotional intelligence competencies and reducing formal didactics in favor of programs that are both interactive and problem-based.
PMCID: PMC2517871  PMID: 18327531
leadership competency; great leaders; organizational success; leadership development
17.  IL10 Polymorphisms Are Associated with Airflow Obstruction in Severe α1-Antitrypsin Deficiency 
Severe α1-antitrypsin (AAT) deficiency is a proven genetic risk factor for chronic obstructive pulmonary disease (COPD), especially in individuals who smoke. There is marked variability in the development of lung disease in individuals homozygous (PI ZZ) for this autosomal recessive condition, suggesting that modifier genes could be important. We hypothesized that genetic determinants of obstructive lung disease may be modifiers of airflow obstruction in individuals with severe AAT deficiency. To identify modifier genes, we performed family-based association analyses for 10 genes previously associated with asthma and/or COPD, including IL10, TNF, GSTP1, NOS1, NOS3, SERPINA3, SERPINE2, SFTPB, TGFB1, and EPHX1. All analyses were performed in a cohort of 378 PI ZZ individuals from 167 families. Quantitative spirometric phenotypes included forced expiratory volume in one second (FEV1) and the ratio of FEV1/forced vital capacity (FVC). A qualitative phenotype of moderate-to-severe COPD was defined for individuals with FEV1 ⩽ 50 percent predicted. Six of 11 single-nucleotide polymorphisms (SNPs) in IL10 (P = 0.0005–0.05) and 3 of 5 SNPs in TNF (P = 0.01–0.05) were associated with FEV1 and/or FEV1/FVC. IL10 SNPs also demonstrated association with the qualitative COPD phenotype. When phenotypes of individuals with a physician's diagnosis of asthma were excluded, IL10 SNPs remained significantly associated, suggesting that the association with airflow obstruction was independent of an association with asthma. Haplotype analysis of IL10 SNPs suggested the strongest association with IL10 promoter SNPs. IL10 is likely an important modifier gene for the development of COPD in individuals with severe AAT deficiency.
PMCID: PMC2176135  PMID: 17690329
chronic obstructive pulmonary disease; genetic modifiers; interleukin 10; family-based association analysis
18.  Risk factors for symptom onset in PI*Z alpha-1 antitrypsin deficiency 
In an early study of highly symptomatic patients with PI*Z alpha-1 antitrypsin deficiency (AAT), tobacco smoking was identified as a risk factor by comparing the age of symptom onset in smokers and nonsmokers. Age of symptom onset has not been well studied in relationship to other environmental exposures.
Environmental exposures were assessed in 313 PI*Z adults through retrospective self-administered questionnaire. Age of onset of symptoms with and without these exposures were analyzed through survival analysis.
Personal smoking was the most important risk factor, associated with earlier onset of cough and wheeze, and showed a dose-dependent relationship with the onset of dyspnea. Childhood environmental tobacco smoke (ETS) exposure was independently associated with younger age of onset of cough. Earlier onset of wheeze was also associated with childhood respiratory infections and family history of emphysema. The report of childhood respiratory infections was associated with childhood ETS exposure, but no statistically significant interactions were noted.
We conclude that both personal and secondhand exposure to tobacco smoke in childhood are likely to accelerate the onset of symptoms in AAT deficient patients. Respiratory infections in childhood may also contribute to this risk.
PMCID: PMC2707814  PMID: 18044105
alpha-1 antitrypsin deficiency; tobacco smoke pollution; respiratory symptoms; lower respiratory illness
19.  Detection of Lung Cancer by Sensor Array Analyses of Exhaled Breath 
Rationale: Electronic noses are successfully used in commercial applications, including detection and analysis of volatile organic compounds in the food industry. Objectives: We hypothesized that the electronic nose could identify and discriminate between lung diseases, especially bronchogenic carcinoma. Methods: In a discovery and training phase, exhaled breath of 14 individuals with bronchogenic carcinoma and 45 healthy control subjects or control subjects without cancer was analyzed. Principal components and canonic discriminant analysis of the sensor data was used to determine whether exhaled gases could discriminate between cancer and noncancer. Discrimination between classes was performed using Mahalanobis distance. Support vector machine analysis was used to create and apply a cancer prediction model prospectively in a separate group of 76 individuals, 14 with and 62 without cancer. Main Results: Principal components and canonic discriminant analysis demonstrated discrimination between samples from patients with lung cancer and those from other groups. In the validation study, the electronic nose had 71.4% sensitivity and 91.9% specificity for detecting lung cancer; positive and negative predictive values were 66.6 and 93.4%, respectively. In this population with a lung cancer prevalence of 18%, positive and negative predictive values were 66.6 and 94.5%, respectively. Conclusion: The exhaled breath of patients with lung cancer has distinct characteristics that can be identified with an electronic nose. The results provide feasibility to the concept of using the electronic nose for managing and detecting lung cancer.
PMCID: PMC2718462  PMID: 15750044
breath tests; bronchogenic cancer; electronic nose; volatile organic compounds
20.  Teambuilding and Leadership Training in an Internal Medicine Residency Training Program 
The purpose of this report is to describe and evaluate the impact of a 1-day retreat focused on developing leadership skills and teambuilding among postgraduate year 1 residents in an internal medicine residency.
A group of organizers, including members of the staff, the chief medical residents, administrative individuals in the residency office, and an internal organizational development consultant convened to organize an off-site retreat with activities that would provide experiential learning regarding teamwork and leadership, including a “reef survival exercise” and table discussions regarding the characteristics of ideal leaders. In addition, several energizing activities and recreational free time was provided to enhance the interaction and teamwork dimensions of the retreat. To evaluate the impact of the retreat, attendees completed baseline and follow-up questionnaires regarding their experience of the retreat.
Attendees universally regarded the retreat as having value for them. Comparison of baseline to postretreat responses indicated that attendees felt that the retreat enhanced their abilities to be better physicians, resident supervisors, and leaders. Follow-up responses indicated significant increases in attendees’ agreement that good leaders challenge the process, make decisions based on shared visions, allow others to act, recognize individual contributions, and serve as good role models. Results on the survival exercise indicated a high frequency with which team-based decisions surpassed individual members’ decisions, highlighting the importance and value of teamwork to attendees.
Our main findings were that: participants universally found this 1-day retreat beneficial in helping to develop teamwork and leadership skills and the experiential learning aspects of the retreat were more especially highly rated and highlighted the advantages of teamwork.
In the context that this 1-day retreat was deemed useful by faculty and residents alike, further study is needed to assess the impact of this learning on actual clinical practice and the durability of these lessons.
PMCID: PMC1492383  PMID: 15209609
leadership; residency training; teambuilding
21.  Successful Lecturing 
In a study conducted over 3 large symposia on intensive review of internal medicine, we previously assessed the features that were most important to course participants in evaluating the quality of a lecture. In this study, we attempt to validate these observations by assessing prospectively the extent to which ratings of specific lecture features would predict the overall evaluation of lectures.
After each lecture, 143 to 355 course participants rated the overall lecture quality of 69 speakers involved in a large symposium on intensive review of internal medicine. In addition, 7 selected participants and the course directors rated specific lecture features and overall quality for each speaker. The relations among the variables were assessed through Pearson correlation coefficients and cluster analysis. Regression analysis was performed to determine which features would predict the overall lecture quality ratings. The features that most highly correlated with ratings of overall lecture quality were the speaker's abilities to identify key points (r = .797) and be engaging (r = .782), the lecture clarity (r = .754), and the slide comprehensibility (r = .691) and format (r = .660). The three lecture features of engaging the audience, lecture clarity, and using a case-based format were identified through regression as the strongest predictors of overall lecture quality ratings (R2= 0.67, P = 0.0001).
We have identified core lecture features that positively affect the success of the lecture. We believe our findings are useful for lecturers wanting to improve their effectiveness and for educators who design continuing medical education curricula.
PMCID: PMC1495460  PMID: 10886470
lecturing; continuing medical education; research; reproducibility of results; medical faculty; evaluation studies

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