A nondegenerate code of deleterious variants in Mendelian loci contributes to complex disease risk.

Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this "Mendelian code." Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases.

The Relative Ability of Comorbidity Ascertainment Methodologies to Predict In-Hospital Mortality Among Hospitalized Community-acquired Pneumonia Patients.

BACKGROUND: Despite widespread use of comorbidities for population health descriptions and risk adjustment, the ideal method for ascertaining comorbidities is not known. We sought to compare the relative value of several methodologies by which comorbidities may be ascertained. METHODS: This is an observational study of 1596 patients admitted to the University of Chicago for community-acquired pneumonia from 1998 to 2012. We collected data via chart abstraction, administrative data, and patient report, then performed logistic regression analyses, specifying comorbidities as independent variables and in-hospital mortality as the dependent variable. Finally, we compared area under the curve (AUC) statistics to determine the relative ability of each method of comorbidity ascertainment to predict in-hospital mortality. RESULTS: Chart review (AUC, 0.72) and administrative data (Charlson AUC, 0.83; Elixhauser AUC, 0.84) predicted in-hospital mortality with greater fidelity than patient report (AUC, 0.61). However, multivariate logistic regression analyses demonstrated that individual comorbidity derivation via chart review had the strongest relationship with in-hospital mortality. This is consistent with prior literature suggesting that administrative data have inherent, paradoxical biases with important implications for risk adjustment based solely on administrative data. CONCLUSIONS: Although comorbidities derived through administrative data did produce an AUC greater than chart review, our analyses suggest a coding bias in several comorbidities with a paradoxically protective effect. Therefore, chart review, while labor and resource intensive, may be the ideal method for ascertainment of clinically relevant comorbidities.

Associations between environmental quality and adult asthma prevalence in medical claims data.

As of 2014, approximately 7.4% of U.S. adults had current asthma. The etiology of asthma is complex, involving genetics, behavior, and environmental factors. To explore the association between cumulative environmental quality and asthma prevalence in U.S. adults, we linked the U.S. Environmental Protection Agency's Environmental Quality Index (EQI) to the MarketScan® Commercial Claims and Encounters Database. The EQI is a summary measure of five environmental domains (air, water, land, built, sociodemographic). We defined asthma as having at least 2 claims during the study period, 2003-2013. We used a Bayesian approach with non-informative priors, implementing mixed-effects regression modeling with a Poisson link function. Fixed effects variables were EQI, sex, race, and age. Random effects were counties. We modeled quintiles of the EQI comparing higher quintiles (worse quality) to lowest quintile (best quality) to estimate prevalence ratios (PR) and credible intervals (CIs). We estimated associations using the cumulative EQI and domain-specific EQIs; we assessed U.S. overall (non-stratified) as well as stratified by rural-urban continuum codes (RUCC) to assess rural/urban heterogeneity. Among the 71,577,118 U.S. adults with medical claims who could be geocoded to county of residence, 1,147,564 (1.6%) met the asthma definition. Worse environmental quality was associated with increased asthma prevalence using the non-RUCC-stratified cumulative EQI, comparing the worst to best EQI quintile (PR:1.27; 95% CI: 1.21, 1.34). Patterns varied among different EQI domains, as well as by rural/urban status. Poor environmental quality may increase asthma prevalence, but domain-specific drivers may operate differently depending on rural/urban status.

Understanding Toxoplasmosis in the United States Through "Large Data" Analyses.

BACKGROUND: Toxoplasma gondii infection causes substantial morbidity and mortality in the United States, and infects approximately one-third of persons globally. Clinical manifestations vary. Seropositivity is associated with neurologic diseases and malignancies. There are few objective data concerning US incidence and distribution of toxoplasmosis. METHODS: Truven Health MarketScan Database and International Classification of Diseases, Ninth Revision (ICD-9) codes, including treatment specific to toxoplasmosis, identified patients with this disease. Spatiotemporal distribution and patterns of disease manifestation were analyzed. Comorbidities between patients and matched controls were compared. RESULTS: Between 2003 and 2012, 9260 patients had ICD-9 codes for toxoplasmosis. This database of patients with ICD-9 codes includes 15% of those in the United States, excluding patients with no or public insurance. Thus, assuming that demographics do not change incidence, the calculated total is 61 700 or 6856 patients per year. Disease was more prevalent in the South. Mean age at diagnosis was 37.5 ± 15.5 years; 2.4% were children aged 0-2 years, likely congenitally infected. Forty-one percent were male, and 73% of women were of reproductive age. Of identified patients, 38% had eye disease and 12% presented with other serious manifestations, including central nervous system and visceral organ damage. Toxoplasmosis was statistically associated with substantial comorbidities, including human immunodeficiency virus, autoimmune diseases, and neurologic diseases. CONCLUSIONS: Toxoplasmosis causes morbidity and mortality in the United States. Our analysis of private insurance records missed certain at-risk populations and revealed fewer cases of retinal disease than previously estimated, suggesting undercoding, underreporting, undertreating, or differing demographics of those with eye disease. Mandatory reporting of infection to health departments and gestational screening could improve care and facilitate detection of epidemics and, thereby, public health interventions.

Environmental and state-level regulatory factors affect the incidence of autism and intellectual disability.

Many factors affect the risks for neurodevelopmental maladies such as autism spectrum disorders (ASD) and intellectual disability (ID). To compare environmental, phenotypic, socioeconomic and state-policy factors in a unified geospatial framework, we analyzed the spatial incidence patterns of ASD and ID using an insurance claims dataset covering nearly one third of the US population. Following epidemiologic evidence, we used the rate of congenital malformations of the reproductive system as a surrogate for environmental exposure of parents to unmeasured developmental risk factors, including toxins. Adjusted for gender, ethnic, socioeconomic, and geopolitical factors, the ASD incidence rates were strongly linked to population-normalized rates of congenital malformations of the reproductive system in males (an increase in ASD incidence by 283% for every percent increase in incidence of malformations, 95% CI: [91%, 576%], p<6×10(-5)). Such congenital malformations were barely significant for ID (94% increase, 95% CI: [1%, 250%], p = 0.0384). Other congenital malformations in males (excluding those affecting the reproductive system) appeared to significantly affect both phenotypes: 31.8% ASD rate increase (CI: [12%, 52%], p<6×10(-5)), and 43% ID rate increase (CI: [23%, 67%], p<6×10(-5)). Furthermore, the state-mandated rigor of diagnosis of ASD by a pediatrician or clinician for consideration in the special education system was predictive of a considerable decrease in ASD and ID incidence rates (98.6%, CI: [28%, 99.99%], p = 0.02475 and 99% CI: [68%, 99.99%], p = 0.00637 respectively). Thus, the observed spatial variability of both ID and ASD rates is associated with environmental and state-level regulatory factors; the magnitude of influence of compound environmental predictors was approximately three times greater than that of state-level incentives. The estimated county-level random effects exhibited marked spatial clustering, strongly indicating existence of as yet unidentified localized factors driving apparent disease incidence. Finally, we found that the rates of ASD and ID at the county level were weakly but significantly correlated (Pearson product-moment correlation 0.0589, p = 0.00101), while for females the correlation was much stronger (0.197, p<2.26×10(-16)).

Sex disparities in diagnosis of bladder cancer after initial presentation with hematuria: a nationwide claims-based investigation.

BACKGROUND: Women have disproportionately higher mortality rates relative to incidence for bladder cancer. Multiple etiologies have been proposed, including delayed diagnosis and treatment. Guidelines recommend ruling out malignancy in men and women presenting with hematuria. This study sought to determine the difference in timing from presentation with hematuria to diagnosis of bladder cancer in women versus men. METHODS: This is a retrospective population-based study examining the timing from presentation with hematuria to diagnosis of bladder cancer, based on data from the MarketScan databases, which include enrollees of more than 100 health insurance plans of approximately 40 large US employers from 2004 through 2010. All study patients presented with hematuria and were subsequently diagnosed with bladder cancer. The primary outcome measure was number of days between initial presentation with hematuria and diagnosis of bladder cancer by sex. RESULTS: A total of 5416 men and 2233 women met inclusion criteria. Mean days from initial hematuria claim to bladder cancer claim was significantly longer in women (85.4 versus 73.6 days, P < .001), and the proportion of women with >6 month delay in bladder cancer diagnosis was significantly higher (17.3% versus 14.1%, P < .001). Women were more likely to be diagnosed with urinary tract infection (odds ratio = 2.32, 95% confidence interval = 2.07-2.59) and less likely to undergo abdominal or pelvic imaging (odds ratio = 0.80, 95% confidence interval = 0.71-0.89). CONCLUSIONS: Both men and women experience significant delays between presentation with hematuria and diagnosis of bladder cancer, with longer delays for women. This may be partly responsible for the sex-based discrepancy in outcomes associated with bladder cancer.

The Impact of Principal Diagnosis on Readmission Risk among Patients Hospitalized for Community-Acquired Pneumonia.

Coding variation distorts performance/outcome statistics not eliminated by risk adjustment. Among 1596 community-acquired pneumonia patients hospitalized from 1998 to 2012 identified using an evidence-based algorithm, the authors measured the association of principal diagnosis (PD) with 30-day readmission, stratified by Pneumonia Severity Index risk class. The 152 readmitted patients were more ill (Pneumonia Severity Index class V 38.8% versus 25.8%) and less likely to have a pneumonia PD (52.6% versus 69.9%). Among patients with PDs of pneumonia, respiratory failure, sepsis, and aspiration, mortality/readmission rates were 3.9/8.5%, 28.8/14.0%, 24.7/19.6%, and 9.0/15.0%, respectively. The nonpneumonia PDs were associated with a greater risk of adjusted 30-day readmission: respiratory failure odds ratio (OR) 1.89 (95% confidence interval [CI], 1.13-3.15), sepsis OR 2.54 (95% CI, 1.52-4.26), and possibly aspiration OR 1.73 (95% CI, 0.88-3.41). With increasing use of alternative PDs among pneumonia patients, quality reporting must account for variations in condition coding practices. Rigorous risk adjustment does not eliminate the need for accurate, consistent case definition in producing valid quality measures.

Discerning asthma endotypes through comorbidity mapping.

Asthma is a heterogeneous, complex syndrome, and identifying asthma endotypes has been challenging. We hypothesize that distinct endotypes of asthma arise in disparate genetic variation and life-time environmental exposure backgrounds, and that disease comorbidity patterns serve as a surrogate for such genetic and exposure variations. Here, we computationally discover 22 distinct comorbid disease patterns among individuals with asthma (asthma comorbidity subgroups) using diagnosis records for >151 M US residents, and re-identify 11 of the 22 subgroups in the much smaller UK Biobank. GWASs to discern asthma risk loci for individuals within each subgroup and in all subgroups combined reveal 109 independent risk loci, of which 52 are replicated in multi-ancestry meta-analysis across different ethnicity subsamples in UK Biobank, US BioVU, and BioBank Japan. Fourteen loci confer asthma risk in multiple subgroups and in all subgroups combined. Importantly, another six loci confer asthma risk in only one subgroup. The strength of association between asthma and each of 44 health-related phenotypes also varies dramatically across subgroups. This work reveals subpopulations of asthma patients distinguished by comorbidity patterns, asthma risk loci, gene expression, and health-related phenotypes, and so reveals different asthma endotypes.

Association of elevated plasminogen activator inhibitor 1 levels with diminished lung function in patients with asthma.

BACKGROUND: We previously reported that plasminogen activator inhibitor 1 (PAI-1) was upregulated in human asthmatic airways and promotes airway fibrosis in an allergen-challenged murine model of asthma. OBJECTIVES: To examine whether elevated plasma levels of PAI-1 are associated with poor lung function in asthmatic patients. METHODS: Five hundred nineteen adults were eligible for the study, and ultimately 353 adults were enrolled and completed the baseline protocol between January 24, 2004, and July 30, 2005. Of these, 231 adults with asthma from the Chicago Initiative to Raise Asthma Health Equity study were randomly selected and the plasma levels of PAI-1 were measured by enzyme-linked immunosorbent assay. Asthma burden, medication, smoking status, and body mass index (BMI) were obtained by history and spirometry was performed. A multivariate regression analysis was performed to evaluate the association of PAI-1 levels and lung function and the potential determinant variables that were associated with PAI-1. RESULTS: We found associations between PAI-1 and BMI (ß = 0.606, P = .002), smoking (ß = 7.526, P = .001), and African American race (ß = -9.061, P = .01). Obese patients showed a significant increase in PAI-1, and current smokers demonstrated higher levels of PAI-1 compared with nonsmokers. When we evaluated the associations between lung function parameters and PAI-1, we found that PAI-1 was negatively associated with forced vital capacity (FVC) (ß = -0.098, P = .011) but not with forced expiratory volume in 1 second (FEV(1)) or the FEV(1)/FVC ratio. There was a negative association between BMI and FVC, and PAI-1 may mediate some of this association. CONCLUSIONS: This study suggests a significant association between PAI-1 and lung function in patients with asthma. The effect of obesity on FVC may in part be mediated by PAI-1.

Obesity and asthma morbidity in a community-based adult cohort in a large urban area: the Chicago Initiative to Raise Asthma Health Equity (CHIRAH).

BACKGROUND: Urban minority populations experience increased rates of obesity and increased asthma prevalence and severity. Objective. The authors sought to determine whether obesity, as measured by body mass index (BMI), was associated with asthma quality of life or asthma-related emergency department (ED)/urgent care utilization in an urban, community-based sample of adults. METHODS: This is a cross-sectional analysis of 352 adult subjects (age 30.9 +/- 6.1, 77.8% females, forced expiratory volume in one second (FEV(1))% predicted = 87.0% +/- 18.5%) with physician-diagnosed asthma from a community-based Chicago cohort. Outcome variables included the Juniper Asthma Quality of Life Questionnaire (AQLQ) scores and health care utilization in the previous 12 months. Bivariate tests were used as appropriate to assess the relationship between BMI or obesity status and asthma outcome variables. Multivariate regression analyses were performed to predict asthma outcomes, controlling for demographics, income, depression score, and beta-agonist use. RESULTS: One hundred ninety-one (54.3%) adults were obese (BMI > 30 kg/m(2)). Participants with a higher BMI were older (p = .008), African American (p < .001), female (p = .002), or from lower income households (p = .002). BMI was inversely related to overall AQLQ scores (r = -.174, p = .001) as well as to individual domains. In multivariate models, BMI remained an independent predictor of AQLQ. Obese participants were more likely to have received ED/urgent care for asthma than nonobese subjects (odds ratio [OR] = 1.8, p = .036). CONCLUSIONS: In a community-based sample of urban asthmatic adults, obesity was related to worse asthma-specific quality of life and increased ED/urgent care utilization. However, compared to other variables measured such as depression, the contribution of obesity to lower AQLQ scores was relatively modest.

Improving asthma self-efficacy: developing and testing a pilot community-based asthma intervention for African American adults.

BACKGROUND: Low-income African American adults in Chicago have disproportionately high asthma morbidity and mortality rates. Interventions that improve asthma self-efficacy for appropriate self-management behaviors might ultimately improve asthma control in this population. OBJECTIVE: We sought to pilot test an intervention to improve asthma self-efficacy for appropriate self-management behaviors. METHODS: Participants for this trial were recruited through 2 primary care clinics located in the largest African American community in Chicago. Participants were then randomized into one of 2 groups. The control group received mailed asthma education materials. The intervention group was offered 4 group sessions led by a community social worker and 6 home visits by community health workers. Telephone interviews were conducted at baseline (before intervention), 3 months (after intervention), and 6 months (maintenance). RESULTS: The 42 participants were predominantly African American and low income and had poorly controlled persistent asthma. The intervention group had significantly higher asthma self-efficacy at 3 months (P < .001) after the completion of the intervention. Asthma action plans were more common in the intervention group at 3 months (P = .06). At 6 months, the intervention group had improved asthma quality of life (P = .002) and improved coping (P = .01) compared with control subjects. Trends in behavioral and clinical outcomes favored the intervention group but were not statistically significant. CONCLUSIONS: This community-based asthma intervention improved asthma self-efficacy, self-perceived coping skills, and asthma quality of life for low-income African American adults. Larger trials are needed to test the efficacy of this intervention to reduce asthma morbidity in similar high-risk populations.

CXCR4 expression heterogeneity in neuroblastoma cells due to ligand-independent regulation.

BACKGROUND: CXCR4, the receptor for the chemokine stromal-derived factor 1 (SDF-1), has been shown to mediate many of the processes essential for cancer progression such as tumor cell proliferation, metastasis, and angiogenesis. To understand the role of CXCR4 in the biology of neuroblastoma, a disease that presents with wide spread metastases in over 50% of patients, we screened ten patient derived-neuroblastoma cell-lines for basal CXCR4 expression and sought to identify characteristics that correlate with tumor cell phenotype. RESULTS: All cell lines expressed CXCR4 mRNA at variable levels, that correlated well with three distinct classes of CXCR4 surface expression (low, moderate, or high) as defined by flow cytometry. Analysis of the kinetics of CXCR4 surface expression on moderate and high expressing cell lines showed a time-dependent down-regulation of the receptor that directly correlated with cell confluency, and was independent of SDF1. Cell lysates showed the presence of multiple CXCR4 isoforms with three major species of approximately 87, 67 and 55 kDa associating with high surface expression, and two distinct species of 45 and 38 kDa correlating with low to null surface expression. Western blot analysis of CXCR4 immunoprecipitates showed that the 87 and 67 kDa forms were ubiquitinated, while the others were not. Finally, treatment of cells with a proteasome inhibitor resulted in down regulation of CXCR4 surface expression. CONCLUSIONS: Taken together, these data show that regulation of CXCR4 surface expression in neuroblastoma cells can occur independently of SDF-1 contribution arguing against an autocrine mechanism. Additionally these data suggest that post-translational modifications of CXCR4, in part through direct ubiquitination, can influence trafficking of CXCR4 to the surface of neuroblastoma cells in a ligand-independent manner.

Ethnic disparities in asthma morbidity in Chicago.

RATIONALE: The role of ethnicity and socioeconomic status in explaining variations in asthma morbidity is unclear. OBJECTIVES: To describe the magnitude of ethnic disparities in asthma morbidity in Chicago and to determine whether differences in socioeconomic status explain these disparities. METHODS: We conducted a survey of 561 school-age children and 353 young adults with asthma and measured their self-reported ethnicity, socioeconomic status (using 11 variables), and asthma morbidity (symptom frequency, asthma-specific quality of life, and frequency of severe asthma exacerbations). MEASUREMENTS AND MAIN RESULTS: White children and adults had better asthma-specific quality of life and fewer severe asthma exacerbations compared to black and Hispanic children and adults. White children also had fewer days with asthma symptoms, but among adults there were no ethnic differences in the frequency of asthma symptoms. Socioeconomic status explained a large portion of the ethnic disparities in asthma quality of life but explained little of the disparities in other aspects of asthma morbidity. CONCLUSIONS: There are large disparities across ethnic groups in Chicago in asthma quality of life and in the frequency of severe exacerbations. Differences in socioeconomic status do not fully explain these disparities.

Characterizing pediatric inpatient sleep duration and disruptions.

OBJECTIVE: To contextualize inpatient sleep duration and disruptions in a general pediatric hospital ward by comparing in-hospital and at-home sleep durations to recommended guidelines and to objectively measure nighttime room entries. METHODS: Caregivers of patients four weeks - 18 years of age reported patient sleep duration and disruptions in anonymous surveys. Average at-home and in-hospital sleep durations were compared to National Sleep Foundation recommendations. Objective nighttime traffic was evaluated as the average number of room entries between 11:00pm and 7:00am using GOJO brand hand-hygiene room entry data. RESULTS: Among 246 patients, patients slept less in the hospital than at home with newborn and infant cohorts experiencing 7- and 4-h sleep deficits respectively (Newborn: 787 ± 318 min at home vs. 354 ± 211 min in hospital, p < 0.001; Infants: 703 ± 203 min at home vs. 412 ± 152 min in hospital, p < 0.01). Newborn children also experienced >2 h sleep deficits at home when compared to NSF recommendations (Newborns: 787 ± 318 min at home vs. 930 min recommended, p < 0.05). Objective nighttime traffic measures revealed that hospitalized children experienced 7.3 room entries/night (7.3 ± 0.25 entries). Nighttime traffic was significantly correlated with caregiver-reported nighttime awakenings (Spearman Rank Correlation Coefficient: 0.83, p < 0.001). CONCLUSION: Hospitalization is a missed opportunity to improve sleep both in the hospital and at home.

Characterizing community-based asthma knowledge in Chicago and its high risk neighborhoods.

The goal of this study was to characterize asthma knowledge in high risk neighborhoods compared to a random sample of residents in the Chicago area. The Chicago Community Asthma Survey-32 (CCAS-32) was administered to 1006 Chicago-area residents and 388 residents in 4 high-risk Chicago inner-city neighborhoods. There was a significant difference in asthma knowledge between groups. The general Chicago-area respondents have an average desirable response rate of 71.6% versus 64.7% for respondents in high-risk communities (p < 0.0001). For some aspects of asthma knowledge, e.g., nocturnal cough, cockroach allergen, and vaporizer use, general knowledge was similarly low. For other aspects, such as the need for asymptomatic asthma visits and chest tightness, there were larger gaps between residents of high risk communities and the general community. High-risk neighborhoods in Chicago had lower asthma knowledge compared to the general Chicago community. This discrepancy may be contributing to the disparities seen in asthma morbidity. Public health efforts to increase asthma knowledge in these high risk minority communities may help reduce these disparities. Important misconceptions exist about asthma triggers, signs and symptoms, especially among lower income African American communities, that should be addressed by physicians.

Cost-effectiveness of coronary artery bypass grafts versus percutaneous coronary intervention for revascularization of high-risk patients.

BACKGROUND: A Department of Veterans Affairs Cooperative Study randomized high-risk patients with medically refractory myocardial ischemia, a group largely excluded from previous trials, to urgent revascularization with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The present study examined the cost-effectiveness of PCI versus CABG for these high-risk patients. METHODS AND RESULTS: Of 454 patients at 16 Department of Veterans Affairs medical centers, 445 were available for the economic analysis (218 PCI and 227 CABG patients). Total costs were assessed at 3 and 5 years from the third-party payer's perspective, and effectiveness was measured by survival. After 3 years, average total costs were 63,896 dollars for PCI versus 84,364 dollars for CABG patients, a difference of 20,468 dollars (95% confidence interval [CI] 13,918 dollars to 27,569 dollars). CIs were estimated by bootstrapping. Survival at 3 years was 0.82 for PCI versus 0.79 for CABG patients (P=0.34). Precision of the cost-effectiveness estimates were assessed by bootstrapping. PCI was less costly and more effective at 3 years in 92.6% of the bootstrap replications. After 5 years, average total costs were 81,790 dollars for PCI versus 100,522 dollars for CABG patients, a difference of 18,732 dollars (95% CI 9873 dollars to 27,831 dollars), whereas survival at 5 years was 0.75 for PCI patients versus 0.70 for CABG patients (P=0.21). At 5 years, PCI remained less costly and more effective in 89.4% of the bootstrap replications. CONCLUSIONS: PCI was less costly and at least as effective for the urgent revascularization of medically refractory, high-risk patients over 5 years.

Changing impact of gastroesophageal reflux in medical and otolaryngology practice.

OBJECTIVES/HYPOTHESIS: A major trend in gastroesophageal reflux disease (GERD) is an observed increased prevalence of the problem, with an associated burden on health care resources. There are relatively few objective reports of increasing prevalence of this disease, and there are no epidemiologic reports that discuss changing practice strategies in managing the disease. The clinical problem is of critical importance to practicing otolaryngologists, who manage the impact of GERD on diseases affecting the ear, nose, and throat. The hypothesis of this thesis is that 1) GERD is an increasing problem affecting outpatient office visits over time, and 2) the disease is increasingly managed with prescription pharmacotherapy. STUDY DESIGN: Retrospective national medical database review using the National Ambulatory Medical Care Survey. METHODS: Twelve years of data (1990-2001) were examined with visits weighted to provide U.S. estimates of care. Average annual frequencies and visit rates were calculated for total visits and by age, sex, race, and physician specialty. Selected issues in GERD treatment were also examined, including prescriptions and physician/patient counseling regarding stress management, tobacco abuse, and diet modification. Trends were reported based on changes in care across three time periods to satisfy statistical significance: 1990 to 1993, 1994 to 1997, and 1998 to 2001. RESULTS: Between 1990 and 1993 and 1998 and 2001, there was a significant increase in U.S. ambulatory care visits for GERD, from a rate of 1.7 per 100 to 4.7 per 100. There were no significant changes in race, although there was a small trend toward increased GERD visits in the age group over 44 years old and in the male sex. Office visits to otolaryngologists increased from 89,000 to 421,000 between the time periods of 1990 to 1993 and 1998 to 2001. This also represented a percent increase in office encounters by otolaryngologists compared with visits by all specialties from 2.9% to 4.4%. Over the three time periods, there was a fall in prescriptions for histamine (H2) blockers from 58.1% to 20.7% of total prescriptions. Over the same three time periods, prescriptions of proton pump inhibitors increased from 13.2% to 64.6%. Physician recommendations for over the counter medications fell from 18.8% to 6.6%. Average annual counseling during ambulatory care visits for GERD was assessed for the period from 1998 to 2001 as follows: diet counseling was provided at 27.2% of encounters, tobacco cessation counseling was provided at 3.9%, and stress management was discussed at 3.9%. CONCLUSIONS: During the 1990s, there was a substantial increase in the use of ambulatory care services for GERD. Although much of this increase was among the primary care community, otolaryngologists appeared to have an increasingly prominent role in the management of this disease. There have also been dramatic changes in physician prescribing patterns for GERD, with the emergence of the predominant role of proton pump inhibitors. However, the use of physician counseling for lifestyle modification of factors known to affect GERD remains very low. The increasing impact of GERD on physician practice emphasizes the importance of both physician and patient education in the delivery of health care related to this disease.

The role of statins for primary prevention in non-elderly colorectal cancer patients.

BACKGROUND: There is conflicting evidence for the role of statins in the primary prevention of colorectal cancer (CRC). We conducted a case control study (N=357,702) in the non-elderly adult US population (age=18-64 years) with the primary objective to examine the association between CRC and statin use. PATIENTS AND METHODS: MarketScan® databases were used to identify patients with CRC. A case was defined as having an incident diagnosis of CRC. Up to ten individually matched controls (age, sex, region and date of diagnosis) were selected per case. Statin exposure was assessed by prescription tracking in the 12 months prior to the index date. Conditional logistic regression was used to adjust for multiple potential confounders and calculate adjusted odds ratios (AOR). RESULTS: The mean age of participants was 54 years; 52% males and 48% females. In a multivariable model, any statin use was associated with 26% reduced odds of CRC (AOR, 0.74, 95% confidence interval (CI), 0.72-0.77, p<0.001). Age-stratified analyses showed a stronger effect of statins on CRC in participants aged 55 years or younger (AOR, 0.67, 95% CI, 0.63-0.71, p<0.001) than in participants aged above 55 years (AOR, 0.79, 95% CI, 0.76-0.82, p<0.001); the age-by-statin interaction was statistically significant (p<0.001). The dose-response analyses performed with simvastatin only showed a trend towards significance between the duration of simvastatin exposure and odds of developing CRC (p=0.06). CONCLUSIONS: Statins appears to reduce the risk of CRC in non-elderly US population. Chemoprevention with statin might be more effective in non-elderly US population.

Defining an episode of care for colonoscopy: work of the High Value Health Care Project characterizing episodes and costs of care.

Working with a group of key stakeholders, the authors developed an episode-based resource use measure focused on the use of colonoscopy. This measure is intended to identify differences in health care resource use in a short time frame surrounding the colonoscopy. The ultimate intent in the development of this measure was to pair it with a measure of quality so that both the cost and quality of care can be evaluated together. In initial testing, the authors found the use of general anesthesia with colonoscopy to be associated with higher episode costs. Eventually, when paired with quality measures, it is hoped this measure will provide actionable information for health care payers and providers to more efficiently provide colonoscopy services without compromising quality.

Asthma morbidity and treatment in the Chicago metropolitan area: one decade after national guidelines.

BACKGROUND: A number of studies have demonstrated disproportionate hospitalization and mortality rates in US urban areas. Yet, no published population-based studies have examined the burden of asthma on the residents of a particular urban area known to be at high risk for poor asthma outcomes. OBJECTIVES: To examine asthma morbidity and medical care in a population-based sample of adults and children with asthma residing in the greater Chicago, IL, metropolitan area and to explore social and demographic influences on morbidity and treatment. METHODS: A telephone survey of adults living in the Chicago metropolitan area was conducted from November 1999 through December 2000. RESULTS: The final sample included 152 adults and children with active asthma. Emergency department visits and hospitalizations for asthma in the previous year were reported by 25.7% and 6.6% of respondents, respectively. Of current medication users, 32.2% reported current regular use of controller medications. After adjusting for age, sex, income, education, and reported current pharmacotherapy, compared with white individuals, African American individuals remained 6.3 times more likely to have experienced an emergency department visit and 12.3 times more likely to have been hospitalized. CONCLUSIONS: These findings suggest that poorly controlled asthma remains a prevalent problem for persons with asthma in this metropolitan area and that a large gap remains between the goals of asthma therapy and appropriate treatment as defined by the National Asthma Education and Prevention Program. The reasons for disparate treatment and health outcomes by race/ethnicity and income need further study and intervention.