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.

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.

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.

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.

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.

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.

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.