Publications

BACKGROUND & AIMS

The relationship between inflammatory bowel disease (IBD) and the incidence and mortality of colorectal adenocarcinoma (CRC) has not been evaluated recently.

METHODS

We calculated the incidence and standardized incidence and mortality rate ratios of CRC among adult individuals with intact colons using Kaiser Permanente of Northern California's database of members with IBD and general membership data for the period of 1998 to June 2010 (data through 2008 were used to calculate mortality). We also evaluated trends in medication use and rates of cancer detection over time.

RESULTS

We identified 29 cancers among persons with Crohn's disease (CD) and 53 among persons with ulcerative colitis (UC). Overall, the incidence rates of cancer among individuals with CD, UC, or in the general membership were 75.0, 76.0, and 47.1, respectively, per 100,000 person-years. In the general population, the incidence of CRC was 21% higher in 2007-2010 than in 1998-2001 (P for trend, <.0001), coincident with the growth of CRC screening programs. The incidence of CRC among individuals with CD or UC was 60% higher than in the general population (95% confidence interval [CI] for CD, 20%-200%; 95% CI for UC, 30%-200%) and was stable over time (P for trend was as follows: CD, .98; UC, .40). During 1998-2008, the standardized mortality ratio for CRC in individuals with CD was 2.3 (95% CI, 1.6-3.0) and 2.0 in those with UC (95% CI, 1.3-2.7). Over the study period, anti-tumor necrosis factor agents replaced other therapies for CD and UC; the rate of colonoscopy increased by 33% among patients with CD and decreased by 9% in those with UC.

CONCLUSIONS

From 1998 to 2010, the incidence of CRC in patients with IBD was 60% higher than in the general population and essentially stable over time.

BACKGROUND

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with an overall poor prognosis. A simple-to-use staging system for IPF may improve prognostication, help guide management, and facilitate research.

OBJECTIVE

To develop a multidimensional prognostic staging system for IPF by using commonly measured clinical and physiologic variables.

DESIGN

A clinical prediction model was developed and validated by using retrospective data from 3 large, geographically distinct cohorts.

SETTING

Interstitial lung disease referral centers in California, Minnesota, and Italy.

PATIENTS

228 patients with IPF at the University of California, San Francisco (derivation cohort), and 330 patients at the Mayo Clinic and Morgagni-Pierantoni Hospital (validation cohort).

MEASUREMENTS

The primary outcome was mortality, treating transplantation as a competing risk. Model discrimination was assessed by the c-index, and calibration was assessed by comparing predicted and observed cumulative mortality at 1, 2, and 3 years.

RESULTS

Four variables were included in the final model: gender (G), age (A), and 2 lung physiology variables (P) (FVC and Dlco). A model using continuous predictors (GAP calculator) and a simple point-scoring system (GAP index) performed similarly in derivation (c-index of 70.8 and 69.3, respectively) and validation (c-index of 69.1 and 68.7, respectively). Three stages (stages I, II, and III) were identified based on the GAP index with 1-year mortality of 6%, 16%, and 39%, respectively. The GAP models performed similarly in pooled follow-up visits (c-index ≥71.9).

LIMITATION

Patients were drawn from academic centers and analyzed retrospectively.

CONCLUSION

The GAP models use commonly measured clinical and physiologic variables to predict mortality in patients with IPF.

Asthma pathogenesis is focused around conducting airways. The reasons for this focus have been unclear because it has not been possible to track the sites and timing of antigen uptake or subsequent antigen presentation to effector T cells. In this study, we use two-photon microscopy of the lung parenchyma and note accumulation of CD11b(+) dendritic cells (DCs) around the airway after allergen challenge but very limited access of these airway-adjacent DCs to the contents of the airspace. In contrast, we observed prevalent transepithelial uptake of particulate antigens by alveolar DCs. These distinct sites are temporally linked, as early antigen uptake in alveoli gives rise to DC and antigen retention in the airway-adjacent region. Antigen-specific T cells also accumulate in the airway-adjacent region after allergen challenge and are activated by the accumulated DCs. Thus, we propose that later airway hyperreactivity results from selective retention of allergen-presenting DCs and antigen-specific T cells in airway-adjacent interaction zones, not from variation in the abilities of individual DCs to survey the lung.

BACKGROUND

Clinical practice guidelines have been criticized for insufficient attention to the unique needs of patients of advanced age and with multiple comorbid conditions. However, little empiric research is available to inform this topic.

METHODS

We conducted telephone interviews with staff physicians and nurse practitioners in 4 VA health care systems. Respondents were asked to rate the usefulness of national heart failure guidelines for patients of different ages and levels of comorbid burden on a 5-point scale and to comment on the reasons for their ratings.

RESULTS

Of 139 clinicians contacted, 65 (47%) completed the interview. Almost half (49%) were women, and 48 (74%) were general internists or family practitioners. On a 5-point scale assessing the usefulness of clinical practice guidelines for heart failure, the mean (SD) response ranged from 4.4 (0.7) for patients younger than 65 years with few comorbid conditions to 3.5 (1.2) for patients older than 80 years with multiple comorbid conditions (P<0.001). The difference in perceived usefulness varied more by patient age than by degree of comorbidity (P = 0.02). Four major concepts underlay the perceived usefulness of guidelines across different patient types: (1) harm of treatment and complexity of the patient's clinical condition and pharmacologic needs, (2) expected benefits of treatment, (3) patient preferences and abilities, and (4) confidence in the validity of guideline recommendations.

CONCLUSION

Clinicians perceive heart failure guidelines to be substantially less useful in patients of older age and with greater comorbid burden. Concerns about the clinical and pharmacologic complexity of these patients and the expected benefits of drug therapy were commonly invoked as reasons for this skepticism.