Publications

BACKGROUND

Information on infliximab use in a community setting is important to understand patterns of medication use and to anticipate and plan for costs associated with the drug. We sought to understand predictors of initiation and discontinuation of infliximab in the community-based setting of Kaiser Permanente, Northern California, which provides integrated care to its members.

METHODS

The cohort study was set during 1998-2006. Predictors of initiation were assessed among 494 Crohn's disease (CD) patients who initiated infliximab and 2470 CD patients who did not initiate infliximab (controls). Data were obtained through linkage of computerized clinical information and were analyzed using logistic regression and Cox survival analysis.

RESULTS

Infliximab infusions have increased rapidly since 2001, with no evidence of leveling off. Initiators were appreciably younger than controls (P < 0.001), but were similar to controls with respect to sex and race/ethnicity. The presence of at least 1 comorbidity was related to a modest increase in the risk of initiating (compared with none: 1 comorbidity, odds ratio [OR] = 1.52 with 95% confidence interval [CI] 1.16-2.00; 2 comorbidities, OR = 1.38 with CI 0.89-2.13). By 3 years after initiating, only 20% of patients remained on infliximab.

CONCLUSIONS

In a community-based setting infliximab use has steadily increased. Age and comorbidity are associated with initiation, but sex and race/ethnicity are not. More information is needed to determine why, in this community-based setting, a large number of patients on infliximab discontinued their treatment.(Inflamm Bowel Dis 2008).

BACKGROUND & AIMS

We sought to evaluate long-term outcomes of patients with severe ulcerative colitis (UC) after their first hospitalization for the disease.

METHODS

A cohort of 656 patients hospitalized for UC during 1996 to 2004 was followed up for 9 years through 2004. Time-to-event was estimated using actuarial methods, and the proportions of those under follow-up evaluation who experienced outcomes at month 3, year 1, and year 5 were determined. Outcome measures studied were time to subsequent colectomy, rehospitalization for inflammatory bowel disease, and restarting steroid medication. We also used survival analysis to evaluate whether patient characteristics predicted the risk of rehospitalization and colectomy.

RESULTS

Among 656 patients initially hospitalized for severe UC, 20% (N = 129) underwent colectomy during their initial hospitalization. Of the remaining 527, a total of 95% (N = 498) were discharged on a steroid taper. At 1 year after discharge, 29% of those remaining under observation were rehospitalized for UC, and an additional 10% required colectomy. At 1 and 5 years after discharge, 34% and 26% received at least a 90-day supply of steroid in the preceding 9 months. Risk of rehospitalization and colectomy were unrelated to the patient's age, sex, or race/ethnicity.

CONCLUSIONS

The risk for colectomy in patients hospitalized for the first time with severe UC is 20%. In the 3 months after hospitalization the risk for colectomy is 6%. After that, risks appear to decrease proportionate to the time since initial hospitalization.

BACKGROUND

Atrial fibrillation (AF) has been linked to an inflammatory process detected through various biomarkers, including C-Reactive Protein (CRP). Early recurrence of AF within the first 3 months after curative AF ablation is not felt to reflect success or failure of the procedure. We hypothesized that this early recurrence is due to an inflammatory response to the ablation itself. We therefore sought to evaluate levels of CRP after AF ablation.

METHODS

We prospectively enrolled subjects undergoing AF ablation. A control group of patients undergoing ablation for supraventricular tachycardia (SVT) was also enrolled. Each patient had CRP drawn on the day of the procedure (prior to ablation) and during their first follow-up (median 49 days, interquartile range [IQR] 37-93) and second follow-up (median 147 days, IQR 141-257) clinic visits. Patient interviews were performed and medical histories reviewed for evidence of recurrent AF prior to the first follow-up.

RESULTS

CRP levels significantly increased from baseline to first follow-up in the AF ablation group (P = 0.0017). CRP did not significantly change after SVT ablation (P = 0.92). Seventeen (45%) of the AF subjects exhibited recurrence of AF prior to first follow-up. After adjusting for multiple potential confounders, AF ablation patients with recurrent AF prior to their first follow-up had a statistically significant greater odds of having an increase in CRP (OR 21, 95% CI 1.1-417, P = 0.045).

CONCLUSIONS

AF ablation generates an inflammatory response that persists for several weeks. This inflammation may explain early recurrence of AF after curative ablation.

OBJECTIVE

To investigate the frequency and outcomes of ventilated patients with newly acquired large burdens of Pseudomonas aeruginosa and to test the hypothesis that large quantities of bacteria are associated with adverse patient outcomes.

DESIGN

A prospective, single-center, observational, cohort study.

SETTING

Medical-surgical intensive care units in a tertiary care university hospital.

PATIENTS

All adult patients requiring > or = 48 hrs of mechanical ventilation and identified as having newly acquired P. aeruginosa in their lower respiratory tracts between October 2002 and April 2006.

INTERVENTIONS

None.

MEASUREMENTS AND MAIN RESULTS

Daily surveillance cultures of endotracheal aspirates were performed on patients intubated > or = 48 hrs; 69 patients with newly acquired P. aeruginosa were enrolled. Daily P. aeruginosa quantification of endotracheal aspirates was performed; clinical signs of infection were noted. Of 45 patients with high P. aeruginosa burdens (> or = 1,000,000 colony-forming units/mL in endotracheal aspirates; > or = 10,000 colony-forming units/mL in bronchoalveolar-lavage), 17 (37.8%) patients did not meet clinical criteria for ventilator-associated pneumonia and had a statistically significant higher risk of death (adjusted hazard ratio, 37.53; 95% confidence interval, 3.79-371.96; p = 0.002) when compared with the patients who had P. aeruginosa ventilator-associated pneumonia. When excluding the ten patients who had ventilator-associated pneumonia attributed to bacteria other than P. aeruginosa or attributed to multiple bacteria including P. aeruginosa, the risk of death remained statistically significant (adjusted hazard ratio, 23.98; 95% confidence interval: 2.49-230.53; p = 0.006). Furthermore, more patients with high P. aeruginosa burdens secreted the type III secretion facilitator protein, PcrV (p = 0.01).

CONCLUSIONS

A group of patients with large burdens of P. aeruginosa who did not meet clinical criteria for ventilator-associated pneumonia had an increased risk of death when compared with patients who had high P. aeruginosa burdens and met ventilator-associated pneumonia criteria. Patients with high P. aeruginosa burden seemed to possess more virulent strains.

Human obesity has a strong genetic component. Most genes that influence an individual's predisposition to gain weight are not yet known. However, the study of extreme human obesity caused by single gene defects has provided a glimpse into the long-term regulation of body weight. These monogenic obesity disorders have confirmed that the hypothalamic leptin-melanocortin system is critical for energy balance in humans, because disruption of these pathways causes the most severe obesity phenotypes. Approximately 20 different genes and at least three different mechanisms have been implicated in monogenic causes of obesity; however, they account for fewer than 5% of all severe obesity cases. This finding suggests that the genetic basis for human obesity is likely to be extremely heterogeneous, with contributions from numerous genes acting by various, yet undiscovered, molecular mechanisms.

In this study we examined the ability of interferon-gamma (IFN-gamma) to regulate mammary epithelial cell growth and gene expression, with particular emphasis on two genes: Maspin (a member of serine protease inhibitor superfamily), and the lysosomal aspartyl endopeptidase cathepsin D (CatD). The protein products of these genes are critically involved in regulation of multitude of biological functions in different stages of mammary tissue development and remodeling. In addition, the expression of Maspin is down-regulated in primary breast cancer and is lost in metastatic disease, while CatD is excessively produced and aberrantly secreted by breast cancer cells. We report that IFN-gamma receptors are expressed in mammary epithelial cells, and receptor engagement by IFN-gamma transduces the IFN-gamma signal via Stat-1 resulting in decreased vacuolar pH. This change in vacuolar pH alters CatD protein processing and secretion concurrent with increased Maspin secretion. In addition, IFN-gamma exerts a suppressive effect on cell growth and proliferation, and induces morphological changes in mammary epithelial cells. Our studies also reveal that breast cancer cells, which are devoid of Maspin, are refractory to IFN-gamma with respect to changes in vacuolar pH and CatD. However, Maspin transfection of breast cancer cells partially sensitizes the cells to IFN-gamma's effect, thus providing new therapeutic implications.