The influence of depression on quality of life in patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract that significantly impacts the health-related quality of life (HR-QOL). A decreased HR-QOL has been demonstrated in patients with active disease compared with patients in remission. In this cross-sectional study, we examined the role of depression and disease activity as independent factors in predicting patient's HR-QOL. METHODS: Hundred and five patients with either Crohn's disease (CD) or ulcerative colitis (UC) were enrolled. Disease activity was evaluated using Crohn's Disease Activity Index or Seo's Activity Index. Depressive symptoms were evaluated using Beck's Depression Inventory-II and Beck's Depression Inventory for Primary Care (BDI-PC). HR-QOL was evaluated using the Short Inflammatory Bowel Disease Questionnaire. Simple and multiple regressions were performed on quality of life score with demographic and clinical variables as predictors. RESULTS: The prevalence of depression in our study population is 25%. In patients with both CD and UC, depression is the most significant predictor to a poor HR-QOL (in CD, P = 8.22 × 10; in UC, P = 2.02 × 10). HR-QOL is weakly affected by disease activity (in CD, P = 0.110; in UC, P = 0.00492). In CD, biological use displays positive effect on HR-QOL (P = 0.00780). In total, the proportion of variance explained by all predictors is 61% for CD and 53% for UC, whereas the depression alone explains 44% and 36%. CONCLUSIONS: Our study demonstrates the importance of depression toward the quality of life in patients with inflammatory bowel disease. The diagnosis of depression should be actively sought out and treated in outpatient inflammatory bowel disease practices.

Loss of macroautophagy promotes or prevents fibroblast apoptosis depending on the death stimulus.

Macroautophagy has been implicated as a mechanism of cell death. However, the relationship between this degradative pathway and cell death is unclear as macroautophagy has been shown recently to protect against apoptosis. To better define the interplay between these two critical cellular processes, we determined whether inhibition of macroautophagy could have both pro-apoptotic and anti-apoptotic effects in the same cell. Embryonic fibroblasts from mice with a knock-out of the essential macroautophagy gene atg5 were treated with activators of the extrinsic and intrinsic death pathways. Loss of macroautophagy sensitized these cells to caspase-dependent apoptosis from the death receptor ligands Fas and tumor necrosis factor-alpha (TNF-alpha). Atg5-/- mouse embryonic fibroblasts had increased activation of the mitochondrial death pathway in response to Fas/TNF-alpha in concert with decreased ATP levels. Fas/TNF-alpha treatment failed to up-regulate macroautophagy, and in fact, decreased activity at late time points. In contrast to their sensitization to Fas/TNF-alpha, Atg5-/- cells were resistant to death from menadione and UV light. In the absence of macroautophagy, an up-regulation of chaperone-mediated autophagy induced resistance to these stressors. These results demonstrate that inhibition of macroautophagy can promote or prevent apoptosis in the same cell and that the response is governed by the nature of the death stimulus and compensatory changes in other forms of autophagy. Experimental findings that an inhibition of macroautophagy blocks apoptosis do not prove that autophagy mediates cell death as this effect may result from the protective up-regulation of other autophagic pathways such as chaperone-mediated autophagy.

Importance of hepatitis C coinfection in the development of QT prolongation in HIV-infected patients.

BACKGROUND: Case reports and unblinded studies suggest that human immunodeficiency virus (HIV) disease is associated with QT prolongation and torsade de pointes ventricular tachycardia. Hepatitis C coinfection is common in patients with HIV disease, and cirrhosis is also associated with QT prolongation. We therefore undertook a systematic analysis of the role of liver injury, nutritional state, and coinfection with hepatitis C in the etiology of QT prolongation in HIV disease. METHODS: We performed a blinded, controlled retrospective cohort study of 1648 patients over a 3-year period at a university-affiliated municipal hospital. All electrocardiograms were included if patients with HIV disease had measurements of CD4 count and viral load within 3 months and serum electrolytes within 30 days (n = 816). Control subjects were chosen randomly from the general medicine service (n = 832). QT interval was measured in lead II and corrected for heart rate by Bazett's formula (QTc). RESULTS: QTc was slightly but significantly longer in patients with HIV disease than in controls (443 +/- 37 vs 436 +/- 36 milliseconds, P < .001). Patients with hepatitis C had more pronounced QTc prolongation (452 +/- 41 vs 437 +/- 35 milliseconds, P < .001). CD4 count, HIV viral load, and HIV medications had no effect on QTc. When patients with hepatitis C were excluded from the analysis, there was no statistical difference between patients with HIV disease and controls (438 +/- 34 vs 436 +/- 36 milliseconds, P = .336). Multiple linear regression revealed that both HIV and hepatitis C infection predicted QTc prolongation, as did age, female sex, history of hypertension, use of opiates, low serum K+ and albumin, and high AST. Hepatitis C coinfection nearly doubled the risk of QTc of 470 milliseconds or greater in patients with HIV disease (29.6% vs 15.8%, P < .001). CONCLUSIONS: Human immunodeficiency virus and hepatitis C infections both independently prolong QTc. Coinfection with hepatitis C greatly increases the likelihood of clinically significant QTc prolongation in patients with HIV disease.

Community-based screening for cardiovascular disease and diabetes using HbA1c.

BACKGROUND: Persons from inner-city immigrant and mixed-ethnic communities are known to be at high risk for cardiovascular disease and diabetes. Such communities may also be underserved for preventive medical care. The authors hypothesized that hemoglobin A1c (HbA1c) could be used as a screening test for a community-based program to detect new cases of diabetes and persons at risk for diabetes and cardiovascular disease. METHODS: Screenings took place in churches, group homes, shelters, community centers, and street corners of the Bronx. Screening data included history of diabetes, age, ethnicity, body mass index, blood pressure, lipid panel, random glucose, and HbA1c. Data were analyzed for number of cases of new diabetes (HbA1c > or =7%), for patients at risk for diabetes (HbA1c 6%-6.99%), and for associations between HbA1c and other variables. The effect of location of screening and self-reported ethnicity on outcome variables was also analyzed. RESULTS: Seven hundred four persons were screened in 25 different sessions. HbA1c and lipid profile were obtained on 539 persons, which formed the cohort for analysis. Mean HbA1c for the cohort was 6.00%. Thirty-two percent of the cohort had HbA1c of more than 6%, and 11.4% had HbA1c of more than 7%. Excluding known diabetics (13% of cohort), 24% had HbA1c of more than 6%, and 3.4% had HbA1c of more than 7%. HbA1c was significantly correlated with total cholesterol, triglycerides, low-density lipoprotein, systolic blood pressure, body mass index, and age; in all cases, correlation coefficients were higher with HbA1c than with random glucose. In addition, significantly higher cardiovascular disease risk factors were found in persons with HbA1c of more than 6%; 6% may be a threshold value for the metabolic syndrome. Mean HbA1c was higher in persons from the South Bronx (which has a higher poverty rate) than the North Bronx (6.08% v 5.74%, p=0.013). There were no statistically significant differences between self-reported ethnic groupings. CONCLUSIONS: There was a high prevalence of undiagnosed diabetes, and of patients at risk for diabetes, in this community setting. Community-based screening can be used as a method for identifying high percentages of patients at risk for diabetes or with undiagnosed diabetes in an inner city, immigrant, mixed-ethnic population.