George J. Eckert

Impact of Pain on Depression Treatment Response in Primary Care

Objective Pain commonly coexists with depression, but its impact on treatment outcomes has not been well studied. Therefore, we prospectively evaluated the impact of comorbid pain on depression treatment response and health-related quality of life. Methods We analyzed data from the ARTIST study, a randomized controlled trial with naturalistic follow-up conducted in 37 primary care clinics. Participants were 573 clinically depressed patients randomized to one of three selective serotonin reuptake inhibitor (SSRI) antidepressants: fluoxetine, paroxetine, or sertraline. Depression as assessed by the Symptom Checklist-20 (SCL-20) was the primary outcome. Secondary outcomes included pain and health-related quality of life. Results Pain was reported by more than two thirds of depressed patients at baseline, with the severity of pain mild in 25% of patients, moderate in 30%, and severe in 14%. After 3 months of antidepressant therapy, 24% of patients had a poor depression treatment response (ie, SCL-20 >1.3). Multivariate odds ratios for poor treatment response were 1.5 (95% confidence interval, 0.8–3.2) for mild pain, 2.0 (1.1–4.0) for moderate pain, and 4.1 (1.9–8.8) for severe pain compared with those without pain. Increasing pain severity also had an adverse impact on outcomes in multiple domains of health-related quality of life. Conclusions Pain is present in two thirds of depressed primary care patients begun on antidepressant therapy, and the severity of pain is a strong predictor of poor depression and health-related quality of life outcomes at 3 months. Better recognition, assessment, and treatment of comorbid pain may enhance outcomes of depression therapy.

Effects of computerized guidelines for managing heart disease in primary care.

BACKGROUND: Electronic information systems have been proposed as one means to reduce medical errors of commission (doing the wrong thing) and omission (not providing indicated care).OBJECTIVE: To assess the effects of computer-based cardiac care suggestions.DESIGN: A randomized, controlled trial targeting primary care physicians and pharmacists.SUBJECTS: A total of 706 outpatients with heart failure and/or ischemic heart disease.INTERVENTIONS: Evidence-based cardiac care suggestions, approved by a panel of local cardiologists and general internists, were displayed to physicians and pharmacists as they cared for enrolled patients.MEASUREMENTS: Adherence with the care suggestions, generic and condition-specific quality of life, acute exacerbations of their cardiac disease, medication compliance, health care costs, satisfaction with care, and physicians’ attitudes toward guidelines.RESULTS: Subjects were followed for 1 year during which they made 3,419 primary care visits and were eligible for 2,609 separate cardiac care suggestions. The intervention had no effect on physicians’ adherence to the care suggestions (23% for intervention patients vs 22% for controls). There were no intervention-control differences in quality of life, medication compliance, health care utilization, costs, or satisfaction with care. Physicians viewed guidelines as providing helpful information but constraining their practice and not helpful in making decisions for individual patients.CONCLUSIONS: Care suggestions generated by a sophisticated electronic medical record system failed to improve adherence to accepted practice guidelines or outcomes for patients with heart disease. Future studies must weigh the benefits and costs of different (and perhaps more Draconian) methods of affecting clinician behavior.

Improvement in Blood Pressure With Inhibition of the Epithelial Sodium Channel in Blacks With Hypertension

Hypertension in blacks is more prevalent and less often controlled than the hypertension of other ethnic groups. We sought to explore the benefit of adding inhibitors of the epithelial sodium channel (ENaC), an aldosterone-regulated site of sodium reabsorption in the distal nephron, to the antihypertensive regimen of black hypertensive patients. In a prospective, randomized, placebo-controlled, double-blind clinical trial, we used a 2-by-2 factorial design with 4 treatment groups: amiloride (a direct inhibitor of ENaC), spironolactone (an aldosterone receptor antagonist), the combination of both drugs, and placebo. The subjects (n=98) had an elevated blood pressure despite treatment that included a diuretic and a calcium channel blocker; the level of plasma renin activity was ≤0.56 ng/L per second. The primary end points were changes from baseline in systolic and diastolic blood pressure over a 9-week period of treatment. The reductions in systolic and diastolic blood pressures (mm Hg) were, respectively, 9.8±1.6 (SE) and 3.4±1.0 for amiloride (P<0.001) and 4.6±1.6 (P=0.006) and 1.8±1.0 for spironolactone (P=0.07). Treatment with either amiloride or spironolactone or the combination was well tolerated; no patient experienced hyperkalemia. In a substudy, plasma endothelin-1 levels were observed to decrease after 3 weeks of treatment with spironolactone (P<0.001), consistent with a non–ENaC-related potential benefit of spironolactone. In conclusion, treatment with either amiloride or spironolactone can provide an additional reduction in blood pressure in blacks already receiving conventional antihypertensive therapy.

Fulminant hepatic failure as the initial presentation of acute autoimmune hepatitis

BACKGROUND & AIMS Autoimmune hepatitis is a common cause of chronic hepatitis, and acute presentation is thought to be uncommon. The aim of this study was to compare clinical, biochemical, and histological features in patients with autoimmune hepatitis presenting with either acute or chronic hepatitis. METHODS Retrospective review of all patients with autoimmune hepatitis presenting to a University medical center from 1993 to 2002. RESULTS One hundred fifteen patients with autoimmune hepatitis were identified. Ten patients with autoimmune hepatitis were identified as having acute presentation (group I), and 20 patients with a classic presentation as chronic hepatitis (group II) served as age- and sex-matched controls. All patients met criteria published by the International Autoimmune Hepatitis Group. Patients with acute presentation differed significantly with regard to encephalopathy, albumin levels, and bilirubin levels. Blinded liver biopsy review demonstrated that those with acute presentation had significantly less fibrosis, and significantly greater interface hepatitis, lobular disarray, lobular hepatitis, hepatocyte necrosis, zone III necrosis, and submassive necrosis. CONCLUSIONS In our study, patients with an acute presentation of autoimmune hepatitis differed from patients with a classical presentation clinically, biochemically, and histologically. In our review, a majority of patients with acute autoimmune hepatitis presented with fulminant hepatic failure. The pattern of zone 3 necrosis may be a specific finding in those with acute autoimmune hepatitis.

Comparison of quality of life measures in heart failure

BackgroundAlthough numerous health-related quality-of-life instruments are available to measure patients’ quality of life, few studies have compared these measures directly to determine how they function in the same group of patients. ObjectiveThe purpose of this study was to empirically compare psychometric properties of the Chronic Heart Failure Questionnaire (CHQ), the Minnesota Living with Heart Failure Questionnaire (LHFQ), and the General Health Survey Short-form-12 (SF-12). SampleA convenience sample of 211 patients with heart failure completed baseline questionnaires; 165 patients completed the entire 26-week study. MethodsPatients completed telephone interviews at baseline and at 4, 8, and 26 weeks after baseline. To compare mode of administration, a subset of patients (n = 173) completed face-to-face and telephone interviews. ResultsPatients reported low-to-moderate health-related quality-of-life overall. Reliability of the three instruments was satisfactory. Responsiveness to changing condition, as evaluated by analysis of variance, receiver operating curve characteristics, and the minimal clinically important difference method, indicated that the CHQ and LHFQ were more responsive to changing conditions than the SF-12. No major differences were noted between the scores of the face-to-face interviews and the baseline telephone interviews. The LHFQ and SF-12 were easier and took less time to administer than the CHQ. ConclusionsWhile all three instruments were reliable and valid, the CHQ and LHFQ were more sensitive than the SF-12 in detecting clinically important changes over time.

The Outcome of Physical Symptoms with Treatment of Depression

AbstractOBJECTIVE: This study examined the prevalence, impact on health-related quality of life (HRQoL), and outcome of physical symptoms in depressed patients during 9 months of anti-depressant therapy. DESIGN: Open-label, randomized, intention-to-treat trial with enrollment occurring April through November 1999. SETTING: Thirty-seven primary care clinics within a research network. PATIENTS: Five hundred seventy-three depressed patients started on one of three selective serotonin reuptake inhibitors (SSRIs) by their primary care physician and who completed a baseline interview. INTERVENTIONS: Patients were randomized to receive fluoxetine, paroxetine, or sertraline. MEASUREMENTS AND MAIN RESULTS: Outcomes assessed included physical symptoms, depression, and multiple domains of HRQoL. Prevalence of physical symptoms was determined at baseline and after 1, 3, 6, and 9 months of treatment. Stepwise linear regression models were used to determine the independent effects of physical symptoms and depression on HRQoL domains.Of the 14 physical symptoms assessed, 13 were present in at least a third to half of the patients at baseline. Each symptom showed the greatest improvement during the initial month of treatment. In contrast, depression continued to show gradual improvement over a 9-month period. Physical symptoms had a predominant effect on pain (explaining 17% to 18% of the variance), physical functioning (13%), and overall health perceptions (13% to 15%). Depression had the greatest impact on mental (26% to 45%), social (14% to 32%), and work functioning (9% to 32%). CONCLUSIONS: Physical symptoms are prevalent in depressed patients and initially improve in the first month of SSRI treatment. Unlike depression, however, improvement in physical symptoms typically plateaus with minimal resolution in subsequent months.

Discriminant properties of commonly used quality of life measures in heart failure.

Health-related quality of life (HRQL) instruments have been used to measure HRQL in heart failure patients, but how different instruments compare in the same groups of patients is not known. The purpose of this study was to compare the reliability and validity of three HRQL measures in 211 heart failure patients recruited from clinics affiliated with an urban hospital. Two disease-specific instruments, the chronic heart failure questionnaire (CHQ) and the living with heart failure questionnaire (LHFQ), and one generic instrument, the short-form 12 (SF-12), were administered. Patients reported moderate to low HRQL scores. Floor or ceiling effects were noted in the disease-specific instruments. Internal consistency reliabilities of the CHQ and LHFQ were satisfactory. Construct, convergent, and discriminant validity were supported for each instrument. Each scale and subscale, except for the SF-12 mental component scale, differentiated between patients with New York Heart Association (NYHA) class I, II, and III plus IV; the LHFQ physical subscale was the only measure to differentiate between patients with NYHA class III and IV. All three instruments were satisfactory for measuring HRQL, but the disease-specific instruments were preferable to the generic instrument. The decision of which instrument to use depends on the purpose of the study.

Risk factors for delirium tremens development.

OBJECTIVE: To identify clinical characteristics associated with inpatient development of delirium tremens so that future treatment efforts can focus on patients most likely to benefit from aggressive therapy.DESIGN: Retrospective cohort study among patients discharged with diagnoses related to alcohol abuse.SETTING: University-affiliated inner-city hospital.PATIENTS/PARTICIPANTS: Two hundred consecutive patients discharged between June 1991 and August 1992 who underwent evaluation and treatment for alcohol withdrawal or detoxification.MEASUREMENTS AND MAIN RESULTS: Mean age was 41.9 years, 85% were male, 57% were white and 84% were unmarried. Forty-eight (24%) of the patients developed delirium tremens during hospitalization. Bivariate analysis indicated that those who developed delirium tremens were more likely to be African-American, unemployed, and homeless, and were more likely to have gone more days since their last drink, and to have concurrent acute medical illness, high admission blood urea nitrogen level and respiratory rate, and low admission albumin level and systolic blood pressure. In multiple logistic regression analyses, patients who developed delirium tremens were more likely to have gone more days since their last drink (odds ratio [OR] 1.3; 95% confidence interval [CI] 1.09, 1.61) and to have concurrent acute medical illness (OR 5.1; 95% CI 2.07, 12.55). These risk factors were combined for assessment of their ability to predict the occurrence of delirium tremens. If no factors were present, 9% developed delirium tremens; if one factor was present, 25% developed delirium tremens; and if two factors were present, 54% developed delirium tremens.CONCLUSIONS: Inpatient development of delirium tremens was common among patients treated for alcohol detoxification or withdrawal and correlated with several readily available clinical variables.

Expression of group IIA secretory phospholipase A2 is elevated in prostatic intraepithelial neoplasia and adenocarcinoma.

Phospholipase A2 (PLA2) enzymes release arachidonic acid from cellular phospholipids in a variety of mammalian tissues, including prostate. Group IIa secretory PLA2 (sPLA2) can generate arachidonate from cellular phospholipids. We examined the group IIa sPLA2 expression in benign prostatic tissues, prostatic intraepithelial neoplasia (PIN), and adenocarcinoma to determine whether sPLA2 expression is altered in the carcinogenesis of human prostatic cancer. Thirty-three of 74 total cases (45%) of benign prostatic tissue showed positive immunohistochemical staining for group IIA sPLA2, whereas 63 of 69 total cases (91%) of high-grade PINs and 70 of 78 total cases (90%) of adenocarcinomas gave positive results. Four of 10 cases of low-grade PIN showed positive immunoreactivity for sPLA2. The number of cells staining for sPLA2 was significantly less in benign epithelium (4%) and low-grade PIN (4%) compared to high-grade PIN (40%) or adenocarcinoma (38%) (P < 0.001). There was no significant difference between high-grade PIN and adenocarcinoma in the number of cells staining positively for sPLA2. The intensity of sPLA2 immunoreactivity was also different among benign prostatic tissue, low-grade PIN, high-grade PIN, and prostatic adenocarcinoma specimens. The malignant cells demonstrated more intense immunohistochemical staining (moderate to strong staining in 81% and 69% cases for high-grade PIN and adenocarcinoma, respectively) than benign glands (moderate staining in 11% of cases). No strong staining was observed in benign glands or low-grade PIN. Our data are consistent with the contention that group IIA sPLA2 expression is elevated in neoplastic prostatic tissue and support the hypothesis that dysregulation of sPLA2 may play a role in prostatic carcinogenesis.

High colonoscopic prevalence of proximal colon serrated polyps in average-risk men and women

BACKGROUND Proximal colon serrated polyps likely contribute to the decreased protection of colonoscopy against right-sided colorectal cancer. OBJECTIVE To estimate the prevalence and extrapolated detection rate of proximal serrated polyps at screening colonoscopy. DESIGN Retrospective study. PATIENTS The study involved secondary analyses that used two databases. The first includes screening colonoscopies performed by 15 attending gastroenterologists at two academic endoscopy units between 2000 and 2009. The second includes average-risk patients who had previously participated in a randomized trial comparing high-definition chromocolonoscopy and white-light colonoscopy. MAIN OUTCOME MEASUREMENTS Prevalence of proximal serrated polyps found by the highest-level detectors and proximal serrated polyp detection rates corresponding to adenoma detection rates of 25% in men and 15% in women, respectively. RESULTS We analyzed 6681 procedures from the first database. Mean (± standard deviation) detection rates for adenomas and proximal serrated polyps were 38% ± 7.8% (range 17%-47%) and 13% ± 4.8% (1%-18%), respectively. There was a significant correlation between detection rates for adenomas and proximal serrated polyps for men (R = 0.71; P = .003) and women (R = 0.73; P = .002). Adenoma detection rates of 25% for men and 15% for women both corresponded to a detection rate of 4.5% for proximal serrated polyps. The prevalence of proximal serrated polyps found by the highest-level detector was 18%. The corresponding rate derived from the high-definition screening colonoscopy database was 20%. LIMITATIONS Retrospective study. CONCLUSION The prevalence of proximal colon serrated polyps in average-risk patients undergoing screening colonoscopy is higher than previously reported. An extrapolated proximal serrated polyp detection rate of 5% is suggested for average-risk men and women.