Susan M. Perkins

Cognitive Deficits in Chronic Heart Failure

Background:Patients with heart failure (HF) have been found to have cognitive deficits, but it remains unclear whether these deficits are associated with HF or with aging or comorbid conditions common in HF. Objectives:The purpose of this study was (a) to determine the types, the frequency, and the severity of cognitive deficits among patients with chronic HF compared with age- and education-matched healthy participants and participants with major medical conditions other than HF, and (b) to evaluate the relationships between HF severity, age, and comorbidities and cognitive deficits. Methods:A sample of 414 participants completed the study (249 HF patients, 63 healthy and 102 medical participants). The HF patients completed measures of HF severity, comorbidity (multiple comorbidity, depressive symptoms), and neuropsychological functioning. Blood pressure and oxygen saturation were assessed at interview; clinical variables were abstracted from records. Participants in the comparison groups completed the same measures as the HF patients except those specific to HF. Results:Compared with the healthy and medical participants, HF patients had poorer memory, psychomotor speed, and executive function. Significantly more HF patients (24%) had deficits in three or more domains. Higher (worse) HF severity was associated with more cognitive deficits; HF severity interacted with age to explain deficits in executive function. Surprisingly, men with HF had poorer memory, psychomotor speed, and visuospatial recall ability than women. Multiple comorbidity, hypertension, depressive symptoms, and medications were not associated with cognitive deficits in this sample. Discussion:HF results in losses in memory, psychomotor speed, and executive function in almost one fourth of patients. Patients with more severe HF are at risk for cognitive deficits. Older patients with more severe HF may have more problems in executive function, and men with HF may be at increased risk for cognitive deficits. Studies are urgently needed to identify the mechanisms for the cognitive deficits in HF and to test innovative interventions to prevent cognitive loss and decline.

Phase I feasibility trial of stereotactic body radiation therapy for primary hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is increasing in incidence and the majority of patients are not candidates for radical therapies. Therefore, interest in minimally invasive therapies in growing.MethodsA Phase I dose escalation trial was conducted at Indiana University to determine the feasibility and toxicity of stereotactic body radiation therapy (SBRT) for primary HCC. Eligible patients had Child-Turcotte-Pugh’s Class (CTP) A or B, were not candidates for resection, had 1–3 lesions and cumulative tumour diameter less than or equal to 6 cm. Dose escalation started at 36 Gy in 3 fractions (12 Gy/fraction) with a subsequent planned escalation of 2 Gy/fraction/level. Dose-limiting toxicity (DLT) was defined as Common Terminology Criteria for Adverse Events v3.0 grade 3 or greater toxicity.ResultsSeventeen patients with 25 lesions were enrolled. Dose was escalated to 48 Gy (16 Gy/fraction) in CTP-A patients without DLT. Two patients with CPC-B disease developed grade 3 hepatic toxicity at the 42-Gy (14 Gy/fraction) level. The protocol was amended for subsequent CTP-B patients to receive a regimen of 5 fractions starting at 40 Gy (8 Gy/fraction) with one patient experiencing progressive liver failure. Four additional patients were enrolled (one died of unrelated causes after an incomplete SBRT course) without DLT. The only factor related to more than one grade 3 or greater liver toxicity or death within 6 months was the CTP score (p=0.03). Six patients underwent a liver transplant. Ten patients are alive without progression with a median FU of 24 months (10–42 months), with local control/stabilisation of the disease of 100%. One and two-year Kaplan-Meier estimates for overall survival are 75% and 60%, respectively.ConclusionsSBRT is a non-invasive feasible and well tolerated therapy in adequately selected patients with HCC. The preliminary local control and survival are encouraging. A confirmatory Phase II trial is currently open to accrual.

Social support and health-related quality of life in chronic heart failure patients

Objectives: Objectives of this study were to: (1) describe perceived social support during a baseline hospitalization and 12 months later among heart failure patients; (2) examine differences in social support as a function of gender and age (less than 65 and 65 years or older); and (3) examine social support as a predictor of health-related quality of life. Background: Social support is a predictor of well-being and mortality, but little is known about support patterns among heart failure patients and how they influence quality of life. Methods: The sample included 227 hospitalized patients with heart failure who completed the Social Support Survey and the Chronic Heart Failure Questionnaire at baseline; 147 patients completed these questionnaires again 12 months after baseline. Results: Mean baseline and 12-month total support scores were 56 and 53, respectively, with a score of 76 indicating the most positive perceptions of support. The ANOVA indicated significant interactions of gender by age for total (F = 5.04; p = 0.03) and emotional/informational support (F = 4.87; p = 0.03) and for positive social interactions (F = 4.43; p = 0.04), with men under age 65 perceiving less support than men aged 65 and older and women in either age group. Baseline support did not predict 12-month health-related quality of life, but changes in social support significantly predicted changes in health-related quality of life (R2 = 0.14). Conclusions: Overall, perceptions of support were moderate to high, but there was wide variation in perceptions over time. Men under age 65 reported less support than other groups of patients. Importantly, changes in social support were significant predictors of changes in health-related quality of life.

Recurrent Seizures and Behavior Problems in Children with First Recognized Seizures: A Prospective Study

Summary:  Purpose: Children with epilepsy have high rates of behavior problems. The purpose was to describe prospectively the association of seizures and behavior problems in children with new‐onset seizures.

Neuropsychological Predictors of Academic Underachievement in Pediatric Epilepsy: Moderating Roles of Demographic, Seizure, and Psychosocial Variables

Summary:  Purpose: Academic underachievement is common in pediatric epilepsy. Attempts to identify seizure and psychosocial risk factors for underachievement have yielded inconsistent findings, raising the possibility that seizure and psychosocial variables play a complex role in combination with other variables such as neuropsychological functioning. This study cross‐validated a neuropsychological measurement model for childhood epilepsy, examined the relation between neuropsychological functioning and academic achievement, and tested the degree to which demographic, seizure, and psychosocial variables moderate that relation.

Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure

PURPOSE Because the bioavailability of oral furosemide is erratic and often incomplete, we tested the hypothesis that patients with heart failure who were treated with torsemide, a predictably absorbed diuretic, would have more favorable clinical outcomes than would those treated with furosemide. PATIENTS AND METHODS We conducted an open-label trial of 234 patients with chronic heart failure (mean [+/- SD] age, 64 +/- 11 years) from an urban public health care system. Patients received oral torsemide (n = 113) or furosemide (n = 121) for 1 year. The primary endpoint was readmission to the hospital for heart failure. Secondary endpoints included readmission for all cardiovascular causes and for all causes, numbers of hospital days, and health-related quality of life. RESULTS Compared with furosemide-treated patients, torsemide-treated patients were less likely to need readmission for heart failure (39 [32%] vs. 19 [17%], P <0.01) or for all cardiovascular causes (71 [59%] vs. 50 [44%], P = 0.03). There was no difference in the rate of admissions for all causes (92 [76%] vs. 80 [71%], P = 0.36). Patients treated with torsemide had significantly fewer hospital days for heart failure (106 vs. 296 days, P = 0.02). Improvements in dyspnea and fatigue scores from baseline were greater among patients treated with torsemide, but the differences were statistically significant only for fatigue scores at months 2, 8, and 12. CONCLUSIONS Compared with furosemide-treated patients, torsemide-treated patients were less likely to be readmitted for heart failure and for all cardiovascular causes, and were less fatigued. If our results are confirmed by blinded trials, torsemide may be the preferred loop diuretic for patients with chronic heart failure.

Brachial plexopathy from stereotactic body radiotherapy in early-stage NSCLC: Dose-limiting toxicity in apical tumor sites

BACKGROUND AND PURPOSE We report frequency of brachial plexopathy in early-stage non-small cell lung cancer treated with stereotactic body radiotherapy. MATERIALS AND METHODS 276 T1-T2, N0 or peripheral T3, N0 lesions were treated in 253 patients with stereotactic radiotherapy at Indiana University and Richard L. Roudebush VAMC from 1998 to 2007. Thirty-seven lesions in 36 patients were identified as apical lesions, defined as epicenter of lesion superior to aortic arch. Brachial plexus toxicity was scored for these apical lesions according to CTCAE v. 3.0 for ipsilateral shoulder/arm neuropathic pain, motor weakness, or sensory alteration. RESULTS The 37 apical lesions (19 Stage IA, 16 IB, and 2 IIB) were treated with stereotactic body radiotherapy to a median total dose of 57 Gy (30-72). The associated brachial plexus of 7/37 apical lesions developed grade 2-4 plexopathy (4 pts--grade 2, 2 pts--grade 3, 1 pt--grade 4). Five patients had ipsilateral shoulder/arm neuropathic pain alone, one had pain and upper extremity weakness, and one had pain progressing to numbness of the upper extremity and paralysis of hand and wrist. The median of the maximum brachial plexus doses of patients developing brachial plexopathy was 30 Gy (18-82). Two-year Kaplan-Meier risk of brachial plexopathy for maximum brachial plexus dose >26 Gy was 46% vs 8% for doses 26 Gy (p=0.04 for likelihood ratio test). CONCLUSIONS Stereotactic body radiotherapy for apical lesions carries a risk of brachial plexopathy. Brachial plexus maximum dose should be kept <26 Gy in 3 or 4 fractions.

Measuring stigma in children with epilepsy and their parents: instrument development and testing

PURPOSE The goal of this work is to describe psychometric properties of two scales measuring perceived stigma in children with epilepsy and their parents. METHODS Data were collected for the parent scale in two samples: parents of 173 children with epilepsy and of 224 children with new-onset seizures. The child scale was tested in the chronic sample. Content validity, internal consistency reliability, and construct validity were tested. RESULTS Both scales had strong internal consistency reliability and construct validity. Higher scores were associated with greater seizure severity scores. In the parent scale, lower scores were associated with more positive mood, less worry, and more family leisure activities. In the child scale, higher scores were correlated with more negative attitude, greater worry, poorer self-concept, and more depression symptoms. CONCLUSIONS Both scales were found to have strong psychometric properties. They are short, and items are easy to understand. These scales have potential for use in research and in the clinical setting to measure stigma.

Behavioral issues involving children and adolescents with epilepsy and the impact of their families: recent research data

OBJECTIVE Using data from a larger study on new-onset seizures, we reported preliminary findings concerning relationships between family factors and child behavioral problems at baseline and 24 months. We also explored which baseline and changes in family factors were associated with changes in child behavioral problems over the 24-month period. METHODS Subjects were 224 children and their primary caregivers. Data were collected using structured telephone interviews and analyzed using multiple regression. RESULTS Deficient family mastery and parent confidence in managing their childs discipline were associated with behavior problems at baseline and at 24 months; they also predicted child behavior problems over time. Decreasing parent confidence in disciplining their child was associated with increasing child behavior problems. Decreases in parent emotional support of the child were associated with increases in child internalizing problems. CONCLUSION Child behavior problems, family environment, and parenting behaviors should be assessed when children present to the clinical setting with new-onset seizures.

The use of propensity scores in pharmacoepidemiologic research

To describe the application of propensity score analysis in pharmacoepidemiologic research using a study comparing the renal effects of two commonly prescribed non‐steroidal anti‐inflammatory drugs (NSAIDs).