Showing papers by "Karla V. Ballman published in 2005"

Cardiovascular death in rheumatoid arthritis: a population-based study.

Abstract: Objective To determine whether systemic inflammation confers any additional risk for cardiovascular death among patients with rheumatoid arthritis (RA), after adjusting for traditional cardiovascular risk factors and comorbidities. Methods Using the population-based data resources of the Rochester Epidemiology Project, we assembled an incidence cohort of all Rochester, Minnesota residents ages ≥18 years who first fulfilled the American College of Rheumatology 1987 criteria for RA between January 1, 1955 and January 1, 1995. All subjects were followed up longitudinally through their complete (inpatient, outpatient) medical records, beginning at age 18 years and continuing until death, migration, or January 1, 2001. Detailed information on the occurrence of various cardiovascular risk factors (personal history of coronary heart disease [CHD], congestive heart failure, smoking, hypertension, dyslipidemia, body mass index [BMI], diabetes mellitus, menopausal status) as well as indicators of systemic inflammation and RA disease severity (rheumatoid factor [RF] seropositivity, erythrocyte sedimentation rate [ESR], joint swelling, radiographic changes, RA nodules, RA complications, RA treatments, disease duration) and comorbidities were collected on all subjects. Causes of death were ascertained from death certificates and medical records. Cox regression models were used to estimate the independent predictors of cardiovascular death. Results This inception cohort comprised a total of 603 RA patients whose mean age was 58 years, of whom 73% were women. During a mean followup of 15 years, 354 patients died and cardiovascular disease was the primary cause of death in 176 patients. Personal history of CHD, smoking, hypertension, low BMI, and diabetes mellitus, as well as comorbidities, including peripheral vascular disease, cerebrovascular disease, chronic pulmonary disease, dementia, ulcers, malignancies, renal disease, liver disease, and history of alcoholism, were all significant risk factors for cardiovascular death (P < 0.01 for each). Multivariable Cox regression analyses, controlled for cardiovascular risk factors and comorbidities, revealed that the risk of cardiovascular death was significantly higher among RA patients with at least 3 ESR values of ≥60 mm/hour (hazard ratio [HR] 2.03, 95% confidence interval [95% CI] 1.45–2.83), RA vasculitis (HR 2.41, 95% CI 1.00–5.81), and RA lung disease (HR 2.32, 95% CI 1.11–4.84). Conclusion These results indicate that markers of systemic inflammation confer a statistically significant additional risk for cardiovascular death among patients with RA, even after controlling for traditional cardiovascular risk factors and comorbidities.

Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: A population-based cohort study

Abstract: Objective To examine the risk of clinical coronary heart disease (CHD) in patients with rheumatoid arthritis (RA) compared with age- and sex-matched non-RA subjects, and to determine whether RA is a risk factor for CHD after accounting for traditional CHD risk factors. Methods We assembled a population-based incidence cohort of 603 Rochester, Minnesota residents ages ≥18 years who first fulfilled the American College of Rheumatology (ACR) 1987 criteria for RA between January 1, 1955 and January 1, 1995, and 603 age- and sex-matched non-RA subjects. All subjects were followed up through their complete inpatient and outpatient medical records, beginning at age 18 years until death, migration, or January 1, 2001. Data were collected on CHD events and traditional CHD risk factors (diabetes mellitus, hypertension, dyslipidemia, body mass index, smoking) using established diagnostic criteria. CHD events included hospitalized myocardial infarction (MI), unrecognized MI, coronary revascularization procedures, angina pectoris, and sudden CHD deaths. Conditional logistic regression and Cox regression models were used to estimate the risk of CHD associated with RA, both prior to and following RA diagnosis, after adjusting for CHD risk factors. Results During the 2-year period immediately prior to fulfillment of the ACR criteria, RA patients were significantly more likely to have been hospitalized for acute MI (odds ratio [OR] 3.17, 95% confidence interval [95% CI] 1.16–8.68) or to have experienced unrecognized MIs (OR 5.86, 95% CI 1.29–26.64), and less likely to have a history of angina pectoris (OR 0.58, 95% CI 0.34–0.99) compared with non-RA subjects. After the RA incidence date, RA patients were twice as likely to experience unrecognized MIs (hazard ratio [HR] 2.13, 95% CI 1.13–4.03) and sudden deaths (HR 1.94, 95% CI 1.06–3.55) and less likely to undergo coronary artery bypass grafting (HR 0.36, 95% CI 0.16–0.80) compared with non-RA subjects. Adjustment for the CHD risk factors did not substantially change the risk estimates. Conclusion Patients with RA have a significantly higher risk of CHD when compared with non-RA subjects. RA patients are less likely to report symptoms of angina and more likely to experience unrecognized MI and sudden cardiac death. The risk of CHD in RA patients precedes the ACR criteria–based diagnosis of RA, and the risk cannot be explained by an increased incidence of traditional CHD risk factors in RA patients.

Phase II Trial of Temsirolimus (CCI-779) in Recurrent Glioblastoma Multiforme: A North Central Cancer Treatment Group Study

Abstract: Background Temsirolimus (CCI-779) is a small-molecule inhibitor of the mammalian target of rapamycin (mTOR) and represents a rational therapeutic target against glioblastoma multiforme (GBM). Methods Recurrent GBM patients with ≤ 1 chemotherapy regimen for progressive disease were eligible. Temsirolimus was administered in a 250-mg intravenous dose weekly. Results Sixty-five patients were treated. The incidence of grade 3 or higher nonhematologic toxicity was 51%, and consisted mostly of hypercholesterolemia (11%), hypertriglyceridemia (8%), and hyperglycemia (8%). Grade 3 hematologic toxicity was observed in 11% of patients. Temsirolimus peak concentration (Cmax), and sirolimus Cmax and area under the concentration-time curve were decreased in patients receiving p450 enzyme–inducing anticonvulsants (EIACs) by 73%, 47%, and 50%, respectively, but were still within the therapeutic range of preclinical models. Twenty patients (36%) had evidence of improvement in neuroimaging, consisting of decrease in T2 si...

The risk of congestive heart failure in rheumatoid arthritis: a population-based study over 46 years.

Abstract: Objective It is hypothesized that the systemic inflammation associated with rheumatoid arthritis (RA) promotes an increased risk of cardiovascular (CV) morbidity and mortality. We examined the risk and determinants of congestive heart failure (CHF) in patients with RA. Methods We assembled a population-based, retrospective incidence cohort from among all individuals living in Rochester, Minnesota, in whom RA (defined according to the American College of Rheumatology 1987 criteria) was first diagnosed between 1955 and 1995, and an age- and sex-matched non-RA cohort. After excluding patients in whom CHF occurred before the RA index date, all subjects were followed up until either death, incident CHF (defined according to the Framingham Heart Study criteria), migration from the county, or until January 1, 2001. Detailed information from the complete medical records (including all inpatient and outpatient care provided by all local providers) regarding RA, ischemic heart disease, and traditional CV risk factors was collected. Cox models were used to estimate the effect of RA on the development of CHF, adjusting for CV risk factors and/or ischemic heart disease. Results The study population included 575 patients with RA and 583 subjects without RA. The CHF incidence rates were 1.99 and 1.16 cases per 100 person-years in patients with RA and in non-RA subjects, respectively (rate ratio 1.7, 95% confidence interval [95% CI] 1.3–2.1). After 30 years of followup, the cumulative incidence of CHF was 34.0% in patients with RA and 25.2% in non-RA subjects (P< 0.001). RA conferred a significant excess risk of CHF (hazard ratio [HR] 1.87, 95% CI 1.47–2.39) after adjusting for demographics, ischemic heart disease, and CV risk factors. The risk was higher among patients with RA who were rheumatoid factor (RF) positive (HR 2.59, 95% CI 1.95–3.43) than among those who were RF negative (HR 1.28, 95% CI 0.93–1.78). Conclusion Compared with persons without RA, patients with RA have twice the risk of developing CHF. This excess risk is not explained by traditional CV risk factors and/or clinical ischemic heart disease.

A prospective study of quality of life in adults with newly diagnosed high-grade gliomas: the impact of the extent of resection on quality of life and survival.

Abstract: OBJECTIVE To describe the quality of life (QOL) over time for adults with newly diagnosed high-grade gliomas and to examine the relationship between QOL and outcome data collected in three prospective cooperative group clinical trials. METHODS The QOL study was a companion protocol for three Phase II high-grade glioma protocols. Five self-administered forms were completed by patients to assess QOL at study entry, 2 months, and 4 months after enrollment. RESULTS QOL data were available for baseline, first, and second subsequent follow-up evaluations for 89%, 71%, and 69% of patients, respectively. A significant proportion of patients (47.1%) experienced impaired QOL (QOL < or = 50) in at least one measure at subsequent evaluations, whereas most patients (88%) with impaired QOL at baseline continued to have impaired QOL at subsequent evaluations. On multivariable analyses, baseline QOL measures were predictive of QOL at the time of follow-up. In addition, patients who underwent a gross total resection were much less likely to have impaired QOL (P = 0.006), were less likely to experience worsening depression (P = 0.0008), and were more likely to have improved QOL (P = 0.003) at their first follow-up evaluation. Changes in QOL measures over time were not found to be associated with survival in multivariable analyses that adjusted for known prognostic variables; variables that were independently associated with improved survival were better performance status (P < 0.001), younger age (P < 0.001), and greater extent of resection (P < 0.001). CONCLUSION Baseline QOL was predictive of QOL over time. Gross total resection was associated with longer survival and improved QOL over time for patients with high-grade gliomas.

Discrete Choice Methods With Simulations

Abstract: (2005). Discrete Choice Methods With Simulations. Journal of the American Statistical Association: Vol. 100, No. 469, pp. 351-352.

How much of the increased incidence of heart failure in rheumatoid arthritis is attributable to traditional cardiovascular risk factors and ischemic heart disease

Abstract: Objective To compare the proportion of the risk for the development of heart failure (HF) that is attributable to traditional cardiovascular (CV) risk factors, ischemic heart disease (IHD), and alcohol abuse between subjects with and subjects without rheumatoid arthritis (RA). Methods A population-based inception cohort of RA patients was assembled along with a similar cohort of subjects without RA. All individuals were followed up through their complete medical records, until HF incidence, death, migration, or January 1, 2001. The attributable risk of HF was estimated as the difference between the observed cumulative incidence of HF in each cohort (estimated from multivariable Cox models and adjusted for the competing risk of death) and the predicted cumulative incidence of HF in the absence of risk factors, with results expressed as a percentage of the observed cumulative incidence. Results A total of 575 RA subjects and 583 non-RA subjects (mean age 57 years, 73% women) without HF at incidence/index date had a mean followup of 15.1 and 17.0 years, respectively. During that period, 165 RA and 115 non-RA subjects had a first episode of HF, with a cumulative incidence of 36.3% and 20.4%, respectively, at age 80 years. Among non-RA subjects, 77% of the HF at age 80 years was attributable to CV risk factors, IHD, and alcohol abuse combined, whereas among RA subjects, only 54% of the HF at age 80 years was attributable to these factors (P < 0.01). Conclusion The excess risk of HF among RA patients is not explained by an increased frequency or effect of CV risk factors and IHD.

Cognitive function after radiotherapy for supratentorial low-grade glioma: a North Central Cancer Treatment Group prospective study.

Abstract: Purpose: To evaluate the effects of cranial radiotherapy (RT) on cognitive function in patients with supratentorial low-grade glioma. Methods and Materials: Twenty adult patients with supratentorial low-grade glioma were treated with 50.4 Gy (10 patients) or 64.8 Gy (10 patients) localized RT. The patients then were evaluated with an extensive battery of psychometric tests at baseline (before RT) and at approximately 18-month intervals for as long as 5 years after completing RT. To allow patients to serve as their own controls, cognitive performance was evaluated as change in scores over time. All patients underwent at least two evaluations. Results: Baseline test scores were below average compared with age-specific norms. At the second evaluation, the groups' mean test scores were higher than their initial performances on all psychometric measures, although the improvement was not statistically significant. No changes in cognitive performance were seen during the evaluation period when test scores were analyzed by age, treatment, tumor location, tumor type, or extent of resection. Conclusions: Cognitive function was stable after RT in these patients evaluated prospectively during 3 years of follow-up. Slight improvements in some cognitive areas are consistent with practice effects attributable to increased familiarity with test procedures and content.

A historical prospective cohort study of carotid artery stenosis after radiotherapy for head and neck malignancies.

Abstract: Purpose: To determine carotid artery stenosis incidence after radiotherapy for head-and-neck neoplasms. Methods and Materials: This historical prospective cohort study comprised 44 head-and-neck cancer survivors who received unilateral neck radiotherapy between 1974 and 1999. They underwent bilateral carotid duplex ultrasonography to detect carotid artery stenosis. Results: The incidence of significant carotid stenosis (8 of 44 [18%]) in the irradiated neck was higher than that in the contralateral unirradiated neck (3 of 44 [7%]), although this difference was not statistically significant (p = 0.13). The rate of significant carotid stenosis events increased as the time after radiotherapy increased. The risk of ipsilateral carotid artery stenosis was higher in patients who had undergone a neck dissection vs. those who had not. Patients with significant ipsilateral stenosis also tended to be older than those without significant stenosis. No other patient or treatment variables correlated with risk of carotid artery stenosis. Conclusions: For long-term survivors after neck dissection and irradiation, especially those who are symptomatic, ultrasonographic carotid artery screening should be considered.

Chromosomal imbalances detected by array comparative genomic hybridization in human oligodendrogliomas and mixed oligoastrocytomas.

Abstract: Loss of heterozygosity and fluorescence in situ hybridization (FISH) studies have shown that deletions of 1p and 19q are highly prevalent in oligodendroglioma. However, these tumors have not been comprehensively screened for other alterations in chromosomal dosage. In this study, we used array-based comparative genomic hybridization (CGHa) of mapped BAC DNA to screen for such alterations in 31 oligodendrogliomas (20 grade II, 9 grade III, and 2 grade IV) and 4 mixed oligoastrocytomas (1 grade I, 1 grade II, and 2 grade IV). The most frequent aberrations were loss of 1p (17 cases; 49%) and 19q (15 cases; 43%) and combined loss of 1p/19q (13 cases; 37%). In addition, deletion of 4q, 5p, 9p, 10q, 11p, and 13q was observed in 10, 4, 8, 4, 4, and 13 cases, respectively; loss of whole chromosomes 4, 9, and 13 in 4, 1, and 7 cases, respectively; gain of 7p, 8q, 10p, and 11q in 6, 6, 5, and 10 cases, respectively, and gain of whole chromosomes 7 and 11 in 2 patients each. Minimally altered regions detected by CGHa involved chromosome bands 1p36.32, 4q33, 5p15, 8q24, 11p15, and 19q13.3. Univariate analysis of all 35 cases suggested that combined deletion of 1p and 19q is associated with better survival (P = 0.03). In addition, 8q gain in the oligodendrogliomas was strongly associated with poor outcome (P = 0.002). Also associated with poor disease outcome were alterations that had low prevalence in the pure oligodendrogliomas, including loss of 3q, 9q, and 12q and gain of 1p, 8p, and 10q. In summary, in oligodendrogliomas, CGHa was able to detect novel small alterations in chromosomal dosage that had not been previously detected by other methods. In addition, our findings support the hypotheses that oligodendroglioma can be classified into several groups by CGHa analysis and that specific alterations in genetic dosage may have biologic or clinical significance.

Polymorphisms in GLTSCR1 and ERCC2 are associated with the development of oligodendrogliomas

Abstract: BACKGROUND Deletions of 19q have been associated with gliomas, especially oligodendrogliomas. In addition, cases with oligodendrogliomas with the 19q deletion have been observed to have a better survival compared with cases without the 19q deletion. The authors have previously described a 150-kilobase minimal deletion region in gliomas that maps to 19q13.33 and contains 3 novel candidate genes (GLTSCR1, EHD2, and GLTSCR2). METHODS The authors performed an association study using 141 cases with gliomas (61 cases with astrocytomas, 40 cases with oligodendrogliomas, 40 cases with mixed oligoastrocytomas) and 108 general controls. They evaluated 7 single nucleotide polymorphisms (SNPs) in 6 genes within and nearby the minimal 19q deletion region (ERCC2, RAI, ASE-1, ERCC1, GLTSCR1, and LIG1). RESULTS The prevalence of a germline GLTSCR1-exon-1 T allele (SNP rs1035938) was 40% in cases with oligodendrogliomas compared with 27% in controls (P = 0.029), and the prevalence of an ERCC2-exon-22 T allele (SNP rs1052555) was 35% in cases with oligodendrogliomas compared with 18% in controls (P = 0.043). One high-risk and 1 low-risk haplotype were associated with oligodendroglioma development (P = 0.003 and 0.026, respectively). Cases with oligodendrogliomas with the 19q deletion had a significantly higher frequency of the GLTSCR1-exon-1 T allele compared with cases without the 19q deletion (P = 0.01). It was noteworthy that cases with gliomas who were homozygous for the GLTSCR1-exon-1 T allele had a significantly better survival: 77% and 68% survival at 2 and 5 years compared with 56% and 34% for other genotypes (P = 0.02, log-rank test). Multivariable analysis identified grade, age, and the GLTSCR1-exon-1 and ERCC2-exon-22 genotypes as independent predictors for survival. CONCLUSIONS These results suggested that alterations in GLTSCR1 (or a closely linked gene) were associated with the development and progression of oligodendroglioma. Cancer 2005. © 2005 American Cancer Society.

Risk factor implications of incidentally discovered uncomplicated bundle branch block.

Abstract: OBJECTIVE To evaluate the long-term outcome of a community-based patient population with incidentally discovered asymptomatic and uncomplicated bundle branch block (BBB). PATIENTS AND METHODS A retrospective observational cohort study was undertaken of patients in Olmsted County, Minnesota, who were evaluated between 1975 and 1999 and were incidentally diagnosed as having BBB. We performed Kaplan-Meier analyses of all-cause mortality and development of first cardiac morbidity after the diagnosis of BBB, along with matched control group comparisons. RESULTS A total of 723 patients with left BBB (LBBB) (58.1%) and right BBB (41.9%) met criteria. Mortality was higher in patients with BBB compared with controls (absolute difference of approximately 10% over 20 years; hazard ratio=1.27; confidence interval, 1.02–1.58; P =.03) as was the development of first cardiac-related morbidity (hazard ratio=1.32; confidence interval, 1.14–1.54; P P =.02). However, comparable mortality was shown between patients with BBB who did not have these risk factors and matched control patients who had these risk factors. The risk of developing cardiac-related morbidity also was increased in the presence of BBB, particularly LBBB. CONCLUSIONS Uncomplicated asymptomatic BBB (notably LBBB) with normal left ventricular ejection fraction is not benign. Our findings indicate that the presence of isolated BBB denotes a high-risk patient subgroup that has a compromised long-term outcome comparable to patients with conventional cardiovascular risk factors.

Phase I trial of erlotinib with radiation therapy (RT) in patients with glioblastoma multiforme (GBM)

Abstract: 1513 Background: EGFR inhibitors may potentiate the therapeutic efficacy of RT in GBM patients. To evaluate the toxicity and maximum tolerated dose (MTD) of erlotinib plus RT in patients with GBM, we performed the following phase I trial. Methods: Patients were stratified based upon the use of enzyme-inducing anticonvulsants (EIACs). Patients with resected or biopsied GBM were treated with erlotinib for a week prior to concurrent erlotinib and 6 weeks (60 Gy) of RT and maintained on erlotinib until progression. The erlotinib dose was escalated in cohorts of 3 with a starting dose of 100mg/day. Intrapatient dose escalation was not allowed. Response was evaluated by MRI and clinical assessment of neurological status every two months. Results: 20 patients were enrolled; 19 are evaluable. There were 14 males/5 females, median age 54 years; 7 had undergone biopsy only/ 5 subtotal resections/ 7 gross total resections. Current dose level is 150mg/day erlotinib for patients not on EIACs (group 1) and 200mg/day fo...

NCCTG 94–72-53: Diagnostic and prognostic significance of 1p and 19q deletions in patients (pts) with low-grade oligodendroglioma and astrocytoma

Abstract: 1502 Background: Tumor deletions of chromosomes 1p and 19q are associated with improved prognosis and responsiveness to chemotherapy in pts with anaplastic oligodendroglioma. Their significance in ...

NCCTG N047D: Relationship between phase II endpoints of 12 month overall survival and 6 month progression-free survival for glioblastoma multiforme (GBM) phase II trials

Abstract: 1508 Background: Common endpoints for GBM Phase II trials are 6 mo progression-free survival (PFS6) & 12 mo OS (OS12). OS12 can be accurately measured, but may be confounded with subsequent therapi...