Effect of serial infusions of reconstituted high-density lipoprotein (CER-001) on coronary atherosclerosis: rationale and design of the CARAT study.

BACKGROUND: High-density lipoprotein (HDL) is believed to have atheroprotective properties, but an effective HDL-based therapy remains elusive. Early studies have suggested that infusion of reconstituted HDL promotes reverse cholesterol transport and vascular reactivity. The CER-001 Atherosclerosis Regression Acute Coronary Syndrome Trial (CARAT) is investigating the impact of infusing an engineered pre-beta HDL mimetic containing sphingomyelin (SM) and dipalmitoyl phosphatidlyglycerol (CER-001) on coronary atheroma volume in patients with a recent acute coronary syndrome (ACS). METHODS: The CARAT is a phase 2, multicenter trial in which 292 patients with an ACS undergoing intracoronary ultrasonography and showing percent atheroma volume (PAV) greater than 30% are randomly assigned to treatment with ten infusions of CER-001 3 mg/kg or matching placebo, administered at weekly intervals. Intracoronary ultrasonography is repeated at the end of the treatment period. RESULTS: The primary endpoint is the nominal change in PAV. Safety and tolerability will also be evaluated. CONCLUSIONS: CARAT will establish whether serial 3 mg/kg infusions of an engineered pre-beta HDL mimetic containing SM and dipalmitoyl phosphatidlyglycerol (CER-001) will regress atherosclerotic plaque in patients with a recent ACS.

Evaluation of a Teleform-based data collection system: a multi-center obesity research case study.

Utilizing electronic data capture (EDC) systems in data collection and management allows automated validation programs to preemptively identify and correct data errors. For our multi-center, prospective study we chose to use TeleForm, a paper-based data capture software that uses recognition technology to create case report forms (CRFs) with similar functionality to EDC, including custom scripts to identify entry errors. We quantified the accuracy of the optimized system through a data audit of CRFs and the study database, examining selected critical variables for all subjects in the study, as well as an audit of all variables for 25 randomly selected subjects. Overall we found 6.7 errors per 10,000 fields, with similar estimates for critical (6.9/10,000) and non-critical (6.5/10,000) variables-values that fall below the acceptable quality threshold of 50 errors per 10,000 established by the Society for Clinical Data Management. However, error rates were found to widely vary by type of data field, with the highest rate observed with open text fields.

Adolescent bariatric surgery program characteristics: the Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study experience.

The number of adolescents undergoing weight loss surgery (WLS) has increased in response to the increasing prevalence of severe childhood obesity. Adolescents undergoing WLS require unique support, which may differ from adult programs. The aim of this study was to describe institutional and programmatic characteristics of centers participating in Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS), a prospective study investigating safety and efficacy of adolescent WLS. Data were obtained from the Teen-LABS database, and site survey completed by Teen-LABS investigators. The survey queried (1) institutional characteristics, (2) multidisciplinary team composition, (3) clinical program characteristics, and (4) clinical research infrastructure. All centers had extensive multidisciplinary involvement in the assessment, pre-operative education, and post-operative management of adolescents undergoing WLS. Eligibility criteria and pre-operative clinical and diagnostic evaluations were similar between programs. All programs have well-developed clinical research infrastructure, use adolescent-specific educational resources, and maintain specialty equipment, including high weight capacity diagnostic imaging equipment. The composition of clinical team and institutional resources is consistent with current clinical practice guidelines. These characteristics, coupled with dedicated research staff, have facilitated enrollment of 242 participants into Teen-LABS.

Overexpression of aminoacylase 1 is associated with colorectal cancer progression.

Aminoacylase 1 (ACY1) is a cytosolic enzyme responsible for amino acid deacylation during intracellular protein degradation. ACY1 has been implicated in a number of human tumor types. However, the exact role of ACY1 in tumor development remains elusive because it was found to be lost in small cell lung cancer and renal cell carcinoma but overexpressed in colorectal cancer (CRC). The present study aims to further clarify the relationship of ACY1 with CRC progression. Immunohistochemical staining was performed in tissue microarrays composed of 120 cases of CRC using a monoclonal anti-ACY1 antibody. Immunoreactivity was analyzed in association with patients' clinicopathologic parameters and survival time. The role of ACY1 in cell proliferation and apoptosis was assessed by silencing its expression in HCT116 cells using a small interfering RNA. Strong expression of ACY1 was found to be significantly associated with more advanced TNM stage, lymph node metastasis, positive vascular invasion, and shorter cancer-specific survival. ACY1 knockdown significantly inhibited cell proliferation and induced apoptosis. We concluded that ACY1 expression in CRC varies with stage and appears to play a role in cell proliferation and apoptosis. Further evaluation of ACY1 as a clinically useful prognostic marker and a potential drug target for CRC would seem worthwhile.

TUFM is a potential new prognostic indicator for colorectal carcinoma.

AIMS: Mitochondrial Tu translation elongation factor (TUFM) is a nuclear encoded protein that participates in mitochondrial polypeptide translation. TUFM has been reported to be over-expressed in many tumour types including colorectal carcinoma (CRC) by proteomics. The present study aims to examine the prognostic implication of TUFM in CRC. METHODS: Immunohistochemical staining was performed in tissue microarrays composed of 123 cases of CRC using a polyclonal anti-TUFM antibody. Immunoreactivity was quantified using Image-Pro plus software, and analysed in association with patients' clinicopathological parameters and survival time. RESULTS: The immunoreactivity of TUFM was negative in 25%, weak in 50% and strong in 25% of CRC cases. TUFM immunoreactivity had no significant association with the clinicopathological parameters examined including TNM stage and grade. However, strong TUFM expression significantly correlated with a higher 5-year recurrence rate (p = 0.024). Kaplan-Meier analysis revealed that patients with strong TUFM expression had significantly shorter cancer-specific survival than patients with negative TUFM (log-rank test, p = 0.038). In multivariate analysis, strong TUFM expression remained a stage-independent unfavourable prognostic indicator (p = 0.024). CONCLUSIONS: Increased expression of TUFM is a promising new prognostic indicator for CRC. Selective inhibition of TUFM in tumour cells may present a new avenue for the targeted therapy of this cancer.

Transforming care at the bedside: an ambulatory model for improving the patient experience.

Transforming Care at the Bedside is a nationwide effort to design a model for improving care to hospitalized patients. With the projected growth of ambulatory services, it is increasingly important to focus on potential methods to increase patient satisfaction and care delivery improvement in the outpatient setting, as well. The authors describe the University of Pittsburgh Medical Center Hillman Cancer Center's adaptation of the Transforming Care at the Bedside care delivery improvement model to its ambulatory services arena and its promising results.

Incidence of seizures in the acute phase of stroke: a population-based study.

PURPOSE: The incidence of seizures within 24 h of acute stroke has not been studied extensively. We aimed to establish the incidence of acute poststroke seizures in a biracial cohort and to determine whether acute seizure occurrence differs by race/ethnicity, stroke subtype, and/or stroke localization. METHODS: We identified all stroke cases between July 1993 and June 1994 and in 1999 within the population of the Greater Cincinnati metropolitan region. Patients with a prior history of seizures/epilepsy were excluded from analysis. RESULTS: A total of 6044 strokes without a history of seizure(s) were identified; 190 (3.1%) had seizures within the first 24 h of stroke onset. Of ICH/SAH patients, 8.4% had a seizure within the first 24 h of stroke onset (p or=1. Race/ethnicity or localization of the ischemic stroke did not influence the risk for seizure development in the studied population. DISCUSSION: The overall incidence of acute seizures after stroke was 3.1%, with a higher incidence seen in hemorrhagic stroke, younger patients, and those presenting with higher prestroke Rankin scores. Acute seizures were associated with a higher mortality at 30 days after stroke.

Temporal trends in the incidence and case fatality of stroke in children and adolescents.

A recent study reported that mortality from stroke in children and adolescents decreased by 58% from 1979 to 1998, although it wasn't clear if the case fatality or the incidence of stroke in this age group is decreasing. We report trends of stroke incidence and case fatality in children and adolescents within a large biracial population. The study involved collection of all strokes in the study population between January 1, 1988 and December 31, 1989, July 1, 1993 and June 30, 1994, and January 1, 1999 and December 31, 1999, at all of the regional hospitals serving the Greater Cincinnati/Northern Kentucky population (only the children's hospital in 1988). Study nurses reviewed the medical records of all inpatients with stroke-related discharge diagnoses and abstracted relevant data. A study physician reviewed each abstract to determine whether a stroke or transient ischemic attack had occurred. A total of 54 strokes occurred in children or adolescents younger than 20 years during the three study periods (30% African American, 70% Caucasian, and 56% female). The overall incidence rate of all strokes in children younger than 15 years was 6.4/100,000 in 1999, a nonsignificant increase when compared to 1988. The 30-day case-fatality rates were 18% in 1988-1989, 9% in 1993-1994, and 9% in 1999. We found that the incidence of strokes in children has been stable over the past 10 years. The previously reported nationwide decrease in overall stroke mortality in children might be due to decreasing case fatality after stroke and not decreasing stroke incidence. Based on our data, we conservatively estimated that approximately 3000 children less than 20 years old would have a stroke in the United States in 2004.

Epidemiology of ischemic stroke in patients with diabetes: the greater Cincinnati/Northern Kentucky Stroke Study.

OBJECTIVE: Diabetes is a well known risk factor for stroke, but the impact of diabetes on stroke incidence rates is not known. This study uses a population-based study to describe the epidemiology of ischemic stroke in diabetic patients. RESEARCH DESIGN AND METHODS: Hospitalized cases were ascertained by ICD-9 discharge codes, prospective screening of emergency department admission logs, and review of coroner's cases. A sampling scheme was used to ascertain cases in the out-of-hospital setting. All potential cases underwent detailed chart abstraction by study nurses followed by physician review. Diabetes-specific incidence rates, case fatality rates, and population-attributable risks were estimated. RESULTS: Ischemic stroke patients with diabetes are younger, more likely to be African American, and more likely to have hypertension, myocardial infarction, and high cholesterol than nondiabetic patients. Age-specific incidence rates and rate ratios show that diabetes increases ischemic stroke incidence at all ages, but this risk is most prominent before age 55 in African Americans and before age 65 in whites. One-year case fatality rates after ischemic stroke are not different between those patients with and without diabetes. CONCLUSIONS: Given the "epidemic" of diabetes, with substantially increasing diabetes prevalence each year across all age- and race/ethnicity groups, the significance of diabetes as a risk factor for stroke is becoming more evident. Diabetes is clearly one of the most important risk factors for ischemic stroke, especially in those patients less than 65 years of age. We estimate that 37-42% of all ischemic strokes in both African Americans and whites are attributable to the effects of diabetes alone or in combination with hypertension.

Ischemic stroke subtypes: a population-based study of incidence rates among blacks and whites.

BACKGROUND AND PURPOSE: Blacks have an excess burden of stroke compared with whites; however, data comparing ischemic stroke subtypes among the 2 groups are limited and typically involve relative frequencies. The objective of this study is to compare the incidence rates of ischemic stroke subtypes between blacks and whites within a large, representative, biracial population. METHODS: The Greater Cincinnati/Northern Kentucky Stroke Study is designed to measure incidence rates and trends of all strokes within a well-defined, large, biracial population. Hospitalized cases were ascertained by International Classification of Disease (9th revision; ICD-9) discharge codes. Out-of-hospital events were ascertained by prospective screening of emergency department admission logs, review of coroners' cases, and monitoring all public health and hospital-based primary care clinics. A sampling scheme was used to ascertain events from nursing homes and all other primary care physician offices. All potential cases underwent detailed chart abstraction and confirmed by physician review. Based on all available clinical, laboratory, and radiographic information, ischemic stroke cases were subtyped into the following categories: cardioembolic, large-vessel, small-vessel, other, and stroke of undetermined cause. Race-specific incidence rates were calculated and compared after adjusting for age and gender, and standardizing to the 1990 US population. RESULTS: Between July 1, 1993, and June 30, 1994, 1956 first-ever ischemic strokes occurred among blacks and whites in the study population. Small-vessel strokes and strokes of undetermined cause were nearly twice as common among blacks. Large-vessel strokes were 40% more common among blacks than whites, and there was a trend toward cardioembolic strokes being more common among blacks. CONCLUSIONS: The excess burden of ischemic strokes among blacks compared with whites is not uniformly spread across the different subtypes. Large-vessel strokes are more common and cardioembolic stroke are as common among blacks, traditionally thought to be more common among whites.

Stroke in a biracial population: the excess burden of stroke among blacks.

BACKGROUND AND PURPOSE: Excess mortality resulting from stroke is an important reason why blacks have higher age-adjusted mortality rates than whites. This observation has 2 possible explanations: Strokes occur more commonly among blacks or blacks have higher mortality rates after stroke. Our population-based epidemiological study is set in the Greater Cincinnati/Northern Kentucky region of 1.31 million people, which is representative of the US white and black populations with regard to many demographic and socioeconomic characteristics. METHODS: Hospitalized cases were ascertained by International Classification of Diseases (ninth revision) discharge codes, prospective screening of emergency department admission logs, and review of coroner's cases. A sampling scheme was used to ascertain cases in the out-of-hospital setting. All potential cases underwent detailed chart abstraction by study nurses, followed by physician review. Race-specific incidence and case fatality rates were calculated. RESULTS: We identified 3136 strokes during the study period (January 1, 1993, to June 30, 1994). Stroke incidence rates were higher for blacks at every age, with the greatest risk (2- to 5-fold) seen in young and middle-aged blacks (<65 years of age). Case fatality rates did not differ significantly in blacks compared with whites. Applying the resulting age- and race-specific rates to the US population in 2002, we estimate that 705,000 to 740,000 strokes have occurred in the United States, with a minimum of 616,000 cerebral infarctions, 67,000 intracerebral hemorrhages, and 22,000 subarachnoid hemorrhages. CONCLUSIONS: Excess stroke-related mortality in blacks is due to higher stroke incidence rates, particularly in the young and middle-aged. This excess burden of stroke incidence among blacks represents one of the most serious public health problems facing the United States.

Eligibility for recombinant tissue plasminogen activator in acute ischemic stroke: a population-based study.

BACKGROUND AND PURPOSE: Acute ischemic stroke patients are infrequently treated with recombinant tissue plasminogen activator (rtPA). We present unique population-based data regarding the eligibility of ischemic stroke patients for rtPA treatment. METHODS: All ischemic strokes presenting to an emergency department (ED) within a biracial population of 1.3 million were identified. The patient was considered eligible for rtPA on the basis of exclusion criteria from the National Institute of Neurological Disorders and Stroke rtPA trial. RESULTS: Of 2308 ischemic strokes, 1849 presented to an ED. Only 22% of all ischemic strokes in the population arrived in the ED in <3 hours from symptom onset; of these, 209 (51%) were ineligible for rtPA on the basis of mild stroke severity, medical and surgical history, or blood tests. CONCLUSIONS: In our population in 1993 to 1994, 8% of all ischemic stroke patients presented to an ED within 3 hours and met other eligibility criteria for rtPA. Even if time were not an exclusion for rtPA, only 29% of all ischemic strokes in our population would have otherwise been eligible for rtPA.

Trends in community knowledge of the warning signs and risk factors for stroke.

CONTEXT: Poor public knowledge of stroke warning signs and risk factors limits effective stroke intervention and prevention. OBJECTIVE: To examine temporal trends in public knowledge of stroke warning signs and risk factors. DESIGN AND SETTING: Population-based random-digit telephone survey conducted in July-November 2000 among individuals in the greater Cincinnati, Ohio, region. PARTICIPANTS: A total of 2173 survey respondents (69% response rate) were randomly identified based on their demographic similarities to the ischemic stroke population with regard to age, race, and sex. MAIN OUTCOME MEASURES: Spontaneous recall of at least 1 important stroke warning sign and 1 established stroke risk factor in comparison with findings from the same survey in 1995. RESULTS: In 2000, 70% of respondents correctly named at least 1 established stroke warning sign vs 57% in 1995 (P<.001), and 72% correctly named at least 1 established stroke risk factor vs 68% in 1995. Groups of individuals with the highest risk and incidence of stroke, such as persons at least 75 years old, blacks, and men, were the least knowledgeable about warning signs and risk factors. Television was the most frequently cited source of knowledge, 32% in 2000 vs 24% in 1995 (P<.001). CONCLUSIONS: Public knowledge of stroke warning signs within the greater Cincinnati region has significantly improved from 1995 to 2000, although knowledge of stroke risk factors did not improve significantly during the same time period. Public education efforts must continue and should focus on groups at the highest risk of stroke.

The effect of race and gender on patterns of rt-PA use within a population.

To date, there have been no population-based data published regarding the influence of the patient's demographic factors on rt-PA use. We present preliminary data regarding the effect of race and gender on patterns of rt-PA use in the pre-FDA approval era, in a population with demographic and socioeconomic characteristics similar to the United States. All ischemic strokes within a biracial population of 1.3 million were identified by review of all primary and secondary hospital ICD-9-CM codes 430-438 from July 1993 to June 1994 at all hospitals in the region. The number of patients treated with rt-PA or placebo as part of the blinded NINDS rt-PA trial, as well as demographic characteristics, were recorded and analyzed. There were a total of 1973 hospitalized ischemic strokes that occurred at a hospital participating in the NINDS rt-PA trial. Patients that received rt-PA were significantly younger than those that did not (mean age 67 v 72, respectively, P = .01). Of the 413 strokes that occurred in African Americans, 2.2% were treated with rt-PA vs. 2.6% of the 1560 non-African Americans. Women (2.0%) and men (3.0%) were equally likely to receive rt-PA. The single academic center was as likely to give rt-PA as the community medical centers. In the Greater Cincinnati/Northern Kentucky population, patterns of rt-PA use in 1993-94 did not appear to vary according to race or gender, or type of medical center. These findings may be in part because of the regionally-based method of stroke care delivery in the area.