Multicenter Consortium Research Articles

A Multi-center Consortium Study of Competing Platforms for Intracranial Stereotactic Irradiation

A Multi-center Consortium Study of Competing Platforms for Intracranial Stereotactic Irradiation

Prevalence of Complicated Gastroesophageal Reflux Disease and Barrett's Esophagus Among Racial Groups in a Multi-Center Consortium

Prevalence of Complicated Gastroesophageal Reflux Disease and Barrett's Esophagus Among Racial Groups in a Multi-Center Consortium

170: Long-Term Outcome of Nonmyeloalative Allografting from HLA-Identical Sibling for Multiple Myeloma (MM)

Background: Allogeneic hematopoietic cell transplantation (HCT) following nonmyeloablative conditioning may be used with lower transplant-related mortality (TRM) in elderly patients (pts) and/or those with comorbidities. In this approach anti-tumor activity relies on graft-versus-tumor effects. Here we analyzed outcomes of nonmyeloablative allografts from HLA-identical sibling performed by a multicenter consortium in pts with multiple myeloma (MM) with a median follow up (FU) of 5 years(y). Patients: Between March 1998 and February 2007, 133 pts with stage II-III MM received alloHCT following 2 Gy TBI +/- fludarabine (48/133 pts). Median age was 52 (range 31–71) y. Forty-eight and 7 pts (36% and 5%) were older than 55 and 65 y, respectively, and 43% had HCT specific comorbidity scores >1. Median number of prior treatments was 1(range 1–6) and 44 pts (33%) received 2 or more lines of therapy. One hundred two pts (77%) received their allografts as consolidation following cytoreductive autografts (conditioning in 97% of pts: melphalan 200 mg/m2). Postgrafting immunosuppression was mycophenolate mofetil (MMF) and cyclosporine (n = 116, 87%) or tacrolimus (n = 17, 13%). At allografting 86 pts (65%) had chemoresponsive disease with 33 and 53 pts (25% and 40%) in complete (CR) and partial remission (PR), respectively, while 32 and 15 pts (24% and 11%) had chemorefractory and progressive disease respectively. Results: Median FU for surviving pts was 5(range 0.3–8.5)y. Fifty four(41%) and 12 pts (9%) had grade 2 to 4 and 3 to 4 acute graft-versus-host-disease (GVHD); 86 pts (65%) had extensive chronic GVHD. The overall response rate was 89%, with 73(55%) and 46(34%) pts achieving CR and PR, respectively. Median time to progression was 3.6 y. Median progression-free survival (PFS) was 2.7 y, and 5-y estimated PFS was 28%. Nonrelapse mortalities (NRM) at 100 days, 1 and 5 y were 1%, 13% and 24%. Median overall survival (OS) was reached after 6.2 y, and 5-y estimated OS was 54%. In the subset of 102 pts who received a tandem auto/allografts, the median time to progression was 4 y, median PFS was 3 y while median OS has not been reached. In this group estimated PFS and OS at 3 and 5-years were 69% and 40%, 80% and 55% respectively. Conclusion: Nonmyeloablative allografting, in particular as part of a planned tandem auto/allo HCT protocol, is a treatment option for MM pts with HLA identical siblings. Future studies are aimed at improving long-term disease control and reducing GVHD.

An evaluation of endoscopic indications and findings related to nonvariceal upper-GI hemorrhage in a large multicenter consortium

The majority of studies on upper-GI hemorrhage (UGIH) to date have been based on clinical experience at academic centers. There is limited information about patients with UGIH who are evaluated by endoscopy at nonacademic settings, which comprise the majority of endoscopic practices in the United States. The aims of this retrospective study were to use a large national endoscopy database to describe the population of patients who received an EGD for nonvariceal upper-GI hemorrhage at diverse clinical practice sites and to characterize their endoscopic diagnoses. Between 2000 and 2004, the Clinical Outcomes Research Initiative (CORI) database received endoscopic reports from 72 diverse practice sites in the United States. All adult patients who underwent an EGD during this period at a CORI site for the indications of hematemesis, melena, or "suspected upper-GI bleed" were identified. Variceal bleeding was excluded. The nonvariceal UGIH cohort was described, and this group's endoscopic findings were characterized by the prevalence, indication, and location of an EGD (inpatient vs outpatient). A repeat EGD within a 2-week period was also evaluated. A total of 243,427 EGDs were performed during the study period; 12,392 (4.9% of all EGDs) were performed for evaluation of hematemesis, melena, or "suspected" upper-GI bleed. Patients in this cohort were more likely to be older, men, and nonwhite compared with their nonbleeding counterparts. Melena was the most common indication for an EGD. The most common endoscopic finding was an ulcer (32.7%), followed by erosion (18.8%). A "normal" EGD was reported on 17.2% of EGDs. Among patients with ulcers, gastric ulcers were more common that duodenal ulcers (54.4% vs 37.1%), whereas clean-based ulcers comprised 52% of all ulcers. Ulcers and Mallory-Weiss tears were significantly more common on inpatient procedures. Ulcers identified on outpatient EGDs were more likely to be clean based. A repeat endoscopy was performed on 4% of the cohort within a 2-week follow-up period, hematemesis was the most common indication for a repeat EGD, and 24.3% of the cohort had a documented therapeutic intervention on their initial EGD. Among inpatients, 6.0% had a repeat EGD within two weeks for an UGIH indication compared with only 1.4% of outpatients (P < .0001). These results allow association of EGD findings with patient presentation. Furthermore, it allows us to characterize endoscopic findings in a particular patient population (those patients with UGIH) in clinical practice, outside of traditional academic medical centers. The CORI database is a valuable resource for characterizing the epidemiology of endoscopic findings and, in particular, patient populations and across diverse practice settings, thus, enabling the development of hypotheses for future studies.

Phase II study of mitoxantrone and ketoconazole for hormone‐refractory prostate cancer

Doxorubicin plus ketoconazole has exhibited significant activity in patients with advanced prostate cancer. However, overall and cardiac-specific toxicity was reported to be high. Mitoxantrone has activity similar to that of doxorubicin, is less cardiotoxic, and is widely used to treat prostate cancer. The current study sought to evaluate the toxicity and activity of mitoxantrone plus ketoconazole in a cohort of patients with hormone-refractory prostate cancer. Progression after medical or surgical castration and, for those patients receiving antiandrogens, progression after withdrawal was required, as was objective evidence of metastasis, castrate levels of testosterone, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and intact cardiac function. After enrollment onto a multicenter local consortium study, subjects were treated with mitoxantrone at a dose of 12 mg/m2 intravenously every 3 weeks plus continuous oral ketoconazole at a dose of 400 mg 3 times daily and ascorbic acid at a dose of 250 mg. Replacement doses of hydrocortisone were given. For 40 enrolled subjects, the median prostate-specific antigen and ECOG performance status were 68 and 1, respectively, 53% had Gleason scores of 8 to 10, and all had metastasis. Predominant Grade 3/4 toxicities were: neutropenia in 13%, neutropenic fever in 10%, and anemia in 13%. Of 37 evaluable patients, 8% achieved a complete remission (CR) and 62% achieved a partial remission (PR), for a CR plus PR rate of 70%. For soft tissue and bone disease, overall response rates were 13% and 8%, respectively. The median progression-free survival and overall survival were 10 months and 18 months, respectively. Mitoxantrone plus ketoconazole is well tolerated, is active in hormone-refractory prostate cancer, and should be studied further.

Endoscopic Therapy for Bleeding Peptic Ulcer: Practice Variation in a Multi-Center Consortium

Background: Peptic ulcer disease is a frequent cause of upper gastrointestinal bleeding (UGIB). The goals of this study were to describe the utilization of endoscopic therapies instituted on bleeding ulcers, and compare their success rates among diverse gastrointestinal practices (Community, VA/Military, Academic). Methods: The Clinical Outcomes Research Initiative (CORI) database received endoscopic reports from 72 diverse practice sites in the U.S. between 2000-2004; all adult patients who underwent EGD during this time period at a CORI site for the indications of hematemesis, melena or suspected UGIB were identified.

Bowel Preparation Results in a Multi-Center Consortium

Objective: Inadequate preparation of the bowel for colonoscopy can result in both missed pathological lesions, cancelled procedures and substantially increase the overall cost of colonoscopy because of repeat procedure. Cleansing quality is a critical factor in determining the quality, difficulty, speed and completeness of colonoscopy. The aim of the study was to assess prep quality by type as well as with respect to age and gender of the patients. Methods: We performed a retrospective analysis of the data gathered from CORI-National Endoscopic database from 2001 to June 30, 2005; the study included all patients (ages 18->80 yr) undergoing colonoscopy with prep results noted. Acceptable prep quality defined as excellent, good or fair adequate by the endoscopists, while unacceptable prep quality was noted as either fair exam compromised or poor. A total of 328,920 adults underwent colonoscopy, 160,759 (48.9%) females and 168,161 (51.1%) males. When assessing prep results stratified by gender, 95.6% of females had an acceptable prep while 94.6% of males did. For both genders, Fleets prep, Golytely and Visicol had between 93.5% and 96.6% acceptable preps. Overall, 95.3% of patients aged less than 65 had acceptable preps as compared to 94.7% of patients 65 or greater. We analyzed the data in the different age groups (starting from 18 years to >80 yrs) .It showed Visicol and Fleets prep were consistently the best preps among each age group. Fewer patients aged 65 or greater received Fleets as a prep (47.0%) than younger patients (56.3%). It is also interesting to note that overall there is a clear linear decrease in proportion with acceptable results with increasing age. Conclusions: The majority of patients undergoing colonoscopy prep have acceptable results (95%). Females and those under age 65 appear to be slightly more likely to have adequate preps for colonoscopy. Fleets prep, Golytely and Visicol all appear to provide preps superior to Mg Citrate and Fleets enemas. Results: Total Colonoscopies = 328,920. Tabled 1 Acceptable Unaccepteable Acceptable over age 65 Prep Used Fleets Prep 15,336 (96.1%) 6808 (4.0%) 95.9% Fleets Enema 544 (82.7%) 114 (17.3%) 79.5% Golytely 140,151 (94.0%) 8900 (6.0%) 93.8% Mg Citrate 798 (683.5%) 158 (16.5%) 85.4% Visicol 5892 (96.4%) 219 (3.6%) 95.4% Total 312,721 (95.1%) 16,199 (4.9%) 94.7% P < 0.0001 Open table in a new tab P < 0.0001

Prevalence of Esophageal Findings in Patients with Non-Cardiac Chest Pain (NCCP) - Among a Large Multi-Center Consortium

Background: Available data on the prevalence of esophageal findings in patients with NCCP are scarce and limited to one center experience. Aims: To determine the prevalence of esophageal findings in patients undergoing upper endoscopy for non-cardiac chest pain only as compared with those undergoing upper endoscopy for classic gastroesophageal reflux disease (GERD) symptoms only, using the national Clinical Outcomes Research Initiative (CORI) database. Methods: During the study period, the CORI database received endoscopic reports from a network of 76 community, university and VAMC practice sites.

Automated State Analyses: Proposed Applications to Neonatal Neurointensive Care

The two principal challenges of neonatal physiologic monitoring device are: (1) the development of computational strategies that consider the rudimentary forms of neonatal sleep state especially for preterm infants and (2) any physiologic monitoring device for clinical applications in a neonatal intensive care setting must be small, portable, and user-friendly. Our multicenter neonatal sleep consortium has acquired more than 1,100 multihour EEG-sleep recordings on over 370 neonates, ranging from 24 to 44 weeks gestation. Each recording was visually-scored for state, arousals, movements, and rapid eye movements, which were used as templates when applying spectral analyses. The authors have defined a brain dysmaturity index to represent functional brain reorganization as the prenate matures to a full-term age; delayed or accelerated physiologic behaviors have been described for the preterm cohort when compared to the full-term group at the same postmenstrual age. Seven EEG-sleep measures comprise this index: quiet sleep percentage, sleep cycle length, rapid eye movements, arousals, spectral beta EEG energies, spectral EEG correlations, and a spectral measure of respiratory regularity. Linear and nonlinear computational algorithms are being developed to automate the computation of the dysmaturity index and to identify new feature types that correlate with dysmaturity. Automated neonatal sleep monitoring system can potentially improve neonatal neurointensive care by facilitating analyses of pervasive neonatal brain disorders expressed primarily as altered sleep state organization, and help predict altered developmental trajectories of children at higher risk for neurologic sequelae.

Genetic factors in end-stage renal disease

Despite more aggressive treatment of diabetes, hypertension, and hyperlipidemia, the incidence and prevalence rates of end-stage renal disease (ESRD) continue to increase worldwide. The likelihood of developing chronic kidney disease in an individual is determined by interactions between genes and the environment. Familial clustering of nephropathy has repeatedly been observed in all population groups studied and for multiple etiologies of kidney disease. A three- to nine-fold greater risk of ESRD is observed in individuals with a family history of ESRD. Marked racial variation in the familial aggregation of kidney disease exists, with high rates in African American, Native American, and Hispanic American families. Disparate etiologies of nephropathy aggregate within African American families, as well. These data have led several investigators to search for genes linked to diabetic and other forms of nephropathy. Evidence for linkage to kidney disease has been detected and replicated at several loci on chromosomes 3q (types 1 and 2 diabetic nephropathy), 10q (diabetic and nondiabetic kidney disease), and 18q (type 2 diabetic nephropathy). Multicenter consortia are currently recruiting large numbers of multiplex diabetic families with index cases having nephropathy for linkage and association analyses. In addition, large-scale screening studies are underway, with the goals of better defining the overall prevalence of chronic kidney disease, as well as educating the population about risk factors for nephropathy, including family history. Given the overwhelming burden of kidney disease worldwide, it is imperative that we develop a clearer understanding of the pathogenesis of nephropathy so that individuals at risk can be identified and treated at earlier, potentially reversible, stages of their illness.

A multicenter in vivo proton-MRS study of HIV-associated dementia and its relationship to age

Differences in diagnostic criteria and methods have led to mixed results regarding the metabolite pattern of HIV-associated brain injury in relation to neurocognitive impairment. Therefore, a multicenter MRS consortium was formed to evaluate the neurometabolites in HIV patients with or without cognitive impairment. Proton magnetic resonance spectroscopy (MRS) at short-echo time (30 ms) was assessed in the frontal white matter, basal ganglia, and parietal cortex of 100 HIV patients [61 with AIDS dementia complex (ADC) and 39 neuroasymptomatic (NAS)] and 37 seronegative (SN) controls. Compared to SN, NAS had higher glial marker myoinositol-to-creatine ratio (MI/Cr) in the white matter (multivariate analyses, adjusted P=0.001), while ADC showed further increased MI/Cr in the white matter and basal ganglia (both P<0.001), and increased choline compounds (Cho)/Cr in white matter (P=0.04) and basal ganglia (P<0.001). Compared to NAS, ADC showed a reduction in the neuronal marker N-acetyl compound (NA)/Cr in the frontal white matter (P=0.007). CSF, but not plasma, viral load correlated with MI/Cr and Cho/Cr in white matter and NAA/Cr in parietal cortex. HIV infection and aging had additive effects on Cho/Cr and MI/Cr in the basal ganglia and white matter. The results suggest that glial activation occurs during the NAS stages of HIV infection, whereas further inflammatory activity in the basal ganglia and neuronal injury in the white matter is associated with the development of cognitive impairment. Aging may further exacerbate brain metabolites associated with inflammation in HIV patient and thereby increase the risk for cognitive impairment.

A decade of myeloablative hla-matched sibling marrow transplantation for children with severe sickle cell disease: outcomes and lessons learned from the Atlanta experience

Allogeneic BMT offers a cure to select patients with sickle cell disease (SCD), but the limited available long-term data and concerns about the risk-to-benefit ratio present dilemmas for families and clinicians. We report favorable outcomes in a large single institution experience with myeloablative matched sibling BMT for children with severe SCD between December 1993 and April 2003. Sixteen patients (12 male) with a median age 7.7 years (3.3–17.1) were transplanted for primary indications of CVA (n = 8), recurrent TIA (n = 1), recurrent ACS (n = 6), and frequent VOC pain (n = 1). Graft source was HLA-identical sibling marrow, with 9 HgbAS donors. Preparative regimen (BU 14 mg/kg, CTX 200 mg/kg, ATG 90 mg/kg) was well tolerated. Special measures included aggressive management of hypertension and hypomagnesemia, maintenance of Hgb 10–12 g/dl and platelets >50k, and prolonged antiepileptics while on CSA for GVHD prophylaxis. The initial 8 patients were treated on a multicenter consortium trial (Walters et al). With median follow-up 36 months (6–84), OS and DFS are 100% and there are no graft failures. Two patients have stable mixed chimerism (72 and 69% donor) with low HgbS (0 and 2.5%) and no clinical SCD. Median WBC engraftment was day 12.5 (10–21) and platelet engraftment day 31.5 (17–46). No patients experienced aGVHD. The two oldest patients had cGVHD related to medication non-compliance. Two of the 8 patients with prior CVA had serious CNS events, including seizure and hemorrhage on day 0 in a moya-moya patient and late progressive cerebrovascular disease in a patient with prior CVA. None had new clinical CVA. One patient (age 16.7 years) without prior CVA had a seizure attributed to “non-compliance rebound” with CSA. Infections included two episodes of Zoster, one early multiorganism bacteremia, and one late pneumococcal bacteremia. All patients have excellent functional status and attend school/college. These favorable outcomes have led our center to offer this transplant treatment as a standard-of-care with principles specific to SCD: 1)careful psychosocial screening and transplantation at a young age, 2)supportive measures to avoid CNS events, and 3) long-term follow-up with attention to infection and cerebrovascular disease that may relate to SCD rather than the BMT. In our experience, collaborative management with a comprehensive sickle cell program optimizes referral of appropriate patients, reduces peritransplant complications, and optimizes outcomes.

Genetic determinants of diabetic nephropathy: The family investigation of nephropathy and diabetes (FIND).

Diabetes mellitus is the leading cause of ESRD in the United States. Family-based studies and segregation analyses suggest that inherited factors play a major role in susceptibility to diabetic renal complications, including albuminuria and chronic kidney failure. The Family Investigation of Nephropathy and Diabetes (FIND) study is a multicenter consortium established by the National Institute of Diabetes, Digestive and Kidney Diseases to identify the gene(s) responsible for diabetic nephropathy. Eight participating centers will enroll nearly 10,000 individuals by September 2004. Two independent strategies to detect causative genes will be used. These include family-based linkage analyses in African-American, American-Indian, Mexican-American, and European-American families (predominantly affected and discordant relative pair analyses) and mapping by admixture linkage disequilibrium (MALD) in African and Mexican Americans. Cell lines are being created from participants, and a repository containing stored urine and serum samples has been developed. This paper describes the enrollment criteria and methods used in FIND to allow for the detection of gene(s) predisposing to diabetic nephropathy.

The effects of local review on informed consent documents from a multicenter clinical trials consortium

There is increasing controversy about the appropriate role of the local institutional review board in the review of multicenter clinical studies. We evaluated the effects of the local review process at 25 study sites on the consent forms from two studies of the Tuberculosis Trials Consortium, a multicenter trials group. Two independent reviewers classified all changes made in the centrally approved consent forms; a third reviewer evaluated those changes if the two initial reviewers disagreed. The median time to initial local approval was 104.5 days (range 31–346). There were no changes in the study protocols as a result of local review. Consent forms became longer and less readable after local review, with a mean increase in grade level of 0.9 (±0.9) reading grade levels ( p<0.001). A median of 46.5 changes (range 3–160) were made in the centrally approved forms. Most changes (85.2%) involved altering wording without affecting meaning. Errors were commonly introduced (11.2% of changes), and 33 of 50 (66%) locally approved consent forms contained at least one error in protocol presentation or a required consent form element. Local approval of two multicenter clinical trials was time-consuming and resulted in many changes in centrally approved consent forms. These changes frequently decreased readability and introduced errors.

Risk factors for dysplasia in patients with Barrett's esophagus (BE): results from a multicenter consortium.

Studies show Barrett's esophagus prevalence increases with age, while mean length of Barrett's esophagus is unchanged. Few data are available about the relationship between age and length on the development of dysplasia. Our aim was to assess age and length as risk factors for dysplasia. Consecutive patients with Barrett's esophagus were enrolled in a multicenter study establishing a tissue bank of Barrett's esophagus patients 1994 and 1998. Demographics, length of Barrett's esophagus (centimeters), and histology were recorded. Risk factors for dysplasia were assessed, including patient age, gender, and length of Barrett's esophagus. Statistical analysis was performed comparing prevalence of dysplasia (which included the presence of any carcinoma and high- or low-grade dysplasia) to age and length. In all, 309 patients were studied [278 (90%) male and 31 (10%) female]: 5 had adenocarcinoma of the esophagus, 11 had high-grade dysplasia, and 29 had low-grade dysplasia. Patients with Barrett's esophagus without dysplasia were younger than those with dysplasia [62 +/- 0.8 years vs 67 +/- 1.7 years (mean +/- SEM, P = 0.02)]. The risk of dysplasia increased by 3.3%/yr of age. Mean length of Barrett's esophagus in patients with Barrett's alone vs dysplasia was 4.0 +/- 0.2 cm vs 5.4 +/- 0.4 cm (P = 0.003). Patients with Barrett's esophagus length > or = 3 cm had a significantly greater prevalence of dysplasia compared to length < 3 cm (23% vs 9%, P = 0.0001). The risk of dysplasia increased by 14%/cm of increased length. Multivariate analysis showed age and length to be independent risk factors. In conclusions: prevalence of dysplasia is strongly associated with age and length of Barrett's esophagus. These preliminary results can be used to develop a strategy for screening/surveillance based on age and length of Barrett's epithelium.

Identification of neonatal hearing impairment: transient evoked otoacoustic emissions during the perinatal period.

1) To describe transient evoked otoacoustic emission (TEOAE) levels, noise levels and signal to noise ratios (SNRs) for a range of frequency bands in three groups of neonates who were tested as a part of the Identification of Neonatal Hearing Impairment multi-center consortium project. 2) To describe the relations between these TEOAE measurements and age, test environment, baby state, and test time. TEOAEs were measured in 4478 graduates of neonatal intensive care units (NICUs), 353 well babies with at least one risk indicator, and 2348 well babies without risk factors. TEOAE and noise levels were measured for frequency bands centered at 1.0, 1.5, 2.0, 3.0, and 4.0 kHz for a click stimulus level of 80 dB SPL. For those ears not meeting "passing" stopping criteria at 80 dB pSPL, a level of 86 dB pSPL was included. Measurement-based stopping rules were used such that a test did not terminate unless the response revealed a criterion SNR in four out of five frequency bands or no response occurred after a preset number of averages. Baby state, test environment, and other test factors were captured at the time of test. TEOAE levels, noise levels and SNRs were similar for NICU graduates, well babies with risk factors and well babies without risk factors. There were no consistent differences in response quality as a function of test environment, i.e., private room, unit, open crib, nonworking isolette, or working isolette. Noise level varied little across risk group, test environment, or infant state other than crying, suggesting that the primary source of noise in TEOAE measurements is infant noise. The most significant effect on response quality was center frequency. Responses were difficult to measure in the half-octave band centered at 1.0 kHz, compared with higher frequencies. Reliable responses were measured routinely at frequencies of 1.5 kHz and higher. TEOAEs are easily measured in both NICU graduates and well babies with and without risk factors for hearing loss in a wide variety of test environments. Given the difficulties encountered in making reliable measurements for a frequency band centered at 1.0 kHz, its inclusion in a screening program may not be justified.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part XI. Clinical milestones in patients with Alzheimer's disease followed over 3 years.

The rate of cognitive decline, measured by psychometric testing, is widely used to track the progression of Alzheimer's disease (AD). As an alternative approach, we studied clinical measures as markers of the progression of dementia in 343 community-dwelling patients with probable AD enrolled in the multi-center Consortium to Establish a Registry for Alzheimer's Disease (CERAD) project. Subjects received standardized evaluations at entry and at annual follow-up. Decline on the Clinical Dementia Rating, loss of instrumental activities of daily living, failure to recall three words on the Mini-Mental State Examination (MMSE), and decline of the total MMSE score to below 10 were high-risk milestones, with cumulative frequencies exceeding 50% at 3 years. Loss of dressing and toileting activities occurred at intermediate rates, while loss of eating ability was rare. The risk of reaching clinical milestones and the annual rate of cognitive decline on the MMSE were directly correlated. Clinical milestones are useful indices of the progression of dementia in patients with AD.

Multimedia Computer-Assisted Instruction in Cardiology

Medical education faces problems caused by increasing restraints on resources. A multicenter consortium combined simulation and multimedia computer-assisted instruction (MCAI) to develop unique interactive teaching programs that can address a number of these problems. We describe the consortium, the MCAI system, the programs, and a multicenter evaluation of technical and educational performance. The MCAI system uses computer-controlled access to full-screen, full-motion, and full-color laser disc video in combination with digitized sound, images, and graphics stored on removable media. The Socratic teaching method enhances interaction and guides learners through the patient's history, cardiovascular physical examination, laboratory evaluation, and therapy. Self-instruction and instructor-led modes of function are possible. The first five programs, based on simulations of specific cardiology problems, were distributed to four medical centers. Questionnaires evaluated technical function and medical student opinions, while behaviors and scores were automatically tracked and tabulated by program administration software. The MCAI system functioned reliably and accurately in all modes and at all sites. The programs were highly rated. Student ratings, scores, and behaviors were independent of institution and mode of use. A multicenter educational consortium developed a system to produce unique, sophisticated MCAI programs in cardiology. Both system and programs functioned reliably at four institutions and were highly rated by fourth-year medical students. With this enthusiastic reception, the economies and strengths associated with MCAI make it an attractive solution to a number of problem areas, and it will likely play an increasingly important role.

Cognitive deficits of men and women with Alzheimer's disease.

We performed two studies of cognitive abilities among men and women who met clinical criteria for Alzheimer's disease (AD). Among 46 AD patients, performance of women on a composite neuropsychological battery was more impaired than that of men when the potentially confounding effects of demographic variables were controlled; the largest group differences were due to significantly worse performance by women with AD on a naming task. Based on these initial findings, we next analyzed an independent data set of 647 demented subjects enrolled in the multicenter Consortium to Establish a Registry for Alzheimer's Disease, hypothesizing that the naming performance of women with AD would be significantly worse than that of men with this illness. Analyses controlling for demographic variables, or separately controlling for dementia severity, confirmed that women with AD performed significantly less well on the naming task and on verbal fluency. Women also performed less well on delayed recall, but there were no significant differences on other tasks. Factor analysis confirmed significant differences on a language factor, implying that men retain verbal skills better than women do during the initial stages of AD. Elderly nondemented women performed as well as or better than nondemented men on all comparisons. We conclude that there are modest differences in how men and women with AD perform on cognitive tasks and that differences may be discrete rather than global in nature.

Effects of Age, Gender, and Education on Cognitive Tests in a Rural Elderly Community Sample: Norms from the Monongahela Valley Independent Elders Survey

A random sample of 1,350 persons aged 65 years and older in a rural community underwent cognitive screening as part of a survey to establish a population-based registry of dementing disorders. The screening battery included the neuropsychological tests of the assessment protocol used in the National Institute on Aging multicenter Consortium to Establish a Registry for Alzheimer's Disease (CERAD). This paper reports a large body of normative neuropsychological data from this sample with members of relatively low socioeconomic status. Age, sex, and educational level were found to have statistically significant effects on test scores. The implications of these findings for the establishment of screening cutoff scores are discussed.