Vincent C. Arena

The Brain Tumor Cooperative Group NIH Trial 87-01: A randomized comparison of surgery, external radiotherapy, and carmustine versus surgery, interstitial radiotherapy boost, external radiation therapy, and carmustine

OBJECTIVE The objective of the Brain Tumor Cooperative Group NIH Trial 87-01 trial was to investigate the effect of additional implanted radiation therapy in newly diagnosed patients with pathologically confirmed malignant gliomas. METHODS The study involved a randomized comparison of surgery, external beam radiotherapy, and carmustine (BCNU) versus surgery, external beam therapy, interstitial radiotherapy boost, and BCNU in newly diagnosed malignant gliomas. (125)I was chosen as best suited for this effort because it allowed preimplantation planning and postimplantation quality assurance review. Two hundred ninety-nine patients met the eligibility criteria and were randomized into the two arms of the study between December 1987 and April 1994. Follow-up continued for an additional 3 years. Twenty-nine patients were identified as having committed protocol violations and were excluded, resulting in 270 subjects in the Valid Study Group. One hundred thirty-seven patients received external beam radiation and BCNU, and 133 underwent the (125)I implantation plus external beam radiation and BCNU therapy. RESULTS The overall median survival for the Valid Study Group was 64.3 weeks. The median survival for patients receiving additional therapy of (125)I was 68.1 weeks, and median survival for those receiving only external beam radiation and BCNU was 58.8 weeks. The cumulative proportion surviving between the two treatment groups was not statistically significantly different (log-rank test, P = 0.101). As in other studies in the literature, age, Karnofsky score, and pathology were predictors of mortality. Additional analyses incorporating an adjustment for these prognostic variables, either in a stratified analysis or Cox proportional hazards model, did not result in statistically significant differences in the cumulative proportion of patients surviving between the two treatment groups. CONCLUSION We conclude that there is no long-term survival advantage of increased radiation dose with (125)I seeds in newly diagnosed glioma patients.

Survival of Patients with Well-Differentiated Astrocytomas Diagnosed in The Era of Computed Tomography

We report 25 verified cases of well-differentiated cerebral astrocytomas in adults treated between 1978 and 1988. All patients were diagnosed by computed tomographic (CT) scans, with 5 undergoing a craniotomy for debulking and 20 undergoing a biopsy alone. The median survival for the entire group was 8.2 years, the longest survival yet reported for a series of patients with these tumors. A review of the literature suggests that the longer survival observed in more recent series is the result of the earlier diagnosis of tumors afforded by modern brain imaging. Twenty of our patients presented with seizures in the absence of any other focal findings and would probably not have had a biopsy in the era before CT scans until their tumors had progressed. Only 8% of our patients had papilledema at the time of presentation, in contrast to almost half of the patients with low-grade astrocytomas reported before 1975, supporting the hypothesis that patients in the CT era are diagnosed earlier. None of our patients died from progressive low-grade disease. One patient died from a squamous cell cancer, and 7 died as a consequence of their tumors dedifferentiating into a more malignant astrocytoma or glioblastoma multiforme, with a median time of approximately 5 years after the diagnosis. Our findings, together with the available data in the literature, suggest that death from a focal low-grade astrocytoma, in the absence of malignant degeneration, may be a rare event. Consequently, future therapeutic efforts should be targeted at preventing dedifferentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment seeking for urinary incontinence in older adults.

Objective: To examine treatment seeking for urinary incontinence among older adults and to identify characteristics associated with treatment‐seeking behavior.

The Duration of Holter Monitoring in Patients With Syncope: Is 24 Hours Enough?

To determine the incremental yield of ambulatory monitoring in the evaluation of syncope, three serial 24-hour Holter recordings were obtained in a consecutive series of 95 patients with syncope, the cause of which was not explained by history, physical examination, or 12-lead electrocardiogram. The mean age of patients was 61 years and 41% were men. Major electrocardiographic abnormalities were found in 26 patients (27%), including unsustained ventricular tachycardia (19 patients), pauses of at least 2 seconds (8 patients), profound bradycardia (1 patient), and complete heart block (1 patient). The first 24-hour Holter recording had at least one major abnormality in 14 patients (15%) (95% confidence interval, 8.3% to 23.4%). Of the 81 patients without a major abnormality on the first Holter recording, the second Holter recording had major abnormalities in 9 (11%) (95% confidence interval, 5.1% to 20.0%). Of the 72 patients without a major abnormality on the first two Holter recordings, only 3 patients (4.2%) had a major abnormality on the third Holter recording (95% confidence interval, 0.8% to 11.7%). Four factors were significantly associated with an increased likelihood of a major abnormality on 72 hours of monitoring: age above 65 years (relative risk, 2.2), male gender (relative risk, 2.0), history of heart disease (relative risk, 2.2), and an initial nonsinus rhythm (relative risk, 3.5). These results suggest that 24 hours of Holter monitoring is not enough to identify all potentially important arrhythmias in patients with syncope. Monitoring may need to be extended to 48 hours if the first 24-hour Holter recording is normal.

Long-term prognosis of patients undergoing electrophysiologic studies for syncope of unknown origin

Long-term prognosis was determined in 70 patients with unexplained syncope who underwent electrophysiologic testing between April 1981 and April 1986. The electrophysiologic study had positive results in 37 patients--31 with ventricular tachycardia, 3 with supraventricular tachycardia and 3 with abnormal conduction. There was no significant difference in the 3-year actuarial recurrence rate between the positive and negative outcomes (32 vs 24%, respectively). At 3 years, patients with positive outcomes had higher rates of sudden death than patients with negative results (48 vs 9%, respectively, p less than 0.002). The 3-year total mortality rate was also markedly higher in patients with positive results than among those with negative outcomes (61 vs 15%, respectively, p less than 0.001). Multivariate analyses showed mortality to be independently associated with unsustained ventricular tachycardia on prolonged electrocardiographic monitoring. It was concluded that patients with electrophysiologically positive results had high rates of sudden death and total mortality that have not been previously well recognized.

Evaluation of housestaff physicians' preparation and interpretation of sputum Gram stains for community-acquired pneumonia

Objective:To evaluate the preparation and interpretation of sputum Gram stains by housestaff physicians in the assessment of patients with community-acquired pneumonia.Design:A prospective, multicenter study.Setting:Two university-affiliated hospitals in Pittsburgh.Patients:Ninety-nine cases of clinically and radiographically established pneumonia occurring in 97 patients.Diagnostic test assessment:Housestaff and microbiology personnel prepared a Gram stain for each case of pneumonia. Housestaff assessed the presence and identity of a predominant microbial organism on the slides they prepared. Two senior staff microbiologists, blinded to patient and preparer, evaluated all slides for preparation, sputum purulence, and identification of the predominant organism. Two reference standards were used to assess the sensitivity, specificity, and predictive values of housestaff’s Gram-stain interpretations: 1) senior staff microbiologists’ determinations of the microbes present using the slides without benefit of culture results, and 2) the etiologic agent derived from results of sputum culture, blood culture, or serology.Measurements and main results:Housestaff physicians completed a Gram stain in 58% of the pneumonia episodes. Gram stains were not made in 42% of cases, primarily because patients were unable to produce sputum. Fifteen percent of housestaff’s smears were judged inadequately prepared, compared with 3% for the laboratory personnel (p<0.01). Housestaff obtained purulent sputum samples significantly more often than did nursing personnel (58% versus 38%; p<0.01). Housestaff’s Gram stains were 90% sensitive for detecting pneumococcus, with a 50% falsepositive rate. The sensitivity of the Gram stain was less for identification of Haemophilus influenzaethan for identification of Streptococcus pneumoniae.A single antimicrobial agent was chosen as initial therapy for 50% of the patients in whom housestaff identified a predominant organism, compared with 30% in whom a predominant organism was not identified (p≤0.05).Conclusions:Although housestaff obtained purulent sputum samples more frequently than did nursing personnel, they made systematic errors in the preparation and interpretation of Gram-stained slides. Housestaff physicians should receive formal training in the preparation and interpretation of Gram stains; the specific defects elucidated in this study warrant special attention.

Cardiovascular Autonomic Neuropathy, HDL Cholesterol, and Smoking Correlate With Arterial Stiffness Markers Determined 18 Years Later in Type 1 Diabetes

OBJECTIVE To examine the relationship between cardiovascular autonomic neuropathy and pulse waveform analysis (PWA) measures of arterial stiffness in a childhood-onset type 1 diabetes population. RESEARCH DESIGN AND METHODS Cardiac autonomic nerve function was measured in the baseline examination of the Pittsburgh Epidemiology of Diabetes Complications Study of childhood-onset type 1 diabetes by heart rate variability (R-R interval) during deep breathing and expressed as expiration-to-inspiration (E/I) ratio. Other cardiovascular and diabetes factors were also assessed. PWA was performed using SphgymoCor Px on 144 participants at the 18-year follow-up examination. Univariate and multivariate analyses for associations between baseline nerve function and other cardiovascular and diabetes-related factors were performed for augmentation index (AIx), augmentation pressure (AP), and subendocardial viability ratio (SEVR), a surrogate marker of myocardial perfusion. RESULTS E/I ratio correlated negatively with both AIx (r = −0.18, P = 0.03) and AP (r = −0.32, P < 0.001) and positively with SEVR (r = 0.47, P < 0.001) univariately. Lower baseline E/I ratio, HDL cholesterol, and a history of smoking were associated with higher follow-up (18 years later) AIx and AP and lower SEVR in multivariate analyses. Higher baseline HbA1 was also associated with higher AP and lower SEVR multivariately. CONCLUSIONS Cardiovascular autonomic neuropathy is associated with increased arterial stiffness measures and decreased estimated myocardial perfusion in those with type 1 diabetes some 18 years later. This association persists after adjustment for potential confounders as well as for baseline HbA1, HDL cholesterol, and smoking history, which were also associated with these PWA measures.

Variation in the use of red blood cell transfusions. A study of four common medical and surgical conditions.

This study assessed variation in red cell transfusion practice among adult patients hospitalized with ulcer disease (ULCER), and those undergoing coronary artery bypass grafting (CABG), hip surgery (HIP), or total knee replacement (KNEE). The study design was a retrospective analysis of the 1989 MedisGroups Hospital Comparative Database, and the participants were adult patients presenting for their first admission with ULCER (N=4,664), CABG (N=6,812), HIP (N=4,131) or KNEE (N=3,042) in the MedisGroups Hospital Comparative Database. Outcome measures were whether a patient ws transfused, and the number of units transfused. Logistic regression was used to analyze the decision to transfuse, and linear regression to analyze the number of units transfused. In these analyses, patient characteristics, hospital characteristics, and unique hospital identity were used as independent variables. The percentage of patients transfused was ULCER 50%, CABG 81%, HIP 69%, and KNEE 51%. The range among hospitals in the percentage of patients transfused was ULCER 11% to 76%, CABG 51% to 100%, HIP 36% to 95%, and KNEE 9% to 97%. When only patient characteristics were entered in the linear regression analyses, the R2 values were ULCER 0.33, CABG 0.11, HIP 0.11, and KNEE 0.07. When hospital was added, the R2 increased to ULCER 0.38, CABG 0.29, HIP 0.19, and KNEE 0.20 (P < 0.0001 for the change for all analyses). The results of the logistic regression analyses of the probability of transfusion were similar. There is substantial interhospital variation in the proportion of patients transfused and number of units transfused in the four conditions studied. Patient demographic and clinical characteristics explain a substantial proportion of the variation in transfusion practices for ulcer patients, but little of the variation in the three surgical conditions.

A randomized trial of yogurt for prevention of antibiotic-associated diarrhea.

Antibiotic-associated diarrhea (AAD) is the most common adverse effect of antibiotic therapy. Our aim was to determine the effectiveness of a dietary supplement of yogurt for prevention of AAD. Two hundred two hospitalized patients receiving oral or intravenous antibiotics were randomized to receive or not receive a dietary yogurt supplement, consisting of 227 grams of commercial yogurt, and followed for 8 days. Mean age of the study group was 70 years and 43% were male. Compliance and 8-day follow-up were 85% and 91%, respectively. Patients receiving yogurt reported less frequent diarrhea (12% vs 24%; P = 0.04), and significantly less total diarrheal days (23 vs 60). The cumulative proportions of patients without diarrhea were significantly different (P = 0.02) between patients receiving and not receiving yogurt. For conclusion, dietary supplementation with yogurt is a simple, effective, and safe treatment that decreases the incidence and duration of AAD.

Measurement of cerebral blood flow during xenon inhalation as measured by the microspheres method.

Measurements of cerebral blood flow (CBF) were performed using the microsphere technique in non-human primates (baboons) to assess the effect of non-radioactive xenon gas inhalation on CBF. Blood flows in small tissue volumes (approximately 1 cm3) were directly measured before and during the inhalation of xenon/oxygen gas mixtures. The results of these studies demonstrated that when inhaled in relatively high concentrations, xenon gas does increase CBF, but the changes are more global than tissue-specific. The problems and limitations of such evaluations are discussed.