Phase II trial of daily oral etoposide in patients with advanced non-small cell lung cancer

Forty-six previously untreated patients with advanced non-small cell lung cancer (NSCLC) were entered into a Hoosier Oncology Group phase II trial of daily oral etoposide 50 mg/m²/d. The dose limiting toxicity was granulocytopenia. The non-hematologic toxicity was mild, with only 19% of patients developing Grade 3 or 4 leukopenia. Two partial responses of 10 and 16 weeks duration were seen in 43 evaluable patients, for an overall response rate of 4%. We conclude that daily oral etoposide has minimal activity in advanced NSCLC, and does not improve response rates over conventional 1–5 day intravenous etoposide administration.from the Hoosier Oncology Group, the Walther Cancer Institute, Indianapolis, IN; Department of Medicine, Indiana University, Indianapolis, IN, USADr. Einhorn is the Walther American Cancer Society Professor of Clinical Oncology.     

Zeitschriften

Ohne Zusammenfassung     

Outcomes of endovascular management of acute thoracic aortic emergencies in an academic level 1 trauma center

Background

Thoracic aortic emergencies account for 10% of thoracic-related admissions in the United States and remain associated with high morbidity and mortality rates. Open repair has declined owing to the emergence of thoracic endovascular aortic repair (TEVAR), but data on emergency TEVAR use for acute aortic pathology remain limited. We therefore reviewed our experience.

Methods

We retrospectively evaluated emergency descending thoracic aortic endovascular interventions performed at a single academic level 1 trauma center between January 2005 and August 2013 including all cases of traumatic aortic injury, ruptured descending thoracic aneurysm, penetrating atherosclerotic ulcer, aortoenteric fistula, and acute complicated type B dissection. Demographics, clinical data, and outcomes were extracted. Stepwise logistic regression was used to identify independent risk factors for death.

Results

During the study period, 51 patients underwent TEVAR; 22 cases (43.1%) were performed emergently (11 patients [50.0%] traumatic aortic injury; 4 [18.2%] ruptured descending thoracic aneurysm; 4 [18.2%] complicated type B dissection; 2 [9.1%] penetrating aortic ulcer; and 1 [4.5%] aortoenteric fistula). Overall, 72.7% (n = 16) were male with a mean age of 54.8 ± 15.9 years. Nineteen patients (86.4%) required only a single TEVAR procedure, whereas 2 (9.1%) required additional endovascular therapy, and 1 (4.5%) open thoracotomy. Four traumatic aortic injury patients required exploratory laparotomy for concomitant intra-abdominal injuries. During a mean hospital length of stay of 18.9 days (range, 1 to 76 days), 3 patients (13.6%) developed major complications. In-hospital mortality was 27.2%, consisting of 6 deaths from traumatic brain injury (1); exsanguination in the operating room before repair could be achieved (2); bowel ischemia (1) and multisystem organ failure (1); and family withdrawal of care (1). A stepwise logistic regression model identified 24-hour packed red blood cell requirements ≥4 units, admission mean arterial pressure <60 mm Hg, and 24-hour fresh frozen plasma to packed red blood cell (pRBC) ratio <1:1.5 as independent risk factors for death in this cohort. During a mean follow-up of 369 days (range, 35 to 957 days), no subsequent major complications or deaths occurred. All patients underwent serial computed tomographic angiography surveillance, and no device-related problems were identified during intermediate follow-up.

Conclusions

Thoracic aortic emergencies remain challenging. Our experience in a moderate-volume center supports the utilization of TEVAR in the acute setting. Twenty-four-hour pRBC requirements ≥4 units, admission mean arterial pressure <60 mm Hg, and 24 hour fresh frozen plasma to pRBC ratio <1:1.5 were independently associated with death.     

National prevalence survey of hospital-acquired infections in Czechoslovakia

A nationwide 1-day prevalence survey of a total of 12,260 patients in 23 hospitals across Czechoslovakia yielded 751 cases of hospital-acquired infection (HAI), a prevalence of 6.1%. Analysis of the data revealed that the prevalence of HAI amongst surgical patients was almost twice that amongst medical patients (8.2% vs. 4.4%). Persons aged over 60 on the urological and surgical wards were at highest risk of acquiring infection. The most frequent site of HAI was the urinary tract (25%), followed by surgical wounds (15%) and the upper respiratory tract (13%). Fifty per cent of infection in gynaecological patients occurred within 6 days of admission compared with 15% in urological patients, and a wide variation was seen in other specialties.     

Measures for evaluation of prognostic improvement under multivariate normality for nested and nonnested models

When comparing performances of two risk prediction models, several metrics exist to quantify prognostic improvement, including the change in the area under the Receiver Operating Characteristic curve, the Integrated Discrimination Improvement, the Net Reclassification Index at event rate, the change in Standardized Net Benefit, the change in Brier score, and the change in scaled Brier score. We explore the behavior and interrelationships between these metrics under multivariate normality in nested and nonnested model comparisons. We demonstrate that, within the framework of linear discriminant analysis, all six statistics are functions of squared Mahalanobis distance, a robust metric that properly measures discrimination by quantifying the separation between the risk scores of events and nonevents. These relationships are important for overall interpretability and clinical usefulness. Through simulation, we demonstrate that the performance of the theoretical estimators under normality is comparable or superior to empirical estimation methods typically used by investigators. In particular, the theoretical estimators for the Net Reclassification Index and the change in Standardized Net Benefit exhibit less variability in their estimates as compared to their empirically estimated counterparts. Finally, we explore how these metrics behave with potentially nonnormal data by applying these methods in a practical example based on the sex-specific cardiovascular disease risk models from the Framingham Heart Study. Our findings aim to give greater insight into the behavior of these measures and the connections existing among them and to provide additional estimation methods with less variability for the Net Reclassification Index and the change in Standardized Net Benefit.     

EEG reactivity correlates with neuropsychological test scores in Down's syndrome

Introduction – Down's syndrome patients express a neurodegenerative disorder and mental retardation. We studied the reactivity of EEG and its correlation with neuropsychological test score in Down's syndrome. Material and methods – We studied 32 patients with Down's syndrome and 31 controls for blocking of occipital EEG activity. The temporo-occipital EEG with eyes open (EO) was compared with resting EEG with eyes closed (EC), (EC/EO ratio). Results – Both Down patients and controls showed significant diminution of alpha, beta and theta activity and decrease of EEG frequency with EO. However, there was a significant impairment in Down patients in the EC/EO ratio in alpha band, compared to controls. The controls had no correlation of the alpha EC/EO ratio with age or gender. The Down patients showed a significant correlation of this variable with age which is in accordance with a gradually progressing disease. They had also significant correlations of the alpha EC/EO ratio and neuropsychological test scores which indicates that this ratio may be a more general measure of cerebral or hemispherical dysfunction than a mere impairment of visual activation. Down patients also showed significant differences in resting EEG variables, compared to the controls, even if the conventional EEG showed normal or mildly slowed dominant occipital rhythm in most of the patients. The correlation analysis between resting EEG and EC/EO ratio variables pointed out that they are relatively independent, representing different factors in the regulation of EEG. Conclusions – We believe that the alpha EC/EO ratio of EEG add a new domain in the assessment of cerebral dysfunction in Down's syndrome.