The treatment of primary central nervous system lymphoma in 122 immunocompetent patients: a population-based study of successively treated cohorts from the British Colombia Cancer Agency

BACKGROUND: The objective of this study was to evaluate the clinical outcome of a population-based cohort of immunocompetent patients with primary central nervous system lymphoma (PCNSL) treated with 3 different strategies over 13 years. METHODS: One hundred twenty-two consecutive patients (median age, 66 years) with PCNSL were identified. Three treatment strategies were employed: 1) whole-brain irradiation with (from January, 1990, to June, 1991) or without (from April, 1995, to December, 1999) cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-type chemotherapy (n=50 patients); 2) combined-modality therapy, including 1 g/m2 methotrexate plus whole-brain irradiation (from July, 1991, to March, 1995; n=34 patients); and 3) 8 g/m2 methotrexate alone (from January, 2000, to March, 2003) with whole-brain irradiation reserved for those with progressive disease (n=38 patients). Treatment failure was defined as progressive disease, disease recurrence, death from toxicity or lymphoma, or toxicity that necessitated a change in primary treatment. RESULTS: The median failure-free survival was 7 months, and the median overall survival (OS) was 17 months. The median OS was similar in all 3 eras. In this population-based analysis, one-third of patients did not receive the treatment strategy of the era. Therefore, the data also were analyzed by treatment received. On multivariate analysis (including era of treatment), 3 factors-age > 60 years, lactate dehydrogenase > normal, and omission of methotrexate-were associated significantly with poorer OS (hazard ratio: 2.3, 2.2, and 2.3, respectively). CONCLUSIONS: Outcomes for a general population with PCNSL remained constant despite different treatment strategies over three eras. For the two-thirds of patients who could receive potentially curative treatment, age, lactate dehydrogenase level, and receipt of > or = 1 g/m2 methotrexate appeared to be important determinants of OS.     

Developing and evaluating a residents' curriculum

This study examines the impact of a Bright Futures-based curriculum designed to teach pediatric residents how to integrate health education principles into everyday clinical practice. A two-phase study was conducted to evaluate the curriculum using both quantitative and qualitative methods. To measure the curriculum's impact on residents' clinical performance, a pre- and post-objective structured clinical examination (OSCE) design was administered to 14 residents in two groups: a control group (n=8) and an intervention group (n=6). Performance scores improved in the intervention group from pre- to post-testing in three core curriculum concepts (there was no change in the control group); performance in a fourth concept improved in both groups; and for the remaining two concepts, there was no change among the intervention group but an improvement in scores among those in the control group. Residents in the intervention group reported the curriculum to be of high quality and low difficulty. This study demonstrated that the curriculum had a positive impact on a resident's perceptions of his or her practice one year after participating in the intervention. The data suggest that each of the modules can be taught, the content learned and the principles applied to one's clinical practice.     

Variation in outcomes in Veterans Affairs intensive care units with a computerized severity measure

OBJECTIVE: To quantify the variability in risk-adjusted mortality and length of stay of Veterans Affairs intensive care units using a computer-based severity of illness measure. DESIGN: Retrospective cohort study. SETTING: A stratified random sample of 34 intensive care units in 17 Veterans Affairs hospitals. PARTICIPANTS: A consecutive sample of 29,377 first intensive care unit admissions from February 1996 through July 1997. INTERVENTIONS: Standardized mortality ratio (observed/expected deaths) and observed minus expected length of stay (OMELOS) with 95% confidence intervals were estimated for each unit using a hierarchical logistic (standardized mortality ratio) or linear (OMELOS) regression model with Markov Chain Monte Carlo simulation. We adjusted for patient characteristics including age, admission diagnosis, comorbid disease, physiology at admission (from laboratory data), and transfer status. MEASUREMENTS AND MAIN RESULTS: Mortality across the intensive care units for the 12,088 surgical and 17,289 medical cases averaged 11% (range, 2-30%). Length of stay in the intensive care units averaged 4.0 days (range, mean unit length of stay 3.0-5.9). Standardized mortality ratio of the intensive care units varied from 0.62 to 1.27; the standardized mortality ratio and 95% confidence interval were <1 for four intensive care units and >1.0 for seven intensive care units. OMELOS of the intensive care units ranged from -0.89 to 1.34 days. In a random slope hierarchical model, variation in standardized mortality ratio among intensive care units was similar across the range of severity, whereas variation in length of stay increased with severity. Standardized mortality ratio was not associated with OMELOS (Pearson's r = .13). CONCLUSIONS: We identified intensive care units whose indicators for mortality and length of stay differ substantially using a conservative statistical approach with a severity adjustment model based on data available in computerized clinical databases. Computerized risk adjustment employing routinely available data may facilitate research on the utility of intensive care unit profiling and analysis of natural experiments to understand process and outcome links and quality efforts.     

Prekallikrein-Kallikrein conversion rate as a predictor of contrast material catastrophies

An in vitro is described that attempts to detect patients with a potential for adverse systemic reactions to contrast material. This test involves measuring the rate of conversion of prekallikrein to kallikrein under certain standard conditions. In a preliminary retrospective study, the test could be used to identify such patients with a sensitivity of 88%, a specificity of 82%, and a predictive value of 79%.     

Cerebrospinal fluid and serum markers of inflammation in autism

Systemic immune abnormalities have no known relevance to brain dysfunction in autism. In order to find evidence for neuroinflammation, we compared levels of sensitive indicators of immune activation: quinolinic acid, neopterin, and biopterin, as well as multiple cytokines and cytokine receptors, in cerebrospinal fluid and serum from children with autism, to control subjects with other neurologic disorders. In cerebrospinal fluid from 12 children with autism, quinolinic acid (P = 0.037) and neopterin (P = 0.003) were decreased, and biopterin (P = 0.040) was elevated, compared with control subjects. In sera from 35 persons with autism, among cytokines, only tumor necrosis factor receptor II was elevated compared with controls (P < 0.02). Decreased quinolinic acid and neopterin in cerebrospinal fluid are paradoxical and suggest dysmaturation of metabolic pathways and absence of concurrent infection, respectively, in autism. Alternatively, they may be produced by microglia but remain localized and not expressed in cerebrospinal fluid.     

Urine vascular endothelial growth factor-A is not a useful marker for endometriosis

OBJECTIVE: To determine whether urine VEGF is elevated in women with endometriosis. DESIGN: Prospective observational study. SETTING: Tertiary care government and private hospitals. PATIENT(S): During laparoscopy for pelvic pain or infertility, urine was collected and possible endometriosis lesions were excised. Of 62 women, 40 had histology-proven endometriosis and 22 had no histological proof of the disease. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Urine VEGF-A(121, 165) was measured and compared in women with and without biopsy-proven endometriosis. RESULT(S): Urine VEGF levels corrected for creatinine excretion were similar in women with (83.6 +/- 11.3 pg/mg Cr) and without (88.5 +/- 10.4 pg/mg Cr) endometriosis (P =.77). The frequency distribution of urine VEGF measurements for women with and without endometriosis was similar. No significant difference was noted in urine VEGF levels when comparing endometriosis stages or in those with endometriomas compared to controls. Urine VEGF did not vary significantly over the menstrual cycle or between groups by cycle phase. No cutoff point discriminated individuals with and without the condition. CONCLUSION(S): It is unlikely that urine VEGF-A(121, 165), as measured in this study, will be a useful non-invasive marker for endometriosis.