Edward L. Spitznagel

Changing Epidemiology of Small-Cell Lung Cancer in the United States Over the Last 30 Years: Analysis of the Surveillance, Epidemiologic, and End Results Database

PURPOSE Small-cell lung cancer (SCLC) is a histologic subtype of lung cancer with a distinct biology and clinical course. It has been observed that the incidence of SCLC has been decreasing over the last several years. METHODS We used the Surveillance, Epidemiologic, and End Results (SEER) database to determine the incidence of SCLC over the last 30 years. In addition, we sought to determine sex- and stage-based differences in the incidence and survival of SCLC among a proportion of reported cases of lung cancer over the last 30 years (1973 to 2002). Joinpoint analyses were applied to test the trends in annual percentage change for statistical significance. RESULTS The proportion of SCLC (among all lung cancer histologic types) decreased from 17.26% in 1986 to 12.95% in 2002. Of all patients with SCLC, the proportion of women with SCLC increased from 28% in 1973% to 50% in 2002. A modest but statistically significant improvement in 2- and 5-year survival was noted among both limited-stage SCLC and extensive-stage SCLC cohorts during the study period. CONCLUSION Our analysis indicates that the incidence of SCLC is decreasing in the United States, and only modest improvements have been seen in survival over the last 30 years. Possible explanations for the decreasing incidence include the decrease in the percentage of smokers and the change to low-tar filter cigarettes. Despite trends toward modest improvement in survival, the outcome remains very poor.

Taking chances: problem gamblers and mental health disorders--results from the St. Louis Epidemiologic Catchment Area Study.

OBJECTIVES This study determined prevalence estimates of problem gambling and relationships to other psychiatric and substance use disorders. METHODS In 1981, the Diagnostic Interview Schedule was used to collect epidemiological information on problem gambling and other disorders from 3004 adults in St. Louis, Mo. RESULTS The lifetime prevalence of pathological gambling was 0.9%; 46% of those surveyed gambled recreationally. Problem gamblers (those reporting at least one gambling-related problem) were 9.2% of the sample and were predominately White (69%), male (78.2%), and young than nongamblers. They were at increased risk for several psychiatric diagnoses, especially for antisocial personality disorder, alcoholism, and tobacco dependence. CONCLUSIONS Clinicians treating alcoholism and tobacco dependence may need to screen for problem gambling. Additional research in the context of increased gambling opportunities is needed.

Differential Prognostic Impact of Comorbidity

PURPOSE Cancer patients with concurrent comorbid conditions have worse outcomes than patients with no comorbidities. We hypothesized that the prognostic impact of comorbidities would be greatest for patients with cancers associated with a long natural history and least in patients with aggressive cancers. PATIENTS AND METHODS Using the Barnes-Jewish Hospital Oncology Data Services cancer registry, we grouped 11,558 patients with breast, lung, colon, or prostate cancer by morphologic stage at diagnosis and then determined the 1-year overall survival rate for each group. Overall, severity of comorbidity was assessed from chart review and classified into one of four groups: none, mild, moderate, or severe. The relative prognostic impact of comorbidity was measured by the hazard ratio and adjusted for the prognostic impact of age, race, and sex. RESULTS One-year overall survival rate ranged from 20% for 1,005 patients with distant spread of lung cancer to 98% for 3,325 patients with localized prostate cancer. Adjusted hazard ratio of moderate/severe comorbidity (relative to none/mild) ranged from 1.04 to 4.48. The correlation between overall survival rate and severity of comorbidity was statistically significant (r2 = 0.56; P < .001). The proportion of variance in outcome explained by comorbidity ranged from less than 1% to almost 9%, depending on tumor site and stage. CONCLUSION Concurrent comorbidities had the greatest prognostic impact among groups with the highest survival rate and the least impact in groups with the lowest survival rate. These findings can be used to help determine the role comorbidity information should play in studies of cancer outcomes.

Factors Associated with Excessive Postoperative Blood Loss and Hemostatic Transfusion Requirements: A Multivariate Analysis in Cardiac Surgical Patients

The purpose of this study was to prospectively evaluate whether heparin and protamine doses administered using a standardized protocol based on body weight and activated clotting time values are associated with either transfusion of hemostatic blood products (HBPs) or excessive postoperative bleeding.Analysis using 10 multiple logistic or linear regression models in 487 cardiac surgical patients included perioperative variables that may have an association with either transfusion of HBP and/or excessive postoperative chest tube drainage (CTD). Prolonged duration of cardiopulmonary bypass (CPB), lower pre-CPB heparin dose, lower core body temperature in the intensive care unit, combined procedures, older age, repeat procedures, a larger volume of salvaged red cells reinfused intraoperatively and abnormal laboratory coagulation results (prothrombin time, activated partial thromboplastin time, and platelet count) after CPB were associated with both transfusion of HBP and increased CTD. Female gender, lower total heparin dose, preoperative aspirin use and the number of HBPs administered intraoperatively were associated only with increased CTD, whereas a larger total protamine dose was associated only with perioperative transfusion of HBPs. Preoperative use of warfarin or heparin was not associated with excessive blood loss of perioperative transfusion of HBPs. In contrast to previous studies using bovine heparin, data from the present study do not support the use of reduced doses of porcine heparin during CPB. (Anesth Analg 1996;82:13-21)

The impact of heparin concentration and activated clotting time monitoring on blood conservation: A prospective, randomized evaluation in patients undergoing cardiac operation*

A whole blood hemostasis system (Hepcon) provides both activated clotting time and accurate whole blood heparin concentration measurements via an automated protamine titration method. This study was designed to prospectively evaluate the impact of heparin and protamine administration using this system on the incidence and treatment of bleeding after cardiopulmonary bypass. Two hundred fifty-four patients requiring cardiopulmonary bypass were enrolled in this prospective study over a 7-month period. Patients treated with antifibrinolytic agents (aprotinin, epsilon-aminocaproic or tranexamic acid) were excluded. Patients were randomly assigned to either a control (n = 127) or intervention (n = 127) group. For control patients, the anticoagulation protocol consisted of an initial fixed dose of 250 U/kg of heparin, and additional 5000 U heparin doses were administered if the activated clotting time was less than 480 seconds. Heparin was neutralized with an initial fixed dose of protamine (0.8 mg protamine per milligram total heparin). For the intervention group, an initial dose of heparin was based on an automated heparin dose-response assay. Additional heparin doses were administered if the heparin concentration was less than the reference concentration or for an activated clotting time less than 480 seconds. The protamine dose was based on the residual heparin concentration. Treatment of excessive bleeding after cardiopulmonary bypass was based on an algorithm using point-of-care testing with whole blood prothrombin time, activated partial thromboplastin time, heparinase activated clotting time, and platelet count. No differences between the two treatment groups were identified in reference to demographic factors, preoperative anticoagulant medications, preoperative coagulation data, number of reoperations, or combined procedures and duration of cardiopulmonary bypass. Indirect evidence for coagulation factor consumption was demonstrated in control patients by more prolonged whole blood prothrombin time and activated partial thromboplastin time values after cardiopulmonary bypass when compared with values obtained in the intervention group. Patients in the intervention cohort received greater doses of heparin (intervention: 612 +/- 147, control: 462 +/- 114 U/kg, p < 0.0001) and had lower protamine to heparin ratios (intervention: 0.70 +/- 0.64, control: 0.94 +/- 0.21, p = 0.0001) compared with control patients. Patients in the intervention cohort received significantly fewer platelet (intervention: 1.7 +/- 3.6 U, control: 3.7 +/- 6.7 U, p = 0.003), plasma (intervention: 0.4 +/- 1.3 U, control: 1.4 +/- 2.5 U, p = 0.0001), and cryoprecipitate units (intervention: 0.0 +/- 0.0 U, control: 0.2 +/- 1.2 U, p = 0.04) during the perioperative interval than control patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Packet classification using extended TCAMs

CAMs are the most popular practical method for implementing packet classification in high performance routers. Their principal drawbacks are high power consumption and inefficient representation of filters with port ranges. A recent paper [Narlikar, et al., 2003] showed how partitioned TCAMs could be used to implement IP route lookup with dramatically lower power consumption. We extend the ideas in [Narlikar, et al., 2003] to address the more challenging problem of general packet classification. We describe two extensions to the standard TCAM architecture. The first organizes the TCAM as a two level hierarchy in which an index block is used to enable/disable the querying of the main storage blocks. The second incorporates circuits for range comparisons directly within the TCAM memory array. Extended TCAMs can deliver high performance (100 million lookups per second) for large filter sets (100,000 filters), while reducing power consumption by a factor of ten and improving space efficiency by a factor of three.

Soy consumption and prostate cancer risk in men: a revisit of a meta-analysis

BACKGROUND Epidemiologic studies have shown that the consumption of soy foods may be associated with a reduction in cancer risk in humans. OBJECTIVE The purpose of this study was to conduct a meta-analysis on the association between soy consumption and prostate cancer risk in men. DESIGN We systematically reviewed studies obtained through a thorough Medline literature search and identified 15 epidemiologic publications on soy consumption and 9 on isoflavones in association with prostate cancer risk. We extracted the most adjusted relative risks (RRs) and odds ratios (ORs) of the highest and the lowest reported categories of intake from each study and conducted this analysis using a random-effects model in which studies with smaller SEEs are given greater weight in the summary measure. RESULTS Our analysis of studies on soy intake yielded a combined RR/OR of 0.74 (95% CI: 0.63, 0.89; P = 0.01). When separately analyzed, studies on nonfermented soy foods yielded a combined RR/OR of 0.70 (95% CI: 0.56, 0.88; P = 0.01) and those on fermented soy foods yielded a combined RR/OR of 1.02 (95% CI: 0.73, 1.42; P = 0.92). The analysis of studies on isoflavones yielded a combined RR/OR of 0.88 (95% CI: 0.76, 1.02; P = 0.09). Further separate analyses showed a combined RR/OR of 0.52 (95% CI: 0.34, 0.81; P = 0.01) from studies with Asian populations and 0.99 (95% CI: 0.85, 1.16; P = 0.91) from studies with Western populations. CONCLUSIONS The results of this analysis suggest that consumption of soy foods is associated with a reduction in prostate cancer risk in men. This protection may be associated with the type and quantity of soy foods consumed.

COMPARISON OF ACTIVATED COAGULATION TIME AND WHOLE BLOOD HEPARIN MEASUREMENTS WITH LABORATORY PLASMA ANTI-XA HEPARIN CONCENTRATION IN PATIENTS HAVING CARDIAC OPERATIONS

Previous reports suggest that activated clotting times do not correlate with heparin concentration during cardiopulmonary bypass. This study was designed to compare whole blood heparin concentration and activated clotting time measurements with laboratory-based plasma heparin concentration. Sixty-two patients having cardiac operations requiring cardiopulmonary bypass were enrolled in this study. The study was conducted in two phases. In phase I of this trial, blood specimens were obtained from 30 patients before heparin administration and after each of three heparin doses (20, 80, and 150 U/kg). In phase II, blood specimens were obtained from 32 patients before heparin administration and 10 minutes after each of the following: heparin administration (250 or 300 U/kg), initiation of cardiopulmonary bypass, achievement of hypothermia, initiation of rewarming, and immediately before discontinuation of bypass. Blood specimens were used to measure activated clotting time (kaolin and celite), whole blood heparin concentration, and anti-factor Xa plasma heparin concentration. In phase I, activated clotting time (celite: r = 0.91; kaolin: r = 0.93) and whole blood heparin concentration (r = 0.98) measurements correlated well with plasma heparin concentration. After initiation of cardiopulmonary bypass (phase II), weak correlations for activated clotting time measurements (celite: r = 0.34; kaolin: r = 0.59) and a strong correlation for whole blood heparin concentration (r = 0.95) were evident when compared with plasma heparin concentration. During bypass, activated clotting time measurements also inversely correlated with temperature (celite: r = -0.21; kaolin: r = -0.19) and hematocrit (celite: r = -0.26; kaolin: r = -0.21). A weak correlation between activated clotting time measurements and plasma heparin concentration is evident during the cardiopulmonary bypass period, probably because of the influence of both reduced hematocrit and temperature on the activated clotting time assay. In contrast, whole blood heparin measurements correlate well with plasma heparin concentration before and during bypass. Further studies are needed to determine whether maintaining heparin levels during cardiopulmonary bypass by monitoring heparin concentration is more effective in preventing consumptive activation of the hemostatic system, reducing bleeding, and minimizing the use of blood products after cardiopulmonary bypass when compared with a protocol based on activated clotting time.

Preschool Depression: Homotypic Continuity and Course Over 24 Months

CONTEXT Childhood depression is a serious and relapsing psychiatric disorder. However, to date studies have focused mostly on children aged 6 years and older. Validation for depression in preschool children has been provided by 2 independent study samples. While several studies have demonstrated stability and poor outcomes of internalizing symptoms in preschoolers, there has not yet been longitudinal data available to inform the course of preschool depression and whether it shows homotypic continuity into early childhood. OBJECTIVE To examine the 24-month course of preschool depression and whether it showed homotypic vs heterotypic continuity or was a developmentally transient phenomenon. DESIGN Blindly rated, prospective, 24-month, longitudinal follow-up study. SETTING Community sites. Patients Three hundred six preschoolers aged 3 to 6 years recruited from community sites and oversampled for symptoms of depression. Main Outcome Measure Recurrence/stability of depression and predictors of course. RESULTS Preschoolers with depression at baseline had the highest likelihood of subsequent depression 12 and/or 24 months later compared with preschoolers with no baseline disorder and with those who had other psychiatric disorders. Preschoolers with depression at baseline were more likely to have later depression rather than other psychiatric disorders. Findings from a logistic regression analysis indicated that when controlling for demographic variables, risk factors, and comorbid disorders, depression during the preschool period and family history of affective disorders were the most robust and significant predictors of later depression. CONCLUSIONS Preschool depression, similar to childhood depression, is not a developmentally transient syndrome but rather shows chronicity and/or recurrence. Homotypic continuity of preschool MDD during a 24-month period was found. These results underscore the clinical and public health importance of identification of depression as early as preschool. Further follow-up of preschoolers with depression is warranted to inform the longitudinal course throughout childhood.

The Course of Ptsd, Major Depression, Substance Abuse, and Somatization After a Natural Disaster

Flood research has used a variety of methods, yielding inconsistent findings. Universal definitions of illness are paramount to the science of psychiatric epidemiology of disasters. St. Louis area survivors (N = 162) of the Great Midwestern Floods of 1993 received a structured diagnostic assessment at 4 and 16 months postdisaster, with 88% follow-up. The purpose of the assessment was to examine predisaster and postdisaster rates of disorders and symptoms. Flood-related posttraumatic stress disorder was diagnosed in 22% and 16% at index and follow-up, respectively. Comorbidity with major depression determined whether the posttraumatic stress disorder would have remitted by 1 year later. Nearly one half of the men in the sample had a pre-existing alcohol use disorder. Virtually no new substance abuse followed the floods, and hence, substance abuse did not develop in response to the disaster or as part of coping with its aftermath. Somatization disorder was not observed; new somatoform symptoms represented a fraction of postflood somatic complaints. Findings are inconsistent with causal attribution of floods in the etiology of alcohol abuse and somatization. Methodological differences may account for much of the apparent discrepancy of these findings, with recent reports of increased alcohol use and somatic symptoms observed after other disasters.