Activation of platelets by heparin-induced thrombocytopenia antibodies in the serotonin release assay is not dependent on the presence of heparin.

The serotonin release assay (SRA) tests for antibodies responsible for heparin-induced thrombocytopenia (HIT). By definition, SRA-positive antibodies cause platelet serotonin release in vitro, in the presence of low concentrations of heparin, but not with excess heparin. Many SRA-positive sera activate platelets in the presence of saline without drug, either as a result of residual heparin in the specimen, or because of intrinsic features of the HIT antibodies. The present experiments show that neither exhaustive heparinase treatment, nor chromatographic removal of heparin abrogates the spontaneous platelet activation caused by these HIT antibodies. This is the first study to systematically demonstrate that in vitro activity of HIT antibodies can be independent of heparin. In addition, T-gel chromatography demonstrated differences among fractions of enzyme-linked-immunosorbent assay (ELISA)-positive HIT antibodies within individual specimens. Certain ELISA-positive fractions had SRA activity while others did not, and the SRA activity was not proportional to HIT antibody ELISA titer. These data suggest that antibodies formed as a result of heparin treatment are heterogeneous, and that some can contribute to the pathogenesis of HIT even when heparin is no longer present.

Causes of death in elderly prostate cancer patients and in a comparison nonprostate cancer cohort.

BACKGROUND: Prostate cancer tends to affect older men and to progress relatively slowly. Since the prevalence of comorbidity increases with advancing age, competing causes of death are important contributors to death rates among prostate cancer patients. Accurate determination of the underlying causes of death in older men dying with prostate cancer may thus also be more difficult. METHODS: We compared the distribution of underlying causes of death in decedents from a population-based cohort of elderly prostate cancer patients to that from a population-based comparison cohort of elderly men without prostate cancer. Among decedents from the prostate cancer patient cohort, we examined associations of patient demographics, disease stage, and initial treatment, with assignment of a prostate cancer underlying cause of death (versus any other cause) by use of multivariable logistic regression. In the subgroup of prostate cancer patient decedents having underlying causes of death other than prostate cancer, the underlying cause distribution was compared with that in nonprostate cancer cohort decedents. RESULTS: Prostate cancer was the underlying cause for 39% (95% confidence interval [CI] = 36.3-41.9) of the decedents in the prostate cancer cohort. Causes of death among prostate cancer patients not dying of prostate cancer were similar to those among the nonprostate cancer cohort decedents. However, in those who were aggressively treated, the adjusted odds of other cancer causes of death were 51% higher (odds ratio [OR] = 1.51; 95% CI = 1.08-2.10) than that in nonprostate cancer patient decedents, while in those treated with watchful waiting the adjusted odds were 34% lower (OR = 0.66; 95% CI = 0.47-0.93). CONCLUSIONS: Initial treatment may influence the underlying cause of death reported in vital statistics for prostate cancer patients.

A sociodemographic and economic comparison of breast reconstruction, mastectomy, and conservative surgery.

BACKGROUND: There are a variety of surgical choices for women with early-stage breast cancer, including breast-conserving surgery, mastectomy, or mastectomy plus reconstructive surgery. This report examines some of the factors that affect these choices and the costs of the various treatment options. METHODS: Data from the Virginia Cancer Registry were linked to insurance claims from the Trigon Blue Cross and Blue Shield Company for women with local and regional staged breast cancer from 1989 to 1991 in Virginia. Multivariate analyses and cost studies were performed. RESULTS: There were 592 women who underwent breast-conserving surgery (BCS, 26%), mastectomy (58%), or mastectomy plus reconstruction (16%). Increasing age reduced the use of reconstruction. The choice of reconstruction was not affected by tumor size, nodal status, or race. Sixty percent of women had immediate breast reconstruction at the time of mastectomy; the majority had the implant procedure. The cost of BCS ($21,582) was higher than that of mastectomy ($16,122, P < .01). The costs for BCS and mastectomy were significantly lower than for mastectomy plus reconstruction ($31,047, P < .05). The 2-year cost for immediate reconstruction was $8200 less than for delayed procedures and was similar to the cost of BCS. CONCLUSIONS: Age was the driving force in reconstruction decisions. Clinical factors such as tumor size and nodal status were more important for the choice between BCS and mastectomy. There are significant cost differences between the various procedures. For a similar cosmetic outcome, BCS is less expensive than breast reconstruction. When reconstruction is required, a simultaneous procedure is less expensive.

Predictors of Medicare costs in elderly beneficiaries with breast, colorectal, lung, or prostate cancer.

BACKGROUND: Determining the apportionment of costs of cancer care and identifying factors that predict costs are important for planning ethical resource allocation for cancer care, especially in markets where managed care has grown. DESIGN: This study linked tumor registry data with Medicare administrative claims to determine the costs of care for breast, colorectal, lung and prostate cancers during the initial year subsequent to diagnosis, and to develop models to identify factors predicting costs. SUBJECTS: Patients with a diagnosis of breast (n = 1,952), colorectal (n = 2,563), lung (n = 3,331) or prostate cancer (n = 3,179) diagnosed from 1985 through 1988. RESULTS: The average costs during the initial treatment period were $12,141 (s.d. = $10,434) for breast cancer, $24,910 (s.d. = $14,870) for colorectal cancer, $21,351 (s.d. = $14,813) for lung cancer, and $14,361 (s.d. = $11,216) for prostate cancer. Using least squares regression analysis, factors significantly associated with cost included comorbidity, hospital length of stay, type of therapy, and ZIP level income for all four cancer sites. Access to health care resources was variably associated with costs of care. Total R2 ranged from 38% (prostate) to 49% (breast). The prediction error for the regression models ranged from < 1% to 4%, by cancer site. CONCLUSIONS: Linking administrative claims with state tumor registry data can accurately predict costs of cancer care during the first year subsequent to diagnosis for cancer patients. Regression models using both data sources may be useful to health plans and providers and in determining appropriate prospective reimbursement for cancer, particularly with increasing HMO penetration and decreased ability to capture complete and accurate utilization and cost data on this population.

A comparison of patterns of care of nonsmall cell lung carcinoma patients in a younger and Medigap commercially insured cohort.

BACKGROUND: The objective of this study was to examine and compare lifetime treatment patterns and hospitalization of incident nonsmall cell lung carcinoma (NSCLC) between pre-Medicare eligible (age < 65 years) and supplemental Medigap (age > or = 65 years) enrollees in a commercially insured cohort using insurance claims. METHODS: Claims from Virginia Blue Cross and Blue Shield beneficiaries with NSCLC submitted between 1989-1991 were merged with records from the Virginia Cancer Registry (VCR). Data from the VCR identified incident cases, disease stage, and type of tumor. Initial treatment categories were stratified using Physicians' Current Procedural Terminology codes. RESULTS: There were 1706 incident NSCLC patients; 349 were age < or = 64 years ("younger") and 1212 were age > or = 65 years ("elderly"). Having commercial insurance was not associated with any survival advantage compared with national averages at 2 years. In comparison with elderly patients, younger patients more often were treated with surgery for local disease (80.2% vs. 54.8%) and surgery alone or in combination with radiation for regional disease (51.9% vs. 32.0%). Radiation was used more often in elderly patients compared with younger patients with local disease (30.5% vs. 14.0%) but less often in patients with distant disease (76.2% vs. 54.9%). Compared with elderly patients, younger patients presenting with distant disease received more chemotherapy (18.8% vs. 5.1%; P <0.001); late palliative use of chemotherapy or radiation occurred in only 4-8% of younger patients. Compared with elderly patients, younger patients with regional or distant disease spent more days in the hospital (compared with national averages at 2 years: regional disease, 30.0 vs. 23.9 days; distant disease, 33.0 vs. 21.4 days; P <0.0001). CONCLUSIONS: The results of this study show that more comprehensive health insurance is not associated with better outcomes in patients with NSCLC. Age specific trends for greater use of surgery, radiation, and total hospitalization in younger patients is consistent with other reports. Commercial health care claims supplemented by clinical staging from cancer registries can address long term practice patterns in patients with cancer.

Costs of care associated with non-small-cell lung cancer in a commercially insured cohort.

PURPOSE: To examine the cost of incident cases of non-small-cell lung cancer (NSCLC) in a commercially insured cohort. METHODS: Claims from Virginia Blue Cross and Blue Shield (BCBS) beneficiaries with lung cancer from 1989 to 1991 were merged with records from the Virginia Cancer Registry (VCR). Data from the VCR identified incident cases, stage, and type of cancer at diagnosis. Costs for all medical care included insurance payment, copayments, and deductibles for 2 years after diagnosis or until death. RESULTS: Three hundred forty-nine incident NSCLC patients were evaluated. The mean 2-year cost for each patient after diagnosis or until death was $47,941 (95% confidence interval, $43,758 to $52,124). Total average costs and hospital days were significantly lower for local disease ($37,514, 21.2 days), but were similar for regional ($52,797, 30.0 days) and distant ($49,382, 33.0 days) disease. Hospital days accounted for 48% and hospital-based claims for 70% of costs. Initial treatments, which included radiation, unadjusted for stage, had the lowest survival rates and the highest costs, and were associated with the most hospital days. Initial stage, race, gender, and age were not predictors of total 2-year costs. The independent predictors of total 2-year costs were type of treatment: any radiation therapy, any surgery, or any chemotherapy (all, P < .001). Inpatient hospital days was only a modest predictor of costs after adjusting for type of treatment. Patients who survived less than 1 year spent 30.5 days in hospital and had an average cost of $47,280. CONCLUSION: The direct health care costs of younger NSCLC patients care are substantial. These results should serve as a benchmark for future comparisons as the United States market shifts to managed care.

Temperature-sensitive lesions in the Francisella novicida valA gene cloned into an Escherichia coli msbA lpxK mutant affecting deoxycholate resistance and lipopolysaccharide assembly at the restrictive temperature.

The valAB locus of Francisella novicida has previously been found to be highly similar at the deduced amino acid level to msbA lpxK of Escherichia coli. Both ValA and MsbA are members of the superfamily of ABC transporters, and they appear to have similar functions. In this study we describe the isolation of a temperature-sensitive valAB locus. DNA sequence analysis indicates that the only changes to the ValAB deduced amino acid sequence are changes of S453 to an F and T458 to an I in ValA. E. coli strains defective in msbA and expressing temperature-sensitive ValA rapidly ceased growth when shifted from a permissive temperature to a restrictive temperature. After 1 h at the restrictive temperature, cells were much more sensitive to deoxycholate treatment. To test the hypothesis that ValA is responsible for the transport or assembly of lipopolysaccharide, we introduced gseA, a Kdo (3-deoxy-D-manno-octulosonic acid) transferase from Chlamydia trachomatis, into a strain with a temperature-sensitive valA allele and a nonfunctional msbA locus. These recombinants were defective in cell surface expression of the chlamydial genus-specific epitope within 15 min of a shift to the nonpermissive temperature. Also, there was enhanced association of the epitope with the inner membrane after a shift to the nonpermissive temperature. Thus, we propose that ValA is involved in the transport of lipopolysaccharide to the outer membrane.

Measuring standards of care for early breast cancer in an insured population.

PURPOSE: To demonstrate the use of a combined data base to evaluate the care for local/regional invasive breast cancer in a large insured population of women aged less than 64 years. PATIENTS AND METHODS: We linked the procedural and hospital claims from Blue Cross Blue Shield (BCBS) of Virginia with clinical stage data from the Virginia Cancer Registry (VCR) from 1989 to 1991. A total of 918 women were assessed with a median age of 50 years; 68% had tumors less than 2 cm, 30% had positive axillary nodes, and 68% were assessed as having local summary stage. A quality-of-care "report card" was used based on standards of care from international Consensus Conferences. RESULTS: Eight percent had a mastectomy as the initial biopsy procedure. Sixty-nine percent of women ultimately underwent mastectomy. Of those women who underwent lumpectomy, 86% had subsequent radiation. Within 3 months of diagnosis, 43% had a bone scan and 20% a computed tomography (CT) scan. Of women with positive axillary lymph nodes, 83% aged less than 51 years and 52% aged 51 to 64 years received chemotherapy. Fifty-six percent of all women had claims from a medical oncologist. Of women having a total mastectomy, 27% had claims from a plastic surgeon. Sixty-six percent to 76% of women had a mammogram, 24% a bone scan, and 14% a CT scan in the 0-18 and 18-36 month intervals following primary treatment. CONCLUSION: This study confirms the feasibility of linking sources of data that provide complementary information needed to develop measurements regarding standards of quality and efficiency of oncologic care. This report should serve as an initial benchmark while we await reports from other populations to define the best practice.

Perceptual and cognitive abnormality model of hypochondriasis: amplification and physiological reactivity in women.

This study investigated the perceptual/cognitive abnormality model of hypochondriasis, which suggests that hypochondriacal patients amplify and misinterpret normal bodily sensations. The hypothesis was evaluated by assessing pain perception and stress reactivity in female hypochondriacal (N = 15) and female nonhypochondriacal control subjects (N = 15). Subjects completed self-report measures and participated in a laboratory stress reactivity assessment consisting of the cold pressor task and an imagery task. Hypochondriacal subjects exhibited a significant increase in heart rate during the cold pressor task and a significant drop in hand temperature relative to controls. Hand temperature remained lower among the hypochondriacal subjects after the cold pressor task was terminated. Hypochondriacal subjects terminated the cold pressor task more frequently, left their feet in the cold water bath a significantly shorter period of time, and rated the cold pressor task as significantly more unpleasant (although not more intense) relative to controls. Group differences were not observed in the imagery task. Of interest, hypochondriacal subjects' baseline heart rate was significantly lower than that of controls. Taken together, these data suggest that hypochondriacal behavior may be mediated, in part, by objective differences in physiological reactivity.

Variation in staging and treatment of local and regional breast cancer in the elderly.

BACKGROUND: Few studies of practice variation in the management of early breast cancer for elderly women have examined the process of care in depth. This study evaluated the effects of age and other factors on surgical staging techniques and treatment. METHODS: Virginia cancer registry data were linked with Medicare claims and 1990 census data. The sample included all newly diagnosed patients with pathologic confirmed local and regional breast cancer in 1985-1989 (n = 3,361). Analyses included descriptive univariate statistics and multiple logistic regression analysis for staging and treatment alternatives. Process of care variables included tumor size determination, axillary lymph node dissection, use of adjuvant therapy, and radiation if breast conserving surgery (BCS) was performed. RESULTS: About 75 percent of women had tumor size and axillary node dissection. Increasing comorbidity was associated with a lower likelihood of axillary node dissection. Nine percent of local compared to 44 percent of regional disease patients received adjuvant therapy. Hormonal therapy increased from 13 percent of women in 1985-1988 to 24 percent in 1989. Hormonal therapy did not vary with patient age. One-third of the patients with positive lymph nodes compared to 8 percent of node negative women received hormonal therapy. Blacks were more likely to present with advanced disease. A logistic regression model evaluated the multiple effects of patients and clinical characteristics: older women were more likely to present with larger tumors, were less likely to have axillary node dissections, and were less likely to receive chemotherapy or radiation. CONCLUSIONS: Younger age was most consistently associated with staging and the use of chemotherapy in this cohort of elderly breast cancer patients. Based on the reported initial treatment plan, hormonal therapy was infrequently used and information from axillary lymph node assessment was used to stratify treatment. Although the low use of adjuvant hormonal therapy in elderly women may compromise survival, neither comorbid nor socioeconomic factors as measured in this study explained this practice pattern.

Serum-sensitive mutation of Francisella novicida: association with an ABC transporter gene.

Francisella novicida is a facultative intracellular pathogen that can survive and grow in macrophages by preventing phagolysosomal fusion. In this study in vitro cassette mutagenesis was used to generate a library of insertion mutants of F.novicida. Two related mutants, KM14 and KM14S, initially identified as defective for growth in macrophages, were found to be sensitive to serum. These mutants were also found to grow approximately 1000-fold less well in the livers and spleens of infected mice. We cloned a genetic locus that was presumably mutagenized in these mutants and found that it included genes that had high similarity in their deduced amino acid sequence to those of msbA and orfE of Escherichia coli. The former is a member of the superfamily of ABC transporter proteins. We named the corresponding genes in F. novicida, valAB. Integration of a cloned valAB locus into the chromosome of KM14S partially restored the serum resistance phenotype found in wild-type F. novicida.