Accuracy of Medicare Claim-based Algorithm to Detect Breast, Prostate, or Lung Cancer Bone Metastases.

BACKGROUND: We had previously developed an algorithm for Medicare claims data to detect bone metastases associated with breast, prostate, or lung cancer. This study was conducted to examine whether this algorithm accurately documents bone metastases on the basis of diagnosis codes in Medicare claims data. METHODS: We obtained data from Medicare claims and electronic medical records of patients 65 years or older with a breast, prostate, or lung cancer diagnosis at a teaching hospital and/or affiliated clinics during 2005 or 2006. We calculated the sensitivity and positive predictive value (PPV) of our algorithm using medical records as the "gold standard." The κ statistic was used to measure agreement between claims and medical record data. RESULTS: The agreement between claims and medical record data for bone metastases among breast, prostate, and lung cancer patients was 0.93, 0.90, and 0.69, respectively. The sensitivities of our algorithm for bone metastasis in patients with breast, prostate, and lung were 96.8% [95% confidence interval (CI)=83.8% to 99.4%], 91.7% (95% CI=78.2% to 97.1%), and 74.1% (95% CI=55.3% to 86.8%), respectively; and the PPVs were 90.9% (95% CI=76.4% to 96.9%), 91.7% (95% CI=78.2% to 97.1%), and 71.4% (95% CI=52.9% to 84.8%), respectively. CONCLUSIONS: The algorithm for detecting bone metastases in claims data had high sensitivity and PPV for breast and prostate cancer patients. Sensitivity and PPV were lower but still moderate for lung cancer patients.

OBSERVE-5 interim analysis: an observational postmarketing safety registry of etanercept for the treatment of psoriasis.

BACKGROUND: Etanercept is approved for the treatment of chronic moderate to severe plaque psoriasis in adults. OBJECTIVE: We sought to evaluate the long-term safety of etanercept in a real-world clinical setting. Assessment of etanercept efficacy was a secondary objective. METHODS: OBSERVE-5 is a 5-year observational safety registry initiated in May 2006 at multiple sites in the United States and Canada. Data collection includes the number of serious adverse events, serious infectious events, and prespecified events of medical interest. Efficacy data include body surface area assessments, physician and patient global assessments of psoriasis, and the Dermatology Life Quality Index. This interim analysis presents data from the first 3 years of the follow-up period. RESULTS: A total of 2511 patients were enrolled. Of 1890 patients continuing in the registry after 3 years, 113 were inactive for 1 to 2 years, and 115 were inactive for longer than 2 years. The 3-year incidence proportions of serious adverse events and serious infectious events based on Kaplan-Meier methodology were 0.14 and 0.04, respectively. The observed numbers of patients experiencing lymphoma, serious infectious events requiring hospitalization, nonmelanoma skin cancer, and malignancies excluding nonmelanoma skin cancer were not higher than the expected number of cases estimated from a large US administrative health claims database. LIMITATIONS: The registry lacks a control group, and the study is too small to measure the frequency of rare events. CONCLUSION: Etanercept demonstrated good tolerability in patients with plaque psoriasis in the clinical setting in this interim analysis. No new or unexpected safety concerns were observed.

Mortality following bone metastasis and skeletal-related events among women with breast cancer: a population-based analysis of U.S. Medicare beneficiaries, 1999-2006.

The aim of the study is to quantify the impact of bone metastasis and skeletal-related events (SREs) on mortality in older breast cancer patients. Using the linked Surveillance, Epidemiology and End Results-Medicare database, we identified women aged 65 years or older diagnosed with breast cancer between July 1, 1999 and December 31, 2005 and followed them to determine deaths occurring through December 31, 2006. We classified patients as having possible bone metastasis and SREs using discharge diagnoses from inpatient claims and diagnoses paired with procedure codes from outpatient claims. We used Cox regression to estimate mortality hazards ratios (HR) among women with bone metastasis with or without SRE, compared with women without bone metastasis. Among 98,260 women with breast cancer (median follow-up, 3.3 years), 7,189 (7.3%) had bone metastasis either at breast cancer diagnosis (1.5%) or during follow-up (5.8%). SREs occurred in 3,319 (46%) of women with bone metastasis. HRs for risk of death were 4.9 (95% CI 4.7-5.1) and 6.2 (95% CI 5.9-6.5), respectively, for women with bone metastasis but no SRE and for women with bone metastasis plus SRE, compared with women without bone metastasis. In analyses restricted to women with bone metastasis, the adjusted HR was 1.5 (95% CI 1.4-1.6) for women with bone metastasis plus SRE, compared with women with bone metastasis but without SRE. Having a bone metastasis, as indicated by Medicare claims, was associated strongly with mortality among women with breast cancer. This association was stronger for bone metastasis complicated by SRE than for bone metastasis without SRE.

Survival in breast cancer patients with bone metastases and skeletal-related events: a population-based cohort study in Denmark (1999-2007).

Bone lesions as a consequence of bone metastases in breast cancer patients can increase risk for skeletal-related events (SREs) (i.e., radiation to the bone, a pathological or osteoporotic fracture event, hypercalcemia, spinal cord compression, or surgery to the bone). The mortality risk for breast cancer patients with SREs subsequent to bone metastases is unclear. We assessed this relationship in a large, population-based cohort of breast cancer patients in Denmark. We identified 35,912 newly diagnosed breast cancer patients from January 1, 1999 to December 31, 2007 in the Danish National Patient Registry (DNPR) and followed them through April 1, 2008. Information on stage and treatment was obtained from the Danish Cancer Registry. We used the Kaplan-Meier method to estimate survival, and Cox's regression analysis to estimate the mortality rate ratio (MRR) by the presence of bone metastases with and without SREs, adjusting for age and comorbidity. The 5-year survival was 75.8% for breast cancer patients without bone metastases, 8.3% for patients with bone metastases, and 2.5% for those with both bone metastases and SREs. The adjusted MRR was 10.5 [95% confidence interval (CI) 9.5-11.6] for breast cancer patients with bone metastases, and 14.4 (95% CI 13.1-15.8) for those with bone metastases and SREs, compared with breast cancer patients with no bone metastases but possibly other sites of metastases. A similar pattern persisted when analyses were stratified by stage or treatment. Breast cancer patients with bone metastases and SREs have a poor prognosis compared to those with and without bone metastases regardless of cancer treatment or stage of disease at diagnosis.

Incidence of bone metastases and skeletal-related events in breast cancer patients: a population-based cohort study in Denmark.

BACKGROUND: Breast cancer (BrCa) is the most commonly diagnosed cancer among women in the industrialized world. More than half of women presenting with metastatic BrCa develop bone metastases. Bone metastases increase the risk of skeletal-related events (SREs), defined as pathological fractures, spinal cord compression, bone pain requiring palliative radiotherapy, and orthopaedic surgery. Both bone metastases and SREs are associated with unfavorable prognosis and greatly affect quality of life. Few epidemiological data exist on SREs after primary diagnosis of BrCa and subsequent bone metastasis. We therefore estimated the incidence of bone metastases and SREs in newly-diagnosed BrCa patients in Denmark from 1999 through 2007. METHODS: We estimated the overall and annual incidence of bone metastases and SREs in newly-diagnosed breast cancer patients in Denmark from January 1, 1999 to December 31, 2007 using the Danish National Patient Registry (DNPR), which covers all Danish hospitals. We estimated the cumulative incidence of bone metastases and SREs and associated 95% confidence intervals (CI) using the Kaplan-Meier method. RESULTS: Of the 35,912 BrCa patients, 178 (0.5%) presented with bone metastases at the time of primary breast cancer diagnosis, and of these, 77 (43.2%) developed an SRE during follow up. A total of 1,272 of 35,690 (3.6%) BrCa patients without bone metastases at diagnosis developed bone metastases during a median follow-up time of 3.4 years. Among these patients, 590 (46.4%) subsequently developed an SRE during a median follow-up time of 0.7 years. Incidence rates of bone metastases were highest the first year after the primary BrCa diagnosis, particularly among patients with advanced BrCa at diagnosis. Similarly, incidence rates of a first SRE was highest the first year after first diagnosis of a bone metastasis. CONCLUSIONS: The high incidence of SREs following the first year after first diagnosis of a bone metastasis underscores the need for early BrCa detection and research on effective treatments to delay the onset of SREs.

Epidemiology of paediatric immune thrombocytopenia in the General Practice Research Database.

This study assessed the incidence of immune thrombocytopenia (ITP) and characteristics associated with ITP in the paediatric population using the General Practice Research Database (GPRD). Two hundred and fifty-seven paediatric ITP patients were identified out of 1145 incident patients with ITP recorded between 1990 and 2005. The age-specific incidence for ITP in paediatric patients was 4.2 per 100,000 person-years (PY) [95% confidence interval (CI): 3.7-4.8 per 100,000 PY], with a statistically significantly higher incidence in boys compared to girls aged 2-5 years [9.7 (95% CI: 7.5-12.2) per 100,000 PY vs. 4.7 (95% CI: 3.2-6.6) per 100,000 PY, respectively]. By contrast, among teenagers aged 13-17 years, the overall incidence was lower [2.4 (95% CI: 1.7-3.3) per 100,000 PY] with a similar incidence in girls and boys. There was a relationship between age and sex with ITP incidence, suggesting that patterns of disease burden differ among children and teenagers. Evidence of an infection or immunization shortly before ITP diagnosis was apparent in 52 (20.2%) and 22 (8.6%) of the 257 paediatric ITP patients, respectively. Two deaths were observed during the study period. ITP is an important although rarely fatal disease in paediatric patients and its aetiology remains unexplained in the majority of cases.

Incidence of myelodysplastic syndromes within a nonprofit healthcare system in western Washington state, 2005-2006.

Myelodysplastic syndromes (MDS) incidence is unclear because of historical lack of population-based registration and possibly because of underdiagnosis. We conducted a study to evaluate completeness of MDS registration in the Seattle-Puget Sound region of the Surveillance, Epidemiology, and End Results (SEER) program-which has reported the highest rates among the SEER registries since mandatory reporting of MDS began in 2001. We identified incident MDS cases of any age that occurred within a nonprofit healthcare system in western Washington State in 2005 or 2006 through the local SEER registry or by relevant diagnostic code followed by medical chart review to classify these patients as unlikely, possible, or definite/probable MDS. We calculated age-standardized incidence rates for all identified MDS cases and for case groups based on identification method, and we summarized medical histories of the MDS patients. MDS incidence in our study population was estimated as 7.0 per 100,000 person-years in 2005-2006 when combining MDS cases identified by SEER and definite/probable cases identified by chart review, which was similar to the rate of 6.9 reported by our local SEER registry. The addition of possible MDS cases identified from chart review increased the rate to 10.2 per 100,000. MDS patients frequently had previous cancer diagnoses (25%) and comorbidities such as high blood pressure and diabetes. Our investigation suggests that although reporting of confirmed MDS diagnoses in our region appears complete, MDS incidence is likely underestimated because of omission of cases who are symptomatic but do not receive definitive diagnoses.

Associations between endogenous sex hormone levels and mammographic and bone densities in premenopausal women.

PURPOSE: Mammographic breast and bone mineral densities (BMD) have been associated with luteal phase hormone concentrations in premenopausal women. We assessed the associations of breast and bone densities with follicular phase hormones and sex hormone binding globulin (SHBG) in premenopausal women, given that follicular phase hormones have been shown to be positively associated with premenopausal breast cancer risk. METHODS: One hundred and ninety-two 40-45-year-old women provided a spot urine and/or blood sample during the follicular phase. Hormone and SHBG concentrations, and bone density were measured and routine mammograms were accessed and digitized to obtain breast density measures. Regression models were fit to assess the associations between hormones and SHBG, and breast and bone densities. RESULTS: Positive associations were observed between percent breast density and SHBG (p trend = 0.02), as well as estradiol (p trend = 0.08), after controlling for body mass index (BMI), number of pregnancies, and breast feeding history. In addition, a statistically significant inverse association was observed between total testosterone and head BMD (p trend = 0.01), after controlling for BMI. CONCLUSIONS: Associations were observed between breast and bone densities, and serum hormone concentrations during the follicular phase of the menstrual cycle.

Associations between Dietary Intake of Fruits and Vegetables in relation to Urinary Estrogen DNA Adduct Ratio.

BACKGROUND: Estrogen exposure plays a role in breast cancer (BC) development. A novel estrogen biomarker, the estrogen DNA adduct (EDA) ratio, was shown to be elevated in women at high-risk of BC and among BC cases. Modifiable factors may impact the EDA ratio, with studies demonstrating that resveratrol reduces EDA ratio in vitro. We sought to examine the hypothesis that dietary intake of fruits and vegetables is inversely associated with EDA ratio. METHODS: This analysis was conducted in 53 pre-menopausal, healthy women aged 40-45 years from a cross-sectional study in which participants provided first-void urine samples and 3-day food records. Urine samples were analyzed using ultraperformance liquid chromatography/tandem mass spectrometry. The EDA ratio was calculated as the estrogen-DNA adducts divided by estrogen metabolites and conjugates. A trend test was used to assess associations between tertiles of dietary intake using linear regression. RESULTS: After adjustment for age, total energy, percent adiposity, serum estradiol and estrone-sulfate, we observed inverse associations of EDA ratio with carbohydrate consumption (P=0.01) and vegetable intake (P =0.01). EDA ratio was inversely associated with 5 botanical groups (Chenopodiaceae: P=0.02; Umbelliferae: P=0.03; Compositae: P=0.01; Ericaceae: P=0.01; Musaceae: P=0.03) but not fruit intake overall. CONCLUSION: Although these data require replication before conclusions are drawn, this report suggests an inverse association between vegetable and carbohydrate consumption and EDA ratio. IMPACT: While more information is still needed, these findings suggest a link between dietary intake and a biomarker that is both associated with high-risk BC status and associated with modifiable factors.

Work readiness of graduate health professionals.

BACKGROUND AND AIM: The current exploratory study investigated work readiness among graduate health professionals. DESIGN AND PARTICIPANTS: A critical incident technique was used to elicit perceptions regarding: strategies and skills that constitute work readiness among health professionals and the work readiness factors that help or hinder health graduates' transition and integration into the workplace. Fifteen medical graduates, 26 nursing graduates and five organisational representatives from a regional hospital in Victoria, Australia participated. METHOD: Data were collected via qualitative interviews. RESULTS: Participants discussed a total of 92 critical incidents; 52 related to helping and 40 to hindering work readiness factors that impacted graduates' transition and integration experiences. A follow-up thematic analysis indentified four critical work readiness factors: social intelligence, organisational acumen, work competence and personal characteristics. While graduates and organisational representatives considered each factor important, some differences between the groups emerged. Organisational representative's perceived social intelligence and clinical skills critical graduate competencies, yet graduates were unprepared in these areas. CONCLUSION: The identified work readiness factors were consistent with past research and warrant further investigation of work readiness among a larger group of graduate health professionals in a range of contexts.

Hospital visits among women with skeletal-related events secondary to breast cancer and bone metastases: a nationwide population-based cohort study in Denmark.

OBJECTIVE: Skeletal-related events (SREs) among women with breast cancer may be associated with considerable use of health-care resources. We characterized inpatient and outpatient hospital visits in a national population-based cohort of Danish women with SREs secondary to breast cancer and bone metastases. METHODS: We identified first-time breast cancer patients with bone metastases from 2003 through 2009 who had a subsequent SRE (defined as pathologic fracture, spinal cord compression, radiation therapy, or surgery to bone). Hospital visits included the number of inpatient hospitalizations, length of stay, number of hospital outpatient clinic visits, and emergency room visits. The number of hospital visits was assessed for a pre-SRE period (90 days prior to the diagnostic period), a diagnostic period (14 days prior to the SRE), and a post-SRE period (90 days after the SRE). Patients who experienced more than one SRE during the 90-day post-SRE period were defined as having multiple SREs and were followed until 90 days after the last SRE. RESULTS: We identified 569 women with SREs secondary to breast cancer with bone metastases. The majority of women had multiple SREs (73.1%). A total of 20.9% and 33.4% of women with single and multiple SREs died in the post-SRE period, respectively. SREs were associated with a large number of hospital visits in the diagnostic period, irrespective of the number and type of SREs. Women with multiple SREs generally had a higher number of visits compared to those with a single SRE in the post-SRE period, eg, median length of hospitalization was 5 days (interquartile range 0-15) for women with a single SRE and 13 days (interquartile range 4-30) for women with multiple SREs. CONCLUSION: SREs secondary to breast cancer and bone metastases were associated with substantial use of hospital resources.

Mortality following bone metastasis and skeletal-related events among patients 65 years and above with lung cancer: A population-based analysis of U.S. Medicare beneficiaries, 1999-2006.

BACKGROUND: To quantify the impact of bone metastasis and skeletal-related events (SREs) on mortality among older patients with lung cancer. MATERIALS AND METHODS: Using the linked Surveillance, Epidemiology and End Results-Medicare database, we identified patients aged 65 years or older diagnosed with lung cancer between July 1, 1999 and December 31, 2005 and followed them to determine deaths through December 31, 2006. We classified patients as having possible bone metastasis and SREs using discharge diagnoses from inpatient claims and diagnoses paired with procedure codes from outpatient claims. We used Cox regression to estimate mortality hazards ratios (HR) among patients with bone metastasis with or without SRE, compared to patients without bone metastasis. RESULTS: Among 126,123 patients with lung cancer having a median follow-up of 0.6 years, 24,820 (19.8%) had bone metastasis either at lung cancer diagnosis (9,523, 7.6%) or during follow-up (15,297, 12.1%). SREs occurred in 12,665 (51%) patients with bone metastasis. The HR for death was 2.4 (95% CI = 2.4-2.5) both for patients with bone metastasis but no SRE and for patients with bone metastasis plus SRE, compared to patients without bone metastasis. CONCLUSIONS: Having a bone metastasis, as indicated by Medicare claims, was associated with mortality among patients with lung cancer. We found no difference in mortality between patients with bone metastasis complicated by SRE and patients with bone metastasis but without SRE.

Fruit intake associated with urinary estrogen metabolites in healthy premenopausal women.

Urinary concentrations of 2:16-hydroxyestrone (2:16-OHE1) approximate concentrations of 2-OHE1 and 16α -OHE1 in breast tissue. As estrogens are purported to be involved in breast cancer development, the 2:16-OHE1 ratio can provide an indication of estrogen metabolite exposure in the breast. With prior studies observing associations between urinary estrogen metabolites and dietary intake of fruits, vegetables, and fiber ascertained from food questionnaires, we examined associations between dietary factors ascertained through 3-day food records and urinary 2:16-OHE1 in 191 pre-menopausal healthy women. Fruit consumption was positively associated with 2:16-OHE1 after adjustment for total energy, ethnicity, body mass index, parity, smoking history, and serum estradiol (p= 0.003). Fruit consumption was positively associated with 2- OHE1 concentrations (p=0.006), but was not associated with 16α-OHE1 (p=0.92). The Musaceae botanical grouping (comprised primarily of bananas) was positively associated with the 2:16-OHE1 ratio, and Rosaceae (comprised of citrus fruits) and Musaceae botanical groupings were positively associated with 2-OHE1 (but not 16α-OHE1) concentrations, after adjustment for confounders. Our data suggest that dietary fruit intake is associated with urinary 2- OHE1 and the 2:16-OHE1 ratio and that breast tissue exposure to estrogen metabolites may thus be influenced by diet.

Daidzein-metabolizing phenotypes in relation to bone density and body composition among premenopausal women in the United States.

BACKGROUND: Bone density has been suggested as a marker of cumulative hormone exposure. Small studies also suggest that patterns of daidzein metabolism may be related to hormone concentrations. To our knowledge, no studies in premenopausal women have compared bone density by daidzein-metabolizing phenotypes in the absence of a soy intervention. OBJECTIVE: The objective was to evaluate the relationship between daidzein-metabolizing phenotypes [equol and O-desmethylangolensin (ODMA) production] and bone density and body composition in premenopausal women in the United States. MATERIALS/METHODS: Two hundred and three women attended a clinic visit during which their bone density and body composition were measured by DXA, and 200 (99 %) provided a urine sample following a 3-day soy challenge. Samples were analyzed for isoflavones to determine daidzein-metabolizing phenotypes. RESULTS: In adjusted analyses, there were no differences in hip, spine, femoral neck, or head bone mineral density (BMD) or body composition between producers and non-producers of either equol or ODMA (P > .05). CONCLUSIONS: In this population of low-soy consuming premenopausal women, there were no associations between daidzein-metabolizing phenotypes and hip, spine, femoral neck, or head BMD or body composition, suggesting that these phenotypes per se do not influence premenopausal bone density or body composition.

Baseline characteristics and predictors of outcome in patients with myelodysplastic syndromes living in Western Pennsylvania.

The myelodysplastic syndromes (MDS) are a collection of hematologic disorders that affect older adults, and whose baseline characteristics and risk factors for evolution to acute myeloid leukemia (AML) and death have not been completely defined. We analyzed a large unselected cohort of 214 patients with MDS from the University of Pittsburgh Network Cancer Registry in Western Pennsylvania. Patients' follow-up was 22 months, at the end of which 72.9% of patients were dead. Overall, the 36-month survival rate was 19.0% (95% CI: 14.0-24.5%); 22.4% (95% CI: 16.4-29.0%) for patients with lower-risk MDS; and 5.0% (95% CI: 0.1-14.8%) for patients with higher-risk MDS (p = 0.0007). During follow-up, 32.9% of the patients developed AML. Family history of cancer and having  ≥5% blasts at diagnosis were statistically significant predictors for progression to AML. A higher risk of death also was associated with age >70 years and previous diagnosis of another cancer. More than three cycles of chemotherapy sessions and a platelet count of ≥50 × 10(3)/mm(3) were inversely associated with death. This study suggests the need to incorporate laboratory results such as percentage blasts and platelet counts as well as epidemiologic data on family history of cancer in future outcome studies on MDS.

Predictors and patterns of red blood cell transfusion use among newly diagnosed cancer patients with chemotherapy-associated anemia in Western Denmark (1998-2003).

OBJECTIVE: Cancer patients receiving chemotherapy are at increased risk of anemia. We conducted a population-based historical cohort study in newly diagnosed cancer patients with chemotherapy-associated anemia in order to characterize red blood cell transfusion (RBCT) use. DESIGN: This study evaluated cancer patients diagnosed between January 1, 1998 and December 31, 2003 using Danish National Patient Registry data. Patients were receiving chemotherapy and had a hemoglobin level ≤10.9 g/dL during the 4 months following cancer diagnosis. We characterized patterns of RBCT use and inpatient and outpatient hospitalization for transfusion. Adjusted Poisson regression models were used to evaluate the likelihood of RBCT, estimated by relative risk (RR), based on demographic and clinical factors. RESULTS: Women constituted 58% of 1782 patients studied; the median age was 58 years. Two-thirds (67%) had solid tumors; 67% had stage III or IV disease at diagnosis. Overall, 713 (40%) patients received an RBCT within 120 days of cancer diagnosis, of which 94% were administered in the inpatient setting; 84% of these patients required subsequent transfusions. The median (Q1, Q3) pretransfusion hemoglobin level was 9.0 (8.4, 9.8) g/dL. Patients aged <20 years were more likely to receive an RBCT than older patients (RR 1.89; 95% confidence interval [CI] 1.44-2.49). Compared with stage IV disease, those with stage II or III disease had a lower likelihood of RBCT (stage II: RR 0.52, 95% CI: 0.37-0.72; stage III: RR 0.68, 95% CI: 0.55-0.83). Patients diagnosed with breast cancer were less likely to receive an RBCT than patients with hematologic cancers (RR 0.34, 95% CI: 0.21-0.55). CONCLUSION: In this study, 40% of cancer patients with chemotherapy-associated anemia in Western Denmark received an RBCT, usually in the inpatient setting; of these, most required subsequent transfusions. Younger age increased the likelihood of receiving an RBCT, and earlier stage or breast cancer decreased RBCT likelihood.

Associations between polymorphisms in glucuronidation and sulfation enzymes and sex steroid concentrations in premenopausal women in the United States.

Glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGT) and sulfation, catalyzed by sulfotransferases (SULT), are pathways through which sex steroids are metabolized to less active compounds. These enzymes are highly polymorphic and genetic variants frequently result in higher or lower activity. The phenotypic effects of these polymorphisms on circulating sex steroids in premenopausal women have not yet been investigated. One hundred and seventy women aged 40-45 years had a blood sample drawn during the follicular phase of the menstrual cycle for sex steroid measures and to obtain genomic DNA. Urine was collected for 2-hydroxy (OH) estrone (E(1)) and 16α-OH E(1) measures. Generalized linear regression models were used to assess associations between sex steroids and polymorphisms in the UGT1A and UGT2B families, SULT1A1, and SULT1E1. Women with the UGT1A1(TA7/TA7) genotype had 25% lower mean estradiol (E(2)) concentrations compared to the wildtype (TA6/TA6) (p=0.02). Similar associations were observed between SULT1A1(R213/H213) and E(1) (13% lower mean E(1) concentration vs. wildtype; p-value=0.02) and UGT2B4(E458/E458) and dehydroepiandrosterone (DHEA) (20% lower mean DHEA vs. wildtype; p-value=0.03). The SULT1E1(A/C) and the UGT1A1(TA7)-UGT1A3(R11) haplotypes were associated with reduced estrogen concentrations. Further study of UGT and SULT polymorphisms and circulating sex steroid measures in larger populations of premenopausal women is warranted.

Mortality risk in splenectomised patients: a Danish population-based cohort study.

BACKGROUND: The extent and magnitude of mortality risk among patients splenectomised for a variety of indications is not well-described in the literature. We assessed mortality risk among splenectomised patients compared to the general population and to un-splenectomised patients with similar underlying medical conditions. METHODS: We conducted a historical population-based cohort study in Denmark between January 1, 1996 and December 31, 2005. Mortality risk was evaluated within 90 days, 91-365 days, and >365 days post-splenectomy, controlling for age, sex, and comorbid conditions using Cox proportional hazards models for a splenectomised cohort compared to the general Danish population and a matched indication cohort. RESULTS: We identified a total of 3812 splenectomised patients, 38,120 population comparisons, and 8310 matched indication comparisons. Within 90 days post-splenectomy, the adjusted relative risk (RR) for death, regardless of indication, was highly elevated compared to the general population: RR 33.6 [95% confidence interval (CI): 6.9, 35.0]. This risk declined substantially after 90 days post-splenectomy but remained higher 365 days post-splenectomy for all indications compared to the general population. When compared to the matched indication cohort, short- and long-term mortality risk with splenectomy was not increased. CONCLUSION: Regardless of indication, the adjusted short- and long-term risk of death for splenectomised patients was higher than the general population. Most of this risk seems to be due to the underlying splenectomy indication and not to splenectomy alone.

Associations between polymorphisms in glucuronidation and sulfation enzymes and mammographic breast density in premenopausal women in the United States.

OBJECTIVE: Sex hormones are metabolized to less active compounds via (a) glucuronidation catalyzed by UDP-glucuronosyltransferases (UGT) and (b) sulfation catalyzed by sulfotransferases (SULT). Functional UGT and SULT polymorphisms can affect clearance of sex hormones, thereby influencing exposure in hormone-sensitive tissues, such as the breast. We assessed relationships between functional polymorphisms in the UGT and SULT genes and breast density in premenopausal women. METHODS: One hundred seventy-five women ages 40 to 45 years, who had a screening mammogram taken within the previous year, provided a genomic DNA sample. Mammograms were digitized to obtain breast density measures. Using generalized linear regression, we assessed associations between percent breast density and polymorphisms in the UGT1A and UGT2B families, SULT1A1, and SULT1E1. RESULTS: Women with the SULT1A1(H213/H213) genotype had 16% lower percent breast density compared with women with the SULT1A1(R213/R213) genotype after controlling for ethnicity (P = 0.001). Breast density was 5% lower among women carrying at least one copy of the UGT1A1(TA7)-UGT1A3(R11)-UGT1A3(A47) haplotype compared with the UGT1A1(TA6)-UGT1A3(W11R)-UGT1A3(V47A) haplotype (P = 0.07). No associations were observed between polymorphisms in the UGT2B family or SULT1E1 and breast density. CONCLUSION: Polymorphisms in SULT1A1 and the UGT1A locus may influence percent breast density in premenopausal women.

Validity of the recorded International Classification of Diseases, 10th edition diagnoses codes of bone metastases and skeletal-related events in breast and prostate cancer patients in the Danish National Registry of Patients.

OBJECTIVE: The clinical history of bone metastases and skeletal-related events (SREs) secondary to cancers is not well understood. In support of studies of the natural history of bone metastases and SREs in Danish prostate and breast cancer patients, we estimated the sensitivity and specificity of hospital diagnoses for bone metastases and SREs (ie, radiation therapy to the bone, pathological or osteoporotic fractures, spinal cord compression and surgery to the bone) in a nationwide medical registry in Denmark. STUDY DESIGN AND SETTING: In North Jutland County, Denmark, we randomly sampled 100 patients with primary prostate cancer and 100 patients with primary breast cancer diagnoses from the National Registry of Patients (NRP), during the period January 1st, 2000 to December 31st, 2000 and followed them for up to five years after their cancer diagnosis. We used information from medical chart reviews as the reference for estimating sensitivity, and specificity of the NRP International Classification of Diseases, 10th edition (ICD-10) coding for bone metastases and SRE diagnoses. RESULTS: For prostate cancer, the overall sensitivity of bone metastases or SRE coding in the NRP was 0.54 (95% confidence interval [CI]: 0.39-0.69), and the specificity was 0.96 (95% CI: 0.87-1.00). For breast cancer, the overall sensitivity of bone metastases or SRE coding in the NRP was 0.58 (95% CI: 0.34-0.80), and the specificity was 0.95 (95% CI: 0.88-0.99). CONCLUSION: We measured the validity of ICD-10 coding in the Danish NRP for bone metastases and SREs in prostate and breast cancer patients and found it has adequate sensitivity and high specificity. The NRP remains a valuable tool for clinical epidemiological studies of bone metastases and SREs.