BRCA1/2 testing among young women with breast cancer in Massachusetts, 2010-2013: An observational study using state cancer registry and All-Payer claims data.

BACKGROUND: Testing for BRCA1/2 pathogenic variants is recommended for women aged ≤45 years with breast cancer. Some studies have found racial/ethnic and socioeconomic disparities in testing. We linked Massachusetts' All-Payer Claims Database with Massachusetts Cancer Registry data to assess factors associated with BRCA1/2 testing among young women with breast cancer in Massachusetts, a state with high levels of access to care and equitable insurance coverage of breast cancer gene (BRCA) testing. METHODS: We identified breast cancer diagnoses in the Massachusetts Cancer Registry from 2010 to 2013 and linked registry data with Massachusetts All-Payer Claims Data from 2010 to 2014 among women aged ≤45 years with private insurance or Medicaid. We used multivariable logistic regression to examine factors associated with BRCA1/2 testing within 6 months of diagnosis. RESULTS: The study population included 2424 women; 80.3% were identified as non-Hispanic White, 6.4% non-Hispanic Black, and 6.3% Hispanic. Overall, 54.9% received BRCA1/2 testing within 6 months of breast cancer diagnosis. In adjusted analyses, non-Hispanic Black women had less than half the odds of testing compared with non-Hispanic White women (adjusted odds ratio [OR] = 0.45, 95% CI = 0.31, 0.64). Medicaid-insured women had half the odds of testing compared with privately-insured women (OR = 0.51, 95% CI = 0.41, 0.63). Living in lower-income areas was also associated with lower odds of testing. Having an academically-affiliated oncology clinician was not associated with testing. CONCLUSION: Socioeconomic and racial/ethnic disparities exist in BRCA1/2 testing among women with breast cancer in Massachusetts, despite equitable insurance coverage of testing. Further research should examine whether disparities have persisted with growing testing awareness and availability over time.

Cancer Rates in Adults After Cardiac Interventions: A Preliminary Observational Report.

BACKGROUND: The postprocedural state after cardiac revascularization interventions is characterized by intense inflammation and activation of inflammatory cytokines due to myonecrosis and ischemia/reperfusion injury. Involvement of similar processes also participates in cellular malignant transformation. In this study, the association between cardiac interventions and subsequent cancer risk development was therefore evaluated. METHODS: The 5-year cumulative incidence of cancer was examined in 2 cardiac care cohorts: all patients undergoing either open heart surgery or percutaneous coronary interventions (PCI) at hospitals in the commonwealth of Massachusetts. The observed cases of cancer were compared with the number of expected cases based on the state cancer rates, adjusting for sex and 5-year age groups. The standardized morbidity ratio (SMR) was used for this comparison. RESULTS: Of 10,301 patients in the surgical cohort, 804 (7.8%) incident cancers developed over 5 years of follow-up, whereas 245.7 incident cancers were expected. This yielded an SMR of 3.27 (95% CI, 3.05-3.51; P<0.0001). In the PCI cohort comprising 13,001 patients, 1029 (7.9%) incident cancers developed over 5 years, resulting in an SMR of 3.53 (95% CI, 3.32-3.75; P<0.0001). Excluding respiratory cancers from the analysis (to limit smoking-related cancers) reduced risk estimates only slightly. For the surgical cohort: SMR=2.80; 95% CI, 2.59-3.01; P<0.0001. For the PCI cohort: SMR=2.97; 95% CI, 2.78-3.18; P<0.0001. CONCLUSIONS: Undergoing heart revascularization procedures was associated with increased rate of cancer development as compared with the state general population. This cohort may warrant increased monitoring.

Rationale and Design of the Women and Inclusion in Academic Medicine Study.

BACKGROUND AND OBJECTIVE: Women of color (WOC) (African American, Hispanic, Native American/Alaskan Native, and Asian American) faculty remain disproportionately underrepresented among medical school faculty and especially at senior ranks compared with White female faculty. The barriers or facilitators to the career advancement of WOC are poorly understood. The Women and Inclusion in Academic Medicine (WIAM) study was developed to characterize individual, institutional and sociocultural factors that influence the entry, progression and persistence, and advancement of women faculty in academic medical careers with a focus on WOC. METHODS: Using a purposive sample of 13 academic medical institutions, we collected qualitative interview data from 21 WOC junior faculty and quantitative data from 3,127 (38.9% of 8,053 eligible women) respondents via an online survey. To gather institutional data, we used an online survey and conducted 23 key administrative informant interviews from the 13 institutions. Grounded theory methodology will be used to analyze qualitative data. Multivariable analysis including hierarchical linear modeling will be used to investigate outcomes, such as the inclusiveness of organizational gender climate and women faculty's intent to stay. CONCLUSION: We describe the design, methods, rationale and limitations of one of the largest and most comprehensive studies of women faculty in academic medicine with a focus on WOC. This study will enhance our understanding of challenges that face women, and, especially WOC, faculty in academic medicine and will provide solutions at both the individual and institutional levels.

Effects of gender and ethnicity on outcomes after aortic valve replacement.

OBJECTIVE: To evaluate the clinical outcomes after aortic valve replacement or aortic valve replacement and coronary artery bypass grafting in a large contemporary population, and to determine if outcomes are associated with patient ethnicity and gender status. METHODS: Using the Massachusetts Cardiac Surgery Database, we identified 6809 adults aged 18 years or older who had undergone isolated aortic valve replacement or aortic valve replacement and coronary artery bypass grafting in all non-federal acute-care Massachusetts hospitals from 2002 to 2008. Univariate and multivariate logistic regression analyses were used to identify differences in patient characteristics, major morbidity, and 30-day and 1-year mortality between men (n=4043) and women (n=2766) and between whites (n=6481) and nonwhites (n=328). RESULTS: The unadjusted 30-day mortality rate was 2.6% for the men and 3.1% for the women (P=.296) and 2.8% for whites and 3.7% for nonwhites (P=.342). In adjusted logistic regression models, the 30-day mortality was not different between the female and male patients (odds ratio, 0.88; 95% confidence interval, 0.26-3.02, P=.84) nor between the nonwhites and whites (odds ratio, 1.57; 95% confidence interval, 0.45-5.44; P=.48). The incidence of postoperative stroke was greater in women (3.0% women and 2.2% men, P=.031), and the incidence of postoperative myocardial infarction (10.9% women and 13.6% men; P=.001) and septicemia (1.2% women and 2.0% men; P=.009) was greater in men. CONCLUSIONS: Ethnicity and gender were not associated with greater 30-day and 1-year mortality after aortic valve replacement or aortic valve replacement and coronary artery bypass grafting. Differences in postoperative outcomes were not observed between ethnic groups.

Predicting the restenosis benefit of drug-eluting versus bare metal stents in percutaneous coronary intervention.

BACKGROUND: Drug-eluting stents (DES) for percutaneous coronary intervention decrease the risk of restenosis compared with bare metal stents. However, they are costlier, require prolonged dual antiplatelet therapy, and provide the most benefit in patients at highest risk for restenosis. To assist physicians in targeting DES use in patients at the highest risk for target vessel revascularization (TVR), we developed and validated a model to predict TVR. METHODS AND RESULTS: Preprocedural clinical and angiographic data from 27 107 percutaneous coronary intervention hospitalizations between October 1, 2004, and September 30, 2007, in Massachusetts were used to develop prediction models for TVR at 1 year. Models were developed from a two-thirds random sample and validated in the remaining third. The overall rate of TVR was 7.6% (6.7% with DES, 11% with bare metal stents). Significant predictors of TVR included prior percutaneous coronary intervention, emergency or salvage percutaneous coronary intervention, prior coronary bypass surgery, peripheral vascular disease, diabetes mellitus, and angiographic characteristics. The model was superior to a 3-variable model of diabetes mellitus, stent diameter, and stent length (c statistic, 0.66 versus 0.60; P<0.001) and was well calibrated. The predicted number needed to treat with DES to prevent 1 TVR compared with bare metal stents ranged from 6 (95% confidence interval, 5.4-7.6) to 80 (95% confidence interval, 62.7-116.3), depending on patients' clinical and angiographic factors. CONCLUSIONS: A predictive model using commonly collected variables can identify patients who may derive the greatest benefit in TVR reduction from DES. Whether use of the model improves the safety and cost-effectiveness of DES use should be tested prospectively.

Variability in the measurement of hospital-wide mortality rates.

BACKGROUND: Several countries use hospital-wide mortality rates to evaluate the quality of hospital care, although the usefulness of this metric has been questioned. Massachusetts policymakers recently requested an assessment of methods to calculate this aggregate mortality metric for use as a measure of hospital quality. METHODS: The Massachusetts Division of Health Care Finance and Policy provided four vendors with identical information on 2,528,624 discharges from Massachusetts acute care hospitals from October 1, 2004, through September 30, 2007. Vendors applied their risk-adjustment algorithms and provided predicted probabilities of in-hospital death for each discharge and for hospital-level observed and expected mortality rates. We compared the numbers and characteristics of discharges and hospitals included by each of the four methods. We also compared hospitals' standardized mortality ratios and classification of hospitals with mortality rates that were higher or lower than expected, according to each method. RESULTS: The proportions of discharges that were included by each method ranged from 28% to 95%, and the severity of patients' diagnoses varied widely. Because of their discharge-selection criteria, two methods calculated in-hospital mortality rates (4.0% and 5.9%) that were twice the state average (2.1%). Pairwise associations (Pearson correlation coefficients) of discharge-level predicted mortality probabilities ranged from 0.46 to 0.70. Hospital-performance categorizations varied substantially and were sometimes completely discordant. In 2006, a total of 12 of 28 hospitals that had higher-than-expected hospital-wide mortality when classified by one method had lower-than-expected mortality when classified by one or more of the other methods. CONCLUSIONS: Four common methods for calculating hospital-wide mortality produced substantially different results. This may have resulted from a lack of standardized national eligibility and exclusion criteria, different statistical methods, or fundamental flaws in the hypothesized association between hospital-wide mortality and quality of care. (Funded by the Massachusetts Division of Health Care Finance and Policy.).

Assessing Geographical Variations in Hospital Processes of Care Using Multilevel Item Response Models.

With health care reform passing in the United States, much effort is directed toward developing and disseminating comparative information on standardized processes of care for health care providers. We propose the use of Bayesian multilevel item response theory models to estimate hospital quality from multiple process measures and to assess geographical variation in hospital quality. Our approach fully incorporates the nesting structure of measures, patients, hospitals, and various levels of geographical units to provide a summary of hospital quality. A national dataset of patients treated for a heart attack, heart failure, or pneumonia illustrates our methods. We find considerable geographical differences in hospital quality for these conditions with variations across census regions and states accounting for slightly more than 10% of the total variation. Some states performed well for all three conditions (e.g., the respective posterior probabilities of having better than the national average performance was close to 1 in Iowa, New Jersey, South Dakota, and Wisconsin). In contrast, quality of other states varied across conditions (e.g., the corresponding posterior probability was close to 1 in Massachusetts for heart attack and heart failure quality, but less than 0.5 for pneumonia care). Our framework provides a comprehensive approach to assessment of hospital performance at both regional and national levels, and might be informative for policy development.

Drug-eluting or bare-metal stenting in patients with diabetes mellitus: results from the Massachusetts Data Analysis Center Registry.

BACKGROUND: Patients with diabetes mellitus (DM) are at high risk for restenosis, myocardial infarction, and cardiac mortality after coronary stenting, and the long-term safety of drug-eluting stents (DES) relative to bare-metal stents (BMS) in DM is uncertain. We report on a large consecutive series of patients with DM followed up for 3 years after DES and BMS from a regional contemporary US practice with mandatory reporting. METHODS AND RESULTS: All adults with DM undergoing percutaneous coronary intervention with stenting between April 1, 2003, and September 30, 2004, at all acute care nonfederal hospitals in Massachusetts were identified from a mandatory state database. According to index admission stent type, patients were classified as DES treated if all stents were drug eluting and as BMS treated if all stents were bare metal; patients treated with both types of stents were excluded from the primary analysis. Mortality rates were obtained from vital statistics records, and myocardial infarction and revascularization rates were obtained from the state database with complete 3 years of follow-up on the entire cohort. Risk-adjusted mortality, myocardial infarction, and revascularization differences (DES-BMS) were estimated with propensity-score matching based on clinical, procedural, hospital, and insurance information collected at the index admission. DM was present in 5051 patients (29% of the population) treated with DES or BMS during the study. Patients with DM were more likely to receive DES than BMS (66.1% versus 33.9%; P<0.001). The unadjusted cumulative incidence of mortality at 3 years was 14.4% in DES versus 22.2% in BMS (P<0.001). Based on propensity-score analysis of 1:1 matched DES versus BMS patients (1476 DES:1476 BMS), the risk-adjusted mortality, MI, and target vessel revascularization rates at 3 years were 17.5% versus 20.7% (risk difference, -3.2%; 95% confidence interval, -6.0 to -0.4; P=0.02), 13.8% versus 16.9% (-3.0%; 95% confidence interval, -5.6 to 0.5; P=0.02), and 18.4% versus 23.7% (-5.4%; confidence interval, -8.3 to -2.4; P<0.001), respectively. CONCLUSIONS: In a real-world diabetic patient population with mandatory reporting and follow-up, DES were associated with reduced mortality, myocardial infarction, and revascularization rates at long-term follow-up compared with BMS.

Long-term clinical outcomes after drug-eluting and bare-metal stenting in Massachusetts.

BACKGROUND: Drug-eluting stents (DES) reduce the need for repeat revascularization, but their long-term safety relative to that of bare-metal stents (BMS) in general use remains uncertain. We sought to compare the clinical outcome of patients treated with DES with that of BMS. METHODS AND RESULTS: All adults undergoing percutaneous coronary intervention with stenting between April 1, 2003, and September 30, 2004, at non-US government hospitals in Massachusetts were identified from a mandatory state database. Patients were classified from the index admission according to stent types used. Clinical and procedural risk factors were collected prospectively. Risk-adjusted mortality, myocardial infarction, and revascularization rate differences (DES-BMS) were estimated through propensity score matching without replacement. A total of 11 556 patients were treated with DES, and 6237 were treated with BMS, with unadjusted 2-year mortality rates of 7.0% and 12.6%, respectively (P<0.0001). In 5549 DES patients matched to 5549 BMS patients, 2-year risk-adjusted mortality rates were 9.8% and 12.0%, respectively (P=0.0002), whereas the respective rates for myocardial infarction and target-vessel revascularization were 8.3% versus 10.3% (P=0.0005) and 11.0% versus 16.8% (P<0.0001). CONCLUSIONS: DES treatment was associated with lower rates of mortality, myocardial infarction, and target-vessel revascularization than BMS treatment in similar patients in a matched population-based study. Comprehensive follow-up in this inclusive population is warranted to identify whether similar safety and efficacy remain beyond 2 years.

Drug-eluting or bare-metal stents for acute myocardial infarction.

BACKGROUND: Studies comparing percutaneous coronary intervention (PCI) with drug-eluting and bare-metal coronary stents in acute myocardial infarction have been limited in size and duration. METHODS: We identified all adults undergoing PCI with stenting for acute myocardial infarction between April 1, 2003, and September 30, 2004, at any acute care, nonfederal hospital in Massachusetts with the use of a state-mandated database of PCI procedures. We performed propensity-score matching on three groups of patients: all patients with acute myocardial infarction, all those with acute myocardial infarction with ST-segment elevation, and all those with acute myocardial infarction without ST-segment elevation. Propensity-score analyses were based on clinical, procedural, hospital, and insurance information collected at the time of the index procedure. Differences in the risk of death between patients receiving drug-eluting stents and those receiving bare-metal stents were determined from vital-statistics records. RESULTS: A total of 7217 patients were treated for acute myocardial infarction (4016 with drug-eluting stents and 3201 with bare-metal stents). According to analysis of matched pairs, the 2-year, risk-adjusted mortality rates were lower for drug-eluting stents than for bare-metal stents among all patients with myocardial infarction (10.7% vs. 12.8%, P=0.02), among patients with myocardial infarction with ST-segment elevation (8.5% vs. 11.6%, P=0.008), and among patients with myocardial infarction without ST-segment elevation (12.8% vs. 15.6%, P=0.04). The 2-year, risk-adjusted rates of recurrent myocardial infarction were reduced in patients with myocardial infarction without ST-segment elevation who were treated with drug-eluting stents, and repeat revascularization rates were significantly reduced with the use of drug-eluting stents as compared with bare-metal stents in all groups. CONCLUSIONS: In patients presenting with acute myocardial infarction, treatment with drug-eluting stents is associated with decreased 2-year mortality rates and a reduction in the need for repeat revascularization procedures as compared with treatment with bare-metal stents.

Discriminating quality of hospital care in the United States.

BACKGROUND AND OBJECTIVE: The Centers for Medicare and Medicaid Services (CMS) report quality of care for patients hospitalized with acute myocardial infarction (AMI), congestive heart failure (CHF), and community-acquired pneumonia (CAP) with the intention of rewarding superior performing hospitals. The aim of the study was to compare identification of superior hospitals for providing financial rewards using 2 different scoring systems: a latent score that weights individual clinical performance measures according to how well each discriminated hospital quality and a raw sum score (the system adopted by CMS). METHODS: This observational cohort study used 2761 acute care hospitals in the United States reporting AMI clinical performance measures, 3271 reporting CHF measures, and 3714 hospitals reporting CAP measures. For each clinical condition, the main outcome measures included the average raw sum score, the latent score estimated from an item response theory (IRT) model, and the percentage of false negative superior designations made on the basis of raw sum scores relative to latent scores. RESULTS: The average raw sum score was highest for AMI (88.8%) and lower for CHF (73.1%) and CAP (76.3%). AMI measures were equally nondiscriminating of hospital quality; hospital discharge instruction was most discriminating of CHF quality; pneumococcal vaccination was most discriminating of CAP quality. False negative rates varied 2-fold: AMI (10%), CHF (16%), and CAP (24%). CONCLUSIONS: Neither the AMI raw sum score nor latent score discriminates hospital quality due to ceiling effects. Current methods for aggregating measures result in different hospital superior designations than those based on the latent score. Organizations that financially reward hospitals on the basis of such scores need to assess predictive validity of scores and determine a minimum level of classification accuracy.

State Medicaid coverage and access to care for low-income adults.

OBJECTIVE: Budgetary pressures have led some states to limit Medicaid eligibility. We evaluated access to care for all low-income adults by the extent of state Medicaid coverage. METHODS: Current Population Survey data compiled by the Kaiser Commission on Medicaid and the Uninsured were used to rank the 48 continental states by the extent of Medicaid coverage for low-income non-elderly adults during 2000-2003. Data from the Behavioral Risk Factor Surveillance System for 2000-2003 were used to assess indicators of access to care, including being unable to see a physician due to cost, not obtaining routine checkups, and four preventive services for appropriate age groups by state. Access gaps were calculated between low-income (under $25,000/year) and high-income ($50,000 or more/year) adults within each state to control for unmeasured economic and health system differences between states. RESULTS: Access gaps between high and low-income people who could not see physicians due to cost were significantly smaller in states with the broadest Medicaid coverage compared with states with the narrowest coverage (19.2% vs. 23.7%, p=.003). Significantly smaller access gaps also occurred in states with broader Medicaid coverage for cholesterol testing (16.0% vs. 18.7%, p=.01), and Pap testing (6.0% vs. 10.8%, p=.002), but not colorectal cancer screening (13.3% vs. 12.5%, p=.28), mammography (14.3% vs. 19.7%, p=.07), and routine checkup within two years (8.0% vs. 9.3%, p=.10). CONCLUSIONS: A state's level of Medicaid coverage was associated with access to physicians' services, cholesterol testing, and cervical cancer screening for low-income adults. Broad Medicaid coverage may be an effective strategy for states to improve access to care and preventive services for low-income adults.

Quality of diabetes care among cancer survivors with diabetes.

BACKGROUND: Among patients with chronic medical conditions, unrelated conditions are often undertreated. OBJECTIVE: To compare the quality of diabetes care delivered to diabetic patients with and without cancer in a large regional integrated delivery system. DESIGN: Observational cohort study using propensity score methods to control for baseline differences between diabetic patients with and without a history of cancer. SUBJECTS: A total of 5773 Kaiser Northern California members with diabetes and previous cancer and 23,092 members with diabetes and no previous cancer. MEASURES: : Nine measures of diabetes technical quality and clinical outcomes in 2003. RESULTS: : Relative to diabetic patients without cancer, those with cancer had higher adjusted rates of HbA1c testing (66.3% vs. 64.4%; P = 0.02), HbA1c control (73.4% vs. 70.9%; P < 0.001), and urine microalbumin testing (59.1% vs. 55.2%; P < 0.001) but lower rates of low-density lipoprotein (LDL) cholesterol control (40.7% vs. 42.2%; P = 0.02) and statin use if LDL >100 mg/dL (76.7% vs. 80.6%; P < 0.001). The groups had similar rates of LDL cholesterol testing, dilated retinal examinations, blood pressure control, and angiotensin converting enzyme (ACE) inhibitor use for hypertension (all P >/= 0.20). CONCLUSIONS: Despite the potential for cancer-related services to compete with delivery of diabetes care, diabetic patients with cancer received care of generally similar quality relative to diabetic patients without cancer in this integrated delivery system. Nevertheless, the quality of diabetes care delivered to all patients could be improved, particularly the control of LDL cholesterol and blood pressure. Combining data from electronic disease registries has the potential for monitoring quality of care delivered to patients with more than 1 major medical illness.

Comparison of clinical and administrative data sources for hospital coronary artery bypass graft surgery report cards.

BACKGROUND: Regardless of statistical methodology, public performance report cards must use the highest-quality validated data, preferably from a prospectively maintained clinical database. Using logistic regression and hierarchical models, we compared hospital cardiac surgery profiling results based on clinical data with those derived from contemporaneous administrative data. METHODS AND RESULTS: Fiscal year 2003 isolated coronary artery bypass grafting surgery results based on an audited and validated Massachusetts clinical registry were compared with those derived from a contemporaneous state administrative database, the latter using the inclusion/exclusion criteria and risk model of the Agency for Healthcare Research and Quality. There was a 27.4% disparity in isolated coronary artery bypass grafting surgery volume (4440 clinical, 5657 administrative), a 0.83% difference in observed in-hospital mortality (2.05% versus 2.88%), corresponding differences in risk-adjusted mortality calculated by various statistical methodologies, and 1 hospital classified as an outlier only with the administrative data-based approach. The discrepancies in volumes and risk-adjusted mortality were most notable for higher-volume programs that presumably perform a higher proportion of combined procedures that were misclassified as isolated coronary artery bypass grafting surgery in the administrative cohort. Subsequent analyses of a patient cohort common to both databases revealed the smoothing effect of hierarchical models, a 9% relative difference in mortality (2.21% versus 2.03%) resulting from nonstandardized mortality end points, and 1 hospital classified as an outlier using logistic regression but not using hierarchical regression. CONCLUSIONS: Cardiac surgery report cards using administrative data are problematic compared with those derived from audited and validated clinical data, primarily because of case misclassification and nonstandardized end points.

Assessing the accuracy of hospital clinical performance measures.

OBJECTIVE: To control costs and improve quality, payers are designing new hospital reimbursement policies that link payment to quality. The authors determine the extent to which quality measures discriminate hospitals into tiers in 2 geographic areas. DATA SOURCES: Administrative and medical record data for patients discharged with acute myocardial infarction (AMI) in 368 California and 81 Massachusetts hospitals. METHODS: Through simulation, the minimum numbers of patients per hospital needed to identify high-quality hospitals with sensitivity ranging from 75% to 95% under a variety of clinical scenarios are determined. RESULTS: Massachusetts hospitals had twice the number of eligible patients per hospital than California hospitals. Regardless of state, few hospitals had sufficient sample size needed to achieve >85% sensitivity for high-variation quality measures. CLINICAL IMPLICATIONS: Reliability of quality-based reimbursement systems relies on the distribution of the hospital sample sizes within geographic areas and the size of practice differences. Selection of conformance thresholds and sensitivity levels depends on the user of the information. To assess the usefulness of performance measures to tier hospitals, information regarding between-hospital variation in quality for specific clinical measures needs to be collected and reported.

Relation of surgeon and hospital volume to processes and outcomes of colorectal cancer surgery.

BACKGROUND: Greater hospital volume has been associated with lower mortality after colorectal cancer surgery. The contribution of surgeon volume to processes and outcomes of care is less well understood. We assessed the relation of surgeon and hospital volume to postoperative and overall mortality, colostomy rates, and use of adjuvant radiation therapy. METHODS: From the California Cancer Registry, we studied 28,644 patients who underwent surgical resection of stage I to III colorectal cancer during 1996 to 1999 and were followed up to 6 years after surgery to assess 30-day postoperative mortality, overall long-term mortality, permanent colostomy, and use of adjuvant radiation therapy. RESULTS: Across decreasing quartiles of hospital and surgeon volume, 30-day postoperative mortality ranged from 2.7% to 4.2% (P < 0.001). Adjusting for age, stage, comorbidity, and median income among patients with colorectal cancer who survived at least 30 days, patients in the lowest quartile of surgeon volume had a higher adjusted overall mortality rate than those in the highest quartile (hazard ratio, 1.16; 95% confidence interval, 1.09-1.24), as did patients in the lowest quartile of hospital volume relative to those treated in the highest quartile (hazard ratio, 1.11; 95% confidence interval, 1.05-1.19). For rectal cancer, adjusted colostomy rates were significantly higher for low-volume surgeons, and the use of adjuvant radiation therapy was significantly lower for low-volume hospitals. CONCLUSIONS: Greater surgeon and hospital volumes were associated with improved outcomes for patients undergoing surgery for colorectal cancer. Further study of processes that led to these differences may improve the quality of colorectal cancer care.

Prevalence of active hepatitis C virus infection in patients with systemic lupus erythematosus.

OBJECTIVE: Hepatitis C virus (HCV) infection is associated with various autoimmune disorders and can mimic systemic lupus erythematosus (SLE) clinically and serologically. There are few reports of prevalence of HCV infection in patients with SLE. The aim of this study was to determine the prevalence of HCV viremia by polymerase chain reaction (PCR) in patients with SLE. METHODS: We tested sera from 40 consecutive patients with SLE collected from 1993 to 2000. All of the patients had HCV viral load measured by PCR. The results were compared with the prevalence of HCV viremia in a control group of blood donors in our geographic area as well as in United States general population. RESULTS: HCV was detected in 4 of 40 patients (10%). The prevalence of HCV in our area blood donors is 130 cases per 100,000 persons (0.13%; P<0.0001). The prevalence of HCV infection in the United States general population, screened by PCR, is 1330 cases per 100,000 people (1.33%; P=0.002). The prevalence of HCV infection was significantly higher in our SLE patients than in our area blood donors. The frequency of HCV infection was also higher than that of the United States general population. CONCLUSION: Our observations support those of other investigators who have reported an increased prevalence of HCV infection in SLE patients. Further detailed investigation of this association may help in understanding the pathogenesis of SLE. HCV infection should be tested when the diagnosis of SLE is considered.

Analysis and quantitation of NF-kappaB nuclear translocation in tumor necrosis factor alpha (TNF-alpha) activated vascular endothelial cells.

Nuclear factor-kappa B (NF-kappaB) is a heterodimeric transcription factor typically composed of p50 and p65 subunits and is a pleiotropic regulator of various inflammatory and immune responses. In quiescent cells, p50/p65 dimers are sequestered in the cytoplasm bound to its inhibitors, the I-kappaBs, which prevent entry into the nucleus. Following cellular stimulation, the I-kappaBs are rapidly degraded, activating NF-kappaB. The active form of NF-kappaB rapidly translocates into the nucleus, binding to consensus sequences in the promoter/enhancer region of various genes, promoting their transcription. In human vascular endothelial cells activated with tumor necrosis factor-alpha, the activation and translocation of NF-kappaB is rapid, reaching maximal nuclear localization by 30 min. In this study, the appearance of NF-kappaB (p65 subunit, p65-NF-kappaB) in the nucleus visualized by immunofluorescence and quantified by morphometric image analysis (integrated optical density, IOD) is compared to the appearance of activated p65-NF-kappaB protein in the nucleus determined biochemically. The appearance of p65-NF-kappaB in the nucleus measured by fluorescence image analysis and biochemically express a linear correlation (R2 = 0.9477). These data suggest that localization and relative protein concentrations of NF-kappaB can be reliably determined from IOD measurements of the immunofluorescent labeled protein.

Impact of treatment with infliximab on anticyclic citrullinated peptide antibody and rheumatoid factor in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the impact of infliximab treatment on anticyclic citrullinated peptide (anti-CCP) antibody and rheumatoid factor (RF) levels in patients with rheumatoid arthritis (RA). METHODS: Sera from 33 RA patients receiving infliximab and disease modifying antirheumatic drugs were tested for anti-CCP antibody, IgA-, IgG- and IgM-RF using a commercially available semiquantitative ELISA at baseline, 30 and 54 weeks after treatment. RESULTS: The serum levels of anti-CCP antibody and IgA-RF decreased significantly after 30 weeks (P = 0.002 and 0.024); however, the decrease was not significant at week 54 (P = 0.147 and 0.207). The decrease in IgG-RF level was not significant at 30 and 54 weeks (P = 0.059 and 0.097). IgM-RF levels, however decreased significantly at 30 and 54 weeks (P = 0.002 and 0.004). A strong correlation between anti-CCP and IgA-, IgG- and IgM-RF was observed at baseline (r(s) = 0.48, 0.43, 0.65, P = < 0.05) and after infliximab treatment at 30 (r(s) = 0.45, 0.46, 0.62, P = < 0.05) and 54 (r(s) = 0.49, 0.45, 0.60, P = < 0.05) weeks. CONCLUSION: Treatment with infliximab results in decreased anti-CCP antibody and IgA-RF early in the course of therapy that is not sustained. IgM-RF declines and remains decreased for at least 54 weeks. Investigations in larger cohorts of RA patients (especially early RA) with longer follow-up are needed to assess the impact of specific therapeutic interventions on anti-CCP antibody and RF levels and the relationship of their levels to disease activity.