If detected early, breast cancer is eminently curable. To detect breast cancer in samples with little cellularity, a high level of sensitivity is needed. Tumor-specific promoter hypermethylation has provided such a valuable tool for detection of cancer cells in biological samples. To accurately assess promoter hypermethylation for many genes simultaneously in small samples, we developed a novel method, quantitative multiplex-methylationspecific PCR (QM-MSP). QM-MSP is highly sensitive (1 in 10 4 -10 5 copies of DNA) and linear over 5 orders of magnitude. For RASSF1A, TWIST, Cyclin D2, and HIN1, we observed significant differences in both the degree (P < 0.003) and incidence (P < 0.02) of hypermethylation between normal and malignant breast tissues. Evaluation of the cumulative hypermethylation of the four genes within each sample revealed a high level of sensitivity (84%) and specificity (89%) of detection of methylation. We demonstrate the application of this technique for detecting hypermethylated RASSF1A, TWIST, Cyclin D2, HIN1, and RARB in 50 -1000 epithelial cells collected from breast ducts during endoscopy or by lavage. Such an approach could be used in a variety of small samples derived from different tissues, with these or different biomarkers to enhance detection of malignancy.

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IMPORTANCE Black patients with advanced osteoarthritis (OA) of the knee are significantly less likely than white patients to undergo surgery. No strategies have been proved to improve access to surgery for black patients with end-stage OA of the knee. OBJECTIVE To assess whether a decision aid improves access to total knee replacement (TKR) surgery for black patients with OA of the knee. DESIGN, SETTING, AND PARTICIPANTS In a randomized clinical trial, 336 eligible participants who self-identified as black and 50 years or older with chronic and frequent knee pain, a Western Ontario McMaster Universities Osteoarthritis Index score of at least 39, and radiographic evidence of OA of the knee were recruited from December 1, 2010, to May 31, 2014, at 3 medical centers. Exclusion criteria were history of major joint replacement, terminal illness, inflammatory arthritis, prosthetic leg, cognitive impairment, lack of a telephone, or contraindications to elective replacement surgery. Data were analyzed on a per-protocol and intention-to-treat (ITT) basis. EXPOSURE Access to a decision aid for OA of the knee, a 40-minute video that describes the risks and benefits of TKR surgery. MAIN OUTCOMES AND MEASURES Receipt of TKR surgery within 12 months and/or a recommendation for TKR surgery from an orthopedic surgeon within 6 months after the intervention. RESULTS Among 336 patients (101 men [30.1%]; 235 women [69.9%]; mean [SD] age, 59.1 [7.2] years) randomized to the intervention or control group, 13 of 168 controls (7.7%) and 25 of 168 intervention patients (14.9%) underwent TKR within 12 months (P = .04). These changes represent a 70% increase in the TKR rate, which increased by 86%(11 of 154 [7.1%] vs 23 of 150 [15.3%]; P = .02) in the per-protocol sample. Twenty-six controls (15.5%) and 34 intervention patients (20.2%) in the ITT analysis received a recommendation for surgery within 6 months (P = .25). The difference in the surgery recommendation rate between the controls (24 of 154 [15.6%]) and the intervention group (31 of 150 [20.7%]) in the per-protocol analysis also was not statistically significant (P = .25). Adjustment for study site yielded similar results: for receipt of TKR at 12 months, adjusted ORs were 2.10 (95%CI, 1.04–4.27) for the ITT analysis and 2.39 (95%CI, 1.12–5.10) for the per-protocol analysis; for recommendation of TKR at 6 months, 1.39 (95%CI, 0.79–2.44) and 1.41 (95%CI, 0.78–2.55). CONCLUSIONS AND RELEVANCE A decision aid increased rates of TKR among black patients. However, rates of recommendation for surgery did not differ significantly. A patient-centered counseling and educational intervention may help to address racial variations in the use of TKR for the management of end-stage OA of the knee. TRIAL REGISTRATION clinicaltrials.gov Identifer: NCT01851785

This study highlights the poor adherence to and premature discontinuation without concurrent switching of RA biologics that should raise concern for clinicians as well as payers.

Objective. To examine racial differences in surgical complications, mortality, and revision rates after total knee arthroplasty. Methods. We studied patients undergoing primary total knee arthroplasty using 2001-2007 Pennsylvania Health Care Cost Containment Council data. We conducted bivariate analyses to assess the risk of complications such as myocardial infarction, venous thromboembolism, wound infections, and failure of prosthesis, as well as 30-day and 1-year overall mortality after elective total knee arthroplasty, between racial groups. We estimated Kaplan-Meier 1-and 5-year surgical revision rates, and fit multivariable Cox proportional hazards models to compare surgical revision by race, incorporating 5 years of followup. We adjusted for patient age, sex, length of hospital stay, surgical risk of death, type of health insurance, hospital surgical volume, and hospital teaching status. Results. In unadjusted analyses, there were no significant differences by racial group for either overall 30-day or in-hospital complication rates, or 30-day and 1-year mortality rates. Conclusion. In this sample of patients who underwent knee arthroplasty, we found no significant racial differences in major complication rates or mortality. However, African American patients, younger patients, and male patients all had significantly higher rates of revision based on 5 years of followup.