A placebo effect appears to exist in the treatment of reflux laryngitis. However, hoarseness, when initially scored low, and throat clearing resulting from reflux laryngitis are effectively treated by omeprazole.

Purpose Multiplex gene panel testing (MGPT) allows for the simultaneous analysis of germline cancer susceptibility genes. This study describes the diagnostic yield and patient experiences of MGPT in diverse populations. Patients and Methods This multicenter, prospective cohort study enrolled participants from three cancer genetics clinics—University of Southern California Norris Comprehensive Cancer Center, Los Angeles County and University of Southern California Medical Center, and Stanford Cancer Institute—who met testing guidelines or had a 2.5% or greater probability of a pathogenic variant (N = 2,000). All patients underwent 25- or 28-gene MGPT and results were compared with differential genetic diagnoses generated by pretest expert clinical assessment. Post-test surveys on distress, uncertainty, and positive experiences were administered at 3 months (69% response rate) and 1 year (57% response rate). Results Of 2,000 participants, 81% were female, 41% were Hispanic, 26% were Spanish speaking only, and 30% completed high school or less education. A total of 242 participants (12%) carried one or more pathogenic variant (positive), 689 (34%) carried one or more variant of uncertain significance (VUS), and 1,069 (53%) carried no pathogenic variants or VUS (negative). More than one third of pathogenic variants (34%) were not included in the differential diagnosis. After testing, few patients (4%) had prophylactic surgery, most (92%) never regretted testing, and most (80%) wanted to know all results, even those of uncertain significance. Positive patients were twice as likely as negative/VUS patients (83% v 41%; P < .001) to encourage their relatives to be tested. Conclusion In a racially/ethnically and socioeconomically diverse cohort, MGPT increased diagnostic yield. More than one third of identified pathogenic variants were not clinically anticipated. Patient regret and prophylactic surgery use were low, and patients appropriately encouraged relatives to be tested for clinically relevant results.

The CCR score threshold appropriately dichotomized patients into low- and high-risk groups for 10-year PCM, and may enable more appropriate selection of patients for AS.

Injudicious use of antibiotics contributes to increased bacterial resistance, and patient expectations encourage physicians to overuse antibiotics. The authors evaluated the level of ill college students' antibiotic-seeking behavior to determine if receiving an antibiotic prescription influenced patients' satisfaction with visits to a clinician. Of 129 students with upper respiratory complaints presenting to a university health center, 55% expected an antibiotic prescription. Antibiotic expectation was significantly more likely among students who thought they had a bacterial versus a viral infection (90% vs 40%; p < .01). A clear diagnosis, an explanation of the rationale for treatment, and an antibiotic prescription were significantly associated with patient satisfaction. Clinicians prescribed an antibiotic for 36% of the students; only 13% of these 46 had requested an antibiotic during the visit. At some previous time, one third of the students had taken an antibiotic prescribed for an earlier illness or for another person. Better patient education and improved clinician-patient communication can potentially help to reduce the injudicious use of antibiotics.

An estimated 1:40 individuals of Ashkenazi Jewish (AJ) ancestry carry one of three common founder mutations in BRCA1 or BRCA2, resulting in the inherited cancer condition, Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Targeted testing for these three mutations (BRCA1 187delAG, BRCA1 5385insC, and BRCA2 6174delT) is therefore recommended for all AJ breast and ovarian cancer patients, regardless of age of diagnosis or family history. Comprehensive analysis of both genes is recommended for a subset of AJ patients in whom founder mutations are not identified, but estimates of the yield from comprehensive analysis in this population vary widely. We sought to determine the proportion of non-founder mutations as a percentage of all mutations in BRCA1 and BRCA2 among AJ patients to inform decisions about HBOC testing strategies in this population. We analyzed the genetic testing results for 37,952 AJ patients for whom clinical testing of BRCA1 and BRCA2 was performed at Myriad Genetic Laboratories from January 2006 through August 2013. Analysis was limited to AJ-only patients for whom the initial test order was either (1) comprehensive testing, or (2) founder mutation testing with instructions to automatically "reflex" to comprehensive analysis if negative. Cases were excluded if a separate follow-up order was placed to reflex to comprehensive analysis only after the founder mutation testing was reported out as negative. Among all BRCA1 and BRCA2 mutations detected in these groups, the percentage of non-founder mutations was 13 % (104/802) and 7.2 % (198/2,769). One-hundred and eighty-nine unique non-founder mutations were detected, 76 in BRCA1 and 113 in BRCA2. Non-founder mutations make up between 7.2 and 13.0 % of all BRCA1 and BRCA2 mutations in Ashkenazi Jews. A wide range of mutations are present, most of which are also seen in non-AJ individuals.

No abstract

MPC-6827 (Azixa) is a small-molecule microtubule-destabilizing agent that binds to the same (or nearby) sites on b-tubulin as colchicine. This phase I study was designed to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics (PK) of MPC-6827 in patients with solid tumors. Patients with advanced/metastatic cancer were treated with once-weekly, 1-to 2-hour intravenous administration of MPC-6827 for 3 consecutive weeks every 28 days (1 cycle). Dose escalation began with 0.3, 0.6, 1, and 1.5 mg/m 2 , with subsequent increments of 0.6 mg/m 2 until the MTD was determined. A 3 þ 3 design was used. Pharmacokinetics of MPC-6827 and its metabolite MPI-0440627 were evaluated. Forty-eight patients received therapy; 79 cycles were completed (median, 1; range, 1-10). The most common adverse events were nausea, fatigue, flushing, and hyperglycemia. The DLT was nonfatal grade 3 myocardial infarction at 3.9 mg/m 2 (1/6 patients) and at 4.5 mg/m 2 (1/7 patients). The MTD was determined to be 3.3 mg/m 2 (0/13 patients had a DLT). Five (10.4%) of the 48 patients achieved stable disease (Response Evaluation Criteria in Solid Tumors) for 4 months or greater.MPC-6827 has a high volume of distribution and clearance. Half-life ranged from 3.8 to 7.5 hours. In conclusion, MPC-6827 administered intravenously over 2 hours at a dose of 3.3 mg/m 2 once weekly for 3 weeks every 28 days was safe in patients with heavily pretreated cancer. Clinical trials with MPC-6827 and chemotherapy are ongoing.

Response data in longitudinal studies and group randomized trials are gathered on units that belong to clusters, within which data are usually positively correlated. Therefore, estimates and confidence intervals for intraclass correlation or variance components are helpful when designing a longitudinal study or group randomized trial. Data simulated from both study designs are used to investigate the estimation of variance and covariance parameters from the following procedures: for continuous outcomes, restricted maximum likelihood (REML) and estimating equations (EE); for binary outcomes, restricted pseudo-likelihood (REPL) and estimating equations (EE). We evaluate these procedures to see which provide valid and precise estimates as well as correct standard errors for the intraclass correlation coefficient or variance components. REML seems the better choice for estimating terms related to correlation for models with normal outcomes, especially in group randomized trial situations. Results for REML and EE are mixed when outcomes are continuous and non-normal. With binary outcomes neither REPL nor EE provides satisfactory estimation or inference in longitudinal study situations, while REPL is preferable for group randomized trials.