Citations

SummaryObjectiveTo better understand the relationship between efficacy and perampanel dose, integrated actual (last) dose data from three phase III trials and an extension study (blinded Conversion Period; open‐label Maintenance Period) were analyzed.MethodsSeizure frequency data were analyzed in patients who were randomized to and completed the 13‐week Maintenance Period of the phase III studies on perampanel 8 mg, and who received an actual (last) dose of 12 mg during (1) the extension 16‐week blinded Conversion Period or (2) weeks 1–13 of the extension Maintenance Period. Due to a treatment‐by‐region interaction (p = 0.042), analyses excluded patients from the Latin America region (n = 162/1,480; 10.9% of the treated cohort).ResultsOf 372 patients randomized to 8 mg in the phase III studies, 273 completed the Maintenance Period at 8 mg and 267 entered the extension study. In patients who then had an actual (last) dose of 12 mg during the extension blinded Conversion Period (n = 217), median percent change in seizure frequency per 28 days improved from −32.4% (8 mg, phase III Maintenance Period) to −44.2% (12 mg, extension blinded Conversion Period); 50% responder rates increased slightly from 37.3% to 42.9%. In patients who completed the phase III studies on 8 mg and had an actual (last) dose of 12 mg during weeks 1–13 of the extension Maintenance Period (n = 181), median percent change in seizure frequency per 28 days improved from −34.1% (phase III Maintenance Period) to −46.0% (weeks 1–13 extension Maintenance Period); 50% responder rates were 39.2% and 46.4%. Seizure control remained substantially unchanged in patients who completed the phase III studies at 12 mg and continued on that dose during the extension.SignificanceIncreasing perampanel dose from 8 to 12 mg can produce additional benefits in seizure control in at least some patients who tolerate the higher dose.

AbstractBackground & AimsSurvival of patients with hepatocellular carcinoma (HCC) is determined by hepatic function and tumour extent. Recently, a new Model to Estimate Survival in Ambulatory HCC patients (MESIAH) was proposed to predict overall survival in ambulatory HCC patients. This study aimed to evaluate the prognostic performance of the MESIAH score in an independent cohort of HCC patients.MethodsA cohort of 1969 patients newly diagnosed with HCC at the National Cancer Center, Korea between January 2004 and December 2009 was used for validation of the MESIAH score. The model's performance was assessed using C‐statistics, the likelihood ratio (LR) χ2 value and Akaike information criterion (AIC).ResultsPatients in the cohort had a median age of 56 years and 83.2% were men. Hepatitis B virus infection was present in 74.6 and 81.6% had a Child–Pugh class A. The median overall survival was 21.4 months. The MESIAH score had a higher degree of discrimination, with a C‐statistic of 0.792 [95% confidence interval (CI), 0.782–0.803], when compared with the Barcelona Clinic Liver Cancer (BCLC) staging system [0.665 (95% CI, 0.653–0.678), P < 0.001]. The LR χ2 value and the AIC of MESIAH were also better than those of BCLC, Cancer of the Liver Italian Program, Japan Integrated Scoring and Tokyo score. The observed survival in the cohort closely matched that predicted by the MESIAH score.ConclusionsThe new prognostication model MESIAH accurately estimated the overall survival of Korean HCC patients and may be useful in future research as well as individual patient care.

The baroreflex plays a key role in human BP (blood pressure) regulation. Its efferent limb consists of a vagal and a sympathetic component. The Valsalva manoeuvre is widely used to quantify vagal baroreflex function [BRS_vagal (vagal baroreflex sensitivity)], but most studies have focused on the R–R interval response to BP decrement, even though the subsequent response to an increment in BP is important and different. In the present study, we sought to evaluate whether BRS_vagal can be determined from BRSvagalinc (BRS_vagal derived from the rise in BP during phases III–IV of the Valsalva manoeuvre), to assess the association between BRSvagalinc and BRSvagaldec (BRS_vagal derived from the preceeding BP decrement) and to validate BRSvagalinc as an index of autonomic function. We studied patients with severe autonomic failure (n=49, 25 female), mild autonomic failure (n=25, 11 female) and matched normal controls (n=29, 15 female). BRSvagalinc and BRSvagaldec were calculated as the regression slope of R–R interval and systolic BP during phases III–IV and the early phase II of the Valsalva manoeuvre respectively, and compared these with other autonomic indices across the groups. BRSvagalinc was calculated in all subjects and correlated highly with BRSvagaldec (r=0.72, P&lt;0.001). BRSvagalinc also correlated significantly with BP changes during phases II and IV of the Valsalva manoeuvre and sympathetic barosensitivity. BRSvagalinc was significantly different between the groups, being highest in the controls and lowest in patients with severe autonomic failure. In conclusion, vagal BRS, determined by relating R–R interval with the BP increase following phase III, is a valuable autonomic index, provides additional information about vagal baroreflex function and reflects overall severity of autonomic failure.

Abstract Background: Breast cancer is not a homogeneous disease, but several different and unique subtypes defined by gene expression analysis. Incidence and mortality rates vary by almost 3-fold between Alaska (highest) and the Southwestern tribes (lowest). We hypothesized that these differences may be due to, in part, varying levels of biologic tumor aggressiveness. Methods: A biorepository of the North Central Cancer Treatment Group with 95 cases of American Indian and Alaska Native (AIAN) women with adenocarcinoma of the breast surgically treated from 1990 to 2000 was tested for several biomarkers. Comparison distributions of biomarker values across state of residence using t tests for continuous (p53, MIB-1, cyclin D) and ordinally scaled markers [EGF receptor (EGFR), BCL-2, Her2] and χ2 tests of significance for binary markers [estrogen receptor (ER), progesterone receptor (PR)] were done. Results: Significant regional differences in some biomarker expression levels were seen. No increase was observed in “triple-negative” breast cancer or Her2 overexpression in these cases. Conclusions: Despite a 3-fold difference in breast cancer mortality in Alaska Native versus Southwestern American Indians, standard biomarkers such as ER, PR, and Her2 neu expression did not explain the disparity. Impact: There is a need for research to understand the biologic basis of breast cancer disparities in AIAN women. Potential for a prospective trial will be explored with tribes. See all articles in this CEBP Focus section, “Community Network Program Centers.” Cancer Epidemiol Biomarkers Prev; 23(3); 409–15. ©2014 AACR.

Background: Although limiting prescription refills is considered as a strategy to increase compliance with the treatment regimen and follow-up, no literature exists to support its effectiveness. We sought to investigate whether decreasing the number of prescription refills affects no-show rate at an urban teaching primary care continuity clinic in New York. Methods: Eight teaching attending physicians and 19 residents implemented a “new prescribing strategy” from February 9 to 22, 2012, which limited the number of refills only to cover until the next intended clinic visit. All adult patient visits were included if follow-up visits were requested to be scheduled within 3 months and prescriptions were given through an electronic prescription system. No-show rates for the first follow-up visits up to 120 days from the initial visits during the interventional period were compared with those during the baseline period (December 15-28, 2011). Results: Two hundred twenty-one patients in the baseline period and 278 in the interventional period were included in the analysis. Median total supply of prescription was 6 and 3 months, respectively ( P < .001). The no-show rates were not significantly different between the 2 periods (19.0% [42/221] vs 16.6% [46/278], P = .5). In multivariate regression analysis, the no-show rate did not change significantly during the interventional period compared with the baseline period (odds ratio [OR] 1.0; 95% confidence interval, 0.6-1.5; P = .8). Younger age (OR 1.03 per year, P = .008), male gender (OR 2.0, P = .003), Medicaid or Medicare insurance (OR 3.7, P = .01; OR 4.2, P = .02), and diagnosis of diabetes (OR 1.8, P = .04) or asthma (OR 2.0, P = .03) were associated with higher no-show rates. Conclusions: Reducing the number of refills did not significantly affect no-show rates in the immediate follow-up. Alternative strategies should be considered to minimize no-shows.