tbuckley/cabot-search huggingface dataset:
Gabepentinoids and Benzodiazepines in Medicare Part D
Authors: Eric D. Weinhandl
Journal: Journal of the American Society of Nephrology (2018)

I have read with interest the observational study regarding risks of adverse outcomes associated with gapapentin and pregabalin use.1 The authors adeptly analyzed data in the US Renal Data System database, including Medicare Part D prescription drug events (i.e., claims), and identified positive associations of gabapentin and pregabalin exposure with adjusted hazards of first episodes of altered mental status, fall, and fracture requiring either an emergency room visit or hospitalization. The study suffers from one unappreciated limitation. The authors attempted to adjust for the influence of concomitant use of benzodiazepines. Evidently, <0.5% of all patients in the study cohort used benzodiazepines. Such low utilization is clinically implausible but can be explained by the design of the Medicare Part D benefit during the study era (i.e., in 2011). The Medicare Modernization Act excluded benzodiazepines from Part D coverage between 2006 and 2012.2 This exclusion was eliminated by the Patient Protection and Affordable Care Act. The fact that the authors identified any use of benzodiazepines during the study era reflects the provision of “enhanced alternative coverage,” which generally offers a higher monthly premium in exchange for added value (e.g., reduced deductible, coverage of drugs not ordinarily included in the Part D benefit, reduced cost sharing in the coverage gap, etc.). Benzodiazepine toxicity is positively associated with risks of altered mental status, fall, and fracture.3 Thus, because of inherent limitations of data ascertained from Medicare Part D, unmeasured confounding by benzodiazepine use cannot be discounted. Because of study design, unmeasured confounding by opioid use also cannot be discounted. Ultimately, polypharmacy is common among patients on dialysis,4 and therefore, observational studies of the efficacy and safety of single drugs or single classes of drugs should be interpreted cautiously. Gabapentinoid toxicity is an observable event, but the magnitude of the associations reported by Ishida et al.1 may be biased. Disclosures E.D.W. is also an employee of NxStage Medical but reports no conflict of interest with this content.
TCT-102 Incidence, Predictors and Outcomes of Device-Related Thrombus After Left Atrial Appendage Closure With The WATCHMAN Device. Insights From the EWOLUTION Real World Registry.
Authors: Alexander Sedaghat, Georg Nickenig, Jan Schrickel, Hüseyin Ince, Boris Schmidt, Alexey Protopopov, Tim Betts, Tommaso Gori, Horst Sievert, Patrizio Mazzone, Marek Grygier, Christof Wald, Elisa Vireca, Kenneth Stein, Lucas Boersma
Journal: Journal of the American College of Cardiology (2018)
An observational study of the efficacy and safety of nivolumab in pretreated patients with advanced non small cell lung cancer (NSCLC): A Galician Lung Cancer Group Clinical Practice.
Authors: Carmen Areses Manrique, Francisco J. Afonso Afonso, Francisca Vazquez Rivera, Martin Lázaro Quintela, Sergio Vazquez-Estevez, Ovidio Fernandez Calvo, Rocío Vilchez Simo, Jorge García González, Eva Perez Lopez, Jesus Garcia Mata, Urbano Anido Herranz, Joaquin Casal Rubio, Jose Luis Firvida Perez
Journal: Journal of Clinical Oncology (2016)

e20612 Background: Nivolumab is an immune checkpoint inhibitor antibody and it has demonstrated durable responses and tolerability in pretreated patients with advanced NSCLC. This is an observational study to evaluate the efficacy and safety of nivolumab in previously treated patients with advanced NSCLC in the expanded access programme. Methods: Elegibility criteria included, histologically confirmed NSCLC clinical stage IIIB vs IV, evaluable disease, at least one prior therapy, performance status of 0/1 and an adequate organ function. Exclusion criteria included, positive test for hepatitis B, C or human immunodeficiency virus, severe autoinmune disease and patients with systemic corticosteroids or immunosuppressive medications. Patients received nivolumab 3 mg/kg IV (60 min) every 2 weeks until progressive disease (PD) or unacceptable toxicity. The aim of the study was to report the efficacy and safety profile of Nivolumab in pretreated patients with advanced NSCLC of our everyday clinical practice. The exploratory assessments include response rate (RR), progression-free survival (PFS), overall survival (OS) and treatment related adverse events (AEs). Results: From August of 2015 to January of 2016, with a median follow time of 6 months, 34 patients were enrolled from 5 different centers. The patients demographics were: median age 62 years, 9 female and 25 male; 14 never smoked and 20 former or current smoker; 22 patients adenocarcinoma, 2 large-cell carcinoma, 8 squamous-cell carcinoma and 2 NSCLC; 13 stage IIIB and 20 stage IV; 7 with central nervous system metastasis; 22 received 2 or more prior therapy lines. Among 20 patients evaluated, 7 had partial response, 10 disease stabilization and 3 disease progression. At the time of database lock, the median of PFS and OS was not reached. Grade 1-2 AEs occurred in 22 patients and the most common ones were fatigue (11) and rash/pruritis (7). Each of the toxicities were manageable and there were no grade 3-4 AEs or treatment-related deaths. Conclusions: Early data from this study suggests that Nivolumab is effective and well tolerated in patients with pretreated advanced NSCLC.
TCT-259 1000 Minimalist TAVR: Sapien through Sapien-3
Authors: Norihiko Kamioka, Patricia Keegan, Stamatios Lerakis, Jose Binongo, Hope Caughron, Shawn Reginauld, Hima Patel, Aneesha Maini, Altayyeb Yousef, Patrick Gleason, Bradley Leshnower, Chandan Devireddy, Kreton Mavromatis, James Stewart, Peter Block, Vinod Thourani, Robert Guyton, Vasilis Babaliaros
Journal: Journal of the American College of Cardiology (2018)
Communication preferences for breast cancer patients.
Authors: Sneha Deepak Phadke, Mark Vander Weg, Najla Itani, Nicole Grogan, Timothy Ginader, Sarah L Mott, Bradley D. McDowell
Journal: Journal of Clinical Oncology (2018)

e22121 Background: Skillful communication is at the heart of the patient-centered care model. With this in mind, there has been increased interest in improving clinician skills in delivering bad news to patients. The aim of this study was to determine the preferred method of receiving test results in a sample of breast cancer patients, using a questionnaire designed by the investigators. Methods: Patients aged 18 and over with a diagnosis of breast cancer or DCIS seen at the Holden Comprehensive Cancer Center between 6/12/17 -10/13/17 were offered a questionnaire at the time of check-in to their clinic visit. Effects of patient and disease characteristics on most preferred method of communicating test results were evaluated using multinomial logistic regression models. Results: Out of 582 patients offered a questionnaire, 452 (78%) were returned and 395 (68%) were deemed adequate for analysis. Most patients preferred a call ASAP regardless of the type of test (biopsy or imaging) or whether the result was good or bad news. Patients with Stage IV cancer were more likely to want in-person communication than patients with Stage I-III cancer for all types of results. Those with no college education were less likely than those with at least some college education to want a message via the electronic patient portal for good news on an imaging test (OR 0.21, CI 0.08-0.55) or a biopsy test (OR 0.32, CI 0.12-0.83). For imaging results, as the age of the patient increased, the odds of preferring in-person communication relative to a phone call ASAP increased (OR 1.04, CI 1.01-1.07). Compared to those with children, patients without children were more likely to want in-person results (OR 2.26, CI 1.17-4.35) or a scheduled call (OR 6.19, CI 1.35-28.41) for bad news on an imaging test versus a call ASAP. Conclusions: These results highlight that patients largely prioritize getting results as quickly as possible but that communication preferences may differ depending on factors such as stage of breast cancer, education level, and family type. Thus, each patient should be asked about their preferences for communication at the initial visit and perhaps again each time a test is ordered, as their preferences may vary in response to personal circumstances.
Abstract 15333: Triglyceride/High-Density Lipoprotein Ratio Among Children With Obesity Stratified by Race/Ethnicity, Sex, and Obesity Severity
Authors: Carter W English, Miranda L Ritterman Weintraub, June M Tester, Erica P Gunderson, Louise C Greenspan, Malini Chandra, Joan C Lo
Journal: Circulation (2017)

Introduction: The triglyceride/high-density lipoprotein ratio (TG/HDL), a measure of dyslipidemia, is considered a prognostic risk indicator for cardiovascular disease (CVD). This study examines demographic differences in TG/HDL among children with varying levels of obesity. Methods: Within a large healthcare system, we identified 2174 children age ≥10 years with BMI ≥95th percentile who had lipid profiles measured <1 year of their well-child visit (2012-2013). We classified obesity as moderate (Class I, BMI=100-119% of the 95th percentile) or severe (BMI≥120% of the 95th percentile, combining Class II BMI=120-139% and Class III BMI≥140%). Median and interquartile range (IQR) TG/HDL levels were examined by obesity severity, sex and race/ethnicity. Results: Among 2174 children (White 21.6%, Black 11.2%, Hispanic 46.7%, Asian 13.3%, Other/unknown race 7.3%), 49.1% were female and the average age was 13.1 ± 2.2 years. There were 54.4%, 29.5% and 16.1% with Class I, II, and III obesity, respectively. Median T...
Phase I open-label, ascending dose trial of AGEN1884, an anti-CTLA-4 monoclonal antibody, in advanced solid malignancies: Dose selection for combination with PD-1 blockade.
Authors: Breelyn A. Wilky, Priya Kumthekar, Robert Wesolowski, Jimmy J. Hwang, Steven I. Park, Igor Proscurshim, Guojun Yuan, Christopher D Dupont, Olga Shebanova, Jean-Marie Cuillerot, Edward Dow, Jeffrey J. Raizer, Carleen Gentry, Ainsley Ross, Elise Drouin, Nicholas Wilson, John M. Goldberg, Jennifer Buell, Robert Benjamin Stein
Journal: Journal of Clinical Oncology (2018)

3075 Background: AGEN1884 is a novel fully human IgG1 monoclonal antibody targeting cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Objective: Assess the safety, maximum tolerated dose, and pharmacokinetic (PK) and pharmacodynamic characteristics of AGEN1884 in patients with advanced and refractory malignancies. Methods: Patients (≥18 years old) with relapsed/refractory lymphoma or solid cancers without curative treatment options received AGEN1884 at 0.1, 0.3, 1, 3 or 6 mg/kg in a “3+3” trial design. An additional 10 patients were enrolled in both 1 and 3 mg/kg dose expansion cohorts. AGEN1884 was administered intravenously (IV) every 3 weeks for 4 doses and then every 3, 6, or 12 weeks at the Investigator’s discretion. Results: As of 03Jan2018 data cutoff, 33 patients were enrolled in the following cohorts: 0.1 mg/kg (n = 5, 2 not evaluable [NE] for dose-limiting toxicity [DLT]), 0.3 mg/kg (n = 3), 1 mg/kg (n = 10), 3 mg/kg (n = 12, 2 NE for DLT) and 6 mg/kg (n = 3). Median age was 61 years (range 26–88), baseline ECOG scores were 0 (N = 4), 1 (N = 25), unknown (4), with a median of 10 (range 3–26) prior therapies. As of Jan 31, 2018, no DLT’s have been reported. Immune-related adverse events were reported in 10 (30.3%) of patients as follows: 0.1 mg/kg (1 [20.0%]), 0.3 mg/kg (1 [33.3%]), 1 mg/kg (1 [10%]), and 3 mg/kg (6 [50%]) and included hypophysitis, colitis, diarrhea, rash and pruritus. Most were mild-moderate consistent with published reports of other CTLA-4 inhibitors. 6 patients (18.2%) came off study due to disease progression or AE’s but none related to treatment. Of 11 subjects evaluable for response, 1 with angiosarcoma treated at 0.1 mg/kg attained a CR at 7 months after achieving a PR. Three subjects with SD: 1 at 0.3 mg/kg with adenoid cystic carcinoma at Week 21 who had SD for 53 weeks; 2 subjects at 3 mg/kg: 1 with breast cancer with SD at Week 6 and 1 with invasive metaplastic breast cancer at Week 12 on study. Conclusions: AGEN1884 was well tolerated at 0.1, 0.3, 1 and 3 mg/kg dose levels. Enrollment continues at 6 mg/kg. Updated safety and PK data will be presented. A starting dose level of 1 mg/kg has been selected for combination with PD-1 blockade. Clinical trial information: NCT02694822.
Real-world data evaluating the value of PET-CT for mediastinal staging in patients diagnosed with non-small cell lung cancer in an area with high prevalence of granulomatous diseases: The LACOG-0114 study.
Authors: Carlos Cezar Fritscher, Mara Lise Zanini, Eduardo Herz Berdichevski, Eduardo Vilas, Bruno Hochhegger, Vinicius Duval da Silva, José Antônio Figueiredo Pinto, Leandro Genehr Fritscher, Louise Hartmann, Marcos Alba, Guilherme Parisotto Sartori, Cristina Matushita, Arthur Vieira, Vanessa Rezende Bortolotto, Rayssa Ruszkowski do Amaral, Facundo Zaffaroni, Jeovany Martínez-Mesa, Gustavo Werutsky, Carlos H. Barrios, Marcio Debiasi
Journal: Journal of Clinical Oncology (2017)

e20065 Background: Evaluation of the mediastinum is critical for therapeutic decision in patients with operable non-small cell lung cancer. This analysis aims to evaluate specificity and positive predictive value (PPV) of PET-CT in mediastinal staging of patients diagnosed with NSCLC in South Brazil, an area with high prevalence of infectious granulomatous disease, such as tuberculosis (estimated incidence of 45 cases/100.000 and only 63.7% of cure rate) (http://www.saude.rs.gov.br/upload/1459169540_RELATÓRIO%20TUBERCULOSE%202016.pdf). Methods: Patients with stages I-III NSCLC underwent 18FDG PET-CT before invasive mediastinal staging. Different SUV cut-offs were evaluated, but for the purpose of this analysis were considered positive all PET-CTs showing any mediastinal uptake &gt; 5 SUV. This abstract shows the specificity and the PPV associated with PET-CT when this high-uptake cut-of is considered. Results: From Aug/2014 to Aug/2016, 100 patients were enrolled, all treated at the Brazilian Public Health System, of which 85 were submitted to mediastinoscopy after PET-CT. Median age was 65 years (range 47-80). At baseline, 49 (58%) patients were male and 68 (80%) white. Current or former smokers accounted for 94% (80/85) of the sample. The prevalence of mediastinal involvement was 27% (23/85) confirmed by histopathological evaluation. PET-CT showed specificity of 79% (95% CI 67%–88%) and PPV of 54% (95% CI 40%–67%) when a SUV &gt; 5 was used as cut-off for positivity (see table). Conclusions: These findings consolidate the clinical impression that a positive PET-CT does not confirm the diagnosis of mediastinal involvement in NSCLC patients treated in areas with high prevalence of infectious granulomatous diseases. In this scenario, all positive findings should be confirmed with histopathological evaluation to assure the diagnosis. Clinical trial information: NCT02664792. [Table: see text]
Abstract 17824: Gemcabene and Atorvastatin Alone and Combined Markedly Reduce LDL-C in LDL Receptor-deficient Mice, a Model of Homozygous Familial Hypercholesterolemia
Authors: Charles L Bisgaier, Bruce J Auerbach
Journal: Circulation (2015)

Background: Gemcabene (Gem) is a late-stage Phase 2 clinical candidate being evaluated for the reduction of low-density lipoprotein cholesterol (LDL-C) in homozygous familial hypercholesterolemia (HoFH) patients. Combination therapy includes statins as standard of care to treat this genetic disorder. LDL-deficient (LDLr) mice have been widely used with lipid-lowering agents to demonstrate LDL-C lowering with good translation to clinical efficacy. We have previously shown that atorvastatin (Atorva) reduces LDL-C and apoB in the LDLr deficient mice and in casein-fed (endogenous hypercholesterolemic) rabbits. Experiment and Results: In the current study, we assessed Gem and Atorva effects alone and in combination on reduction of LDL-C in chow-fed LDLr deficient mice, an animal model of HoFH. Baseline LDL-C and total cholesterol were 246±20 mg/dL and 329±23 mg/dL in these mice Female LDLr deficient mice (n=10) were treated with Atorva alone (60mg/kg/day), Gem alone (60/mg/kg/day) or the agents combined (Atorva + Gem)(each at 60 mg/kg/day) for 14 days. Following treatments with Atorva, Gem, and Atorva+Gem, fasting LDL-C reduced by 22%, 55% and 72%, respectively, and total cholesterol by 21%, 47%, and 58%, respectively; showing additional reduction of 50% LDL-C by Gem on top of Atorva alone. Since LDLr are absent in these mice, similar to HoFH patients, the LDL-C lowering by Gem could be due to reduced VLDL production rates. Indeed, our studies in rat hepatocytes and in apoB100-only mice (apobec-1 knockout) showed reduced radioactivity in cholesterol and triglyceride fractions in the hepatocytes and in the plasma and liver of mice administered 14C acetate, suggesting cholesterol and fatty acid synthesis inhibition as a mechanism of LDL-C lowering. Gem also enhances the clearance of VLDL in normal rats. We propose both mechanisms may contribute to LDL-C reduction in LDLr deficient mice. A more detailed kinetic study of Gem in LDLr deficient models is underway to verify these proposed mechanisms. Conclusions: Gemcabene alone and combined with atorvastatin significantly (55-72%) reduced LDL-C in this predictive in-vivo HoFH disease model. These findings suggest that treatment with Gem on top of standard of care therapy by statins may benefit HoFH patients.
Prognostic significance of free testosterone levels during chemotherapy with carboplatin plus docetaxel (CD) in metastatic castration- and docetaxel-resistant prostate cancer (mDRPC).
Authors: Christoph W. Reuter, Philipp Ivanyi, Christoph A. J. von Klot, Axel Stuart Merseburger, Viktor Grünwald, Arnold Ganser
Journal: Journal of Clinical Oncology (2016)

5029 Background: Carboplatin plus docetaxel may be effective in mDRPC. Platinum(II)-complexes have been shown to interfere with steroid biosynthesis lowering testosterone levels by inhibiting the cholesterol side chain cleavage enzyme (CYP11A1), 3β-hydroxysteroid dehydrogenase (HSD3B1,2) and 17α hydroxylase/C17,20-lyase (CYP17A1). Methods: Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Treatment consisted of at least 2 cycles of carboplatin AUC5 iv for 30 min on day 1 every 4 weeks (q4w), docetaxel (35 mg/m2) iv for one hour on days 1, 8, (15) plus prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. Free testosterone (FT) levels were measured before (n = 70) and during CD chemotherapy (n = 62). Results: Of the 93 pts. treated since February 2005, 95.7% had bone, 41.9% lymph node, 26.9% liver and 19.4% lung metastases. At the time of the current analysis, the median follow-up time was 15.4 months. The objective response rate was 38.6% and the disease control rate 71.4% in the 57 pts. with measureable disease. Response of prostate-specific antigen ( ≥ 50%) was observed in 46/93 (49.5%) patients. Median PFS was 7.2 months (CI 95% 6.2, 8.1) and median OS was 15.6 months (CI 95% 11.5, 19.8). The most common reversible grade 3/4 toxicity was leukopenia/ neutropenia (40.0/38.1%). Median FT levels were 0.65 pg/ml before and < 0.18 pg/ml during carboplatin/docetaxel treatment (nadir levels, p < 0.001; detection limit < 0.18 pg/ml). Median serum androgene levels (T+DHT) were 0.1 ng/ml before and below the detection limit of < 0.05 ng/ml during DC treatment. In multivariate analyses, LDH, PSA response, FT nadir levels below the detection limit ( < 0.18 pg/mL) during CD treatment were associated with longer OS (p < 0.05). Conclusions: These data suggest that CD may be an important second-line treatment option for mDRPC patients by inhibiting the testosterone biosynthesis.
KRAS and P53 mutations and FDG-PET as a measure of glycolytic activity in metastatic non-small cell lung cancer patients.
Authors: Seo-Hyun Kim, Ammar Karo, Sanjib Basu, Jeffrey Allen Borgia, Philip Bonomi, Marta Batus, Mary J. Fidler
Journal: Journal of Clinical Oncology (2016)

9086 KRAS and P53 Mutations and FDG-PET as a Measure of Glycolytic Activity in Metastatic Non-Small Cell Lung Cancer Patients. Background: Early data suggests metabolic reprograming as a mechanism driving growth and proliferation in KRAS mutated non-small cell lung cancer. In addition, P53 and STK11 have been shown to alter metabolic programing. The loss of p53 leads to loss of its inhibitory effect on glycolysis, while STK11 mutations prevent the shut off of cellular signaling which occurs in hypoglycemic environment, shifting cells to anaerobic respiration. The aim for this study was to correlate KRAS, p53, and STK11 mutations with maximal standardized uptake value (SUVmax) on routinely performed FDG-PET scans. Methods: Stage IV non-small cell lung cancer patients with Foundation One testing results and baseline FDG-PET scans were included. Associations between mutations and SUVmax uptake were assessed using the Kruskal-Wallis test. Results: 53 patients had PET CT scans and genomic analyses of their tumors. 17 (32%) patients had KRAS mutations, 31 (58%) patients had P53 mutations, and 5 (9%) patients had STK11 mutations. Patients who had concurrent KRAS and P53 mutations had higher PET SUV activity (median SUVmax18.82) compared to only KRAS mutation (median 8.15), only P53 mutation (median 8.25), and no mutation (median 6.25, p = 0.006). Although individual numbers were small, mutational analysis of KRAS by subtype did not show any significant correlation with SUVmax. There were four patients who had concurrent p53 and STK11 mutations while only one patient who had both KRAS and STK11 mutations and neither appeared to significantly impact SUVmax. Conclusions: Mutations in KRAS and P53 correlated with increased SUVmax. Using SUV on PET CT as a surrogate of glycolysis, it appears mutations in both KRAS and P53 may be associated with increased glycolytic activity. Patients with P53 and KRAS mutations and /or with high SUV uptakes may be candidates for targeting cellular metabolism.