tbuckley/cabot-search huggingface dataset:
Abstract P163: Disparities By Patient Sex? Treatment Duration and Outcomes Of P2Y <sub>12</sub> Inhibitor Therapy in Women Compared to Men After an Acute Myocardial Infarction Among Medicare Beneficiaries
Authors: Ryan P Hickson, Anna M Kucharska-Newton, Jo Ellen Rodgers, Allison E Aiello, Betsy Sleath, Gang Fang
Journal: Circulation (2020)

Introduction: P2Y 12 inhibitors prevent ischemic events while increasing bleeding risk. It is unclear if clinical differences by sex justify different therapy durations after myocardial infarction (MI). Hypothesis: Women will discontinue P2Y 12 inhibitor therapy earlier than men after MI. Methods: MI hospitalizations in 2008-2013 were identified in a 20% Medicare administrative claims sample. Patients were ≥66 years old; had no recent P2Y 12 inhibitor indication; and had a P2Y 12 inhibitor prescription fill within 30 days post-MI. Therapy duration was measured using days supply and 30-day drug-free interval; duration was modeled as risk of discontinuation over time. Patients were followed up to 24 months. Adjusting for sociodemographics, clinical risks, prescriber characteristics, and contextual factors, disease risk scores (DRSs) were estimated from 4 hazard models predicting P2Y 12 inhibitor discontinuation and 3 competing risks: 1) death or hospice admission, 2) ischemic event (MI, ischemic stroke, revascularization), and 3) bleeding event. Male and female patients were matched 1:1 on the 4 DRSs using Mahalanobis distance. Cause-specific risk differences (RDs) were estimated with the Aalen-Johansen estimator and bootstrapped confidence intervals (CIs). Results: Median time on P2Y 12 inhibitor was 388 days (interquartile range 133-720). Of 30,613 patients (51.2% female), 20,002 were matched. At 24 months, women compared to men had a similar risk of treatment discontinuation (RD 0.84%; 95% CI -0.52, 2.19). While still on a P2Y 12 inhibitor, women were less likely to experience death/hospice admission (RD -0.82%; 95% CI -1.39, -0.24) or ischemic event (RD -0.92%; 95% CI -1.81, 0.06) at 24 months but had a similar bleeding risk (RD -0.07%; 95% CI -0.52, 0.39). Conclusions: Duration of P2Y 12 inhibitor use was similar in men and women. Risks for death/hospice admission and ischemic events while taking a P2Y 12 inhibitor were lower in women, suggesting a differential response to therapy that should be investigated further.
Abstract 10710: Global Knockout of LDLRAP1 Regulates Atherosclerosis, Insulin Resistance, and VSMC Foam Cell Formation
Authors: Tani Leigh, Sheri Kelemen, Mitali Ray, Christine Vrakas, Allison Herman, Gavin Landesberg, Rachael Okune, Rosario Scalia, Michael Autieri
Journal: Circulation (2019)

Introduction: Atherosclerotic vascular syndromes account for 50% of all deaths in the United States, and are a considerable medical and socioeconomic problem contributing to mortality of many condi...
Endoxifen for breast cancer: Multiple-dose, dose-escalation study characterizing pharmacokinetics and safety in metastatic breast cancer patients.
Authors: Ateeq Ahmad, S. Sheikh, R. Nagarkar, J. K. Singh, S. Krishnan, S. Shrivastav, P. Shetty, P. Kale, R. C. Rane, I. Ahmad
Journal: Journal of Clinical Oncology (2012)

3089^ Background: Endoxifen is an active metabolite of tamoxifen, a drug used in the treatment of breast cancer. To be clinically effective, tamoxifen must be converted to endoxifen by CYP2D6. Direct administration of endoxifen would not be subject to pharmacogenetic variations or drug-drug interactions. Our preclinical studies (Breast Cancer Treat 122, 579-584, 2010) have validated the concept of using endoxifen for the treatment of breast cancer. In human (Clin. Pharmacol. Ther. 88, 814-817, 2010), the single oral doses tested up to 4 mg of endoxifen were safe, well tolerated and bioavailable. Methods: A multiple-dose escalating study was conducted in 3 cohorts and each cohort had 6 patients (18 metastatic breast cancer patients). Endoxifen at 3 dose levels (2, 4, or 8 mg) was given once daily for 28 days. Routine laboratory tests, vital signs and electrocardiograms were measured throughout the study. Blood samples for PK analysis were collected after 28 days post dose. Endoxifen in plasma samples was determined using LC-MS/MS. Results: Endoxifen was found to be safe up to 8.0 mg. At steady state, it displays dose-proportional PK with respect to C max and AUC ( see Table below). Conclusions: Multiple daily endoxifen doses of 4.0-8.0 mg resulted in endoxifen exposures that would be sufficient for effective therapy. The favorable safety and multiple-dose PK profile of endoxifen warrants further evaluation of safety and efficacy of endoxifen in breast cancer patients. [Table: see text]
Renal and Cardiovascular Outcomes After Weight Loss From Gastric Bypass Surgery in Type 2 Diabetes: Cardiorenal Risk Reductions Exceed Atherosclerotic Benefits
Authors: Vasileios Liakopoulos, Stefan Franzén, Ann-Marie Svensson, Naveed Sattar, Mervete Miftaraj, Staffan Björck, Johan Ottosson, Ingmar Näslund, Soffia Gudbjörnsdottir, Björn Eliasson
Journal: Diabetes Care (2020)

OBJECTIVE We examined detailed renal and cardiovascular (CV) outcomes after gastric bypass (GBP) surgery in people with obesity and type 2 diabetes mellitus (T2DM), across several renal function categories, in a nationwide cohort study. RESEARCH DESIGN AND METHODS We linked data from the National Diabetes Register and the Scandinavian Obesity Surgery Register with four national databases holding information on socioeconomic variables, medications, hospitalizations, and causes of death and matched 5,321 individuals with T2DM who had undergone GBP with 5,321 who had not (age 18–65 years, mean BMI &amp;gt;40 kg/m2, mean follow-up &amp;gt;4.5 years). The risks of postoperative outcomes were assessed with Cox regression models. RESULTS During the first years postsurgery, there were small reductions in creatinine and albuminuria and stable estimated glomerular filtration rate (eGFR) in the GBP group. The incidence rates of most outcomes relating to renal function, CV disease, and mortality were lower after GBP, being particularly marked for heart failure (hazard ratio [HR] 0.33 [95% CI 0.24, 0.46]) and CV mortality (HR 0.36 [(95% CI 0.22, 0.58]). The risk of a composite of severe renal disease or halved eGFR was 0.56 (95% CI 0.44, 0.71), whereas nonfatal CV risk was lowered less (HR 0.82 [95% CI 0.70, 0.97]) after GBP. Risks for key outcomes were generally lower after GBP in all eGFR strata, including in individuals with eGFR &amp;lt;30 mL/min/1.73 m2. CONCLUSIONS Our data suggest robust benefits for renal outcomes, heart failure, and CV mortality after GBP in individuals with obesity and T2DM. These results suggest that marked weight loss yields important benefits, particularly on the cardiorenal axis (including slowing progression to end-stage renal disease), whatever the baseline renal function status.
Retrospective analysis of data from a phase I trial with a new adaptive method
Authors: C. Meille, L. Favier, B. Coudert, D. Barbolosi, A. Iliadis, F. Biville, J. Garnier, R. Ferri-Dessens
Journal: Journal of Clinical Oncology (2007)

1067 Background: The phase I trial CAPEV CGFL 01 [ESMO, Vienne, Austria: 2004.V 52–53] aimed to find the Maximum Tolerated Dose (MTD) of i.v. Vinorelbine when associated with oral Capecitabine for three cycles of 21 days in metastatic breast cancer (MBC). Method: Vinorelbine was administered at d1 and d15 and Capecitabine b.i.d. from d1 to d14 (fixed at 2,000 mg/m 2 /day). Trial design was based on “3+3” scheme with predetermined dose levels of Vinorelbine starting at 25 mg/m 2 /day. Ten patients (age 46–67 years) with MBC were enrolled in this trial. A new phase I adaptive method [Statistical Methods in Biopharmacy. Statistical Innovations in Clinical trials, Paris September 2005] under validation was used to analyze data available from the CAPEV trial. This method performs precise definition of Dose Limiting Toxicity (DLT) and modeling of all the grades of toxicity. The method allows sequential real time analysis of data by alternating estimation and design steps. Results: Most frequent toxicities were hematological (anemia and neutropenia) and cytolysis. Three DLTs occurred for the first 6 patients included at the starting level of Vinorelbine. De-escalation to 20 mg/m 2 was done at the 7 th patient but a new DLT occurred for the 7 th patient and lead to trial ending at the 10 th patient. Firstly, by analyzing all available data, Vinorelbine MTD was calculated at 20.2±4.04 mg/m 2 /day. Secondly, data was processed according to the inclusion time of patients; the adaptive method calculated a Vinorelbine MTD equal to 19.5±8.34 mg/m 2 /day as early as the 4 th patient. Conclusion: The administration scheme of i.v. Vinorelbine and oral Capecitabine tried in this study cannot be retained for MBC treatment. However, early convergence of adaptive method clearly shows its high performance in the de-escalation scheme and Vinorelbine MTD determination. With this method Vinorelbine MTD could have been determined with the 4 th patient data without needing the inclusion of 6 additional patients (4 th and not 7 th patient). This method should be used in prospective phase I trials and in parallel with classical and clinical method of MTD determination. No significant financial relationships to disclose.
Using fractional exhaled nitric oxide to guide step-down treatment decisions in patients with asthma: a systematic review and individual patient data meta-analysis
Authors: Kay Wang, Jan Y. Verbakel, Jason Oke, Alexander Fleming-Nouri, Josh Brewin, Nia Roberts, Norihiro Harada, Ryo Atsuta, Kazuhisa Takahashi, Kazutaka Mori, Tomoyuki Fujisawa, Toshihiro Shirai, Tomotaka Kawayama, Hiromasa Inoue, Stephen Lazarus, Stanley Szefler, Fernando Martinez, Dominick Shaw, Ian D. Pavord, Mike Thomas
Journal: European Respiratory Journal (2020)

Background High exhaled nitric oxide fraction ( F ENO ) levels are associated with greater risk of asthma exacerbation. However, it is not clear how F ENO can be used to guide safe reductions in inhaled corticosteroid (ICS) doses in asthma patients. This study assesses the ability of F ENO to guide ICS reductions. Methods Systematic searching of electronic databases identified prospective observational studies and randomised controlled trials which recruited participants with mild-to-moderate asthma aged ≥12 years and measured F ENO before reducing ICS. We performed multilevel mixed-effects logistic regression in relation to acute exacerbations and estimated each participant's exacerbation risk using our logistic regression model. Results We included data from seven out of eight eligible studies, representing 384 participants. ICS doses were halved in four studies and withdrawn in three studies. A baseline F ENO measurement of ≥50 ppb was associated with increased risk of exacerbations (crude OR 3.14, 95% CI 1.41–7.00, p=0.005; adjusted OR 3.08, 95% CI 1.36–6.98, p=0.007) and corresponded to an estimated exacerbation risk cut-off of 15%. Reducing ICS when estimated exacerbation risk was &lt;15% versus &lt;10% would result in fewer patients remaining on the same ICS dose (40 (10.4%) out of 384 versus 141 (36.7%) out of 384), but similar proportions of patients avoiding exacerbations (222 (91.4%) out of 243, 95% CI 87.1–94.6% versus 311 (90.4%) out of 344, 95% CI 86.8–93.3%). Conclusion In patients with mild-to-moderate asthma, gradual ICS reduction when F ENO is &lt;50 ppb may help decrease ICS use without increasing exacerbations. Future research should aim to validate these findings in larger populations.
Abstract 50: Associations of Dietary Saturated Fatty Acids With Incident Coronary Heart Disease Depend on the Food Sources: EPIC-CVD Prospective Case-cohort Study in Nine European Countries
Authors: Marinka Steur
Journal: Circulation (2020)

Introduction: The associations of dietary total fatty acids and the classes saturated, monounsaturated, and polyunsaturated fatty acids (SFAs, MUFAs, and PUFAs) with coronary heart disease (CHD) remain contentious. Moreover, the role of isocaloric macronutrient substitutions and specific food sources of SFAs, particularly in European context, is unclear. Hypothesis: We evaluated the hypothesis that associations of dietary fatty acids vary depending on specific macronutrient substitutions and food sources of SFAs. Methods: We conducted case-cohort analyses including 10,529 incident CHD cases and a random subcohort of 16,730 men and women selected from 385,747 eligible participants in nine countries of the European Prospective Investigation into Cancer and Nutrition Study. Habitual diet was assessed using country-specific dietary questionnaires, and macronutrient intakes were estimated using standardised nutrient databases. Country-specific HRs (95% CIs) per 5% energy intake from dietary total fatty acids, SFAs, MUFAs, and PUFAs were estimated using Prentice-weighted Cox regression models and pooled using random-effects meta-analyses, with and without considering isocaloric macronutrient substitutions. The associations of dietary SFAs from different food sources, including specific macronutrient substitutions, with CHD were also investigated. Results: There was no evidence of associations of dietary total fatty acids, SFAs, MUFAs, or PUFAs with incident CHD, regardless of the substitution macronutrient. Each 1% higher energy intake of SFAs from yoghurt, cheese, and fish were associated with a 7% (95% CI 1-12%), 2% (0-4%) and 13% (0-25%) lower CHD incidence, while SFAs from red meat and butter were associated with a 7% (2-12%) and 2% (0-4%) higher CHD incidence, respectively. Conclusions: There was no evidence of associations of dietary total fatty acids, SFAs, MUFAs, and PUFAs, with CHD incidence, regardless of the substitution nutrients, within the range of intakes in this European population. The opposite direction of associations of SFAs from different food sources such as red meat versus fermented dairy products suggests that public health recommendations should consider foods and overall diets, alongside the macronutrients they contain.
A three-dimensional hyaluronic acid-based niche enhances the therapeutic efficacy of human natural killer cell-based cancer immunotherapy
Authors: Young Ha Ahn, Long Ren, Seok Min Kim, Sang-Hwan Seo, Cho-Rok Jung, Da Seul Kim, Ji-Yoon Noh, Soo Yun Lee, Hyunseung Lee, Mi Young Cho, Haiyoung Jung, Suk Ran Yoon, Jung-Eun Kim, Sang Nam Lee, Sohyun Kim, Il Woo Shin, Hong Sik Shin, Kwan Soo Hong, Yong Taik Lim, Inpyo Choi, Tae-Don Kim
Journal: Biomaterials (2020)
Trends in the quality of external beam radiotherapy for elderly men with localized prostate cancer
Authors: J. E. Bekelman, M. J. Zelefsky, T. L. Jang, E. M. Basch, D. Schrag
Journal: Journal of Clinical Oncology (2007)

6507 Background: External beam radiotherapy (EBRT) is a commonly used for treatment of clinically localized prostate cancer. Yet, secular trends in the delivery of this highly technical therapy have received little attention. Methods: Using data from the linked Surveillance, Epidemiology, and End Results (SEER) Medicare program, we evaluated trends in five EBRT quality measures among 23,018 patients age 65 or older diagnosed from 1994 to 2002 with clinically localized prostate cancer and treated with primary EBRT. Using tumor registry data from SEER and Medicare claims, we excluded 6,956 patients who received brachytherapy and 7,009 patients who received combination EBRT and brachytherapy. We identified treating radiation oncologists via unique physician identification numbers reported on claims and obtained board certifications from the AMA Masterfile. We assessed the five EBRT quality measures proposed by a RAND expert panel that were amenable to analysis using SEER-Medicare data: 1) use of conformal radiotherapy treatment planning; 2) use of high-energy (=10MV) photons; 3) use of custom immobilization; 4) radiation oncologist board certification; and 5) completion of two follow-up visits with a radiation oncologist in the year following therapy. Results: As shown in the table , conformal radiotherapy increased over the study period. Approximately one-third of patients received consistent follow-up from a radiation oncologist in the year following therapy. Notably, however, claims data revealed that 80% of patients completed at least two follow-up visits with either urologists or radiation oncologists. Conclusions: Conformal radiotherapy is now routine for elderly men with localized prostate cancer. Observed practice patterns deviate from the RAND metric for patient follow-up, suggesting that this measure merits clarification. Future research should examine whether variation in receipt of these quality measures affects important clinical outcomes. No significant financial relationships to disclose. [Table: see text]
Abstract MP75: Recalibration and Additional Data Domains Leads to Modestly Improved Performance of Risk Calculators for Heart Failure Readmission
Authors: Samuel T Savitz, Keane Lee, Jamal S Rana, Thomas K Leong, Grace Tabada, Sue Hee Sung, Alan S Go
Journal: Circulation (2020)

Introduction: Heart failure (HF)-related hospitalizations are a growing public health burden. We evaluated two published risk calculators for predicting 30-day readmission after HF hospitalizations: 1) using the original coefficients, 2) updating the coefficients 3) developing a new model with additional variables and updated coefficients. Hypothesis: Recalibrating model coefficients and adding variables would improve the performance of existing 30-day readmission risk calculators. Methods: We identified 45,059 adults hospitalized for HF between 2012-2017 within Kaiser Permanente Northern California, an integrated healthcare delivery system. We used split sampling for development and validation testing. The risk calculators tested included: LACE+ Index and Yale CORE. We used logistic regression on our population to derive the recalibrated coefficients. For the model with additional variables, we included all variables used in the original models plus additional variables, including cardiovascular medication use and socioeconomic status. We used gradient boosting with k-fold cross validation to avoid overfitting. We assessed model performance using area under the curve (AUC) and calibration plots. Results: Discrimination (AUC) was poor using original models: LACE+ [0.56 (0.54-0.58)] and Yale CORE [0.55 (0.54-0.57)]. Recalibrating coefficients resulted in small improvements for LACE+ [0.58 (0.57, 0.60)] and Yale CORE [0.58 (0.57, 0.60)]. Adding variables resulted in a modest improvement for the gradient boosting model [0.61 (0.59, 0.62)]. Calibration plots (Figure 1) showed good calibration except for the Yale CORE model with the original coefficients. Conclusions: Recalibrating coefficients and incorporating prior medication and socioeconomic status led to modest, significant improvements in discrimination while maintaining good calibration. However, overall performance improvements are needed to increase the utility of these published risk calculators to predict readmission.
Retrospective study of relapsed ALL in a single institution in Brazil
Authors: J. F. Marconcini, C. F. Gomes, E. Delbuono, V. Costa, C. D. Pacheco, A. Seber, M. M. Lee
Journal: Journal of Clinical Oncology (2007)

20018 Background: With contemporary protocols, 25–30% of children with ALL who achieve first complete remission (CR1) are expected to relapse. Although the majority of patients can achieve a second complete remission (CR2) with re-induction chemotherapy, only a few will maintain prolonged clinical remission. To study the pattern of ALL relapse in our institution, we performed a retrospective analysis of such events between 1994 and 2006. Methods: In the study period, 65 out of 292 (22%) patients treated at our institution for ALL suffered isolated or combined relapse. Median age was 7.2 years (range 0.4–18.2 years); 65% were male. Patients were analyzed according to immunophenotype, WBC, site of relapse and time to relapse. Kaplan-Meier life-table analyses were used to estimate survival; differences were assessed by the log-rank test. Results: Of 63 relapsed ALL that were immunophenotyped, 65% were B-cell precursors and 35% were T-cell. WBC was &gt;50,000/mm 3 in 47% of patients; 54% of them had isolated bone marrow (BM) relapse, 23% combined relapse and 23% isolated extramedullary (EM) relapse (11CNS and 4 testicular relapse); 58% had very early relapse (VER) (&lt;18 months from CR1), 17% early relapse (ER) (18–30 months from CR1) and 25% late relapse (LR) (&gt;30 months from CR1). The therapeutic approach was chemotherapy in 60 patients and BMT in five. CR2 was achieved in 63% of patients. Of these, 35% had a second relapse. Death rate was 66% with median follow-up of 5,3 months; 40% had cumulative survival rate = 4 years. Initial imunophenotype and WBC did not affect outcome. Patients with isolated EM relapse presented a significant superior outcome when compared with those with combined relapse (p=0.024). There was no difference in survival between isolated BM and combined relapse. As for the time to relapse, there was significant inferior outcome for patients with VER when compared with ER (p=0.0089) and LR (p=0.0041). However, there was no difference in survival between ER and LR group. Conclusions: In our casuistic, time to relapse was the main predictor of outcome. Despite continuous improvement in therapy of childhood ALL, survival rate of relapsed patients remains disappointing. No significant financial relationships to disclose.
Phase II study of primary chemotherapy with paclitaxel plus gemcitabine in patients with stage II and III breast cancer
Authors: K. S. Lee, Y. Kwon, H. S. Kang, E. A. Kim, S. W. Kim, E. S. Lee, K. H. Shin, J. Ro
Journal: Journal of Clinical Oncology (2007)

11080 Background: Adding taxane in the preoperative therapy increases both clinical and pathologic responses in pts with early breast cancer (BC). Clinical outcomes were superior by adding gemcitabine (G) to paclitaxel (P) compared with P alone in metastatic BC. This study evaluated clinical and pathological response rates and adverse events by primary chemotherapy with P and G in stage II and III BC. Methods: Patients (pts) with histologically confirmed stage II and III BC with positve axillary nodes by PET or positive FNA under sono guidance, age = 18 years, adequate organ functions and good PS were eligible. No prior hormonal or chemo-therapy, radiation, or surgery was allowed. Pts received P 80 mg/m 2 and G 1,200 mg/m 2 , intravenously, d1/d8 every 3 weeks x 4. Postoperatively, doxorubicin 60 mg/m 2 and cyclophosphamide 600 mg/m 2 , intravenously, d1 every 3 weeks x 4 were given followed by radiation therapy. Assessment for clinical response was majorly done by ultrasound. Results: All planned 44 pts were enrolled between September 2005 and April 2006. The median age was 43 years (range, 30–72 years), the median primary tumor size was 5.5 cm (range, 2.1 to 12.4 cm) with 27%, stage II and 73%, stage III BC. Thirty three tumors (75%) were multiple and 25 %, single. Thirty tumors (68 %) were ER or PR positive and 32 %, HER2 IHC 3+. The median relative dose intensities were 0.97 for both P and G . Clinical responses were 1-CR (2%), 34-PR (77%), 7-SD (16%) and 1-PD (2%). One pt did not return after 1st cycle (2%). 43 pts underwent surgery with 28 (64%) breast conserving surgery. Eight pts achieved pathologic CR in primary tumors (18%), 11 in axillary nodes (25%), and 5 in combined tumor and axillary nodes (11%). Grade III/IV toxicities were neutropenia (57%), leucopenia (14 %), febrile neutropenia (2%), and headache (2%). Conclusions: Preoperative P and G combination therapy given on d1/d8 every 3 weeks for 4 cycles is well tolerable and effective for stage II and III breast cancer. Supported in part by NCC Grant No. 06102240 and SHIN POONG PHARM CO., LTD. which provided paclitaxel and gemcitabine. No significant financial relationships to disclose.
Effects of CoQ10 Supplementation on Serum Lipoprotein, Il-6, ICAM-1 and Plasma Fibrinogen in Hyperlipidemic Patients with Myocardial Infarction
Authors: Farzad Shidfar, Mona Mohseni, Mohammadreza Vafa, Seyedjavad Hajimiresmail, Abbas Rahimi
Journal: Journal of the American College of Cardiology (2013)