tbuckley/cabot-search huggingface dataset:
Abstract P176: Trends in Prescription- and Payment-related Factors That Promote Adherence to Medications Used to Treat Hypertension, 2009-2014
Authors: Matthew D Ritchey, Stavros Tsipas, Fleetwood Loustalot, Gregory Wozniak
Journal: Circulation (2016)

Background: Effective hypertension management often necessitates patients’ adherence to their prescribed blood pressure (BP)-lowering medication regimen. Improving adherence is complex, but can be related to several prescription- and payment-related factors, including: reducing patient out-of-pocket burden with low copayments, increasing generic medication use, prescribing fixed-dose combination pills with more than one BP-lowering medication per pill, limiting the number of pills to take per day, increasing the days’ supply per fill—for example, 90-day vs 30-day allotments, and using mail order pharmacies. These factors are often controlled by prescribers, filling pharmacies, pharmacy benefit managers, and/or patients’ health insurance plans, but not by patients. This study describes patterns and trends in these factors that the literature reports are associated with increased adherence to BP-lowering medication. Methods and Findings: We use a robust source of United States prescription sales data—IMS Health’s National Prescription Audit (NPA)—to describe BP-lowering medication fill counts and spending for 2009-2014. The NPA includes outpatient prescription information from ~87% of the retail and ~70% of the mail order universe. IMS Health applies a patented projection methodology to the collected data to create the national level estimates within the NPA. We describe patterns and trends in the adherence-promoting factors described above across age groups, payment sources, and medication classes. During 2009-2014, an average of 628 million BP-lowering medication prescriptions was filled annually and encouraging trends in adherence-promoting factors included: the share of generic fills increased from 82.5% to 95.0%; average days’ supply per fill increased from 45.9 to 51.8 days; and average total (patient contribution) spending per years’ supply decreased from $359 ($54) to $311 ($37). Possibly undesirable trends included: the percentage of fills for fixed-dose combinations decreased from 17.1% to 14.2% and acquired via mail order decreased from 10.7% to 8.2%. In 2014: 653.0 million fills occurred accounting for $28.8B in spending; adults aged 45-64 years had the highest percentage of fixed-dose combinations fills (16.9%); and fills with Medicaid as the payment source had the lowest average patient spending per fill ($1.19). Conclusions: Annual outpatient BP-lowering medication fill counts and spending were substantial during 2009-2014. We identified both encouraging and possibly undesirable patterns and trends in prescription- and payment-related factors that have been shown to be associated with improved adherence, but are often outside of patients’ control. Continued tracking of these data can be used to identify areas that can be addressed by clinical and policy interventions to improve adherence for medications commonly used to treat hypertension.
Cytological method or PTH detection for rapid detection of parathyroid glands during thyroid surgery.
Authors: Hongliang Wei, Jing Fan, Ting Wang, Mengxuan Li, Songpeng Li, Jingjing Xiao, Meiling Huang, Rui Ling
Journal: Journal of Clinical Oncology (2018)

e18091 Background: Protecting parathyroid glands in situ is pretty crucial to thyroid cancer patients. Recently, advances in surgical technique focused on how these diseases affect patient-reported quality of life before and after surgery.In this study, we developed two methods of intra-operative rapid identification and registered inclinicaltrials.gov (NCT03268785). The successful identification may improve the protection of parathyroid glands. Methods: During lymph node dissection process, parathyroid glands were firstly judged by clinician. Then, rapid cytological detection and PTH measurement were used for identification.Cytological: The needle puncture should be repeated for 2-3 times from different orientation guaranteed the sample volume. Following the rapid emptying of syringe, the sample was smeared as a thin and uniform cytological smears. A rapid Diff-quik staining was used, according to the instruction. Based on the outcomes achieved under high power microscope, the suspicious parathyroid could be ensured and protected by pathological experts. PTH rapid: The liquid was at least 90 ul for PTH examination. According to the instruction of PTH detection kit, the liquid was dropped on specified test paper and cultured for 12 min.PTH dose more than 130 pg/ml of PTH was regarded as the standard to justify the node as parathyroid gland. Frozen pathology was also proceeded as golden standard. Intra-operative frozen pathological examination was regarded as the golden standard to evaluate their diagnostic value. Results: A total of 21 parathyroid nodes were judged by clinician. In comparison with the diagnosis of clinician, the accuracy, sensitivity and specificity rate of cytological detection and PTH measurement were 94.4% vs 85.0% vs 60.0% , 100% vs 100% vs 100% and 88.9% vs 66.7% vs 11.1%, respectively. Consistency analysis demonstrated that the kappa value was 0.889 vs 0.688 vs 0.121, AUC area was 0.944 vs 0.914 vs 0.554. Besides, our method was time-saving and exerted no significant influence on post-operative biochemical parameters. Conclusions: Cytological detection and PTH examination maybe potential for in-situ preservation of parathyroid glands. Clinical trial information: NCT03268785.
Infection perturbs Bach2- and Bach1-dependent erythroid lineage ‘choice’ to cause anemia
Authors: Hiroki Kato, Ari Itoh-Nakadai, Mitsuyo Matsumoto, Yusho Ishii, Miki Watanabe-Matsui, Masatoshi Ikeda, Risa Ebina-Shibuya, Yuki Sato, Masahiro Kobayashi, Hironari Nishizawa, Katsushi Suzuki, Akihiko Muto, Tohru Fujiwara, Yasuhito Nannya, Luca Malcovati, Mario Cazzola, Seishi Ogawa, Hideo Harigae, Kazuhiko Igarashi
Journal: Nature Immunology (2018)
Exposure to Humidifier Disinfectants Increases the Risk for Asthma in Children
Authors: Jisun Yoon, So-Yeon Lee, Seung-Hwa Lee, Eun Mi Kim, Sungsu Jung, Hyun-Ju Cho, Eun Lee, Song-I Yang, Soo-Jong Hong
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

across the genome, including pathways highly relevant to PAH pathogenesis, such as WNT signaling (8, 10,11).One of the findings in our study was that the positive effect of SRY on BMPR2 expression had an upper limit, above which adding more SRY did not result in a corresponding increase in BMPR2 expression.This is not a surprising finding, as most transcription factors have a limited range of function.Furthermore, BMPR2 expression is likely controlled by a coordinated action of multiple different transcriptional regulators, and thus one transcription factor would not be expected to modify its expression to an unlimited extent.For example, previous studies have identified other factors that regulate BMPR2 expression, such as estrogen receptor a (4, 5).Thus, the integration of multiple factors may explain why SRY has a limited, but important, capacity to increase BMPR2 expression.Each factor may play a role in PAH susceptibility or resilience.It is important to acknowledge that in some assays, the effect sizes were modest; this may reflect the fact that multiple factors likely contribute to BMPR2 expression, not simply SRY activity.Finally, much of this work was conducted using PAH fibroblasts because of the low expression of SRY in typical lung vascular cells.Although the amount of data suggesting that fibroblasts may contribute to PAH pathogenesis is growing, future work will determine whether SRY contributes to variations in lung vascular cell health and function.In conclusion, SRY binds to and positively regulates BMPR2 expression.This builds on recent novel work by Umar and colleagues, which demonstrated the relevance of the Y chromosome to pulmonary hypertension (7).Our findings advance the concept that protective factors on the Y chromosome contribute to pulmonary hypertension, with a focus on the reduced male incidence in PAH via sex-specific BMPR2 regulation.
Abstract 14021: Increased Cardiac Conduction Abnormalities After Tricuspid Annuloplasty During Cardiac Transplantation: A Single Center 3 Year Retrospective Review
Authors: Geoffrey Rubin, Joseph Bayne, Raymond Givens, Meghana Noonavath, Hiroo Takayama, Koji Takeda, Yoshifumi Naka, Hasan Garan, Maryjane Farr, Elaine Wan
Journal: Circulation (2016)

Introduction: Tricuspid annuloplasty (TA) performed in donor hearts at time of orthotopic cardiac transplantation to reduce tricuspid regurgitation and preserve right ventricular function in transplant recipients has been shown to improve transplant outcomes. However, after incorporation of TA into our surgical protocol, we have observed an increased incidence of conduction abnormalities including right bundle branch block and heart block suggestive of AV nodal injury after incorporation of TA into the transplant surgical protocol. Methods: We conducted a retrospective review of medical charts of 97 adult cardiac transplantation recipients, as well as, information available on the donor hearts over a three year time period from 2014 to 2016 at Columbia University Medical Center, New York, NY. Results: No donor hearts had RBBB prior to harvest. Before vs. after incorporation of the TA procedure into the transplant protocol: the mean age of transplant recipients was 52 ± 1.7 s.e.m years of age vs. 57 ± 1.3 s.e.m years of age. 6 patients (11.8%, n=51) vs. 19 TA patients (42.2%, n=45) had RBBB postoperatively (p&lt;0.005). Development of RBBB was increased in 27 mm (52%) vs 25 mm TA (35%), p=NS. Only 1 recipient (1.9%, n=51) vs. 4 TA recipients (8.8 %, n=45) had complete heart block within 30 days postoperatively (p=0.19), two of whom went on to receive implantation of permanent pacemakers. One of the two patients ultimately recovered AV conduction. Conclusions: There was a 3.6 fold increase in RBBB and 4.6 fold increase in incidence of AV block after incorporation of TA to the transplant surgical protocol at our center. Our results suggest that TA may cause injury to the conduction system of the donor heart. This is the first retrospective study demonstrating significant conduction abnormalities after incorporation of TA into the transplant surgical protocol.
Rapid 3D bioprinting of decellularized extracellular matrix with regionally varied mechanical properties and biomimetic microarchitecture
Authors: Xuanyi Ma, Claire Yu, Pengrui Wang, Weizhe Xu, Xueyi Wan, Cheuk Sun Edwin Lai, Justin Liu, Anna Koroleva-Maharajh, Shaochen Chen
Journal: Biomaterials (2018)
Usability of the international HAVNet hepatitis A virus database for geographical annotation, backtracing and outbreak detection
Authors: Annelies Kroneman, Rita de Sousa, Linda Verhoef, Marion P G Koopmans, Harry Vennema
Journal: Eurosurveillance (2018)

Background HAVNet is an international laboratory network sharing sequences and corresponding metadata on hepatitis A virus in an online database. Aim: We give an overview of the epidemiological and genetic data and assess the usability of the present dataset for geographical annotation, backtracing and outbreak detection. Methods: A descriptive analysis was performed on the timeliness, completeness, epidemiological data and geographic coverage of the dataset. Length and genomic region of the sequences were reviewed as well as the numerical and geographical distribution of the genotypes. The geographical signal in the sequences was assessed based on a short common nt stretch using a 100% identity analysis. Results: The 9,211 reports were heterogeneous for completeness and timeliness, and for length and genomic region of the sequences. Some parts of the world were not represented by the sequences. Geographical differences in prevalence of HAV genotypes described previously could be confirmed with this dataset and for a third (1,075/3,124) of the included sequences, 100% identity of the short common sequence coincided with an identical country of origin. Conclusion: Analysis of a subset of short, shared sequences indicates that a geographical annotation on the level of individual countries is possible with the HAVNet data. If the current incompleteness and heterogeneity of the data can be improved on, HAVNet could become very useful as a worldwide reference set for geographical annotation and for backtracing and outbreak detection.
Clinical and molecular characterization of patients with metastatic colorectal cancer harbouring DNA mismatch repair deficiency.
Authors: Romain Cohen, Elisabeth Hain, Pascale Cervera, Olivier Buhard, Sylvie Dumont, Armelle Bardier, Jean-Baptiste Bachet, Jean Marc Gornet, Sarah Dumont, Rachid Kaci, Philippe Bertheau, Florence Renaud, Frederic Bibeau, Yann Parc, Alex Duval, Magali Svrcek, Thierry Andre
Journal: Journal of Clinical Oncology (2017)

3563 Background: Prognosis of patients (pts) with metastatic colorectal cancer (mCRC) harboring microsatellite instability (MSI) is poorly characterized. We aimed to assess the clinical relevance of distinguishing sporadic (SP) from Lynch syndrome (LS)-related mismatch repair deficiency (dMMR). Methods: Pts with diagnostic of dMMR and/or MSI mCRC between 1998 and 2016 were retrospectively identified in 6 French hospitals. Tumor samples were systematically collected and screened for RAS/RAF mutations and MLH1 promotor methylation. dMMR and MSI statuses were confirmed using immunohistochemistry and Pentaplex© PCR assay. Sporadic cases were molecularly defined as those displaying MLH1 loss of expression with BRAFV600E mutation and/or MLH1 hypermethylation. Clinical data (demographic data, metastatic sites, therapeutic strategies) were recorded. Results: 129 pts, of which 48 SP and 81 LS, were included. Compared with LS, SP were associated with female (P &lt; .001), older age at diagnostic (P &lt; .001), proximal colon (P = 0.002), and less liver metastasis (25% vs 47%, P = .02). For initially localized CRC, median disease free survivals (DFS) were 9.1 months (m) for SP (n = 22) and 12.3 m for LS (n = 47) (hazard ratio (HR) = 0.5, 95%CI 0.28-0.90, P = .02). Median overall survivals (OS) from stage IV diagnosis were 43.9 m in the overall population, 23 m for SP and not reached for LS (HR = 0.23, 95%CI 0.10-0.52, P &lt; .001). BRAF mutation was harbored by 29 SP tumors (60%) and did not impact OS among SP pts (P = .52). Metastatic disease was less frequently resectable for SP than LS (21% vs 56%, P &lt; .001). Median DFS for pts with resected metastatic disease (n = 55) were respectively 6.7 and 10.5 m (HR = 0.28, 95%CI 0.10-0.73, P = .01). At the data cut-off date, 16 pts (15 LS and 1 SP) were still in complete remission. Median progression free survivals with first-line chemotherapy for pts with unresectable metastasis (n = 61) were 3.9 m for SP and 5.0 m for LS (P = .71). Conclusions: This retrospective study suggests a worse prognosis of pts with SP MSI mCRC compared to these with LS-related mCRC.
Off treatment survival (OTS) in patients (pts) with advanced melanoma after anti-PD1 therapy.
Authors: Shelly Ann Christiansen, David Swoboda, Kellie Gardner, Suthee Rapisuwon, Michael B. Atkins, Geoffrey Thomas Gibney
Journal: Journal of Clinical Oncology (2018)

9554 Background: Anti-PD1 alone and combined with anti-CTLA4 therapy has improved survival in pts with advanced melanoma. Optimal treatment duration has not been defined and it is unclear if survival is compromised when pts discontinue (DC) therapy. Methods: A single institution review of pts with advanced melanoma treated with nivolumab or pembrolizumab monotherapy (anti-PD1) or nivolumab plus ipilimumab (nivo-ipi) was performed. Response rate (RR; provider assessed), reason for treatment DC and survival were analyzed. Outcomes in pts after treatment DC with CT scan response, PET/CT and/or biopsy of residual disease was assessed. OTS in pts with disease control was defined from time of last anti-PD1 dose to time of subsequent systemic therapy or death. Results: Of 96 pts, 44 received anti-PD1 and 52 received nivo-ipi. Median age 64 yrs, 62% male, 95% ECOG 0-1, 73% stage M1c, 37% BRAF mutant, 39% elevated LDH, and 28% brain metastasis. Overall RR was 34% for anti-PD1 and 63% for nivo-ipi. Another 25% and 6% of pts had stable disease, respectively. Median overall survival (OS) was not reached, although survival was significantly greater with nivo-ipi (P = 0.007). At 24 months, 80% of nivo-ipi pts were alive vs 51% anti-PD1 pts. 41 pts with disease control DC treatment for toxicity (n = 21) or pt/provider choice (n = 20). Of the latter, 17 pts DC treatment after one year for partial/complete response on CT scan (n = 4), negative PET/CT scan (n = 9), and positive PET/CT with negative biopsy (n = 4). 3 pts DC treatment after 2 years for positive PET/CT and negative biopsy. Median OTS was not reached for either group (91% and 77% were event free at 18 months); median follow up was 13.5 and 27.5 months, respectively. In the pt/provider choice group, 1 pt had progressive disease (PD) managed surgically and 1 pt died from non-melanoma causes; none received further systemic treatment. In the toxicity group, 4 pts had PD requiring further systemic therapy. Conclusions: In our experience, superior OS was seen with nivo-ipi over anti-PD-1 alone. OTS appears durable in pts with disease control if treatment DC due to toxicity or pt/provider decision. PET/CT and biopsy may be an effective strategy for safe DC of therapy after 1 year. Further prospective study is warranted.
Pre-existing symptoms, resource utilization, and healthcare costs prior to diagnosis of neuroendocrine tumors: A SEER-Medicare database study.
Authors: Chan Shen, Yiyi Chu, A. Dasari, Shouhao Zhou, Daniel M. Halperin, Ying Xu, Ya-Chen T. Shih, James C. Yao
Journal: Journal of Clinical Oncology (2017)

4092 Background: The incidence and prevalence of neuroendocrine tumors (NETs) are continually increasing. While it is known that NET symptoms often predate diagnosis, the prevalence of these symptoms and the impacts on resource utilization and costs are largely unknown. Methods: We identified 12,052 elderly patients diagnosed with NET between 1/2003 and 12/2011 by ICD-O-3 codes from the Surveillance, Epidemiology and End Results (SEER)-Medicare database with continuous Medicare Parts A and B enrollment during the one year before NET diagnosis. We used propensity score matching to identify a group of comparable elderly patients from a non-cancer Medicare cohort. We captured patients’ potentially relevant conditions (defined as &gt; 1 indicative claim), resource utilization and costs from patients’ medical claims during the year before diagnosis. We examined a) resource utilization in terms of number of outpatient visits, percentage of patients having any emergency room (ER) visits and hospitalizations, and b) health care costs including inpatient, outpatient and total costs. We used chi-square test for categorical variables and Mann-Whitney U test for continuous variables. Results: NET patients were more likely to have diagnoses of diarrhea (8% vs. 2%), abdominal pain (37% vs. 8%), irritable bowel syndrome (1.5% vs. 0.6%), hypertension (72% vs. 55%), heart failure (16% vs. 8%), and peripheral edema (7% vs. 4%) compared to the non-cancer control group. They also had much higher resource utilization including number of outpatient visits (mean: 27.25 vs. 18.45); and percentage with ER visits (64% vs. 36%), and hospitalizations (66% vs. 34%). Similarly, NET patients incurred significantly higher total (mean: $32924 vs. $10048), outpatient (mean: $8869 vs. 4580), and inpatient costs (mean: $24055 vs. $10048). All p &lt; 0.001. Conclusions: To the best of our knowledge, this is the first population-based study to examine potentially relevant pre-existing symptoms, resource utilization and healthcare costs before NET diagnosis. NET patients were more likely to have certain conditions and incurred higher resource utilizations and costs in the year preceding diagnosis of NET.
Validation of a 3-gene signature and development of an authentic cohort database to improve overall survival prediction and clinical treatment decision for patients with newly diagnosed prostate cancer.
Authors: Chunde Li, Zhuochun Peng, Karl Andersson, Johan Lindholm, Olga Dethlefsen, Yudi Pawitan, Monica Nistér, Sten Nilsson
Journal: Journal of Clinical Oncology (2016)

5047 Background: since the majority of newly diagnosed prostate cancers are indolent and slowly progressing, a better prognostic tool is needed to improve survival prediction accuracy so as to make better treatment decisions at the time of diagnosis. Methods: a previously reported 3-gene signature (VGLL3, IGFBP3 and F3) was validated in improving survival time prediction at diagnosis when combined with clinical parameters such as: age at diagnosis, Gleason score, tumor stage and PSA in formalin fixed paraffin embedded prostate needle biopsy materials. A cohort-based algorithm, the classification of prostatic malignancy algorithm (CPMA), collected gene expression values of 3 genes and four clinical parameters derived from 452 historical patients with complete documented 7 to 11 year clinical follow-up. Patients were selected from a population based cohort (Stockholm area) and were diagnosed from 2004-2008. The actual overall, cancer-specific and non-cancer-specific survival time were compared with the corresponding estimations by the CPMA parameters, the NCCN risk groups and the CAPRA risk scores by using both the Weibull regression model and the CPMA algorithm. Results: In Weibull regression model, AUC for overall survival prediction is significantly increased, from 0.68 for NCCN risk groups, 0.72 for CAPRA risk groups (0-2, 3-5 and 6-10) and up to 0.81 for CPMA parameters. For 234 individuals who did not treated with prostatectomy/radiation we performed survival prediction accuracy using either CAPRA risk score or CPMA algorithm. The overall survival prediction accuracy is 88% for CAPRA 0-2 group, 56 % for CAPRA 3-5 and 66% for CAPRA 6-10. Comparatively, the overall accuracy is increased to 88%, 76% and 83%, respectively, when using the CPMA parameters. Conclusions: the CPMA parameters and its clinically implemented database algorithm (CPMA) significantly increased overall survival time prediction accuracy compared to the currently wide-used prognostic risk tools. It is justified to consider the use of CPMA in clinical practice.