tbuckley/cabot-search huggingface dataset:
Hospital Variation in Adherence Rates to Secondary Prevention Medications and the Implications on Quality
Authors: Robin Mathews, William Wang, Lisa A. Kaltenbach, Laine Thomas, Rashmee U. Shah, Murtuza Ali, Eric D. Peterson, Tracy Y. Wang
Journal: Circulation (2018)

Background: Medication adherence is important to improve the long-term outcomes after acute myocardial infarction (MI). We hypothesized that there is significant variation among US hospitals in terms of medication adherence after MI, and that patients treated at hospitals with higher medication adherence after MI will have better long-term cardiovascular outcomes. Methods: We identified 19 704 Medicare patients discharged after acute MI from 347 US hospitals participating in the ACTION Registry-GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines) from January 2, 2007, to October 1, 2010. Using linked Medicare Part D prescription filling data, medication adherence was defined as proportion of days covered &gt;80% within 90 days after discharge. Cox proportional hazards modeling was used to compare 2-year major adverse cardiovascular events among hospitals with high, moderate, and low 90-day medication adherence. Results: By 90 days after MI, overall rates of adherence to medications prescribed at discharge were 68% for β-blockers, 63% for statins, 64% for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and 72% for thienopyridines. Adherence to these medications up to 90 days varied significantly among hospitals: β-blockers (proportion of days covered &gt;80%; 59% to 75%), statins (55% to 69%), thienopyridines (64% to 77%), and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (57% to 69%). Compared with hospitals in the lowest quartile of 90-day composite medication adherence, hospitals with the highest adherence had lower unadjusted and adjusted 2-year major adverse cardiovascular event risk (27.5% versus 35.3%; adjusted hazard ratio, 0.88; 95% confidence interval, 0.80–0.96). High-adherence hospitals also had lower adjusted rates of death or readmission (hazard ratio, 0.90; 95% confidence interval, 0.85–0.96), whereas there was no difference in mortality after adjustment. Conclusions: Use of secondary prevention medications after discharge varies significantly among US hospitals and is inversely associated with 2-year outcomes. Hospitals may improve medication adherence after discharge and patient outcomes through better coordination of care between inpatient and outpatient settings.
BATF-dependent IL-7RhiGM-CSF+ T cells control intestinal graft-versus-host disease
Authors: Evelyn Ullrich, Benjamin Abendroth, Johanna Rothamer, Carina Huber, Maike Büttner-Herold, Vera Buchele, Tina Vogler, Thomas Longerich, Sebastian Zundler, Simon Völkl, Andreas Beilhack, Stefan Rose-John, Stefan Wirtz, Georg F. Weber, Sakhila Ghimire, Marina Kreutz, Ernst Holler, Andreas Mackensen, Markus F. Neurath, Kai Hildner
Journal: Journal of Clinical Investigation (2018)

Acute graft-versus-host disease (GVHD) represents a severe, T cell–driven inflammatory complication following allogeneic hematopoietic cell transplantation (allo-HCT). GVHD often affects the intestine and is associated with a poor prognosis. Although frequently detectable, proinflammatory mechanisms exerted by intestinal tissue–infiltrating Th cell subsets remain to be fully elucidated. Here, we show that the Th17-defining transcription factor basic leucine zipper transcription factor ATF-like (BATF) was strongly regulated across human and mouse intestinal GVHD tissues. Studies in complete MHC-mismatched and minor histocompatibility–mismatched (miHA-mismatched) GVHD models revealed that BATF-expressing T cells were functionally indispensable for intestinal GVHD manifestation. Mechanistically, BATF controlled the formation of colon-infiltrating, IL-7 receptor–positive (IL-7R+), granulocyte-macrophage colony-stimulating factor–positive (GM-CSF+), donor T effector memory (Tem) cells. This T cell subset was sufficient to promote intestinal GVHD, while its occurrence was largely dependent on T cell–intrinsic BATF expression, required IL-7–IL-7R interaction, and was enhanced by GM-CSF. Thus, this study identifies BATF-dependent pathogenic GM-CSF+ effector T cells as critical promoters of intestinal inflammation in GVHD and hence putatively provides mechanistic insight into inflammatory processes previously assumed to be selectively Th17 driven.
High Risk of Advanced Colorectal Neoplasia in Patients With Primary Sclerosing Cholangitis Associated With Inflammatory Bowel Disease
Authors: Shailja C. Shah, Joren R. ten Hove, Daniel Castaneda, Carolina Palmela, Erik Mooiweer, Jean-Frédéric Colombel, Noam Harpaz, Thomas A. Ullman, Ad A. van Bodegraven, Jeroen M. Jansen, Nofel Mahmmod, Andrea E. van der Meulen-de Jong, Cyriel Y. Ponsioen, Christine J. van der Woude, Bas Oldenburg, Steven H. Itzkowitz, Joana Torres
Journal: Clinical Gastroenterology and Hepatology (2018)
Abstract 16124: Aurora - A Noninvasive, Wrist-worn Device for Ambulatory Hemodynamic Monitoring
Authors: Jeremiah D Wander, Dan Morris, Desney Tan
Journal: Circulation (2015)

Introduction: Continuous, minimally invasive monitoring of arterial health has significant potential for both improving our understanding of early progression of arteriosclerosis/atherosclerosis and enabling early treatment. Though devices exist that can report heart rate and heart rate variability in fully ambulatory settings, monitoring of pulse pressure wave morphology, including pulse wave velocity (PWV) and augmentation index (AIx) - two emerging indicators of arterial stiffness - is still currently limited to benchtop systems requiring an expert operator or cuff-based systems that are not well tolerated. Objective: To develop and validate a device capable of continuous monitoring of hemodynamic and electrophysiological signals, including computation of derived vascular stiffness indicators (peripheral PWV and AIx) comparable to current standards. Methods: We developed a wrist-worn device for continuous radial pulse wave capture and analysis (e.g., peripheral AIx computation) and pulse wave velocity measurement (measured from EKG landmarks to the radial pulse arrival time). The core sensors on the device are (1) a pressure sensor that rests over the radial artery, (2) a pair of dry EKG electrodes in lead-I configuration, and (3) a six-axis motion sensor. It includes a Bluetooth radio for data streaming, and sufficient on-board storage for 2 weeks of ambulatory studies. To validate the device against the current gold standard for radial tonometry, we recorded multiple 60-second sessions of tonometric data using both our device (2 sessions) and the standard Millar SPT-301 tonometer (3 sessions) in 28 subjects. We then compared AIx computed from these two devices. Results: Using our wrist-worn device we calculated AIx values that were highly consistent with those of the Millar tonometer (r = 0.927, mean difference ± SD of 0.026 ± 0.049). Conclusions: This platform enables continuous non-invasive hemodynamic monitoring. We intend to utilize it in future studies about how peripheral AIx and PWV behave over longer time periods, how they correlate to daily activities, including sleep, exercise, and food/medication intake, and - most importantly - whether they can serve as new, ambulatory indicators of cardiovascular risk.
The impact of severe mental disorders and psychotropic medications on sexual health and its implications for clinical management
Authors: Angel L. Montejo, Laura Montejo, David S. Baldwin
Journal: World Psychiatry (2018)

Sexual dysfunction often accompanies severe psychiatric illness and can be due to both the mental disorder itself and the use of psychotropic treatments. Many sexual symptoms resolve as the mental state improves, but treatment-related sexual adverse events tend to persist over time, and are unfortunately under-recognized by clinicians and scarcely investigated in clinical trials. Treatment-emergent sexual dysfunction adversely affects quality of life and may contribute to reduce treatment adherence. There are important differences between the various compounds in the incidence of adverse sexual effects, associated with differences in mechanisms of action. Antidepressants with a predominantly serotonergic activity, antipsychotics likely to induce hyperprolactinaemia, and mood stabilizers with hormonal effects are often linked to moderate or severe sexual dysfunction, including decreased libido, delayed orgasm, anorgasmia, and sexual arousal difficulties. Severe mental disorders can interfere with sexual function and satisfaction, while patients wish to preserve a previously satisfactory sexual activity. In many patients, a lack of intimate relationships and chronic deterioration in mental and physical health can be accompanied by either a poor sexual life or a more frequent risky sexual behaviour than in the general population. Here we describe the influence of psychosis and antipsychotic medications, of depression and antidepressant drugs, and of bipolar disorder and mood stabilizers on sexual health, and the optimal management of patients with severe psychiatric illness and sexual dysfunction.
We must support junior doctors working after hours
Authors: Vikas Wadhwa, Jenny Brookes
Journal: BMJ (2018)

For junior doctors, working in hospitals after hours is vastly different to, and more challenging than, shifts during routine hours. After hours shifts bring reduced staffing, greater responsibilities, and time pressures. Doctors are often required to cover units with limited clinical experience, training, or induction and where they have to work beyond their competence.1 Doctors may be uncertain about policies, …
Acute graft-versus-host disease following lung transplantation in a patient with a novel <i>TERT</i> mutation
Authors: Jonathan R Brestoff, Alexandre T Vessoni, Kirsten A Brenner, Geoffrey L Uy, John F DiPersio, Morey Blinder, Chad A Witt, Derek E Byers, Ramsey R Hachem, Elbert P Truclock, Dayna S Early, Milan J Anadkat, Amy Musiek, Cylen Javidan-Nejad, Dennis M Balfe, Ilana S Rosman, Chang Liu, Lingxin Zhang, George J Despotis, Marianna B Ruzinova, Jennifer K Sehn, Ina Amarillo, Jonathan W Heusel, Wojcieh Swat, Brian S Kim, Lukas D Wartman, Roger D Yusen, Luis F Z Batista
Journal: Thorax (2018)

Familial pulmonary fibrosis is associated with loss-of-function mutations in telomerase reverse transcriptase ( TERT ) and short telomeres. Interstitial lung diseases have become the leading indication for lung transplantation in the USA, and recent data indicate that pathogenic mutations in telomerase may cause unfavourable outcomes following lung transplantation. Although a rare occurrence, solid organ transplant recipients who develop acute graft-versus-host disease (GVHD) have very poor survival. This case report describes the detection of a novel mutation in TERT in a patient who had lung transplantation for familial pulmonary fibrosis and died from complications of acute GVHD.
An open-label, phase 1b, dose-escalation study (CA180-373) of dasatinib plus nivolumab, an investigational anti-programmed cell death 1 (PD-1) antibody, in patients (pts) with previously treated chronic myeloid leukemia (CML).
Authors: Kimmo Porkka, Michael J. Mauro, Jeffrey Howard Lipton, Francois-Xavier Mahon, Lewis C. Strauss, William J. Geese, Glenn Scott Kroog, Satu Mustjoki
Journal: Journal of Clinical Oncology (2014)

TPS7119 Background: CML has become a chronic disease for many pts treated with BCR-ABL1 tyrosine kinase inhibitors (TKIs). However, new approaches are needed to increase the prevalence of deep responses suitable for treatment discontinuation and to treat resistant/recurrent CML. Immune cell–mediated approaches (eg, stem cell transplantation, interferon-α) can be effective. PD-1 ligation provides a negative costimulatory signal governing the balance between T-cell activation and tolerance. The potent second-generation TKI dasatinib may have synergy with nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody. Nivolumab has shown encouraging clinical activity against several solid tumors. PD-1 is upregulated on CD8+ T cells in CML pts (Christiansson PLoS ONE 2013;8:e55818) and blocking the PD-1/ligand interaction prolonged survival in a murine model (Mumprecht Blood 2009;114:1528-36). The study will assess safety, tolerability, and preliminary efficacy of dasatinib + nivolumab in previously treated CML in chronic or accelerated phase (CP/AP). Methods: In this open-label, phase 1b dose-escalation study, pts must be aged ≥18 years (y) and have Philadelphia chromosome–positive CML-CP/AP, ECOG performance status ≤1, and no known dasatinib-resistant BCR-ABL1 mutations. Pts must have received ≥2 prior TKIs, be progressing, or have had resistance, intolerance, or suboptimal response to the most recent therapy. Treatment in the dose-escalation phase is dasatinib 100 mg (CP) or 140 mg (AP) once daily with nivolumab 0.3 mg/kg (dose level [DL] –1), 1 mg/kg (DL 1), or 3 mg/kg (DL 2) by intravenous injection every 2 weeks for ≤2 y, followed by ≤1 y of dasatinib only. Treatment in the expansion phase will be dasatinib (same doses) + nivolumab (dose based on safety). The primary objective is to determine safety and tolerability. Secondary endpoints are major molecular response (MMR) and molecular response (MR)4.5 rates at 6, 12, 24, and 36 months and time to and duration of MMR and MR4.5 up to 36 months. Estimated completion: August 2018. Clinical trial information: NCT02011945.
Impact of hepatitis B vaccination on acute hepatitis B epidemiology in European Union/European Economic Area countries, 2006 to 2014
Authors: Alessandro Miglietta, Chantal Quinten, Pier Luigi Lopalco, Erika Duffell
Journal: Eurosurveillance (2018)

Hepatitis B prevention in European Union/European Economic Area (EU/EEA) countries relies on vaccination programmes. We describe the epidemiology of acute hepatitis B virus (HBV) at country and EU/EEA level during 2006-2014. Using a multi-level mixed-effects Poisson regression model we assessed differences in the acute HBV infection notification rates between groups of countries that started universal HBV vaccination before/in vs after 1995; implemented or not a catch-up strategy; reached a vaccine coverage ≥ 95% vs < 95% and had a hepatitis B surface antigen prevalence ≥ 1% vs < 1%. Joinpoint regression analysis was used to assess trends by groups of countries, and additional Poisson regression models to evaluate the association between three-dose HBV vaccine coverage and acute HBV infection notification rates at country and EU/EEA level. The EU/EEA acute HBV infection notification rate decreased from 1.6 per 100,000 population in 2006 to 0.7 in 2014. No differences (p > 0.05) were found in the acute HBV infection notification rates between groups of countries, while as vaccine coverage increased, such rates decreased (p < 0.01). Countries with universal HBV vaccination before 1995, a catch-up strategy, and a vaccine coverage ≥ 95% had significant decreasing trends (p < 0.01). Ending HBV transmission in Europe by 2030 will require high vaccine coverage delivered through universal programmes, supported, where appropriate, by catch-up vaccination campaigns.
A novel quantitative microarray antibody capture assay identifies an extremely high hepatitis delta virus prevalence among hepatitis B virus–infected mongolians
Authors: Xiaohua Chen, Odgerel Oidovsambuu, Ping Liu, Rosslyn Grosely, Menashe Elazar, Virginia D. Winn, Benjamin Fram, Zhang Boa, Hongjie Dai, Bekhbold Dashtseren, Dahgwahdorj Yagaanbuyant, Zulkhuu Genden, Naranbaatar Dashdorj, Andreas Bungert, Naranjargal Dashdorj, Jeffrey S. Glenn
Journal: Hepatology (2016)

Hepatitis delta virus (HDV) causes the most severe form of human viral hepatitis. HDV requires a hepatitis B virus (HBV) coinfection to provide HDV with HBV surface antigen envelope proteins. The net effect of HDV is to make the underlying HBV disease worse, including higher rates of hepatocellular carcinoma. Accurate assessments of current HDV prevalence have been hampered by the lack of readily available and reliable quantitative assays, combined with the absence of a Food and Drug Administration-approved therapy. We sought to develop a convenient assay for accurately screening populations and to use this assay to determine HDV prevalence in a population with abnormally high rates of hepatocellular carcinoma. We developed a high-throughput quantitative microarray antibody capture assay for anti-HDV immunoglobulin G wherein recombinant HDV delta antigen is printed by microarray on slides coated with a noncontinuous, nanostructured plasmonic gold film, enabling quantitative fluorescent detection of anti-HDV antibody in small aliquots of patient serum. This assay was then used to screen all HBV-infected patients identified in a large randomly selected cohort designed to represent the Mongolian population. We identified two quantitative thresholds of captured antibody that were 100% predictive of the sample either being positive on standard western blot or harboring HDV RNA detectable by real-time quantitative PCR. Subsequent screening of the HBV
Quantitation of mitoxantrone accumulation, efflux and modulation in MDR human MDA-MB-435 cancer cells
Authors: Fei Shen, Exing Wang, Kenneth Dunn, Williams T. Beck, Leonard C. Erickson
Journal: Cancer Research (2005)

531   Drug resistance of cancer cells remains one of the major obstacles to successful chemotherapy. Overexpression of P-glycoprotein in cancer cells causes resistance of cancer cells to a number of structurally and functionally diverse anticancer agents, i.e. Multidrug Resistance (MDR). Previously, we have reported that decreased uptake and increased efflux of doxorubicin (DOX) in MDR-1 transduced human MDA-MB-435 cancer cells (MDR cells) compared to wild type MDA-MB-435 cells. We identified that nuclei in MDR cells were the main target site in decreasing DOX uptake and increasing DOX efflux by Pgp. In the current study, we have determined accumulation and efflux of the fluorescent anticancer drug mitoxantrone (MX), in wild type MDA-MB-435 cells and MDR cells, and quantified the inhibition of Pgp modulators on MX uptake and efflux in the MDR cells. MDA-MB-435 cells grown on cover slips were sequentially perfused with culture medium, containing MX for two hours, and then fresh culture medium for an additional hour. Serial images at two-minute intervals were collected and analyzed (Metamorph™ software) as mean MX fluorescent intensity per pixel in regions of the nucleus or cytoplasm of the cells. MDR cancer cells were also pretreated with Pgp inhibitors before perfusion as described above. Our results showed that accumulation of MX in MDR cells were three times less than that in the wild type cells. When pretreated with Pgp modulators, verapamil, cyclosporine A, and PSC833, MDR cells had at least the same MX accumulation level as the wild type cells. MX entered into wild type and MDR cells slowly. Although there was about 2.5-time greater MX uptake in wild type cells  versus  MDR cells, unlike DOX, MX nuclear steady state uptake was similar to its cytosol uptake in MDR cells, indicating intracellular targets of MX and DOX may differ and Pgp may function differently on MX and DOX. MX was mostly effluxed from MDR cells after its removal from perfusates while under the same condition it remained in wild type cells. Results from cell perfusion studies showed that the Pgp inhibitor, PSC833 increased MX uptake and reduced its efflux in MDR cells. These results suggest active MDR function is present in the MDR cells. We conclude that Pgp decreases MX uptake and increases MX efflux in MDR human MDA-MB-435 cells and compared to DOX, MX may have different cellular targets and interact differently with Pgp.
Bacteroides fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells
Authors: Liam Chung, Erik Thiele Orberg, Abby L. Geis, June L. Chan, Kai Fu, Christina E. DeStefano Shields, Christine M. Dejea, Payam Fathi, Jie Chen, Benjamin B. Finard, Ada J. Tam, Florencia McAllister, Hongni Fan, Xinqun Wu, Sudipto Ganguly, Andriana Lebid, Paul Metz, Sara W. Van Meerbeke, David L. Huso, Elizabeth C. Wick, Drew M. Pardoll, Fengyi Wan, Shaoguang Wu, Cynthia L. Sears, Franck Housseau
Journal: Cell Host & Microbe (2018)
Treatment results of neo-adjuvant chemotherapy in advanced head and neck cancer in Oman
Authors: A. Khalifa, M. Al-Khabouri
Journal: Journal of Clinical Oncology (2004)

A prospective, single-arm study was carried out to evaluate the safety and efficacy of neo-adjuvant chemotherapy in advanced head and neck cancer (HNC) in Oman.The study was carried out in the Oncology and Ear, Nose and Throat (ENT) Departments, Muscat, Oman between October 1998 and December 2001. Eligible, previously untreated patients with confirmed diagnosis of locally advanced non-metastatic carcinoma of the head and neck were examined. A maximum of three cycles of neo-adjuvant chemotherapy (Cisplatin 100mg/m2 Day 1 plus 5-Fluorouracil 1gm/m2 continuous infusion for four days) were administered, followed by radical radiotherapy according to primary site. The main end-points were toxicity, response rate, disease-free survival and overall survival.Seventy-three patients (45 males and 28 females) were eligible; all were evaluable for response and toxicity. The median age of studied patients was 52 years (range: 17-83 years). Forty-four patients (60%) had stage III disease and 29 (40%) had stage IV disease. After neo-adjuvant chemotherapy, Overall Response (OR) [Complete Response (CR) + Partial Response (PR)] was observed in 50 patients (68%), 33 patients (45%) had clinical CR and 17 patients (23%) had PR. Sixteen patients (22%) showed Stable Disease (SD) and 7 patients (10%) progressed while on chemotherapy. After completion of radiotherapy, the OR rate was 80%. Forty patients (55%) had clinically confirmed CR, 18 (25%) had PR, 9 patients (12%) had SD and 6 patients (8%) had progressive disease (PD). The median follow-up period was 16 months (range 3-48 months). The initial response to chemotherapy had a significant effect on survival (p= 0.011). The nasopharyngeal primary was significantly associated with high CR and longer survival (p= 0.01 and 0.02 respectively).Head and neck carcinoma is not a common malignancy in Oman. The treatment results with cisplatin and 5-FU compare favorably to similar international studies and treatment-related toxicities are tolerable.