tbuckley/cabot-search huggingface dataset:
Estimating the cost-savings of a comprehensive hospital-based palliative care program.
Authors: Sarina Isenberg, Chunhua Lu, John P McQuade, Thomas J. Smith, A. Rab Razzak
Journal: Journal of Clinical Oncology (2016)

2 Background: In FY 2012, Johns Hopkins Medicine (JHM) established a palliative care inpatient unit (PCU). The PCU received patients as transfers and direct admissions. PCUs can improve care (Roza K, et al. JPM 2015) and lower per diem costs compared to usual care (Smith TJ, et al. JPM 2003; Goldstein J, et al. JPSM 2015). This project studied the financial impact of the PCU and PC program on JHM. Methods: Using one fiscal year of admissions, the team calculated the per day variable cost of pre-transfer in to palliative care (from ED) and palliative care transfer. These fees were multiplied by the number of patients transferred to the PCU (153) and by the average length of stay in the PCU (5.11 days). These variable costs were added together to reach the combined savings. Consultation savings were estimated using established methods (Morrison RS, et al. Arch Int Med 2008; adjusted to 2014 dollars). Results: The PCU operated at 54% occupancy in the first year. The daily loss pre-transfer of $1,672 was reduced 59% to $785 post-transer. Over 60% of transfers came from the ICU, freeing beds. The PCU saved JHM $367,751 in direct costs; additional cost savings for PC consultation were estimated at $4.3M (1,335 live discharges × $2,374, 165 decedent discharges × $6,872) and $370,000 was collected in professional fees, for a total contribution of approximately $5M. Conclusions: The PCU and PC program had a favorable impact on the health system. As JH moves to an acountable care organization model being both provider and insurer, such improved quality, cost savings, and increased ICU availability are desirable.
West Nile virus transmission: results from the integrated surveillance system in Italy, 2008 to 2015
Authors: Caterina Rizzo, Christian Napoli, Giulietta Venturi, Simonetta Pupella, Letizia Lombardini, Paolo Calistri, Federica Monaco, Roberto Cagarelli, Paola Angelini, Romeo Bellini, Marco Tamba, Alessandra Piatti, Francesca Russo, Giorgio Palù, Mario Chiari, Antonio Lavazza, Antonino Bella
Journal: Eurosurveillance (2016)

In Italy a national Plan for the surveillance of imported and autochthonous human vector-borne diseases (chikungunya, dengue, Zika virus disease and West Nile virus (WNV) disease) that integrates human and veterinary (animals and vectors) surveillance, is issued and revised annually according with the observed epidemiological changes. Here we describe results of the WNV integrated veterinary and human surveillance systems in Italy from 2008 to 2015. A real time data exchange protocol is in place between the surveillance systems to rapidly identify occurrence of human and animal cases and to define and update the map of affected areas i.e. provinces during the vector activity period from June to October. WNV continues to cause severe illnesses in Italy during every transmission season, albeit cases are sporadic and the epidemiology varies by virus lineage and geographic area. The integration of surveillance activities and a multidisciplinary approach made it possible and have been fundamental in supporting implementation of and/or strengthening preventive measures aimed at reducing the risk of transmission of WNV trough blood, tissues and organ donation and to implementing further measures for vector control.
Failure of naloxone to reduce manic symptoms
Authors: G C Davis, I Extein, V I Reus, W Hamilton, R M Post, F K Goodwin, W E Bunney
Journal: American Journal of Psychiatry (1980)

The authors conducted a double-blind placebo-controlled study in which patients with a wide range of manic symptoms were administered 20 mg of naloxone subcutaneously. Naloxone failed to improve manic severity, activation-arousal, or elation-grandiosity for intervals up to 3 hours. Global nurse ratings of mania did not improve over an 8-hour period. The authors suggest that the question of endorphin involvement in mania has not been resolved and recommend clinical studies with longer acting oral narcotic antagonists such as naltrexone.
Abstract 12837: Effect of 10mg and 40mg Atorvastatin on Endothelial Progenitor Cells, Carotid Intima-Media Thickness, High Sensitive C Reactive Protein and Cardiac Events in Statin NaïVe Patients
Authors: Stephen Lee, Shun Ling Kong, Pak Hei Chan, Kelvin Ki Wan Chan, Simon Cheung Chi Lam, Jo-jo Siu Han Hai, Yui Ming Lam, Frankie Chor Cheung Tam, William Kong To Hau, Raymond Hon Wah Chan
Journal: Circulation (2012)

Background:Statin has been shown to retard the progression of or even reverse atherosclerosis. Besides, it has anti-inflammatory properties and reduces cardiovascular events. This study aims to ass...
Effect of chlorpromazine on human growth hormone
Authors: A A Beg, V K Varma, R J Dash
Journal: American Journal of Psychiatry (1979)

The authors studied basal HGH levels and HGH response to insulin-induced hypoglycemia in 12 schizophrenic patients who had been treated with 200--450 mg/day of chlorpromazine for 6 months to 4 years compared with 12 schizophrenic patients who had received no drugs and 15 normal control subjects. They found no significant differences among the three groups in basal HGH levels or in maximum response HGH levels. No significant correlation was found between duration or dose of chlorpromazine therapy and HGH secretion. Longitudinal study in 5 previously untreated schizophrenic patients during 13 weeks of chlorpromazine administration showed a nonsignificant reduction in HGH response. Thus, the authors' findings fail to demonstrate any significant effect of chlorpromazine on growth hormone secretion in man.
Increased Conformational Flexibility of HLA–B*27 Subtypes Associated With Ankylosing Spondylitis
Authors: Bernhard Loll, Heinz Fabian, Hans Huser, Chee‐Seng Hee, Alexander Ziegler, Barbara Uchanska‐Ziegler, Andreas Ziegler
Journal: Arthritis & Rheumatology (2016)

Dissimilarities in antigen processing and presentation are known to contribute to the differential association of HLA-B*27 subtypes with the inflammatory rheumatic disease ankylosing spondylitis (AS). In support of this notion, previous x-ray crystallographic data showed that peptides can be displayed by almost identical HLA-B*27 molecules in a subtype-dependent manner, allowing cytotoxic T lymphocytes to distinguish between these subtypes. For example, a human self-peptide derived from vasoactive intestinal peptide receptor type 1 (pVIPR; sequence RRKWRRWHL) is displayed in a single conformation by B*27:09 (which is not associated with AS), while B*27:05 (which is associated with AS) presents the peptide in a dual binding mode. In addition, differences in conformational flexibility between these subtypes might affect their stability or antigen presentation capability. This study was undertaken to investigate B*27:04 and B*27:06, another pair of minimally distinct HLA-B*27 subtypes, to assess whether dual peptide conformations or structural dynamics play a role in the initiation of AS.Using x-ray crystallography, we determined the structures of the pVIPR-B*27:04 and pVIPR-B*27:06 complexes and used isotope-edited infrared (IR) spectroscopy to probe the dynamics of these HLA-B*27 subtypes.As opposed to B*27:05 and B*27:09, B*27:04 (which is associated with AS) displays pVIPR conventionally and B*27:06 (which is not associated with AS) presents the peptide in a dual conformation. Comparison of the 4 HLA-B*27 subtypes using IR spectroscopy revealed that B*27:04 and B*27:05 possess elevated molecular dynamics compared to the nonassociated subtypes B*27:06 and B*27:09.Our results demonstrate that an increase in conformational flexibility characterizes the disease-associated subtypes B*27:04 and B*27:05.
P-200 A study on response for irreversible electroporation of colon cancer cell using multiphoton microscopy
Authors: B. Keum, I.K. Yoo, J.M. Lee, S.H. Kim, H.S. Choi, E.S. Kim, Y.T. Jeen, H.J. Chun, C.D. Kim
Journal: Annals of Oncology (2016)
HLA–DPB1 as a Risk Factor for Relapse in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis: A Cohort Study
Authors: Marc Hilhorst, Fabian Arndt, Michael Joseph Kemna, Stefan Wieczorek, Yoni Donner, Benjamin Wilde, Jörg Thomas Epplen, Pieter van Paassen, Jan Willem Cohen Tervaert
Journal: Arthritis & Rheumatology (2016)

The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) form a group of small-vessel vasculitides with systemic involvement. Although the etiology of AAVs remains largely unknown, both genetic and environmental factors have been implicated. Recently, certain alleles in the HLA-DPB1 region on chromosome 6 were shown to be associated with proteinase 3 (PR3)-ANCA-positive AAV but not with myeloperoxidase (MPO)-ANCA-positive AAV. The aim of this study was to investigate whether different alleles in the HLA-DPB1 region have clinical and/or prognostic implications in AAV.One hundred seventy-four patients with a diagnosis of AAV were recruited at the Maastricht University Medical Centre between 2000 and 2009. Seventeen different HLA-DPB1 alleles were determined using the restriction fragment length polymorphism technique. A validation cohort of 170 AAV patients from the Vasculitis Centre of Luebeck/Bad Bramstedt was included.In the initial cohort, the distribution of HLA-DPB1 alleles was significantly different between PR3-ANCA-positive compared with MPO-ANCA-positive AAV patients, ANCA-negative AAV patients, and healthy controls. Importantly, HLA-DPB1*04:01 was present in 90% of PR3-ANCA-positive AAV patients compared with 63% of MPO-ANCA-positive AAV patients, 58% of ANCA-negative patients, and 63% of healthy controls. Patients homozygous for HLA-DPB1*04:01 had relapses more often compared with heterozygous patients and noncarrier patients. This association persisted after correction for ANCA subtype and diagnosis. In the validation cohort, patients homozygous for HLA-DPB1*04:01 and those heterozygous for HLA-DPB1*04:01 had relapses more often compared with noncarrier patients. When both patient cohorts were merged (n = 344), homozygous patients relapsed most often, followed by heterozygous patients and noncarrier patients.Carriage of HLA-DPB1*04:01 in patients with AAV is significantly associated with an increased risk of relapse compared with HLA-DPB1*04:01-negative patients, irrespective of ANCA status or clinical AAV entity.
John Richardson
Authors: William H. Sprunt
Journal: New England Journal of Medicine (1955)

IT is difficult for the casual reader to decide whether John Richardson should be considered first and foremost a physician or a naturalist. Chronologically, he was first a physician. On the basis of his writings and posthumous fame, he was first a naturalist. It was in the combined capacity of physician and naturalist that he went farthest afield, geographically speaking at least, as an Arctic explorer.Richardson was born in Dumfries, Scotland, in 1787. His father was chief magistrate and justice of the peace, and a friend of the town's most famous citizen, Robert Burns. Between bouts of congestive heart . . .
Case 34-1968
Authors: Denise J. Strieder, Benjamin Castleman
Journal: New England Journal of Medicine (1968)

Presentation of CaseA sixty-four-year-old man entered the hospital because of a cough and loss of weight.Four years previously he had been treated for tetanus, with an uneventful recovery. He had no cough or hemoptysis at that time, and an x-ray film of the chest was normal. Three months before entry there was the onset of a persistent cough that was nonproductive except for occasional hemoptysis. He became fatigued and anorectic, with a loss of 20 pounds in weight. Pleuritic pain in the left anterior portion of the chest developed. Two weeks before admission he was examined by a . . .
Update on Alzheimer's Disease Therapy and Prevention Strategies
Authors: W. Vallen Graham, Alessandra Bonito-Oliva, Thomas P. Sakmar
Journal: Annual Review of Medicine (2017)

Alzheimer's disease (AD) is the primary cause of age-related dementia. Effective strategies to prevent and treat AD remain elusive despite major efforts to understand its basic biology and clinical pathophysiology. Significant investments in therapeutic drug discovery programs over the past two decades have yielded some important insights but no blockbuster drugs to alter the course of disease. Because significant memory loss and cognitive decline are associated with neuron death and loss of gray matter, especially in the frontal cortex and hippocampus, some focus in drug development has shifted to early prevention of cellular pathology. Although clinical trial design is challenging, due in part to a lack of robust biomarkers with predictive value, some optimism has come from the identification and study of inherited forms of early-onset AD and genetic risk factors that provide insights about molecular pathophysiology and potential drug targets. In addition, better understanding of the Aβ amyloid pathway and the tau pathway—leading to amyloid plaques and neurofibrillary tangles, respectively, which are histopathological hallmarks of AD—continues to drive significant drug research and development programs. The main focus of this review is to summarize the most recent basic biology, biochemistry, and pharmacology that serve as a foundation for more than 50 active advanced-phase clinical trials for AD prevention and therapy.
Agonist-Induced Thromboxane A2 Generation Requires Signaling Through Apoptosis Signal-Regulating Kinase 1 (ASK1): Genetic Ablation of Ask1 Severely Affects In Vivo Thrombosis
Authors: Meghna Ulhas Naik, Ramya Turaga, Hidinori Ichijo, Ulhas P Naik
Journal: Blood (2011)
Case 37-1969
Authors: Bernard M. Jacobson, Benjamin Castleman
Journal: New England Journal of Medicine (1969)

Presentation of CaseA seventy-nine-year-old man was admitted to the hospital because of weakness.Two months previously he became aware of progressive fatigue and weakness, with difficulty in climbing one flight of stairs. Anorexia and episodes of vomiting and diarrhea occurred. There was no soreness of the mouth, tongue or throat or bleeding from the gums, nose or rectum. Swelling of the ankles developed. He had no fever or chills.For sixty years he had smoked 1 package of cigarettes daily. He had had a chronic cough and mild dyspnea on exertion. During the three years before admission there had . . .
Clinical activity and safety of HM61713, an EGFR-mutant selective inhibitor, in advanced non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutations who had received EGFR tyrosine kinase inhibitors (TKIs).
Authors: Dong-Wan Kim, Dae Ho Lee, Jin Hyoung Kang, Keunchil Park, Ji-Youn Han, Jong-Seok Lee, In-Jin Jang, Hyo-Yeon Kim, Jeewoong Son, Joo-Hang Kim
Journal: Journal of Clinical Oncology (2014)

8011 Background: HM61713 is a novel, oral, selective inhibitor for EGFR mutations including both activating mutations and T790M, but not EGFR wild-type. This phase 1 trial was conducted to evaluate the safety, pharmacokinetics, and preliminary efficacy of HM61713 in the pts with advanced NSCLC harboring EGFR mutations who had failed to previous EGFR-TKIs (NCT01588145). Methods: EGFR TKIs pre-treated, advanced NSCLC pts with EGFR mutation positive tumors were enrolled. The 3+3 dose-escalation scheme was used in dose-escalation cohort. Expansion cohort was implemented at the dose 300mg qd; pts were assigned to either arm A or B according to elapsed time interval after prior EGFR-TKIs (Arm A: <4 weeks; Arm B: ≥4 weeks) and underwent mandatory tissue biopsy at baseline to analyze EGFR T790M mutation status. Results: To date, a total of 93 pts have been enrolled in both dose escalation and expansion cohorts (35:58 respectively). These pts received HM61713 up to 500 mg/day and maximum tolerated dose has not been determined yet and subsequent dose escalation is ongoing. Drug-related adverse events (AEs) reported in ≥10% of pts were skin exfoliation, nausea, diarrhea, rash, decreased appetite and pruritus. Most of AEs were typically Gr 1/2, easily manageable and reversible without interruption of dosing. Two cases of Gr3 or more drug-related AEs were reported. A total of 7 unconfirmed partial responses (uPR) were observed so far out of 42 evaluable pts (arm A: 3/16; arm B: 4/26) in expansion cohort. Disease control rate was 76.5% and 73.1% in arm A and B, respectively. Among 27 patients who had T790M mutation at baseline biopsy, 18 pts showed decreased size in the target lesions and all the uPR observed were T790M mutation positive cases. Conclusions: HM61713 showed good safety profile and promising anti-tumor activity in pts with EGFR mutated NSCLC who failed to EGFR-TKIs, especially in pts with T790M mutation. Clinical trial information: NCT01588145.
Age-Dependence of Hepatic Dimethylnitrosamine-Demethylase Activity in the Rat2
Authors: D. L. Davies, G. M. Bryant, J. C. Arcos, M. F. Argus
Journal: JNCI Journal of the National Cancer Institute (1976)

The mixed-function oxidase which activates the carcinogen dimethylnitrosamine (DMN) was determined in the rat liver as a function of animal age. DMN-demethylase activity increased considerably at first to reach a maximum on day 29, and then substantially decreased to day 59; thereafter, enzyme activity remained essentially stable up to at least day 110. Pretreatment with 3-methylcholanthrene, which caused a pronounced decrease in this enzyme activity, did not affect the general shape of the age-dependence curve. The results suggest that rats between weaning and sexual maturity are more susceptible to the carcinogenic effects of pulse doses of DMN than are neonates or adult animals.
BMA annual meeting: Doctors vote to maintain opposition to assisted dying
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

Doctors at the BMA’s annual representatives meeting in Belfast have voted 63% to 37% for the association to maintain its opposition to assisted dying, in response to a motion urging it to adopt a neutral stance on the issue.

The debate went ahead after representatives voted 50:50 on an earlier motion proposed by Andrew Mowat that it should not take place.1 He argued that MPs in the Scottish parliament and the House of Commons had recently rejected bills on physician assisted dying and that the issue had been debated at seven of the last 10 BMA annual meetings.

“The issue of [physician …
The combination of ibrutinib and venetoclax (ABT-199) to achieve complete remissions in patients with relapsed/refractory mantle cell lymphoma: Preliminary results of the phase II AIM study.
Authors: Constantine Si Lun Tam, Andrew Warwick Roberts, Mary Ann Anderson, Sarah-Jane Dawson, Rodney J Hicks, Christiane Pott, David A. Westerman, Glenda Burke, Sarah Kamel, Martin H. Dreyling, Mark A Dawson, John Francis Seymour
Journal: Journal of Clinical Oncology (2016)

7548 Background: The targeted agents ibrutinib (IB) & venetoclax (A; ABT-199) individually achieve response rates of 68-75% in patients (pts) with relapsed/refractory (R/R) mantle cell lymphoma (MCL). However, individually both drugs are associated with complete remissions (CR) in < 25%, & median remissions < 18 months. As preclinical models show synergy, we evaluate the combination in the clinic. Methods: AIM is an ongoing, investigator-initiated phase II study. Pts have R/R MCL, ECOG ≤ 2, adequate marrow & organ function. Treatment: 4 week IB induction 560mg daily, followed by a 4 week ramp-up of A (target dose 400mg daily) with tumour lysis syndrome (TLS) monitoring, & continuation of both drugs thereafter. At full recruitment (n = 24), the study is powered to show improvement in CR rate after 4 months (primary endpoint) from a historic 9% for IB alone, to ≥ 30%. Pts are restaged using FDG PET/CT scans & minimal residual disease (MRD) by flow cytometry, ASO-PCR and circulating tumor DNA. Results: As of 29-Jan-2016, 8 pts are enrolled: median follow-up 38 days (range, 1-188), median age 72 yr (53–77), median 2 (1–7) therapies, high MIPI score 63%. Most common adverse events (AE, all grade 1-2): nausea (n = 4), diarrhea (2), oral candidiasis (2). 6 serious AE have occurred: none related to study drugs. Response to IB induction (4 weeks): 2 partial responses (PR), 2 stable disease, 1 progressive disease; 3 still receiving induction. The full dose of 400mg was reached in all 4 pts entering A ramp-up, without occurrence of TLS. Three pts have completed staging at 4 months (1 month of IB and 3 months of A+IB), with 2 achieving CR (normalization of PET ± endoscopy, and complete clearance of previous marrow involvement, including flow cytometry at > 10-4sensitivity). The remaining pt had non-FDG avid, small volume disease following IB induction that was inadequately visualized on the 4-month PET/CT scan, & was thus classified as PR. Updated safety, efficacy & MRD data will be presented at the meeting. Conclusions: The early experience with ibrutinib and venetoclax in combination shows no unexpected safety signals, and indicates promising efficacy. Clinical trial information: NCT02471391.
Thyroid Disease: Endocrinology, Surgery, Nuclear Medicine, and Radiotherapy
Journal: Annals of Internal Medicine (1991)

This volume, edited by a well-known thyroid surgeon, is composed of a series of clinically related chapters on all prac- tical aspects of thyroid disease. The editor has recruited experts from many clinical disciplines to write chapters on facets of thyroid physiology, pathology, diagnosis, and management, which will certainly act as a very useful guide for clinicians who frequently encounter dis- eases of the thyroid gland on a day-to- day basis. It is not surprising that there is a tilt toward surgical management in this volume, reflecting the interest of the editor; indeed, a great deal of space is given over to chapters on surgical anat-