tbuckley/cabot-search huggingface dataset:
Estimation of Potential Savings Through Therapeutic Substitution
Authors: Michael E. Johansen, Caroline Richardson
Journal: JAMA Internal Medicine (2016)

Therapeutic substitution offers potential to decrease pharmaceutical expenditures and potentially improve the efficiency of the health care system.To estimate potential savings through therapeutic substitution in terms of both overall and out-of-pocket expenditures of branded drugs when a generic in the same class with the same indication was available.Repeated cross-sectional study using the 107 132 individuals included in the nationally representative Medical Expenditure Panel Survey (2010-2012) along with their reported prescribed medicine use. The Orange Book, company financial statements, US Food and Drug Administration records, and published research were used for adjunctive information.Estimated excess expenditure due to branded drug overuse when a lower-cost generic in the same class with the same indication was available.The study included 107 132 individuals between 2010 and 2012, of whom 62.1% (95% CI, 61.4%-62.8%) reported use of any prescribed medicine. A total of 31.5% (95% CI, 30.7%-32.2%) used a medication from an included drug class, whereas 16.6% (95% CI, 16.0%-17.1%) of the population used a branded drug from the included classes compared with 24.0% (95% CI, 23.4%-24.7%) who used a generic and 9.1% (95% CI, 8.7%-9.4%) who used both. In the included drug classes, the majority of the drugs were generics, with a total of 93.5 billion standardized doses compared with 47.4 billion standardized doses of branded drugs. Total expenditure of the branded drugs accounted for $147 (95% CI, $137-$156) billion compared with $62.7 (95% CI, $58.9-$66.5) billion for the generics. Between 2010 and 2012, an estimated $73.0 (95% CI, $67.6-$78.5) billion in total excess expenditure and $24.6 (95% CI, $22.6-$26.5) billion in out-of-pocket excess expenditure was attributable to branded drug overuse. The excess was present across numerous drug classes throughout many aspects of medicine and equates to 9.6% of total and 14.1% of out-of-pocket prescribed medicine expenses. The drug classes with the highest excess expenditure included statins ($10.9 [SE, $0.41] billion), atypical antipsychotics ($9.99 [SE, $1.03] billion), proton pump inhibitors ($6.12 [SE, $0.38] billion), selective serotonin reuptake inhibitors ($6.08 [SE, $0.49] billion), and angiotensin receptor blockers ($5.53 [SE, $0.35] billion).Although therapeutic substitution is controversial, it offers a potential mechanism to significantly decrease drug costs if it can be implemented in a way that does not negatively affect quality of care.
Intra-arterial Injection of Thiopentone--Curare Mixture
Authors: W. N. Rollason
Journal: BMJ (1950)

±4-8 Curare .. 38 2 5.3% ± 3-7 (Local) .. (128) (27) (21 *09%8) (+3 7)The figures for local analgesia are included for rough comparison, but they are not strictly comparable with the others.agreed that, though the mortality in this group is very high, it is difficult to incriminate the anaesthetic technique, especially when the favourable results encountered in the corresponding group of mature infants are taken into consideration. SummaryThe advantages of local analgesia and curare with light general anaesthesia for caesarean section are discussed.A statistical analysis of the neonatal mortalityoccurring after caesarean section performed under ordinary general anaesthesia, curare sequence, and local analgesia supports the view that local analgesia is to be preferred to ordinary general anaesthesia.There is no evidence to indicate clearly the position of the curare sequence in the three methods considered.We gratefully acknowledge our debt to the authorities of the Liverpool Maternity Hospital for giving us access to their records, and to Professor T. N. A. Jeffcoate for his helpful criticism.
The Revised IPSS (IPSS-R) Predicts Response To Erythropoietic Stimulating agents (ESA) In Pts With Classical IPSS Low Or Intermediate-1 (int 1)- MDS: A Joint Retrospective Study Of The GFM, Düsseldorf Registry and Fism
Authors: Valeria Santini, Jennifer Schemenau, Alessandro Levis, Enrico Balleari, Rosa Sapena, Lionel Ades, Agnès Guerci, Odile Beyne-Rauzy, Marie Pierre Gourin, Stéphane Cheze, Aspasia Stamatoullas, Alessandro Sanna, Daniela Gioia, Giani Cametti, Dario Ferrero, Emmanuel Raffoux, Christian Rose, Poloni Antonella, Thomas Prebet, Shanti Ame, Laurence Legros, Pierre Fenaux, Ulrich Germing, Francois Dreyfus, Sophie Park
Journal: Blood (2013)
288O Role of FDG-PET/CT and gastrointestinal endoscopy in the staging of diffuse large B-cell lymphoma (DLBCL)
Authors: T. Honda, D. Maruyama, H. Kurihara, A.M. Maeshima, S. Yuda, K. Toyoda, N. Yamauchi, S. Makita, S. Fukuhara, W. Munakata, Y. Kobayashi, H. Taniguchi, Y. Saito, K. Tobinai
Journal: Annals of Oncology (2015)
Engot-Ov16/Nova: a Phase 3 Randomized Double-Blind Trial of Maintenance with Parp-Inhibitor Niraparib Versus Placebo in Patients with Platinum-Sensitive Ovarian Cancer
Authors: M.R. Mirza, B.J. Monk, J.A. Ledermann, A.M. Oza, J.M. Del Campo, J.S. Berek, S. Mahner, R.M. Wenham, I.B. Vergote, M. Fabbro, C. Marth, A. Dørum, D. Lorusso, D. Katsaros, I. Bruchim, S. Malander, J. Herrstedt, S. Agarwal, R.E. Martell, U. Matulonis
Journal: Annals of Oncology (2014)
Goserelin plus anastrozole (G+A) as first-line systemic therapy for premenopausal estrogen receptor positive (ER+) advanced breast cancer (ABC)— clinical and endocrine data
Authors: A. Agrawal, L. Winterbottom, J. F. Robertson, K. L. Cheung
Journal: Journal of Clinical Oncology (2008)

1091 Background: Trials have shown superiority of aromatase inhibitors over tamoxifen for postmenopausal ER+ ABC. We previously reported the use of G+A as second-line endocrine therapy for premenopausal ER+ ABC. We report clinical and endocrine data from G+A as first-line systemic therapy. Methods: Thirty-six patients (median age = 44 [30–59] years) with UICC assessable disease (metastatic = 30; else = locally advanced) were administered G+A (3.6 mg 4-weekly + 1 mg daily respectively) for ≥6 months (unless progressed prior). Serum estradiol, DHEAS, testosterone, FSH and LH levels were measured by standardized and sensitive (estradiol only) hormone assays in six patients who consented for blood samples. Results: Thirty-two patients (67%) derived clinical benefit (CB) (5% complete response, 31% partial response, 31% stable disease for ≥6 months) with median time-to-progression and duration of CB of 7(2–48) and 23+(6–64+) months, respectively. Therapy was well tolerated with no withdrawals. Thirteen patients were receiving therapy at analysis. G+A resulted in 98%, 15%, 33%, 35% and 95% reduction (from pretreatment to 6-month) in median levels (pmol/L) of estradiol [574.5 (170- 3204) - 13.45 (5.4–35)], DHEAS [4.05 (2.5–6.4) - 3.45 (3.0–5.9)], testosterone [1.25 (0.79–2.38) - 0.85 (0.36–1.14)], FSH [8.2 (6.5–22) - 5.3 (2.7–8.5)] and LH [3.05 (2.4–21) - 0.15 (0.09–0.27)], respectively. Conclusions: G+A as first-line therapy produces sustained CB and minimal side effects in premenopausal ER+ ABC with significant reduction in estradiol levels. G+A should be considered in appropriate patients with hormone-sensitive ABC. Acknowledgement: M Dowsett, Institute of Cancer Research, London for performing hormone assays Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca Oncology AstraZeneca Oncology AstraZeneca Oncology AstraZeneca Oncology
A Phase II Multi-Center Trial Of Pentostatin Plus Cyclophosphamide With Ofatumumab (PCO) In Older Previously Untreated Chronic Lymphocytic Leukemia (CLL) Patients
Authors: Marco Montillo, Davide Rossi, Marina Motta, Giulia Quaresmini, Marianna Rossi, Marta Coscia, Antonella Anastasia, Fausto Rossini, Agostino Cortelezzi, Guido Nador, Lydia Scarfò, Roberto Cairoli, Daniela Dal Ceggio, Lorenzo De Paoli, Enrica Morra, Alessandro Rambaldi, Ester Orlandi, Massimo Massaia, Alessandra Tedeschi
Journal: Blood (2013)
Clinical and prognostic significance of serum levels of von Willebrand factor and ADAMTS-13 antigens in AL amyloidosis
Authors: Efstathios Kastritis, Ioannis Papassotiriou, Evangelos Terpos, Maria Roussou, Maria Gavriatopoulou, Anna Komitopoulou, Chrysanthi Skevaki, Evangelos Eleutherakis-Papaiakovou, Constantinos Pamboucas, Erasmia Psimenou, Efstathios Manios, Stavroula Giannouli, Marianna Politou, Harikleia Gakiopoulou, Elektra Papadopoulou, Kimon Stamatelopoulos, Anna Tasidou, Meletios A. Dimopoulos
Journal: Blood (2016)
Quality and Safety in Health Care, Part XIII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2016)

There are many ways to help determine the incidence of errors in diagnosis including reviewing autopsy data, health insurance and malpractice claims, patient health records, and surveys of doctors and patients. However, all of these methods have positive and negative points. There are also a variety of ways to analyze diagnostic errors and many recommendations about how to decrease the frequency of errors in diagnosis. Overdiagnosis is an important quality and safety issue but is not considered an error.
Spontaneous Cavitation and Progressive Accumulation of Air in a Metastatic Mediastinal Lymph Node
Authors: Madhu Pendurthi, Van Hoang, Donald R. Lazarus, Roberto F. Casal
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

A 70-year-oldman presentedwith progressive dyspnea, cough, andmild hemoptysis. Chest X-ray showed multiple cavitary lesions, prompting a computed tomography (CT) scan. The latter showed areas of ground-glass attenuation around multiple cystic lung lesions (Figure 1A), enlarged and necrotic mediastinal lymph nodes (LN), and, strikingly, a small amount of air within a necrotic LN in station 4R (Figure 1B). Bronchoscopy with bronchoalveolar lavage, transbronchial lung biopsies, and endobronchial ultrasound–guided transbronchial needle aspiration were performed. The airway was normal. Both LN and lung tumor were consistent with an angiosarcoma, and infection was ruled out. Subsequent images (positron emission tomography–CT) obtained for staging purposes within 45 days of original CT findings showed progressive accumulation of air in a 4R LN (Figures 1C and 1D), with the patient being asymptomatic. Of note, this particular LN showed only necrosis and tumor cells by endobronchial ultrasound–guided transbronchial needle aspiration, and intranodal air was, in fact, Figure 1. (A) Ground-glass attenuation surrounding a cystic lung lesion (arrow). (B–D) Progressive accumulation of air in a metastatic right paratracheal lymph node (arrow).
Managing the Medical–Industrial Complex
Authors: Alan L. Hillman, David B. Nash, William L. Kissick, Samuel P. Martin
Journal: New England Journal of Medicine (1986)

Emerging trends toward competition, entrepreneurship, and incorporation within both nonprofit and proprietary health care organizations have been discussed in these pages with increasing frequency. Some commentators have challenged the morality, integrity, and efficiency of such trends.1 , 2 Some have complained that business people have become the most important participants in health care or that administrators have changed from being servants to being masters.3 , 4 Some essays have defended the potential benefits of these trends.5 , 6 Most writers have called on the medical community to study and control the evolution of the medical–industrial complex.This challenge has been neglected so far. Instead of planning . . .
Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia Accelerates Count Recovery and Increases Response Rates
Authors: Danielle M. Townsley, Bogdan Dumitriu, Phillip Scheinberg, Ronan Desmond, Xingmin Feng, Olga Rios, Barbara Weinstein, Janet Valdez, Thomas Winkler, Marie Desierto, Harshraj Leuva, Colin Wu, Katherine R. Calvo, Andre Larochelle, Cynthia E. Dunbar, Neal S. Young
Journal: Blood (2015)
Study of anti-PD-1 antibody pembrolizumab and pegylated-interferon alfa-2b (Peg-IFN) for advanced melanoma.
Authors: Hassane M. Zarour, Hussein Tawbi, Ahmad A. Tarhini, Hong Wang, Cindy Sander, Amy Rose, Julien J. Fourcade, Joe-Marc Chauvin, Zhaojun Sun, Ornella Pagliano, John M. Kirkwood
Journal: Journal of Clinical Oncology (2015)

e20018 Background: The anti-PD-1 antibody pembrolizumab provides durable clinical benefits to 30-40% of patents with advanced melanoma.A number of murine and human studies suggest that pre-existing CD8+ T cell responses to melanoma and presence of an IFN-a gene signature may correlate with clinical response to immunotherapies, including PD-1 blockade. In this trial, we have tested the hypothesis that Peg-IFN stimulates T cell response to melanoma, increasing clinical response to PD-1 blockade. Methods: This safety and dose-seeking study of combination pembrolizumab and Peg-IFN for patients ( ≥ 18) with recurrent inoperable AJCC stage III and metastatic stage IV melanoma. Pembrolizumab is given 2 mg/kg q3 weeks for 2 years while Peg-IFN is given SC at 3 dose levels (1, 2 and 3 mcg/kg) to identify the recommended phase 2 dose (RP2D) prior to dose expansion up to 32 patients. Results: . Twelve patients have been enrolled in this trial (4 patients at each dose level). Previous treatments include adjuvant IFN, IL-2, vemurafenib, chemotherapy, radiotherapy. No dose limiting toxicity has been observed to date. Most common side adverse events were grade 1 liver toxicities (n = 4), grade 1 neutropenia (n = 4), grade 1 skin rash (n = 3) and grade 1 anemia (n = 2). The only grade 3/4 toxicities were lymphopenia (n = 2) and hyponatremia (n = 1). Six out of 12 patients were evaluated for clinical responses at week 12 and we observed 1CR, 4SD and 1PD with mixed clinical responses. Conclusions: The combination of pembrolizumab and Peg-IFN is well tolerated and clinically active. The clinical activity and immune responses to melanoma induced by the combination is being evaluated in dose expansion studies Clinical trial information: NCT02112032.
O<scp>pening the</scp> D<scp>ebate on the</scp> N<scp>ew</scp> S<scp>epsis</scp> D<scp>efinition</scp>Defining Sepsis: A Case of Bounded Rationality and Fuzzy Thinking?
Authors: Derek C. Angus
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

The Sepsis-3 Task Force recently offered a conceptual definition of sepsis as life-threatening organ dysfunction secondary to a dysregulated host response to infection (1).As with prior definitions, the task force acknowledged there is no "gold standard" by which to operationalize this definition.Nonetheless, they believed there was a need to offer some standard and, based on several domains of validity, reliability, and practicality, recommended sepsis be defined clinically as an increase of two or more Sequential Organ Failure Assessment (SOFA) points in the setting of infection.The task force reached its recommendations after vigorous debate; opinions were not unanimous, and the subsequent reaction in the broader community reflects many of the same points of contention.Debate is welcomed, but one disconnect is the certainty with which some views have been expressed, despite the widely acknowledged uncertainties plaguing sepsis.
Abstract 275: Electrophysiological Consequences of AAV9 mediated SERCA2a Gene Transfer to Normal Rat Myocardium
Authors: Chaoqin Xie, Dongtak Jeong, Erik Kohlbrenner, Roger J Hajjar, Fadi G Akar
Journal: Circulation Research (2014)

SERCA2a gene transfer to the failing heart improves its mechanical function and inhibits arrhythmic triggers caused by aberrant calcium waves. The majority of arrhythmias occur before onset of end-stage heart failure when SR function is not compromised. Examination of the electrophysiological (EP) consequences of SERCA2a gene therapy in normal hearts is imperative in determining its potential toxicity as a preventive therapy during early stages of remodeling. We hypothesized that AAV9 mediated gene transfer of SERCA2a to normal rat hearts may promote the incidence of arrhythmic triggers under conditions of intracellular calcium (Ca2+) overload. Methods: Rats underwent tail vein injection of 5x10E11vg AAV9.SERCA2a (N=8) or AAV9.GFP (N=3). 6 naïve uninjected rats served as controls (Ctl). Using high resolution optical action potential (AP) imaging, we characterized the EP substrate 6 weeks post gene transfer. Ex vivo hearts were examined during normoxic perfusion and challenge with low flow ischemia for 1h followed by reperfusion. Arrhythmia susceptibility was determined under conditions of Ca2+ overload. Results: Surprisingly, AAV9.GFP hearts exhibited markedly prolonged AP durations (APD) and slower conduction velocities (CV) compared to AAV9.SERCA2a and Ctl hearts. Challenge of AAV9.GFP but not AAV9.SERCA2a or Ctl hearts with burst pacing always resulted in VF. Remarkably, APD &amp; CV rate relationships were identical in Ctl and AAV9.SERCA2a hearts (p=NS). Elevation of pacing rate resulted in a comparable level of AP alternans followed by loss of 1:1 capture in both groups. No evidence of triggered APs was found in AAV9.SERCA2a or Ctl hearts in response to burst stimulation. Ischemia for 1hr produced comparable changes in APD and CV. Challenge with burst stimuli during ischemia elicited arrhythmias in 2/6 Ctl and 6/8 AAV9.SERCA2a hearts (p=0.277, NS). Upon reperfusion, 1/4 &amp; 0/2 remaining Ctl and AAV9.SERCA2a hearts exhibited VF. Conclusion: Surprisingly, AAV9.GFP but not AAV9.SERCA2a gene transfer to normal rat myocardium alters EP properties and promotes Ca2+ mediated arrhythmias. Lack of an EP phenotype of AAV9.SERCA2a suggests an upper limit of endogenous SERCA2a expression in normal rodent myocardium that is not exceeded by gene transfer.
Refractory chylothorax in HIV/AIDS-related disseminated mycobacterial infection
Authors: Takeshi Tanaka, Nobuo Saito, Masahiro Takaki, Akitsugu Furumoto, Konosuke Morimoto, Koya Ariyoshi
Journal: Thorax (2016)

A 38-year-old man presented to a previous hospital in December 2011 with a high fever and acute abdominal pain. He was found to have abdominal lymphadenopathy and was diagnosed with HIV infection. His CD4 count was 25/mm3 and viral load was 490 000 copies/mL. He was transferred to our department for further investigations and treatment. Whole body CT revealed bulky, widespread lymphadenopathy, especially in the abdomen, but no ascites or pleural effusion (figure 1A, B). Stool, bone marrow and an abdominal lymph node specimen were positive for acid-fast bacillus stain. A diagnosis of disseminated non-tuberculous mycobacterial …
Nasal immunization with mannan-decorated mucoadhesive HPMCP microspheres containing ApxIIA toxin induces protective immunity against challenge infection with Actinobacillus pleuropneumoiae in mice
Authors: Hui-Shan Li, Min-Kyoung Shin, Bijay Singh, Sushila Maharjan, Tae-Eun Park, Sang-Kee Kang, Han-Sang Yoo, Zhong-Shan Hong, Chong-Su Cho, Yun-Jaie Choi
Journal: Journal of Controlled Release (2016)
Case 49-1965
Authors: Roman W. DeSanctis, Benjamin Castleman
Journal: New England Journal of Medicine (1965)

Presentation of CaseA seventy-eight-year-old woman was admitted to the hospital because of weakness.She had been well until four years previously, when fatigue and anemia developed. Stool specimens gave positive guaiac tests, but no source of bleeding was demonstrated. Six months later she entered the hospital because of the abrupt onset of diplopia. Physical examination disclosed palsy of the right abducens nerve, a murmur indicative of aortic stenosis and enlargement of the heart. A heart murmur had been audible since the age of fifty-eight years. An electrocardiogram (Fig. 1 ) showed a pattern of left ventricular strain. X-ray films with . . .
A Suprainstitutional Network for Remote Extracorporeal Life Support
Authors: Hug Aubin, George Petrov, Hannan Dalyanoglu, Diyar Saeed, Payam Akhyari, Gerrit Paprotny, Maximillian Richter, Ralf Westenfeld, Hubert Schelzig, Malte Kelm, Detlef Kindgen-Milles, Artur Lichtenberg, Alexander Albert
Journal: JACC Heart Failure (2016)
Intractable Pruritus as a Manifestation of Secondary Hyperparathyroidism in Uremia
Authors: Shaul G. Massry, Mordecai M. Popovtzer, Jack W. Coburn, Dwight L. Makoff, Morton H. Maxwell, Charles R. Kleeman
Journal: New England Journal of Medicine (1968)

PRURITUS, a common symptom in uremic patients, is usually observed in the absence of visible skin lesions.1 , 2 The underlying cause of the itching in these patients is unknown, but the "toxic" effect of uremia has usually been implicated. However, improvement of the uremic state by adequate hemodialysis or peritoneal dialysis does not always relieve the itching, and in certain cases pruritus may even worsen,3 suggesting that factors other than uremia itself may be involved.We have previously observed the disappearance of severe pruritus after subtotal parathyroidectomy in two patients with chronic renal failure who were maintained with adequate hemodialysis.†3 This . . .
Integration of hepatitis B vaccination into national immunisation programmes
Authors: P. Van Damme, M. Kane, A. Meheus
Journal: BMJ (1997)

<h3>Abstract</h3> Hepatitis B is a major public health problem even though safe and effective vaccines have been available for over 10 years. Because hepatitis B infection is largely asymptomatic with long term complications occurring after many years it has not received the attention it deserves. Strategies to immunise those at high risk have failed to control the disease. Delegates to the World Health Assembly of the World Health Organisation recommended in May 1992 that all countries should integrate hepatitis B vaccination into their national immunisation programmes by 1997. Some western European countries remain unconvinced that the burden of disease warrants the expense of universal vaccination. However, epidemiological data and economic evaluation show that universal hepatitis B vaccination is cost effective in countries with low endemicity and that it will control hepatitis B, reinforcing the necessity for action.
Pulmonary hypertension associated with ponatinib therapy
Authors: Fleur-Marie Quilot, Marjolaine Georges, Nicolas Favrolt, Guillaume Beltramo, Clément Foignot, Aurélie Grandvuillemin, David Montani, Philippe Bonniaud, Philippe Camus
Journal: European Respiratory Journal (2016)

Over 50 drugs, including anorexigens, abused substances and recently the tyrosine kinase inhibitor (TKI) dasatinib, have been temporally and/or mechanistically related to the development of pulmonary arterial hypertension (PAH) in humans (where the evidence base for causality is wide ranging) and in animal models [1–3]. The TKIs imatinib, dasatinib, nilotinib and bosutinib are available to treat chronic myelogenous leukaemia (CML) and acute lymphoblastic leukaemia. These drugs are associated with distinctive respiratory adverse effects (AEs), including pleural and/or pericardial effusion, PAH (an AE so far almost exclusively restricted to dasatinib) and pulmonary infiltrates [1, 4–6]. The novel TKI ponatinib is prescribed for the same indications as above, in patients whose haematological malignancy has become resistant to, or who develop intolerance to the earlier TKIs [7]. Here, we present a female CML patient with prior exposure to dasatinib who developed PAH 6 months into ponatinib therapy, an association that has not previously been reported. Signs and symptoms of PAH improved following drug discontinuation and institution of targeted anti-PAH therapy. A case of pulmonary hypertension associated with ponatinib therapy in a chronic myelogenous leukaemia patient <http://ow.ly/V8reI> We thank Jean-Christophe Eicher (Dept of Cardiology, CHU de Bourgogne, Dijon, France), who performed the right heart catheterisation, and Philip Bastable (UFR Médecine, Université de Bourgogne, Dijon, France) for his help.
Negative Effects on Psychological Health and Quality of Life of Genuine Irritable Bowel Syndrome–type Symptoms in Patients With Inflammatory Bowel Disease
Authors: David J. Gracie, Christopher J.M. Williams, Ruchit Sood, Saqib Mumtaz, M. Hassan Bholah, P. John Hamlin, Alexander C. Ford
Journal: Clinical Gastroenterology and Hepatology (2016)