tbuckley/cabot-search huggingface dataset:
Etiologies and Clinical Characteristics of 97 Patients Diagnosed with Severe Cutaneous Adverse Reactions from Six Tertiary Medical Centers in Thailand
Authors: Jettanong Klaewsongkram, Pawinee Rerknimitr, Ticha Rerkpattanapipat, Kumutnart Chanprapaph, Papapit Tuchinda, Leena Chularojanamontri, Napatra Tovanabutra, Wareeporn Disphanurat, Panlop Chakkavittumrong, Chutika Srisuttiyakorn, Pattarawat Thantiworasit, Chonlaphat Sukasem, Yuttana Srinoulprasert
Journal: Journal of Allergy and Clinical Immunology (2016)
Men gain more disability-free years in older age than women, US study finds
Authors: Michael McCarthy
Journal: BMJ (2016)

Although older women continue to live longer than men, they no longer live more years free of disability, a US study has found.1

The study, which looked at aging and disability trends from 1982 to 2011, found that while overall survival after age 65, and survival without disability, had increased in men and women, the gain in years without disability was much greater in men than …
In vitro pharmacological characterization of two novel dual-acting MABA compounds (LAS190792 and LAS191351)
Authors: Montserrat Miralpeix, Carla Carcasona, Israel Ramos, Carlos Puig, Dolors Vilella, Amadeu Gavaldà, Mònica Aparici
Journal: European Respiratory Journal (2014)

Background 

This study assessed the in vitro pharmacological profile of two novel bifunctional M3-antagonist/β2-agonist (MABA) compounds in development for chronic respiratory diseases with airflow limitation.

Methods 

Receptor binding and s-adrenergic activity was assessed using CHO cell membranes expressing human M1, M2 and M3, and β1 and β2 receptors. Electrical-field stimulated (EFS) guinea pig tracheal preparations were used to assess global functional MABA potency, onset and duration of action (DoA); functional M3 potency (in the presence of propranolol) and β2 potency (in resting tone [RT] preparations) were tested. β1 activity was assessed by change in force of contraction in guinea pig left atria. Comparators were tiotropium and indacaterol.

Results 

LAS191351 had human M3-receptor affinity similar to tiotropium; LAS190792 was 5-fold lower. LAS190792 was the most potent β2-agonist in inducing cAMP production and trachea relaxation (RT, IC50: 0.23 nM). Both compounds had similar or higher s1/s2 selectivity vs indacaterol. Global potency (IC50: LAS190792, 1.3 nM; LAS191351, 2.6 nM) was similar to tiotropium (1.2 nM) and indacaterol (0.8 nM). Functional M3 potency was greater for LAS191351 than LAS190792 (IC50: 2.8 vs 4.3 nM, respectively). Both MABAs had an onset of action faster than tiotropium; DoAs were LAS190792 206 min, LAS191351 >480 min, indacaterol 200 min and tiotropium >480 min.

Conclusion 

LAS190792 and LAS191351 are potent and selective MABAs with different M3/β2 activity in vitro . Further studies are needed to determine duration and bronchodilator efficacy of these MABAs in humans with the aim of developing a long-acting triple therapy for asthma and COPD.
Clinically Significant Pocket Hematoma Increases Long-Term Risk of Device Infection
Authors: Vidal Essebag, Atul Verma, Jeff S. Healey, Andrew D. Krahn, Eli Kalfon, Benoit Coutu, Felix Ayala-Paredes, Anthony S. Tang, John Sapp, Marcio Sturmer, Arieh Keren, George A. Wells, David H. Birnie, Martin Green, Pablo Nery, Robert Lemery, Michael Gollob, Darryl Davis, Calum Redpath, Lloyd Duchesne, Leslie Carlin, Karen MacDonald, Rosemary Dunne, Rochelle Fleming, Elizabeth Yeltsir, Li Chen, My-Linh Tran, Doug Coyle, Tomy Hadjis, Martin L. Bernier, Alexander Omelchenko, Fiorella Rafti, Johannie Beaudoin, Johanne Bureau, Isabelle Coutu, Emilie Vaillancourt, Jaimie Manlucu, Raymond Yee, Allan Skanes, Lorne Gula, George Klein, Peter Leong-Sit, Lynn Nyman, Cathy Bentley, Denise Hulley, Carlos Morillo, Stuart Connolly, Girish Nair, S. Divakaramenon, S. Ribas, John Eikelboom, Wendy Meyer, Victoria Malcolm, Sandra Carroll, Christopher S. Simpson, Adrian Baranchuk, Hashiar Abdollah, Kevin Michael, Damian Redfearn, Sharlene Hammond, Gwen Ewart, Sharon Fair, Glenda O’Reilly, Paul Novak, Laurence Sterns, Richard Leather, Reg Smith, Chris Lane, Mona Bastell, Debbie Parfett, Andrea Green, Heather Jackson, Magdy Basta, Martin Gardner, Ratika Parkash, Chris Gray, Ann Fearon, Karen Giddens, Lisa Carroll, Teresa Kus, Tomy Hadjis, Guiliano Becker, Ann Langlois, Carole Sirois, Yaariv Khaykin, Zaev Wulffhart, Bernice Tsang, Alfredo Pantano, Kellie Winger, Sherri Patterson, Annette Nath, Colette Seifer, Kevin Wolfe, Ali Khadem, Alex Tischenko, Jan Polson, Jean-Francois Roux, Mariano Badra, Stephanie Cote, Lyne Lavallee, Rene Houde, Eugene Crystal, Ilan Lashevsky, Ching Lau, Avishag Laish-Farkash, Atilio Costa Vitali, Sheldon Singh, Irving Tiong, Fahema Ahmadzai, Mamta Khurana, Meena Lakhanpal, Maria Lukomsky, Mohammed Shurrab, Paolo Costi, Isabelle Greiss, Fadi Mansour, Jean-Marc Raymond, Martine Bergeron, Nancy Roby, Kamran Ahmad, Paul Dorian, Iqwal Mangat, Victoria Korley, Arnold Pinter, Theresa Aves, Zana Mariano, Antonio Estacio, Claus Rinne, Irene Janzen, Donna Lowery, Naomi Kenyon, Kaler Jonson, Satish Toal, Robert Stevenson, Gregory Searles, Geoffrey Douglas, Ricardo Bessoudo, Ansar Hassan, Elizabeth Collings, Corinne Braam, Fabia Fitzgerald, Donna Kent, Luana Mychaluk, Katherine Kavanagh, Derek Exner, John Burgess, John Rothschild, Vikas Kuriachan, Glen Linnell Sumner, Debbie Keller, Brian Yuen, Leslie Jackson-Carter, Sandra Dorey, Tiago L.L. Leiria, Roberto Tofani Sant’Anna, Rafail de March Ronsoni, M.A. Moraes Pereira, Antonieta Moraes, Juliane Rodrigues
Journal: Journal of the American College of Cardiology (2016)
Daily cost of antimicrobial therapy-related costs
Authors: Dominique Vandijck, Stijn Blot, Mieke Depaemelaere, Sandra Oeyen, Kirsten Colpaert, Lieven Annemans, Koenraad Vandewoude, Renaat Peleman, Franky Buyle, Sonia Labeau, Johan Decruyenaere
Journal: Intensive Care Medicine (2007)
FACT-Gastric: A new international measure of QOL in gastric cancer
Authors: S. L. Eremenco, J. Cashy, K. Webster, Y. Ohashi, G. Y. Locker, G. Pelletier, D. Cella
Journal: Journal of Clinical Oncology (2004)

8123 Background: A disease-specific subscale for gastric cancer was developed for the FACIT Measurement System. We developed it concurrently in North America and Asia to ensure its suitability outside of the US. Methods: The FACT-Ga subscale underwent a standard development process: item generation (17 pts and 12 experts), scale construction, initial validation (30 pts) and scale refinement. The item generation phase yielded 65 candidate items, which were reduced to 36 after a rigorous qualitative data review. Next, 13 experts from the US, Canada, and Japan rated the items on relevance and importance. Results led to removal of 10 items rated below an accepted median rating. The 26-item FACT-Ga was translated into Japanese using the FACIT translation methodology, followed by validation in Japan and Canada. Results: The Japanese (n=20) and Canadian (n=10) scale construction participants had mean ages of 57 and 66 years, respectively. All Japanese patients were diagnosed with gastric cancer: 70% were on treatment, and 65% were ECOG 0 or 1. The Canadian sample included 30% diagnosed with cancer of the gastric cardia, 70% with gastric cancer: 10% were on treatment, and 80% were ECOG 0 or 1. Patients completed the FACT-Ga and an Item Rating Survey to evaluate relevance and importance of each item. Interviews were also conducted to elicit feedback on appropriateness of item wording and content. The FACT-Ga performed well in this initial evaluation, with high reliability in both patient groups. Cronbach's alpha for the combined sample was .90 (.87 JPN and .94 ENG). Patients in both groups who had undergone total gastrectomy found it difficult to answer items containing the word “stomach” or related to nausea and vomiting, leading to their eventual removal. Seven items were removed from the scale for redundancy. This resulted in a 19-item questionnaire (Cronbach's alpha=.84 JPN;.93 ENG). Conclusions: The FACT-Ga in English and Japanese shows acceptable initial psychometric characteristics and performs well with patient groups in diverse countries, providing evidence of conceptual equivalence in both languages. It is suitable for use in research studies and clinical trials in English and Japanese. No significant financial relationships to disclose.
Impact of miscoding dose-limiting toxicities in dose-escalation phase I studies.
Authors: A. Iasonos, S. Zohar, J. O'Quigley
Journal: Journal of Clinical Oncology (2010)

e13007 Background: We assess the impact on estimating the maximum tolerated dose (MTD) of miscoding dose-limiting toxicities (DLT) for the “3+3” dose-escalation scheme (SM) and the Continual Reassessment Method (CRM). Methods: Comparisons were carried out through 1,000 simulated trials under six different scenarios by varying the location of the true MTD, testing six dose levels. Both CRM and SM start at the lowest dose, and do not allow skipping dose levels. Two errors are considered: miscoding a DLT as a non-DLT (MT); or miscoding a non-DLT as DLT (MNT).The impact of these errors on accuracy, patient allocation, safety and study duration was evaluated by increasing the probability of occurrence of each error from 0 to 0.3. Results: Under no errors, CRM is up to 35% more accurate than SM in finding the true MTD. This superior accuracy remains in the presence of errors of type MT. A toxicity must be missed (coded as non-toxicity) 30% of the times to allow the SM to experiment at higher doses, and to be closer to CRM's accuracy. With accrual of 3 patients per month, SM takes on average 9.7 months to test six levels under no errors, but under MT errors the trial duration increases 20% without improved accuracy. CRM takes 9.2 months to complete with or without errors since the sample is fixed at 24 patients. SM assigns 10-20% fewer patients at the MTD compared to CRM in the presence or absence of MT errors. As MNT increases from 0 to 0.3, patient allocation at the MTD decreases from 26% to 4%, since CRM lowers experimentation at lower dose levels by de-escalating. For SM, 27% of patients are treated at dose level one (d1) compared to 67% when MNT is 0 and 0.3 respectively, resulting in 38% of trials recommending d1 as the MTD compared to 15% under no errors. Conclusions: SM is less robust to coding errors than the CRM. When, for the first cohort, a non-DLT is flagged incorrectly as a DLT, the SM stops early by not escalating beyond d1.The trial duration, sample size and accuracy are influenced by such errors when using the SM. CRM uses all available data and the dose escalation process is less sensitive to individual patient errors leading to a more accurate MTD, provided that the coding errors occur in ≤2/10 patients. No significant financial relationships to disclose.
Large type I post-ERCP perforation closed immediately through the duodenoscope with through-the-scope endoclips
Authors: Alvaro Martínez-Alcalá García, Felipe Martínez-Alcalá García, Jose Perez Pozo, Jose Ciria Avila, Felipe Martínez Alcalá
Journal: Endoscopy (2016)

Duodenal perforation as complication of endoscopic retrograde cholangiopancreatography (ERCP) is a rare but serious secondary event with an incidence of 0.6 % – 0.99 % [1].
First-line gefitinib versus first-line chemotherapy by carboplatin (CBDCA) plus paclitaxel (TXL) in non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutations: A phase III study (002) by North East Japan Gefitinib Study Group
Authors: K. Kobayashi, A. Inoue, M. Maemondo, S. Sugawara, H. Isobe, S. Oizumi, Y. Saijo, A. Gemma, S. Morita, K. Hagiwara, T. Nukiwa
Journal: Journal of Clinical Oncology (2009)

8016 Background: Based on our promising results of phase II studies estimating gefitinib in NSCLC pts with sensitive EGFR mutations (JCO 2006, BJC 2006), this multicenter phase III trial compared progression free survival (PFS) of first line gefitinib versus first line chemotherapy in EGFR mutation positive pts with stage IIIB/IV NSCLC. Per protocol, an analysis for safety except response, PFS and overall survival were estimated. Methods: PNA-LNA PCR clamp test, which had been developed and validated by us (Cancer Res 2005, Cancer Sci 2007), was employed to detect EGFR mutations using cytological samples or histological samples. Pts having sensitive EGFR mutations, measurable site(s), ECOG PS 0–1, age of 20–75 years, and no prior chemotherapy were randomized (1:1 ratio; balanced for institution, sex, and stage) to receive Arm A: gefitinb (250 mg/ day) orally, or Arms B: CBDCA AUC 6 and TXL 200mg/m2 in 21-day cycles until disease progression. The primary endpoint was PFS, and the sample size was calculated to be 320 in total (alpha=5%, power=80%) to confirm the superiority of Arm A (hazard ratio = 0.69). Results: From April 2006 to July 2008, 155 pts were enrolled (Arm A=80; Arm B=75). Their characteristics were well balanced between arms: median age=65 years; 64% female; 77% Stage IV; 93% adenocarcinoma, 61% non-smoker. There were several differences in toxicities between Arm A and Arm B (grade 4 neutropenia: 1% vs. 29%, grade 3–4 liver dysfunction: 24% vs. 1%, grade 3 neuropathy: 0% vs. 5%, respectively, p&lt;0.01). But these were tolerable in both arms. Furthermore, there were no interstitial lung disease and no toxic deaths in both arms. Analyzing both arms together, preliminary response rate and PFS of the 155 pts were 53.7% and 6.5 mos, respectively. Conclusions: This is the first prospective study to compare first line gefitinib with first line chemotherapy for advanced NSCLC pts harboring EGFR mutations. Due to acceptable toxicities, the independent safety committee decided to continue this study further. At the end of 2008, 200 pts have been entered to this study, and, per protocol, an interim analysis to investigate PFS will be performed in May 2009. No significant financial relationships to disclose.
Attainment of LDL-Cholesterol Treatment Goals in Patients With Familial Hypercholesterolemia
Authors: Leopoldo Perez de Isla, Rodrigo Alonso, Gerald F. Watts, Nelva Mata, Adriana Saltijeral Cerezo, Ovidio Muñiz, Francisco Fuentes, José Luís Diaz-Diaz, Raimundo de Andrés, Daniel Zambón, Patricia Rubio-Marin, Miguel A. Barba-Romero, Pedro Saenz, Juan F. Sanchez Muñoz-Torrero, Ceferino Martinez-Faedo, José P. Miramontes-Gonzalez, Lina Badimón, Pedro Mata, Rocío Aguado, Fátima Almagro, Francisco Arrieta, Miguel Ángel Barba, Ángel Brea, Jose María Cepeda, Raimundo De Andrés, Gonzalo Díaz, José L. Díaz, Francisco Fuentes, Jesús Galiana, Juan Antonio Garrido, Luis Irigoyen, Laura Manjón, Alberto Martin, Mar Piedecausa, Ceferino Martínez-Faedo, Marta Mauri, Pablo Miramontes, Ovidio Muñiz, Francisca Pereyra, Leire Pérez, Xavier Pintó, Pedro Pujante, Enrique Ruiz, Pedro Sáenz, Juan F. Sánchez, Jose I. Vidal, Rosa Argüeso, Daniel Zambón
Journal: Journal of the American College of Cardiology (2016)
Abstract 17748: Impact of Triglyceride-Rich High-Density Lipoprotein Composition on Development of Angiographic Coronary Artery Disease
Authors: Atsushi Nohara, Akihiro Inazu, Tohru Noguchi, Hayato Tada, Mika Mori, Chiaki Nakanishi, Masa-aki Kawashiri, Kunimasa Yagi, Junji Kobayashi, Masakazu Yamagishi, Hiroshi Mabuchi
Journal: Circulation (2010)
Effectiveness of neoadjuvant FOLFOX chemotherapy in Japanese patients with colorectal cancer liver metastases
Authors: H. Baba, T. Beppu, S. Honda, N. Yoshida, H. Komori, N. Hayashi, E. Toyama, K. Horino, N. Miyanari
Journal: Journal of Clinical Oncology (2008)

15097 Background: Patients (Pts) with colorectal cancer (CRC) liver metastases have a poor prognosis and may benefit from perioperative chemotherapy and curative resection. However, neoadjuvant settings of FOLFOX for CRC liver metastases have not yet established in Japan and need to be assessed. Methods: Pts with CRC liver metastasis potentially curable by resection after preoperative chemotherapy were eligible for the single institute, non-randomized phase II trial. Eligible criteria were synchronous or metachronous liver metastases, initially unresectable, organs function preserved, and PS less than 2. Pts received FOLFOX for 6–8 cycles preoperatively. Clinical response, adverse effects, histopathological analysis of tumoral and nontumoral liver, primary lesion and lymph nodes and survival data were assessed. Results: 21 pts were operated after a median of 7.4 cycles of FOLFOX. 2 pts were received additional 3 and 9 cycles of FOLFIRI, and 1 pt had 1 cycles of sLV5FU2, respectively for peripheral neurotoxicity. 21 pts underwent hepatectomy, and 8 pts also had primary tumor resection. There was no severe perioperative complication, and intra-operative increased bleeding. Clinical and histopathological response rate were 66.7% and 27.8%, respectively. Complete tumor necrosis of liver metastases was observed in 2 pts (11.1%) and of primary tumor was in 1 pt. Lesional lymph nodal metastases were observed in 4 nodes from 2 pts over 83 dissected nodes (4.8%) totally from all 8 synchronous cases. Two year disease free and over all survival was 50% and 89%, respectively. Conclusions: These data suggest that FOLFOX can be safely administered for Japanese as an neoadjuvant setting in CRC liver metastases without increasing perioperative complications. Moreover, high response, respectability, and superior survival data were obtained with this preoperative chemotherapy and hepatectomy, suggesting that a future nationwide clinical trial can be warranted. No significant financial relationships to disclose.
Classic Teachings in Clinical Cardiology: a Tribute to W Proctor Harvey, by Ed Michael A Chizner
Authors: J F Goodwin
Journal: BMJ (1997)

Ed Michael A Chizner: Laennec Publishing, $145, pp 1526 ISBN 1 886128 06 5

This two volume work is in praise of Dr Proctor Harvey's lifelong dedication to clinical examination and assessment of physical signs of the cardiovascular system in health and disease. Proctor Harvey was not merely a brilliant teacher but also an inventor, and he introduced many teaching machines to reproduce cardiac pulsations and sounds and murmurs. This tribute to a great physician and cardiologist is welcome at a time when complex investigations with sophisticated diagnostic techniques tend to thrust aside the support of …
Soundings: Let the patients decide
Authors: Colin Douglas
Journal: BMJ (2005)

“And this pain... How would you rate it on a scale of one to 10?” The patient flinches at the memory and rolls her eyes. “Eleven... And I've had two children...”

Her interrogator looks puzzled. Perhaps she is gathering her thoughts for her next question. Eventually it emerges. “And where did you say the pain started?”

“Here.” She clutches her right loin. “And where did you say it went to again?” “My groin. My right groin.” She even points. The questioner nods, perhaps on to something at last. “And have you ever had any trouble with your gall bladder before?”

We watch them, the helpful and the possibly unhelpable, for five more minutes. It gets worse, then a little better. The patient leaves and we interrogate the interrogator. Perhaps less anxious now, she begins to redeem herself and by the 20 minute mark has clawed her way—just—on to the lowest slopes of a generously defined pass grade.

She leaves and her “patient”—in fact a surrogate patient with a clinical and teaching background—returns, shaking her head and laughing. It would be impolite not to join in, so we do. And why weep? Our medical school is doing its best, and its last five potential outputs this morning have all been fine. What does she think of its latest offering? “Poor lass... But a bit less awful towards the end.”

It is much the same in the short cases. A nice man I have known for years has interesting hands and knows the routines inside out. The students come and go. After some he nods, after others he looks doubtful, and one in particular evokes a frown a hanging judge might deem excessive.

Eight hours of it, and we are released: from the ritual, the stuffy rooms, the timing bells, the awful coffee, the grim treadmill of examining, to brilliant late afternoon sunshine.

In the hospital grounds I meet a colleague, cheerful and casually dressed, whom I would have expected to be examining with us. “I never examine,” he explains. I am puzzled. He is quite firm. “It's boring and repetitive, so I'm no good at it. And it's quite easy to give up. You just say no.”

He has a point. But surely someone has to judge our students as potential doctors. And an idea has just occurred to me...
<scp>GARP</scp> inhibits allergic airway inflammation in a humanized mouse model
Authors: H. Meyer‐Martin, S. A. Hahn, H. Beckert, C. Belz, A. Heinz, H. Jonuleit, C. Becker, C. Taube, S. Korn, R. Buhl, S. Reuter, A. Tuettenberg
Journal: Allergy (2016)

Abstract Background Regulatory T cells (Treg) represent a promising target for novel treatment strategies in patients with inflammatory/allergic diseases. A soluble derivate of the Treg surface molecule glycoprotein A repetitions predominant ( sGARP ) has strong anti‐inflammatory and regulatory effects on human cells in vitro as well as in vivo through de novo induction of peripheral Treg. The aim of this study was to investigate the immunomodulatory function of sGARP and its possible role as a new therapeutic option in allergic diseases using a humanized mouse model. Methods To analyze the therapeutic effects of sGARP , adult NOD / Scid γc −/− ( NSG ) mice received peripheral blood mononuclear cells ( PBMC ) derived from allergic patients with sensitization against birch allergen. Subsequently, allergic inflammation was induced in the presence of Treg alone or in combination with sGARP . Results In comparison with mice that received Treg alone, additional treatment with sGARP reduced airway hyperresponsiveness ( AHR ), influx of neutrophils and macrophages into the bronchoalveolar lavage ( BAL ), and human CD 45 + cells in the lungs. Furthermore, the numbers of mucus‐producing goblet cells and inflammatory cell infiltrates were reduced. To elucidate whether the mechanism of action of sGARP involves the TGF ‐β receptor pathway, mice additionally received anti‐ TGF ‐β receptor II ( TGF ‐β RII ) antibodies. Blocking the signaling of TGF ‐β through TGF ‐β RII abrogated the anti‐inflammatory effects of sGARP , confirming its essential role in inhibiting the allergic inflammation. Conclusion Induction of peripheral tolerance via sGARP is a promising potential approach to treat allergic airway diseases.