tbuckley/cabot-search huggingface dataset:
A randomized trial of postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus neoadjuvant chemotherapy for clinical stage II/III squamous cell carcinoma of the thoracic esophagus (JCOG 9907)
Authors: H. Igaki, H. Kato, N. Ando, M. Shinoda, H. Shimizu, T. Nakamura, S. Ozawa, H. Yabusaki, N. Aoyama, A. Kurita, H. Fukuda
Journal: Journal of Clinical Oncology (2008)

4510 Background: The phase III trial (JCOG9204) comparing postoperative adjuvant chemotherapy using cisplatin plus 5- fluorouracil (5-FU) with surgery alone showed superior disease-free survival in postoperative chemotherapy for patients (pts) with esophageal squamous cell carcinoma (ESCC) (Ando N, et al, J Clin Oncol 2003). This phase III trial was conducted to determine the optimal timing for giving chemotherapy. Methods: Pts with c-stage II, III (excluding T4) ESCC were randomized. In arm A, two courses of chemotherapy with cisplatin (80 mg/m2, div day1) plus 5-FU (800 mg/m2, ci day1–5) were given following surgery of transthoracic esophagectomy with lymphadenectomy. In arm B, two courses of chemotherapy same as arm A were given before surgery. Minimization method was used to balance nodal status (cN0/cN1) and institution. Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), % complete resection, adverse events and surgical complications. Sample size was 330 pts to detect about 13% improvement in 5y-PFS with one-sided alpha 0.05 and power 0.80. Results: Between May 2000 and May 2006, 330 pts (A/B; 166/164, cN0/N1; 114/216) from 24 institutions were randomized. Median age was 61/61 years. No remarkable difference was seen in toxicity and complications between the arms. One treatment-related death was seen in each arm. The planned second interim analysis after completion of accrual was carried out in Mar 2007. Hazard ratio (HR) of PFS was 0.76 (favor in arm B, one-sided stratified logrank p = 0.044) which did not meet the prespecified stopping criteria (p < 0.0254; O’Brien & Fleming alpha spending function), however, arm B was highly superior in overall survival (OS) (HR 0.64, 95%CI: 0.45–0.91, two-sided p = 0.014). Data and Safety Monitoring Committee recommended the early publication. In updated analyses in Aug 2007, median PFS was 2.0 y in arm A, and 2.9 y in arm B, median OS was 2.9 y in arm A and was not reached in arm B. Conclusions: Preoperative chemotherapy with cisplatin plus 5-FU followed by surgery can be regarded as a new standard treatment for stage II/III ESCC. No significant financial relationships to disclose.
Emotional Distress in Doctors: Sources, Effects and Help Sought
Authors: M B King, A Cockcroft, C Gooch
Journal: Journal of the Royal Society of Medicine (1992)

All doctors in a London Teaching Hospital were sent a self-administered, anonymous questionnaire, to study past episodes of emotional distress. We inquired about frequency of past and current emotional distress, sources of distress, effects on work and home life, type of help sought and perceived outcome of that help. Of 320 doctors, 210 (66%) responded. One hundred and forty-one (68%) reported previous episodes of moderate or severe emotional distress. Logistic regression revealed that distress was significantly more common in younger doctors and in women. Many respondents reported work problems as causing their distress and work was frequently adversely affected by episodes of distress. Professional help was rarely sought; non-professional help was from family and friends. Current emotional distress was related to a history of past distress, especially among the most junior doctors. We conclude that past emotional distress is reported by most doctors, with work pressures an important contributing factor. Doctors do not appear to use available sources of professional help. Our findings confirm that doctors have difficulty disclosing psychological problems. Specific programmes aimed at prevention and management of distress in doctors need to be initiated and evaluated.
A puzzling airway problem
Authors: R. C. Costello, C. R. Whittet, S. T. Browning
Journal: BMJ (2015)

A fit and well 11 month old girl who was living with her single mother and 3 year old brother presented to the emergency department with acute shortness of breath and cough. Her mother had not witnessed any episodes of foreign body inhalation. A diagnosis of bronchiolitis was made and the child was discharged after oxygen therapy and observation. One week later she presented with the same symptoms and signs. Chest radiography was performed and was reported as normal. Again she was diagnosed and treated for bronchiolitis and made a complete recovery. Six weeks after the initial presentation she re-presented with a two day history of increasing shortness of breath, cough, and stridor. Signs of respiratory distress were noted, and chest auscultation identified bilateral wheeze and transmitted upper airway noises. Her symptoms improved with salbutamol and adrenaline nebulisers, but an apparent stridor remained. A repeat chest radiograph during this time was also normal. She was admitted and treated with nebulisers, oxygen, and steroids. Her symptoms improved but did not resolve completely. An ear, nose, and throat nasoendoscopic examination showed a normal epiglottis, but no clear laryngeal views were obtained. Again the mother denied any witnessed aspiration of a foreign body but reported that her two children sometimes played together unsupervised.
Phase I/II safety and pharmacokinetic (PK) study of ARN-509 in patients with metastatic castration-resistant prostate cancer (mCRPC): Phase I results of a Prostate Cancer Clinical Trials Consortium study.
Authors: Dana E. Rathkopf, Daniel Costin Danila, Michael J. Morris, Susan F. Slovin, Jill Elise Steinbrecher, Gabrielle Arauz, Peter J. Rix, Edna Chow Maneval, Isan Chen, Josef J. Fox, Martin Fleisher, Steven M. Larson, Howard I. Scher
Journal: Journal of Clinical Oncology (2012)

43 Background: In CRPC, androgen receptor (AR) overexpression is associated with resistance to first-generation anti-androgen therapy such as bicalutamide. ARN-509 is a novel small molecule AR antagonist that impairs AR nuclear translocation and binding to DNA, inhibiting tumor growth and promoting apoptosis, with no partial agonist activity. Preclinical data shows that ARN-509 binds AR with 5-fold greater affinity than bicalutamide, and induces tumor regression in hormone-sensitive and CRPC xenograft models. Methods: In this open-label, Phase 1/2 study, mCRPC patients received ARN-509 orally on a continuous daily dosing schedule. In Phase 1 , 7 doses (30, 60, 90, 120, 180, 240, 300 mg) were tested using standard 3x3 dose escalation criteria to assess safety, PK, and determine the recommended Phase 2 dose (RP2D). Preliminary anti-tumor activity was assessed by PSA kinetics, radiographic responses, circulating tumor cells (CTCs), and FDHT-PET imaging. Results: Twenty-four patients (median age 68 yrs, Gleason Score 8; prior docetaxel 13%) were enrolled. The most common Grade 1-2 treatment-related adverse events were fatigue (38%), nausea (29%), and pain (24%). There was only 1 treatment-related Grade 3 adverse event (abdominal pain) at 300 mg, possibly related to a higher pill burden, which led to an additional 3 patients being enrolled at the highest dose with no further dose limiting toxicities. PK was shown to be linear and dose-dependent. Twelve patients (55%) had ≥ 50% PSA declines. To date, 7 patients have discontinued the study due to progression, with the longest patient still on study for more than 1 year. FDHT-PET imaging demonstrated AR blockade at 4 weeks across multiple dose levels. Based on preclinical assessment of maximum efficacious dose, PK, and promising activity across all doses, 240 mg was selected as the RP2D. Conclusions: In this Phase 1 study, ARN-509 was shown to be safe and well tolerated, with promising preliminary activity based on PSA and pharmacodynamic evidence of AR antagonism. The Phase 2 portion of the study will enroll up to 90 patients with treatment-naïve non-metastatic and mCRPC.
Seven day GP access scheme in Yorkshire is abandoned owing to lack of demand
Authors: G. Iacobucci
Journal: BMJ (2015)

A pilot scheme designed to test the government’s plans for seven day access to routine general practice services is to be discontinued because of a lack of demand from patients.

NHS Hambleton, Richmondshire and Whitby Clinical Commissioning Group in North Yorkshire has decided not to continue its seven day opening scheme beyond 30 June, after an evaluation found little appetite among patients to attend weekend clinics. Commissioners decided that patients would be better served if resources were directed to other areas, such as …
Abstract 17304: Web-Based 12-Week Activity Intervention (American Heart Association Choose to Move Program) Improved Compliance with Guideline Recommendations
Authors: Sarah B Lieber, Rita F Redberg, Roger S Blumenthal, Anu Gandhi, Karen J Robb, Samia Mora
Journal: Circulation (2010)

Background: Increased activity is associated with reduction of cardiac risk factors and prevention of cardiac disease. We evaluated results of the American Heart Association (AHA) web-based Choose ...
Abstract 3819: Clinical potential of the Eph/ephrin profile in breast cancer
Authors: Gizeh Perez-Tenorio, Anna-Maria Husa, Olle Stål
Journal: Cancer Research (2014)

Abstract The Eph receptors belong to a large family of receptors tyrosine kinase. The Ephs and their ligands ephrins are aberrantly expressed in cancer. However, due their complex signaling and promiscuous interactions, a wide screening of the entire family will be important to determine their clinical value. Purpose: The Eph receptor tyrosine kinase family has been implicated in breast cancer but their role in tumor progression remains elusive. Therefore we aimed to profile the Eph receptors and their ligands ephrins in breast cancer samples to define them as potential clinical markers or therapeutic targets. Experimental design: Gene expression of Eph/ephrins was quantified by RT-PCR using a TaqMan® Micro Fluidics Cards Microarray custom designed for 21 Eph/ephrin family members: EphA1-A8, EphB1-B4 and EphB6, ephrinA1-A5, ephrinB1-B3 and 2 endogenous controls: GAPDH and HPRT1 in 70 breast cancer tumors. Results: We found that high expression of EphBs, and particularly EphB2, was associated to worse outcome among postmenopausal patients with lymph node infiltration. Additionally high EphB2 expression correlated with HER2 positive status. Conclusions: Our results suggest that the EphB receptor family may have prognostic value for postmenopausal breast cancer patients with lymph nodal infiltration. We will continue this study in a larger patient material in order to better evaluate the therapeutic impact of this family. Citation Format: Gizeh Perez-Tenorio, Anna-Maria Husa, Olle Stål. Clinical potential of the Eph/ephrin profile in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3819. doi:10.1158/1538-7445.AM2014-3819
Abstract 10050: Chronic Utilization of Medications with Metabolic Effects and Risk for Incident Diabetes in Postmenopausal Women
Authors: Rhonda M Cooper-DeHoff, Cyndi Garvan, J A Delaney, Almut G Winterstein, Anthony Bavry, Barbara V Howard, Chu Chen, Joanne Manson, Larry S Phillips, Simin Liu, Yiqing Song, Ronald I Shorr, Marian Limacher
Journal: Circulation (2012)

BACKGROUND Studies suggest thiazide diuretics (TD), statins (ST), β blockers (BB), and antidepressants (AD) can impair glucose homeostasis and increase risk for diabetes. Data are needed on the pre...
GAO: The Way Medicare Pays Certain Hospitals Could Lead to Overspending
Authors: Rita Rubin
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Combined effect of bevacizumab with erlotinib and irradiation in head and neck cancer. A preclinical study on an orthotopic model
Authors: Alexandre Bozec, Anne Sudaka, Patricia Formento, jean-louis fischel, Marie-Christine Etienne-Grimaldi, Gerard Milano
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4109 

Clinical benefit has been demonstrated in patients with head and neck tumors receiving an anti-epidermal growth factor receptor (EGFR) agent in combination with radiotherapy. Recent preclinical and clinical studies suggest beneficial effects from combining antiangiogenic drugs with radiotherapy.

To investigate the effect of combining these approaches, we evaluated in vivo the anti-tumor efficacy of the anti-angiogenic compound bevacizumab, a highly specific monoclonal antibody directed against the vascular endothelial growth factor (VEGF), erlotinib, an EGFR tyrosine kinase inhibitor, and irradiation given alone and in combination. Investigations were performed using a VEGF-secreting human head and neck tumor cell line, CAL33, with a high EGFR content, injected as orthotopic xenografts into the mouth floor of nude mice. Three days after tumor cell injection, bevacizumab (5 mg/kg 5 days /week, i.p.), erlotinib (100 mg/kg 5 days/week, orally) and irradiation ([Rt] 6 Gy, 3 days/week), were administered alone and in combination for 10 days (ten animals per treatment group). At that time, animals were sacrificed and weighed tumor dimensions and weights were measured and bilateral node chain dissection performed. Tumor mass, number of inflammatory nodes either invaded or not, and tumor cell proliferation (Ki67 with immunohistochemistry) were examined and the results were compared between the different treatment groups using the Mann and Whitney non parametric statistic test. The interactions between combined treatments were measured by calculating the combination ratio (CR); CR = FTv A x FTv B / FTv (A+B), where FTvx is the fractional tumor volume for the agent x.

As compared with the control, concomitant administration of drugs produced a marked and significant synergistic (p< 0.05 , CR = 2) decrease in tumor mass ; the addition of irradiation almost completely abolished tumor growth (p< 0.001, CR = 2.3). The drug association significantly reduced the number of invaded nodes (p = 0.03) and the triple combination significantly reduced the total node number as compared with controls (p = 0.001). The Rt-induced proliferation, reflected by Ki67 labeling (p<0.01),was reduced to control level with the triple combination (p< 0.001). The efficacy of such new combination of bevacizumab-erlotinib and Rt may be of clinical importance in the management of head and neck cancer .
Effect of exemestane on bone: A randomized placebo controlled study in postmenopausal women with early breast cancer at low risk
Authors: P. E. Lonning, J. Geisler, L. E. Krag, L. Ottestad, Y. Bremnes, A. I. Hagen, E. Schlichting, A. Polli, J. Paolini, G. Massimini
Journal: Journal of Clinical Oncology (2004)

518 Background: Studies with non-steroidal aromatase inhibitors indicated an increased bone loss risk in postmenopausal early breast cancer (EBC) patients (pts). Exemestane (E, Aromasin), a steroidal aromatase inactivator, might have no bone detrimental effect due to its 17-hydro-metabolite. Methods: We conducted a randomized, double-blind study evaluating the effect of E or placebo (P) on bone metabolism, endocrinological and metabolic parameters in postmenopausal pts with pT1N0 or T2N0 and no other risk factors or ductal carcinoma in situ (DCIS), with bone mineral density (BMD) within 2 standard deviations of the mean level for women of 65 years (yrs). Pts were randomized to receive either E 25 mg or P p.o. daily for 2 yrs, with a 1-yr follow-up. Primary objective was to demonstrate non-inferiority on BMD, determined at 6, 12 and 24 months on treatment. Planned sample size was 128 evaluable pts, assuming a yearly BMD loss of 1% on P and 2.1% on E. Results: 147 pts have been enrolled, 73 E and 74 P. Median age: 61 yrs (E) and 60 yrs (P). Performance status (PS) 0: 51 on E, 53 on P; PS 1: 22 on E, 21 on P. Median time from menopause: 9.7 yrs E and 8.0 yrs P. ER and/or PgR: +ve 130 pts, unknown 17 (15 of them DCIS). E was well tolerated, 70% of pts had drug-related events on E and 73% on P. Twelve pts withdrew for adverse events, 9 on E and 3 on P; 5 withdrew consent, 3 on E and 2 on P. Six pts relapsed, 1 on E and 5 on P. Results on BMD evaluable pts, 62 on E and 66 on P, are in Table. Baseline (BS) osteoporosis (BMD ≤ 2.5 SD of the young adult mean) of the spine was detected in 7 pts on E and 5 pts on P, of the femoral neck in 17 pts on E and 5 on P. No normal BMD pt became osteoporotic, 6 pts on E and 5 on P with osteopenia at BS became osteoporotic on L1-L4 and 3 on E and 5 on P on femoral neck. Nine pts had fractures, 4 on E and 5 on P. Conclusions: There is no E effect on spine, and a small effect on the femoral neck. Bone loss was higher than expected in the P arm. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Italia S.p.A. Pfizer Co. Pfizer Co.
Glycolysis controls the induction of human regulatory T cells by modulating the expression of FOXP3 exon 2 splicing variants
Authors: Veronica De Rosa, Mario Galgani, Antonio Porcellini, Alessandra Colamatteo, Marianna Santopaolo, Candida Zuchegna, Antonella Romano, Salvatore De Simone, Claudio Procaccini, Claudia La Rocca, Pietro Biagio Carrieri, Giorgia Teresa Maniscalco, Marco Salvetti, Maria Chiara Buscarinu, Adriana Franzese, Enza Mozzillo, Antonio La Cava, Giuseppe Matarese
Journal: Nature Immunology (2015)
The influence of angiotensin-converting enzyme (ACE) genotype on the development of severe perinatal asphyxia in the neonates
Authors: Natalia Gorovenko, Svetlana Kyryachenko, Zoya Rossokha
Journal: European Respiratory Journal (2011)

Background:  The cardiovascular disturbances are the important pathways in the development of perinatal asphyxia. Study of genetic markers associated with the development of severe asphyxia in newborns is of great practical importance to develop preventive measures and child health in the future. The aim of this study was to evaluate the influence of the (I/D) gene polymorphism on the development of severe perinatal asphyxia.   Methods:  We conducted a case-control study of 80 cases of severe perinatal asphyxia and 110 control group. For the genotyping was used polymerase chain reaction (PCR) with further restriction fragments length polymorphism analyses. The differences in comparative groups were assessed by the Pearson chi-square test analyses and Odds Ratio determination.   Results:  The incidence of the homozygous DD alleles in the neonates with severe perinatal asphyxia was 33 (41,25%), of the heterozygous ID alleles 37 (46,25%), of the homozygous II alleles 10 (12,50%). The neonates of control group had following alleles: DD - 15 (13,64%), ID- 44 (40,00%), II -51 (46,36%).   Conclusion:  DD gene polymorphism of the neonates is a risk factor for the development of perinatal asphyxia. We suggest using these genetic markers in prognosis of severe perinatal asphyxia in the neonates.
Care-continuity for COPD patients
Authors: Maggie Lit Pik Kee, Kuen Han Lee, Amy Tsoi Lai Fong, Man Po Lee, O. Wing Hing, Johnny Chan Wai Man
Journal: European Respiratory Journal (2012)

ntroduction   A multi-disciplinary integrated COPD programme has commenced since 2011 to reduce unplanned readmission and provide post-discharge care. Respiratory-nurse acts as a case-manager for disease management and provision of continuitycare in nurse-led COPD clinic.   Objectives   A prospective study is conducted from January to December 2011 aimed to review the subsequent outcomes in the programme.   Methodology   COPD Clinical Pathway is being adopted for in-patient recruitment including suspected patients with clinical features of COPD. We stressed on inhaler and spacer technique, appropriateness of the inhaler9s prescription, and early diagnosis detection before discharge.  Proper referral will be coordinated for early rehabilitation, home-visit care and advanced specialty care. All recruited cases were scheduled for nurse-clinic visit and subsequent follow-up. The wide range of advanced specialized nursing care are including symptoms assessment, spirometry monitoring, self care plan education, optimizing inhaler9s using skill and making referral.   Results   355 in-patients, predominantly male (87.6%), had been recruited and 26.5% are referred to nurse clinic. 20.8% are chronic smokers and over 70% has successfully quitted smoking. However 80% were knowledge deficit regarding COPD. 87.3% demonstrated failed inhalers and spacer technique but a significant improvement is found after continuous education. 53.8% vs. 28.8% (p=0.001). Overall, 92.3% express satisfaction and will continue follow-up in the clinic.   Conclusion   Respiratory nursing care plays a vital role in optimizing therapy and self-home plans management. The long term effectiveness and particularly unplanned readmission rates needs to be evaluated in prospective controlled trials.
The use of bispectral index (BIS) as a marker of sleep staging
Authors: Cristina Estirado, Nuria Grau, Encarna Guardiola, Miquel A. Felez, Carles Sanjuás, Lluis Gallart, Fernando Escolano, Mauricio Orozco Levi
Journal: European Respiratory Journal (2012)

Background:   The bispectral index (BIS) is a parameter which reflects brain electrical activity (EEG) in a range of values between 0 au (minimum value, no EEG) and 100 au .  Aim:  We further assessed whether BIS can be useful for identifying sleep and the difference between its stages.   Methods:   The study was conducted in 14 patients being investigated for sleep apnea/hypopnea syndrome (OSA) .  A full polysomnography through a night9s sleep was recorded and analyzed manually according to standard criteria for sleep staging. Throughout the process, from initial waking up to awakening, a continuous record of the BIS time-synchronized with the manual analysis of the PSG was performed. The average BIS value every minute was used as the dependent variable in the analysis.   Results:   Thirteen patients were diagnosed from OSA, with an apnea/hipoapnea index (AHI) of 53.6 ± 26.1. We analyzed a total of 5.579 minutes with synchronized measurements of BIS and PSG data. Overall, 91% of all EEG records corresponded to sleep period, representing 5.4% of stage 1, 68.9% of stage 2, 15.7% of stage 3-4 and 9.9% REM sleep. The mean BIS value was 88.9 ± 9.5 (mean ± SD) in wakeful state, 84.9 ± 12.4 in stage 1, 77.7 ± 11.4 in stage 2, 56.1 ± 13.4 in stages 3-4 and 76.8 ± 17.7 in REM sleep. Significant differences were observed between wakefulness and sleep in any stage (p  ( 3-4 ) .   Conclusions:   BIS values decrease during sleep and change according to its stages. BIS values below 70 have a high sensitivity and specificity for detecting deep sleep stages.