tbuckley/cabot-search huggingface dataset:
The Surgeon's Role in the Quality of Oncologic Care
Authors: Clifford Ko, Janak Parikh, Irina Yermilov, James Tomlinson
Journal: Journal of the National Comprehensive Cancer Network (2007)

The Surgeon's Role in the Quality of Oncologic CareQuality should be the right treatment for the right patient at the right time.In response to widely varying patient outcomes, national cancer organizations are emphasizing improvement in the quality of cancer care.The National Quality Forum, National Comprehensive Cancer Network, American Society of Clinical Oncology, and American College of Surgeons' Commission on Cancer, for example, have all defined quality measures and performed pilot projects to show how to measure and improve quality.Additionally, recent pay-for-performance initiatives have brought even more attention to quality improvement.Because cancer care is complex and multidisciplinary, surgeons must play an integral role in quality improvement.Providing good quality surgical care is essential and involves several considerations.This commentary discusses 6 of them. Recognize the populationPeople older than 65 years comprise the fastest growing population in the United States.The U.S. Census Bureau estimates that they will represent 13% of the population by 2010 and more than 50% by 2020.In 1999, they accounted for 40% of hospital discharges and 48% of inpatient care days. 1 Because the risk for most cancers increases with age, this group represents a large cohort of patients who will need oncologic care.Moreover, this group of patients has unique issues, such as the need for evaluating their decision-making capacity, drafting of a living will or durable power of attorney, evaluation of functional status, need for assistance with activities of daily living (ADLs) postoperatively, and the management of polypharmacy.These issues, along with complex comorbidities, underscore the need for a multidisciplinary team approach to cancer care in the elderly.
Radiology guidelines could be improved
Authors: M Dudley
Journal: BMJ (1995)

EDITOR,--Radiologist's suggestions to help reduce unnecessary x ray examinations in patients prescribing to accident and emergency departments have been welcome. Eugene McNally and colleagues suggest that this reduction can be sustained by the use of posters.1 I am concerned, however, about the content of the two examples of their posters shown in their paper.

The poster illustrating the guidelines for x ray examination of the skull states, “Do not x-ray patients who are to be admitted.” A linear fracture is important …
A study of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic tumors.
Authors: Roy S. Herbst, Michael S. Gordon, Gregg Daniel Fine, Jeffrey Alan Sosman, Jean-Charles Soria, Omid Hamid, John D. Powderly, Howard A. Burris, Ahmad Mokatrin, Marcin Kowanetz, Maya Leabman, Maria Anderson, Daniel S. Chen, F. Stephen Hodi
Journal: Journal of Clinical Oncology (2013)

3000 Background: Tumor PD-L1 mediates cancer immune evasion. Therefore, inhibition of PD-L1 binding represents an attractive strategy to restore tumor-specific T-cell immunity.MPDL3280A, a human monoclonal antibody containing an engineered Fc-domain designed to optimize efficacy and safety, targets PD-L1, blocking PD-L1 from binding its receptors, including PD-1 and B7.1. Methods: A study was conducted with MPDL3280A administered IV q3w in pts with locally advanced or metastatic solid tumors, including 3+3 dose-escalation and expansion cohorts. ORR was assessed by RECIST v1.1 and includes u/cCR and u/cPR. Results: As of Jan 10, 2013, 171 pts were evaluable for safety. Administered doses include ≤1 (n=9), 3 (n=3), 10 (n=35), 15 (n=57) and 20 mg/kg (n=67). Pts in the dose-escalation cohorts did not experience DLTs. No MTD was identified. Pts had received MPDL3280A for a median duration of 127 days (range 1-330). 39% of pts reported G3/4 AEs, regardless of attribution. AEs of special interest included hepatitis, rash and colitis. No G3-5 pneumonitis was observed. MPDL3280A PK was linear at doses ≥1 mg/kg. 122 pts enrolled prior to Jul 1, 2012 were evaluable for efficacy. RECIST responses were observed in multiple tumor types including NSCLC, RCC, melanoma, CRC and gastric cancer. An ORR of 21% (25/122) was observed in nonselected solid tumors, including several pts who demonstrated tumor shrinkage within days of initiating treatment. Additional pts had delayed responses after apparent radiographic progression (not included in the ORR). Some responders demonstrated prolonged SD prior to RECIST responses. The 24-week PFS was 44%. Pts with PD-L1–positive tumors (from archival samples) showed an ORR of 39% (13/33) and a PD rate of 12% (4/33). In contrast, patients with PD-L1–negative tumors showed an ORR of 13% (8/61) and a PD rate of 59% (36/61). As of the cutoff date, all responses are ongoing or improving. Updated data will be presented. Conclusions: MPDL3280A was well tolerated, with no pneumonitis-related deaths. Durable responses were observed in a variety of tumors. PD-L1 tumor status appears to correlate with responses to MPDL3280A. PK supports q3w dosing at 15 mg/kg or fixed-dose equivalent. Clinical trial information: NCT01375842.
Dose-intensive chemotherapy in refractory germ cell cancer--a phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation.
Authors: C R Nichols, G Tricot, S D Williams, K van Besien, P J Loehrer, B J Roth, L Akard, R Hoffman, R Goulet, S N Wolff
Journal: Journal of Clinical Oncology (1989)

Between September 1986 and March 1988, 33 patients with refractory germ cell cancer were entered on a phase I/II trial of two courses of high-dose carboplatin plus etoposide with autologous bone marrow support. All patients had extensive prior treatment and had either cisplatin-refractory disease (67%) defined as progression within 4 weeks of the last cisplatin dose or failed at least two cisplatin-based regimens (35%) including a cisplatin-ifosfamide salvage regimen. Patients received a fixed total dose of etoposide of 1,200 mg/m2 with each cycle. The carboplatin dose ranged from 900 mg/m2 to 2,000 mg/m2. Twenty of the 33 patients received the second cycle of therapy. Despite extensive prior therapy with cisplatin, neurotoxicity, nephrotoxicity, or hearing impairment with high-dose carboplatin and etoposide was unusual. The most common nonhematologic toxicity was moderate enterocolitis. The hematologic toxicity of this regimen was substantial at each dose level. All 53 courses were accompanied by granulocytopenic fevers. Seven of the 33 patients (21%) died from treatment. All of these deaths occurred during the granulocyte nadir, and five were related to documented sepsis. Overall, 14 of 32 patients (44%) evaluable for response obtained an objective response, including eight complete remissions. Four patients remain in complete remission, with three patients being continuously free of disease in excess of 1 year. Eight responders (including four complete remissions) had progressed while receiving cisplatin. We conclude that carboplatin and etoposide can be administered in combination at high dosages and this regimen may have curative potential for patients with germ cell tumors resistant to conventional-dose cisplatin-based therapies.
Phase I and Pharmacokinetic Study of Oral Paclitaxel
Authors: Mirte M. Malingré, Jetske M. Meerum Terwogt, Jos H. Beijnen, Hilde Rosing, Franciska J. Koopman, Olaf van Tellingen, Ken Duchin, Wim W. Ten Bokkel Huinink, Martha Swart, Jan Lieverst, Jan H. M. Schellens
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To investigate dose escalation of oral paclitaxel in combination with dose increment and scheduling of cyclosporine (CsA) to improve the systemic exposure to paclitaxel and to explore the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT). PATIENTS AND METHODS: A total of 53 patients received, on one occasion, oral paclitaxel in combination with CsA, coadministered to enhance the absorption of paclitaxel, and, on another occasion, intravenous paclitaxel at a dose of 175 mg/m 2 as a 3-hour infusion. RESULTS: The main toxicities observed after oral intake of paclitaxel were acute nausea and vomiting, which reached DLT at the dose level of 360 mg/m 2 . Dose escalation of oral paclitaxel from 60 to 300 mg/m 2 resulted in significant but less than proportional increases in the plasma area under the concentration-time curve (AUC) of paclitaxel. The mean AUC values ± SD after 60, 180, and 300 mg/m 2 of oral paclitaxel were 1.65 ± 0.93, 3.33 ± 2.39, and 3.46 ± 1.37 μmol/L·h, respectively. Dose increment and scheduling of CsA did not result in a further increase in the AUC of paclitaxel. The AUC of intravenous paclitaxel was 15.39 ± 3.26 μmol/L·h. CONCLUSION: The MTD of oral paclitaxel was 300 mg/m 2 . However, because the pharmacokinetic data of oral paclitaxel, in particular at the highest doses applied, revealed nonlinear pharmacokinetics with only a moderate further increase of the AUC with doses up to 300 mg/m 2 , the oral paclitaxel dose of 180 mg/m 2 in combination with 15 mg/kg oral CsA is considered most appropriate for further investigation. The safety of the oral combination at this dose level was good.
19 COST-EFFECTIVENESS OF NON-INVASIVE METHODS FOR THE DIAGNOSIS OF LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS B IN THE UK
Authors: C. Crossan, L. Longworth, M. Tsochatzis, K. Gurusamy, B. Davidson, A. Burroughs, M. Rodriguez-Peralvarez, K. Mantzoukis, J. O'Brien, E. Thalassinos, V. Papastergiou
Journal: Journal of Hepatology (2013)
Novel Tumor-Targeted, Engineered IL-2 Variant (IL2v)-Based Immunocytokines For Immunotherapy Of Cancer
Authors: Christian Klein, Inja Waldhauer, Valeria Nicolini, Claire Dunn, Anne Freimoser-Grundschober, Gerrits Danny, Otto Boerman, Tapan Nayak, Sylvia Herter, Erwin Van Puijenbroek, Oliver Ast, Thomas Hofer, Ralf Hosse, Sabine Lang, Sebastian Neumann, Hubert Kettenberger, Markus Neubauer, Ingo Gorr, Dietrich Tuerck, Stefan Evers, Christian Gerdes, Victor Levitsky, Marina Bacac, Ekkehard Moessner, Pablo Umana
Journal: Blood (2013)
Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results
Authors: Michael L. Wang, Kristie A. Blum, Peter Martin, Andre Goy, Rebecca Auer, Brad S. Kahl, Wojciech Jurczak, Ranjana H. Advani, Jorge E. Romaguera, Michael E. Williams, Jacqueline C. Barrientos, Ewa Chmielowska, John Radford, Stephan Stilgenbauer, Martin Dreyling, Wieslaw Wiktor Jedrzejczak, Peter Johnson, Stephen E. Spurgeon, Liang Zhang, Linda Baher, Mei Cheng, Dana Lee, Darrin M. Beaupre, Simon Rule
Journal: Blood (2015)
Phase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients.
Authors: N Ellison, C L Loprinzi, J Kugler, A K Hatfield, A Miser, J A Sloan, D B Wender, K M Rowland, R Molina, T L Cascino, A M Vukov, H S Dhaliwal, C Ghosh
Journal: Journal of Clinical Oncology (1997)

PURPOSE A minority of cancer survivors develops long-term postsurgical neuropathic pain. Based on evidence that capsaicin, the pungent ingredient in hot chili peppers, might be useful for treating neuropathic pain, we developed the present clinical trial. PATIENTS AND METHODS Ninety-nine assessable patients with postsurgical neuropathic pain were entered onto this study. After stratification, patients were to receive 8 weeks of a 0.075% capsaicin cream followed by 8 weeks of an identical-appearing placebo cream, or vice versa. A capsaicin/placebo cream was to be applied to the painful site four times daily. Treatment evaluation was performed by patient-completed weekly questionnaires. RESULTS During the first 8-week study period, the capsaicin-cream arm was associated with substantially more skin burning, skin redness, and coughing (P &lt; .0001 for each). Nonetheless, treatment was stopped for patient refusal or toxicity just as often while patients were receiving the placebo as compared with the capsaicin. The capsaicin cream arm had substantially more pain relief (P = .01) after the first 8 weeks, with an average pain reduction of 53% versus 17%. On completion of the 16-week study period, patients were asked which treatment period was most beneficial. Of the responding patients, 60% chose the capsaicin arm, 18% chose the placebo arm, and 22% chose neither (P = .001). CONCLUSION A topical capsaicin cream decreases postsurgical neuropathic pain and, despite some toxicities, is preferred by patients over a placebo by a three-to-one margin among those expressing a preference.
Assessing asthma risk in primary care: Can the AAA test predict future asthma attacks?
Authors: Samantha Walker, John Blakey, Sunni Murdock, Dominic Clarke
Journal: European Respiratory Journal (2014)

Background 

The AAA (Avoid Asthma Attacks) test (Blakey J et al. Thorax 2012;67(2):A31) assesses risk of an asthma attack but requires validation before utility can be confirmed.

Methods 

We searched records of 14,191 people with asthma from 26 UK general practices. The AAA test consists of 8 factors which have been shown to have a consistent and clinically important (OR>1.25) association with asthma attacks. Factors are weighted in proportion to effect size when expressed as an odds ratio (table 1).

View this table:



Adherence was defined as collecting >80% of prescriptions for inhaled preventer therapy over the previous year. Daily reliever use was inferred from the frequency of prescription of short-acting bronchodilators. Patients' risk was retrospectively (Dec 2012) categorised as: low (no noted risks=0), medium (1-4 points) or high (>4 points). Primary outcome was defined as a composite of emergency admission or ED attendance for asthma; asthma attack treated in primary care;or acute drop in FEV1 of >10% in the following 12mths . 

Results 

View this table:





There was increased risk of an unscheduled emergency asthma event in people with a risk score >5 across all categories of event. People in the 'high' risk category were >11 times more likely to see a worsening of their condition or significant event (admission/AE attendance).

Conclusion 

Factors in the AAA test appear to identify those at increased risk of asthma attacks but require further validation.
Abstract 565: The Activation of AMP-Activated Protein Kinase Ameliorates the Severity of Heart Failure in Dogs
Authors: Hideyuki Sasaki, Hiroshi Asanuma, Masashi Fujita, Hiroyuki Takahama, Masakatsu Wakeno, Masanori Asakura, Jiyoong Kim, Tetsuo Minamino, Kazuo Komamura, Naoki Mochizuki, Masafumi Kitakaze
Journal: Circulation (2007)

Backgrounds; Since AMP-activated protein kinase (AMPK) is activated in the pressure-overloaded hypertrophic hearts, we investigated whether the activation of AMPK caused by metformin attenuates the progression of heart failure induced by rapid pacing in dogs and decreases cellular damage caused by oxidative stress in neonatal rat cardiac myocytes. Methods and Results; Heart failure was induced by right ventricular (RV) pacing at 230 bpm for 4 weeks in dogs. Treatment of dogs with metformin (100mg/kg/day, orally, n=8, Met group) for 4 weeks prevented significantly the progression of pacing-induced heart failure evaluated by echocardiographical and hemodynamic measurement compared with the control group (n=8). Left ventricular (LV) diastolic and systolic dimension (LVDd and LVDs) were smaller (32.8±0.4 and 26.7±0.9 mm, respectively) and fractional shortening (FS) and ejection fraction (EF) were preserved in Met group (18.6±1.8 and 45.5±3.5 %, respectively) compared with the control group (LVDd and LVDs; 36.5±1.0 and 33.0±1.0 mm, FS and EF; 9.6±0.7 and 27.0±1.9 %, p&lt;0.05 vs. Met group each). Furthermore, both pulmonary capillary wedge pressure (PCWP) and mean pulmonary arterial pressure (mPA) were significantly lower in Met group (11.1±0.9 and 18.1±1.4 mmHg, respectively) compared with the control group (21.0±2.2 and 26.8±2.8 mmHg, respectively). Treatment of cultured cardiac myocytes with a maximal physiological concentration of metformin (10μmol/L) attenuated the cellular damage against H 2 O 2 exposure (50μmol/L). These effects were blunted by an AMPK inhibitor, compound-C (20μmol/L), suggesting that the activation of AMPK increased the cellular viability during H 2 O 2 exposure. Conclusions; Metformin that activates AMPK prevented the progression of heart failure induced by rapid pacing in dogs and attenuated the cellular damage against H 2 O 2 exposure in cardiac myocytes. AMPK may be one of new targets for preventing heart failure in clinical settings.
Over-diagnosis of COPD in UK primary care
Authors: Wai Yee James, David Jolliffe, Kamrul Islam, Christopher Griffiths, Adrian Martineau
Journal: European Respiratory Journal (2012)

Background  Mis-diagnosis of COPD was reported to be common in Australia primary care practice. We conducted a study to evaluate the frequency of this problem in United Kingdom primary care.  Objectives  To determine the prevalence and correlates of mis-diagnosis of COPD and associated prescribing in UK primary care.  Methods  The records of COPD patients registered with 47 General Practices in London were searched electronically to identify patients with a ≥15 pack year of smoking history and age group of ≥40.  Spirometry was performed on those who were consented in the Trial of Vitamin D supplementation study, and the characteristics of those who met ATS/ERS spirometric criteria for COPD (FEV1/FVC ratio  70%. The prescription among patients who did not meet these criteria was assessed.  Results  A total of 264 patients were screened, of whom 232 (87.9%) were confirmed to have COPD by spirometric criteria and 32(12.1%) were not. 10/32 had evidence of restrictive lung disease and 22/32 had normal spirometry. 6/32 patients wrongly diagnosed with COPD were prescribed respiratory medication: 11/32 were prescribed tiotropium, 13/32 were prescribed a combination inhaler (LABA & ICS); 5/32 were prescribed inhaled corticosteroids, 2/32 were prescribed Xanthine, 21/32 were prescribed inhaled short acting brochodilator.  Conclusions  Misdiagnosis of COPD is common in UK primary care and it is associated with a significant degree of inappropriate prescribed respiratory medication. Tackling this problem has the potential to prevent needless adverse effects of non-indicated therapy, and to save costs of inappropriate prescribing.
Parasternal muscle contractility increases with aminophylline
Authors: Jenny Jagers, Bruce Rothwell, Paul Easton
Journal: European Respiratory Journal (2011)

Introduction: The traditional theophylline bronchodilator, Aminophylline, is still widely used, especially in the treatment of COPD. However, in COPD patients the effects of theophylline have been inconsistent. Recently, Aminophylline was shown to increase ventilation and costal diaphragm contractility in awake canines (Jagers et al. Resp. Phys. 2009;167:273-280).

Aim: To investigate the effect of Aminophylline at therapeutic levels on the primary chest wall muscle, Parasternal Intercostal.

Methods: Sonomicrometry transducers and EMG electrodes were implanted in the left parasternal muscle. After recovery, the animals were studied awake, unanesthetized and breathing through a snout mask; air flow, ETCO2, heart rate, muscle length and shortening, and moving average EMG were recorded during room air, and CO2 stimulated ventilation, before and after loading and continuous infusion of Aminophylline at therapeutic levels.

Results: For N=5 dogs (mean 31.1 kg) 24 days post implantation. Aminophylline serum levels were 66.4 umol/L (therapeutic range 55-110). Minute ventilation increased significantly with Aminophylline: 6.7, 7.84, 11.8 and 16.6 L/min at room air, low (46), medium (52) and high (57 mmHg) CO2 stimulated breathing respectively. Parasternal contractility increased significantly.

![Figure][1] 



Conclusion: Parasternal muscle contractility increases with greater muscle shortening per EMG, in awake, intact canines, at therapeutic levels of Aminophylline.

 [1]: pending:yes
The airways effects of inhaled chlorbutol in asthmatic subjects
Authors: H Windom, C Burgess, J Crane, R Beasley
Journal: European Respiratory Journal (1990)

Chlorbutol is an antibacterial and antifungal agent incorporated in terbutaline (Bricanyl) nebulizer solution. Ten stable atopic asthmatic subjects undertook bronchial challenge testing, according to a double-blind protocol. Patients inhaled doubling concentrations of either methacholine (0.13-4.0 mg.ml-1) or chlorbutol (0.16-5.0 mg.ml-1) for 2 min until the forced expiratory volume in one second (FEV1) had fallen by 20% from baseline. If this had not occurred following the administration of the final concentration, then this highest concentration was repeated for 4 min. The nine subjects completing the study had a geometric mean provocation concentration producing a 20% fall from baseline FEV1 (PC20) methacholine of 0.16 mg.ml-1 (range less than 0.125-0.475 mg.ml-1). After inhalation of 2.5 mg.ml-1 chlorbutol one subject experienced a fall in FEV1 greater than 20%. In the remaining eight subjects, inhalation of chlorbutol did not affect airway calibre. We conclude that chlorbutol, in the concentration present in Bricanyl nebulizer solution, has no clinically significant effect on airway calibre.
Skin reactivity and eosinophil count in relation to the outcome of childhood asthma
Authors: RJ Roorda, J Gerritsen, WM van Aalderen, K Knol
Journal: European Respiratory Journal (1993)

The aim of this study was to determine whether an association can be found between childhood skin reactivity and the outcome of asthma in young adulthood in a group of 406 asthmatic children, of whom 348 (86%) could be followed up in adulthood. A complete data set on skin tests and eosinophil count was available in 259 allergic subjects. They were stratified into three classes, according to initial skin test score in childhood. An increase in skin reactivity was noted from childhood to adulthood, while the differences in skin reactivity between the three classes remained significant. In childhood, a marked difference in total eosinophil count was found between the classes. Towards adulthood, a decrease in eosinophil count was noted, and the differences between the classes were no longer significant. The children with lowest skin reactivity also had the lowest symptom score in childhood. In adulthood, the prevalence of respiratory symptoms in this class was lower than in the other two classes. The prevalence of bronchial responsiveness to histamine was lowest in subjects with the lowest skin test score in childhood. Ventilatory parameters revealed no differences between the three classes. We conclude that although a low skin reactivity in childhood might be associated with a relatively favourable prognosis for asthma symptoms in adulthood, there is only limited evidence to support this hypothesis in our study.
The Dual Role of Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2–Positive Primary Breast Cancer
Authors: Sibylle Loibl
Journal: JAMA Oncology (2015)

Roberto Salgado, MD, PhD; Carsten Denkert, MD, PhD; Christine Campbell, MSc; Peter Savas, MD; Paolo Nuciforo, MD; Claudia Aura, MD; Evandro de Azambuja, MD, PhD; Holger Eidtmann, MD; Catherine E. Ellis, PhD; José Baselga, MD; Martine J. Piccart-Gebhart, MD, PhD; Stefan Michiels, PhD; Ian Bradbury, PhD; Christos Sotiriou, MD, PhD; Sherene Loi, MD, PhD
Clinical significance of the detection of Candida albicans germ tube-specific antibodies in critically ill patients
Authors: R. Zaragoza, J. Pemán, G. Quindos, J.R. Iruretagoyena, M.S. Cuétara, P. Ramírez, M.D. Gómez, J.J. Camarena, A. Viudes, J. Pontón
Journal: Clinical Microbiology and Infection (2009)