tbuckley/cabot-search huggingface dataset:
Five year update of cardiac dysfunction on NSABP B-31, a randomized trial of sequential doxorubicin/cyclophosphamide (AC)→paclitaxel (T) vs. AC→T with trastuzumab (H)
Authors: P. Rastogi, J. Jeong, C. E. Geyer, J. P. Costantino, E. H. Romond, M. S. Ewer, D. L. Keefe, T. Levine, S. M. Swain, N. Wolmark
Journal: Journal of Clinical Oncology (2007)

LBA513 Background: Trastuzumab (H) has been shown to improve survival in HER2 positive, node-positive breast cancer patients when combined with paclitaxel following AC (Romond NEJM 2005:353;1673–1684). Cardiac dysfunction is the major toxicity associated with this regimen. Methods: NSABP B-31 compared doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel plus 52 weeks of trastuzumab beginning concurrently with paclitaxel in patients with node- positive, HER2-positive breast cancer. Initiation of trastuzumab required normal post-AC left ventricular ejection fraction (LVEF) on MUGA scan. If symptoms suggestive of congestive heart failure (CHF) developed, source documents were blindly reviewed by a panel of cardiologists to determine whether criteria were met for a cardiac event (CE), defined as NYHA class III or IV CHF or possible/probable cardiac death. Among patients with normal post-AC LVEF who began post-AC treatment, 10 of 872 (1.3%) control patients subsequently had confirmed CEs (9 CHFs and 1 cardiac death) compared with 35 of 932 (3.9%) trastuzumab-treated patients (35 CHFs and no cardiac deaths). The difference in cumulative incidence at 5 years was 2.7%. Risk factors for CHF were age 50 (5.2–5.3%), requirement for hypertension medication (7.7%), and post AC-LVEF values of 50–54% (13.0%). Conclusion: Administering trastuzumab with paclitaxel after AC increases incidence of CHF. Risk factors for increased risk of cardiotoxicity should be carefully considered when discussing benefits and risks of this therapy. No significant financial relationships to disclose.
Acute postdisaster psychiatric disorders: identification of persons at risk
Authors: E M Smith, C S North, R E McCool, J M Shea
Journal: American Journal of Psychiatry (1990)

This study examined the prevalence of four psychiatric disorders--posttraumatic stress disorder, major depression, generalized anxiety disorder, and alcohol abuse/dependence--in survivors of a jet plane crash into a hotel. Forty-six subjects were interviewed with the Diagnostic Interview Schedule/Disaster Supplement within 4-6 weeks of the event. More than half of the subjects met criteria for a psychiatric disorder after the disaster. More than two-thirds of the cases of acute postdisaster psychiatric disorders were predicted by identifying the subjects who had predisaster psychiatric histories. Predisaster psychiatric disorder predicted postdisaster psychopathology with a sensitivity of 72% and a specificity of 90%.
Role of Midwives. (Letter)
Authors: Duncan Ts
Journal: New England Journal of Medicine (1977)

Dr. Alfano (New England Journal of Medicine 296:  1126 1977) is certainly entitled to his personal opinions but when they appear in a major publication in a setting that calls for factual information they cannot go unchallenged.  Midwives have played and continue to play a major part in maternal-infant services in many advanced European countries.  Combined midwife-physician services in Sweden Finland Japan Netherlands Denmark Norway and Switzerland produced infant mortality rates in 1972 superior to those reported by Dr. Alfano for the Commonwealth of Massachusetts in 1974.  Even in 1967 Sweden and the Netherlands (where most infants are delivered by midwives) had infant mortality rates respectively of 12.9 and 13.4/100 live births.  These numbers of course do not mean that midwives are superior to doctors but they do not seem to prove them inferior when they are employed in an appropriate setting.  In Oregon (where certified nurse-midwives have been employed for some years) the professional midwife is found mainly in the expensive practices so that if there is a 3rd-level of care it is delivered to the well-to-do rather than the  indigent.  It is a little early to tell but the impression around here is that although the quality of the birth experience may be changed by addition of midwives to an upper-middle-class practice the outcome in terms of numbers of live babies is no  different.  This finding may not apply when 1 is dealing with the economically disadvantaged.  A striking study from California demonstrated a definite improvement in fetal outcome when certified midwives were added to an established program and a tendency for the infant mortality rate to rise again when their services were  discontinued for lack of funds.  A similar program is under way in Oregon but it is much too early for results to be apparent.  This letter is not written in defense of midwives - it is a plea for balance and rationality.  Medicine is no place for a territorial imperative.  Only by calling on the expertise of all qualified members of a society can one hope to progress and to improve the human condition.(Full text)
Efficacy of adjuvant chemotherapy for patients with resectable head and neck cancer: a subset analysis of the Head and Neck Contracts Program.
Authors: C Jacobs, R Makuch
Journal: Journal of Clinical Oncology (1990)

To evaluate the efficacy of adjuvant chemotherapy for patients with advanced head and neck squamous cancer, the Head and Neck Contracts Program conducted a three-arm study comparing standard surgery and radiation, induction chemotherapy (cisplatin and bleomycin) plus standard therapy, and induction chemotherapy plus standard therapy followed by maintenance cisplatin for 6 months. As previously reported, this trial of 462 patients demonstrated no significant difference in disease-free survival or survival, but a significantly lower metastatic rate in the maintenance arm. To determine whether particular subgroups may have benefited from adjuvant therapy, we evaluated results based on primary site, and tumor (T) and node (N) stage. Of the 192 patients with oral cavity cancer, those on the maintenance arm had a significantly improved 3-year disease-free survival (67%) compared with the standard arm (49%) or induction arm (44%) (overall P = .05). For hypopharyngeal and laryngeal cancers there was no marked overall benefit. For the 106 patients with T1 plus T2 disease, there was marginal improvement in disease-free survival for the maintenance group (72%) compared with the standard group (47%) or induction group (43%) (overall P = .09). There was no advantage for patients with T3 and T4 disease. There was superior disease-free survival for patients with N1 disease on the maintenance arm (70%) compared with the standard arm (42%) (P = .024). The same was true for disease-free survival in 109 patients with N2 disease: standard (52%), induction (30%), maintenance (84%) (overall P less than .001). There was no benefit for N3 disease. A significant survival advantage with maintenance chemotherapy was only seen for N2 disease (overall P = .04). Since head and neck cancer patients are a heterogeneous group, there may be particular sites and stages for which adjuvant chemotherapy would be advantageous, and subset analysis can help indicate directions for new trials.
Safety and immunogenicity of the heterologous prime-boost Ebolavirus vaccine regimen CHAD3-EBO Z and MVA-BN® FILO in healthy UK adults
Authors: Tommy Rampling, Katie Ewer, Georgina Bowyer, Danny Wright, Navin Venkatraman, Ruth Payne, Alfredo Nicosia, Nancy Sullivan, Barney Graham, Andrew Pollard, Simon Draper, Ripley Ballou, Alison Lawrie, Sarah Gilbert, Adrian Hill
Journal: Journal of Infection (2015)
Optimal pressure determination for CPAP in the treatment of obstructive sleep apnea syndrome (OSAS). Comparison of prediction equations and autoCPAP titration
Authors: Berta Román, Eva Maria Rosillo, Luis Hernández, Lucia Zamora, Baeza Carlos
Journal: European Respiratory Journal (2013)

To analyze whether there is a good correlation between the pressure setting by autoCPAP and the one calculated by mathematical prediction formulas proposed by Hoffstein et al.([(0.16xBMI)+(0.13xNC)+(0.04xAHI)-5.12], (AmJRespirCritCareMed1994) and Series et al [(0.193xBMI)+(0.077xNC)+(0.02xAHI)–0,611] (Chest2008).  Consecutive patients with OSAS diagnosis after a sleep study between December-2003 to December-2012. Patients underwent an attended sleep study for CPAP titration with an autoCPAP device (REMstar ®). The pressure was set from 4 to 15 cmH20. We analyze the correlations (Pearson r coefficient and Bland-Altman plots) between the pressure calculated by the formulas and the one obtained by autoCPAP.  We included 2514 male patients. Mean values were: age 54 years±12.5, neck circumference(NC) 43.8±3.6 cm, BMI 33±6kg/m2; AHI 49±22. Although there was a good correlation between the pressures calculated by both formulas (r=0.97, p  When comparing with autoCPAP titration, Hoffstein formula underestimates CPAP pressure values >7cmH2O. The opposite happens with the Series formula, which overestimates the pressure throughout the usual range of values except for pressures >12cmH2O.
Sensitivity of C-Tb: a novel RD-1-specific skin test for the diagnosis of tuberculosis infection
Authors: Soren T. Hoff, Jonathan G. Peter, Grant Theron, Mellissa Pascoe, Pernille N. Tingskov, Henrik Aggerbeck, Daniel Kolbus, Morten Ruhwald, Peter Andersen, Keertan Dheda
Journal: European Respiratory Journal (2015)

C-Tb, a novel Mycobacterium tuberculosis and 6-kDa early secretory antigenic target/10-kDa culture filtrate protein (ESAT-6/CFP-10)-specific skin test, has high specificity in bacille Calmette–Guerin-vaccinated healthy controls. However, the sensitivity of C-Tb has hitherto not been determined. The objective was to determine the sensitivity of C-Tb in patients with active tuberculosis (TB) in comparison with the tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube (QFT-GIT). C-Tb and TST were randomly administered in a double-blinded fashion to one or the other forearm in 253 patients with active TB with or without HIV co-infection. QFT-GIT testing was performed prior to skin testing. Using a receiver operating characteristic curve-derived cut-point of 5 mm, C-Tb sensitivity was similar to QFT-GIT (73.9 (95% CI 67.8–79.3) versus 75.1 (95% CI 69.3–80.2)), and similar in HIV-infected and HIV-uninfected patients (76.7 (95% CI 69.0–83.3) versus 69.5 (95% CI 59.2–78.5)). However, sensitivity was significantly diminished in HIV-infected patients with CD4 counts &lt;100 cells·mm –3 . C-Tb and QFT-GIT combined had significantly higher sensitivity than C-Tb alone (p&lt;0.0001). C-Tb was safe with no significant adverse events. The 5 mm cut-point corresponded to that found in the previously published specificity study (TESEC-04). C-Tb has similar sensitivity compared with QFT-GIT for the diagnosis of M. tuberculosis infection. Sensitivity was reduced only in HIV-infected patients with severe immunosuppression. Further studies in different settings are required to validate the proposed 5 mm cut-point.
Cellular immunotherapy in late stage breast cancer patients with reactivated autologous Memory T-cells derived from bone marrow
Authors: F. Schuetz, I. Diel, P. Beckhove, K. Ehlert, V. Schirrmacher, A. Schneeweiss, I. Lauschner, G. Bastert, H.-J. Strittmatter
Journal: Journal of Clinical Oncology (2005)

714 Background: We have previously shown an enrichment of tumor-specific MTC in BM in 66% of breast cancer patients by using IFN-γ ELISPOT. Upon specific restimulation with dendritic cells (DC) in vitro BM T cells exert specific effector functions like IFN-gamma production and cytotoxicity. Furthermore we have shown in NOD/Scid-mice that reactivated MTC are able to infiltrate tumor tissue, proliferate and kill tumor cells. Furthermore we were able to show that endocrine and cytostatic cancer therapies only have a limited influence on the frequency of tumorspecific MTC in BM. Thus we have done a phase I trial with autologous reactivated MTC of BM in metastatic breast cancer (MBC) patients. Methods: BM aspirate was tested by IFN-γ ELISPOT for MTCs that are reactive against lysate of breast cancer cell line (MCF-7) in each patient. If reactive MTCs were found these cells were reactivated by incubating them with autologous DC pulsed with MCF-7 lysate. Reactivated MTCs and pulsed DCs are injected intravenously into the same patient after 12 days of incubation time in 11 patients who had metastatic lesions to bon (50%), lung (20%), liver (30%), and other sides (25%). Primary objectives were feasibility, and toxicity. Secondary objectives were clinical response, and immuno-response. Results: Vaccination therapy was feasable in all patients without any side effects during and after T-cell injection. We were able to applicate 5x107 T-cells in mean per patient. There was a clinical response shown in two of four measurable patients. Immunodiagnostic of the follow up will be shown on the meeting. Conclusions: Cellular immunotherapy with autologous MTC is a feasible way of MBC treatment. Efficiacy will be shown in a phase II trial. No significant financial relationships to disclose.
Sarcomatoid (metaplastic) carcinoma of the breast: The U.T. M.D. Anderson Cancer Center (MDACC) and SEER database experience
Authors: B. Hennessy, S. Giordano, K. Broglio, G. N. Hortobagyi, V. Valero
Journal: Journal of Clinical Oncology (2005)

614 Background: Sarcomatoid (metaplastic) carcinoma of the breast is a rare disease which contains overtly carcinomatous and sarcoma-like elements on light microscopy; its clinical behaviour is not well documented. Methods: To better define the clinical features of sarcomatoid breast carcinoma, MDACC records were searched for patients diagnosed from 1985–2002. We also searched the SEER database for patients with this disease registered between 1988 and 2001. Descriptive statistics were used to summarize patient characteristics. Results: From the MDACC records, we identified 100 sarcomatoid breast cancer patients. Their median follow-up was 55 months (range, 4–252).The median age at diagnosis was 48 years (range, 26–77), 76% had grade 3 disease, 66% had node-negative disease, and 57% had stage 2 disease. Six percent had ER-positive and 9% had PR-positive tumors. Of 26 patients with a known HER2/neu status, 24 were HER2/neu-negative. Of 94 patients with localized disease at diagnosis, all but 1 had surgery, 82% received adjuvant chemotherapy, and 54% radiotherapy. The median recurrence-free survival (RFS) of these patients was 74 months (range, 3 to 252), with a 52% RFS rate at 5 years. The median overall survival (OS) of these patients was not reached, with 64% alive at 5 years. Fifty percent of first recurrences were local. Median survival from the time recurrent disease was recognized was only 14 months (range, 1 to 50). The 5-year RFS was low and not statistically different between patients who did and did not receive adjuvant chemotherapy, although all 3 patients treated with an anthracycline/ifosfamide-based regimen did remain recurrence-free. The SEER database registered 213 cases of sarcomatoid breast cancer of a total of 281,382 breast cancers. Information from this database was remarkably consistent with our findings. Conclusions: Sarcomatoid (metaplastic) cancer of the breast is rare, usually receptor-negative, and often aggressive and treatment-refractory. The role of ifosfamide with standard chemotherapy should be explored. The biology of this disease needs to be better defined with the aid of gene array and other new technologies to develop targeted therapies. No significant financial relationships to disclose.
Abstract 12068: Sex Differences in Lifetime Risk and First Manifestation of Cardiovascular Disease: An Evidence Gap in Preventive Cardiology
Authors: Maarten J Leening, Bart S Ferket, Maryam Kavousi, Ewout W Steyerberg, Jaap W Deckers, Daan Nieboer, Jan Heeringa, Marileen L Portegies, Albert Hofman, Arfan Ikram, Myriam G Hunink, Oscar H Franco, Bruno H Stricker, Jacqueline C Witteman, Jolien W Roos-Hesselink
Journal: Circulation (2014)

Introduction:  Knowledge on the first manifestation of cardiovascular disease (CVD) is relevant for primary prevention and data on sex differences of first manifestations of CVD are scarce.   Hypothesis:  We sought to evaluate differences in first CVD manifestations between men and women in a competing risks framework.   Methods:  We used data from 8419 participants (60.9% women), aged 55 years and older, of the prospective population-based Rotterdam Study cohorts to estimate lifetime risks of CVD and its first-incident fatal or nonfatal manifestations (coronary heart disease [CHD], cerebrovascular disease, heart failure, and other CVD death) at various ages. Competing risks among the different first CVD manifestations and non-cardiovascular death were taken into account in all analyses. Regression models were adjusted for cardiovascular risk factors.   Results:  During a follow-up of up to 20.1 years, 2888 participants developed CVD. Lifetime risk of CVD at age 55 was similar for both sexes with 67.1% (95% CI 64.7-69.5) for men and 66.4% (95% CI 64.2-68.7) for women (P=0.34 for difference between sexes). Lifetime risks of first CVD manifestations coronary heart disease, cerebrovascular disease, heart failure, and other CVD death were 27.2% (95% CI 24.1-30.3), 22.8% (95% CI 20.4-25.1), 14.9% (95% CI 13.3-16.6), and 2.3% (95% CI 1.6-2.9) for men, and 16.9% (95% CI 13.5-20.4)(P   Conclusions:  At age 55, men and women have similar lifetime risks of CVD. However, sex differences in the first manifestation of CVD are large with coronary heart disease being the most common initial manifestation of CVD in men, whereas in women CVD unveils itself most frequently with cerebrovascular disease followed by heart failure. Our results underscore the importance of adequate risk factor control for stroke and heart failure in women.
Abstract 16827: Double-chambered Right Ventricle Diagnosed in Late Adulthood by Multi-modality Imaging. Report of Two Cases With Associated Aortopathy
Authors: Valeria E Duarte, Rayan Yousefzai, Timothy Paterick, Jamil Tajik
Journal: Circulation (2015)

Introduction: Double-chambered right ventricle (DCRV) is a rare congenital disorder. The right ventricle (RV) is divided into two: a high-pressure inlet and a low-pressure outlet by an abnormal muscle bundle. Rarely diagnosed in adulthood, it is associated with other congenital defects. Association with aortopathy is not described. Patient 1: 67 year-old male with dyspnea: PE: grade 4 harsh systolic murmur radiating to the base. Echo: DCRV with obstruction -peak gradient (PG) 75mmHg (Fig 1-C), hypertrophied/dilated RV, decreased function; small perimembranous VSD, small right-to-left shunt. Ascending aorta aneurysm: 49 mm (Fig 1-D). Normal aortic valve. MRI: DCRV with muscle bundle causing RVOT obstruction. RV with delayed gadolinium enhancement (Fig 2). Heart cath: severe RV obstruction (PG 105 mmHg). Surgery: Resection of the muscular bundle, VSD closure and grafting of ascending aorta. Follow-up: significant improvement. Patient 2: 56 year-old female with VSD. PE: 4/6 holosystolic murmur at left sternal border. Echo: DCRV: Mean gradient (MG) 30 mmHg (Fig 1-B), small perimembranous VSD. Ascending aorta: 39 mm. Functionally bicuspid aortic valve, mild AR. Exercise echo: sub-pulmonary resting MG 35, stress MG 52 and PG 90 mmHg. MRI: DCRV with a membrane causing RVOT stenosis. Gene testing for TAAD/Marfan negative. Surgery: VSD closure and resection of RV membrane. Follow up: asymptomatic. Conclusion: DCRV should be considered with an elevated RV systolic pressure and intracavitary gradient. Comprehensive echocardiographic examination of the RV is essential. CMR is useful providing anatomic detail. Surgical correction has successful short and long term outcomes.
Abstract 13208: Time-Dependent Interactions of Prasugrel vs Clopidogrel on the Long-Term Risks of Stroke after Acute Coronary Syndromes: Results from the TRILOGY ACS Trial
Authors: Chee Tang Chin, Benjamin Neely, E. M Ohman, Paul W Armstrong, Harvey D White, Dorairaj Prabhakaran, Keith A Fox, Kenneth J Winters, Matthew T Roe
Journal: Circulation (2014)

Introduction: The role of more intense, sustained platelet inhibition in preventing post-ACS stroke is unclear. We previously observed a signal for a reduced risk of stroke in the TRILOGY ACS trial after 12 months of treatment with prasugrel vs clopidogrel in medically managed ACS patients. Methods: We examined the TRILOGY efficacy population (7243 ACS patients <75 y), analyzing differences in baseline characteristics between patients with/without a stroke event through 30 months with a Cox proportional hazards model. Patients with prior stroke and/or need for chronic anticoagulation were excluded. We also assessed the impact of prasugrel vs clopidogrel on risk of all stroke events and ischemic stroke over time with an extended Cox proportional hazards model. Results: There were few stroke events (n=77; ischemic stroke=62; hemorrhagic stroke=15) through 30 months. Patients with stroke were older, had more comorbidities including atrial fibrillation, and had a higher GRACE long-term mortality risk score vs...
Analysis of Impact of Post-Treatment Biopsies in Phase I Clinical Trials
Authors: Randy F. Sweis, Michael W. Drazer, Mark J. Ratain
Journal: Journal of Clinical Oncology (2015)

The use of biopsy-derived pharmacodynamic biomarkers is increasing in early-phase clinical trials. It remains unknown whether drug development is accelerated or enhanced by their use. We examined the impact of biopsy-derived pharmacodynamic biomarkers on subsequent drug development through a comprehensive analysis of phase I oncology studies from 2003 to 2010 and subsequent publications citing the original trials.We conducted a search to identify and examine publications of phase I oncology studies including the use of biopsy-derived pharmacodynamic biomarkers between 2003 and 2010. Characteristics of those studies were extracted and analyzed, along with outcomes from the biomarker data. We then compiled and reviewed publications of subsequent phase II and III trials citing the original phase I biomarker studies to determine the impact on drug development.We identified 4,840 phase I oncology publications between 2003 and 2010. Seventy-two studies included a biopsy-derived pharmacodynamic biomarker. The proportion of biomarker studies including nondiagnostic biopsies increased over time (P = .002). A minimum of 1,873 tumor biopsies were documented in the 72 studies, 12 of which reported a statistically significant biomarker result. Thirty-three percent of studies (n = 24) were referenced by subsequent publications specifically with regard to the biomarkers. Only five positive biomarker studies were cited subsequently, and maximum tolerated dose was used for subsequent drug development in all cases.Despite their increased use, the impact of biopsy-derived pharmacodynamic biomarkers in phase I oncology studies on subsequent drug development remains uncertain. No impact on subsequent dose or schedule was demonstrated. This issue requires further evaluation, given the risk and cost of such studies.
Preoperative versus postoperative docetaxel–cisplatin–fluorouracil (TCF) chemotherapy in locally advanced resectable gastric carcinoma: 10-year follow-up of the SAKK 43/99 phase III trial
Authors: N. Fazio, R. Biffi, R. Maibach, S. Hayoz, S. Thierstein, P. Brauchli, J. Bernhard, R. Stupp, B. Andreoni, G. Renne, C. Crosta, R. Morant, A. Chiappa, F. Luca, M.G. Zampino, O. Huber, A. Goldhirsch, F. de Braud, A.D. Roth, U. Pace, S. Cenciarelli, S. Pozzi, E. Bertani, S. Mura, K. Lorizzo, G. Di Meglio, D. Ravizza, S. Boselli, M. Matter, M. Richter, S. Monfardini, C. Dittrich, M. Häfner, M. Clemens
Journal: Annals of Oncology (2015)