tbuckley/cabot-search huggingface dataset:
Impact of built-in software analysis on monitoring patients under home mechanical ventilation
Authors: Juan Cascón, Ramón Fernández, Andrés Quezada, Gemma Rubinos, Francisco R. Jerez, Claudio Rabec, Pere Casan
Journal: European Respiratory Journal (2013)

INTRODUCTION: Ventilators for Home mechanical ventilation (HMV) has built-in software (BIS) that provide information about patient-ventilator interaction that could improve patient's management.

OBJECTIVE: To assess the impact of adding BIS to basic monitoring techniques (BMT) on the detection of unsatisfactory HMV.

METHODS: Patients under HMV were included. BMT were: clinical interview, arterial blood gas (ABG) and home nocturnal oximetry (HNO). HMV was satisfactory (S-HMV) if the following criteria were met: 1-Comfort and improvement of symptoms, 2-ABG: pO2>60 mmHg and pCO2 4 h/night, respiratory rate <25 breaths/min, average leak <60 L/min (facial mask) and <50 L/min (nasal mask), and asynchronies in <50% of the whole record (pressure slope). HMV was unsatisfactory (U-HMV) if any of the criteria fail. Changes in treatment were recorded. Vivo 30/40 and their BIS were used in all cases.

RESULTS: Fifty patients aged 60(9) yrs, 60% male and 21(7) months under HMV were included. Conditions were: 29 Obesity-hypoventilation, 5 chest wall disorders, 4 neuromuscular diseases, 4 COPD and 8 mixed conditions. Thirteen cases (26%) were S-HMV. Seventy-nine U-HMV causes were detected, 34 by BIS and 45 by BMT. Fifty-nine changes were made in 33 patients: 15 interfaces, 15 ventilator settings, 11 harnesses, 5 added humidifier, 5 added O2, 5 withdrew O2 and 3 changes of ventilator. BIS detected 12 (32%) of the 37 U-HMV cases with no abnormalities in BMT.

CONCLUSIONS: Applying simple criteria to the analysis of ventilator BIS increases our ability to detect U-HMV and promotes changes that could improve the quality of treatment.
Efficacy of third-line chemotherapy for recurrent ovarian, peritoneal and fallopian tube carcinoma
Authors: A. Tremblay, F. Harel, A. Lavoie, R. Leblanc, P. Ouellet, C. Tessier, M. Lalancette
Journal: Journal of Clinical Oncology (2005)

5136 Background: Various types of chemotherapy have been studied in patients with refractory/relapsing ovarian carcinoma. However there is very limited information regarding the usefulness of chemotherapy in ovarian cancer patients who have received several lines of treatment. Methods: All patients with ovarian epithelial, primary peritoneal or fallopian tube carcinoma who received at least three different types of chemotherapy in our institution were evaluated retrospectively. Those included in the analysis had to have received at least one platin-based regimen as their 1st line treatment and Topotecan as their 2nd line. The primary endpoint was response rate (RR). Responses were analysed according to the RECIST criteria for measurable disease, and the CA-125 criteria defined by the Gynecologic Cancer Intergroup (GCIG). Secondary endpoints were time to progression (TTP), disease stabilization, and overall survival (OS). Results: Fifty-two patients met our entry criteria. Ten (19.2%) had responded to Topotecan as their 2nd line treatment. Liposomal doxorubicin was the most often used third-line therapy (40.4%). The overall RR was 13.5% for third-line agent (1 CR and 6 PR). Median TTP was 50.7 weeks (95% CI 30 to 86 weeks) and disease stabilization was noted in 23% of patients with a median duration of 17.7 weeks. The median OS from the start of 3rd line therapy was 11.7 months (95% CI 7.7 to 15.3 months). It was significantly better for patients who responded to 3rd line treatment compared to non-responders (24.6 vs 7.3 months, p=0.0017). The only prognostic factor that strongly influenced the OS was the type of response to previous Topotecan (p = 0.0596) with a median OS from the start of 3rd line of 19.5 months for Topotecan responders compared to 10.3 months for the others. Conclusions: Disease response or stabilization occurs in about a third of patients receiving 3rd line treatment. The type of response to 2nd line therapy (Topotecan in this study) can help predict the responsiveness and perhaps usefulness of subsequent chemotherapy. This is the first study to show that median OS is significantly improved in responders compared to non-responders in women receiving 3rd line therapy for ovarian carcinoma. No significant financial relationships to disclose.
Long-term safety of pirfenidone in RECAP, an open-label extension study in patients with idiopathic pulmonary fibrosis, interim results
Authors: Ulrich Costabel, Carlo Albera, Elizabeth Fagan, Williamson Bradford, Talmadge King, Paul Noble, Steven Sahn, Dominique Valeyre, Roland du Bois
Journal: European Respiratory Journal (2014)

Introduction: Pirfenidone (PFD) is an antifibrotic agent approved in mild-to-moderate idiopathic pulmonary fibrosis (IPF). The long-term safety of PFD is being assessed in the open-label RECAP study in IPF patients (pts) who completed the CAPACITY trials.

Objectives: To compare the safety of PFD in the long- (RECAP) and short-term (CAPACITY).

Methods: Of 628 pts who completed CAPACITY, 603 enrolled in RECAP. An interim analysis of RECAP from enrolment (September 2008) to August 2013 is presented.

Results: The median PFD (2403 mg/day) exposure in RECAP was 163 weeks (range 1–257). The cumulative total exposure was 1,727 person exposure years. 99% of pts reported at least 1 treatment-emergent adverse event (TEAE, Table 1). Rash and photosensitivity were less prominent in RECAP (16% and 9%) than in CAPACITY (32% and 12%). TEAEs led to treatment discontinuation in 45% of pts. Discontinuations (>1.0% of pts) were due to IPF (16%), respiratory failures (3.2%), rash (1.5%) and nausea (1.3%). Serious TEAEs were reported in 62% of pts; the most common was IPF (23%). Of the 141 (23%) TE-deaths, the most common was from IPF (13%).

Conclusions: Safety data from IPF pts receiving PFD for up to 163 weeks demonstrate that long-term PFD treatment is safe and generally well tolerated.

View this table:

Table 1. Frequency of the most frequent TEAEs in RECAP compared to CAPACITY (median exposure 163 weeks vs 74 weeks)
Patient and transplant center factors associated with 100D mortality after receiving allogeneic hematopoietic stem cell transplantation (HSCT)
Authors: F. R. Loberiza, M. Zhang, J. D. Rizzo, S. J. Lee, J. P. Klein, B. R. Logan, M. Eapen, D. S. Serna, C. F. Lemaistre, M. M. Horowitz
Journal: Journal of Clinical Oncology (2004)

6026
Physiological effects associated with the use of respiratory devices
Authors: Dmitriy Uryumtsev, Oleg Grishin, Viktor Grishin
Journal: European Respiratory Journal (2014)

Background: The study of gas exchange and ventilation was previously carried out on a group of healthy subjects, where the response to the use of respiratory devices consisted of a decrease in respiratory rate, oxygen consumption, and carbon dioxide emission, as well as an increase in respiratory volume.

Aim: To assess the impact of respiratory devices on ventilation and gas exchange parameters in patients with COPD.

Methods: The study included patients with COPD (n= 21) of both sexes with the mean age of 59. The values of VE, f, Vt, VO2, VCO2, RER, VE/VO2 were recorded on a spirometabolic complex at the initial state and after connecting respiratory devices (Valve 22F-22V and Y - piece 22M, 22M/15F, Intersurgical). Each record was conducted successively over five minutes, while the subject was sitting ar rest and breathing ambient air.

Results: It was found that the ventilation parameters did not significantly change during the study, while there was an 18% decrease in oxygen consumption (VO2) and 17% decrease in carbon dioxide elimination (VCO2); the ventilatory equivalent of oxygen (VE/VO2) increased by 15.5%, and the respiratory exchange ratio (RER) did not change.

Conclusions: The observed decrease in gas exchange parameters is manifested in both healthy subjects and in patients with COPD. Yet, as opposed to healthy subjects, the patients with COPD show no changes in ventilation values. Thus, during the examination of patients, the impact of respiratory devices should be taken into account, which can vary depending on the respiratory system function.
Herpesvirus saimiri -lnduced Lymphoproliferative Disease in Howler Monkeys 2
Authors: S. R. S. Rangan, Louis N. Martin, Frederick M. Enright, Christian R. Abee
Journal: JNCI Journal of the National Cancer Institute (1977)

Four of 5 howler monkeys (Alouatta caraya) experimentally infected with Herpesvirus saimiri (HVS) developed a rapidly fatal malignant lymphoma accompanied by peripheral T-cell lymphocytosis. HVS was isolated from fresh and tissue cultured blood and tissue lymphocytes and from cell cultures derived from nonlymphoid organs. Humoral antibodies against HVS-induced antigens were detected in the sera of the animals. The in vitro response of the peripheral blood lymphocytes to mitogenic stimulants was depressed following HVS infection.
Tanespimycin plus bortezomib in patients with relapsed and refractory multiple myeloma: Final results of a phase I/II study
Authors: P. G. Richardson, A. Chanan-Khan, S. Lonial, A. Krishnan, M. Carroll, M. Alsina, M. Albitar, D. Berman, S. Kaplita, K. Anderson
Journal: Journal of Clinical Oncology (2009)

8503 Background: Tanespimycin (Tan) disrupts HSP90, a key molecular chaperone for signal transduction proteins critical to myeloma (MM) growth, survival and drug resistance. Preclinical data show anti-tumor synergy between Tan and bortezomib (Bz) and suggest Tan may be neuroprotective, including reversibility of Bz-induced peripheral neuropathy (PN). A phase I study of single agent Tan in advanced MM showed favorable tolerability and modest activity. Methods: 72 patients (pts) with relapsed/refractory MM received 0.7 - 1.3 mg/m 2 Bz as IVB followed by 1-hr infusion of 100 -340 mg/m 2 Tan on days 1, 4, 8,11 q 21d, with 42 pts receiving the highest dose of both drugs as part of a phase II expansion. Toxicities were assessed by CTCAE v3 and response by modified EBMT criteria. Results: Of 72 pts, 72% had IgG subtype with a median age of 60 yo. Median time since MM diagnosis was 50 mos with median of 5 (1–15) prior regimens. Prior treatments included stem cell transplant (69%), thalidomide (74%), Bz (69%), lenalidomide (28%) and Hsp90 inhibitors (13%). 58 pts with measurable disease were treated at 1 or 1.3 mg/m 2 Bz. Response rates (≥ MR) were 41%, 20% and 14% in the Bz-naive, -pretreated and -refractory pts respectively. In the subgroup with 1–3 prior therapies and who were Bz-naive, the response rate was 56%. Median duration of response (DOR) for all pts with response (n=14) was 10.7 mos, including 3 Bz-refractory pts who had durable PR through mos 12, 22 and 28. 3 other pts remain in response through 24 mos. Of the 72 pts, the most frequent AEs were diarrhea (60%), nausea (49%), fatigue (49%), thrombocytopenia (40%) and AST elevation (28%), which proved manageable with dose reduction and supportive care. Most frequent G3–4 AEs included thrombocytopenia (25%), diarrhea, anemia and fatigue (7% each), as well as back pain and AST elevation (4% each). Only 21% of pts had G1–2 PN; no G3–4 PN was seen. Conclusions: Tan + Bz is active and well tolerated in relapsed/refractory MM, with durable responses in Bz-naive, -pretreated and -refractory pts. Median DOR for the combination compares favorably to Bz monotherapy. Final PFS data will be presented. No severe PN has been observed, consistent with Tan's neuroprotective effect in pre-clinical models. A phase III study of Tan + Bz vs Bz is ongoing. [Table: see text]
A Novel Epigenetic Signature for Early Diagnosis in Lung Cancer
Authors: Angel Diaz-Lagares, Jesus Mendez-Gonzalez, David Hervas, Maria Saigi, Maria J. Pajares, Diana Garcia, Ana B. Crujerias, Ruben Pio, Luis M. Montuenga, Javier Zulueta, Ernest Nadal, Antoni Rosell, Manel Esteller, Juan Sandoval
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Lung cancer remains as the leading cause of cancer-related death worldwide, mainly due to late diagnosis. Cytology is the gold-standard method for lung cancer diagnosis in minimally invasive respiratory samples, despite its low sensitivity. We aimed to identify epigenetic biomarkers with clinical utility for cancer diagnosis in minimally/noninvasive specimens to improve accuracy of current technologies. Experimental Design: The identification of novel epigenetic biomarkers in stage I lung tumors was accomplished using an integrative genome-wide restrictive analysis of two different large public databases. DNA methylation levels for the selected biomarkers were validated by pyrosequencing in paraffin-embedded tissues and minimally invasive and noninvasive respiratory samples in independent cohorts. Results: We identified nine cancer-specific hypermethylated genes in early-stage lung primary tumors. Four of these genes presented consistent CpG island hypermethylation compared with nonmalignant lung and were associated with transcriptional silencing. A diagnostic signature was built using multivariate logistic regression model based on the combination of four genes: BCAT1, CDO1, TRIM58, and ZNF177. Clinical diagnostic value was also validated in multiple independent cohorts and yielded a remarkable diagnostic accuracy in all cohorts tested. Calibrated and cross-validated epigenetic model predicts with high accuracy the probability to detect cancer in minimally and noninvasive samples. We demonstrated that this epigenetic signature achieved higher diagnostic efficacy in bronchial fluids as compared with conventional cytology for lung cancer diagnosis. Conclusions: Minimally invasive epigenetic biomarkers have emerged as promising tools for cancer diagnosis. The herein obtained epigenetic model in combination with current diagnostic protocols may improve early diagnosis and outcome of lung cancer patients. Clin Cancer Res; 22(13); 3361–71. ©2016 AACR.
<i>In vitro</i> effects of the prenyl transferase inhibitor AZD3409 on prostate cancer epithelial cells
Authors: R. Khafagy, T. Stephens, C. Hart, V. Ramani, M. Brown, N. Clarke
Journal: Journal of Clinical Oncology (2004)

4744 Background: Prostate cancer is the most common malignancy in men with a predilection to metastasize to the bone. There is a requirement for a chemotherapeutic agent capable of preventing or slowing down the growth of bone metastases. AZD3409 is a novel oral prenyl transferase inhibitor with anticancer potential. Methods: The effect of escalating doses of AZD3409 on proliferation of the malignant PC-3 and LNCaP, and non-malignant PNT2-C2 prostate epithelial cell lines was determined by CASY TT cell counter. PC-3 and PNT2-C2 colony formation was studied in co-culture using long-term human bone marrow stroma harvested from individuals with benign disease. Prostatic epithelial colony growth was measured using standardized quantitative techniques in the presence of escalating doses of AZD3409. Prostatic cellular invasion through matrigel (synthetic basement membrane) and cultured endothelial monolayers was measured in invasion chambers in the presence and absence of drug using cytokeratin labeled quantitation of migrating cells. Results: AZD3409 displayed marked anti-proliferative properties on non-malignant (PNT2-C2) and malignant (PC-3 and LNCaP) prostate epithelial cells, with a concentration of 10 nM resulting in a 50% inhibition of growth after 5 days. AZD3409 inhibits invasion through bone marrow endothelium towards bone marrow stroma, with a concentration of 4 μM inhibiting 50% of PC-3 invasion. Pre-treatment resulted in a 1000-fold decrease in the invasion IC50 with inhibition of invasion occurring at 10 nM, levels known to be attainable in vivo. AZD3409 inhibits colony formation in bone marrow stroma co-cultures resulting in reduced numbers of colonies (50% inhibition at 4 μM) and a reduction in epithelial colony size (50% reduction at 8 μM). Conclusions: AZD3409 is a potent inhibitor of prostate epithelial cell proliferation and its anti-colony formation in bone marrow stroma co-culture suggests potential as an anti-metastatic agent. This hypothesis is strengthened by the fact that AZD3409 shows significant inhibition of prostate cancer cell invasion through human bone marrow endothelium. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca UK
Fluorouracil and recombinant alfa-2a-interferon: an active regimen against advanced colorectal carcinoma.
Authors: S Wadler, E L Schwartz, M Goldman, A Lyver, M Rader, M Zimmerman, L Itri, V Weinberg, P H Wiernik
Journal: Journal of Clinical Oncology (1989)

Based on in vitro studies that have demonstrated synergy between recombinant alfa-2a-interferon (rIFN alpha-2a) and the fluoropyrimidine, fluorouracil (5FU), against two human colon cancer cell lines, a pilot clinical trial was initiated to determine the effects of the combination of 5FU and rIFN alpha-2a in patients with advanced, unresectable colorectal carcinoma. A total of 30 patients were enrolled; all were evaluable. 5FU was administered as a loading course, 750 mg/m2 daily for 5 days by continuous infusion followed by weekly bolus therapy, rIFN alpha-2a, 9 MU, was administered subcutaneously three times per week. Of 17 previously untreated patients evaluable for response, 13 achieved a response. Three patients had disease progression. No previously treated patients had a major response. There was one death clearly related to therapy, an event preceded by watery diarrhea and neutropenic sepsis. Other toxicities were reversible and responded to dose reduction. With a median follow-up of 16+ months, median survival has not been reached among the previously untreated patient cohort. We conclude that the combination of 5FU and rIFN alpha-2a is an active regimen against disseminated colorectal cancer in previously untreated patients.
Inhibition of Deoxynucleotide-Polymerizing Enzyme Activities of Human Leukemia Lymphoblasts and Simian Sarcoma Virus by Tilorone and Thirteen of Its Analogs 2
Authors: Richard A. DiCioccio, B. I. Sahai Srivastava
Journal: JNCI Journal of the National Cancer Institute (1978)

Tilorone, which is 2,7-bis[2-(diethylamino)ethoxy)- 9H-fluoren-9-one dihydrochloride, and 13 of its analogs inhibited human cellular DNA polymerases α and β assayed with activated DNA as template and also cellular DNA polymerase γ and DNA polymerase from simian sarcoma virus assayed with poly(A)- (dT)12-1ϰ as template. Terminal deoxynucleotidyltransferase (TdT), which has no template requirement, was not inhibited by any of the 14 compounds when d(A)12-1ϰ or d(G)12-1ϰ was used as initiator. Three compounds did not inhibit TdT assayed with activated DNA as Initiator, but 11 compounds did, and these 11 compounds were generally less inhibitory to TdT than to the other DNA polymerases. The three compounds that did not inhibit TdT assayed with activated DNA but did inhibit the other DNA polymerases will be useful in the characterization of TdT activity. Modifications of the polycyclic ring structure of tilorone and the kinds of substituent groups attached to the ring structures influenced the degree of inhibition of all enzymes.
Estimated Lifetime Medical and Work-Loss Costs of Emergency Department–Treated Nonfatal Injuries — United States, 2013
Authors: Curtis Florence, Tamara Haegerich, Thomas Simon, Chao Zhou, Feijun Luo
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

A large number of nonfatal injuries are treated in U.S. emergency departments (EDs) every year. CDC's National Center for Health Statistics estimates that approximately 29% of all ED visits in 2010 were for injuries. To assess the economic impact of ED-treated injuries, CDC examined injury data from the National Electronic Injury Surveillance System--All Injury Program (NEISS-AIP) for 2013, as well as injury-related lifetime medical and work-loss costs from the Web-Based Injury Statistics Query and Reporting System (WISQARS). NEISS-AIP collects data from a nationally representative sample of EDs, using specific guidelines for recording the primary diagnosis and mechanism of injury. Number of injuries, crude- and age-specific injury rates, and total lifetime work-loss costs and medical costs were calculated for ED-treated injuries, stratified by sex, age groups, and intent and mechanism of injury. ED-treated injuries were further classified as those that were subsequently hospitalized or treated and released. The rate of hospitalized injuries was 950.8 per 100,000, and the rate of treated and released injuries was 8,549.8 per 100,000. Combined medical and work-loss costs for all ED-treated injuries (both hospitalized and treated and released) were $456.9 billion, or approximately 68% of the total costs of $671 billion associated with all fatal and ED-treated injuries. The substantial economic burden associated with nonfatal injuries underscores the need for effective prevention strategies.
Practical wisdom: A qualitative study of the care and management of non-invasive ventilation patients by experienced intensive care nurses
Authors: Dorthe Soerensen, Kirsten Frederiksen, Grøfte Thorbjørn, Kirsten Lomborg
Journal: European Respiratory Journal (2014)

Introduction: Treatment success for patients on non-invasive ventilation remains challenging. Understanding the reasoning and actions of experienced nurses that care for patients with non-invasive ventilation can identify how nurses contribute to treatment success, and this information can be used to train less experienced nurses to provide excellent care.

Design: Qualitative descriptive study. A secondary analysis on data of qualitative participant observations during non-invasive ventilation treatment and additional 6 interviews with experienced ICU nurses was carried out in 2012.

Results: The experienced nurses exhibited 'practical wisdom'. Each could read yet stay alert to the patient's condition and respond to any changes. Conceptualisation of the complexities in nurses' reasoning and actions illustrated their tendency to separate problematic situations into three interrelated components: (1) achieving non-invasive adaptation, (2) ensuring effective ventilation, and (3) responding attentively to patients' perceptions of non-invasive ventilation. Each component comprises a set of nursing reasoning and actions that experienced nurses use to achieve treatment success.

Conclusions: Understanding how experienced nurses think and act during non-invasive ventilation care may help optimize continuing professional development and help educate junior nurses.
The enduring effects of psychodynamic treatments vis-à-vis alternative treatments: A multilevel longitudinal meta-analysis
Authors: D. Martin Kivlighan, Simon B. Goldberg, Maleeha Abbas, Brian T. Pace, Noah E. Yulish, Joel G. Thomas, Megan M. Cullen, Christoph Flückiger, Bruce E. Wampold
Journal: Clinical Psychology Review (2015)
Abstract 12047: Model of End-Stage Liver Disease Scoring in Patients With Acute Decompensated Heart Failure
Authors: Michael Scholfield, Matthew Schabath B Matthew, Maya Guglin
Journal: Circulation (2013)

Study Purpose: The goal of this analysis was to assess the association between the Model of End-stage Liver Disease-eXcluding INR (MELD-XI) scoring system and clinical outcomes among patients admitted with acute decompensated heart failure (ADHF). Methods: We conducted a post hoc analysis using data from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial, a large multicenter trial of patients treated for ADHF. Among 346 individuals, we analyzed the association between admission MELD-XI scores and a composite endpoint of death, re-hospitalization, or heart transplant (Htx). Baseline MELD-XI scores were categorized by tertile values (≤27.4 vs. ≥27.4 to ≤33.2 vs. ≥33.2) and by dichotomization (≤39 vs. ≥39). Results: Patients in the highest tertile of MELD-XI scores exhibited a significantly increased risk (Hazard Ratio [HR]=1.32; 95% CI 1.11-1.58) for re-hospitalization/death/Htx compared to the first two tertiles (figure 1). When the MELD-XI da...