tbuckley/cabot-search huggingface dataset:
The effect of CPAP withdrawal on blood pressure in OSA: Data from three radomised-controlled trials
Authors: Esther I. Schwarz, Christian Schlatzer, Valentina A. Rossi, Christoph Nowak, Konrad E. Bloch, John R. Stradling, Malcolm Kohler
Journal: European Respiratory Journal (2014)

Background   Based on meta-analyses, the blood pressure (BP) lowering effect of continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA) is reported to be 2mmHg. This figure is derived from trials often limited by poor CPAP compliance, thus, underestimating the effect of CPAP treatment. We analysed BP data from randomised-controlled CPAP withdrawal trials which included only optimally CPAP compliant patients.   Methods   145 OSA patients on CPAP were randomised to continue therapeutic (n=62) or to withdraw CPAP (n=83) for two weeks. Morning BP was measured at home before and in hospital after sleep studies.   Results   CPAP withdrawal was associated with a return of OSA (apnoea-hypopnoea index (AHI) at baseline 2.8/h, at follow-up 33.2/h). Systolic office BP increased in the CPAP withdrawal group compared to CPAP continuation by +6.5mmHg (95%CI 2.6-10.4mmHg, p=0.001) and systolic home BP by +9.7mmHg (95%-CI 6.3-13.0mmHg, p  AHI, baseline systolic BP, statins, gender and number of antihypertensive drugs were independently associated with systolic BP change in multivariate analysis controlled for age, BMI, smoking, diabetes, and sleepiness. Change in diastolic BP was independently predicted by AHI, baseline diastolic BP, and statins.   Conclusions   Short-term CPAP withdrawal results in a clinically relevant increase in BP, which is considerably higher than in conventional CPAP trials and may be underestimated if only office BP values are used. OSA severity and baseline BP seem to be predictors of BP response to CPAP.
Mutations in LMAN1 and MCFD2 May Account for All Cases of Combined Deficiency of Factor V and Factor VIII.
Authors: Bin Zhang, Beth McGee, William C. Nichols, Hugo Guglielmone, Katherine Downes, Flora Peyvandi, Norma B. de Bosch, Arlette Ruiz-Saez, Bernard Chatelain, Marian Olpinski, Paula Bockenstedt, Wolfgang Sperl, Randal J. Kaufman, David Ginsburg
Journal: Blood (2005)
Subjective experience of illness and treatment received in depressed oncologic patients: A qualitative analysis.
Authors: B. Rodriguez Vega, P. Orgaz, G. Torres Sancho, C. Bayón Perez, A. Fernandez Liria, A. Palao Tarrero
Journal: Journal of Clinical Oncology (2010)

e19582 Background: Qualitative analysis may provide a better way to analyze the subjective experience of patients and may give important insight to guide the decision among the interventions. The goal of this study was to analyze the narrative of depressed oncologic patients and the differences between the group who received combined treatment versus the group who received antidepressant plus usual care. Methods: A qualitative research design using grounded theory was used. 72 subjects (mean age 54.6 years), predominantly female, with non-metastatic breast, lung and colon cancer and depressive disorder (DSM-IV-TR) were randomized to receive combined treatment (n = 39) or escitalopram plus usual care (n = 33).Focal discussion groups for each group of treatment were organized as a semi-structured group interview. Results: Subjects receiving combined treatment may speak more explicitly about feelings, consider that they have got learning from the experience of illness generating a change of values and perceive more support from the medical team. The words “death,” “illness” and “cancer” are used more frequently compared to the group who received usual care plus antidepressant (p<.005). Conclusions: Combined treatment in depressed oncologic patients is related to a different experience of illness in which predominates learning, resources and feelings. This study is part of the FIS PI07/90348 and PI07/90452 Investigation Project. No significant financial relationships to disclose.
Abstract 11614: Prognostic Model for Stable Coronary Artery Disease Based on 101,956 Patients From Linked Electronic Health Records
Authors: Eleni Rapsomaniki, Anoop Shah, Julie George, Liam Smeeth, Adam Timmis, Harry Hemingway
Journal: Circulation (2012)

Context: There are no validated prognostic models for stable coronary artery disease in clinical use. Objectives: We developed, validated and evaluated the clinical utility of prognostic models bas...
Impact on quality of life (QL) during chemotherapy (CT) of FEC-T compared to FEC or E-CMF: Results from the UK NCRI Taxotere as Adjuvant Chemotherapy Trial (TACT)
Authors: P. Hopwood, P. Ellis, P. Barrett-Lee, J. M. Bliss, E. Hall, L. Johnson, D. Lawrence, S. Russell, D. Cameron
Journal: Journal of Clinical Oncology (2005)

661 Background: TACT (ISRCTN79718493) randomised 4162 pts to FECx4 followed by taxotere x4 (FEC-T) v standard anthracycline regimens of similar duration (FECx8 or epirubicin x4 followed by CMFx4 (E-CMF)) in patients with operable early stage breast cancer. The primary endpoint is disease-free survival. Overall survival, acute toxicities and QL are secondary endpoints. Methods: Pts completed EORTC QLQ-C30, BR23 and Hospital Anxiety & Depression Scale (HADS) questionnaires before randomisation, before 5th & after 8th cycles of CT, and at 9, 12, 18 & 24 mths. In this report, impact of CT was compared via mean QL change scores from baseline to cycle 8. Differences in domain scores of ≥10 points are considered clinically relevant. Clinical threshold scores for HADS were applied. A significance level of α=0.01 allowed for multiple testing. Results: In a 1 yr period, 829 pts from selected centres (71% pts randomised from those centres) entered the QL study: median age 49yrs (range 27–70); 270 FEC-T v 264 FEC, 147 FEC-T v 148 E-CMF. Compliance with QL was 99% at baseline and 79% at cycle 8. FEC-T was associated with worse global QL (p=0.002 v FEC; p=0.18 v E-CMF) & decreased physical function (p=0.007 v FEC; p=0.003 v E-CMF) after cycle 8, but magnitude of differences did not appear clinically relevant. No other significant differences between regimens were found but there was a trend for FEC-T to have greater impact on QLQC30 & BR23 domains. Anxiety was high at all time points (>20% pts with HADS scores >11) and depression rates increased 3-fold from baseline to end of CT with no differences between regimens. There was a significant and clinically relevant increase in BR23 body image concerns in all regimens during CT. Conclusions: Within the context of a general negative impact of CT on QL, FEC-T had a greater impact than standard anthracycline containing CT but magnitude of differences was below that considered clinically relevant. Relationships between QL and clinician assessed toxicity will be explored. Analysis of post-treatment QL will establish if effects are observed longer term. Any QL impairment will need to be balanced against therapeutic efficacy when these data are available. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Funding from Aventis, Cancer Research UK, Pharmacia, and Roche supports The Institute of Cancer Research
Standardised mortality ratios should not be used to benchmark hospitals, study concludes:
Authors: Jacqui Wise
Journal: BMJ (2015)

Standardised mortality ratios do not provide an accurate picture of how many deaths could have been avoided and should not be used to benchmark hospitals’ quality of care, a study published in The BMJ has found.1

The research was commissioned by Bruce Keogh, after his review of 14 trusts in 2013 questioned the value of standardised mortality ratios.2 Researchers examined 3400 hospital deaths in 34 randomly selected acute hospital trusts in England in 2009 and 2012-13. Experienced doctors …
Effect of androgen-ablation and hormonal cycling on docetaxel (D) clearance in patients with metastatic prostate cancer (MPC)
Authors: S. D. Baker, H. I. Scher, J. Li, K. W. Beekman, J. Stewart, C. Collins, V. J. Sinibaldi, J. Walczak, R. Pili, M. A. Carducci
Journal: Journal of Clinical Oncology (2005)

4608 Background: D is registered for the treatment of MPC at a dose of 75mg/m2 once every 3 wks with daily low-dose prednisone (LDP). Standard treatment involves androgen-ablation (AA) therapy as maintenance with D therapy. Grade 3/4 neutropenia occurs in 32% of patients (pts) with MPC, which is approximately one-half that in lung cancer pts receiving D monotherapy at 75mg/m2. The objective was to evaluate D clearance (CL) in the presence of AA compared to cycling of testosterone (T) in patients with MPC. Methods: Twenty pts receiving AA therapy were treated with D 25–35 mg/m2 (N=16) or D 75 mg/m2 (N=4) (study 1); serial plasma samples were obtained during wk1 (last sample 168h). Ten non-castrate pts received triptorelin immediately followed by D 75 mg/m2 on d1 of wk 1, T gel was administered for 7d during wk 4, and triptorelin and D were given again on d1 of wk 5 (study 2); during wks 1 and 5, serial plasma samples were obtained (last sample 168h). D concentrations were measured using a validated LC/MS/MS method and D CL was determined by compartmental analysis. A sample size of 20 pts in each study (cycle 1) will detect an effect size of 1.5, assuming a CV% of 50% with α=0.05 and β=0.12. Results: In study 1, mean CL was 40L/h (range, 20–95L/h; CV%, 44); 1 pt receiving concurrent LDP had a CL value of 20 L/h. In study 2, CL was reduced by 48% as was the associated interpatient variation (CV%) (mean, 21L/h; range, 13–27L/h; CV%, 24); CL and CV% were similar during week 5 (mean, 20L/h; range, 11–28L/h; CV%, 27). D clearance will be determined in 10 additional pts on study 2. T plasma concentrations are pending. Conclusions: Pts with non-castrate T concentrations undergoing rapid hormonal cycling have reduced D CL in the range of values in pts with moderate liver impairment (Baker SD Proc ASCO, 2004) and may require a reduced D dose. Pts with castrate T concentrations resulting from AA therapy have increased D CL which may account for, in part, the reduced incidence of grade 3/4 neutropenia in pts with MPC. Optimal dosing for docetaxel in MPC should be explored. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis
BMA attacks government for “chasing headlines” instead of tackling NHS problems
Authors: Matthew Limb
Journal: BMJ (2015)

The BMA has accused ministers of alienating doctors and attacking their professionalism in a fierce critique of the government’s first 100 days in office.

The BMA’s chair of council, Mark Porter, said that the government had been “chasing headlines” since its general election win in May 2015 rather than tackling the country’s health problems. Porter said on 15 August that the government’s efforts so far had been wrongly focused and were characterised by “rhetoric at the expense of detail.”

He said, “We have seen no detail on how the £22bn [€31bn; $34bn] black hole in NHS finances in England is going to be closed, no definition about seven day services, and an apparent intention to water down safeguards for patients and …
Inhibition of Human Plasmacytoma Cell Growth by a Novel JAK Kinase Inhibitor.
Authors: Renate Burger, Steven Legouill, Yu-Tzu Tai, Reshma Shringarpure, Klaus Podar, Laurence Catley, Pierfrancesco Tassone, Paola Neri, Teru Hideshima, Dharminder Chauhan, Jordan S. Fridman, Kenneth C. Anderson
Journal: Blood (2004)
Immunotoxins: a clinical review of their use in the treatment of malignancies.
Authors: A A Hertler, A E Frankel
Journal: Journal of Clinical Oncology (1989)

Immunotoxins are a new class of antitumor agents consisting of tumor-selective ligands (generally monoclonal antibodies [MoAbs]) linked to highly toxic protein molecules that have been modified to remove their normal tissue-binding domains. These immuno-conjugates combine the potency of the parent toxin with the specificity of the attached ligand. Toxins used in the construction of immunotoxins belong to a group of peptides that catalytically inhibit the elongation step of protein synthesis, and include ricin, abrin, pokeweed antiviral protein, gelonin, Pseudomonas exotoxin A, diptheria toxin, and alpha-sarcin. To synthesize immunotoxins, the normal cell-binding function must be removed by chemical cleavage or modification, or in the case of toxins that have been cloned, genetic engineering used to delete amino acids critical to cell binding. Covalent linkage of toxin to ligand generally involves a disulfide or thioether bond, though recently, recombinant toxin molecules with ligands that are genetically engineered into the protein have been made. The most successful clinical application of immunotoxins has been in the depletion of T cells from allogeneic bone marrow grafts to prevent graft-versus-host disease (GVHD). Clinical trials have been conducted using immunotoxins for the systemic treatment of chronic lymphocytic leukemia (CLL), GVHD, and selected solid tumors. With the possible exception of GVHD, responses have been limited. Obstacles have included rapid systemic clearance, poor delivery to extravascular tumor deposits, and humoral immune responses to the immunotoxin. Research to overcome these problems is in progress and should lead to a better definition of the role of immunotoxins in the therapy of malignancies.
Outcome of colorectal liver metastases vanishing under chemotherapy and finally missing after surgery.
Authors: S. Gaujoux, D. Goéré, P. Misitano, P. Burtin, F. Dumont, V. Boige, D. Malka, C. Dromain, M. Ducreux, D. Elias
Journal: Journal of Clinical Oncology (2010)

3548 Background: Complete pathological response of colorectal liver metastases (CRLM) after chemotherapy is a rare phenomenon. Furthermore, complete clinical response does not mean complete pathological response, and does not mean cure. However, CRLM may disappear on preoperative imaging studies and become undetectable during hepatectomy, hence left in place and considered as missing CRLM. The aim of this study was to assess the long-term outcome of such missing CRLM. Methods: Between 1999 and 2007, among 523 patients operated for CRLM, missing CRLM were observed in 27 patients (5.1%). All of these patients received preoperative chemotherapy. Hepatic arterial infusion (HAI) of oxaliplatin associated to systemic 5-FU was administrated in 21 patients (10 before hepatectomy and 11 after). Hepatic resection was performed at least 3 months after CRLM vanishing on imaging. Results: These 27 patients initially presented with 286 LM (mean number of LM per patient: 10.6, range: 2-42). Among the 128 vanishing CRLM resected because still detectable during surgery, a complete pathologic response was observed in 29% of cases (n = 37). Overall, 158 missing CRLM were left in place in 27 patients (range per patient: 1 to 37). After a median follow-up of 56 months (15-129), hepatic recurrence was diagnosed in 13 patients (48%), and was significantly lower in patients who received adjuvant HAI compared to others (18% vs. 69%, p = 0.028). Recurrence occurred on the site of missing CRLM in 7 (26%) patients, including only one of the 11 patients who received adjuvant HAI. The overall 5-year survival rate of these highly chemosensitive patients was 85%. Conclusions: Vanishing but not missing metastases are still viable in 71% of cases. Vanishing and missing CRLM are definitively cured in 74% of cases. These excellent results are likely to be due to patient selection (on the duration of response to chemotherapy) and to the administration of adjuvant HAI oxaliplatin. No significant financial relationships to disclose.
LPS-activated dendritic cell vaccine in combination with immunomodulatory dose of cytoxan in patients with stage IV melanoma: Phase I/IIa clinical trial.
Authors: A. K. Palucka, H. Ueno, J. W. Fay, J. Banchereau
Journal: Journal of Clinical Oncology (2010)

TPS313 Background: Our studies demonstrate that patients with stage IV melanoma who undergo DC vaccination mount an immune response to tumor antigens presented on the vaccines. However, only a fraction of patients experience durable clinical responses (∼10-15% CR and PR combined). Two immune parameters appear linked to clinical outcome: 1) objective clinical response is associated with induction of melanoma-specific effector cells; and 2) all patients display melanoma-specific Tregs that may counteract effector cells. Thus, we need to identify the next generation DC vaccines able to tilt the balance toward strong effector cells that can overcome Tregs control and combination therapies that would permit to further limit Tregs. Our pre-clinical results demonstrate that LPS (TLR4 ligand) is superior to poly I:C (TLR3) and/or a mixture of inflammatory cytokines in priming IFN-DCs to secrete IL12p70 upon interaction with T cells. LPS-activated IFN-DCs loaded with killed allogeneic melanoma cells induce stronger proliferation of autologous CD8+ T cells. Thus, such vaccine is expected to induce stronger and more diverse immune responses in patients, thereby leading to better clinical outcomes. Methods: We have initiated a phase I/II clinical trial (IRB #006-025; BB-IND #12919) enrolling patients with stage IV melanoma. Patients receive seven injections of DC vaccine generated from monocytes by culturing with GM- CSF and Type I interferon, loaded with killed allogeneic Colo829 melanoma cells and activated with lipopolysaccharide (LPS). Patients receive cyclophosphamide 300 mg/m2, administered intravenously 24 hours prior to DC vaccinations #1, 3, 5, 6 and 7. The trial is based on an initial toxicity evaluation in the first 10 patients on top of a 2-stage response rule–1/19 to continue and 5/30 to accept. The trial is expected to accrue a total of 33 subjects. The primary endpoints of this trial are the rate of objective clinical response and the safety/feasibility of the vaccination preparation. To date 21 patients have been accrued of which 18 received DC vaccinations. No significant financial relationships to disclose.
Ex vivo assay prediction of progression free interval following platinum chemotherapy in primary ovarian cancer
Authors: A. Nickles Fader, J. Comerci, J. Kelley, H. Schellhas, S. Hosford
Journal: Journal of Clinical Oncology (2005)

5098 Background: The purpose of this study was to determine the correlation between an ex-vivo cell based assay prediction of sensitivity to platinum and progression free interval (PFI) following platinum based chemotherapy in women with ovarian cancer. Methods: We conducted an IRB-approved retrospective study of 84 patients (pts.) with Stage II-IV primary epithelial ovarian cancer from 3 institutions whose tumors had been tested with the ChemoFx assay between 5/00 and 11/03. All pts had been treated with platinum-based (carboplatin, cisplatin) chemotherapy. Results: The hazard ratio (HR) for progression of pts. with assay-predicted platinum resistance was 2.9 times that of patients with non-resistant tumors (p<0.007). Graded prediction of response (resistant, intermediate, and sensitive) was also significantly related to outcome. The HR for progression of pts. with platinum resistant tumors was 2.9 (p=0.009) and 5.9 (p=0.10) times respectively that of pts. whose tumors were intermediately sensitive or sensitive to platinum therapy ex-vivo. In the cohort of patients with Stage III disease, the resistant group had HRs of 4.1 and 7.7, respectively, compared to pts. in the intermediate (p=0.0006) and sensitive (p=0.05) groups. A trend toward increased survival according to assay prediction was also observed. Conclusions: Ex-vivo chemosensitivity assay assessment of response to platinum was predictive of clinical outcome, measured by PFI, following platinum-based chemotherapy in women with primary ovarian cancer. These findings suggest the incorporation of chemosensitivity assay information into treatment planning has potential to improve outcome in women with ovarian cancer. No significant financial relationships to disclose.
Prediction of response and progression in multiple myeloma (MM) with serum-free light chains (sFLC): Corroboration of the International Myeloma Working Group (IMWG) criteria
Authors: R. N. Khoriaty, M. A. Hussein, J. Lally, M. Kelly, M. Kalaycio, R. Baz
Journal: Journal of Clinical Oncology (2007)

8047 Background: The sFLC assay was proposed as a tool for the assessment of response in patients with non-secretory or oligosecretory MM and patients with primary amyloidosis. Response and progression criteria have been proposed by the IMWG, but have not been thoroughly validated. Methods: Electronic records of patients (pts) with MM enrolled in various clinical trials at the Cleveland Clinic between 4/2004 and 12/2006 were reviewed. Response to treatment and progression were assessed using the European Blood and Bone Marrow Transplantation (EBMT) criteria for all pts. sFLC responses were defined per IMWG criteria: response (R, decrease in the difference between the involved and uninvolved light chain by greater than 50%), progression (P, increase in the difference between the involved and uninvolved light chain by greater than 25%), and stable disease (SD, not meeting the criteria for either R or P). sFLC responses were assessed in pts with involved FLC =10 mg/dL (=100mg/L) per the IMWG criteria. Results: 89 pts were identified. The median age was 61 years (range 41–87) and 58 pts were males. The involved light chain was kappa in 67 pts (75%), and lambda in the remainder. By EBMT criteria, 4 pts had a complete response, 22 a partial response, 34 stable disease, 26 progressive disease and 3 were inevaluable. Only 43/89 pts (48%) had an involved sFLC=10mg/dL; of which 14 had R, 8 had SD, 18 had P, and 3 were inevaluable. Table 1 reviews the test characteristics for sFLC assay for the prediction of response or progression. Conclusions: sFLC reliably predicts response and progression in MM pts. However, half the pts had an involved sFLC that would not be considered evaluable by IMWG, which limits its potential use. No significant financial relationships to disclose. [Table: see text]