tbuckley/cabot-search huggingface dataset:
Diagnostic performance of the non-contacting device SleepMinder in diagnosis of sleep apnea
Authors: Gerhard Weinreich, Philip de Chazal, Yi Wang, Helmut Teschler
Journal: European Respiratory Journal (2011)

Background: Due to the unattended design screening of sleep-disordered breathing (SDB) has an error rate of 5-30%. Possible reasons for the screening failure are off-centered or unfixed sensors. Therefore often another screening is mandatory which is both expensive and impeding for the patient. In order to minimise screening failure it is desirable to develop non-contacting screening devices.

Methods: In 30 patients (5 no SDB, 19 obstructive sleep apnea, 6 central sleep apnea) we studied the diagnostic accuracy of SleepMinder (Biancamed, Dublin, Ireland) that was placed approx. 1m from the patient. SleepMinder emits a very weak electromagnetic radiation (factor 10-100 less compared to common household devices) and detects thorax and abdomen movement by measuring the Doppler effect. The diagnostic accuracy was validated against respiratory inductive plethysmography (RIP) in gold standard polysomnography (PSG).

Results: Apnea-hypopnea index (AHI) of SleepMinder correlated well with PSG-AHI on simultaneous application (r=0.90, p 15/h and SleepMinder-AHI cut-off >13.4/h, sensitivity was 77.3% and specificity was 100%. Furthermore, SleepMinder correlated with PSG regarding total sleep time (r=0.59, p=0.001), sleep efficiency (r=0.49, p<0.006) and time to sleep (r=0.41, p=0.03).

Conclusions: This study showed that SleepMinder, a non-contacting screening device, detects sleep apnea with sufficient diagnostic accuracy. Moreover, SleepMinder correlates with total sleep time, sleep efficiency and time to sleep.
Abstract 9900: Implantation of Adipose-Derived Regenerative Cells Enhances Lymphangiogenesis and Improves Secondary Lymphedema
Authors: Yuuki Shimizu, Satoshi Shintani, Rei Shibata, Yusuke Izumi, Yasuhiro Ogura, Masakazu Ishii, Toyoaki Murohara
Journal: Circulation (2011)

Introduction: Secondary lymphedema often occurs as a complication of surgery or radiotherapy for cancer. Although it deteriorates patient's quality of life, there are few therapeutic options. We previously reported that implantation of adipose-derived regenerative cells (ADRCs) augmented neovascularization. Accordingly, we tested our hypothesis that ADRCs implantation promotes lymphangiogenesis and improves secondary lymphedema. Methods: ADRCs and bone-marrow mononuclear cells (BM-MNCs) were isolated from C57BL/6J or GFP-transgenic mice. We established a modified model of mouse tail lymphedema, and mice were randomly divided into four groups (ADRCs implantation (2×10 6 /mouse), BM-MNCs implantation(2×10 6 /mouse), recombinant VEGF-C injection(4μ g/mouse), or PBS injection). Real time RT-PCR and ELISA were performed at postoperative day 5. Four weeks after implantation, tail diameter was measured and histological analysis was performed to detect new lymphatic vessels using ant-LYVE-1 antibody. In vitro study, we performed migration and proliferation assay of human lymphatic endothelial cells (hLECs), which were stimulated by ADRCs conditioned medium (ADRC-CM). In addition, we measured phosphorylated eNOS and Erk, which have been shown to play an important role in promoting migration and proliferation of hLECs. Results: Expression of VEGF-C mRNA at the edematous tissue and plasma VEGF-C levels were greater in the ADRC group compared to the PBS group (p&lt;0.05). Lymphedema was significantly improved in ADRCs group to the level similar to VEGF-C or BM-MNCs groups at 4 weeks after cell therapy (p&lt;0.001, vs PBS group). Moreover, lymphatic capillary density in the edematous tissue was greater in the ADRC group than in the PBS group (p&lt;0.000005). Only few GFP positive cells were incorporated into new lymphatic vessels, and most of LECs constructing lymph vessels were negative for anti-GFP-FITC mAb. In vitro, we confirmed that ADRC-CM contained VEGF-C protein. Treatment of hLECs stimulated migration and proliferation of hLECs, and which was accompanied by increased phosphorylation of eNOS and Erk. Conclusions: The implantation of ADRCs seemed to be a novel strategy for therapeutic lymphangiogenesis in secondary lymphedema.
Air Pollution and Lung Cancer
Authors: G M Böhm
Journal: BMJ (1952)

Epidemiological evidence proves conclusively that lung cancer correlates with air pollution. However, data on lung cancer death rates and smoking show that mankind accepts the risk of long-term and low-level exposure to carcinogens. As a rule, immediate benefits are sought and remote hazards ignored. Fear of atmospheric contamination by radioactive fallout seems to be the main factor for awareness of air pollution. Experimental works help us to understand physics of particle deposition in the lungs (inertial impactation, sedimentation, Brownian movement), shed light on carcinogenesis (eg, bay region theory in case of polycyclic aromatic hydrocarbons and surface charge changes regarding asbestos), show that atmospheric particulates accepted as harmless may act as co-carcinogens (eg, iron and benzo(a)pyrene) and stress the importance of in vitro researches (bacterial mutation tests, organ cultures, sister chromatid exchange system) to screen pollutants for their malignant potential and study their pathogenesis.
Analysis of phase III clinical studies for palonosetron, ondansetron, dolasetron, and granisetron in the prevention of chemotherapy-induced nausea and vomiting (CINV).
Authors: S. Y. Barbour, G. R. Morrow, R. Ahmed, G. Ballinari, M. D. Thorn, D. Cox, L. S. Schwartzberg
Journal: Journal of Clinical Oncology (2011)

9091 Background: Controlling CINV is integral to treatment success in cancer patients. Palonosetron HCl (PALO) is a potent 5-HT3 receptor antagonist with a longer t½ & a distinctly different receptor binding profile compared to 1st generation 5-HT3 receptor antagonists (1st 5HT3-RA). Methods: We conducted an analysis of 4 multicenter, phase III, randomized, double-blind, parallel & active comparator studies to assess the comparative safety & effectiveness of single IV doses of PALO 0.25mg / 0.75mg to 1st 5HT3-RAs ondansetron 32mg, dolasetron 100mg, & granisetron 3mg in the prevention of CINV. Results: Pooled patient-level data was used from all 4 phase III clinical studies in CINV. The primary efficacy assessment was a comparison of complete response (CR), defined as no emetic episode & no rescue medication for 0-24hrs (acute), >24-120hrs (delayed), & 0-120hrs (overall) using a logistic regression model with terms for PALO 0.25, PALO 0.75, HEC, MEC, Japanese study, Breast Cancer, Lung Cancer, & interaction terms for Breast Cancer & Lung Cancer with PALO. A comparative descriptive safety assessment was also conducted. A total of 2969 patients were included in the analysis-PALO 0.25mg, n=609; PALO 0.75mg, n=1182; & 1st 5HT3-RA, n=1178. Significantly higher CR rates were demonstrated for all PALO doses vs. 1st 5HT3-RA during the acute (0-24hr) phase, OR=0.89; p<0.01; delayed (>24-120hr) phase, OR=0.81, p<0.0001; & overall (0-120hr) phase, OR=0.81, p<0.0001. The adverse event (AE) profile of all doses of PALO was similar to 1st 5HT3-RA in all trials, with up to 96.8% of patients reporting an AE. The incidence of treatment-related AEs was also similar across trials; PALO 0.25mg, up to 20.5%; PALO 0.75mg, up to 28.8%; & 1st 5HT3-RA, up to 32.2%. The most notable TEAEs were constipation (PALO 0.25mg, up to 4.5%; PALO 0.75mg, up to 16.6%; 1st 5HT3-RA, up to 15.4%.) & headache (PALO 0.25mg, up to 9.7%; PALO 0.75mg, up to 12.4%; 1st Gen 5HT3-RA, up to 11.0%). Conclusions: This analysis demonstrated a similar safety profile & significantly improved CINV prophylaxis in the acute, delayed, and overall phase for palonosetron compared to 1st 5HT3-RA.
Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2+ breast cancer
Authors: L. P. Garrison, E. A. Perez, A. Dueck, D. Lalla, V. Paton, D. Lubeck
Journal: Journal of Clinical Oncology (2006)

6023 Background: The addition of trastuzumab (H) to a standard adjuvant therapy regimen (doxorubicin, cyclophosphamide, and paclitaxel; AC→T) is associated with a 52% reduction in risk (p &lt; 0.0001) of disease recurrence in patients with HER2 positive operable breast cancer (Romond et al, NEJM 2005). A cost-effectiveness analysis was performed to assess the lifetime clinical and economic implications of this important clinical finding. Methods: A Markov model with three health states (disease-free survival [DFS], recurrence, and death) was used to estimate the likely cost-effectiveness (CE) for a 50 yr old woman. Efficacy results from both trials (NCCTG N9831/NSABP B-31) were used through 4 years, and projections of time to recurrence and death were based on the literature (EBCTCG, Lancet 2005). After 4 years, annual transition probabilities to recurrence and death are assumed to be the same in both arms. Cardiotoxicity was higher with H (Perez EA, ASCO 2005). Actual total dose of H was used which was lower than scheduled dose. Incremental costs associated with addition of H to adjuvant therapy were estimated using average wholesale prices, Medicare reimbursement rates and other published data. These costs included testing for HER2 status, drug and administration costs for H, cardiac monitoring, treatment of cardiotoxicity, treatment following recurrence, and end-of-life costs for dying patients. Utility estimates were derived from the literature. Results: Over a lifetime, the cost per quality-adjusted life year gained (QALY; discount rate 3%) is $27,800, with a range of $17,900 to $39,100 under multi-way sensitivity analysis. Projected life expectancy from the Markov model is 3 years longer for H patients (19.4 v 16.4 yrs). Over a 20-year horizon, addition of H to AC→T is estimated to cost an additional $46,300 on average, with an expected gain of 1.28 QALYs-a cost/QALY of $36,100. The key drivers of CE are the cost of treatment and the improvement in DFS. Conclusion: The model projects a cost-utility ratio that is below that of many treatments used for oncology patients. The use of trastuzumab in the adjuvant setting for HER2+ breast cancer is projected to be cost-effective. [Table: see text]
<i>BRCA1</i> mutation site may associate with nuclear DNA content in <i>BRCA1</i>-associated ovarian carcinomas
Authors: M. Aghmesheh, M. Friedlander, P. J. Russell, L. Edwards, J.-L. Yang, K. Kconfab, J. M. Nesland, H. Danielson, J. Kaern, K. M. Tucker
Journal: Journal of Clinical Oncology (2004)

5040 Background:In vitro studies suggest that BRCA1 has a role in maintaining normal nuclear DNA content during cell division and that BRCA1 inactivation may result in DNA aneuploidy and cancer progression. BRCA1-linked breast cancers are more aneuploid and have a worse prognosis compared with sporadic ones. To date, there have been no published reports comparing the DNA content of BRCA1-linked ovarian cancers with sporadic cases. In this study, we investigated the potential association between BRCA1 mutations and DNA aneuploidy in BRCA1-linked ovarian cancers, and compared DNA content in BRCA1-linked tumors with matched sporadic ovarian cancers. Methods: Tumor blocks from 21 BRCA1-associated ovarian cancers were matched with 21 sporadic ovarian carcinomas for histologic subtype, patient age, stage and grade (potential factors which may influence tumor cell DNA content). Nuclei DNA content was measured by Feulgen-Schiff staining and image cytometry. Results: Out of 18 informative BRCA1-linked tumors, 6/6 (100%) with a stop codon between 1–500 aa of the BRCA1 protein had a significantly higher frequency of non-diploidy compared with those with stop codon above 500 aa (7/12, 58%)(p=0.033). A diploid peak was detected in 28% of BRCA1-associated and 33% of sporadic ovarian cancers. No significant difference between the two study groups with respect to their DNA content was observed. Conclusions: BRCA1-associated ovarian tumors with a stop codon closer to the N-terminus of the BRCA1 protein may have a higher risk of DNA aneuploidy. Although it is tempting to postulate that BRCA1 mutations resulting in a stop codon prior to 500 aa may have a worse prognosis, this needs to be formally tested in a larger, prospectively-collected population. No significant financial relationships to disclose.
Competency assessment of foundation year 1 doctors in the prescription and use of oxygen
Authors: David Tarpey, Diana Lees, Ana De Ramon
Journal: European Respiratory Journal (2011)

Introduction:  Oxygen is a commonly used drug in hospital medicine, with at least 25% of ward based patients receiving it at any one time. The UK National Patient Safety Agency (NPSA) report on oxygen therapy in hospitals (2009) detailed over 200 incidents due to inappropriate oxygen prescription, with a subsequent mandate that all oxygen should be prescribed as per national guidelines.   Aim:  To assess competence levels in Foundation year 1 (F1) doctors in oxygen prescription in our hospital trust.   Method:  A questionnaire was completed at the beginning of the F1 year, to assess understanding of oxygen prescription. This was repeated 6 months later following teaching sessions and clinical experience.   Results:  22/30 (73% of F1 doctors) took the survey with a mean score of 58% (range 40-80%). 18 (60% of the original cohort) took the test six months later with an increased mean score of 67% (range 50-80%) p0.04.  Improvement was seen in the use of emergency oxygen in patients with normal saturations (45% vs 78%), on oxygen prescription (63% vs 100%) and in the correct procedure for stopping oxygen (45% vs 55%) Persistent knowledge gaps were seen with target saturations (72% to 70%) and increasing flow rates to match patient needs (32% vs 22%).   Conclusions:  Results demonstrate a lack of knowledge of national guidance amongst junior doctors. Improvement was demonstrated following teaching sessions and clinical experience. Future training sessions should focus on areas where improvement was not seen to increase adherence to guidelines and improve patient care.
Abstract 16492: MiR-92a Controls Metabolism and Obesity
Authors: Daniela Penzkofer, Timon Seeger, Angelika Bonauer, Ariane Fischer, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Circulation (2013)

Obesity and type 2 diabetes are key risk factors for the development of coronary artery disease. MicroRNAs (miRs) are small non-coding RNA molecules, which act as negative regulators of gene expres...
Randomized, multicenter, crossover phase II trial to compare exemestane (E) vs. anastrozole (A) in postmenopausal patients (pt) with advanced breast cancer (ABC) and positive hormone receptors (HR). Final efficacy analysis of GEICAM 2001–03 study
Authors: J. Mayordomo, A. Llombart, M. Martín, A. Antón, A. Barnadas, S. Antolín, J. Alés-Martínez, I. Álvarez
Journal: Journal of Clinical Oncology (2006)

638 Background: Head-to-head comparison of a steroidal aromatase inhibitor (AI) (E) vs. a non-steroidal AI (A) with crossover at the time of progression to evaluate the sequence of administration. Principal and secondary objectives were overall response rate (ORR), clinical benefit (CB) and time to progression (TTP). Methods: Postmenopausal pt with measurable ABC and positive HR, were stratified [previous tamoxifen (tam) (yes vs. no), previous chemotherapy (ct) (yes vs. no) and stage (IIIb vs. IV)], and randomized to E (25mg/day), or A (1mg/day) until progression. As per Simon’s test, with a p1 of 25% ORR and a p0 of 10% ORR, α and β errors 0.05 and 10%, 50 pt per arm were needed. Results: 103 (51 vs. 52) pt were recruited between 2002 and 2004. Main pt characteristics: median age 70 and 73 years, 82 vs. 88% stage IV, 12 vs. 17% previous ct, 51 vs. 50% previous tam, median size of lesions of 5 vs. 4 cm, mean number of lesions of 1.4 in both arms. Most frequent site of lesions were breast (33 vs. 35%), lymph nodes (22% vs. 25%) and connective tissue (27% vs. 23%). Efficacy: For initial treatment ORR was 37% (CI95% 24–51) in arm E vs. 52% (CI95% 38–66) in arm A (p= 0.151). 47% of pt in E vs. 60% in A presented CB (p=0.202). Mean TTP for arm E was 8.1 months (m) (1.1–15.2) and for arm A was 12.1 m (6.6–17.6) (p=0.4716). 11 pt (arm E) and 12 (arm A) crossed-over after progression. Following crossover mean TTP for E was 4.4 m (3.7–5.1) and for second line A was 1.9 m (0.1–3.7) (p=0.0172). Conclusions: E and A seem to be equivalent in terms of efficacy as first treatment for postmenopausal pt with ABC and positive HR. We suggest a possible advantage of the steroidal AI, exemestane, following disease progression on the non-steroid AI anastrozole. [Table: see text]
The clinical spectrum of adult acute myeloid leukemia (AML) associated with core binding factor (CBF) translocations
Authors: F. R. Appelbaum, K. J. Kopecky, M. L. Slovak, H. M. Gundacker, M. Tallman, H. Kim, G. W. Dewald, E. Estey, H. Kantarjian, S. Pierce
Journal: Journal of Clinical Oncology (2005)

6513 Background: Although adults with AML containing CBF translocations [t(8;21) or inv(16)/t(16;16)] have a high complete response (CR) rate and improved overall survival (OS) compared to other AML patients (pts), not everyone does well. Methods: In order to better understand the spectrum of CBF-associated AML, we analyzed 373 pts with newly diagnosed CBF-related AML treated on SWOG, ECOG or MDA protocols. Results: Pts ranged in age from 16–83 (median 39) with a slight male predominance (56%). Overall, 53% of pts had inv(16) or t(16;16) while 47% had t(8;21); 58% had chromosomal abnormalities in addition to the CBF translocation. Pts with t(8;21) tended to be younger (p=0.03), have lower white counts (p<0.0001) and more often have additional chromosomal abnormalities (p<0.0001). CR was achieved in 86% of pts (95% confidence interval [CI] 82–89%) and the estimated resistant disease (RD) rate was 8% (CI 5–12%). Increasing age was the major factor associated with a decreased CR rate (p=0.0029) and increased incidence of RD (p=0.0014). OS at 10 years was 43% (CI 38–49%), and was significantly lower in older pts (p<0.0001) and those with higher peripheral blast percentage (p=0.0001). Relapse-free survival (RFS) was 40% (CI 34–46%) at 10 years and likewise was associated with age and peripheral blast percent. The treatment results did not differ significantly between pts with t(8:21) versus inv(16) and were not significantly influenced by the presence of additional chromosomal abnormalities. Conclusions: Although pts with CBF-associated AML do relatively well with 43% 10-year OS, considerable improvement is needed, particularly in older patients and those presenting with a higher percent of blasts in their peripheral blood. No significant financial relationships to disclose.
Pharmacokinetics and toxicity of intraperitoneal cisplatin combined with regional hyperthermia.
Authors: E L Zakris, M W Dewhirst, J E Riviere, P J Hoopes, R L Page, J R Oleson
Journal: Journal of Clinical Oncology (1987)

Hyperthermia (HT) potentiates in vitro cytotoxicity of cisplatin, providing a rationale for HT enhancement of cisplatin effect in vivo. In this study, regional abdominal HT was combined with intraperitoneal (IP) cisplatin in canines to characterize temperature distributions, as well as pharmacokinetics and toxicity of IP cisplatin with and without HT. Cisplatin (65 mg/m2) in normal saline was administered IP with a two-hour dwell time in ten Beagle dogs. Five of the ten dogs were randomly selected to receive concurrent regional microwave-producing HT at approximately 41.5 degrees C (IP) for a 60-minute period. Systemic temperatures in heated animals ranged from 37 degrees C to 40 degrees C; IP temperatures ranged from 39 degrees C to 44 degrees C. Initial IP temperatures ranged from 39 degrees C to 44 degrees C. Initial IP cisplatin concentrations were ten to 22 times greater than serum levels; the IP drug half-lives were 133 +/- 9 minutes and 68 +/- 15 minutes in heated and unheated dogs, respectively (P less than .001). Total concentrations of serum and urine cisplatin did not differ between the heated and unheated controls. The area under the concentration v time curve for free, ultrafilterable cisplatin in serum in units of percent minutes was 40 +/- 8 in heated and 60 +/- 7 in unheated controls (P = .006). Except for transient nausea and vomiting, no evidence of serious toxicity was observed in serum chemistries or histopathologic sections at 21 days post-treatment. Experiments involving in vitro incubation of cisplatin in normal saline were performed as a function of saline temperature; these showed that the amount of reactive cisplatin metabolites formed increased linearly with temperature by approximately 30% from 38 degrees C to 44 degrees C. This study supports the hypothesis that, with IP temperature elevation, there is an increased rate of generation and retention of reactive metabolites of cisplatin in the peritoneal cavity relative to unheated controls. In spite of these differences in pharmacokinetics, no significant toxicity was encountered. This study provides a model for treatment of IP malignancy such as ovarian carcinoma with IP cisplatin and regional HT.
An expanded study of the relationship between osteopontin, tumor pO<sub>2</sub> and prognosis in head and neck squamous cell carcinomas
Authors: D. W. Petrik, H. Cao, Y. Zhu, P. Wong, P. Sutphin, A. J. Giaccia, A. A. Koong, Q. T. Le
Journal: Journal of Clinical Oncology (2005)

5521 Background: We have previously found a correlation between osteopontin (OPN), tumor oxygenation (pO2) and prognosis in 54 patients with head and neck squamous cell carcinomas (HNSCC). Here, we expanded the study to further evaluate these relationships. Methods: Between October 1998 and March 2004, 139 patients with newly diagnosed HNSCC were prospectively enrolled in this study. Plasma OPN levels were assessed in all patients by an ELISA method. Tumor pO2 measurements were performed in 86 patients using the Eppendorf microelectrode. The relationship between plasma OPN level and tumor pO2 was determined using Spearman’s rank correlation. The associations of freedom from relapse (FFR) and overall survival (OS) with OPN, tumor pO2, and other independent variables were explored using univariate log rank tests, and confirmed with multivariate Cox proportional hazards models. The median follow up for all patients was 15.4 months (range: 1 - 70). Results: The median OPN level for the entire group was 495 ng/ml (range: 22 - 1521). There was an inverse correlation between plasma OPN levels and median tumor pO2 (rho = -0.23, p = 0.03) and a direct correlation between OPN and hypoxic fraction < 5 mmHg (rho = 0.26, p = 0.01), though the correlation coefficients were not as strong as previously observed. Two year FFR and OS for the entire group were 59% and 62%, respectively. Using a cut off value of 450 ng/ml, OPN continued to be a strong prognostic factor for FFR and OS; for patients with OPN ≤ 450 ng/ml vs. > 450 ng/ml, the 2-year FFR and OS rates were 70% vs. 49% and 78% vs. 48%, respectively (p = 0.017 and p < 0.0001). On multivariate analysis, younger age, oropharyngeal tumor location, lower T- and N-stage, and radiotherapy were significant prognostic factors for better FFR and OS; OPN was significant for OS (p = 0.004), but not for FFR (p = 0.14). Conclusions: In this expanded study, plasma OPN levels continue to correlate with tumor pO2 parameters, though the correlation was weaker. More importantly, OPN persists as a significant independent prognostic marker in HNSCC, suggesting that it is a potential target for anticancer therapy. (supported by USPHS Grant CA 67166, Kaplan Fellowship, and Alberta Cancer Board Fellowship) No significant financial relationships to disclose.