tbuckley/cabot-search huggingface dataset:
Determinants of hospital costs in community-acquired pneumonia
Authors: S. Reyes, R. Martinez, J. M. Valles, E. Cases, R. Menendez
Journal: European Respiratory Journal (2008)

Community-acquired pneumonia (CAP) has a high incidence and involves an important consumption of healthcare resources. The present authors analysed the influence of comorbidity, initial severity and complications upon the direct costs associated with hospitalised CAP patients. Direct hospitalisation costs (room cost, treatment, laboratory and diagnostic tests) were assessed in a prospective, observational study of 271 patients admitted to a hospital ward due to CAP. The mean±sd patient age was 70±15 yrs. The mortality rate was 11.1%. Complications were found in 72.3% and comorbidities in 74.9%. The median (interquartile range) total cost was \#8364;1,683 (\#8364;1,291–2,471) and the component costs were: room cost \#8364;1,286 (\#8364;857–1,714); laboratory tests \#8364;212 (\#8364;171–272); treatment \#8364;187 (\#8364;114–304); and diagnostic procedures \#8364;58 (\#8364;29–122). Complications and higher Pneumonia Severity Index increased the costs, but age and comorbidity did not. A logistic regression analysis to predict high cost (&gt;\#8364;1,683) showed that infectious (odds ratio 6.8, 95% confidence interval 1.3–36), digestive (5.9 (1.5–22.8)), pulmonary (2.6 (1.4–4.7)) and other complications (3.9 (1.8–8.4)) were independent risk factors, as were previous hospitalisation (2.3 (1.2–4.3)) and hypoalbuminaemia (2 (1.1–3.6)). Complications, hypoalbuminaemia and previous hospitalisation were the main determinants of high direct costs of hospitalisation due to community-acquired pneumonia. Neither age nor comorbidities were independently associated with cost.
Clinicopathological analysis of GATA3-positive breast cancers with special reference to response to neoadjuvant chemotherapy
Authors: N. Tominaga, Y. Naoi, K. Shimazu, T. Nakayama, N. Maruyama, A. Shimomura, S.J. Kim, Y. Tamaki, S. Noguchi
Journal: Annals of Oncology (2012)
SKUP<sup>3</sup>randomised controlled trial: polysomnographic results after uvulopalatopharyngoplasty in selected patients with obstructive sleep apnoea
Authors: Nanna Browaldh, Pia Nerfeldt, Michael Lysdahl, Johan Bring, Danielle Friberg
Journal: Thorax (2013)

<h3>Objective</h3> To assess the 6-month efficacy of uvulopalatopharyngoplasty (UPPP) compared with expectancy in selected patients with obstructive sleep apnoea syndrome (OSAS). <h3>Design</h3> A prospective single-centre randomised controlled trial with two parallel arms stratified by Friedman stage and body mass index (BMI). <h3>Participants</h3> 65 consecutive patients with moderate to severe OSAS (apnoea-hypopnoea index (AHI) ≥15 events/h sleep), BMI &lt;36 kg/m<sup>2</sup>, Epworth sleepiness scale ≥8, Friedman stage I or II. <h3>Intervention</h3> Surgical treatment with UPPP. The control group underwent UPPP after a delay of 6 months. <h3>Outcomes</h3> Changes in AHI and other polysomnography parameters at baseline compared with the 6-month follow-up. <h3>Results</h3> All patients (32 in the intervention group and 33 in the control group) completed the trial. The mean (SD) AHI in the intervention group decreased significantly (p&lt;0.001) by 60% from 53.3 (19.7) events/h to 21.1 (16.7) events/h . In the control group the mean AHI decreased by 11% from 52.6 (21.7) events/h to 46.8 (22.8) events/h, with a significant difference between the groups (p&lt;0.001). The mean time in the supine position and the BMI were unchanged in both groups. Subgroup analyses for Friedman stage, BMI group and tonsil size all showed significant reductions in AHI in the intervention group compared with controls. There were no severe complications after surgery. <h3>Conclusions</h3> This trial demonstrates the efficacy of UPPP in treating selected patients with OSAS with a mean reduction in AHI of 60% compared with 11% in controls, a highly significant and clinically relevant difference between the groups. <h3>Trial registration number</h3> NCT01659671.
Exemestane for Breast-Cancer Prevention in Postmenopausal Women
Authors: Paul E. Goss, James N. Ingle, José E. Alés-Martínez, Angela M. Cheung, Rowan T. Chlebowski, Jean Wactawski-Wende, Anne McTiernan, John Robbins, Karen C. Johnson, Lisa W. Martin, Eric Winquist, Gloria E. Sarto, Judy E. Garber, Carol J. Fabian, Pascal Pujol, Elizabeth Maunsell, Patricia Farmer, Karen A. Gelmon, Dongsheng Tu, Harriet Richardson
Journal: New England Journal of Medicine (2011)

Tamoxifen and raloxifene have limited patient acceptance for primary prevention of breast cancer. Aromatase inhibitors prevent more contralateral breast cancers and cause fewer side effects than tamoxifen in patients with early-stage breast cancer.In a randomized, placebo-controlled, double-blind trial of exemestane designed to detect a 65% relative reduction in invasive breast cancer, eligible postmenopausal women 35 years of age or older had at least one of the following risk factors: 60 years of age or older; Gail 5-year risk score greater than 1.66% (chances in 100 of invasive breast cancer developing within 5 years); prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ; or ductal carcinoma in situ with mastectomy. Toxic effects and health-related and menopause-specific qualities of life were measured.A total of 4560 women for whom the median age was 62.5 years and the median Gail risk score was 2.3% were randomly assigned to either exemestane or placebo. At a median follow-up of 35 months, 11 invasive breast cancers were detected in those given exemestane and in 32 of those given placebo, with a 65% relative reduction in the annual incidence of invasive breast cancer (0.19% vs. 0.55%; hazard ratio, 0.35; 95% confidence interval [CI], 0.18 to 0.70; P=0.002). The annual incidence of invasive plus noninvasive (ductal carcinoma in situ) breast cancers was 0.35% on exemestane and 0.77% on placebo (hazard ratio, 0.47; 95% CI, 0.27 to 0.79; P=0.004). Adverse events occurred in 88% of the exemestane group and 85% of the placebo group (P=0.003), with no significant differences between the two groups in terms of skeletal fractures, cardiovascular events, other cancers, or treatment-related deaths. Minimal quality-of-life differences were observed.Exemestane significantly reduced invasive breast cancers in postmenopausal women who were at moderately increased risk for breast cancer. During a median follow-up period of 3 years, exemestane was associated with no serious toxic effects and only minimal changes in health-related quality of life. (Funded by Pfizer and others; NCIC CTG MAP.3 ClinicalTrials.gov number, NCT00083174.).
Balance between GP and hospital doctor numbers may need to shift, says new NHS chief
Authors: A. O'Dowd
Journal: BMJ (2014)

Workforce numbers among general practitioners have not risen as quickly as those of hospital consultants despite a shift in the NHS to provide more care outside hospitals, the new head of the NHS in England has said.

Simon Stevens, chief executive of NHS England, who appeared before MPs on the parliamentary health select committee on 29 April, said that he intended to deal with the issue of GP workforce shortages soon. He also said that he expected health spending to rise between now and 2021 as long as the United Kingdom’s economy grew in that time.

As part of their inquiry into the work of NHS England, MPs asked about workforce issues in primary care. …
Screening of Obstructive Sleep Apnea Syndrome by Heart Rate Variability Analysis
Authors: Frédéric Roche, Jean-Michel Gaspoz, Isabelle Court-Fortune, Pascal Minini, Vincent Pichot, David Duverney, Frédéric Costes, Jean-René Lacour, Jean-Claude Barthélémy
Journal: Circulation (1999)

Background —Enhanced nocturnal heart rate variability (HRV) has been evoked in sleep-related breathing disorders. However, its capacity to detect obstructive sleep apnea syndrome (OSAS) has not been systematically determined. Thus, we evaluated the discriminant power of HRV parameters in a first group of patients (G1) and validated their discriminant capacity in a second group (G2). Methods and Results —In G1, 39 of 91 patients (42.8%) were identified as diseased by polysomnography, as were 24 of 52 patients (46%) in G2. Time-domain HRV variables (SD of NN intervals [SDNN], mean of the standard deviations of all NN intervals for all consecutive 5-minute segments of the recording [SDNN index], square root of the mean of the sum of the squares of differences between adjacent normal RR intervals [r-MSSD], and SD of the averages of NN intervals in all 5-minute segments of the recording [SDANN]) were calculated for daytime and nighttime periods, as well as the differences between daytime and nighttime values (Δ[D/N]). Correlations between HRV variables and OSAS status were analyzed in G1 by use of receiver-operating characteristic (ROC) curves and logistic regression analysis. By ROC curve analysis, 7 variables were significantly associated with OSAS. After adjustment for other variables through multiple logistic regression analysis, Δ[D/N]SDNN index and Δ[D/N] r-MSSD remained significant independent predictors of OSAS, with ORs of 8.22 (95% CI, 3.16 to 21.4) and 2.86 (95% CI, 1.21 to 6.75), respectively. The classification and regression tree methodology demonstrated a sensitivity reaching 89.7% (95% CI, 73.7 to 97.7) with Δ[D/N] SDNN index and a specificity of 98.1% (95% CI, 86.4 to 100) with Δ[D/N] SDNN using appropriate thresholds. These thresholds, applied to G2, yielded a sensitivity of 83% using Δ[D/N] SDNN index and a specificity of 96.5% using Δ[D/N] SDNN. Conclusions —Time-domain HRV analysis may represent an accurate and inexpensive screening tool in clinically suspected OSAS patients and may help focus resources on those at the highest risk.
Introduction
Authors: Shehan Hettiaratchy, Peter Dziewulski
Journal: BMJ (2004)

<h3>Objectives</h3> Immigrants with common mental disorders (CMDs) are reported to have a higher risk of disability pension (DP) compared with native residents; however, the reasons for this are not fully understood. This study aimed to investigate (1) differences in morbidity (3 measures) and socioeconomic status in native Swedes, ‘Western’ and ‘non-Western’ immigrants with CMDs and (2) interactions between morbidity and socioeconomic status and immigrant status regarding subsequent DP. <h3>Design</h3> The study was a prospective population-based cohort study using national register data. Crude and multivariate HRs with 95% CIs were calculated using the Cox regression (2007–2010). <h3>Participants</h3> All individuals aged 18–59 with an incident sick-leave spell due to CMDs during 2006 were included in the study (N=66 097). The study population was divided into 3 groups based on country of birth: (1) Sweden, (2) immigrants from ‘Western’ countries (EU25, Norway, Iceland, North America and Oceania) and (3) immigrants from ‘non-Western’ countries (east Europe, Africa, Asia and South America). <h3>Results</h3> Particularly, immigrants born in non-Western countries had higher levels of morbidity and lower socioeconomic status than natives (p&gt;0.001). No significant differences in the associations between specialised psychiatric and somatic care with regard to subsequent DP were found between immigrants and native Swedes. Being prescribed more than 1 type of psychiatric medication was associated with higher HRs for DP in immigrants from Western (HR 3.34; CI 2.3 to 4.9) and non-Western countries (3.6; 1.9 to 6.4) than in native Swedes (2.55; 2.3 to 2.8) (p<sub>interaction</sub>=0.003). Low education was a marginally stronger predictor for DP in non-Western immigrants than in native Swedes and Western immigrants (p<sub>interaction</sub>=0.03). <h3>Conclusions</h3> Morbidity measured by medication, but not by specialised healthcare, was a stronger predictor for DP in immigrants than in native Swedes, warranting scrutiny of differences in care and treatment in immigrants and native Swedes with CMDs.
Tumors Escape CD4+ T-cell–Mediated Immunosurveillance by Impairing the Ability of Infiltrating Macrophages to Indirectly Present Tumor Antigens
Authors: Anders Aune Tveita, Fredrik Schjesvold, Ole Audun Haabeth, Marte Fauskanger, Bjarne Bogen
Journal: Cancer Research (2015)

Abstract Tumors cells can escape cytotoxic CD8+ T cells by preventing MHC I display of tumor antigens. It is unknown how tumors evade CD4+ T-cell responses, but because many tumor cells lack MHC II expression, novel mechanisms would be required. We have investigated this issue in a model in which MHC IINEG myeloma cells secrete a monoclonal Ig containing a V region L chain (VL) epitope recognized by CD4+ T cells. Infiltrating macrophages process and present the secreted tumor antigen to Th1 cells, resulting in induction of macrophage cytotoxicity and apparent rejection of the tumor. Despite long-term tumor protection in VL-specific T-cell receptor transgenic mice, we here describe that some myeloma cells persisted in a dormant state and, eventually, formed expanding tumors. Escape tumor cells maintained their secretion of complete (H+L) monoclonal Ig with unchanged sequence, while secretion of surplus free L chain was severely diminished. Although free L chains were efficiently processed and presented by tumor-infiltrating macrophages to CD4+ T cells, complete (H+L) monoclonal Ig was not. Forced overexpression of free L chain secretion reinstated tumor rejection. These results show that tumors can escape CD4+ T-cell–mediated rejection by impairing indirect presentation of tumor antigen by infiltrating macrophages. This occurs through a novel mechanism of immunoediting, in which modulation of the quaternary structure of the secreted tumor-specific antigen reduces its immunogenicity. Cancer Res; 75(16); 3268–78. ©2015 AACR.
Surrogate Endpoint Analysis: An Exercise in Extrapolation
Authors: Stuart G. Baker, Barnett S. Kramer
Journal: JNCI Journal of the National Cancer Institute (2012)

Surrogate endpoints offer the hope of smaller or shorter cancer trials. It is, however, important to realize they come at the cost of an unverifiable extrapolation that could lead to misleading conclusions. With cancer prevention, the focus is on hypothesis testing in small surrogate endpoint trials before deciding whether to proceed to a large prevention trial. However, it is not generally appreciated that a small surrogate endpoint trial is highly sensitive to a deviation from the key Prentice criterion needed for the hypothesis-testing extrapolation. With cancer treatment, the focus is on estimation using historical trials with both surrogate and true endpoints to predict treatment effect based on the surrogate endpoint in a new trial. Successively leaving out one historical trial and computing the predicted treatment effect in the left-out trial yields a standard error multiplier that summarizes the increased uncertainty in estimation extrapolation. If this increased uncertainty is acceptable, three additional extrapolation issues (biological mechanism, treatment following observation of the surrogate endpoint, and side effects following observation of the surrogate endpoint) need to be considered. In summary, when using surrogate endpoint analyses, an appreciation of the problems of extrapolation is crucial.
A simple, fast, and accurate method of phylogenomic inference
Authors: Martin Wu, Jonathan A Eisen
Journal: Genome biology (2008)

Abstract The explosive growth of genomic data provides an opportunity to make increased use of protein markers for phylogenetic inference. We have developed an automated pipeline for phylogenomic analysis (AMPHORA) that overcomes the existing bottlenecks limiting large-scale protein phylogenetic inference. We demonstrated its high throughput capabilities and high quality results by constructing a genome tree of 578 bacterial species and by assigning phylotypes to 18,607 protein markers identified in metagenomic data collected from the Sargasso Sea.
Illness during the 2010 Super 14 Rugby Union tournament – a prospective study involving 22 676 player days
Authors: Martin Schwellnus, Wayne Derman, Tony Page, Michael Lambert, Clint Readhead, Craig Roberts, Ryan Kohler, Esme Jordaan, Robert Collins, Stephen Kara, Ian Morris, Org Strauss, Sandra Webb
Journal: British Journal of Sports Medicine (2012)

Illness accounts for a significant proportion of consultations with a team physician travelling with elite athletes.To determine the incidence, type, cause and consequences of illness in Rugby Union players participating in a 16-week tournament.8 teams participating in the 2010 Super 14 Rugby tournament Participants A cohort of 259 elite rugby players from eight teams was recruited.All players were followed daily over the 16-week competition period (22 676 player days). Each day, team physicians completed an illness log with 100% compliance. Information included the daily squad size and illness details including system affected, final diagnosis, type and onset of symptoms, training/match days lost and suspected cause.Incidence of illness (illness per 1000 player days).The incidence of illness in the cohort was 20.7/1000 player days (95% CI 18.5 to 23.1) with the highest incidence of illness in the respiratory system (6.4: 95% CI 5.5 to 7.3), gastrointestinal system (5.6: 95% CI 4.9 to 6.6) and the skin and subcutaneous tissue (4.6; 95% CI 4.0 to 5.4). Infections accounted for 54.5% of all illness and 26.1% of illness resulted in time loss of ≥1 day. In over 50% of illnesses, symptoms were present for ≥1 day before being reported to the team physician.Infective illness involving the respiratory tract and gastrointestinal tract together with dermatological illness was common in elite rugby players participating in this international tournament. A delay in reporting of symptoms >24 h could have important clinical implications in player medical care.
Thymosin α 1 activates dendritic cells for antifungal Th1 resistance through Toll-like receptor signaling
Authors: Luigina Romani, Francesco Bistoni, Roberta Gaziano, Silvia Bozza, Claudia Montagnoli, Katia Perruccio, Lucia Pitzurra, Silvia Bellocchio, Andrea Velardi, Guido Rasi, Paolo di Francesco, Enrico Garaci
Journal: Blood (2004)
Surfactant replacement therapy.
Authors: M J Kresch, W H Lin, R S Thrall
Journal: Thorax (1996)

In 1959 Avery and Mead discovered that the lungs of infants who died of hyaline membrane disease (HMD) were deficient in surfactant.1 Surfactant reduces surface tension and sta- bilises alveoli at low lung volumes and may act as an "anti-stick" or lubricant allowing the alveolar walls to remain open.2"HMD is char- acterised by progressive atelectasis and res- piratory failure in premature infants and is a major cause of morbidity and mortality in the neonatal period.56Numerous studies of the development of the pulmonary surfactant sys- tem have led to the clinical use of phospholipid composition ofhuman amniotic fluid to predict lung maturity and to the use of antenatal hormones to accelerate lung maturation.Recently, this research has culminated in successful at- tempts to treat HMD in premature infants with surfactant replacement therapy (SRT).We will begin this article with a brief review of the pulmonary surfactant system and the various types ofsurfactants used in replacement therapy.This will be followed by a review of the animal and clinical studies investigating SRT in various disease conditions.
A phase Ib/II study of XL184 (BMS 907351) with and without erlotinib (E) in patients (pts) with non-small cell lung cancer (NSCLC).
Authors: H. A. Wakelee, S. N. Gettinger, J. A. Engelman, P. A. Janne, H. J. West, D. S. Subramaniam, J. W. Leach, M. B. Wax, Y. Yaron, P. Lara
Journal: Journal of Clinical Oncology (2010)

3017 Background: MET and VEGF play important roles in the pathobiology of NSCLC, and are associated with resistance to E. XL184 is an oral, potent inhibitor of MET, VEGFR2, and RET, with antitumor activity in combination with E in NSCLC xenografts with acquired E resistance. Thus, XL184 + E may be effective in pts with acquired E resistance. Methods: Adults with previously treated advanced NSCLC received daily doses of XL184 + E in a 3 + 3 design using combination doses across 5 cohorts in 2 parallel arms (A and B). Objectives include safety, pharmacokinetics (PK), pharmacodynamics, and maximum tolerated dose (MTD) determination. RECIST response is assessed every 8 weeks. Pts with at least 2 post-baseline tumor assessments or pts who discontinued early for PD or AE were assessable for response. Results: 54 NSCLC pts have been enrolled in phase Ib, the majority had prior E. The dose levels were: arm B (75 mg XL184 + 150 mg E and 50 mg XL184 + 150 mg E (MTD) and arm A (75 mg XL184 + 100 mg E; 125 mg XL184 + 100 mg E; and 125 mg XL184 + 50 mg E). MTD determination of arm A is ongoing. Across all dose levels, 12 pts experienced at least 1 DLT: diarrhea, elevated AST, palmar-plantar erythrodysesthesia, mucositis, hypertension, hypokalemia, elevated lipase, and fatigue. Of 34 pts in safety database, most frequent frade 3/4 AEs were diarrhea (26%), fatigue (15%), dyspnea (12%), and hypoxia (9%). Preliminary PK analysis does not show evidence of DDI. Genotyping plasma tumor DNA from 28 pts revealed EGFR T790M mutations in 7 pts (25%). FISH analysis of circulating tumor cells from 7 pts revealed MET copy number gain in 2 pts (28%). Six of 36 pts assessable for response including at least 3 pts with prior E therapy had ≥ 30% reduction in tumor measurements on at least 1 post-baseline scan, including 3 with a cPR (1 with MET amplification). Prolonged SD ≥ 4 months has been observed in some pts including one pt for 9+ months and one pt with EGFR T790M. Conclusions: The overall safety and tolerability profile of XL184 + E appears acceptable without evidence of a XL184/E DDI. Encouraging clinical activity of XL184 + E was observed in a largely E pretreated population, including pts with EGFR T790M and MET amplification. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Exelixis Bristol-Myers Squibb, Exelixis, Genentech, OSI, Roche Exelixis Exelixis, Genentech
The ATM gene in the pathogenesis of mantle-cell lymphoma
Authors: S. Stilgenbauer, C. Schaffner, D. Winkler, G. Ott, E. Leupolt, M. Bentz, P. Möller, H.K. Müller-Hermelink, M.R. James, P. Lichter, H. Döhner
Journal: Annals of Oncology (2000)
Structure of the Kidney Slit Diaphragm Adapter Protein CD2-Associated Protein as Determined with Electron Microscopy
Authors: Brian D. Adair, Mehmet M. Altintas, Clemens C. Möller, M. Amin Arnaout, Jochen Reiser
Journal: Journal of the American Society of Nephrology (2014)

CD2-associated protein (CD2AP) is a multidomain scaffolding protein that has a critical role in renal function. CD2AP is expressed in glomerular podocytes at the slit diaphragm, a modified adherens junction that comprises the protein filtration barrier of the kidney, and interacts with a number of protein ligands involved in cytoskeletal remodeling, membrane trafficking, cell motility, and cell survival. The structure of CD2AP is unknown. We used electron microscopy and single particle image analysis to determine the three-dimensional structure of recombinant full-length CD2AP and found that the protein is a tetramer in solution. Image reconstruction of negatively stained protein particles generated a structure at 21 Å resolution. The protein assumed a roughly spherical, very loosely packed structure. Analysis of the electron density map revealed that CD2AP consists of a central coiled-coil domain, which forms the tetramer interface, surrounded by four symmetry-related motifs, each containing three globular domains corresponding to the three SH3 domains. The spatial organization exposes the binding sites of all 12 SH3 domains in the tetramer, allowing simultaneous binding to multiple targets. Determination of the structure of CD2AP provides novel insights into the biology of this slit diaphragm protein and lays the groundwork for characterizing the interactions between key molecules of the slit diaphragm that control glomerular filtration.