tbuckley/cabot-search huggingface dataset:
The UN Commission on Life Saving Commodities 3 years on: global progress update and results of a multicountry assessment
Authors: Paul M Pronyk, Bennett Nemser, Blerta Maliqi, Nora Springstubb, Diana Sera, Rouslan Karimov, Elizabeth Katwan, Benedicte Walter, Pascal Bijleveld
Journal: The Lancet Global Health (2016)

<h2>Summary</h2><h3>Background</h3> In September, 2012, the UN Commission on Life Saving Commodities (UNCoLSC) outlined a plan to expand availability and access to 13 life saving commodities. We profile global and country progress against these recommendations between 2012 and 2015. <h3>Methods</h3> For 12 countries in sub-Saharan Africa that were off-track to achieve the Millennium Development Goals for maternal and child survival, we reviewed key documents and reference data, and conducted interviews with ministry staff and partners to assess the status of the UNCoLSC recommendations. The RMNCH fund provided short-term catalytic financing to support country plans to advance the commodity agenda, with activities coded by UNCoLSC recommendation. Our network of technical resource teams identified, addressed, and monitored progress against cross-cutting commodity-related challenges that needed coordinated global action. <h3>Findings</h3> In 2014 and 2015, child and maternal health commodities had fewer bottlenecks than reproductive and neonatal commodities. Common bottlenecks included regulatory challenges (ten of 12 countries); poor quality assurance (11 of 12 countries); insufficient staff training (more than half of facilities on average); and weak supply chains systems (11 of 12 countries), with stock-outs of priority commodities in about 40% of facilities on average. The RMNCH fund committed US$175·7 million to 19 countries to support strategies addressing crucial gaps. $68·2 million (39·0%) of the funds supported systems-strengthening interventions with the remainder split across reproductive, maternal, newborn, and child health. Health worker training ($88·6 million, 50·4%), supply chain ($53·3 million, 30·0%), and demand generation ($21·1 million, 12·0%) were the major topics of focus. All priority commodities are now listed in the WHO Essential Medicines List; appropriate price reductions were secured; quality manufacturing was improved; a fast-track registration mechanism for prequalified products was established; and methods were developed for advocacy, quantification, demand generation, supply chain, and provider training. Slower progress was evident around regulatory harmonisation and quality assurance. <h3>Interpretation</h3> Much work is needed to achieve full implementation of the UNCoLSC recommendations. Coordinated efforts to secure price reductions beyond the 13 commodities and improve regulatory efficiency, quality, and supply chains are still needed alongside broader dissemination of work products. <h3>Funding</h3> Governments of Norway (NORAD) and the UK (DFID).
Abstract 12624: Increased Level of T Cell Specific Chemokines Revealed the Existence of T Cell Driven Inflammation in Human Hypertension
Authors: Jong-Chan Youn, Sungha Park, Jino Lee, Hee Tae Yu, Eui-Cheol Shin, Beom Jin Lim, Jaewon Oh, Sang-Hak Lee, Seok-Min Kang, Yangsoo Jang
Journal: Circulation (2011)

Background: Recently pathogenic role of T cell in hypertension development are well documented in animal study. However, it is not well known the existence and the characteristics of T cell driven ...
Effects of formoterol on TGF-β1 induced factors of extracellular matrix composition
Authors: Christopher Lambers, Leopold Stiebellehner, Bernhard Burian, Petra Binder, Ventzislav Petkov, Lutz-Henning Block
Journal: European Respiratory Journal (2011)

Introduction: COPD is characterised by chronic airway inflammation resulting in extensive airway remodelling. The origin of the remodelling pathology in COPD is unknown and may result from increased EMT (epithelial-mesenchymal transition). EMT is a process which is mediated by hypoxia and several growths factors, such as transforming growth factor-beta (TGF-β1). Formoterol is a long acting beta2 agonist which can exert antiinflammatory effects by the regulation of intracellular cAMP levels. The aim of our study was to determine if formoterol can modulate down-stream mediators of EMT by cAMP induction.

Methods: Human bronchial smooth muscle cell culture was performed using standard protocols.Cells were stimulated with Formoterol (10-10 to -6 M), Dideoxyadenosin (DDA, 100μM), and/or TGF-β1 (5ng/ml); Forskolin was used as a positive control. cAMP measurement was performed by ELISA (at 1, 3 and 6 hours).CTGF, Collagen 1A1 (Col1) and Collagen4 (Col4) mRNA transcription was measured by quantitative real time PCR (18S mRNA served as reference gene). All experiments were performed as triplicates.

Results: Formoterol significantly increased intracellular cAMP after 1, 3 and 6 hours compared to untreated cells, whereas the maximum effect was observed after 1 hour. The cAMP increase was effectively blocked by the addition of DDA at any time point. After 24 hours, Formoterol significantly reduced TGF-β1 stimulated Col1 and CTGF but not Col4 mRNA transcription. The addition of DDA reversed this effect for Col1 but not for CTGF.

Conclusion: Treatment with formoterol resulted in a decrease of TGF-β1 induced mediators of extracellular matrix composition. These new findings suggest a potential role for formoterol in EMT.
Prevention of chemotherapy-induced delayed nausea and vomiting with aprepitant in patients recieving highly emetogenic-five day cisplatin regimens
Authors: A. J. Joshi, H. Singh, S. Chawla
Journal: Journal of Clinical Oncology (2007)

14125 Background: It has been shown that addition of the NK 1 receptor antagonist aprepitant to 5HT 3 antagonist plus dexamethasone is more effective than just the 5HT 3 antagonist plus dexamethasone for prevention of acute and delayed emesis due to high dose cisplatin and also that this effect lasts for multiple cycles. This study evaluated whether the antiemetic efficacy of aprepitant could be sustained for 5 day cisplatin regimens. Methods: Patients receiving cisplatin 20mg/m2/day for 5 days (PEB and TCF regimens ) were randomized to one of the following two regimens: (1) aprepitant 125 mg 1 hour before cisplatin on day 1 and aprepitant 80 mg on days 2 and 3 (n = 17); (2) placebo before cisplatin on days 2 to 7 (n = 19). All groups received ondansetron 32 mg and dexamethasone 20 mg before cisplatin, and dexamethasone 8 mg on days 2 to 7. The primary end point was complete response (no emesis and no rescue therapy) over 7 days following cisplatin in up to six cycles analyzed by a modified intent-to-treat approach. Secondary end point was evaluated using Functional Living Index-Emesis questionnaire. Treatment comparisons were made using logistic regression models and P value calculated using the chi square test due to small sample size. Results: In the acute period, 83% and 56% of patients were without emesis in groups I and II, respectively (P &lt; .01 for group I v group II). In the delayed period upto day 5, the proportion of patients without emesis in groups I and II, was 59% and 32%, respectively (P &lt; .01 for groups I v group II). In the extended period day 6 and 7 the proportion of patients without emesis in groups I and II was 50% and 38% respectively (P&lt; .01 for groups I v II). The distribution of nausea scores in the delayed period beyond day 5 was lower when comparing group I with group II (P &lt; .05 for days 6 and 7). Two serious adverse events of diarrhea were probably attributed to aprepitant. Conclusions: Once daily oral administration of aprepitant was effective and superior in reducing delayed emesis and nausea after 5 days cisplatinum regimen when added to 5HT3 antagonist plus dexamethasone. This benefit persists upto day 7. Confirming and extending previous results aprepitant should be used in triple combination in patients receiving 5 day cisplatin regimens. No significant financial relationships to disclose.
Sequential Use of Treatment Options in Advanced Renal-Cell Carcinoma (RCC): A Retrospective Analysis of 42 Patient Cases
Authors: L. Derosa, L. Galli, A. Fontana, E. Biasco, R. Marconcini, C. Cianci, A. Farnesi, F. Orlandi, A. Falcone
Journal: Annals of Oncology (2012)
CD137 stimulation of natural killer cells to enhance the antilymphoma activity of rituximab.
Authors: H. E. Kohrt, R. Houot, M. Goldstein, K. Weiskopf, L. Chen, T. Tedder, R. Levy
Journal: Journal of Clinical Oncology (2010)

8068 Background: Rituximab, a monoclonal antibody (mAb) directed against CD20, has significantly improved the outcome of patients with lymphoma. Antibody-dependant cell-mediated cytotoxicity (ADCC), mediated largely by natural killer (NK) cells, is thought to play an important role in rituximab's efficacy. In the current study, we hypothesized that the antilymphoma activity of rituximab could be enhanced by stimulation of NK cells with an anti-CD137 agonistic mAb. CD137 (4-1BB) is a costimulatory molecule expressed on a variety of activated immune cells, including T and NK cells. Methods: Rituximab-induced upregulation of CD137 on NK cells was assessed using lymphoma cell lines and primary lymphoma patient samples. In vitro NK cell degranulation and cytotoxicity were assessed by CD107a mobilization and chromium release. A murine lymphoma tumor model targeted by mouse anti-mouse CD20 mAb was used to assess in vivo synergy of anti-CD20 and anti-CD137 mAbs. Results: Using human primary lymphoma samples, we found that, while resting human NK cells do not express CD137 at baseline, these cells highly upregulate CD137 when encountering rituximab-coated tumor B cells. Furthermore, anti-CD137 agonistic mAb significantly enhances rituximab-induced NK cell degranulation and cytotoxicity as measured by CD107a mobilization (p=0.006) and chromium release (p=0.01). In a murine lymphoma model, anti-CD137 mAb significantly enhances anti-tumor activity of anti-CD20 mAb leading to complete tumor resolution (p<0.001) and prolonged survival (p=0.048). This synergistic effect is dependent upon sequential administration of anti-CD20 mAb followed by anti-CD137 mAb (p=0.027). Consistent with this observation, we show that in vivo administration of anti-CD20 mAb induces upregulation of CD137 on mouse NK cells (p=0.001), allowing subsequent targeting with anti- CD137 mAb. Additionally, NK cell depletion completely abrogates the therapeutic effect of anti-CD20 plus anti-CD137 mAb combination (p<0.001). Conclusions: Our results support a novel, sequential antibody approach to enhance rituximab's efficacy in patients with B cell malignancies by stimulation of rituximab-activated NK cells with anti-CD137 mAb. No significant financial relationships to disclose.
Readmissions, Observation, and the Hospital Readmissions Reduction Program
Authors: Rachael B. Zuckerman, Steven H. Sheingold, E. John Orav, Joel Ruhter, Arnold M. Epstein
Journal: New England Journal of Medicine (2016)

The Hospital Readmissions Reduction Program, which is included in the Affordable Care Act (ACA), applies financial penalties to hospitals that have higher-than-expected readmission rates for targeted conditions. Some policy analysts worry that reductions in readmissions are being achieved by keeping returning patients in observation units instead of formally readmitting them to the hospital. We examined the changes in readmission rates and stays in observation units over time for targeted and nontargeted conditions and assessed whether hospitals that had greater increases in observation-service use had greater reductions in readmissions.We compared monthly, hospital-level rates of readmission and observation-service use within 30 days after hospital discharge among Medicare elderly beneficiaries from October 2007 through May 2015. We used an interrupted time-series model to determine when trends changed and whether changes differed between targeted and nontargeted conditions. We assessed the correlation between changes in readmission rates and use of observation services after adoption of the ACA in March 2010.We analyzed data from 3387 hospitals. From 2007 to 2015, readmission rates for targeted conditions declined from 21.5% to 17.8%, and rates for nontargeted conditions declined from 15.3% to 13.1%. Shortly after passage of the ACA, the readmission rate declined quickly, especially for targeted conditions, and then continued to fall at a slower rate after October 2012 for both targeted and nontargeted conditions. Stays in observation units for targeted conditions increased from 2.6% in 2007 to 4.7% in 2015, and rates for nontargeted conditions increased from 2.5% to 4.2%. Within hospitals, there was no significant association between changes in observation-unit stays and readmissions after implementation of the ACA.Readmission trends are consistent with hospitals' responding to incentives to reduce readmissions, including the financial penalties for readmissions under the ACA. We did not find evidence that changes in observation-unit stays accounted for the decrease in readmissions.
Seizures in Children and Adolescents Aged 6–17 Years — United States, 2010–2014
Authors: Wanjun Cui, Rosemarie Kobau, Matthew M. Zack, Sandra Helmers, Marshalyn Yeargin-Allsopp
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

A seizure is a brief change in normal electrical brain activity resulting in alterations in awareness, perception, behavior, or movement. Seizures affect persons of all ages, but are particularly common in childhood. There are many causes of seizures in children, including epilepsy; high fever (febrile seizures); head injuries; infections (e.g., malaria, meningitis, and gastrointestinal illness); metabolic, neurodevelopmental, and cardiovascular conditions; and complications associated with birth (1–3). Outcomes associated with single or recurring seizures in children vary by seizure type (febrile compared with nonfebrile) and multiple risk factors (age, illness, family history, and family context). Outcomes range from no complications to increased risk for behavioral problems, epilepsy, or sudden unexpected death (3–6). No nationally representative estimates have been reported for the number of U.S. children and adolescents with seizures, co-occurring conditions, or health service utilization. To address these information gaps, CDC analyzed combined data on children and adolescents aged 6–17 years from the National Health Interview Survey (NHIS) for the period 2010–2014. Overall, 0.7% of children and adolescents (weighted national estimate = 336,000) were reported to have had at least one seizure during the preceding year. Compared with children and adolescents without seizures, a higher percentage of those with seizures were socially and economically disadvantaged. Children and adolescents with seizures had higher prevalences of various mental, developmental, physical, and functional co-occurring conditions than those without seizures; however, only 65.6% of those with seizures had visited a medical specialist (defined as a medical doctor who specializes in a particular medical disease or problem, other than an obstetrician/gynecologist, psychiatrist, or ophthalmologist) during the preceding 12 months. Public health agencies can work with other health and human service agencies to raise awareness about childhood seizures, implement strategies to prevent known causes and risk factors for seizures, study the associations between sociodemographic characteristics and seizure incidence, and ensure linkages for children with seizures to appropriate clinical and community providers.... Language: en
OC-087 Can faecal calprotectin reduce the demand for colonoscopy in patients with irritable bowel syndrome?: Abstract OC-087
Authors: S J Whitehead, L Lee, Z Fang, G Sisson, J Hutton, R P H Logan
Journal: Gut (2010)

<h3>Introduction</h3> The diagnosis of irritable bowel syndrome (IBS) in primary care relies on typical clinical features, absence of alarm symptoms and normal tests. Apart from usual blood tests, patients are often referred to secondary care and often undergo GI imaging (Barium studies or endoscopy), despite NICE guidelines recommendation to the contrary. Faecal calprotectin (FC) appears to be a very sensitive test for activated neutrophils from the small and large bowel and so may allow the diagnosis of IBS to be established in primary care. <h3>Methods</h3> 1. Outcomes based analysis of patients having a FC test between Jan 05-Jan 09 using HES, PACS and SNOMED CT pathology data sets. 2. Statistical analysis using Bayesian MCMC modelling of patient population data to determine cut-offs for computer modelling. 3. Linear modelling of two diagnostic strategies for costs and outcomes using a decision tree approach for a cohort of 1000 suspected IBS patients until diagnosis confirmed. Costs were limited to direct healthcare costs (ie, tests, endoscopies, drugs and outpatient visits). Outcomes were analysed for the number of correctly diagnosed IBS and IBD patients. Data inputs were drawn from published studies, established national databases, and expert clinical opinion. <h3>Results</h3> From a data set of &gt;16 000, 2419 patients aged &lt;45 years (63% women) attending for the first time, were identified. PACS, ePR and patholology data bases identified pathology in 58% patients with FC &gt;50. For the 1750 patients with negative results, computer modelling indicated that cut-offs &lt;125 would represent 95% of normal population. For cost-effectiveness, modelling showed that cost-savings varied with sensitivity and specificity (see Abstract 087). In the base case, in comparison with ESR plus CRP, FC resulted in an additional 63 correctly diagnosed IBS patients and an additional 55 correctly diagnosed IBD patients at the initial test. Total costs were £312 143 for the FC cohort compared to £325 606 for the ESR plus CRP cohort, making the FC diagnostic strategy cost-saving. Sensitivity analysis identified the specificity and sensitivity of the tests as being key drivers of the results, in addition to the cost of colonoscopy and FC ELISA. <h3>Conclusion</h3> These studies show that faecal calprotectin is more effective, in terms of diagnostic accuracy, and is a less costly diagnostic strategy for distinguishing IBS from IBD than the use of ESR plus CRP. Faecal calprotectin has the potential to improve the management of IBS patients in primary care by increasing the confidence with which diagnoses are made by healthcare professionals, and reducing the need for referral to secondary care.
Clinical outcome and molecular characterization of patients receiving systemic therapy for metastatic sarcomatoid renal cell carcinoma.
Authors: Joann Hsu, Sumanta Kumar Pal, Przemyslaw Twardowski, Courtney Carmichael, Junmi Saikia, Xueli Liu, Timothy G. Wilson, Robert A. Figlin, Jeremy Jones
Journal: Journal of Clinical Oncology (2012)

e15084 Background: Sarcomatoid metastatic renal cell carcinoma (mRCC) represents an aggressive subset of disease, and a definitive therapeutic strategy is lacking. Methods: From an institutional database including 270 patients with mRCC, we identified 34 patients with documented sarcomatoid features. Within this cohort, we assessed 21 patients who received systemic therapy. Survival was assessed in the overall cohort and in subgroups divided by clinicopathologic characteristics, including the extent of sarcomatoid features, MSKCC risk criteria, and the nature of systemic therapy given. Available tissue from 11 of these patients has been identified for correlative studies to assess markers of epithelial to mesenchymal transition (EMT). Tissue will be obtained from a cohort of patients matched for age and MSKCC risk status (but lacking a sarcomatoid component) for comparison. Results: Of the 21 patients assessed, 2 patients received chemotherapy, 7 patients received immunotherapy, and 12 patients received targeted agents as their first line treatment. Median overall survival (OS) in the overall cohort was 18.0 months (95%CI 6.9-22.0). By MSKCC status, patients with poor-risk disease had a median OS of 4.7 months, as compared to 20.1 months for patients with intermediate-risk disease (HR 0.02, 95%CI 0.003-0.15; P=0.0001). Survival in subgroups stratified by the Heng criteria will be presented at the meeting. There was no significant difference in survival in patients with sarcomatoid predominant disease (&gt;20%) vs non-predominant disease (HR 0.62, 95%CI 0.23-1.65; P=0.34), nor was there a difference amongst patients who received targeted therapies vs non-targeted therapies (HR 1.0, 95%CI 0.61-1.40; P=0.36). Correlative analyses are ongoing, and will be presented at the meeting. Conclusions: As compared to previous retrospective series (Golshayan et al JCO 2009) and prospective trials (Haas et al Med Oncol 2011) assessing patients with sarcomatoid mRCC, the survival in our cohort was substantially prolonged. Further clinical and translational studies are needed to refine current prognostic schema for this disease, and to define the optimal therapeutic strategy.
Abstract 14086: Optical Coherence Tomography Analysis of Attenuated Plaques Detected by Intravascular Ultrasound in Patients With Acute Coronary Syndromes
Authors: Takashi Kubo, Yoshiki Matsuo, Teruaki Wada, Satoshi Ueno, Yasushi Ino, Takashi Tanimoto, Kohei Ishibashi, Kenichi Komukai, Hironori Kitabata, Atsushi Tanaka, Keizo Kimura, Toshio Imanishi, Takashi Akasaka
Journal: Circulation (2011)

Background. Recent intravascular ultrasound (IVUS) studies have demonstrated that hypoechoic plaque with deep ultrasound attenuation despite absence of bright calcium is common in acute coronary sy...
<i>p53</i> mutation as a determinant of prognosis in GIST patients treated with imatinib mesylate
Authors: M.-H. Ryu, H. Lee, T. W. Kim, H. M. Chang, J.-L. Lee, W. K. Kang, Y.-J. Bang, D. B. Shin, K. H. Lee, Y. H. Park, Y.-K. Kang
Journal: Journal of Clinical Oncology (2005)

9018 Background: Mutation of p53 has been demonstrated to be a poor prognostic factor in many types of human cancer. This study was performed to determine prognostic significance of p53 in patients with metastatic or unresecable malignant GIST who were treated with Imatinib mesylate. Methods: Clinical data of 105 GIST patients treated with Imatinib mesylate at 8 institutions in Korea between June 2001 and April 2004 were reviewed. In 68 cases, paraffin-embedded tissues were available for DNA extraction and direct sequencing to detect mutation of p53 gene (exon 4 - 8) and c-kit gene (exon 9, 11, 13, and 17). Results: Of 68 cases analyzed, p53 mutations were found in 12 cases (18%) at exon 5 (n = 3), exon 7 (n = 6), and exon 8 (n = 3). c-kit gene mutations were observed in 62 cases (91%) at exon 11 (n = 58) and exon 9 (n = 4). c-kit gene mutation rate was significantly higher in cases without p53 mutation (95%) than in cases with p53 mutation (75%) (P = 0.029). Response rates (CR + PR) and disease control rates (CR + PR + SD) were not different according to p53 mutation (68% and 86% for p53 mutation negative cases, and 58% and 83% for p53 mutation positive cases) (P > 0.5). With a median follow-up of 18 months (range, 6 to 38 months), 2-yr progression-free survival (PFS) tended to be lower in p53 mutation positive cases (58%) than in p53 mutation positive cases (65%) (P = 0.2322). 2-yr overall survival (OS) was better in p53 mutation negative cases (89%) than p53 mutation positive cases (75%) (P = 0.0156). A multivariate analysis including p53 mutation and c-kit mutation revealed that presence of p53 mutation remained a poor prognostic factor for survival (relative risk, 5.3; 95% confidence interval, 1.1 - 24.9; P = 0.037) Conclusions: These data suggest that p53 mutation could be a poor prognostic factor in GIST patients treated with Imatinib mesylate. No significant financial relationships to disclose.