tbuckley/cabot-search huggingface dataset:
A longitudinal modelling study estimates acute symptoms of community acquired pneumonia recover to baseline by 10 days
Authors: Daniel G. Wootton, Laura Dickinson, Henry Pertinez, Joanne Court, Odiri Eneje, Lynne Keogan, Laura Macfarlane, Sarah Wilks, Jane Gallagher, Mark Woodhead, Stephen B. Gordon, Peter J. Diggle
Journal: European Respiratory Journal (2017)

Our aims were to address three fundamental questions relating to the symptoms of community-acquired pneumonia (CAP): Do patients completely recover from pneumonia symptoms? How long does this recovery take? Which factors influence symptomatic recovery?We prospectively recruited patients at two hospitals in Liverpool, UK, into a longitudinal, observational cohort study and modelled symptom recovery from CAP. We excluded patients with cancer, immunosuppression or advanced dementia, and those who were intubated or palliated from admission. We derived a statistical model to describe symptom patterns.We recruited 169 (52% male) adults. Multivariable analysis demonstrated that the time taken to recover to baseline was determined by the initial severity of symptoms. Severity of symptoms was associated with comorbidity and was inversely related to age. The pattern of symptom recovery was exponential and most patients' symptoms returned to baseline by 10 days.These results will inform the advice given to patients regarding the resolution of their symptoms. The recovery model described here will facilitate the use of symptom recovery as an outcome measure in future clinical trials.
Adverse health outcomes in relationship to hypogonadism (HG) after platinum-based chemotherapy: A multicenter study of North American testicular cancer survivors (TCS).
Authors: Mohammad Issam Abu Zaid, Alvaro G. Menendez, Omar El Charif, Chunkit Fung, Patrick O. Monahan, Darren R. Feldman, Robert James Hamilton, David J. Vaughn, Clair Beard, Ryan Cook, Sandra K. Althouse, Howard D. Sesso, Shirin Ardeshirrouhanifard, Paul C Dinh, Lawrence Einhorn, Sophie Fosså, Lois B. Travis
Journal: Journal of Clinical Oncology (2017)

LBA10012 Background: HG affects a substantial percentage of TCS and can contribute to significant morbidity, but few studies have examined the relationship between HG and adverse health outcomes (AHO), taking into account genetic variation. Methods: Eligible TCS were &lt; 55 y at diagnosis and treated with only first line chemotherapy after 1990. TCS underwent physical exams and genotyping, and completed questionnaires regarding 16 AHO and health behaviors. HG was defined as serum testosterone ≤ 3.0 ng/mL or the use of testosterone replacement therapy. Results: We evaluated 491 TCS. Median age at evaluation was 38 y (range 19-68). 38.5% had HG. Two SNPs in the sex-hormone-binding globulin ( SHBG) locus previously implicated in increased HG risk in the general population (Ohlsson et al, PLOS Genetics 2011) displayed effect sizes consistent with prior reports (rs6258, OR = 1.3; rs12150660, OR = 0.79), but were not statistically significant. However, TCS with ≥ 2 risk alleles for the two SNPs in the SHBG locus vs no risk alleles had 2-fold increased risk for HG (OR = 2.2, P = .12). Multivariate analysis identified risk factors for HG including: age (OR = 1.4 per 10 year increase, P = .007), and BMI ≥ 25 kg/m 2 (OR = 2.2, P = .003). Vigorous-intensity physical activity appeared protective (OR = 0.6, P = .06). Type of chemotherapy regimen and socioeconomic factors did not correlate with HG. Only 35% of TCS with HG vs 49% of those without HG reported none or 1 AHO ( P = .003). TCS with HG were more likely to take medications for dyslipidemia (20% vs 6%, P &lt; .001), hypertension (19% vs 11%, P = .01), erectile dysfunction (ED) (20% vs 12%, P = .02), diabetes (6% vs 3%, P = .07), or anxiety/depression (15% vs 10%, P = 0.06) compared to TCS with normal levels, and also to have peripheral neuropathy (PN) (31% vs 23%, P = .04). HG status did not correlate with oto- or renal toxicity. Conclusions: Over a third of TCS have HG at a relatively young age. HG was associated with increased cardiovascular disease risk factors, ED, and PN. SHBG polymorphisms appear important in TCS, but our study was underpowered to confirm an association. Providers should screen TCS for HG and treat those who are symptomatic.
Strength Duration Test: An Old Tool with New Usefulness
Authors: EI Eguare, P Neary, J Crosbie, SM Johnston, B McGovern, KC Conlon, FBV Keane
Journal: Endoscopy (2004)

Introduction: Our present inability to fully elucidate pelvic neuropathy has lead to a reconsideration of the strength-duration test (SDT) as a complimentary investigation for Pelvic-floor dysfunction (PFD). Combined with manometric, SDT could discriminate between normal and faecal incontinence patients with a sensitivity and specificity of 95% and 100% respectively.
Exploratory Pharmacokinetic/Pharmacodynamic and Tolerability Study of BCMAxCD3 in Cynomolgus Monkeys
Authors: Suzette Girgis, Shoba Shetty, Trina Jiao, Chidozie Amuzie, Dan Weinstock, Rebecca Grimme Watson, Joyce Ford, Kodandaram Pillarisetti, Eric Baldwin, Kevin Bellew
Journal: Blood (2016)
Endocuff-assisted vs. standard colonoscopy in the fecal occult blood test-based UK Bowel Cancer Screening Programme (E-cap study): a randomized trial
Authors: Rupam Bhattacharyya, Fergus Chedgy, Kesavan Kandiah, Carole Fogg, Bernard Higgins, Ben Haysom-Newport, Lisa Gadeke, Fergus Thursby-Pelham, Richard Ellis, Patrick Goggin, Gaius Longcroft-Wheaton, Pradeep Bhandari
Journal: Endoscopy (2017)

Abstract Background and study aims Up to 25 % colorectal adenomas are missed during colonoscopy. The aim of this study was to investigate whether the endocuff could improve polyp detection in an organized bowel cancer screening program (BCSP). Patients and methods This parallel group, single-blinded, randomized controlled trial included patients with positive fecal occult blood test (FOBT) who were attending for BCSP colonoscopy. The primary outcome was the number of polyps per patient. Secondary outcomes included the number of adenomas per patient, adenoma and polyp detection rates, and withdrawal times. Results A total of 534 BCSP patients were randomized to endocuff-assisted or standard colonoscopy. The mean age was 67 years and the male to female ratio was 1.8:1. We detected no significant difference in the number of polyps per patient (standard 1.8, endocuff 1.6; P = 0.44), adenomas per patient (standard 1.4, endocuff 1.3; P = 0.54), polyp detection rate (standard 69.8 %, endocuff 70.3 %; P = 0.93), adenoma detection rate (standard 63.0 %, endocuff 60.9 %; P = 0.85), advanced adenoma detection rate (standard 18.5 %, endocuff 16.9 %; P = 0.81), and cancer detection rate (standard 5.7 %, endocuff 5.3 %; P = 0.85). The mean withdrawal time was significantly shorter among patients in the endocuff group compared with the standard colonoscopy group (16.9 vs. 19.5 minutes; P &lt; 0.005). The endocuff had to be removed in 17/266 patients (6.4 %) because of inability to pass through the sigmoid colon. Conclusions This study did not find improved polyp or adenoma detection with endocuff-assisted colonoscopy in the FOBT-positive BCSP population. A shorter withdrawal time with endocuff may reflect improved views and stability provided by the endocuff. Trial registered at ClinicalTrials.gov (NCT02529007).
The limitations of humanising healthcare
Authors: Mongjam Meghachandra Singh, Reeta Devi
Journal: BMJ (2017)

Youngson and Blennerhassett discuss the humanisation of healthcare.1 New technologies and equipment are rapidly changing patient care. Clinical methods for diagnosis are being replaced by scans and laboratory tests. Thus, the need for detailed questions about health problems is also declining. Doctors, paramedics, and nurses are …
Erratum: Ceruloplasmin gene defect associated with epilepsy in EL mice
Authors: Carla Rosenberg', Ralph Florijn', Frans Van De Rijke, Lau Blonden', Tonk Raap, Gert-Jan Van Ommen', M Kamboh', Dharambir Sanghera, Robert Ferrell', Steven Dekosky'
Journal: Nature Genetics (1995)
Pembrolizumab in advanced endometrial cancer: Preliminary results from the phase Ib KEYNOTE-028 study.
Authors: Patrick Alexander Ott, Yung-Jue Bang, Dominique Berton-Rigaud, Elena Elez, Michael J. Pishvaian, Hope S. Rugo, Igor Puzanov, Mark Aloysuis Morgan, Janice M. Mehnert, Kyaw Lwin Aung, Marion Carrigan, Sanatan Saraf, Mei Chen, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2016)

5581 Background: There are currently no treatment options for pts with endometrial cancer who progress on chemotherapy. Pembrolizumab is an anti–PD-1 antibody that blocks interaction between PD-1 and its ligands, PD-L1/PD-L2. The safety and efficacy of pembrolizumab were evaluated in advanced solid tumors in the KEYNOTE-028 study (NCT02054806). Preliminary results from the endometrial carcinoma cohort are presented. Methods: Key inclusion criteria were advanced endometrial carcinoma (excluded sarcomas, mesenchymal tumors), failure of prior systemic therapy, ECOG PS 0-1, and PD-L1 expression in ≥ 1% of tumor or stroma cells by IHC. Pembrolizumab 10 mg/kg every 2 wk was given for up to 24 mo or until confirmed progression, intolerable toxicity, death, or consent withdrawal. Response was assessed every 8 wk for the first 6 mo and every 12 wk thereafter. The primary end point was ORR per RECIST v1.1 by investigator assessment. Results: In the 24 pts enrolled, median age was 67.0 y; 66.7% had an ECOG PS of 1; 62.4% received ≥ 2 prior therapies for metastatic disease. As of Dec 10, 2015, median follow-up duration was 69.9 wk (range, 5.4-84.4). Treatment-related AEs (TRAEs) occurred in 13 (54.2%) pts; most common were pruritus (n = 4, 16.7%), asthenia, fatigue, pyrexia, and decreased appetite (n = 3 each; 12.5%). Three pts experienced grade 3 TRAEs: 1 pt had back pain and asthenia (both resolved), 1 pt had diarrhea (resolved), 1 pt had asthenia, anemia, hyperglycemia, and hyponatremia (all unresolved). No pts died or discontinued pembrolizumab because of a TRAE. ORR (confirmed) was 13.0% (PR, n = 3; 95% CI, 2.8-33.6); median duration of response was not yet reached (range, 40.3+ to 65.1+ wk). Three pts achieved stable disease (13%; 95% CI, 2.8-33.6; median duration, 24.6 wk [range, 13.1-24.6]). Six-mo PFS and OS rates were 19.0% and 68.8%, respectively. At data cutoff, all 3 pts with PRs remained on treatment. Conclusions: Pembrolizumab demonstrated an acceptable safety profile and preliminary antitumor activity in heavily pretreated PD-L1+ advanced endometrial cancer pts. The clinical benefit of pembrolizumab for advanced endometrial cancer is being further investigated in the phase 2 KEYNOTE-158 trial (NCT02628067). Clinical trial information: NCT02054806.
Induction of HO-1 reduces the metabolic and nitro/oxidative effects of ischemia-reperfusion in diabetic rat hearts
Authors: D Neglia, C Vecoli, D Giannessi, M Maltinti, Ottaviano, S Baldi, M Novelli, P Masiello, A Paolicchi, R Barsacchi, Ng Abraham, A L'Abbate
Journal: Journal of the American College of Cardiology (2008)
Formulate, don't formularise
Authors: C Donaldson
Journal: BMJ (1994)

to the community served by the hospital, and thus enlist the recipients and politicians in crucial decision making processes on the delivery ofhealth care.Finally, is the model and its application fair?The answer to this lies partly in whether rationing can be considered as fair.It has been stated that "unfairness lies also in doing things until the money runs out"'"I and that "rationing becomes a morally acceptable option if the need is great enough and if other methods have been exhausted."33In our case the need had become acute, other methods were not sufficient to meet our requirements, and we could not wait for the ultimate cost saving benefits of the drug utilisation review programme to take effect.A method was therefore needed to provide a more equitable approach to this decision making process.
Competition between DNA Methylation, Nucleotide Synthesis, and Antioxidation in Cancer versus Normal Tissues
Authors: Sha Cao, Xiwen Zhu, Chi Zhang, Hong Qian, Heinz-Bernd Schuttler, Jianping Gong, Ying Xu
Journal: Cancer Research (2017)

Global DNA hypomethylation occurs in many cancer types, but there is no explanation for its differential occurrence or possible impact on cancer cell physiology. Here we address these issues with a computational study of genome-scale DNA methylation in 16 cancer types. Specifically, we identified (i) a possible determinant for global DNA methylation in cancer cells and (ii) a relationship between levels of DNA methylation, nucleotide synthesis, and intracellular oxidative stress in cells. We developed a system of kinetic equations to capture the metabolic relations among DNA methylation, nucleotide synthesis, and antioxidative stress response, including their competitions for methyl and sulfur groups, based on known information about one-carbon metabolism and trans-sulfuration pathways. We observed a kinetic-based regulatory mechanism that controls reaction rates of the three competing processes when their shared resources are limited, particularly when the nucleotide synthesis rates or oxidative states are high. The combination of this regulatory mechanism and the need for rapid nucleotide synthesis, as well as high production of glutathione dictated by cancer-driving forces, led to the nearly universal observations of reduced global DNA methylation in cancer. Our model provides a natural explanation for differential global DNA methylation levels across cancer types and supports the observation that more malignant cancers tend to exhibit reduced DNA methylation levels. Insights obtained from this work provide useful information about the complexities of cancer due to interplays among competing, dynamic biological processes. Cancer Res; 77(15); 4185-95. ©2017 AACR.
Two in a Bed, does Helicobacter Pylori Spread?
Authors: S Farrell, I Milliken, MD Shields, WA McCallion
Journal: Endoscopy (2004)

Introduction: Drumm et al. first described intra-familial clustering of Helicobacter pylori (HP) infection (1). Vertical transmission has been inferred, whilst spread among siblings close in age has been suggested. Intra-familial dynamics, which result in transmission, are still unknown. Our aim was to establish whether sharing a bed or bedroom with an infected family member is a risk factor for HP infection during childhood.
Polymorphisms of ERCC1 C8092A and glutathione-S-transferase T1 (GSTT1) associated with survival and response after platinum-based chemotherapy in patients with epithelial ovarian cancer
Authors: Hee Seung Kim, Jae Weon Kim, Soon-Beom Kang
Journal: Clinical Cancer Research (2007)

A54  Background : The purpose of this study was to evaluate the role of genetic polymorphisms in ERCC1 C8092A and glutathione-S-transferase T1 (GSTT1) in the prognosis of patients with epithelial ovarian cancer after platinum based chemotherapy.  Methods : The clinical data of 152 patients with epithelial ovarian cancer between July 1999 and Novemver 2006 were reviewed restrospectively. They were treated with platinum based chemotherapy after staging laparotomy. We investigated the genotypes of each polymorphism of ERCC1 C8092A and GSTT1. Progression-free survival (PFS) and overal survival (OS) were evaluated using Kaplan-Meier method with log-rank test. Prognostic factors affecting PFS and OS were analyzed using Cox regression models. Response after primary therapy was evaluated using Chi square test.  Results : Among 152 patients with epithelial ovarian cancer, data about polymorphisms of ERCC1 C8092A and GSTT1 were collected from 105 and 118 patients, respectively. In polymorphism of ERCC1 C8092A, C/C, C/A and A/A genotypes were detected in 69 (65.7%), 29 (27.6%) and 7 (6.7%) patients. Median PFS were 94 (C/C) and 13 (C/A or A/A) months (P=.005). Mean OS were 153 (C/C) and 63 (C/A or A/A) months (P=.046). In polymorphism of GSTT1, null and non-null genotypes were detected in 69 (58.5%) and 49 (41.5%) patients. Median PFS were 34 months (null) and 11 months (non-null) (P=.013). Mean OS were 152 (null) and 61 (non-null) months (P=.006). However, they were not independent prognostic factors on multivarate Cox regression model (P>.05). When the polymorphisms of ERCC1 C8092A and GSTT1 were combined, data were reviewed from 92 patients. We divided them into group 1 (72 patients; C/C with null or C/C with non-null or C/A with non-null genotypes) and group 2 (20 patients; A/A with non-null genotype). Median PFS were 34 (group 1) and 8 (group 2) months. Mean OS were 152 (group 1) and 50 (group 2) months. Polymorhpism according to the combination of ERCC1 C8092A and GSTT1 was a prognostic factor for PFS in patients with epithelial ovarian cancer (HR=2.317, 95% CI=1.044-5.144, P=.039) although it was not a significant factor on OS on mutivariate Cox-regression analysis. For the evaluation of the roles of ERCC1 C8092A and GSTT1 on response after platinum based chemotherapy, patients were divided into poor responder (PFS
Dacomitinib versus gefitinib for the first-line treatment of advanced EGFR mutation positive non-small cell lung cancer (ARCHER 1050): A randomized, open-label phase III trial.
Authors: Tony Mok, Ying Cheng, Xiangdong Zhou, Ki Hyeong Lee, Kazuhiko Nakagawa, Seiji Niho, Fumito Tsuji, Rafael Rosell, Jesus Corral Jaime, Maria Rita Migliorino, Adam Pluzanski, Rolf Gerhard Linke, Eric Sbar, Tao Wang, Yi-Long Wu
Journal: Journal of Clinical Oncology (2017)

LBA9007 Background: Dacomitinib is a 2nd generation EGFR TKI with encouraging clinical activity as 1st-line therapy in patients with EGFR-activating mutation positive advanced NSCLC (Jänne, Lancet Oncol 2014). We performed the first randomized phase III trial, currently ongoing, comparing dacomitinib (D) with gefitinib (G) as 1st-line therapy (1L) (NCT01774721). Methods: Patients (pts) with newly diagnosed stage IIIB/IV/ recurrent NSCLC harboring an EGFR- activating mutation (exon 19 del or exon 21 L858R mu +/- exon 20 T790M mu) were randomized 1:1 to D 45 mg PO QD or G 250mg PO QD; stratification was by race and EGFR mutation subtype. The primary endpoint was PFS per blinded independent review (IRC) analyzed by Kaplan-Meier method with log-rank test and Cox model. Secondary endpoints included: overall survival, objective response rate (ORR), duration of response (DR), PFS per Investigator (INV), time to treatment failure (TTF), restricted mean survival time (RMST) for PFS, safety and patient-reported outcomes (PROs). Results: The ITT population included 452 pts with baseline characteristics fairly well balanced between the arms. ORR per IRC was similar between arms (75% [95% CI: 69, 80] for D and 72% [95% CI: 65, 77]; 2-sided p-value = 0.39; OS is not mature. The most commonly reported grade 3 adverse events with dacomitinib were dermatitis acneiform (13.7%) and diarrhea (8.4%) and with gefitinib ALT (8.5%); no new safety signals were identified. Conclusions: ARCHER 1050 was the first phase III head-to-head study of EGFR TKIs and demonstrated statistically significant and clinically meaningful improvement in efficacy of D vs. G in 1L NSCLC pts with EGFR-activating mutations with a manageable safety profile, to offer a new 1L treatment option. Clinical trial information: NCT01774721. [Table: see text]
TLR7/8 activation in neutrophils impairs immune complex phagocytosis through shedding of FcgRIIA
Authors: Christian Lood, Sabine Arve, Jeffrey Ledbetter, Keith B. Elkon
Journal: The Journal of Experimental Medicine (2017)

Neutrophils play a crucial role in host defense. However, neutrophil activation is also linked to autoimmune diseases such as systemic lupus erythematosus (SLE), where nucleic acid-containing immune complexes (IC) drive inflammation. The role of Toll-like receptor (TLR) signaling in processing of SLE ICs and downstream inflammatory neutrophil effector functions is not known. We observed that TLR7/8 activation leads to a furin-dependent proteolytic cleavage of the N-terminal part of FcgRIIA, shifting neutrophils away from phagocytosis of ICs toward the programmed form of necrosis, NETosis. TLR7/8-activated neutrophils promoted cleavage of FcgRIIA on plasmacytoid dendritic cells and monocytes, resulting in impaired overall clearance of ICs and increased complement C5a generation. Importantly, ex vivo derived activated neutrophils from SLE patients demonstrated a similar cleavage of FcgRIIA that was correlated with markers of disease activity, as well as complement activation. Therapeutic approaches aimed at blocking TLR7/8 activation would be predicted to increase phagocytosis of circulating ICs, while disarming their inflammatory potential.
Acral Bullae in a Young Girl
Authors: Elizabeth Hargroder, Robert M. Gathings, Lara Wine Lee
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Marketing Claims for Infant Formula Additives and Infant Formula
Authors: George Kent
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal