tbuckley/cabot-search huggingface dataset:
Changes in chlamydia prevalence and duration of infection estimated from testing and diagnosis rates in England: a model-based analysis using surveillance data, 2000–15
Authors: Joanna Lewis, Peter J White
Journal: The Lancet Public Health (2018)

BackgroundChlamydia screening programmes have been implemented in several countries, but the effects of screening on incidence, prevalence, and reproductive sequelae remain unclear. In England, despite increases in testing with the rollout of the National Chlamydia Screening Programme (NCSP; 2003–08), prevalence estimated in 10-yearly population-based surveys was similar before (1999–2001) and after (2010–12) the programme. However, the precision of these previous estimates was limited by the low numbers of infections. We aimed to establish annual, rather than 10-yearly, estimates of chlamydia prevalence and infection duration.MethodsIn this model-based analysis, we used previously published minimum and maximum estimates and Public Health England data for chlamydia test coverage and diagnoses in men and women aged 15–24 years in England, before, during, and after the scale-up of national chlamydia screening. We used a mechanistic model, which accounted for symptomatic chlamydia testing and asymptomatic screening, to estimate changes in prevalence and average duration of infections for each year. We describe estimates derived from the maximum and minimum numbers of tests and diagnoses as maximum and minimum estimates, regardless of their relative magnitude.FindingsThe data included numbers of tests and diagnoses in men and women aged 15–19 years and 20–24 years in England each year from 2000 to 2015. We estimated reductions in prevalence and average infection duration in both sexes once screening was fully implemented. From 2008 to 2010, estimated posterior median prevalence reductions in people aged 15–24 years were 0·68 percentage points (95% credible interval 0·26–1·40; minimum) and 0·66 percentage points (0·25–1·37; maximum) for men and 0·77 percentage points (0·45–1·27) for women (minimum and maximum estimates were the same for women). Over the same time period, mean duration of infection reduced by 75 days (95% credible interval 17–255; minimum) and 74 days (95% credible interval 17–247; maximum) in men and 30 days (22–40) in women. Since 2010, some of the progress made by the NCSP has been reversed, alongside a reduction in testing.InterpretationOur analysis provides the first evidence for a reduction in chlamydia prevalence in England concurrent with large-scale population testing. It also shows a consistent decline in the average duration of infections, which is a measure of screening effectiveness that is unaffected by behavioural changes.FundingNational Institute for Health Research, Medical Research Council.
Randomized phase III study of docetaxel plus bavituximab in previously treated advanced non-squamous non-small-cell lung cancer
Authors: D.E. Gerber, L. Horn, M. Boyer, R. Sanborn, R. Natale, R. Palmero, P. Bidoli, I. Bondarenko, P. Germonpre, D. Ghizdavescu, A. Kotsakis, H. Lena, G. Losonczy, K. Park, W -C Su, M. Tang, J. Lai, N.L. Kallinteris, J.S. Shan, M. Reck, D.R. Spigel
Journal: Annals of Oncology (2018)

BackgroundBavituximab is a monoclonal antibody that targets phosphatidylserine in the presence of β2 glycoprotein 1 (β2GP1) to exert an antitumor immune response. This phase III trial determined the efficacy of bavituximab combined with docetaxel in patients with previously treated advanced non-small-cell lung cancer (NSCLC).Patients and methodsKey eligibility criteria included advanced non-squamous NSCLC with disease progression after treatment with platinum-based doublet chemotherapy, evidence of disease control after at least two cycles of first-line therapy, presence of measurable disease, ECOG performance status 0 or 1, adequate bone marrow and organ function, and no recent history of clinically significant bleeding. Eligible patients were randomized 1 : 1 to receive up to six 21-day cycles of docetaxel plus either weekly bavituximab 3 mg/kg or placebo until progression or toxicity. The primary end point was overall survival (OS).ResultsA total of 597 patients were enrolled. Median OS was 10.5 months in the docetaxel + bavituximab arm and was 10.9 months in the docetaxel + placebo arm (HR 1.06; 95% CI 0.88–1.29; P = 0.533). There was no difference in progression-free survival (HR 1.00; 95% CI 0.82–1.22; P = 0.990). Toxicities were manageable and similar between arms. In subset analysis, among patients with high baseline serum β2GP1 levels ≥200 µg/ml, a nonsignificant OS trend favored the bavituximab arm (HR 0.82; 95% CI 0.63–1.06; P = 0.134). Among patients who received post-study immune checkpoint inhibitor therapy, OS favored the bavituximab arm (HR 0.46; 95% CI 0.26–0.81; P = 0.006).ConclusionsThe combination of bavituximab plus docetaxel is not superior to docetaxel in patients with previously treated advanced NSCLC. The addition of bavituximab to docetaxel does not meaningfully increase toxicity. The potential benefit of bavituximab observed in patients with high β2GP1 levels and in patients subsequently treated with immune checkpoint inhibitors requires further investigation.Clinical trial numberNCT01999673.
Risk-adapted therapy for young children with medulloblastoma (SJYC07): therapeutic and molecular outcomes from a multicentre, phase 2 trial
Authors: Giles W Robinson, Vasilisa A Rudneva, Ivo Buchhalter, Catherine A Billups, Sebastian M Waszak, Kyle S Smith, Daniel C Bowers, Anne Bendel, Paul G Fisher, Sonia Partap, John R Crawford, Tim Hassall, Daniel J Indelicato, Frederick Boop, Paul Klimo, Noah D Sabin, Zoltan Patay, Thomas E Merchant, Clinton F Stewart, Brent A Orr, Jan O Korbel, David T W Jones, Tanvi Sharma, Peter Lichter, Marcel Kool, Andrey Korshunov, Stefan M Pfister, Richard J Gilbertson, Robert P Sanders, Arzu Onar-Thomas, David W Ellison, Amar Gajjar, Paul A Northcott
Journal: The Lancet Oncology (2018)
Association of <i>SMAD4</i> gene mutation with incidence of peritoneal involvement in unresectable metastatic colorectal cancer.
Authors: Diego Vicente, Takashi Mizuno, Andrew Loehrer, Preparim Limani, Scott Kopetz, Jean-Nicolas Vauthey
Journal: Journal of Clinical Oncology (2018)

772 Background: Dorsophilia protein, mothers against decapentaplegic homolog 4 (SMAD4) is involved in TGF- β and Bone Morphogenic Protein (BMP) signaling pathways. Dysregulation in these signaling pathways has been associated with carcinogenesis and poor prognosis in colorectal cancer (CRC). Recent evidence suggests that SMAD4 mutations in CRC may be associated ovarian metastasis, however, the link to peritoneal involvement has not been established. Methods: Patients with next generation sequencing of 50 cancer related genes and unresectable metastatic CRC were identified from a prospectively maintained medical oncology department database. Clinicopathological variables, metastatic sites, and genetic mutations were compared between patients with SMAD4 mutant and SMAD4 wild type patients. Multivariable analysis was then performed to evaluate for factors associated with peritoneal involvement. Results: 324 patients with unresectable metastatic CRC were identified and of these 36 (11%) were SMAD4 mutants. Clinicopathologic variables and additional cancer related gene mutations were similar between SMAD4 mutant and wild type patients. Patients with SMAD4 mutations were more likely to present with peritoneal metastatic disease (50% vs. 24%, p = 0.002) and less likely to present with hepatic metastasis (39% vs 59%, p = 0.021). Metastatic rates to the lungs, distant lymph nodes, and multiple metastatic sites at presentation were similar between the two groups. In patients with metachronous metastatic disease (n = 131), SMAD4 mutation patients demonstrated a trend towards shorter interval to metastatic recurrence (12 vs. 23 months, p = 0.059). During a median follow up of 26 months, SMAD4 mutation patients were more likely to develop peritoneal involvement at either presentation or in progression of disease (58 vs. 35%, p = 0.010). Multivariable analysis showed that compared to other mutations, only the SMAD4 mutation was associated with a higher risk of peritoneal metastasis (OR 2.5, 195% CI 1.2-5.6, p = 0.025). Conclusions: In patients with unresectable metastatic colorectal cancer, SMAD4 mutation is independently associated with peritoneal metastasis.
Quality and Safety in Health Care, Part XLIII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2018)

To compare outcome results from different institutions in a registry, it is necessary to have a way to take into account differences in the risk characteristics of the patients. This model has been constructed for the Implantable Cardioverter Defibrillator (ICD) Registry, and the most important variables have been identified. In another study, it has also been found that many of these patients have comorbidities, and the mortality rate 60 months after a replacement ICD was 41.2%. In a third study, it was determined that for individuals at least 65 years of age, 60 months after ICD placement, 50.9% of the recipients used hospice services or were dead.
Comparable outcomes in CLL patients treated with reduced-dose ibrutinib: Results from a multi-center study.
Authors: Colleen Timlin, Rahul Banerjee, Christina Howlett, Chaitra Shankar Ujjani, Alan P. Skarbnik, Molly Fanning, Stephen J. Schuster, Jakub Svoboda, David L. Porter, Sunita Nasta, Edward A. Stadtmauer, Daniel Jeffrey Landsburg, Tatyana Feldman, Allison Rago, Colleen Dorsey, Donna L. Capozzi, Jennifer Morganroth, Andre Goy, Bruce D. Cheson, Anthony R. Mato
Journal: Journal of Clinical Oncology (2016)

7529 Background: Ibrutinib (Ibr) is a first-in-class oral covalent inhibitor of Bruton's tyrosine kinase (BTK) dosed according to FDA labeling at 420 mg daily to achieve > 90% BTK occupancy (≥ 2.5 mg/kg/day). Although fewer pts achieve > 90% occupancy at < 420 mg, it is unknown whether lower doses translate into inferior outcomes. To address this question, we conducted a multi-center study to capture experiences of CLL pts treated with Ibr below suggested starting doses. Methods: Multi-center, IRB approved, retrospective study of all Ibr-treated CLL pts between 2010-2015. Demographics, Ibr dose, responses, and outcomes were recorded. Reduced dose was defined as sustained Ibr dosing ( < 420 mg/day), reduced within 3 mos of initiation. The primary endpoint was PFS determined by the Kaplan Meier method, stratified by dose. For comparison, log rank tests and Cox regressions were performed. Results: 197 Ibr-treated CLL pts were identified, of which 37 (19%) received reduced dose Ibr. For reduced dose pts, median (med) dose was 4.3 mg/kg/day (4% < 2.5 mg/kg/day, 5% on CYP3A4 inhibitor). Best ORR (CR+PR+PR-L) was 85% (vs. 84% reduced dose). Most common reasons for reducing Ibr dose were GI toxicity, bleeding, rash, cardiotoxicity, renal insufficiency. Med PFS and OS for the entire cohort (n = 197) were 37 mos and not reached, respectively. Ibr dose did not impact PFS and OS (Table 1). Conclusions: We describe the largest real world experience of reduced dose Ibr in CLL pts. Reduced doses do not appear to affect clinical outcomes. Most pts treated with doses < 420 mg/day maintained a dose of > 2.5 mg/kg/day and therefore adequate BTK occupancy. Weight based dosing should be considered in future studies and pharmacoeconomic analyses. Comparative analyses of toxicity profiles stratified by Ibr dose are underway. Standard dose Reduced dose N 160 37 Med follow up (mos) 13.5 Med PFS (mos) 37.4 Not reached (p = 0.6, LR test) Med OS Not reached Not reached (p = 0.5, LR test) HR reduced dose Ibr, PFS 1.2 (95% CI 0.5-2.6, p = 0.6) HR reduced dose Ibr, OS 0.6 (95% CI,0.14-2.7 p = 0.5)
Abstract A49: Using IL10-/- mouse model to assess heavy-ion radiation exposure-associated colitis and colorectal cancer incidence
Authors: Shubhankar Suman, Bo-Hyun Moon, Albert J. Fornace, Kamal Datta
Journal: Cancer Research (2018)

Abstract Underlying risk of γ-ray-induced colitis and colorectal cancer incidence is emphasized by the studies on atom bomb survivors and also in patients undergoing radiotherapy. However, uncertainties in colitis and CRC risk prediction after exposure to high-LET space (particle) radiation exposure has not been realized due to lack of reliable in vivo data. Here we report IL10-/- mice as a suitable mouse model for assessment of colitis and CRC risk after exposure to space radiation. Male mice (n=12 mice/group) were whole-body exposed to sham-radiation, γ-rays (137Cs-source, 2.0 Gy), and 28Si-ion (300 MeV/n; 70 keV/μm; 1.4 Gy). We used γ-ray equitoxic doses using relative biologic effectiveness (RBE) values determined earlier. Mice were sacrificed 90 days after irradiation, and colon swiss rolls were prepared and histopathologic assessment of colitis score and CRC grade was noted. Further, inflammation-associated gene-expression analysis was conducted in both radiation-induced tumor and adjoining normal tissue area. Immunohistochemistry (β-catenin, Cyclin-D1, and phospho-histone H3) was also performed to assess HZE-induced proliferative signaling. Relative to controls and γ-ray, colitis score, colon tumor incidence, size, and grade were significantly higher after space (28Si-ion) radiation exposure. Additionally, tumor incidence per unit of radiation (per cGy) was also higher after 28Si-ion radiation relative to γ radiation. Higher number of phospho-histone H3-positive cells in 28Si-ion exposed mouse colon demonstrated increased proliferative index resulting in increased intestinal tumors of larger size and grade was due to greater activation of β-catenin and its downstream effector cyclin D1. Inflammatory gene signature was more pronounced after 28Si-ion exposure. Significant upregulation of GATA4, ICAM1, ITGA2, and EGFR was exclusive to 28Si-ion exposed mouse colon; however, PTGES and TGFβ1 were upregulated in both γ and 28Si-ion exposed mice. Overall, our findings suggest that IL10-/- mice are a suitable model to assess IR-induced colitis and CRC risk and space radiation carries higher risk of colitis and CRC incidence, relative to γ-rays at comparable doses. This study has implications for risk prediction in astronauts planning for deep-space missions and also for cancer patients planning to undergo particle radiotherapy. Citation Format: Shubhankar Suman, Bo-Hyun Moon, Albert J. Fornace, Jr., Kamal Datta. Using IL10-/- mouse model to assess heavy-ion radiation exposure-associated colitis and colorectal cancer incidence [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A49.
Role of adjuvant therapy in resected gallbladder cancer.
Authors: Mohamed Abdelrahim Muddathir Hassan, Nicha Wongjarupong, Cristobal T. Sanhueza, Mindy L. Hartgers, Fatima Hassan, Lewis R. Roberts, Amit Mahipal
Journal: Journal of Clinical Oncology (2018)

452 Background: Surgical resection is the only curative treatment for patients with gallbladder cancer, despite surgical advances many patients ultimately develop recurrent disease. Management of resected gallbladder cancer mostly relies on single-arm trials and retrospective observations. The purpose of our study is to assess the role of adjuvant therapy in stage I-III gallbladder cancer patients who have undergone surgical resection. Methods: Clinical data were collected on 251 patients who underwent surgical resection for stage I-III gallbladder cancer and presented to Mayo clinic from January 2000-December 2015. Patients were then classified into adjuvant treatment group and surveillance only group. Overall survival and recurrence were compared between the two groups. Results: 78 (31.1%) patients received adjuvant therapy while 173 patients were observed only. Patients who received adjuvant tended to be younger (63.0[SD 11] vs 66.2 [SD 13.1]), have higher stage, and underwent extended surgery. Most patients received chemoradiotherapy (55) with 5-Fluorouracil (67.3%) and capecitabine (25.5%) as radiosensitizing agents. 21 patients received additional adjuvant chemotherapy. 27% of patients received chemotherapy as the sole adjuvant treatment. The most common chemo regimens included gemcitabine (52.3%) and gemcitabine plus cisplatin combination (23.8%). On multivariate analysis patients &gt; 65 years(HR 1.53 [1.07-2.19], p = 0.02), males (HR 1.7 [1.2-2.4], p = 0.003), positive margins (2.77 [1.69-4.38], p &lt; 0.01), and stage III (HR 1.91 [1.35-2.70], p &lt; 0.01) had worse overall survival. Patients who underwent extended radical resection (HR 0.73 [0.51-1.05], p = 0.09) had better overall survival. Adjuvant therapy had no statistical significant effect on overall survival (HR 1.10 [0.75-1.59], p = 0.63 or disease free survival (HR 1.05 [0.69-1.59], p = 0.81) on overall population. However, in stage IIIB, patients receiving adjuvant therapy had better overall survival (HR 0.51 [0.25-1.01], p = 0.05) and disease free survival (HR 0.45 [0.19-1.09], p = 0.06). Conclusions: In our study, adjuvant treatment, especially chemoradiation therapy, was only beneficial in patients with stage IIIb gallbladder cancer patients.
A Novel Deep Learning Approach for Automated Diagnosis of Acute Ischemic Infarction on Computed Tomography
Authors: Ashley N. Beecy, Qi Chang, Khalil Anchouche, Lohendran Baskaran, Kimberly Elmore, Kranthi Kolli, Hao Wang, Subhi Al’Aref, Jessica M. Peña, Ashley Knight-Greenfield, Praneil Patel, Peng Sun, Tong Zhang, Hooman Kamel, Ajay Gupta, James K. Min
Journal: JACC. Cardiovascular imaging (2018)
Moral demands truly <i>are</i> externally imposed
Authors: Jan-Willem van Prooijen
Journal: Behavioral and Brain Sciences (2018)

Abstract Most moral demands indeed are externally imposed, as violations are subject to social condemnation. While in modern society objectified moral demands may serve as a cue for desirable interaction partners, human morality evolved in small tribes that offered little choice regarding with whom to cooperate. Instead, it was adaptive to objectify moral demands to avoid the costs of social exclusion.
GP at Hand: Where have the new patients come from?
Authors: Gareth Iacobucci
Journal: BMJ (2018)

A new analysis has shown the extent to which patients from across London and beyond have registered with the GP at Hand digital appointment service.

The service, launched by the digital health company Babylon Health at a general practice in Hammersmith, west London, late last year,1 allows people living outside the Hammersmith and Fulham Clinical Commissioning Group’s catchment area to access virtual GP consultations 24 hours a day on …
Outcome after ablation in patients with low-risk thyroid cancer (ESTIMABL1): 5-year follow-up results of a randomised, phase 3, equivalence trial
Authors: Martin Schlumberger, Sophie Leboulleux, Bogdan Catargi, Desiree Deandreis, Slimane Zerdoud, Stephane Bardet, Daniela Rusu, Yann Godbert, Camille Buffet, Claire Schvartz, Pierre Vera, Olivier Morel, Danielle Benisvy, Claire Bournaud, Marie-Elisabeth Toubert, Antony Kelly, Ellen Benhamou, Isabelle Borget
Journal: The Lancet Diabetes & Endocrinology (2018)
Evolutionary Associations of Endosymbiotic Ciliates Shed Light on the Timing of the Marsupial–Placental Split
Authors: Peter Vďačný
Journal: Molecular Biology and Evolution (2018)

Trichostome ciliates are among the most conspicuous protists in the gastrointestinal tract of a large variety of vertebrates. However, little is still known about phylogeny of the trichostome/vertebrate symbiotic systems, evolutionary correlations between trichostome extrinsic traits, and character-dependent diversification of trichostomes. These issues were investigated here, using the relaxed molecular clock technique along with stochastic mapping of character evolution, and binary-state speciation and extinction models. Clock analyses revealed that trichostomes colonized the vertebrate gastrointestinal tract ∼135 Ma, that is, near the paleontological minimum for the split of therian mammals into marsupials and placentals. According to stochastic mapping, the last common ancestor of trichostomes most likely invaded the hindgut of a mammal. Although multiple shifts to fish/amphibian or avian hosts and to the foregut compartments took place during the trichostome phylogeny, only transition to the foregut was recognized as a key innovation responsible for the explosive radiation of ophryoscolecid trichostomes after the Cretaceous/Tertiary boundary, when ungulates began their diversification. Since crown radiations of main trichostome lineages follow those of their mammalian hosts and are in agreement with their historic dispersal routes, the present time-calibrated phylogeny might help to elucidate controversies in the geological and molecular timing of the split between marsupials and placental mammals.
New Physician Requirements to Use Permanent Birth Control Device
Authors: Rebecca Voelker
Journal: JAMA (2018)

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New European Academy of Allergy and Clinical Immunology definition on pollen season mirrors symptom load for grass and birch pollen‐induced allergic rhinitis
Authors: K. Karatzas, N. Katsifarakis, M. Riga, B. Werchan, M. Werchan, U. Berger, O. Pfaar, K.‐C. Bergmann
Journal: Allergy (2018)

The use of allergen immunotherapy (AIT) for allergic rhinitis and its clinical efficacy in clinical trials depends on the effective determination of pollen allergen exposure time periods. We evaluate pollen data from Germany to examine the new definitions on pollen season and peak pollen period start and end as proposed by the European Academy of Allergy and Clinical Immunology (EAACI) in a recently published Position Paper. The aim was to demonstrate the ability of these definitions to mirror symptom loads for grass and birch pollen-induced allergic rhinitis based on real-life data.Data coming from four pollen monitoring stations in the Berlin and Brandenburg area in Germany and for 3 years (2014-2016) were used to investigate the correlation of season definitions, birch and grass pollen counts and total nasal symptom and mediation scores as reported by patients in "Patients Hay fever Diaries" (PHDs). After the identification of pollen periods on the basis of the EACCI criteria, a statistical analysis was employed, followed by a detailed graphical investigation.The analysis revealed that the definitions of pollen season as well as peak pollen period start and end as proposed by the EAACI are correlated to symptom loads for grass and birch pollen-induced allergic rhinitis reported by patients in PHDs.Based on our analysis, the validity of the EAACI definitions on pollen season is confirmed. Their use is recommended in future clinical trials on AIT as well as in daily routine for optimal patient care.