tbuckley/cabot-search huggingface dataset:
Association Between Serum Antibodies to Periodontal Bacteria and Rheumatoid Factor in the Third National Health and Nutrition Examination Survey
Authors: Charlene E. Goh, Jacob Kopp, Panos N. Papapanou, Jerry A. Molitor, Ryan T. Demmer
Journal: Arthritis & Rheumatology (2016)

Alterations in the microbiome, including the periodontal microbiome, may be a risk factor for rheumatoid arthritis (RA). Most studies that have analyzed this association are relatively small, focus primarily on a single periodontal pathogen (Porphyromonas gingivalis), and are not population based. This study was undertaken to investigate the association between elevated serum levels of IgG antibodies to 19 periodontal species and the prevalence of rheumatoid factor (RF) in a large nationally representative sample of adults.The Third National Health and Nutrition Examination Survey (NHANES-III) is a cross-sectional sample of the noninstitutionalized US population (n = 33,994). Our study population included all dentate participants who were 60 years and older, did not have RA as defined by a modified version of the American College of Rheumatology 1987 criteria, and had complete data for both serum IgG antibodies against periodontal bacteria and serum RF antibody titer (n = 2,461).Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) summarizing the relationship between the 19 periodontal serum IgG antibodies and RF seropositivity ranged from 0.53 (95% CI 0.29-0.97) to 1.27 (95% CI 0.79-2.06), and 17 of the 19 observed ORs were <1.0. The ORs for RF seropositivity among participants with elevated Prevotella intermedia (0.53 [95% CI 0.29-0.97]) and Capnocytophaga ochracea (0.54 [0.31-0.95]) IgG levels were statistically significant.Our findings indicate that elevated levels of IgG antibodies to periodontal bacteria are mostly unassociated with RF seropositivity in the nationally representative NHANES-III. Elevated levels of antibodies to P intermedia and C ochracea are associated with lower odds of RF seropositivity.
Phase II study of combination therapy with pegylated liposomal doxorubicin (PLD)and carboplatin in patients (pts) with relapsed, platinum sensitive and platinum semi-sensitive ovarian cancer
Authors: B. L. Rapoport, D. A. Vorobiof, C. Slabber, G. Cohen, A. S. Alberts, H. S. Hlophe
Journal: Journal of Clinical Oncology (2008)

5555 Background: To assess the anti-tumor effect and safety of carboplatin and PLD administration in pts with relapsed, platinum sensitive and platinum semi-sensitive ovarian cancer. Methods: The objective of this phase II second line study is to determine efficacy and toxicity of PLD at a dose of 50mg/m2 in combination with carboplatin (AUC = 5) q 28days, in pts with recurrent ovarian cancer with a disease free interval (DFI) greater than 6 months. Pts were divided into 2 groups: Group 1 (G1) with a DFI of 6 months to 1 year (semisensitive disease), and group 2 (G2) with DFI longer than 1 year (sensitive disease). Fourty pts were enrolled (G1 = 19 pts and G2 = 21pts). Median age was 58 years (range 34–75), 21 pts had an ECOG PS of 1 and 19 had PS of 0. Median CA 125 at presentation is 129 U/ml (range 3–8,894). A total of 227 cycles have been administered, median 6 cycles (range 1–8). Results: Response: A total of 27 pts responded to treatment (67.5%) (95% confidence interval 50.8% - 81.4%). There were 14 CR and 13 PR. In the G1 10/19 pts responded (52.6%) (6 pts (38.1%) attained a CR). Among the G2 pts, 17/21 responded to treatment 80.95% (8 pts (38.1%) attained a CR). The median response duration among the 27 responders was 373 days (53–1856 days). The median response duration for pts attaining a CR was 462 days (94- 1856).The median survival was 911 days (range 129–2037) with 10 pts alive.Toxicity: No toxic related deaths were documented. Grade III and IV haematological toxicity includes anaemia (grade III: 4 pts), neutropenia (grade III: 15 pts; grade IV: 5 pts) and thrombocytopenia (grade III: 12 pts; grade IV: 1 pt). Febrile neutropenia: Six pts. No active bleeding was documented.Grade III and IV non haematological toxicity included nausea and vomiting (grade III in 3 pts). Other relevant toxicities included PPE (grade I: 5 pts; grade II: 12 pts; grade III: 3 pts). Stomatitis (grade I: 6 pts; grade II: 14 pts; grade III: 2 pts) and aesthenia (grade I-III: 28 pts). No renal toxicity has been observed. Conclusions: The combination of PLD 50mg/m2 with carboplatin AUC = 5, is a safe and active second line chemotherapy regime for advanced platinum sensitive and semi-sensitive ovarian cancer. No significant financial relationships to disclose.
Risk of developing tuberculosis disease among persons diagnosed with latent tuberculosis infection in the Netherlands
Authors: Connie G.M. Erkens, Erika Slump, Maurits Verhagen, Henrieke Schimmel, Frank Cobelens, Susan van den Hof
Journal: European Respiratory Journal (2016)

Diagnosis and preventive treatment of latent tuberculosis infection (LTBI) among high-risk groups is recommended to achieve tuberculosis (TB) elimination in low-incidence countries.We studied TB incidence rates among those notified with LTBI in the Netherlands from 2005 to 2013 and analysed associated risk factors. We stratified analyses by target group for screening, and by initiation and completion of preventive treatment.The incidence for those completing, stopping and not receiving preventive treatment was 187, 436 and 355 per 100 000 person-years for contacts of TB patients, respectively, and 63, 96 and 110 per 100 000 person-years for other target groups. The rate ratio for TB development among contacts compared to other target groups was 3.1 (95% CI 2.0-4.9). In both groups, incidence was highest in the first year after diagnosis. Independent factors associated with progression to TB among contacts were age <5 years and stopping preventive treatment within 28 days compared to those not receiving preventive treatment. Among other target groups, being foreign born was the only risk factor associated with the risk of developing TB.We conclude that the epidemiological impact of preventive treatment is highest in contacts of TB patients and limited in other target groups for LTBI management in the Netherlands.
IMA901, a multipeptide cancer vaccine, plus sunitinib versus sunitinib alone, as first-line therapy for advanced or metastatic renal cell carcinoma (IMPRINT): a multicentre, open-label, randomised, controlled, phase 3 trial
Authors: Brian I Rini, Arnulf Stenzl, Romauld Zdrojowy, Mikhail Kogan, Mikhail Shkolnik, Stephane Oudard, Steffen Weikert, Sergio Bracarda, Simon J Crabb, Jens Bedke, Joerg Ludwig, Dominik Maurer, Regina Mendrzyk, Claudia Wagner, Andrea Mahr, Jens Fritsche, Toni Weinschenk, Steffen Walter, Alexandra Kirner, Harpreet Singh-Jasuja, Carsten Reinhardt, Tim Eisen
Journal: The Lancet Oncology (2016)
Phase I study of cetuximab, irinotecan, and vandetanib (ZD6474) in previously treated metastatic colorectal cancer (mCRC).
Authors: J. A. Meyerhardt, D. Schrag, M. Kulke, P. C. Enzinger, J. A. Chan, L. S. Blaszkowsky, M. Goldstein, B. Allen, E. Regan, T. A. Abrams
Journal: Journal of Clinical Oncology (2010)

e14055 Background: Given limits of individual targeted therapies in the treatment of mCRC, combining agents is increasingly attractive. ZD6474 is an orally bioavailable inhibitor of VEGFR-2 and EGFR tyrosine kinases. Methods: Phase I trial with cetuximab, irinotecan, and ZD6474 in previously treated patients with mCRC (initiated March 2007 but amended August 2008 to limit to KRAS wild type after first 7 pts). Standard phase I design of 3 pts/dose level with expansion of 3 more pts if DLT observed; 2 DLTs defined maximum tolerated dose (MTD) as dose level -1 (dose levels 1 and 3 required pt replacements). After a loading dose, 250 mg/m2 of cetuximab was administered weekly. Irinotecan was 180 mg/m2 every other week. Oral ZD6474 was tested at 100 mg, 200 mg, and 300 mg daily. Dose level 1 did not include irinotecan. Ten patients will be tested at the MTD. Results: Between March 2007 and December 2009, 24 patients were enrolled at 4 dose levels and at the MTD (Table). Median age = 53; male: female = 11:13. 56% had prior irinotecan; 78% prior oxaliplatin. KRAS status: 17 wild type, 2 mutant, and 5 unknown. The MTD was determined to be 200 mg ZD6474 daily. Of 21 evaluable (2 withdrew prior to staging; 1 not staged to date), 10% partial response, 62% stable disease (SD), and 18% progressed. Of those with SD, 38% had at least 20% shrinkage. Median progression-free survival (PFS) is 3.9 months (m) (95% CI, 3.5-5.7) and median overall survival (OS) is 13.5 m (95% CI, 4.8-20.6) in all patients; PFS is 4.9 m (95% CI, 3.5-11.7) and OS is not reached when limited to KRAS wildtype. Grade 3/4 toxicities occurring in more than 1 patient: grade 3 diarrhea 29%, grade 3 electrolyte change 21%, grade 3 neutropenia 13%, grade 3 abdominal/pelvis pain 8%, grade 3 rash 8% and grade 3 renal dysfunction due to dehydration 8%. Conclusions: ZD6474 at 200 mg daily can be combined with cetuximab and irinotecan for mCRC. The trial is ongoing and updated efficacy and safety will be available for June 2010. Dose level # of pts ZD6474 Cetuximab Irinotecan DLTs 1 4 100 mg X – None 2 3 100 mg X X None 3 5 200 mg X X None 4 5 300 mg X X * Grade 3 QTc prolongation (n=1)* Grade 3 diarrhea (n=1) MTD 7 200 mg X X Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Bristol-Myers Squibb, sanofi-aventis Bristol-Myers Squibb
Fine-Tuning Motile Cilia and Flagella: Evolution of the Dynein Motor Proteins from Plants to Humans at High Resolution
Authors: Martin Kollmar
Journal: Molecular Biology and Evolution (2016)

The flagellum is a key innovation linked to eukaryogenesis. It provides motility by regulated cycles of bending and bend propagation, which are thought to be controlled by a complex arrangement of seven distinct dyneins in repeated patterns of outer- (OAD) and inner-arm dynein (IAD) complexes. Electron tomography showed high similarity of this axonemal repeat pattern across ciliates, algae, and animals, but the diversity of dynein sequences across the eukaryotes has not yet comprehensively been resolved and correlated with structural data. To shed light on the evolution of the axoneme I performed an exhaustive analysis of dyneins using the available sequenced genome data. Evidence from motor domain phylogeny allowed expanding the current set of nine dynein subtypes by eight additional isoforms with, however, restricted taxonomic distributions. I confirmed the presence of the nine dyneins in all eukaryotic super-groups indicating their origin predating the last eukaryotic common ancestor. The comparison of the N-terminal tail domains revealed a most likely axonemal dynein origin of the new classes, a group of chimeric dyneins in plants/algae and Stramenopiles, and the unique domain architecture and origin of the outermost OADs present in green algae and ciliates but not animals. The correlation of sequence and structural data suggests the single-headed class-8 and class-9 dyneins to localize to the distal end of the axonemal repeat and the class-7 dyneins filling the region up to the proximal heterodimeric IAD. Tracing dynein gene duplications across the eukaryotes indicated ongoing diversification and fine-tuning of flagellar functions in extant taxa and species.
Alternative Strategies to Inpatient Hospitalization for Acute Medical Conditions
Authors: Jared Conley, Colin W. O’Brien, Bruce A. Leff, Shari Bolen, Donna Zulman
Journal: JAMA Internal Medicine (2016)

<h3>Importance</h3> Determining innovative approaches that better align health needs to the appropriate setting of care remains a key priority for the transformation of US health care; however, to our knowledge, no comprehensive assessment exists of alternative management strategies to hospital admission for acute medical conditions. <h3>Objective</h3> To examine the effectiveness, safety, and cost of managing acute medical conditions in settings outside of a hospital inpatient unit. <h3>Evidence Review</h3> MEDLINE, Scopus, CINAHL, and the Cochrane Database of Systematic Reviews (January 1995 to February 2016) were searched for English-language systematic reviews that evaluated alternative management strategies to hospital admission. Two investigators extracted data independently on trial design, eligibility criteria, clinical outcomes, patient experience, and health care costs. The quality of each review was assessed using the revised AMSTAR tool (R-AMSTAR) and the strength of evidence from primary studies was graded according to the Oxford Centre for Evidence-Based Medicine. <h3>Findings</h3> Twenty-five systematic reviews (representing 123 primary studies) met inclusion criteria. For outpatient management strategies, several acute medical conditions had no significant difference in mortality, disease-specific outcomes, or patient satisfaction compared with inpatient admission. For quick diagnostic units, the evidence was more limited but did demonstrate low mortality rates and high patient satisfaction. For hospital-at-home, a variety of acute medical conditions had mortality rates, disease-specific outcomes, and patient and caregiver satisfaction that were either improved or no different compared with inpatient admission. For observation units, several acute medical conditions were found to have no difference in mortality, a decreased length of stay, and improved patient satisfaction compared to inpatient admission; results for some conditions were more limited. Across all alternative management strategies, cost data were heterogeneous but showed near-universal savings when assessed. <h3>Conclusions and Relevance</h3> For low-risk patients with a range of acute medical conditions, evidence suggests that alternative management strategies to inpatient care can achieve comparable clinical outcomes and patient satisfaction at lower costs. Further study and application of such opportunities for health system redesign is warranted.
Breast cancer patients access to screening, radiotherapy, and cancer drugs in 18 European, Asian, and Latin American countries.
Authors: N. E. Wilking, J. Bergh, B. Jönsson, F. Kasteng
Journal: Journal of Clinical Oncology (2010)

612 Background: Breast cancer has a better prognosis compared many other cancer forms, with 10- year relative survival rates of up to 80% in some countries. Still, the burden of breast cancer is considerable both in terms of suffering for patients and economic burden to society. Survival differs greatly between countries that appear to have comparable resources dedicated to healthcare. This study reviews patients' access to screening, radiotherapy and breast cancer drugs, all important in the development towards optimizing breast cancer care. The study includes European countries (Denmark, Finland, France, Germany, Hungary, Italy, the Netherlands, Norway, Poland, Slovenia, Spain, Sweden and the UK) as well as China, Brazil, Mexico, Russia and Turkey. Methods: A review of literature and public databases was performed. Epidemiologic data from Globocan 2002 and Eurocare-4 was used as well as information about available radiotherapy resources from the DIRAC, IAEA data. Drug usage (mg of use in correlation to breast cancer cases) was based on data from IMS Health. Results: The lack of clinical and epidemiological data in many countries is a severe limitation, when identifying trends in cancer prevention, care, treatment and outcomes over time as well as when making intercountry comparisons. Still, we found a 15x variation in breast cancer care spending per capita; a variation in 5-year survival from 55-90% ; variation in screening attendance from 15-85%,; a variation in access to radiotherapy of 10x and variations in access to breast cancer drugs (tamoxifen of 5x; aromatase inhibitors 25x; taxanes 50x and trastuzumab of > 50x). Radiotherapy and drug access were adjusted for breast cancer mortality. Conclusions: There is a need for registries to capture not only incidence and mortality but also access to screening and treatment in relation to outcome. In order to achieve high quality and equal care, guidelines need to be evidence-based, regularly updated and monitored. It is essential that regulations, funding, and care organisation are coordinated to provide all patients with the most appropriate, cost-effective and evidence-based treatment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pierre Fabre Medicament, Roche Pierre Fabre Medicament, Roche
Updated survival-based analysis using inverse probability of censoring weighted analysis (IPCW) to estimate the cost-effectiveness of letrozole and anastrozole versus tamoxifen as adjuvant therapy in postmenopausal women with early breast cancer.
Authors: J. Karnon, S. Kaura
Journal: Journal of Clinical Oncology (2010)

656 Background: The latest update of the BIG 1-98 study (74 months) applied IPCW to estimate treatment effect in the presence of selective crossover (25% of TAM pts). The IPCW hazard ratio for overall survival (OS) is 0.83 (95% CI 0.71 - 0.97, p < 0.05) for 5 yrs letrozole (LET) vs. tamoxifen (TAM). At 100 months, ATAC remains to show a significant OS benefit for anastrozole (ANA) compared to TAM. This study uses observed differences in OS to estimate the incremental cost per quality adjusted LY (QALY) gained of 5 yrs LET vs. 5 yrs TAM in ER+ postmenopausal women, from a UK NHS perspective. Methods: Annual survival probabilities post-surgery were extracted from updated BIG 1-98 and ATAC results. Survival was extrapolated to 20 yrs using data reported by the EBCTG for women receiving 5 years TAM. Conservatively, equivalent annual survival probabilities were assumed for TAM and AI groups post-follow-up. Published adverse event (AE) costs and 5yr costs for locoregional recurrence (LR) and metastases (METS) were applied. Published utility weights for DFS with AEs, LR, and METS were used. Costs and health benefits were discounted at 3.5% annually. Results: Over a 20-year period, the discounted additional treatment costs of LET are ≤ 3,618. When accounting for AEs and the reduced frequency of recurrence, the total cost difference between LET and TAM is ≤ 2,964. The model estimated a difference in discounted QALYs of 0.297, with an incremental cost per QALY gained of ≤ 9,999. For ANA, over the same period, the discounted additional treatment costs are ≤3,736. Accounting for AEs and the reduced frequency of recurrence, the total discounted cost difference between ANA and TAM is ≤ 2,929. The incremental cost per QALY gained for ANA over TAM is ≤ 46,829. Conclusions: Economic analysis of 5yrs LET compared to 5yrs TAM based on observed differences in OS produces similar results to earlier modelled extrapolations based on differences in time to recurrence, and confirm that LET is a cost-effective use of healthcare resources. These analyses show LET to be substantially more cost-effective than ANA. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis
A Retrospective Population-Based Study of a Series of 307 Treatment-naïve Patients with Chronic Lymphocytic Leukemia (CLL): Study of the Clinical Features and Efficacy of First-Line Therapy
Authors: Eva Ma Donato, Rafa Andreu, Aurelio Lopez, Ana Vicente, Ana Carral, Isidro Jarque, M. Angeles Ruiz, Felix Carbonell, Mar Osma, Margarita Blanes, Rosa Ferrer, Alfonso Garcia, Francisca Marin, Pablo Lorente, Ma Dolores Garcia, Ma Fernanda Palmero, Jose Antonio Fernandez, Mario Montagud, Miguel Blanquer, Ma Jose Lis, Paula Irene Petruskevicius, Mar Tormo, María José Terol
Journal: Blood (2010)
Associations between Environmental Quality and Mortality in the Contiguous United States, 2000–2005
Authors: Yun Jian, Lynne C. Messer, Jyotsna S. Jagai, Kristen M. Rappazzo, Christine L. Gray, Shannon C. Grabich, Danelle T. Lobdell
Journal: Environmental Health Perspectives (2016)

Assessing cumulative effects of the multiple environmental factors influencing mortality remains a challenging task.This study aimed to examine the associations between cumulative environmental quality and all-cause and leading cause-specific (heart disease, cancer, and stroke) mortality rates.We used the overall Environmental Quality Index (EQI) and its five domain indices (air, water, land, built, and sociodemographic) to represent environmental exposure. Associations between the EQI and mortality rates (CDC WONDER) for counties in the contiguous United States (n = 3,109) were investigated using multiple linear regression models and random intercept and random slope hierarchical models. Urbanicity, climate, and a combination of the two were used to explore the spatial patterns in the associations.We found 1 standard deviation increase in the overall EQI (worse environment) was associated with a mean 3.22% (95% CI: 2.80%, 3.64%) increase in all-cause mortality, a 0.54% (95% CI: -0.17%, 1.25%) increase in heart disease mortality, a 2.71% (95% CI: 2.21%, 3.22%) increase in cancer mortality, and a 2.25% (95% CI: 1.11%, 3.39%) increase in stroke mortality. Among the environmental domains, the associations ranged from -1.27% (95% CI: -1.70%, -0.84%) to 3.37% (95% CI: 2.90%, 3.84%) for all-cause mortality, -2.62% (95% CI: -3.52%, -1.73%) to 4.50% (95% CI: 3.73%, 5.27%) for heart disease mortality, -0.88% (95% CI: -2.12%, 0.36%) to 3.72% (95% CI: 2.38%, 5.06%) for stroke mortality, and -0.68% (95% CI: -1.19%, -0.18%) to 3.01% (95% CI: 2.46%, 3.56%) for cancer mortality. Air had the largest associations with all-cause, heart disease, and cancer mortality, whereas the sociodemographic index had the largest association with stroke mortality. Across the urbanicity gradient, no consistent trend was found. Across climate regions, the associations ranged from 2.29% (95% CI: 1.87%, 2.72%) to 5.30% (95% CI: 4.30%, 6.30%) for overall EQI, and larger associations were generally found in dry areas for both overall EQI and domain indices.These results suggest that poor environmental quality, particularly poor air quality, was associated with increased mortality and that associations vary by urbanicity and climate region. Citation: Jian Y, Messer LC, Jagai JS, Rappazzo KM, Gray CL, Grabich SC, Lobdell DT. 2017. Associations between environmental quality and mortality in the contiguous United States, 2000-2005. Environ Health Perspect 125:355-362; http://dx.doi.org/10.1289/EHP119.
Bulky Disease Does Not Adversely Affect Overall Survival in Early Stage Hodgkin Lymphoma: Role of Interim PET and Possible Omission of Radiotherapy in Select Patients
Authors: Priyanka A Pophali, Lisa A. Rybicki, Kathleen B Fenner, Deepa Jagadeesh, Robert M Dean, Brad Pohlman, Mitchell R. Smith, Brian T. Hill
Journal: Blood (2014)
Next Generation Flow (NGF) for High Sensitive Detection of Minimal Residual Disease (MRD) in Multiple Myeloma (MM)
Authors: Juan A Flores-Montero, Bruno Paiva, Luzalba Sanoja-Flores, Noemi Puig, Omar García, Sebastian Böttcher, José J Pérez-Morán, Maria Belen Vidriales, Maria-Victoria Mateos, Ramon Garcia-Sanz, Cristina Jimenez, Marcos González, Joaquin Martinez-López, María Consuelo Cañizo, Jesus San Miguel, Brian Durie, Jacques J.M. van Dongen, Alberto Orfao
Journal: Blood (2015)
Clofarabine Based Chemotherapy in Adult Relapsed/Refractory Acute Lymphoblastic Leukemia/Lymphoma-a Single Institution Experience
Authors: Hassan B Alkhateeb, Moussab Damlaj, Tasha Lin, Aref Al-Kali, Lisa Sproat, Jeffrey Alan Betcher, Jason N. Barreto, Shahrukh K. Hashmi, Mrinal M Patnaik, Naseema Gangat, Michelle Elliott, Mark R Litzow, William J Hogan
Journal: Blood (2015)