tbuckley/cabot-search huggingface dataset:
AB1028 Rates of Switching and Healthcare Costs Associated with Switching Biological Disease-Modifying Antirheumatic Drugs in A Commercial Population: Evidence from Real-World Observational Studies
Authors: A. Nadkarni, F. Lobo, T. Juday
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Several biological disease-modifying antirheumatic drugs (bDMARDs) are approved for the treatment of moderate-to-severe RA. Switching between bDMARD therapies is common in real-world settings, and may have an impact on healthcare costs. <h3>Objectives</h3> To evaluate bDMARD switching and associated healthcare costs in patients with RA across two commercially insured populations in the US. <h3>Methods</h3> Two retrospective cohort studies of adult patients with RA who initiated a bDMARD were conducted using US commercial insurance claims databases. Patients were categorized into first- and second-line bDMARD cohorts. The first-line bDMARD cohort included patients who newly initiated a bDMARD (adalimumab, etanercept, infliximab or abatacept). The second-line bDMARD cohort included patients who initiated a second bDMARD. Patients in both first- and second-line bDMARD cohorts were required to have continuous eligibility 6 months before (pre-index) and 12 months after (post-index) initiation of first- or second-line bDMARD treatment. Patients in both cohorts were categorized into switchers and non-switchers. Switchers had a claim for a different bDMARD within a 200% gap in days supply for the index bDMARD. Non-switchers stayed on their index bDMARD in the post-index period. Switch rates were compared for each bDMARD. Patients who discontinued their index bDMARD and did not switch in the post-index period were excluded from the analyses. Rates of bDMARD switching, and pre- and post-index healthcare costs for switchers and non-switchers were examined. <h3>Results</h3> The first- and second-line bDMARD cohorts included 9757 and 2174 patients, respectively, in Study 1, and 6320 and 1297 patients, respectively, in Study 2. In both studies, rates of switching for the first- and second-line bDMARD cohorts were lower for abatacept compared with adalimumab, etanercept and infliximab (Table 1). Pre- and post-index healthcare costs in both studies were higher for first- and second-line bDMARD switchers compared with non-switchers (Table 2). <h3>Conclusions</h3> Patients on first- or second-line abatacept switched less frequently than patients on other bDMARDs. Post-index monthly healthcare costs were higher for first- and second-line bDMARD switchers versus non-switchers, suggesting there may be an economic benefit to using abatacept as the first- or second-line bDMARD in patients with moderate-to-severe RA. <h3>Disclosure of Interest</h3> A. Nadkarni Employee of: Bristol-Myers Squibb, F. Lobo Employee of: Bristol-Myers Squibb, T. Juday Employee of: Bristol-Myers Squibb <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1139
Abstract P5-10-23: Frequency and Cost of Chemotherapy-Related Serious Adverse Effects in a Canadian Population Sample of Women with Estrogen and/or Progesterone Receptor Positive Early Stage Breast Cancer
Authors: MB Hannouf, M Brackstone, G. Zaric
Journal: Cancer Research (2010)

Abstract Background: Chemotherapy-related serious adverse effects (CSAE) reported by clinical trials of chemotherapy and by population-based assessments of CSAE in breast cancer populations with different clinicopathological characteristics may not reflect the experiences of women with estrogen and/or progesterone receptor positive (ER+/PR+) early stage breast cancer (ESBC). We aimed to characterize the risks and economic impact of CSAE among women in the Canadian general population treated with chemotherapy for ER+/PR+ ESBC. Methods: We used the Manitoba Cancer Registry to identify all women (n=665) diagnosed with ER+/PR+ ESBC during the period from January 1, 2000 to December 31, 2002. One-year of follow-up information from diagnosis, including hospitalizations and emergency room visits for all adverse effects that are typically related to chemotherapy, were identified by linking with Manitoba Administrative Databases including the Hospital Discharge Database and the Physician Claims Database. 251 women received chemotherapy during the 12 months after the initial diagnosis with ESBC. Hospitalizations or emergency room visits for CSAE and health care expenditures were compared between women who did and did not receive chemotherapy. We assessed the effect of chemotherapy on rate of CSAE using logistic regression, adjusting for menopausal status, lymph node status, anthracycline-containing chemotherapy agents, and comorbid indices. All statistical tests were two-sided. Results: Women who received chemotherapy were more likely than those who did not to be hospitalized or visit an emergency room for CSAE (2.6% versus 9%, mean difference =6.4%, 95% CI=3.5% to 10%, p=0.01). In a logistic regression analysis, the rate of CSAE was found to be significantly greater for women with post-menopausal status (post-versus pre-menopausal, odds ratio 2.4; CI= 1.7 to 2.8) and 1-3 lymph node positive (LN+) (0 versus 1-3 LN+, odds ratio, 3.1; CI= 2.5 to 3.6). Chemotherapy recipients incurred large incremental expenditures for CSAE (pre-menopausal LN-: $1100 per person per year; post-menopausal LN-: $1600 per person per year; post-menopausal 1-3 LN+: $2200 per person per year). Conclusions: The impact and costs of CSAE among ER+/PR+ ESBC are larger than predicted from clinical data and vary significantly by lymph node and menopausal status. Our findings, when combined with recent population-based data suggesting that women with ER+/PR+ ESBC may not gain benefit from chemotherapy as much as reported in clinical trials, have important implications for quality of life and could affect decisions regarding the use of chemotherapy in these patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-23.
IMPACT OF CHRONIC KIDNEY DISEASE ON PLATELET P2Y12 RECEPTOR SIGNALING IN PATIENTS WITH DIABETES MELLITUS
Authors: Lydia R. Engwenyu, Fabiana Rollini, Francesco Franchi, Jung Rae Cho, Mona Bhatti, Christopher DeGroat, Zeina Alobaidi, Elisabetta Ferrante, Joseph Jakubowski, Atsuhiro Sugdiachi, Martin Zenni, Luis Guzman, Theodore Bass, Dominick Angiolillo
Journal: Journal of the American College of Cardiology (2015)
Abstract 2521: The pan-RAF inhibitor PLX4032 inhibits ERK signaling and tumor cell proliferation in a V600E BRAF mutant-selective manner
Authors: Eric W. Joseph, Christine A. Pratilas, Poulikos I. Poulikakos, Madhavi Tadi, WeiQing Wang, Barry S. Taylor, Yogindra Persaud, Feng Xing, Ensar Halilovic, Agnes Viale, Paul Chapman, James Tsai, Gideon Bollag, Neal Rosen, David B. Solit
Journal: Cancer Research (2010)

Abstract Activation of the RAS/RAF/MEK/ERK pathway occurs often in human cancer. Tumors with mutant BRAF and some with mutant RAS are dependent upon ERK signaling for proliferation and their growth is suppressed by selective inhibitors of MEK. In contrast, tumor cells with HER-kinase activation proliferate in a MEK-independent manner. These findings have led to the development of RAF and MEK inhibitors as anticancer agents. Like MEK inhibitors, the pan-RAF kinase inhibitor PLX4032 inhibits the proliferation of V600E BRAF mutant tumor cells, but not that of HER kinase dependent tumors. However, tumors with RAS mutation that are sensitive to MEK inhibition are insensitive to PLX4032. Whereas MEK inhibitors inhibit ERK phosphorylation in all normal and tumor cells, PLX4032 only inhibits ERK signaling in tumor cells with BRAF mutation. In contrast, the drug activates MEK and ERK phosphorylation in cells with wild-type BRAF. In mutant BRAF cells, the MEK and RAF inhibitors affect the expression of a common set of genes, whereas they have opposite effects on the expression of these genes in tumors with mutant RAS. Furthermore, PLX4032 inhibits ERK signaling output in mutant BRAF cells, but transiently activates it in tumor cells with wild-type RAF. Thus, PLX4032 inhibits ERK signaling output in a BRAF mutant-selective manner. These data suggest that PLX4032 may have a broader therapeutic index and help to explain the greater antitumor activity observed with this drug compared to MEK inhibitors, which inhibit ERK signaling in all cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2521.
899 SIGNIFICANCE OF MICRO RNA-122 IN PATIENTS WITH CHRONIC HEPATITIS C ON INTERFERON THERAPY
Authors: Y. Kamo, H. Miyaaki, T. Ichikawa, S. Uchida, E. Yoshimura, Y. Kubota, T. Yamaguchi, H. Shibata, T. Honda, N. Taura, H. Isomoto, F. Takeshima, K. Nakao
Journal: Journal of Hepatology (2012)
P224 Evaluation of inhaled corticosteroid related pneumonia mortality in patients with COPD who would not fit the criteria for inclusion in randomised controlled trials
Authors: A Singanayagam, S Schembri, AR Akram, R Archibald, L Peet, G Fleming, J Taylor, P Williamson, P Short, J Chalmers
Journal: Thorax (2013)

<h3>Background</h3> Large randomised controlled trials such as TORCH (towards a revolution in chronic obstructive pulmonary disease (COPD) health) report an increased risk of pneumonia associated with use of inhaled corticosteroids (ICS) in COPD but no corresponding increase in pneumonia-related mortality. However, these trials exclude patients who are elderly, comorbid, have co-existing lung conditions or use long-term oxygen therapy and may not be representative of ‘real-world’ practice. We hypothesised that ICS use in patients that are ineligible for TORCH would be associated with increased risk of pneumonia hospitalisations and mortality. <h3>Methods</h3> We carried out an analysis of 2 independent cohorts. The EXODUS cohort included patients admitted with COPD exacerbation and considered outcomes over 1 year including pneumonia hospitalisations and pneumonia-related mortality. The Edinburgh pneumonia study included patients hospitalised with community-acquired pneumonia with the primary outcome of 30-day mortality. A secondary analysis of patients from this cohort with spirometry-confirmed COPD during clinical stability was conducted. <h3>Results</h3> There were 977 patients included from the EXODUS cohort. 106 patients (10.8%) were hospitalised for pneumonia and 18 patients (1.8%) had pneumonia-related mortality within 12 months of initial admission. 497 patients (50.9%) would have been ineligible for the TORCH study. In a Cox proportional hazards model, adjusting for relevant confounders, patients who were ineligible for TORCH had an increased risk of pneumonia hospitalisation (HR 1.60; 95% CI 1.04–2.45) and an increased risk of pneumonia-related mortality (HR 6.1; 95% CI 1.7–22.0). Figure 1 shows a cox adjusted survival curve for pneumonia hospitalisations in patients eligible and ineligible for TORCH. There were 376 patients with COPD included from the Edinburgh pneumonia study. The 30-day mortality rate was 12.0%. 186 patients (38.0%) would have been ineligible for TORCH. After adjustment for relevant confounders, ICS use in patients classified as ineligible for TORCH was associated with increased risk of 30-day mortality (HR 1.85 95% CI 1.00–2.41). <h3>Conclusion</h3> Patients ineligible for RCTs such as TORCH are at increased risk of ICS related pneumonia mortality and hospitalisation. Existing studies may therefore underestimate the true impact of ICS related pneumonia in the “real-world” setting.
THU0414 Determination and quantification of synovial inflammation by magnetic resonance imaging in systemic sclerosis
Authors: B.N. Stamenkovic, A.M. Stankovic, A.N. Dimic, J.M. Nedovic, N. Damjanov, S.K. Stojanovic, D. Menkovic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Magnetic resonance imaging (MRI) is useful method for detection and quantification of subclinical synovial inflammation and joint damage with better precision than radiography in systemic sclerosis (SSc). Early aggressive treatment of inflammation may prevent joint damage and improve the outcomes <h3>Objectives</h3> To determine and quantify synovial inflammation by MRI in SSc; to examine the relationship of MRI findings with clinical and radiography features <h3>Methods</h3> 82 scleroderma patients (77 women and 5 male, mean age 54y,) underwent low field MR imaging with gadolinium at the dominant (clinically most active) hand including wrist and MCP joints 2-5. Assessment of bone marrow edema, synovitis, bone erosions and tenosynovitis was performed by the OMERACT RA MRI scoring system. Clinically features of musculoskeletal manifestations- articular or periarticular pain, joint contractures, swelling were recorded. Standard AP radiographs of the hand and wrist were obtained in 2 planes. Radiologically, we recorded articular (joint space narrowing-JSN, erosions, synovitis), soft tissue (calcification, tenosynovitis) and bone (osteopenia, bone resorption) changes <h3>Results</h3> 14/82 (17,1%) pts had clinically arthritis; 66/82 pts (80,5%) had arthralgias. Of 82% with scleroderma, 65/82 (79,3%) had inflammatory MR findings with synovitis in 64/82 (78%), erosions in 52 (63,4%) or tenosynovitis in 11 pts (14,1%) Synovitis was more frequently detected on MRI (78%) than clinically (17,1%), p&lt;0,001. Of 52 pts (63,4%) with MRI erosions, only 22 (27,5%) had radiographic erosions (p&lt;0,01). There was no statistically significant difference in prevalence of joint contractures by clinical examination- 28pts, 34,1% compared to radiography- 25pts, 32,1%, p=0,617. There was no difference, also, between clinical and MRI finding of tenosynovitis in SSc pts (p=0,617). Applying the OMERACT RAMRIS system, there was no difference between mean synovitis, erosion and oedema score between limited and diffuse SSc subtypes (synovitis, wrist: p=0,222, MCP: p=0,443; erosions, wrist:p=0,371, MCP:p=0,281; oedema, wrist: p=0,229; MCP: p=0,651). <h3>Conclusions</h3> MRI is more sensitive method than clinical examination and radiological finding of inflammation in scleroderma. Our study demonstrate the presence of persistant inflammatory, erosive arthropathy of the hand in SSc patients. RAMRIS scoring system, used in RA, also can be used to quantify the inflammatory arthritis in SSc <h3>Disclosure of Interest</h3> None Declared
FLAIL MITRAL LEAFLET OR PRESENCE OF THE COANDA EFFECT ARE NOT INVARIABLY ASSOCIATED WITH SEVERE MITRAL REGURGITATION AS ASSESSED BY MRI
Authors: Donna Chelle Morales, Seth Uretsky, Konstantinos Koulogiannis, Leo Marcoff, Lillian Aldaia, Edgar Argulian, Steven Wolff, Linda Gillam
Journal: Journal of the American College of Cardiology (2016)
Abstract 5329: Degradable multimodal nanoparticles with fluorescence and magnetic resonance contrast
Authors: Rao V. Papineni, William McLaughlin, Douglas Vizard, Ram Reddy
Journal: Cancer Research (2011)

Abstract Molecular Imaging is making rapid strides as a tool in understanding and the cure of cancer. Like no panacea, here again a need of multimodality exists, where more than one modality is becoming a necessity to cogently decipher the role or action of the biomolecule in the pathology or cure. Here, we developed a multimodal nanoparticle (NP) that can be simultaneously be imaged by optical, and magnetic resonance Imaging (MRI) modalities. In combination, the two modalities compensate each other's deficiencies in the spatial resolution, sensitivity, and the depth detection. Encapsulation of MR contrast and amine functionalization was performed in a one pot synthesis by microemulsion technique with supra magnetic iron oxide (SPIO). The hydrodynamic radii of nanoparticle and zeta potential were measured using Nicomp 380 zls particle sizer. 9L gliosarcoma tumor bearing rat model was administered with the SPIO nanoparticles and validated using 7 tesla MRI scanner. PEGylated SPIO nanoparticles after conjugation with water soluble, near-infrared (NIR) tricarbocyanine, cyclic enamine-functionalized dye, were injected intratumorally and monitored noninvasively using near-IR fluorescence imager. Steady retention in the tumor as compared to the free near-infrared (NIR) dye injected into the control mice indicates the dye-colloidal particle dwell characteristics and suitability for targeted diagnostics. In summary, we have described the development of a simple and efficient dynamic Imaging multimodal nanoparticle to be used for NIRF and MR Imaging. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5329. doi:10.1158/1538-7445.AM2011-5329
THU0511 Macrophage Growth by Polyploidization in Chronic Inflammation
Authors: A. Triantafyllopoulou, I. Nanda, T. Haaf, P. Henneke, R. Voll
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> How macrophages grow at sites of chronic inflammation is not well understood. In rheumatoid arthritis and several granulomatous autoimmune diseases, such as sarcoidosis, giant cell arteriitis and granulomatosis with polyangiitis, macrophages are thought to increase their size by cell to cell fusion thus producing multinucleated giant cells and osteoclasts. However, the underlying molecular and cellular programs for multinucleation and cell growth of macrophages at sites of chronic inflammation remain unclear. <h3>Objectives</h3> In this study, we aimed to elucidate the mechanisms of macrophage growth in the presence of proinflammatory cytokines in vitro and in a microbial model of chronic granulomatous inflammation in vivo. <h3>Methods</h3> We stimulated mouse bone marrow- derived macrophages with TNF in vitro and examined macrophage growth, cell cycle and ploidy using long term live cell imaging, image cytometry, molecular biological approaches and cytogenetics. To examine macrophage growth in a TNF-rich granulomatous environment in vivo, we injected mice i.p. with Mycobacterium bovis BCG and examined macrophage size and ploidy in liver granulomas using immunofluorescence and image cytometry. <h3>Results</h3> We show that the proinflammatory cytokine TNF can induce macrophage growth by polyploidization producing giant cells which contain nuclei with increased DNA content. Using long term live cell imaging, we found that polyploid macrophages can be generated by cytokinesis failure due to supernumerary centrosomes and DNA trapped at the cleavage furrow. TNF regulated cell cycle events by modulating the expression of cell cycle proteins and promoting the proliferation and survival of polyploid rather than diploid macrophages. <h3>Conclusions</h3> TNF can induce macrophage polyploidization by regulating the cell cycle and promoting cytokinesis failure. This pathway of macrophage polyploidization is distinct from the previously described macrophage polyploidization by cell to cell fusion which is not known to require cell cycle regulation. We propose that macrophage polyploidization by TNF-modulated cell cycle regulation may be an important mechanism for the growth and survival of macrophages in chronic inflammatory diseases. <h3>Acknowledgements</h3> Funding: Federal Ministry for Education and Research, Germany and Marie Curie FP7 International Reintegration Grant. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2468
Hyperparathyroidism in Relation to Pregnancy
Authors: George D. Ludwig
Journal: New England Journal of Medicine (1962)

RECENTLY, 2 patients presenting the problem of pregnancy and primary hyperparathyroidism were observed. The first spontaneously aborted during the sixth month of gestation. The second manifested symptoms and signs suggesting primary hyperparathyroidism early in the course of her second pregnancy. To advise her properly, information was sought about whether primary hyperparathyroidism during gestation increases the incidence of complications of pregnancy, of fetal death or of neonatal morbidity. Since no discussion of this subject was found in any of the standard textbooks of medicine or obstetrics, or in any of the monographs on parathyroid disease,1 2 3 a search of the literature was . . .
A paper that saved my life: Mobile intensive care units
Authors: P. Arnold
Journal: BMJ (2001)

Sometime in 1967, I came across a report in the BMJ on a paper by Pantridge and Geddes in the Lancet .1 A purpose designed and equipped ambulance that carried a team led by a doctor had been introduced in Belfast for the prompt assessment of suspected myocardial ischaemia. Some months earlier, a patient of mine had died soon after I had visited him at home. I had suspected myocardial ischaemia and, as was the practice at that time, had given him morphine, recommended bed rest, and arranged for …
Presurgical Localization of Abnormal Parathyroid Glands Using a Single Injection of Tc-99m Sestamibi
Authors: ANNE KIRSTINE ARVESCHOUG, HENRIK BERTELSEN, BIRTHE VAMMEN
Journal: Clinical Nuclear Medicine (2002)

Purpose Scintigraphy using Tc-99m sestamibi is sensitive in localizing abnormal parathyroid glands in patients with hyperparathyroid disease (HPT). Various methods have been described to increase the sensitivity of the single-tracer technique, such as SPECT, factor analysis of dynamic structures, and use of a pinhole collimator, but often the gain in sensitivity is accompanied by a loss of specificity. Purpose In this study, the authors compared the sensitivity and specificity of side localization of the diseased gland(s) using the double-phase single-tracer method performed with and without the addition of a pinhole collimator in the early and late phases of imaging. The combined high-resolution parallel-hole and pinhole collimator imaging protocol was further validated by investigation of interobserver and intraobserver variation. Materials and Methods Forty-seven patients with primary HPT and 16 patients with secondary HPT examined from 1996 to 1999 with the Tc-99m sestamibi double-phase technique and who had subsequent surgery formed the basis of the study. Their histologic and follow-up data were also factored into this analysis. Tc-99m sestamibi (750 to 900 MBq; 18.9 to 24.3 mCi) was injected. Ten-minute neck and mediastinum images acquiring 1,000 K counts were obtained with the high-resolution parallel-hole collimator, and a neck image containing 500 K counts was obtained with the pinhole collimator. Two to three hours later, the same parallel-hole and pinhole collimator images were obtained that had the same acquisition time as the early images. Two observers who were nuclear medicine specialists independently viewed all the parallel-hole scintigrams and afterward all parallel-hole and pinhole scintigrams two times. Results Thirty-eight (81%) of the patients with primary HPT had a single adenoma. The sensitivity and specificity for the correct side of localization were 54% and 89%, respectively, using the high-resolution parallel-hole collimator, and 88% and 77%, respectively, with the addition of the pinhole collimator in all patients with primary HPT. In patients with secondary HPT, the sensitivity and specificity for localization of the correct side were 58% and 100%, respectively, using the high-resolution parallel-hole collimator, and 85% and 100%, respectively, with the addition of the pinhole collimator. The interobserver agreement was acceptable, with an overall agreement of 84% and a κ value of 0.67. The intraobserver agreement was even better, with an overall agreement of 88% and 90% and κ values of 0.76 and 0.79 for the two observers. Conclusions Sensitivity is increased considerably when the pinhole collimator is added to the imaging protocol of parathyroid scintigraphy in patients with primary or secondary HPT. A loss of specificity occurred only in patients with primary HPT. The precision of the combined approach is very high.