tbuckley/cabot-search huggingface dataset:
FRI0555 Long Term Effectiveness of Herpes Zoster Vaccine among Patients with Autoimmune and Inflammatory Diseases
Authors: H. Yun, F. Xie, J.W. Baddley, K. Winthrop, L. Chen, J.R. Curtis
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Recent results from long-term follow-up of healthy older participants of the Shingles Prevention Study (SPS) demonstrated that the herpes zoster (HZ) vaccination lost most of its benefit after approximately 10 years. However, the duration of protection among patients with autoimmune or inflammatory (AI) diseases is unclear. <h3>Objectives</h3> Current study aimed to evaluate the duration of HZ vaccine effectiveness in preventing HZ among older patients with autoimmune diseases. <h3>Methods</h3> Using Medicare data from 2006–2013 for patients with AI diseases, this retrospective cohort study identified patients who had HZ vaccination. To control for confounding, patients without HZ vaccination were matched 2:1 to vaccinated patients on year of vaccination, age, gender, race, type of AI diseases, and use of biologics, DMARDs and glucocorticoids. Follow up began one month after vaccination and ended at: HZ, death, loss of coverage or 12/31/2012. We calculated HZ incidence rates for each year and used Poisson regression to calculate the adjusted risk ratio of HZ for each year. <h3>Results</h3> Of 59,627 vaccinated patients with AIs matched to 119,254 unvaccinated AI patients, we identified 1,242 and 3,183 HZ events during follow-up respectively. Incidence rates among vaccinated increased from 0.75 per 100 person years (PY) during the first year post vaccination to 1.36 during the 6th year post. After multivariable adjustment, vaccinated patients had a significantly lower risk of HZ compared to unvaccinated patients through 5 years but not beyond. <h3>Conclusions</h3> Among patients with autoimmune diseases, the effectiveness of HZ vaccination waned over time, and a significant benefit to reduce HZ risk compared to non-vaccinated patients was found only through 5 years post vaccination. <h3>Disclosure of Interest</h3> H. Yun: None declared, F. Xie: None declared, J. Baddley: None declared, K. Winthrop: None declared, L. Chen: None declared, J. Curtis Grant/research support from: Roche/Genentech, UCB, Janssen, Corrona, Amgen, Pfizer, BMS, Crescendo, AbbVie, Consultant for: Roche/Genentech, UCB, Janssen, Corrona, Amgen, Pfizer, BMS, Crescendo, AbbVie
Long‐term clinical impact and cost‐effectiveness of obeticholic acid for the treatment of primary biliary cholangitis
Authors: Sumeyye Samur, Matthew Klebanoff, Reiner Banken, Daniel S. Pratt, Rick Chapman, Daniel A. Ollendorf, Anne M. Loos, Kathleen Corey, Chin Hur, Jagpreet Chhatwal
Journal: Hepatology (2016)

Primary biliary cholangitis (PBC) is a chronic, progressive autoimmune liver disease that mainly affects middle‐aged women. Obeticholic acid (OCA), which was recently approved by the Food and Drug Administration for PBC treatment, has demonstrated positive effects on biochemical markers of liver function. Our objective was to evaluate the long‐term clinical impact and cost‐effectiveness of OCA as a second‐line treatment for PBC in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA. We developed a mathematical model to simulate the lifetime course of PBC patients treated with OCA+UDCA versus UDCA alone. Efficacy data were derived from the phase 3 PBC OCA International Study of Efficacy trial, and the natural history of PBC was informed by published clinical studies. Model outcomes were validated using the PBC Global Study. We found that in comparison with UDCA, OCA+UDCA could decrease the 15‐year cumulative incidences of decompensated cirrhosis from 12.2% to 4.5%, hepatocellular carcinoma from 9.1% to 4.0%, liver transplants from 4.5% to 1.2%, and liver‐related deaths from 16.2% to 5.7% and increase 15‐year transplant‐free survival from 61.1% to 72.9%. The lifetime cost of PBC treatment would increase from $63,000 to $902,000 (1,330% increment). The discounted quality‐adjusted life years with UDCA and OCA+UDCA were 10.74 and 11.78, respectively, and the corresponding costs were $142,300 and $633,900, resulting in an incremental cost‐effectiveness ratio of $473,400/quality‐adjusted life year gained. The results were most sensitive to the cost of OCA. Conclusion : OCA is a promising new therapy to substantially improve the long‐term outcomes of PBC patients, but at its current annual price of $69,350, it is not cost‐effective using a willingness‐to‐pay threshold of $100,000/quality‐adjusted life year; pricing below $18,450/year is needed to make OCA cost‐effective. (H epatology 2017;65:920‐928).
Palbociclib and Letrozole in Advanced Breast Cancer
Authors: Richard S. Finn, Miguel Martin, Hope S. Rugo, Stephen Jones, Seock-Ah Im, Karen Gelmon, Nadia Harbeck, Oleg N. Lipatov, Janice M. Walshe, Stacy Moulder, Eric Gauthier, Dongrui R. Lu, Sophia Randolph, Véronique Diéras, Dennis J. Slamon
Journal: New England Journal of Medicine (2016)

A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than with letrozole alone in the initial treatment of postmenopausal women with estrogen-receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer. We performed a phase 3 study that was designed to confirm and expand the efficacy and safety data for palbociclib plus letrozole for this indication.
OP0256 Presence of Risk Factors for Cardiovascular Disease Predates The Onset of Symptoms of Rheumatoid Arthritis
Authors: H. Kokkonen, S. Rantapää-Dahlqvist
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) are at increased risk of developing cardiovascular (CV) comorbidity compared with the general population. Contradictory results concerning CV disease prior to onset of RA have been reported. Of the known CV risk factors, a more atherogenic lipid profile and smoking have been presented prior to RA onset. <h3>Objectives</h3> In this study, lifestyle factors, lipid levels, presence of hypertension, and diabetes were evaluated in individuals prior to onset of symptoms of RA and matched population controls from northern Sweden. <h3>Methods</h3> A nested case-control study was based on information from The Västerbotten Intervention Programme (VIP) and the WHO Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA). Data were collected by questionnaire (socioeconomic and lifestyle factors), assessments by a nurse (body mass index;BMI, waist and blood pressure), and blood sampling (lipids and glucose loading). The registers of patients with RA (ARA criteria) attending the Department of Rheumatology, Umeå was co-analysed with the registers from VIP and MONICA. This study included 547 pre-symptomatic individuals (mean age 51.5years; 372f/175m, median (IQR) predating time 5.0 (7.0) years), and 1654 controls (mean age 51.6years; 1123f/531m). CV risk factors were defined as: hypertension (systolic≥140 mmHg, diastolic≥90 mmHg), ApoB/ApoA1 ratio (females ≥0.7, males ≥0.8), BMI≥25, diabetes, and ever smoker. <h3>Results</h3> Lower levels of ApoA1 (OR=2.0 (95%CI1.25, 3.25) and increased ApoB/ApoA1 ratio (OR=2.25 95%CI1.25, 4.06) were associated with RA development, particularly in females besides smoking, BMI and waist range. Plasma glucose at baseline was related to disease development, particularly in males (OR=1.18 95%CI1.01, 1.37). Blood pressure did not differ between the groups. Conditional logistic regression models identified elevated ApoB/ApoA1 ratio (OR=1.25 95%CI1.01, 1.56), being ever smoker (OR=2.00 95%CI1.63, 2.47), BMI≥25 (OR=1.33 95%CI1.09, 1.63) and diabetes (OR=1.98 95%CI1.06, 3.68) but not hypertension (OR=0.89 95%CI 0.72–1.11) to be associated with RA development. The pre-symptomatic individuals had significantly higher frequency of these risk factors, 32.3% of these individuals had ≥3 of these factors compared with 23.2% of the matched controls (OR=2.52 95%CI1.67, 3.83). <h3>Conclusions</h3> Several of the CV risk factors are present in individuals already years before onset of symptoms of RA. One third of the pre-symptomatic individuals had at least 3 of these factors present. These results urge early CV prevention in patients with RA. <h3>Acknowledgement</h3> The Medical Biobank of northern Sweden is acknowledged. <h3>Disclosure of Interest</h3> None declared
Multi-Parameter Phenotypic Analysis of Members of Chronic Lymphocytic Leukemia Clones Identifies Distinct Proliferative and Resting/Re-Entry Compartments with Discrete Gene Expression Profiles.
Authors: Carlo Calissano, Rajendra N Damle, Xiao J. Yan, Wentian Li, Sonia Marsilio, Jonathan E. Kolitz, Matthew S. Kaufman, Steven L Allen, Kanti R. Rai, Nicholas Chiorazzi
Journal: Blood (2009)
Elevated Heat Shock Protein 70 (HSP70) Serum Levels After Tumor Radiofrequency Ablation Might Represent a Favorable Prognostic Marker.
Authors: Sebastian P. Haen, Philippe L. Pereira, Stephan Clasen, Diethard Schmidt, Andreas Boss, Alexandra von Herbay, Lothar Kanz, Hans-Georg Rammensee, Cecile Gouttefangeas
Journal: Blood (2009)
IPH2101, a Novel Anti-Inhibitory KIR Monoclonal Antibody, and Lenalidomide Combine to Enhance the Natural Killer (NK) Cell Versus Multiple Myeloma (MM) Effect.
Authors: Don Benson, Courtney E Bakan, Shuhong Zhang, Lana Alghothani, Jing Liang, Craig Hofmeister, Shivani Srivastava, Megan K Smith, Carli N Greenfield, Pascale Andre, Patrick Squiban, Francois Romagne, Michael A. Caligiuri, Sherif Farag
Journal: Blood (2009)
Monocytes Are a Particularly Favorable Target for Surface Platelet Factor 4 (PF4) Antigenic Complex Formation in Heparin-Induced Thrombocytopenia: New Insights into the Thrombotic Risk in HIT
Authors: Lubica Rauova, Gowthami M Arepally, Douglas B. Cines, Mortimer Poncz
Journal: Blood (2008)
Dramatic Reduction of Chronic Lymphocytic Leukemia (CLL) Cells Following Adoptive Transfer of Cord Blood (CB) Natural Killer (NK) Cells Using CB-Engrafted NOD-SCID IL2Rγnull (NSG) Mice as a Model.
Authors: Dongxia Xing, Alan G. Ramsay, William Decker, Sufang Li, Simon Robinson, Hong Yang, Nina Shah, Chitra Hosing, Catherine M. Bollard, John G. Gribben, Elizabeth J. Shpall
Journal: Blood (2009)
Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) as Salvage Treatment for Relapsing Multiple Myeloma (MM): A “Donor” vs. “No Donor” Comparison.
Authors: Hugues de Lavallade, Patrick Ladaique, Catherine Faucher, Sabine Furst, Jean El-Cheikh, Anne-Marie Stoppa, Diane Coso, Reda Bouabdallah, Norbert Vey, Danielle Sainty, Christian Chabannon, Jean-Albert Gastaut, Didier Blaise, Mohamad Mohty
Journal: Blood (2006)
Varicella-Zoster-Virus-Specific CD4+ Cytotoxic T Cells as Tumor-Specific Effector Cells in Cancer Immunotherapy.
Authors: Silke Landmeier, Sibylle Pscherer, Bodo Eing, Cliona M. Rooney, Heribert Juergens, Claudia Rossig
Journal: Blood (2005)
The Midostaurin (PKC412) Metabolite CGP52421 Shows Little Growth-Inhibitory Activity Against Against Neoplastic Mast Cells but Retains Inhibitory Effects on IgE-Dependent Activation and Histamine Release
Authors: Barbara Peter, Katharina Blatt, Gabriele Stefanzl, Emir Hadzijusufovic, Catherine Dutreix, Stefan H Gross, Johannes L Roesel, Peter Valent
Journal: Blood (2011)
Impact of Renal Impairment (RI) on Outcomes after Treatment (Tx) with Lenalidomide and Low-Dose Dexamethasone (Rd) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts): First Trial Results
Authors: Meletios A. Dimopoulos, Matthew C Cheung, Murielle Roussel, Ting Liu, Barbara Gamberi, Brigitte Kolb, H. Guenter Derigs, Hyeon Seok Eom, Karim Belhadj, Pascal Lenain, Richard H. van der Jagt, Sophie Rigaudeau, Mamoun Dib, Rachel Hall, Arnaud Jaccard, Axel Tosikyan, Lionel Karlin, William Bensinger, Rik Schots, Guang Chen, Jennifer Marek, Annette Ervin-Haynes, Thierry Facon
Journal: Blood (2014)
THU0460 What Is The Best Lumbar Spine Vertebrae Combination To Predict Major Osteoporotic Fracture? The Osteolaus Cohort Study:
Authors: H. Mraihi, O. Lamy, M. Metzger, S. Soares, B. Aubry-Rozier, D. Stoll, D. Hans
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The international guidelines recommend to use the average bone mineral density (BMD) over L1 to L4 in the management of osteoporosis and prediction of fracture. Exclusion of certain vertebrae is recommended according to specific rules (ISCD position). The spine Trabecular Bone score (TBS), a surrogate of bone micro-architecture, has been newly introduced into international guidelines and the FRAX® tool for clinical use in conjunction with BMD and clinical risk factors. <h3>Objectives</h3> The aim of this study is to test several TBS vertebrae combinations in regard to major osteoporotic fracture prediction. <h3>Methods</h3> The osteoLaus cohort (Lausanne, Switzerland) included 1500 woman 50 to 80 years old. All women had a detailed questionnaire related to clinical risk factors and treatment known to influence bone metabolism, BMD measurement (hip, spine and whole body), vertebral fracture assessment and TBS. The primary outcome was the prevalence of major osteoporotic fracture (MOF) according to TBS per-vertebral combination. Appropriate statistics and necessary adjustment for confounding factors were performed. L1-L4 TBS was used as reference value. <h3>Results</h3> Out of 19466 women included in the study (mean age 64.5±7.6 years, BMI 25.7±4.4), 12.7% suffered from MOF. The odd ratios per standard deviation decreased (OR) were 1.53 (1.29 – 1.80) and 1.80 (1.50 – 2.15) for the spine and total femur BMD respectively. Adjusted (age &amp; glucocorticoids status) OR and area under the curve of different combination of vertebrae can be found in the following table for TBS. <h3>Conclusions</h3> It seems that excluding L4 tends to improve the fracture risk prediction. TBS is very sensitive to vertebra positioning (e.g. projection). To compensate for the natural lordosis of the spine, one has to lift the legs of the patient. L4 is often still angled which could explained such results. Further prospective studies are needed to confirm these results. <h3>Disclosure of Interest</h3> None declared
Clinical Outcomes for Chronic Lymphocytic Leukemia (CLL) Patients with 11q Deletion in British Columbia (BC), Canada: Results of a Population-Based Cohort
Authors: Jennifer Goy, Tanya L. Gillan, Huang J.T. Steven, Helene Bruyere, Monica Anne Hrynchak, Aly Karsan, Khaled Ramadan, Adam C. Smith, Cynthia L. Toze, Alina S. Gerrie
Journal: Blood (2014)
Aberrant Overexpressions of MicroRNA-21 and MicroRNA-155 Activate AKT Signaling Via Downregulation of Tumor Suppressors in NK-Cell Lymphoma/Leukemia.
Authors: Hiroyuki Tagawa, Yasuo Yamanaka, Atsushi Watanabe, Naoto Takahashi, Ken-ichi Sawada
Journal: Blood (2009)
Complete Inhibition of STAT5 Phosphorylation Is Achieved By Combination of JAK1/2 and PI3K/mTOR Inhibitors in in Vitro and In Vivo MPN Models
Authors: Niccolò Bartalucci, Laura Calabresi, Serena Martinelli, Manjola Balliu, Jean-Luc Villeval, Francesco Annunziato, Alessandro M. Vannucchi
Journal: Blood (2015)
Effect of Rituximab on the Incidence of GVHD in Lymphoma Patients who Received the BEAM-Conditioning and an Allogeneic Stem Cell Transplantation.
Authors: Issa F. Khouri, Rima M. Saliba, Daniel R. Couriel, Grace-Julia Okoroji, Sandra Acholonu, Farzaneh Maadani, Richard E. Champlin
Journal: Blood (2004)
SAT0503 Relationships between Weight, Physical Activity and Back Pain in Young Adult Women
Authors: S.R.E. Brady, S.M. Hussain, W.J. Brown, S. Heritier, B. Billah, Y. Wang, H. Teede, D.M. Urquhart, F.M. Cicuttini
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Back pain is a major global health problem, causing greater disability worldwide than any other condition. It is associated with a significant economic burden and major disability, as therapeutic options have limited efficacy. Given limited treatment options, clarifying predictors of back pain is important in order to optimize preventive strategies. Furthermore, as previous episodes of back pain are predictive of future recurrence, understanding risk factors associated with back pain in early adulthood is particularly important. <h3>Objectives</h3> The study aims were to identify whether modifiable risk factors, weight and physical activity, are predictive of back pain in young adult women. <h3>Methods</h3> Community dwelling women born between 1973 and 1978 were randomly selected from the Australian national health insurance scheme database to participate in the Australian Longitudinal Study of Women9s Health. Women were recruited nationally with intentional oversampling from rural and remote areas. Self-reported data on back pain in the last 12 months, age, weight, physical activity, depression and other socio-demographic factors were collected in 2000, 2003, 2006, 2009 and 2012. In 2000, 9,688 women completed the questionnaire and 83% completed follow up 12 years later. <h3>Results</h3> At baseline, median age was 24.6 years and 41% had self-reported back pain. For every 5kg higher weight at baseline, there was a 5% (95% CI 4% - 6%) increased risk of back pain over the next 12 years, after adjusting for age, height, education status, physical activity and depression. Higher weight also predicted back pain risk over each 3 year survey interval (p&lt;0.001). The effects of weight on back pain were most significant in those with body mass index ≥25 kg/m<sup>2</sup> and were observed at all levels of physical activity. Inadequate physical activity and depression were independent predictors of back pain over the following 12 years (both p&lt;0.001), after adjusting for above confounders. <h3>Conclusions</h3> Back pain is common in community-based young adult women. Higher weight, inadequate levels of physical activity and depression were all independent predictors of back pain over the following decade. Furthermore, the adverse effects of weight on back pain were not mitigated by physical activity. Our findings highlight the role of both higher weight and physical inactivity in back pain among young adult women and suggest potential opportunities for future prevention. <h3>Disclosure of Interest</h3> None declared
Quantitative Analysis of Wild Type and V617F JAK-2 Expression in Neutrophils of Polycythemia Vera and Essential Thrombocythemia Patients at Diagnosis.
Authors: Eric Lippert, Francois Girodon, Robert Kralovics, Marjorie Boissinot, Irene Dobo, Vincent Praloran, Nathalie Boiret, Radek C. Skoda, Sylvie Hermouet
Journal: Blood (2005)
A retrospective analysis of tolerability in EGFR-mutated NSCLC patients who received afatinib
Authors: Haruki Koriyama, Kiyotaka Yoh, Keisuke Kirita, Shigeki Umemura, Shingo Matsumoto, Seiji Niho, Hironobu Ohmatsu, Koichi Goto
Journal: Annals of Oncology (2015)
CRISPR/Cas9 Editing of Murine Induced Pluripotent Stem Cells for Engineering Inflammation‐Resistant Tissues
Authors: Jonathan M. Brunger, Ananya Zutshi, Vincent P. Willard, Charles A. Gersbach, Farshid Guilak
Journal: Arthritis & Rheumatology (2016)

Objective Proinflammatory cytokines such as interleukin‐1 (IL‐1) are found in elevated levels in diseased or injured tissues and promote rapid tissue degradation while preventing stem cell differentiation. This study was undertaken to engineer inflammation‐resistant murine induced pluripotent stem cells (iPSCs) through deletion of the IL‐1 signaling pathway and to demonstrate the utility of these cells for engineering replacements for diseased or damaged tissues. Methods Targeted deletion of the IL‐1 receptor type I (IL‐1RI) gene in murine iPSCs was achieved using the RNA‐guided, site‐specific clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 genome engineering system. Clonal cell populations with homozygous and heterozygous deletions were isolated, and loss of receptor expression and cytokine signaling was confirmed by flow cytometry and transcriptional reporter assays, respectively. Cartilage was engineered from edited iPSCs and tested for its ability to resist IL‐1–mediated degradation in gene expression, histologic, and biomechanical assays after a 3‐day treatment with 1 ng/ml of IL‐1α. Results Three of 41 clones isolated possessed the IL‐1RI +/− genotype. Four clones possessed the IL‐1RI −/− genotype, and flow cytometry confirmed loss of IL‐1RI on the surface of these cells, which led to an absence of NF‐κB transcription activation after IL‐1α treatment. Cartilage engineered from homozygous null clones was resistant to cytokine‐mediated tissue degradation. In contrast, cartilage derived from wild‐type and heterozygous clones exhibited significant degradative responses, highlighting the need for complete IL‐1 blockade. Conclusion This work demonstrates proof‐of‐concept of the ability to engineer custom‐designed stem cells that are immune to proinflammatory cytokines (i.e., IL‐1) as a potential cell source for cartilage tissue engineering.
THU0110 Effectiveness of Biologic and Nonbiologic Antirheumatic Drugs on Anemia in Adult Patients (PTS) with Rheumatoid Arthritis (RA): New Evidence from Real-World Data: Table 1.
Authors: S.K. Paul, K. Klein, J.H. Best, S. Gale, A. Pethö-Schramm, K. Sarsour
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Anemia, a common complication of RA, has a negative impact on RA symptoms and QOL and is associated with a more severe form of RA. Roles of biologic DMARDs (BDMARDs), including the IL-6 pathway–inhibiting biologic tocilizumab (TCZ), in the pathophysiology of anemia have not been well explored at the population level. <h3>Objectives</h3> Evaluate the impact of treatment (Tx) with nonbiologic (NB) and BDMARDs on hemoglobin (Hb) and hematocrit (Hct) in a real-world setting. <h3>Methods</h3> Using the GE EMR database, a longitudinal cohort study was conducted on 153,672 adult RA pts in the US who had ≥6-mo follow-up. 4 mutually exclusive DMARDTx groups (TxGs) were identified: TCZ, tofacitinib (TOFA), other BDMARDs (OBDMARD), and other NBDMARDs (ONBDMARD). To evaluate changes in Hb and Hct at 6 and 12 mo from index date (ID) in different TxGs, unadjusted and adjusted mean (95% CI) changes were obtained, adjusting for age, sex, smoking status, RA duration, concomitant medications, CRP, and other covariates. Separate analyses were conducted for pts with Hb &lt;12/13.5 g/dL for women/men (anemic). <h3>Results</h3> Demographics of the cohort were: 55 y mean age, 76% female, 59% white, 57% current or ex-smokers, 44% obese (mean BMI 30 kg/m<sup>2</sup>). 2% of pts had ischemic heart disease, 2% renal disease, and 7% diabetes. Mean Hb and Hct levels at ID across TxGs were 13.3 g/dL and 40%. Average CRP (1.6 mg/dL) and ESR (23 mm/h) were clinically similar across TxGs at ID. Adjusting for covariates, increases in Hb and Hct levels at 6 and 12 mo were significantly higher in the TCZ group vs the other TxGs (Table). Among anemic pts at ID, increases in Hb and Hct at 6 mo were significantly higher in the TCZ group vs the other TxGs. Significantly greater reductions in ESR and CRP levels over all follow-up periods were observed in the TCZ group vs the other TxGs. <h3>Conclusions</h3> This study suggests significant increases in Hb and Hct levels after TCZ therapy vs other nonbiologic and biologic therapies in RA pts with anemia, in line with the potential role of IL-6 in RA pts with anemia. Further study is needed to better evaluate the role of IL-6–based OBDMARDs as a Tx option for RA pts with anemia. <h3>Disclosure of Interest</h3> S. Paul Grant/research support from: Genentech, AstraZeneca, Novo Nordisk, Consultant for: GI Dynamics, Speakers bureau: AstraZeneca, GI Dynamics, Novo Nordisk, K. Klein Grant/research support from: Genentech, AstraZeneca, Novo Nordisk, Consultant for: GI Dynamics, J. Best Shareholder of: Roche, Employee of: Genentech, S. Gale Shareholder of: Roche, Employee of: Roche, A. Pethö-Schramm Employee of: F. Hoffmann-La Roche, K. Sarsour Shareholder of: Roche, Employee of: Roche