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1. Racial disparities in positive airway pressure therapy adherence among veterans with obstructive sleep apnea

Author: Armand Ryden, Nancy Hsu, Michelle Zeidler, and Constance H. Fung
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Positive airway pressure, Humans, Medicine, Patient compliance, Retrospective Studies, Veterans, Sleep Apnea, Obstructive, Continuous Positive Airway Pressure, business.industry, Health Status Disparities, Therapy adherence, medicine.disease, Scientific Investigations, Obesity, Obstructive sleep apnea, 030228 respiratory system, Neurology, Patient Compliance, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: STUDY OBJECTIVES: Black individuals are disproportionately affected by diabetes, cardiovascular disease, obesity, and OSA. Adherence to PAP therapy has been reported to be lower among black individuals. This study seeks to examine associations between black race and PAP adherence among veterans with OSA. METHODS: This was a retrospective study. Veterans newly diagnosed with OSA at a single Department of Veterans Affairs sleep center who were prescribed a modem-enabled PAP device between January 2015 and November 2017 were enrolled. PAP adherence was defined as ≥ 4 hours nightly usage for at least 70% of nights measured at 30 days from PAP setup. We examined the relationship between race and adherence, controlling for sex, marital status, age, socioeconomic status, residual apnea-hypopnea index), and mask leak. RESULTS: Of 3013 patients identified with OSA, 2571 (85%) were newly started on PAP therapy (95% male, aged 59 years ± 14 years, 45% married, 8% with neighborhood socioeconomic disadvantage). Twenty-five percent of participants were black, and 57% were white. PAP adherence at 30 days was 50% overall (42% among blacks, 53% among nonblacks). Black race was associated with reduced 30-day PAP adherence in unadjusted (P < .001) and adjusted logistic regression models (odds ratio = 0.64; 95% CI, 0.53 – 0.78; P < .001). CONCLUSIONS: Among veterans with OSA, black race was associated with reduced PAP adherence. These findings suggest health inequality among black individuals in the treatment of OSA. CITATION: Hsu N, Zeidler MR, Ryden AM, Fung CH. Racial disparities in positive airway pressure therapy adherence among veterans with obstructive sleep apnea. J Clin Sleep Med. 2020;16(8):1249–1254.
Published: 2020
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2. Role of Combination Antiplatelet and Anticoagulation Therapy in Diabetes Mellitus and Cardiovascular Disease

Author: Deepak L. Bhatt, John W. Eikelboom, Stuart J. Connolly, P. Gabriel Steg, Sonia S. Anand, Subodh Verma, Kelley R.H. Branch, Jeffrey Probstfield, Jackie Bosch, Olga Shestakovska, Michael Szarek, Aldo Pietro Maggioni, Petr Widimský, Alvaro Avezum, Rafael Diaz, Basil S. Lewis, Scott D. Berkowitz, Keith A.A. Fox, Lars Ryden, Salim Yusuf, V. Aboyans, M. Alings, P. Commerford, N. Cook-Bruns, G. Dagenais, A. Dans, G. Ertl, C. Felix, T. Guzik, R. Hart, M. Hori, A. Kakkar, K. Keltai, M. Keltai, J. Kim, A. Lamy, F. Lanas, Y. Liang, L. Liu, E. Lonn, P. Lopez-Jaramillo, K. Metsarinne, P. Moayyedi, M. O’Donnell, A. Parkhomenko, L. Piegas, N. Pogosova, M. Sharma, S. Stoerk, A. Tonkin, C. Torp-Pedersen, J. Varigos, P. Verhamme, D. Vinereanu, K. Yusoff, and J. Zhu
Subjects: Male, medicine.medical_specialty, Arterial disease, MEDLINE, Disease, Coronary artery disease, Double-Blind Method, Rivaroxaban, Physiology (medical), Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Humans, Aged, Aspirin, business.industry, Anticoagulants, Middle Aged, medicine.disease, Cardiovascular Diseases, Cardiology, Platelet aggregation inhibitor, Drug Therapy, Combination, Female, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, Factor Xa Inhibitors
Abstract: Background: Patients with established coronary artery disease or peripheral artery disease often have diabetes mellitus. These patients are at high risk of future vascular events. Methods: In a prespecified analysis of the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies), we compared the effects of rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg daily) versus placebo plus aspirin in patients with diabetes mellitus versus without diabetes mellitus in preventing major vascular events. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included all-cause mortality and all major vascular events (cardiovascular death, myocardial infarction, stroke, or major adverse limb events, including amputation). The primary safety end point was a modification of the International Society on Thrombosis and Haemostasis criteria for major bleeding. Results: There were 10 341 patients with diabetes mellitus and 17 054 without diabetes mellitus in the overall trial. A consistent and similar relative risk reduction was seen for benefit of rivaroxaban plus aspirin (n=9152) versus placebo plus aspirin (n=9126) in patients both with (n=6922) and without (n=11 356) diabetes mellitus for the primary efficacy end point (hazard ratio, 0.74, P =0.002; and hazard ratio, 0.77, P =0.005, respectively, P interaction =0.77) and all-cause mortality (hazard ratio, 0.81, P =0.05; and hazard ratio, 0.84, P =0.09, respectively; P interaction =0.82). However, although the absolute risk reductions appeared numerically larger in patients with versus without diabetes mellitus, both subgroups derived similar benefit (2.3% versus 1.4% for the primary efficacy end point at 3 years, Gail-Simon qualitative P interaction P interaction =0.02; 2.7% versus 1.7% for major vascular events, P interaction P interaction =0.001). Conclusions: In stable atherosclerosis, the combination of aspirin plus rivaroxaban 2.5 mg twice daily provided a similar relative degree of benefit on coronary, cerebrovascular, and peripheral end points in patients with and without diabetes mellitus. Given their higher baseline risk, the absolute benefits appeared larger in those with diabetes mellitus, including a 3-fold greater reduction in all-cause mortality. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01776424.
Published: 2020
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3. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice

Author: Visseren, F. L. J., Mach, F., Smulders, Y. M., Carballo, D., Koskinas, K. C., Back, M., Benetos, A., Biffi, A., Boavida, J. -M., Capodanno, D., Cosyns, B., Crawford, C., Davos, C. H., Desormais, I., DI Angelantonio, E., Franco, O. H., Halvorsen, S., Hobbs, F. D. R., Hollander, M., Jankowska, E. A., Michal, M., Sacco, S., Sattar, N., Tokgozoglu, L., Tonstad, S., Tsioufis, K. P., Van DIs, I., Van Gelder, I. C., Wanner, C., Williams, B., De Backer, G., Regitz-Zagrosek, V., Aamodt, A. H., Abdelhamid, M., Aboyans, V., Albus, C., Asteggiano, R., Borger, M. A., Brotons, C., Ielutkiene, J., Cifkova, R., Cikes, M., Cosentino, F., Dagres, N., De Backer, T., De Bacquer, D., Delgado, V., Den Ruijter, H., Dendale, P., Drexel, H., Falk, V., Fauchier, L., Ference, B. A., Ferrieres, J., Ferrini, M., Fisher, M., Fliser, D., Fras, Z., Gaita, D., Giampaoli, S., Gielen, S., Graham, I., Jennings, C., Jorgensen, T., Kautzky-Willer, A., Kavousi, M., Koenig, W., Konradi, A., Kotecha, D., Landmesser, U., Lettino, M., Lewis, B. S., Linhart, A., Lochen, M. -L., Makrilakis, K., Mancia, G., Marques-Vidal, P., Mcevoy, J. W., Mcgreavy, P., Merkely, B., Neubeck, L., Nielsen, J. C., Perk, J., Petersen, S. E., Petronio, A. S., Piepoli, M., Pogosova, N. G., Prescott, E. I. B., Ray, K. K., Reiner, Z., Richter, D. J., Ryden, L., Shlyakhto, E., Sitges, M., Sousa-Uva, M., Sudano, I., Tiberi, M., Touyz, R. M., Ungar, A., Verschuren, W. M. M., Wiklund, O., Wood, D., Zamorano, J. L., Crawford, C. A., Franco Duran, O. H., Richard Hobbs, F. D., Dis, I. V., Group, ESC Scientific Document, Clinical sciences, Cardio-vascular diseases, and Cardiology
Subjects: medicine.medical_specialty, Epidemiology, Population, air pollution, population, Guidelines, blood pressure, climate change, diabetes, healthy lifestyle, lifetime benefit, lifetime risk, lipids, nutrition, personalized, prevention, psychosocial factors, risk estimation, risk management, shared decision-making, smoking, stepwise approach, Risk Assessment, Humans, Primary Prevention, Risk Factors, Cardiovascular Diseases, Diabetes mellitus, medicine, Intensive care medicine, education, 610 Medicine & health, Risk management, education.field_of_study, business.industry, medicine.disease, Clinical Practice, Blood pressure, guidelines, Heart failure, Lifetime risk, Disease prevention, Cardiology and Cardiovascular Medicine, business, Stepwise approach, 360 Social problems & social services
Abstract: These are the clinical practice guidelines from the European Society of Cardiology on cardiovascular disease prevention in clinical practice, from 2021.
Published: 2022
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4. Shaken not stirred: A pilot study testing a gyroscopic spoon stabilization device in Parkinson's disease and tremor

Author: P. Clouston, Elie Matar, Lauren E. Ryden, Jennifer Y. Y. Szeto, Deborah A Hammond, and Simon J.G. Lewis
Subjects: medicine.medical_specialty, Parkinson's disease, Physical medicine and rehabilitation, business.industry, Medicine, Neurology (clinical), business, medicine.disease, Letters to the Editor, lcsh:Neurology. Diseases of the nervous system, lcsh:RC346-429
Published: 2020

5. Abstract 15586: Burden of Cardiovascular or Fatal Outcomes in People With Type 2 Diabetes and Cardiovascular Risk Factors Treated With Dulaglutide a Post Hoc Analysis From the Rewind Trial

Author: Lars E Ryden, Mark Lakshmanan, Leanne Dyal, Hertzel C. Gerstein, Helen Colhoun, Charles Atisso, and Gilles R. Dagenais
Subjects: Agonist, medicine.medical_specialty, medicine.drug_class, business.industry, Cardiovascular risk factors, Incretin, Type 2 diabetes, medicine.disease, Clinical trial, Physiology (medical), Diabetes mellitus, Internal medicine, Post-hoc analysis, medicine, Dulaglutide, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: Introduction: In the REWIND (Researching cardiovascular Events with a Weekly INcretin in Diabetes) trial, weekly subcutaneous dulaglutide 1.5 mg, a glucagon-like peptide-1 receptor agonist, compared with matched placebo reduced MACE (cardiovascular [CV] death, non-fatal myocardial infarction or non-fatal stroke) (594 versus 663 events) in 9901 participants with type 2 diabetes at moderate CV risk [mean (SD) age 66.2 (6.5) years, 46.3% women, 31% with chronic CV disease and the others with CV risk factors] and followed for a median of 5.4 years. These findings, based on a time to first event analysis, do not reflect total CV event or mortality burden. Objective: To better reflect the burden of disease, the following outcomes were assessed: 1) total number of MACE or fatal events and 2) total number of CV (MACE, unstable angina, heart failure or revascularization) or fatal events in the REWIND participants. Methods: Incidence was estimated per 1000 person-years (py), and hazard ratios (HR) were calculated using conditional time gap and proportional means models. Results: A total of 1972 MACE outcomes or deaths and of 3673 CV outcomes or deaths occurred in the 9901 participants. Of the1128 all-cause deaths, 465 were non-CV. The incidence of total MACE or deaths was 35.8 in the dulaglutide group versus 40.3/1000 py in the placebo group [absolute reduction=4.5/1000 py; conditional time gap HR, 0.90 (95%CI, 0.82-0.98), P =0.020, and proportional means HR, 0.89 (95% CI, 0.80-0.98), P =0.022]. The incidence of total CV or fatal events on dulaglutide was 67.1 and 74.7/1000 py on placebo [absolute reduction=7.6/1000 py; conditional time gap HR, 0.93 (95% CI, 0.87-0.99), P =0.023, and proportional means HR, 0.90 (95% CI 0.82-0.99), P =0.028]. Similar effect sizes were noted for the first occurrence of MACE or deaths such that the absolute risk reduction was 4.1/ 1000 py. Conclusions: These findings suggest that weekly subcutaneous dulaglutide was associated with reduced total MACE, CV or fatal event burden in people with type 2 diabetes and moderate CV risk. This analysis illustrates the clinical relevance of assessing total events in addition to first events in clinical trials. Clinical Trial Registration: https://www.clinicaltrials.gov. Unique Identifier NCT01394952)
Published: 2020
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6. Abstract 13307: An Oral Antisense Oligonucleotide for PCSK9 Inhibition in Humans

Author: Yanfeng Wang, Anna Tivesten, Niclas Clemmensen, Dinko Rekić, Mikko Hölttä, Marie Elebring, Lloyd G. Tillman, Catarina Nilsson, Björn Carlsson, stanley riney, Rosie Z. Yu, Kristina Ryden-Bergsten, Brett P. Monia, Rosanne M. Crooke, Daniel Lindén, Jane Knoechel, Katrin Walter, Eva Hurt-Camejo, Rasmus Jansson-Löfmark, Cristina S. J. Rocha, Peter Gennemark, Ulf Andersson, and Nigel Davies
Subjects: business.industry, PCSK9, Arteriosclerosis, 030204 cardiovascular system & hematology, Pharmacology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Antisense oligonucleotides, Medicine, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business, PCSK9 Inhibitors
Abstract: Current PCSK9 inhibitors are administered via subcutaneous (SC) injection. Here, we present a highly potent, chemically modified PCSK9 antisense oligonucleotide (ASO) with potential for oral delivery. Past attempts at oral delivery using earlier ASO chemistries and intestinal permeation enhancers provided encouraging data, suggesting that improving potency of the ASO could make oral delivery a reality. The constrained ethyl chemistry and liver targeting enabled by tri-antennary N -acetyl galactosamine (GalNAc) conjugation make this ASO highly potent. A single SC dose of 90 mg reduces PCSK9 by >90% in humans with elevated LDL-C (A), and a once monthly SC dose of 25 mg ([20, 30], 90% CI) is predicted to reduce PCKS9 by 80% at steady-state. To investigate the feasibility of oral administration, we developed an oral solid tablet wherein the ASO is co-formulated with a transient permeation enhancer. Repeated oral daily dosing of tablets to dogs resulted in a bioavailability of 7% in the liver (target organ), approximately 5-fold greater than the plasma bioavailability (B). Favourable liver uptake following oral administration is supported by similar bioavailability in plasma and kidney. Since the ASO is not active in rodents or dogs, we used a rat-specific GalNAc- Malat-1 ASO with the same chemistry to confirm target engagement. Intrajejunal administration resulted in ≥78% mRNA knockdown in the liver for single doses of 3-40 mg/kg. A monkey tolerability study of the PCSK9 ASO further supports oral feasibility with all tested doses (28-56 mg/day) significantly reducing LDL-C already after 7 days of daily oral dosing. Based on available animal and human data, and an assumption of 5% oral bioavailability in humans, a daily dose of 15 mg ([10, 20], 90% CI) in man is predicted to reduce PCSK9 in plasma by 80% at steady-state. This supports the development of the compound for subcutaneous and oral administration to treat dyslipidemia.
Published: 2020
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7. Inhibiting cardiac myeloperoxidase alleviates the relaxation defect in hypertrophic cardiomyocytes

Author: Chrishan J A Ramachandra, Li-Ming Gan, Katarina Ryden-Markinhuhta, Elisa A. Liehn, Malin K.B. Jonsson, Sakthivel Sadayappan, Philip Wong, Regina Fritsche-Danielson, Ying-Hsi Lin, Sauri Hernández-Reséndiz, Myu Mai Ja Kp, Hak Chiaw Tang, Jasper Chua, Winston Shim, Ratan Bhat, Ralph Knöll, Derek J. Hausenloy, and Erik Michaëlsson
Subjects: Male, Physiology, Human-induced pluripotent stem cells (hiPSCs), Left ventricular hypertrophy, medicine.disease_cause, Ventricular Function, Left, AcademicSubjects/MED00200, Myocytes, Cardiac, Enzyme Inhibitors, Phosphorylation, Myeloperoxidase, biology, Hypertrophic cardiomyopathy, Cardiology, Diastolic dysfunction, Hypertrophy, Left Ventricular, medicine.symptom, Cardiology and Cardiovascular Medicine, Cardiac Remodelling and Heart Failure, medicine.medical_specialty, Induced Pluripotent Stem Cells, Diastole, Hypertrophic cardiomyopathy (HCM), Mutation, Missense, macromolecular substances, Exercise intolerance, Cell Line, Physiology (medical), Internal medicine, medicine, Animals, Humans, cardiovascular diseases, Peroxidase, Myosin Heavy Chains, business.industry, Original Articles, Cardiomyopathy, Hypertrophic, medicine.disease, Myocardial Contraction, Mice, Inbred C57BL, Disease Models, Animal, Oxidative stress, biology.protein, Tyrosine, MYH7, business, Carrier Proteins, Reactive Oxygen Species, Cardiac Myosins, Cardiac myosin binding protein-C (MYBPC3)
Abstract: Aims Hypertrophic cardiomyopathy (HCM) is characterized by cardiomyocyte hypertrophy and disarray, and myocardial stiffness due to interstitial fibrosis, which result in impaired left ventricular filling and diastolic dysfunction. The latter manifests as exercise intolerance, angina, and dyspnoea. There is currently no specific treatment for improving diastolic function in HCM. Here, we investigated whether myeloperoxidase (MPO) is expressed in cardiomyocytes and provides a novel therapeutic target for alleviating diastolic dysfunction in HCM. Methods and results Human cardiomyocytes derived from control-induced pluripotent stem cells (iPSC-CMs) were shown to express MPO, with MPO levels being increased in iPSC-CMs generated from two HCM patients harbouring sarcomeric mutations in the MYBPC3 and MYH7 genes. The presence of cardiomyocyte MPO was associated with higher chlorination and peroxidation activity, increased levels of 3-chlorotyrosine-modified cardiac myosin binding protein-C (MYBPC3), attenuated phosphorylation of MYBPC3 at Ser-282, perturbed calcium signalling, and impaired cardiomyocyte relaxation. Interestingly, treatment with the MPO inhibitor, AZD5904, reduced 3-chlorotyrosine-modified MYBPC3 levels, restored MYBPC3 phosphorylation, and alleviated the calcium signalling and relaxation defects. Finally, we found that MPO protein was expressed in healthy adult murine and human cardiomyocytes, and MPO levels were increased in diseased hearts with left ventricular hypertrophy. Conclusion This study demonstrates that MPO inhibition alleviates the relaxation defect in hypertrophic iPSC-CMs through MYBPC3 phosphorylation. These findings highlight cardiomyocyte MPO as a novel therapeutic target for improving myocardial relaxation associated with HCM, a treatment strategy which can be readily investigated in the clinical setting, given that MPO inhibitors are already available for clinical testing., Graphical Abstract
Published: 2020

8. Neural Network Improves Upon Prior Models for Predicting Non-Diagnostic Home Sleep Apnea Tests

Author: Jennifer L. Martin, Michelle Zeidler, Robert Stretch, D. Hwang, Constance H. Fung, and Armand Ryden
Subjects: medicine.medical_specialty, Physical medicine and rehabilitation, Artificial neural network, business.industry, Medicine, Sleep apnea, business, medicine.disease
Published: 2020
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9. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD

Author: Cosentino, F., Grant, P. J., Aboyans, V., Bailey, C. J., Ceriello, A., Delgado, V., Federici, M., Filippatos, G., Grobbee, D. E., Hansen, T. B., Huikuri, H. V., Johansson, I., Juni, P., Lettino, M., Marx, N., Mellbin, L. G., Ostgren, C. J., Rocca, Bianca, Roffi, M., Sattar, N., Seferovic, P. M., Sousa-Uva, M., Valensi, P., Wheeler, D. C., Piepoli, M. F., Birkeland, K. I., Adamopoulos, S., Ajjan, R., Avogaro, A., Baigent, C., Brodmann, M., Bueno, H., Ceconi, C., Chioncel, O., Coats, A., Collet, J. -P., Collins, P., Cosyns, B., Di Mario, C., Fisher, M., Fitzsimons, D., Halvorsen, S., Hansen, D., Hoes, A., Holt, R. I. G., Home, P., Katus, H. A., Khunti, K., Komajda, M., Lambrinou, E., Landmesser, U., Lewis, B. S., Linde, C., Lorusso, R., Mach, F., Mueller, C., Neumann, F. -J., Persson, F., Petersen, S. E., Petronio, A. S., Richter, D. J., Rosano, G. M. C., Rossing, P., Ryden, L., Shlyakhto, E., Simpson, I. A., Touyz, R. M., Wijns, W., Wilhelm, M., Williams, B., Windecker, S., Dean, V., Gale, C. P., Hindricks, G., Iung, B., Leclercq, C., Merkely, B., Zelveian, P. H., Scherr, D., Jahangirov, T., Lazareva, I., Shivalkar, B., Naser, N., Gruev, I., Milicic, D., Petrou, P. M., Linhart, A., Hildebrandt, P., Hasan-Ali, H., Marandi, T., Lehto, S., Mansourati, J., Kurashvili, R., Siasos, G., Lengyel, C., Thrainsdottir, I. S., Aronson, D., Di Lenarda, A., Raissova, A., Ibrahimi, P., Abilova, S., Trusinskis, K., Saade, G., Benlamin, H., Petrulioniene, Z., Banu, C., Magri, C. J., David, L., Boskovic, A., Alami, M., Liem, A. H., Bosevski, M., Svingen, G. F. T., Janion, M., Gavina, C., Vinereanu, D., Nedogoda, S., Mancini, T., Ilic, M. D., Fabryova, L., Fras, Z., Jimenez-Navarro, M. F., Norhammar, A., Lehmann, R., Mourali, M. S., Ural, D., Nesukay, E., Chowdhury, T. A., Clinical sciences, Cardio-vascular diseases, Cardiology, Human Physiology and Special Physiology of Physical Education, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Zurich, and Cosentino, Francesco
Subjects: Settore MED/09 - Medicina Interna, Epidemiology, [SDV]Life Sciences [q-bio], 10265 Clinic for Endocrinology and Diabetology, Psychological intervention, Disease, Impaired glucose tolerance, Diabetes mellitus, Health care, risk factors, Guidelines, cardiovascular diseases, cardiovascular risk assessment, diabetes mellitus, epidemiology, impaired glucose tolerance, patient management, patient-centred care, pharmacological treatment, prevention, revascularization, Prediabetes, ComputingMilieux_MISCELLANEOUS, Societies, Medical, ddc:616, Cardiovascular risk assessment, 3. Good health, Europe, Cardiovascular diseases, Pre diabetes, Practice Guidelines as Topic, Cardiology and Cardiovascular Medicine, Pharmacological treatment, medicine.medical_specialty, Patient management, Patient-centred care, Prevention, Revascularization, Risk factors, Settore BIO/14 - FARMACOLOGIA, Cardiology, 610 Medicine & health, 2705 Cardiology and Cardiovascular Medicine, Prediabetic State, medicine, Humans, business.industry, medicine.disease, Diabetes Mellitus, Type 2, Family medicine, business
Abstract: This is the second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions. The growing awareness of the strong biological relationship between DM and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007. Some assert that too many guidelines are being produced but, in this burgeoning field, five years in the development of both basic and clinical science is a long time and major trials have reported in this period, making it necessary to update the previous Guidelines.
Published: 2020
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10. The generalisability of randomised clinical trials : an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer

Author: de Boniface, Jana, Ahlgren, Johan, Andersson, Yvette, Bergkvist, Leif, Frisell, Jan, Lundstedt, Dan, Olofsson Bagge, Roger, Ryden, Lisa, Sund, Malin, Christiansen, Peer, Filtenborg Tvedskov, Tove, Offersen, Birgitte Vrou, Reimer, Toralf, Kuehn, Thorsten, Kontos, Michalis, Gentilini, Oreste, Reitsamer, Roland, and Department of Surgery
Subjects: Oncology, Cancer Research, SURGERY, 0302 clinical medicine, Breast cancer, Sentinel lymph node biopsy, Interim, Multicenter Studies as Topic, 030212 general & internal medicine, Mastectomy, Randomized Controlled Trials as Topic, Aged, 80 and over, Disease Management, WOMEN, Middle Aged, Combined Modality Therapy, Tumor Burden, Omission of axillary dissection, Clinical trial, Treatment Outcome, 030220 oncology & carcinogenesis, Lymphatic Metastasis, SURVIVAL, BIOPSY, Female, Sentinel Lymph Node, RADIOTHERAPY, Adult, medicine.medical_specialty, Sentinel lymph node, 3122 Cancers, Breast Neoplasms, External validity, 03 medical and health sciences, Internal medicine, medicine, Humans, Aged, Sweden, Cancer och onkologi, business.industry, Kirurgi, Axillary Lymph Node Dissection, medicine.disease, PHASE-III, AXILLARY DISSECTION, Cancer and Oncology, Axilla, Lymph Node Excision, Surgery, business
Abstract: Purpose None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC). Methods In the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1–T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are eligible interventions. Data from NKBC were extracted for the years 2016 and 2017, and patient and tumour characteristics compared with Swedish trial participants from the same years. Results Overall, 306 NKBC cases from non-participating and 847 NKBC cases from participating sites (excluding SENOMAC participants) were compared with 463 SENOMAC trial participants. Patients belonging to the middle age groups (p = 0.015), with smaller tumours (p = 0.013) treated by breast-conserving therapy (50.3 versus 47.1 versus 65.2%, p p = 0.001) were over-represented in the trial population. Time trends indicated, however, that differences may be mitigated over time. Conclusions This interim external validity analysis specifically addresses selection mechanisms during an ongoing trial, potentially increasing generalisability by the time full accrual is reached. Similar validity checks should be an integral part of prospective clinical trials. Trial registration: NCT 02240472, retrospective registration date September 14, 2015 after trial initiation on January 31, 2015
Published: 2020

11. Vaginitis and Vulvar Conditions

Author: Swati Shroff and Janice Ryden
Subjects: Vaginal discharge, medicine.medical_specialty, Trichomoniasis, integumentary system, business.industry, Cervicitis, medicine.disease, Dermatology, female genital diseases and pregnancy complications, medicine.anatomical_structure, Pelvic inflammatory disease, medicine, Vagina, Vulvodynia, medicine.symptom, Bacterial vaginosis, business, Vaginitis
Abstract: Women with vaginitis often present to primary care settings. The most common types of vaginitis are bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis. Less commonly, vaginitis results from a noninfectious etiology. In addition to vaginitis, a woman presenting with vaginal discharge may have physiologic discharge, cervicitis, or pelvic inflammatory disease; it is critical to exclude an upper genital tract infection in women presenting with vaginal discharge. Clinical assessment includes a combination of history, exam, assessment of vaginal pH, the whiff test, microscopy, and/or point-of-care testing for the three common infectious causes. Yeast vaginitis and bacterial vaginosis often recur, necessitating review of contributing factors and consideration of long-term management. Although vulvar symptoms more commonly result from discharge originating from the vagina or cervix, primary vulvar processes also occur and can present with pruritus, burning pain, dyspareunia, dysuria, or rarely with bleeding or a palpable mass. Primary vulvar conditions include contact and allergic dermatitis, chronic vulvar dermatoses, vulvar malignancies, and vulvodynia.
Published: 2020
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12. Advances in Positive Pressure Therapy and Noninvasive Ventilation in the Treatment of Sleep Disorders

Author: William LeMaster, Michelle Zeidler, Melisa Chang, and Armand Ryden
Subjects: medicine.medical_specialty, Positive pressure therapy, Central sleep apnea, business.industry, Nocturnal hypoventilation, medicine.disease, Sleep in non-human animals, Obstructive sleep apnea, Internal medicine, Positive airway pressure, medicine, Cardiology, Non-invasive ventilation, Noninvasive ventilation, business
Published: 2020
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13. Effect of Clot Stiffness on Recombinant Tissue Plasminogen Activator Lytic Susceptibility in Vitro

Author: Hendrik J. Vos, Robert T. Kleven, Hermes Aponte Rivera, Christy K. Holland, Ryden Lewis, Karla P. Mercado-Shekhar, Todd Abruzzo, Kunal B. Karani, Kevin J. Haworth, and Cardiology
Subjects: medicine.medical_specialty, Acoustics and Ultrasonics, Swine, Biophysics, Urology, In Vitro Techniques, Article, 030218 nuclear medicine & medical imaging, Food and drug administration, 03 medical and health sciences, 0302 clinical medicine, Reference Values, Animals, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Recombinant tissue plasminogen activator, Intracerebral hemorrhage, Radiological and Ultrasound Technology, Phantoms, Imaging, business.industry, Ultrasound, Thrombosis, Blood flow, Therapeutic decision making, medicine.disease, In vitro, Lytic cycle, Tissue Plasminogen Activator, Models, Animal, Elasticity Imaging Techniques, business, 030217 neurology & neurosurgery
Abstract: The lytic recombinant tissue plasminogen activator (rt-PA) is the only drug approved by the Food and Drug Administration for treating ischemic stroke. Less than 40% of patients with large vessel occlusions who are treated with rt-PA have improved blood flow. However, up to 6% of all patients receiving rt-PA develop intracerebral hemorrhage. Predicting the efficacy of rt-PA treatment a priori could help guide therapeutic decision-making, such that rt-PA is administered only to those individuals who would benefit from this treatment. Clot composition and structure affect the lytic efficacy of rt-PA and have an impact on elasticity. However, the relationship between clot elasticity and rt-PA lytic susceptibility has not been adequately investigated. The goal of this study was to quantify the relationship between clot elasticity and rt-PA susceptibility in vitro. Human and porcine highly retracted and mildly retracted clots were fabricated in glass pipettes. The rt-PA lytic susceptibility was evaluated in vitro using the percent clot mass loss. The Young’s moduli of the clots were estimated using ultrasound-based single-track-location shear wave elasticity imaging. The percent mass loss in mildly retracted porcine and human clots (28.9 ± 6.1% and 45.2 ± 7.1%, respectively) were significantly higher (p < 0.05) than those in highly retracted porcine and human clots (10.9 ± 2.1% and 25.5 ± 10.0%, respectively). Furthermore, the Young’s moduli of highly retracted porcine and human clots (5.33 ± 0.92 kPa and 3.21 ± 1.97 kPa, respectively) were significantly higher (p < 0.05) than those of mildly retracted porcine and human clots (2.66 ± 0.55 kPa and 0.79 ± 0.21 kPa, respectively). The results revealed an inverse relationship between the percent clot mass loss and Young’s modulus. These findings motivate continued investigation of ultrasound-based methods to assess clot stiffness in order to predict rt-PA thrombolytic efficacy.
Published: 2018
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14. Whole blood FPR1 mRNA expression predicts both non-small cell and small cell lung cancer

Author: Kirk Ryden, D. K. Hogarth, David Mallery, Glen J. Weiss, Donald A. Richards, Scott Morris, Troy Shelton, Harvey I. Pass, Anil Vachani, William N. Rom, and George C. Runger
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.disease, Clinical trial, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, TaqMan, Medicine, Biomarker (medicine), Blood test, Non small cell, business, Lung cancer, Lung cancer screening, Whole blood
Abstract: While long-term survival rates for early-stage lung cancer are high, most cases are diagnosed in later stages that can negatively impact survival rates. We aim to design a simple, single biomarker blood test for early-stage lung cancer that is robust to preclinical variables and can be readily implemented in the clinic. Whole blood was collected in PAXgene tubes from a training set of 29 patients, and a validation set of 260 patients, of which samples from 58 patients were prospectively collected in a clinical trial specifically for our study. After RNA was extracted, the expressions of FPR1 and a reference gene were quantified by an automated one-step Taqman RT-PCR assay. Elevated levels of FPR1 mRNA in whole blood predicted lung cancer status with a sensitivity of 55% and a specificity of 87% on all validation specimens. The prospectively collected specimens had a significantly higher 68% sensitivity and 89% specificity. Results from patients with benign nodules were similar to healthy volunteers. No meaningful correlation was present between our test results and any clinical characteristic other than lung cancer diagnosis. FPR1 mRNA levels in whole blood can predict the presence of lung cancer. Using this as a reflex test for positive lung cancer screening computed tomography scans has the potential to increase the positive predictive value. This marker can be easily measured in an automated process utilizing off-the-shelf equipment and reagents. Further work is justified to explain the source of this biomarker.
Published: 2018
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15. 1218 Obstructive Sleep Apnea Due To Oromandibular Dystonia And Treated With Botulinum Toxin

Author: Armand Ryden, Melisa Chang, Caleb Hsieh, Aaron Thomas, Michelle Zeidler, and Nancy Hsu
Subjects: Obstructive sleep apnea, business.industry, Physiology (medical), Anesthesia, medicine, Neurology (clinical), medicine.disease, business, Oromandibular dystonia, Botulinum toxin, nervous system diseases, respiratory tract diseases, medicine.drug
Abstract: Introduction Abnormalities of the upper airway are an underrecognized cause of obstructive sleep apnea (OSA). Oromandibular dystonia (OMD) is characterized by involuntary contractions of the masticatory, facial, pharyngeal or laryngeal muscles usually resulting in pain, dysarthria, dysphagia, or impaired mastication. We present a patient with OMD manifest as episodic OSA and sleep maintenance insomnia treated effectively with botulinum toxin injections of the temporalis and masseter muscles. Report of Case A 51-year-old man was referred for fatigue and insomnia. History was notable for prior facial trauma requiring jaw surgeries with titanium prostheses and chronic OMD requiring periodic botulinum toxin injections of the temporalis and masseter muscles. An initial home sleep test (HST) 43 days after the last botulinum toxin injection showed a respiratory event index of 6.5 events/hour. Given severity of symptoms, positive airway pressure (PAP) was initiated; however, due to poor tolerance and persistent symptoms, he was referred for attended polysomnography (PSG). The PSG was done 13 days after an injection and showed apnea-hypopnea index (AHI) of 0 events/hour. Because the patient continued to endorse episodically severe symptoms that he felt paralleled the severity of OMD and waning of botulinum toxin effect, a repeat PSG was performed at a subjective botulinum toxin effect nadir. This PSG done at 83 days post-injection demonstrated AHI of 84 events/hour. PAP therapy was thus resumed, and the patient’s symptoms improved with increased frequency of botulinum toxin treatments. Conclusion To our knowledge, this is the first report of OSA due to chronic dystonia of the facial muscles. Botulinum toxin has demonstrated benefit in the treatment of OMD with efficacy generally lasting three to six months. While PAP remains the first-line treatment for OSA, in patients with structural or functional abnormalities of the upper airway, it is important to also consider treatment of the underlying anatomical defect.
Published: 2020
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16. Predicting Nondiagnostic Home Sleep Apnea Tests Using Machine Learning

Author: Constance H. Fung, Stephen Liu, Michelle Zeidler, Robert Stretch, Nicolás Della Penna, Babak Saedi, Armand Ryden, Jennifer L. Martin, Joanne Martires, Vidhya Balasubramanian, and Dennis Hwang
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Sleep Apnea, Polysomnography, Clinical Sciences, Sensitivity and Specificity, Decision Support Techniques, predictive model, Machine Learning, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Surveys and Questionnaires, Psychology, Medicine, Humans, home sleep apnea testing, Lung, obstructive sleep apnea, Aged, Retrospective Studies, screening and diagnosis, Sleep Apnea, Obstructive, Other Medical and Health Sciences, Neurology & Neurosurgery, Obstructive, business.industry, Sleep apnea, Middle Aged, medicine.disease, Scientific Investigations, respiratory tract diseases, Obstructive sleep apnea, Self Care, Detection, Good Health and Well Being, 030228 respiratory system, Neurology, Calibration, Physical therapy, Female, Neurology (clinical), Sleep Research, business, 030217 neurology & neurosurgery, 4.2 Evaluation of markers and technologies
Abstract: STUDY OBJECTIVES: Home sleep apnea testing (HSAT) is an efficient and cost-effective method of diagnosing obstructive sleep apnea (OSA). However, nondiagnostic HSAT necessitates additional tests that erode these benefits, delaying diagnoses and increasing costs. Our objective was to optimize this diagnostic pathway by using predictive modeling to identify patients who should be referred directly to polysomnography (PSG) due to their high probability of nondiagnostic HSAT. METHODS: HSAT performed as the initial test for suspected OSA within the Veterans Administration Greater Los Angeles Healthcare System was analyzed retrospectively. Data were extracted from pre-HSAT questionnaires and the medical record. Tests were diagnostic if there was a respiratory event index (REI) ≥ 5 events/h. Tests with REI < 5 events/h or technical inadequacy—two outcomes requiring additional testing with PSG—were considered nondiagnostic. Standard logistic regression models were compared with models trained using machine learning techniques. RESULTS: Models were trained using 80% of available data and validated on the remaining 20%. Performance was evaluated using partial area under the precision-recall curve (pAUPRC). Machine learning techniques consistently yielded higher pAUPRC than standard logistic regression, which had pAUPRC of 0.574. The random forest model outperformed all other models (pAUPRC 0.862). Preferred calibration of this model yielded the following: sensitivity 0.46, specificity 0.95, positive predictive value 0.81, negative predictive value 0.80. CONCLUSIONS: Compared with standard logistic regression models, machine learning models improve prediction of patients requiring in-laboratory PSG. These models could be implemented into a clinical decision support tool to help clinicians select the optimal test to diagnose OSA. CITATION: Stretch R, Ryden A, Fung CH, Martires J, Liu S, Balasubramanian V, Saedi B, Hwang D, Martin J, Della Penna N, Zeidler M. Predicting nondiagnostic home sleep apnea tests using machine learning. J Clin Sleep Med. 2019;15(11):1599–1608.
Published: 2019

17. Association of Race with Outcome Expectancy for Positive Airway Pressure Therapy Among Older Veterans with Obstructive Sleep Apnea

Author: Cathy A. Alessi, Ron D. Hays, Constance H. Fung, Michelle Zeidler, Emily S. Patterson, Armand Ryden, Jennifer L. Martin, Nancy Hsu, Karen R. Josephson, and Nananda F. Col
Subjects: Obstructive sleep apnea, medicine.medical_specialty, Race (biology), business.industry, Internal medicine, Positive airway pressure, Outcome expectancy, medicine, medicine.disease, Association (psychology), business
Published: 2019
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18. Use of Machine Learning to Predict Non-Diagnostic Home Sleep Apnea Tests

Author: Armand Ryden, C.H. Fung, Robert Stretch, and Michelle Zeidler
Subjects: medicine.medical_specialty, Physical medicine and rehabilitation, business.industry, medicine, Sleep apnea, business, medicine.disease
Published: 2019
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19. A 38-Year-Old Man With Well Treated OSA on CPAP With Persistent Nocturnal Hypoxemia

Author: Deborah Hong, Armand Ryden, Jesse Currier, Sharon De Cruz, Michelle Zeidler, Jonathan M. Tobis, and David Culpepper
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_treatment, Polysomnography, Nocturnal, Critical Care and Intensive Care Medicine, Severity of Illness Index, Hypoxemia, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Severity of illness, medicine, Humans, 030212 general & internal medicine, Continuous positive airway pressure, Hypoxia, Sleep Apnea, Obstructive, medicine.diagnostic_test, Continuous Positive Airway Pressure, business.industry, Sleep apnea, Hypoxia (medical), medicine.disease, nervous system diseases, respiratory tract diseases, 030228 respiratory system, Anesthesia, medicine.symptom, Polycythemia rubra vera, Cardiology and Cardiovascular Medicine, business
Abstract: Case Presentation A 38-year-old male with a prior diagnosis of severe OSA (apnea-hypopnea index [AHI] 99/h) presented for transfer of care. He was successfully titrated to CPAP of 10 cm H2O at an outside laboratory and was compliant with therapy with residual AHI 1.9/h. On presentation, he was polycythemic, with negative evaluation for primary polycythemia, and evaluation for hypoxemia was initiated.
Published: 2019

20. POS1425 ANTIBODIES TO PORPHYROMONAS GINGIVALIS ASSOCIATE WITH THE PRESENCE OF RHEUMATOID ARTHRITIS-RELATED AUTOANTIBODIES IN PATIENTS WITH PERIODONTITIS

Author: C. De Vries, Jan Potempa, Natalie Sippl, L. Ryden, Björn Klinge, B. A. Potempa, Elisabet Svenungsson, G. Ruacho, and Karin Lundberg
Subjects: Periodontitis, biology, business.industry, Immunology, Autoantibody, medicine.disease, biology.organism_classification, General Biochemistry, Genetics and Molecular Biology, Rheumatology, Rheumatoid arthritis, biology.protein, medicine, Immunology and Allergy, In patient, Antibody, business, Porphyromonas gingivalis
Abstract: Background:Epidemiologic studies have demonstrated a link between periodontitis (PD) and rheumatoid arthritis (RA), specifically RA characterized by anti-citrullinated protein antibodies (ACPA). The keystone pathogen driving PD, Porphyromonas gingivalis (Pg), is the only pathogen known to express peptidylarginine deiminase (PAD), a citrullinating enzyme. Hence, Pg has been proposed to be involved in triggering the ACPA response, by generating citrullinated antigens in an inflammatory milieu(1). Another major virulence factor of Pg is arginine gingipain B (RgpB), a proteinase which cleaves proteins so that P.PAD can access the site where citrullination takes place. We have previously shown elevated anti-RgpB IgG levels in ACPA+ RA patients, even before clinical onset(2, 3), and we hypothesize that anti-RgpB IgG could serve as a serological marker to identify PD patients with increased risk of developing ACPA+ RA.Objectives:Based on this hypothesis, we set out to investigate whether anti-RgpB IgG was associated with PD, PD severity, autoimmunity in general, and the ACPA response in particular.Methods:Anti-RgpB IgG, as well as RA- and systemic lupus erythematosus (SLE)-related autoantibodies targeting cyclic citrullinated peptide(s) (CCP2), rheumatoid factor (RF), dsDNA, cardiolipin, and β2 glycoprotein, were measured by ELISA in serum samples from the ParoKrank study, which is a well-characterized cohort of 805 patients with a first myocardial infarction and 805 matched controls, where periodontal status has been determined by dentists(4). In this study, individuals with PD (n=941) were compared to individuals without PD (n=557).Results:We detected significantly elevated (pConclusion:Our data demonstrates a specific association between severe PD, elevated anti-RgpB IgG levels and RA-related autoantibodies, supporting a role for Pg in linking PD to ACPA+ RA. Further investigation will be needed to confirm whether anti-RgpB IgG can be used as a serological marker to identify PD patients with increased risk of developing ACPA+ RA.References:[1]Rosenstein ED, Greenwald RA, Kushner LJ, Weissmann G. Hypothesis: the humoral immune response to oral bacteria provides a stimulus for the development of rheumatoid arthritis. Inflammation. 2004;28(6):311-8.[2]Kharlamova N, Jiang X, Sherina N, Potempa B, Israelsson L, Quirke AM, et al. Antibodies to Porphyromonas gingivalis Indicate Interaction Between Oral Infection, Smoking, and Risk Genes in Rheumatoid Arthritis Etiology. Arthritis Rheumatol. 2016;68(3):604-13.[3]Johansson L, Sherina N, Kharlamova N, Potempa B, Larsson B, Israelsson L, et al. Concentration of antibodies against Porphyromonas gingivalis is increased before the onset of symptoms of rheumatoid arthritis. Arthritis Res Ther. 2016;18(1):201.[4]Rydén L, Buhlin K, Ekstrand E, Faire Ud, Gustafsson A, Holmer J, et al. Periodontitis Increases the Risk of a First Myocardial Infarction. Circulation. 2016;133(6):576-83.Disclosure of Interests:None declared
Published: 2021
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21. APPLYING REWIND CVD CRITERIA TO SUSTAIN 6 AND PIONEER 6: AN EXPLORATORY ANALYSIS OF CV OUTCOMES WITH SEMAGLUTIDE

Author: Lars E. Ryden, Subodh Verma, Maria Sejersten Ripa, Søren Rasmussen, Udi Fainberg, Mansoor Husain, and John B. Buse
Subjects: Agonist, endocrine system, medicine.medical_specialty, medicine.drug_class, business.industry, Semaglutide, digestive, oral, and skin physiology, Type 2 diabetes, Exploratory analysis, Placebo, medicine.disease, Internal medicine, medicine, Dulaglutide, In patient, Cardiology and Cardiovascular Medicine, business, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract: In the REWIND cardiovascular (CV) outcomes trial (CVOT), the glucagon-like peptide-1 receptor agonist (GLP-1RA) dulaglutide reduced CV risk vs placebo in patients with type 2 diabetes (T2D) and elevated CV risk. The SUSTAIN 6 ([NCT01720446][1]) and PIONEER 6 ([NCT02692716][2]) CVOTs of the GLP-1RA
Published: 2020
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22. Parkinson's Disease in the Era of Personalised Medicine: One Size Does Not Fit All

Author: Lauren E. Ryden and Simon J.G. Lewis
Subjects: medicine.medical_specialty, Parkinson's disease, media_common.quotation_subject, MEDLINE, Disease, Disease course, 03 medical and health sciences, Presentation, 0302 clinical medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Precision Medicine, Intensive care medicine, media_common, business.industry, Age Factors, Parkinson Disease, medicine.disease, Clinical Practice, Disease Progression, Approaches of management, Geriatrics and Gerontology, Construct (philosophy), business, 030217 neurology & neurosurgery
Abstract: The concept of personalised medicine in Parkinson’s disease has arrived where the implications of findings made in research are certain to have an increasing impact upon clinical practice. Disease heterogeneity in Parkinson’s disease has been well described and lends itself to the construct of personalised medicine where it is hypothesised that a greater understanding of genetic and pathophysiological contributions may underpin the sub-groups described. This in turn has driven the development of potentially individualised disease-modifying therapies where, for example, we are beginning to see treatments that target patients with Parkinson’s disease with specific genetic mutations. Furthermore, clinicians are increasingly recognising the need to tailor their management approach to patients depending on their age of presentation, acknowledging differential side-effect profiles and responses especially when considering the use of device-assisted technologies such as infusion or surgery. Clearly, individualising the treatment of both motor and non-motor symptoms will remain imperative but, in the future, personalised medicine may provide clearer insights into various aspects of a patient’s symptomatology, disease course and thus the best therapeutic approaches.
Published: 2018

23. P5085Optimizing outreach strategy to identify individuals at risk for diabetes and/or cardiovascular disease: a study of the Sodertalje municipality in Sweden

Author: Viveca Gyberg, S H Hasselberg, L R Ryden, L M Mellbin, Bahira Shahim, and O S Bolt Christmas
Subjects: Outreach, medicine.medical_specialty, business.industry, Diabetes mellitus, Family medicine, Medicine, Disease, Cardiology and Cardiovascular Medicine, business, medicine.disease
Published: 2018
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24. Is atrial fibrillation a risk factor for in-hospital cardiac arrest?: a Swedish retrospective cohort study

Author: Andreas Claesson, Per Nordberg, Therese Djärv, Mattias Ringh, Alexander Ryden, Johan Engdahl, and Jacob Hollenberg
Subjects: Adult, Male, medicine.medical_specialty, Epidemiology, medicine.medical_treatment, Comorbidity, 030204 cardiovascular system & hematology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Primary outcome, Risk Factors, Internal medicine, Atrial Fibrillation, medicine, Humans, 030212 general & internal medicine, Cardiopulmonary resuscitation, Hospital Mortality, Risk factor, Aged, Retrospective Studies, Aged, 80 and over, Sweden, Adult patients, business.industry, Research, Retrospective cohort study, Atrial fibrillation, General Medicine, Middle Aged, medicine.disease, University hospital, mortality, Survival Analysis, Cardiopulmonary Resuscitation, Heart Arrest, IHCA, charlson comorbidity index, Female, business, Cohort study
Abstract: Introduction Atrial fibrillation (AF) is associated with increased morbidity and mortality. Recent findings suggest that AF is also associated with out-of-hospital cardiac arrest. However, whether that association can be generalised to in-hospital cardiac arrests (IHCAs) is still unknown. Aims To examine whether there is a stronger association with IHCA among hospitalised patients with AF compared with patients without AF. Materials and methods All adult patients admitted to the Karolinska University Hospital, Stockholm, Sweden during 2014–2015 were included. Data were drawn from their medical file and matched against the Swedish Registry for Cardiopulmonary Resuscitation. Patients who were documented as ever having the International Classification of Diseases, 10th revision code I48 prior to the current hospitalisation were categorised to the AF group and the remaining were categorised to the non-AF group. The primary outcome was occurrence of an IHCA. Results In all, 102 416 patients were included. Among these, 10% had been diagnosed with AF and
Published: 2018

25. Patient-Reported Symptoms and Impact of Treatment With Osimertinib Versus Chemotherapy in Advanced Non-Small-Cell Lung Cancer: The AURA3 Trial

Author: Lee, C. K., Novello, S., Ryden, A., Templeton, A., Rüdell, K., Mann, H., Ghiorghiu, S., and Mok, T.
Subjects: Cancer Research, medicine.medical_specialty, Lung Neoplasms, Piperazines, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Quality of life, law, Internal medicine, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Osimertinib, 030212 general & internal medicine, Progression-free survival, Patient Reported Outcome Measures, Lung cancer, Protein Kinase Inhibitors, Acrylamides, Aniline Compounds, business.industry, Hazard ratio, Cancer, Odds ratio, medicine.disease, Progression-Free Survival, Oncology, 030220 oncology & carcinogenesis, Quality of Life, business
Abstract: Purpose Capturing patient-reported outcome data is important for evaluating the overall clinical benefits of new cancer therapeutics. We assessed self-reported symptoms of advanced non–small-cell lung cancer in patients treated with osimertinib or chemotherapy in the AURA3 phase III trial. Patients and Methods Patients completed the European Organisation for Research and Treatment of Cancer 13-item Quality of Life Questionnaire-Lung Cancer Module (EORTC QLQ-LC13) questionnaire on disease-specific symptoms and the EORTC 30-item Core Quality of Life Questionnaire (EORTC QLC-C30) on general cancer symptoms, functioning, global health status/quality of life. We assessed differences between treatments in time to deterioration of individual symptoms and odds of improvement (a deterioration or improvement was defined as a change in score from baseline of ≥ 10). Hazard ratios (HRs) were calculated using a log-rank test stratified by ethnicity; odds ratios (ORs) were assessed using logistic regression adjusted for ethnicity. Results At baseline, the questionnaires were completed by 82% to 88% of patients, and 30% to 70% had individual key symptoms. Time to deterioration was longer with osimertinib than with chemotherapy for cough (HR, 0.74; 95% CI, 0.53 to 1.05), chest pain (HR, 0.52; 95% CI, 0.37 to 0.73), and dyspnea (HR, 0.42; 95% CI, 0.31 to 0.58). The proportion of symptomatic patients with improvement in global health status/quality of life was higher with osimertinib (80 [37%] of 215) than with chemotherapy (23 [22%] of 105; OR, 2.11; 95% CI, 1.24 to 3.67; P = .007). Proportions were also higher for appetite loss (OR, 2.50; 95% CI, 1.31 to 4.84) and fatigue (OR, 1.96; 95% CI, 1.20 to 3.22). Conclusion Time to deterioration of key symptoms was longer with osimertinib than with chemotherapy, and a higher proportion of patients had improvement in global health status/quality of life, demonstrating improved patient outcomes with osimertinib.
Published: 2018

26. Advanced Positive Airway Pressure Modalities

Author: Ravi S. Aysola, Gregory B. Bierer, and Armand Ryden
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Central sleep apnea, Ejection fraction, business.industry, medicine.disease, respiratory tract diseases, Sudden cardiac death, Obstructive sleep apnea, Neurology, Heart failure, Positive airway pressure, medicine, Breathing, Neurology (clinical), Intensive care medicine, business
Abstract: Auto-adjusting positive airway pressure (PAP) devices are increasingly becoming the first line treatment for obstructive sleep apnea (OSA). More complex sleep- disordered breathing such as Cheyne-Stokes respirations and central sleep apnea related to heart failure as well as complex sleep-disordered breathing related to chronic hypoventilation syndromes may require the use of advanced positive airway pressure modalities such as automated servo ventilation (ASV) and volume targeted pressure limited ventilation. Identifying patients with complex sleep-disordered breathing that will benefit from treatment with advanced modalities re- mains an area of active investigation. A recent and surprising development found ASV to be associated with an increased risk of sudden cardiac death when used to treat central sleep apnea in patients with symptomatic systolic heart failure and an ejection fraction less than 45 %. The optimal treatment of central sleep apnea in heart failure and the role of ASV are currently in question. The following chapter is intended to provide the clinician with a description of newer PAP modal- ities; a review of evidence supported indications for use as well as provide a framework for managing patients with ad- vanced positive airway pressure therapy.
Published: 2015
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27. Treatment of Anemia with Darbepoetin Alfa in Systolic Heart Failure

Author: Karl Swedberg, James B. Young, Inder S. Anand, Sunfa Cheng, Akshay S. Desai, Rafael Diaz, Aldo P. Maggioni, John J. V. McMurray, Christopher O'Connor, Marc A. Pfeffer, Scott D. Solomon, Yan Sun, Michal Tendera, Dirk J. van Veldhuisen, Young J, Grinfeld L, Krum H, Vanhaecke J, Olivera Clausell N, Goudev A, Howlett J, Corbalan R, Hradec J, Kober L, Eha J, Cohen Solal A, Anker SD, Chopra V, Lewis B, Erglis A, Sakalyte G, Cardona Munoz E, Dunselman P, Dickstein K, Ponikowski P, Seabra Gomes R, Apetrei E, Mareev V, Murin J, Dalby A, Lopez Sendon J, Willenheimer R, Cleland J, Adams K, Anand I, Butler J, Dunlap M, Felker M, Ghali J, Levy W, Carson P, Cohn J, Drexler H, Pocock S, Ryden L, Poole Wilson P, Fishbane S, Ivanovich P, Nissenson A, Katz S, Barkoudah E, Campbell P, Desai A, Finn PV, Hartley L, Kasabov R, Odutayo KA, Rajesh V, Solomon S, Weinrauch LA, Albizem M, Cheng S, Chou W, Deegenaars M, Dougherty M, Fouqueray B, Froissart M, Froment A, Gadd S, Ghosh S, Grazette L, Guillet S, Gulabani D, Haddock B, Harris C, Jaffer A, Kerns C, Kim J, Knussel B, Law H, Mather R, Mix C, Moore L, Moyes R, Polu K, Rossert J, Scarlata D, Smirnakis K, Smith L, Snyder W, Sun Y, Trotman ML, Wasserman S, Watkins A, Wong M, Zhang Y, Amuchastegui M, Belziti C, Bluguermann J, Caccavo M, Cartasegna L, Colque R, Cuneo C, Fernandez A, Gabito A, Goicochea R, Gonzalez M, Gorosito V, Hominal M, Kevorkian R, Litvak Bruno M, Llanos J, Mackinnon I, Manuale O, Marzetti E, Nul D, Perna E, Riccitelli M, Sanchez A, Santos D, Schygiel P, Toblli J, Vogel D, Aggarwal A, Amerena J, De Looze F, Fletcher P, Hare D, Ireland M, Lattimore J, Marwick T, Sindone A, Thompson P, Waites J, Altenberger J, Ebner C, Lenz K, Pacher R, Poelzl G, Charlier F, de Ceuninck M, De Keulenaer G, Dendale P, Maréchal P, Mullens W, Thoeng J, Vanderheyden M, Weytjens C, Wollaert B, Albuquerque D, Almeida D, Aspe y. Rosas J, Bocchi E, Bordignon S, Clausell N, Kaiser S, Leaes P, Martins Alves S, Montera M, Moura L, Pereira de Castro R, Rassi S, Reis A, Saraiva J, Simões M, Souza Neto J, Teixeira M, Benov H, Chompalova B, Donova T, Georgiev P, Gotchev D, Grigorov M, Guenova D, Hergeldjieva V, Ivanov D, Kostova E, Manolova A, Marchev S, Nikolov F, Popov A, Raev D, Tzekova M, Czarnecki W, Giannetti N, Haddad H, Heath J, Huynh T, Lepage S, Liu P, Lonn E, Ma P, Manyari D, Moe G, Parker J, Pesant Y, Rajda M, Ricci J, Roth S, Sestier F, Sluzar V, Sussex B, Vizel S, Antezana G, Bugueno C, Castro P, Conejeros C, Manriquez L, Martinez D, Potthoff S, Stockins B, Vukasovic J, Gregor P, Herold M, Jerabek O, Jirmar R, Kuchar R, Linhart A, Podzemska B, Soucek M, Spac J, Spacek R, Vodnansky P, Bronnum Schou J, Clemmensen K, Egstrup K, Jensen G, Kjoller Hansen L, Markenvard J, Rokkedal J, Skagen K, Torp Pedersen C, Tuxen C, Videbak L, Laks T, Vahula V, Harjola V, Kettunen R, Kotila M, Bauer F, Coisne D, Davy J, De Groote P, Dos Santos P, Funck F, Galinier M, Gibelin P, Isnard R, Neuder Y, Roul G, Sabatier R, Trochu J, Denny S, Dreykluft T, Flesch M, Genth Zotz S, Hambrecht R, Hein J, Jeserich M, John M, Kreider Stempfle H, Laufs U, Muellerleile K, Natour M, Sandri M, Schäufele T, von Hodenberg E, Weyland K, Winkelmann B, Tse H, Yan B, Barsi B, Csikasz J, Dezsi C, Edes I, Forster T, Karpati P, Kerekes C, Kis E, Kosa I, Lupkovics G, Nagy A, Preda I, Ronaszeki A, Tomcsanyi J, Zamolyi K, Agarwal D, Bahl V, Bordoloi A, Chockalingam K, Chopda M, Dugal J, Ghaisas N, Grant P, Hiremath S, Iyengar S, Jagadeesa Subramania B, Jain P, Joshi A, Khan A, Mullasari A, Naik S, Oomman A, Pai V, Pareppally Gopal R, Parikh K, Patel T, Prakash V, Sastry B, Sathe S, Sinha N, Srikanthan V, Subburamakrishnan P, Thacker H, Wander G, Admon D, Katz A, Klainman E, Marmor A, Moriel M, Mosseri M, Shotan A, Weinstein J, Zimlichman R, Agostoni P, Albanese M, Alunni G, Bini R, Boccanelli A, Bolognese L, Campana C, Carbonieri E, Carpino C, Checco L, Cosmi F, Angelo GD, De Cristofaro M, Floresta A, Fucili A, Galvani M, Ivleva A, Marra S, Musca G, Peccerillo N, Picchio E, Russo T, Scelsi L, Senni M, Tavazzi L, Jasinkevica I, Kakurina N, Veze I, Volans E, Bagdonas A, Berukstis E, Celutkiene J, Dambrauskaite A, Jarasuniene D, Luksiene D, Rudys A, Sliaziene S, Aguilar Romero R, Cardona Muñoz E, Castro Jimenez J, Chavez Herrera J, Chuquiure Valenzuela E, De la Pena G, Herrera E, Leiva Pons J, Lopez Alvarado A, Mendez Machado G, Ramos Lopez G, Basart D, Buijs E, Cornel J, de Leeuw M, Dijkgraaf R, Freericks M, Hamraoui K, Lenderlink T, Linssen G, Lodewick P, Lodewijks C, Lok D, Nierop P, Ronner E, Somsen A, van Dantzig J, van der Burgh P, van Kempen L, van Vlies B, Voors A, Wardeh A, Willems F, Gundersen T, Hole T, Thalamus J, Westheim A, Dabrowski M, Gorski J, Korewicki J, Kuc K, Miekus P, Musial W, Niegowska J, Piotrowski W, Podolec P, Polonski L, Rynkiewicz A, Szelemej R, Trusz Gluza M, Ujda M, Wojciechowski D, Wysokinski A, Camacho A, Fonseca C, Monteiro P, Bruckner I, Carasca E, Coman I, Datcu M, Dragulescu S, Ionescu P, Iordachescu Petica D, Manitiu I, Popa V, Pop Moldovan A, Radoi M, Stamate S, Tomescu M, Vita I, Aroutiounov G, Ballyuzek M, Bart B, Churina S, Glezer M, Goloshchekin B, Kobalava Z, Kostenko V, Lopatin Y, Martynov A, Orlov V, Semernin E, Shogenov Z, Sidorenko B, Skvortsov A, Storzhakov G, Sulimov V, Talibov O, Tereshenko S, Tsyrline V, Zadionchenko V, Zateyshchikov D, Dzupina A, Hranai M, Kmec J, Micko K, Pella D, Sojka G, Spisak V, Vahala P, Vinanska D, Badat A, Bayat J, Dawood S, Delport E, Ellis G, Garda R, Klug E, Mabin T, Naidoo D, Pretorius M, Ranjith N, Van Zyl L, Weich H, Anguita M, Berrazueta J, Bruguera i. Cortada J, de Teresa E, Gómez Sánchez M, González Juanatey J, Gonzalez Maqueda I, Jordana R, Lupon J, Manzano L, Pascual Figal D, Pulpón L, Recio J, Ridocci Soriano F, Rodríguez Lambert J, Roig Minguell E, Romero J, Valdovinos P, Klintberg L, Kronvall T, Lycksell M, Morner S, Rydberg E, Swedberg K, Timberg I, Wikstrom G, Moccetti T, Ashok J, Banerjee P, Carr White G, Connolly E, Francis M, Greenbaum R, Kadr H, Lindsay S, McMurray J, Megarry S, Memon A, Murdoch D, Senior R, Squire I, Tan L, Witte K, Adamson P, Adler A, Altschul L, Altschuller A, Amirani H, Andreou C, Ansari M, Antonishen M, Banchs H, Banerjee S, Banish D, Bank A, Barbagelata A, Barnard D, Bellinger R, Benn A, Berk M, Berry B, Bethala V, Bilazarian S, Bisognano J, Bleyer F, Blum M, Boehmer J, Bouchard A, Boyle A, Bozkurt B, Brown C, Burlew B, Burnham K, Call J, Cambier P, Cappola T, Carlson R, Chandler B, Chandra R, Chandraratna P, Chernick R, Colan D, Colfer H, Colucci W, Connelly T, Costantini O, Dadkhah S, Dauber I, Davis J, Davis S, Denning S, Drazner M, Dunlap S, Egbujiobi L, Elkayam U, Elliott J, El Shahawy M, Essandoh L, Ewald G, Fang J, Farhoud H, Felker G, Fernandez J, Festin R, Fishbein G, Florea V, Flores E, Floro J, Gabris M, Garg M, Gatewood R, Geller M, Ghumman W, Gibbs G, Gillespie E, Gilmore R, Gogia H, Goldberg L, Gradus Pizlo I, Grainger T, Gudmundsson G, Gunawardena D, Gupta D, Hack T, Hall S, Hamroff G, Hankins S, Hanna M, Hargrove J, Haught W, Hauptman P, Hazelrigg M, Herzog C, Heywood J, Hill T, Hilton T, Hirsch H, Hunter J, Ibrahim H, Imburgia M, Iteld B, Jackson B, Jaffrani N, Jain D, Jain A, James M, Jimenez J, Johnson E, Kale P, Kaneshige A, Kapadia S, Karia D, Karlsberg R, Katholi R, Kerut E, Khoury W, Kipperman R, Klapholz M, Kosinski E, Kozinn M, Kraus D, Krueger S, Kumar S, Lader E, Lee C, Lewis E, Light McGroary K, Loh I, Lombardi W, Machado C, Maislos F, Mancini D, Markus T, Mather P, McCants K, McGrew F, McLaurin B, McMillan E, McNamara D, Meyer T, Meymandi S, Miller A, Minami E, Modi M, Mody F, Mohanty P, Moscoso R, Moskowitz R, Moustafa M, Mullen M, Naz T, Noonan T, O. Brien T, Oellerich W, Oren R, Pamboukian S, Pereira N, Pitt W, Porter C, Prabhu S, Promisloff S, Ratkovec R, Richardson R, Ross A, Saleh N, Saltzberg M, Sarkar S, Schmedtje J, Schneider R, Schuyler G, Shanes J, Sharma A, Siegel C, Siegel R, Silber D, Singh N, Singh J, Singh V, Sklar J, Small R, Smith A, Smith E, Smull D, Sotolongo R, Staniloae C, Stapleton D, Steele P, Stehlik J, Stein M, Tang W, Thadani U, Torre Amoine G, Trichon B, Tsai C, Tummala R, Van Bakel A, Vicari R, Vijay N, Vijayaraghavan K, Vittorio T, Vossler M, Wagoner L, Wallis D, Ward N, Widmer M, Wight J, Wilkins C, Williams C, Williams G, Winchester M, Winkel E, Wittmer B, Wood D, Wormer D, Wright R, Xu Z, Yasin M, Zolty R., PERRONE FILARDI, PASQUALE, Karl, Swedberg, James B., Young, Inder S., Anand, Sunfa, Cheng, Akshay S., Desai, Rafael, Diaz, Aldo P., Maggioni, John J. V., Mcmurray, Christopher, O'Connor, Marc A., Pfeffer, Scott D., Solomon, Yan, Sun, Michal, Tendera, Dirk J., van Veldhuisen, Young, J, Grinfeld, L, Krum, H, Vanhaecke, J, Olivera Clausell, N, Goudev, A, Howlett, J, Corbalan, R, Hradec, J, Kober, L, Eha, J, Cohen Solal, A, Anker, Sd, Chopra, V, Lewis, B, Erglis, A, Sakalyte, G, Cardona Munoz, E, Dunselman, P, Dickstein, K, Ponikowski, P, Seabra Gomes, R, Apetrei, E, Mareev, V, Murin, J, Dalby, A, Lopez Sendon, J, Willenheimer, R, Cleland, J, Adams, K, Anand, I, Butler, J, Dunlap, M, Felker, M, Ghali, J, Levy, W, Carson, P, Cohn, J, Drexler, H, Pocock, S, Ryden, L, Poole Wilson, P, Fishbane, S, Ivanovich, P, Nissenson, A, Katz, S, Barkoudah, E, Campbell, P, Desai, A, Finn, Pv, Hartley, L, Kasabov, R, Odutayo, Ka, Rajesh, V, Solomon, S, Weinrauch, La, Albizem, M, Cheng, S, Chou, W, Deegenaars, M, Dougherty, M, Fouqueray, B, Froissart, M, Froment, A, Gadd, S, Ghosh, S, Grazette, L, Guillet, S, Gulabani, D, Haddock, B, Harris, C, Jaffer, A, Kerns, C, Kim, J, Knussel, B, Law, H, Mather, R, Mix, C, Moore, L, Moyes, R, Polu, K, Rossert, J, Scarlata, D, Smirnakis, K, Smith, L, Snyder, W, Sun, Y, Trotman, Ml, Wasserman, S, Watkins, A, Wong, M, Zhang, Y, Amuchastegui, M, Belziti, C, Bluguermann, J, Caccavo, M, Cartasegna, L, Colque, R, Cuneo, C, Fernandez, A, Gabito, A, Goicochea, R, Gonzalez, M, Gorosito, V, Hominal, M, Kevorkian, R, Litvak Bruno, M, Llanos, J, Mackinnon, I, Manuale, O, Marzetti, E, Nul, D, Perna, E, Riccitelli, M, Sanchez, A, Santos, D, Schygiel, P, Toblli, J, Vogel, D, Aggarwal, A, Amerena, J, De Looze, F, Fletcher, P, Hare, D, Ireland, M, Lattimore, J, Marwick, T, Sindone, A, Thompson, P, Waites, J, Altenberger, J, Ebner, C, Lenz, K, Pacher, R, Poelzl, G, Charlier, F, de Ceuninck, M, De Keulenaer, G, Dendale, P, Maréchal, P, Mullens, W, Thoeng, J, Vanderheyden, M, Weytjens, C, Wollaert, B, Albuquerque, D, Almeida, D, Aspe y., Rosas J, Bocchi, E, Bordignon, S, Clausell, N, Kaiser, S, Leaes, P, Martins Alves, S, Montera, M, Moura, L, Pereira de Castro, R, Rassi, S, Reis, A, Saraiva, J, Simões, M, Souza Neto, J, Teixeira, M, Benov, H, Chompalova, B, Donova, T, Georgiev, P, Gotchev, D, Grigorov, M, Guenova, D, Hergeldjieva, V, Ivanov, D, Kostova, E, Manolova, A, Marchev, S, Nikolov, F, Popov, A, Raev, D, Tzekova, M, Czarnecki, W, Giannetti, N, Haddad, H, Heath, J, Huynh, T, Lepage, S, Liu, P, Lonn, E, Ma, P, Manyari, D, Moe, G, Parker, J, Pesant, Y, Rajda, M, Ricci, J, Roth, S, Sestier, F, Sluzar, V, Sussex, B, Vizel, S, Antezana, G, Bugueno, C, Castro, P, Conejeros, C, Manriquez, L, Martinez, D, Potthoff, S, Stockins, B, Vukasovic, J, Gregor, P, Herold, M, Jerabek, O, Jirmar, R, Kuchar, R, Linhart, A, Podzemska, B, Soucek, M, Spac, J, Spacek, R, Vodnansky, P, Bronnum Schou, J, Clemmensen, K, Egstrup, K, Jensen, G, Kjoller Hansen, L, Markenvard, J, Rokkedal, J, Skagen, K, Torp Pedersen, C, Tuxen, C, Videbak, L, Laks, T, Vahula, V, Harjola, V, Kettunen, R, Kotila, M, Bauer, F, Coisne, D, Davy, J, De Groote, P, Dos Santos, P, Funck, F, Galinier, M, Gibelin, P, Isnard, R, Neuder, Y, Roul, G, Sabatier, R, Trochu, J, Denny, S, Dreykluft, T, Flesch, M, Genth Zotz, S, Hambrecht, R, Hein, J, Jeserich, M, John, M, Kreider Stempfle, H, Laufs, U, Muellerleile, K, Natour, M, Sandri, M, Schäufele, T, von Hodenberg, E, Weyland, K, Winkelmann, B, Tse, H, Yan, B, Barsi, B, Csikasz, J, Dezsi, C, Edes, I, Forster, T, Karpati, P, Kerekes, C, Kis, E, Kosa, I, Lupkovics, G, Nagy, A, Preda, I, Ronaszeki, A, Tomcsanyi, J, Zamolyi, K, Agarwal, D, Bahl, V, Bordoloi, A, Chockalingam, K, Chopda, M, Dugal, J, Ghaisas, N, Grant, P, Hiremath, S, Iyengar, S, Jagadeesa Subramania, B, Jain, P, Joshi, A, Khan, A, Mullasari, A, Naik, S, Oomman, A, Pai, V, Pareppally Gopal, R, Parikh, K, Patel, T, Prakash, V, Sastry, B, Sathe, S, Sinha, N, Srikanthan, V, Subburamakrishnan, P, Thacker, H, Wander, G, Admon, D, Katz, A, Klainman, E, Marmor, A, Moriel, M, Mosseri, M, Shotan, A, Weinstein, J, Zimlichman, R, Agostoni, P, Albanese, M, Alunni, G, Bini, R, Boccanelli, A, Bolognese, L, Campana, C, Carbonieri, E, Carpino, C, Checco, L, Cosmi, F, Angelo, Gd, De Cristofaro, M, Floresta, A, Fucili, A, Galvani, M, Ivleva, A, Marra, S, Musca, G, Peccerillo, N, PERRONE FILARDI, Pasquale, Picchio, E, Russo, T, Scelsi, L, Senni, M, Tavazzi, L, Jasinkevica, I, Kakurina, N, Veze, I, Volans, E, Bagdonas, A, Berukstis, E, Celutkiene, J, Dambrauskaite, A, Jarasuniene, D, Luksiene, D, Rudys, A, Sliaziene, S, Aguilar Romero, R, Cardona Muñoz, E, Castro Jimenez, J, Chavez Herrera, J, Chuquiure Valenzuela, E, De la Pena, G, Herrera, E, Leiva Pons, J, Lopez Alvarado, A, Mendez Machado, G, Ramos Lopez, G, Basart, D, Buijs, E, Cornel, J, de Leeuw, M, Dijkgraaf, R, Freericks, M, Hamraoui, K, Lenderlink, T, Linssen, G, Lodewick, P, Lodewijks, C, Lok, D, Nierop, P, Ronner, E, Somsen, A, van Dantzig, J, van der Burgh, P, van Kempen, L, van Vlies, B, Voors, A, Wardeh, A, Willems, F, Gundersen, T, Hole, T, Thalamus, J, Westheim, A, Dabrowski, M, Gorski, J, Korewicki, J, Kuc, K, Miekus, P, Musial, W, Niegowska, J, Piotrowski, W, Podolec, P, Polonski, L, Rynkiewicz, A, Szelemej, R, Trusz Gluza, M, Ujda, M, Wojciechowski, D, Wysokinski, A, Camacho, A, Fonseca, C, Monteiro, P, Bruckner, I, Carasca, E, Coman, I, Datcu, M, Dragulescu, S, Ionescu, P, Iordachescu Petica, D, Manitiu, I, Popa, V, Pop Moldovan, A, Radoi, M, Stamate, S, Tomescu, M, Vita, I, Aroutiounov, G, Ballyuzek, M, Bart, B, Churina, S, Glezer, M, Goloshchekin, B, Kobalava, Z, Kostenko, V, Lopatin, Y, Martynov, A, Orlov, V, Semernin, E, Shogenov, Z, Sidorenko, B, Skvortsov, A, Storzhakov, G, Sulimov, V, Talibov, O, Tereshenko, S, Tsyrline, V, Zadionchenko, V, Zateyshchikov, D, Dzupina, A, Hranai, M, Kmec, J, Micko, K, Pella, D, Sojka, G, Spisak, V, Vahala, P, Vinanska, D, Badat, A, Bayat, J, Dawood, S, Delport, E, Ellis, G, Garda, R, Klug, E, Mabin, T, Naidoo, D, Pretorius, M, Ranjith, N, Van Zyl, L, Weich, H, Anguita, M, Berrazueta, J, Bruguera i., Cortada J, de Teresa, E, Gómez Sánchez, M, González Juanatey, J, Gonzalez Maqueda, I, Jordana, R, Lupon, J, Manzano, L, Pascual Figal, D, Pulpón, L, Recio, J, Ridocci Soriano, F, Rodríguez Lambert, J, Roig Minguell, E, Romero, J, Valdovinos, P, Klintberg, L, Kronvall, T, Lycksell, M, Morner, S, Rydberg, E, Swedberg, K, Timberg, I, Wikstrom, G, Moccetti, T, Ashok, J, Banerjee, P, Carr White, G, Connolly, E, Francis, M, Greenbaum, R, Kadr, H, Lindsay, S, Mcmurray, J, Megarry, S, Memon, A, Murdoch, D, Senior, R, Squire, I, Tan, L, Witte, K, Adamson, P, Adler, A, Altschul, L, Altschuller, A, Amirani, H, Andreou, C, Ansari, M, Antonishen, M, Banchs, H, Banerjee, S, Banish, D, Bank, A, Barbagelata, A, Barnard, D, Bellinger, R, Benn, A, Berk, M, Berry, B, Bethala, V, Bilazarian, S, Bisognano, J, Bleyer, F, Blum, M, Boehmer, J, Bouchard, A, Boyle, A, Bozkurt, B, Brown, C, Burlew, B, Burnham, K, Call, J, Cambier, P, Cappola, T, Carlson, R, Chandler, B, Chandra, R, Chandraratna, P, Chernick, R, Colan, D, Colfer, H, Colucci, W, Connelly, T, Costantini, O, Dadkhah, S, Dauber, I, Davis, J, Davis, S, Denning, S, Drazner, M, Dunlap, S, Egbujiobi, L, Elkayam, U, Elliott, J, El Shahawy, M, Essandoh, L, Ewald, G, Fang, J, Farhoud, H, Felker, G, Fernandez, J, Festin, R, Fishbein, G, Florea, V, Flores, E, Floro, J, Gabris, M, Garg, M, Gatewood, R, Geller, M, Ghumman, W, Gibbs, G, Gillespie, E, Gilmore, R, Gogia, H, Goldberg, L, Gradus Pizlo, I, Grainger, T, Gudmundsson, G, Gunawardena, D, Gupta, D, Hack, T, Hall, S, Hamroff, G, Hankins, S, Hanna, M, Hargrove, J, Haught, W, Hauptman, P, Hazelrigg, M, Herzog, C, Heywood, J, Hill, T, Hilton, T, Hirsch, H, Hunter, J, Ibrahim, H, Imburgia, M, Iteld, B, Jackson, B, Jaffrani, N, Jain, D, Jain, A, James, M, Jimenez, J, Johnson, E, Kale, P, Kaneshige, A, Kapadia, S, Karia, D, Karlsberg, R, Katholi, R, Kerut, E, Khoury, W, Kipperman, R, Klapholz, M, Kosinski, E, Kozinn, M, Kraus, D, Krueger, S, Kumar, S, Lader, E, Lee, C, Lewis, E, Light McGroary, K, Loh, I, Lombardi, W, Machado, C, Maislos, F, Mancini, D, Markus, T, Mather, P, Mccants, K, Mcgrew, F, Mclaurin, B, Mcmillan, E, Mcnamara, D, Meyer, T, Meymandi, S, Miller, A, Minami, E, Modi, M, Mody, F, Mohanty, P, Moscoso, R, Moskowitz, R, Moustafa, M, Mullen, M, Naz, T, Noonan, T, O., Brien T, Oellerich, W, Oren, R, Pamboukian, S, Pereira, N, Pitt, W, Porter, C, Prabhu, S, Promisloff, S, Ratkovec, R, Richardson, R, Ross, A, Saleh, N, Saltzberg, M, Sarkar, S, Schmedtje, J, Schneider, R, Schuyler, G, Shanes, J, Sharma, A, Siegel, C, Siegel, R, Silber, D, Singh, N, Singh, J, Singh, V, Sklar, J, Small, R, Smith, A, Smith, E, Smull, D, Sotolongo, R, Staniloae, C, Stapleton, D, Steele, P, Stehlik, J, Stein, M, Tang, W, Thadani, U, Torre Amoine, G, Trichon, B, Tsai, C, Tummala, R, Van Bakel, A, Vicari, R, Vijay, N, Vijayaraghavan, K, Vittorio, T, Vossler, M, Wagoner, L, Wallis, D, Ward, N, Widmer, M, Wight, J, Wilkins, C, Williams, C, Williams, G, Winchester, M, Winkel, E, Wittmer, B, Wood, D, Wormer, D, Wright, R, Xu, Z, Yasin, M, Zolty, R., Faculteit Medische Wetenschappen/UMCG, and Cardiovascular Centre (CVC)
Subjects: Male, CHRONIC KIDNEY-DISEASE, Darbepoetin alfa, Ciencias de la Salud, Kaplan-Meier Estimate, law.invention, Hemoglobins, DOUBLE-BLIND, Randomized controlled trial, law, hemic and lymphatic diseases, Treatment Failure, Hazard ratio, Ética Médica, Anemia, General Medicine, Middle Aged, Shock, Septic, Stroke, purl.org/becyt/ford/3 [https], Female, medicine.drug, medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, Placebo, CONTROLLED-TRIAL, purl.org/becyt/ford/3.3 [https], MORBIDITY, Double-Blind Method, Darbepoetin, Internal medicine, Thromboembolism, parasitic diseases, medicine, Humans, Adverse effect, Erythropoietin, Aged, Proportional Hazards Models, CITY CARDIOMYOPATHY QUESTIONNAIRE, business.industry, Proportional hazards model, MORTALITY, equipment and supplies, medicine.disease, Surgery, REDUCTION, EPOETIN, Heart failure, Hematinics, business, Systolic heart failure, Heart Failure, Systolic
Abstract: BACKGROUND: Patients with systolic heart failure and anemia have worse symptoms, functional capacity, and outcomes than those without anemia. We evaluated the effects of darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anemia. METHODS: In this randomized, double-blind trial, we assigned 2278 patients with systolic heart failure and mild-to-moderate anemia (hemoglobin level, 9.0 to 12.0 g per deciliter) to receive either darbepoetin alfa (to achieve a hemoglobin target of 13 g per deciliter) or placebo. The primary outcome was a composite of death from any cause or hospitalization for worsening heart failure. RESULTS: The primary outcome occurred in 576 of 1136 patients (50.7%) in the darbepoetin alfa group and 565 of 1142 patients (49.5%) in the placebo group (hazard ratio in the darbepoetin alfa group, 1.01; 95% confidence interval, 0.90 to 1.13; P=0.87). There was no significant between-group difference in any of the secondary outcomes. The neutral effect of darbepoetin alfa was consistent across all prespecified subgroups. Fatal or nonfatal stroke occurred in 42 patients (3.7%) in the darbepoetin alfa group and 31 patients (2.7%) in the placebo group (P=0.23). Thromboembolic adverse events were reported in 153 patients (13.5%) in the darbepoetin alfa group and 114 patients (10.0%) in the placebo group (P=0.01). Cancer-related adverse events were similar in the two study groups. CONCLUSIONS: Treatment with darbepoetin alfa did not improve clinical outcomes in patients with systolic heart failure and mild-to-moderate anemia. Our findings do not support the use of darbepoetin alfa in these patients. (Funded by Amgen; RED-HF ClinicalTrials.gov number, NCT00358215.). Fil: Swedberg, Karl. University of Gothenburg; Suecia Fil: Young, James B.. Cleveland Clinic; Estados Unidos Fil: Anand, Inder S.. University of Minnesota; Estados Unidos Fil: Cheng, Sunfa. Amgen; Estados Unidos Fil: Desai, Akshay S.. Brigham and Women’s Hospital; Estados Unidos Fil: Diaz, Rafael. Estudios Clínicos Latinoamérica; Argentina Fil: Maggioni, Aldo P.. Italian Association of Hospital Cardiologists Research Center; Italia Fil: McMurray, John J.V.. University of Glasgow; Reino Unido Fil: O’Connor, Christopher. University of Duke; Estados Unidos Fil: Pfeffer, Marc A.. Brigham and Women’s Hospital; Estados Unidos Fil: Solomon, Scott D.. Brigham and Women’s Hospital; Estados Unidos Fil: Sun, Yan. Amgen; Estados Unidos Fil: Tendera, Michal. Medical University of Silesia; Polonia Fil: van Veldhuisen, Dirk J.. University of Groningen; Países Bajos Fil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Published: 2013
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28. Off-label use of rituximab for systemic lupus erythematosus in Europe

Author: Ryden-Aulin, Monica, Boumpas, Dimitrios, Bultink, Irene, Rubio, Jose Luis Callejas, Caminal-Montero, Luis, Castro, Antoni, Colodro Ruiz, Agustin, Doria, Andrea, Domer, Thomas, Gonzalez-Echavarri, Cristina, Gremese, Elisa, Houssiau, Frederic A., Huizinga, Tom, Inana, Murat, Isenberg, David, Luliano, Annamaria, Jacobsen, Soren, Jimenez-Alonso, Juan, Kovacs, Laszlo, Mariette, Xavier, Mosca, Marta, Nived, Ola, Oristrell, Joaquim, Ramos-Casals, Manuel, Rascon, Javier, Ruiz-Irastorza, Guillermo, Saez-Comet, Luis, Salvador Cervello, Gonzalo, Cervello, Gonzalo Salvador, Sebastiani, Gian Domenico, Squatrito, Danilo, Szucs, Gabriella, Voskuyl, Alexandre, van Vollenhoven, Ronald, Rheumatology, AII - Inflammatory diseases, [Ryden-Aulin, Monica] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Unit Clin Therapy Res, Stockholm, Sweden, [van Vollenhoven, Ronald] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Unit Clin Therapy Res, Stockholm, Sweden, [Boumpas, Dimitrios] Natl & Kapodestrian Univ Athens, Attikon Univ Hosp, Joint Acad Rheumatol Program, Med Sch, Athens, Greece, [Boumpas, Dimitrios] Natl & Kapodestrian Univ Athens, Attikon Univ Hosp, Dept Med 4, Med Sch, Athens, Greece, [Bultink, Irene] Amsterdam Rheumatol & Immunol Ctr, Tepartment Rheumatol, Amsterdam, Netherlands, [Rubio, Jose Luis Callejas] Hosp San Cecilio, Unit Autoimmune Dis, Granada, Spain, [Caminal-Montero, Luis] Hosp Univ Cent Asturias, Internal Med Dept, Autoimmune System Dis Unit, Oviedo, Spain, [Castro, Antoni] Rovira & Virgili Univ URV, Univ Hosp Sant Joan Reus, lnternal Med Dept Univ, IISPV, Reus, Spain, [Colodro Ruiz, Agustin] Pasaje Nueva Victoria,2,2do C, Jaen, Spain, [Doria, Andrea] Univ Padua, Dept Med, Rheumatol Unit, Padua, Italy, [Domer, Thomas] Charite Univ Med Berlin, Dept Med Rheumatol & Clin Immunol, Berlin, Germany, [Gonzalez-Echavarri, Cristina] Univ Basque Country, Cruces Univ Hosp, BioCruces Hlth Res Inst, Autoimmune Dis Res Unit,Dept Internal Med, Baracaldo, Spain, [Ruiz-Irastorza, Guillermo] Univ Basque Country, Cruces Univ Hosp, BioCruces Hlth Res Inst, Autoimmune Dis Res Unit,Dept Internal Med, Baracaldo, Spain, [Gremese, Elisa] Univ Cattolica Sacro Cuore, Inst Rheumatol & Affine Sci IRSA, Rome, Italy, [Houssiau, Frederic A.] Catholic Univ Louvain, Pole Pathol Rhumatismales Inflammatoires & Syst, Clin Univ St Luc, Serv Rhumatol, Brussels, Belgium, [Huizinga, Tom] Leiden Univ, Med Ctr, Dept Rheumatol, C1-41, Leiden, Netherlands, [Inana, Murat] Istanbul Univ, Istanbul Fac Med, Dept Internal Med, Div Rheumatol, Istanbul, Turkey, [Isenberg, David] UCL, Rayne Bldg, London, England, [Luliano, Annamaria] San Camillo Hosp, Rheumatol Unit, Rome, Italy, [Jacobsen, Soren] Univ Copenhagen, Rigshosp, Ctr Rheumatol & Spine Dis, Copenhagen Lupus & Vasculitis Clin, Copenhagen, Denmark, [Jimenez-Alonso, Juan] Univ Virgen Nieves Hosp, lnternal Dept, Granada, Spain, [Kovacs, Laszlo] Univ Szeged, Albert Szent Gyorgyi Hlth Ctr, Fac Med, Dept Rheumatol, Szeged, Hungary, [Mariette, Xavier] Univ Paris Sud, Hopitaux Univ Paris Sud, Rhumatol Responsable Unite Rech Clin, INSERM U1184, Paris, France, [Mosca, Marta] Rheumatol Unit, Pisa, Italy, [Nived, Ola] Skane Univ Hosp, Rheumatol Clin, Lund, Sweden, [Oristrell, Joaquim] Univ Autonoma Barcelona, Hosp Sabadell, Internal Med Dept, Catalunya, Spain, [Ramos-Casals, Manuel] CELLEX IDIBAPS, Josep Font Autoimmune Lab, ICMiD, Dept Autoimmune Dis, Barcelona, Spain, [Rascon, Javier] Carrer Sabateres, 9-1,Alare, Islas Baleares, Spain, [Saez-Comet, Luis] Hosp Univ Miguel Servet Zaragoza, Unidad Enfermedades Autoinmunes Sistem, Paseo Isabel Catolica, Zaragoza, Spain, [Salvador Cervello, Gonzalo] Hosp Univ & Politecn La Fe, Inmunopathol & Autoimmune Area, Dept Internal Med, Valencia, Spain, [Sebastiani, Gian Domenico] Osped San Camillo, UOC Reumatol, Circonvallaz Gianicolense 87, Rome, Italy, [Squatrito, Danilo] Univ Florence, Dept Sperimental & Clin Med, Florence, Italy, [Szucs, Gabriella] Univ Debrecen, Inst Med, Dept Rheumatol, Debrecen, Hungary, [Voskuyl, Alexandre] Vrije Univ Amsterdam, Med Ctr, Amsterdam Rheumatol & Immunol Ctr ARC, Amsterdam, Netherlands, [van Vollenhoven, Ronald] Karolinska Univ Hosp Stockholm, Rheumatol Clin, Stockholm, Sweden, [van Vollenhoven, Ronald] Amsterdam Rheumatol & Immunol Ctr ARC, AMC Mail F4-105, Amsterdam, Netherlands, MSD, Lilly Netherlands, Roche, UCB, Sanofi, and RvV
Subjects: medicine.medical_specialty, Disease duration, Immunology, Lupus nephritis, DMARDs (biologic), Klinikai orvostudományok, Off-label use, Systemic Lupus Erythematosus, Article, Disease activity, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Internal medicine, medicine, Lupus Nephritis, Medicine (all), In patient, 030212 general & internal medicine, skin and connective tissue diseases, 030203 arthritis & rheumatology, business.industry, Orvostudományok, General Medicine, medicine.disease, Disease control, 3. Good health, Rituximab, business, medicine.drug
Abstract: OBJECTIVES: Rituximab (RTX) is a biological treatment used off-label in patients with systemic lupus erythematosus (SLE). This survey aimed to investigate the off-label use of RTX in Europe and compare the characteristics of patients receiving RTX with those receiving conventional therapy.METHODS: Data on patients with SLE receiving RTX were taken from the International Registry for Biologics in SLE retrospective registry and complemented with data on patients with SLE treated with conventional therapy. For nationwide estimates of RTX use in patients with SLE, investigators were asked to provide data through case report forms (CRFs). Countries for which no data were submitted through CRFs, published literature and/or personal communication were used, and for European countries where no data were available, estimates were made on the assumption of similarities with neighbouring countries.RESULTS: The estimated off-label use of RTX in Europe was 0.5%-1.5% of all patients with SLE. In comparison with patients with SLE on conventional therapy, patients treated with RTX had longer disease duration, higher disease activity and were more often treated with immunosuppressives. The most frequent organ manifestations for which either RTX or conventional therapy was initiated were lupus nephritis followed by musculoskeletal and haematological. The reason for treatment was, besides disease control, corticosteroid-sparing for patients treated with conventional therapy.CONCLUSIONS: RTX use for SLE in Europe is restrictive and appears to be used as a last resort in patients for whom other reasonable options have been exhausted.
Published: 2016
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29. Unspeakable Horror: Outing Syphilis in Joseph Conrad’s Heart of Darkness

Author: Wendy Ryden and Nicole Cosentino
Subjects: Psychoanalysis, media_common.quotation_subject, Character (symbol), Representation (arts), Art, Morality, medicine.disease, Rhetoric, Novella, medicine, Syphilis, Parallels, media_common, Megalomania
Abstract: The authors posit syphilis as the source for Kurtz’s affliction in Joseph Conrad’s Heart of Darkness and argue for understanding the novella as a deployment of the rhetoric of disease, which yokes together medical fears and problematic sexual morality with a global violence infecting self-congratulatory European benevolence and charity. Conrad’s tale is both implicitly and explicitly eroticized as well as steeped in gothic representation of the hidden and revealed to manage an unsayable horror. As such, the language of the story parallels pervasive late nineteenth-century syphilis discourse that likewise relies on obfuscation and silences. Descriptions of Kurtz’s megalomania resonate with the symptomatology of syphilis and perceived syphilitics, such as Nietzsche and Columbus, who might have served as models for the character.
Published: 2017
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30. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Author: Alberro, JA, Ballester, B, Deulofeu, P, Fabregas, R, Fraile, M, Gubern, JM, Janer, J, Moral, A, de Pablo, JL, Penalva, G, Puig, P, Ramos, M, Rojo, R, Santesteban, P, Serra, C, Sola, M, Solarnau, L, Solsona, J, Veloso, E, Vidal, S, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Ohashi, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Coles, CE, Haybittle, JL, Moebus, V, Leonard, CF, Calais, G, Garaud, P, Collett, V, Davies, C, Delmestri, A, Sayer, J, Harvey, VJ, Holdaway, IM, Kay, RG, Mason, BH, Forbe, JF, Franci, PA, Wilcken, N, Balic, M, Bartsch, R, Fesl, C, Fitzal, F, Fohler, H, Gnant, M, Greil, R, Jakesz, R, Marth, C, Mlineritsch, B, Pfeiler, G, Singer, CF, Steger, GG, Stoeger, H, Canney, P, Yosef, HMA, Focan, C, Peek, U, Oates, GD, Powell, J, Durand, M, Mauriac, L, Di Leo, A, Dolci, S, Larsimont, D, Nogaret, JM, Philippson, C, Piccart, MJ, Masood, MB, Parker, D, Price, JJ, Lindsay, MA, Mackey, J, Martin, M, Hupperets, PSGJ, Bates, T, Blamey, RW, Chetty, U, Ellis, IO, Mallon, E, Morgan, DAL, Patnick, J, Pinder, S, Lohrisch, C, Nichol, A, Bartlett, JMS, Bramwell, VH, Chen, BE, Chia, SKL, Gelmon, K, Goss, PE, Levine, MN, Parulekar, W, Pater, JL, Pritchard, KI, Shepherd, LE, Tu, D, Whelan, T, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Norton, L, Weiss, RB, Abu-Zahara, HT, Karpov, A, Portnoj, SL, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett-Lee, PJ, Manse, RE, Monypenny, IJ, Gordon, NH, Davis, HL, Cuzick, J, Sestak, I, Lehingue, Y, Romestaing, P, Dubois, JB, Delozier, T, Griffon, B, Lesec'h, J Mace, Mustacchi, G, Petruzelka, L, Pribylova, O, Owen, JR, Meier, P, Shan, Y, Shao, YF, Wang, X, Zhao, DB, Howell, A, Swindell, R, Albano, J, de Oliveira, CF, Gervasio, H, Gordilho, J, Ejlertsen, B, Jensen, M-B, Mouridsen, H, Gelman, RS, Harris, JR, Hayes, D, Henderson, C, Shapiro, CL, Christiansen, P, Ewertz, M, Jensen, MB, Mouridsen, HT, Fehm, T, Trampisch, HJ, Dalesio, O, de Vries, EGE, Rodenhuis, S, van Tinteren, H, Comis, RL, Davidson, NE, Gray, R, Robert, N, Sledge, G, Solin, LJ, Sparano, JA, Tormey, DC, Wood, W, Cameron, D, Dixon, JM, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, JGM, Treurniet-Donker, AD, van Putten, WLJ, Rotmensz, N, Veronesi, U, Viale, G, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, JP, Poortmans, PM, Rutgers, E, van de Velde, CJH, Cunningham, MP, Huovinen, R, Joensuu, H, Costa, A, Bonadonna, G, Gianni, L, Valagussa, P, Goldstein, LJ, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Lupors, E, Namer, M, Carrasco, E, Segui, MA, Eierman, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, JU, Costa, SD, Eidtmann, H, Gerber, B, Jackisch, C, Loib, S, von Minckwitz, G, de Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, MC, Sacco, M, Valentini, M, McArdle, CS, Smith, DC, Stallard, S, Dent, DM, Gudgeon, CA, Hacking, A, Murray, E, Panieri, E, Werner, ID, De Salvo, GL, Del Bianco, P, Zavagno, G, Leone, B, Vallejo, CT, Zwenger, A, Galligioni, E, Lopez, M, Erazo, A, Medina, JY, Horiguchi, J, Takei, H, Fentiman, IS, Hayward, JL, Rubens, RD, Skilton, D, Scheurlen, H, Sohn, HC, Untch, M, Dafni, U, Markopoulos, C, Bamia, C, Fountzilas, G, Koliou, G-A, Manousou, K, Mavroudis, D, Klefstrom, P, Blomqvist, C, Saarto, T, Gallen, M, Canavese, G, Tinterri, C, Margreiter, R, de Lafontan, B, Mihura, J, Roche, H, Asselain, B, Salmon, RJ, Vilcoq, JR, Brain, E, de La Lande, B, Mouret-Fourme, E, Andre, F, Arriagada, R, Delaloge, S, Hill, C, Koscienly, S, Michiels, S, Rubino, C, A'Hern, R, Bliss, J, Ellis, P, Kilburn, L, Yarnold, JR, Benraadt, J, Kooi, M, van de Velde, AO, van Dongen, JA, Vermorken, JB, Castiglione, M, Coates, A, Colleoni, M, Collins, J, Forbes, J, Gelbe, RD, Goldhirsch, A, Lindtner, J, Price, KN, Regan, MM, Rudenstam, CM, Senn, HJ, Thuerlimann, B, Bliss, JM, Chilvers, CED, Coombes, RC, Hall, E, Marty, M, Buyse, M, Possinger, K, Schmid, P, Wallwiener, D, Foster, L, George, WD, Stewart, HJ, Stroner, P, Borovik, R, Hayat, H, Inbar, MJ, Peretz, T, Robinson, E, Camerini, T, Formelli, F, Martelli, G, Di Mauro, MG, Perrone, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Musolino, A, Passalacqua, R, Iwata, H, Shien, T, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Sadoon, M, Tulusan, AH, Kohno, N, Miyashita, M, Takao, S, Ahn, J-H, Jung, KH, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, Liefers, GJ, Christiaens, R, Neven, P, Paridaens, R, Van den Bogaert, W, Gazet, JC, Corcoran, N, Deshpande, N, di Martino, L, Douglas, P, Host, H, Lindtner, A, Notter, G, Bryant, AJS, Ewing, GH, Firth, LA, Krushen-Kosloski, JL, Nissen-Meyer, R, Anderson, H, Killander, F, Malmstrom, P, Ryden, L, Arnesson, L-G, Carstense, J, Dufmats, M, Fohlin, H, Nordenskjold, B, Soderberg, M, Sundqvist, M, Carpenter, TJ, Murray, N, Royle, GT, Simmonds, PD, Albain, K, Barlow, W, Crowley, J, Gralow, J, Hortobagyi, G, Livingston, R, Martino, S, Osborne, CK, Ravdin, PM, Bergh, J, Bondesso, T, Celebiogl, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Goransson, E, Iiristo, M, Johansson, U, Lenner, E, Lofgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, af Trampe, E, Wadstrom, C, Janni, W, Maibach, R, Thurlimann, B, Hadji, P, Hozumi, J, Holli, K, Rouhento, K, Safra, T, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, AHG, Fyles, A, Meakin, JW, Panzarella, T, Bahi, J, Lemonnier, J, Martin, AL, Reid, M, Spittle, M, Bishop, H, Bundred, NJ, Forbes, JF, Forsyth, S, George, WS, Pinder, SE, Deutsch, GP, Kwong, DLW, Pai, VR, Peto, R, Senanayake, F, Boccardo, F, Rubagotti, A, Baum, M, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, JS, Carlomagno, C, De Laurentiis, M, De Placido, S, Schem, C, Williams, L, Bell, R, Coleman, RE, Dodwell, D, Hinsley, S, Marshall, HC, Pierce, LJ, Basso, SMM, Lumachi, F, Solomayer, E, Horsman, JM, Lester, J, Winter, MC, Buzdar, AU, Hsu, L, Love, RR, Ahlgren, J, Garmo, H, Holmberg, L, Lindman, H, Warnberg, F, Asmar, L, Jones, SE, Aft, R, Gluz, O, Harbeck, N, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, BK, Chlebowski, RT, Caffier, H, Brufsky, AM, Llombart, HA, Asselain, B, Barlow, W, Bartlett, J, Bradley, R, Braybrooke, J, Davies, C, Dodwell, D, Gray, R, Mannu, G, Taylor, C, Peto, R, McGale, P, Pan, H, Wang, Y, Wang, Z, Department of Oncology, Clinicum, HUS Comprehensive Cancer Center, Medical Oncology, Cancer Research UK, and Pfizer Limited
Subjects: 0301 basic medicine, Oncology, Time Factors, SURGERY, medicine.medical_treatment, menopause, chemotherapy, Mastectomy, Segmental, Rate ratio, THERAPY, aromatase inhibitors, CEA, 0302 clinical medicine, Risk Factors, Medicine and Health Sciences, Breast, Neoplasm Metastasis, Randomized Controlled Trials as Topic, RISK, tamoxifen, breast tumor, CA15-3, axillary dissection, mastectomy, Middle Aged, Neoadjuvant Therapy, METHOTREXATE, 3. Good health, trastuzumab, Treatment Outcome, quadrantectomy, Chemotherapy, Adjuvant, axillary lymphnodes, 030220 oncology & carcinogenesis, Meta-analysis, SURVIVAL, Disease Progression, Female, Life Sciences & Biomedicine, axillary clearance, RADIOTHERAPY, medicine.drug, Adult, medicine.medical_specialty, Anthracycline, 3122 Cancers, Antineoplastic Agents, Breast Neoplasms, axillary nodes, sentinel node biopsy, 03 medical and health sciences, breast cancer, Breast cancer, SDG 3 - Good Health and Well-being, HER2, Internal medicine, Journal Article, medicine, cancer, Humans, Breast, breast cancer, breast diseases, cancer, malignancy, menopause, surgery, mastectomy, quadrantectomy, lumpectomy, axillary nodes, axillary lymphnodes, axillary dissection, axillary clearance, sentinel node biopsy, sentinel node, BRCA1, BRCA2, tamoxifen, aromatase inhibitors, breast tumor, osteoporosis, bisphosphonates, denosumab, trastuzumab, HER2, CEA, CA15-3, tumor marker, chemotherapy, endocrine therapy, Oncology & Carcinogenesis, RECURRENCE, bisphosphonates, Pathological, Neoplasm Staging, lumpectomy, Chemotherapy, Science & Technology, breast diseases, endocrine therapy, business.industry, denosumab, BRCA1, medicine.disease, BRCA2, osteoporosis, Radiation therapy, STIMULATING FACTOR, 030104 developmental biology, sentinel node, tumor marker, Methotrexate, Neoplasm Recurrence, Local, business, 1112 Oncology And Carcinogenesis, malignancy
Abstract: BACKGROUND: Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. METHODS: We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). FINDINGS: Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4-8·6]; rate ratio 1·37 [95% CI 1·17-1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92-1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95-1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94-1·15]; p=0·45). INTERPRETATION: Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy. FUNDING: Cancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health. ispartof: LANCET ONCOLOGY vol:19 issue:1 pages:27-39 ispartof: location:England status: published
Published: 2017
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31. Mechanisms of Anesthetic Action and Neurotoxicity: Lessons from Molluscs

Author: Fahad Iqbal, Saba Riaz, Tiffany Rice, Sean Hasan, Ryden Armstrong, and Naweed I. Syed
Subjects: medicine.medical_specialty, Physiology, neurons, Review, Anesthetic Agent, Neurotransmission, Biology, anesthesia, lcsh:Physiology, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Postsynaptic potential, Physiology (medical), Anesthesiology, medicine, synaptic transmission, Lymnaea, molluscs, lcsh:QP1-981, Neurotoxicity, Surgical procedures, medicine.disease, 3. Good health, Action (philosophy), Anesthetic, cytotoxicity, synapses, Neuroscience, 030217 neurology & neurosurgery, medicine.drug
Abstract: Anesthesia is a prerequisite for most surgical procedures in both animals and humans. Significant strides have been made in search of effective and safer compounds that elicit rapid induction and recovery from anesthesia. However, recent studies have highlighted possible negative effects of several anesthetic agents on the developing brain. The precise nature of this cytotoxicity remains to be determined mainly due to the complexity and the intricacies of the mammalian brain. Various invertebrates have contributed significantly toward our understanding of how both local and general anesthetics affect intrinsic membrane and synaptic properties. Moreover, the ability to reconstruct in vitro synapses between individually identifiable pre- and postsynaptic neurons is a unique characteristic of molluscan neurons allowing us to ask fundamental questions vis-a-vis the long-term effects of anesthetics on neuronal viability and synaptic connectivity. Here, we highlight some of the salient aspects of various molluscan organisms and their contributions toward our understanding of the fundamental mechanisms underlying the actions of anesthetic agents as well as their potential detrimental effects on neuronal growth and synaptic connectivity. We also present some novel preliminary data regarding a newer anesthetic agent, dexmedetomidine, and its effects on synaptic transmission between Lymnaea neurons. The findings presented here underscore the importance of invertebrates for research in the field of anesthesiology while highlighting their relevance to both vertebrates and humans.
Published: 2017

32. 4879Heart failure with mid range ejection fraction, characteristics and prognosis in patients with and without type 2 diabetes

Author: I. Johansson, U. Dahlstrom, M. Edner, P. Nasman, L. Ryden, and A. Norhammar
Subjects: medicine.medical_specialty, animal structures, Ejection fraction, business.industry, Internal medicine, Heart failure, Cardiology, medicine, In patient, Type 2 diabetes, Cardiology and Cardiovascular Medicine, medicine.disease, business
Abstract: Heart failure with mid range ejection fraction, characteristics and prognosis in patients with and without type 2 diabetes.
Published: 2017
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33. ATS Core Curriculum 2014: Part III. Adult Sleep Medicine

Author: Ronald Szymusiak, Barry G. Fields, Kingman P. Strohl, Alon Y. Avidan, Armand M. Ryden, Patrick J. Strollo, Ilene M. Rosen, Grace W. Pien, and Robert C. Stansbury
Subjects: Adult, Sleep Wake Disorders, Pulmonary and Respiratory Medicine, Automobile Driving, medicine.medical_specialty, Posture, Rapid eye movement sleep, Sleep, REM, Core curriculum, Non-rapid eye movement sleep, Sleep medicine, Part iii, Risk Factors, Orthodontic Appliances, Removable, Weight Loss, Homeostasis, Humans, Medicine, Restless legs syndrome, Wakefulness, Fatigue, Neurons, Sleep disorder, Continuous Positive Airway Pressure, business.industry, Oxygen Inhalation Therapy, medicine.disease, Preoptic Area, Obstructive sleep apnea, Practice Guidelines as Topic, Physical therapy, Bruxism, Education, Medical, Continuing, Suprachiasmatic Nucleus, Sleep, business
Published: 2014
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34. Prognosis, disease progression, and treatment of atrial fibrillation patients during 1 year: follow-up of the Euro Heart Survey on Atrial Fibrillation

Author: Nieuwlaat R., Prins M. H., Le Heuzey J. -Y., Vardas P. E., Aliot E., Santini M., Cobbe S. M., Widdershoven J. W. M. G., Baur L. H., Levy S., Crijns H. J. G. M., Olsson B., Breithardt G., Manini M., Bramley C., Laforest V., Taylor C., Del Gaiso S., Huber K., De Backer G., Sirakova V., Cerbak R., Thayssen P., Lehto S., Blanc J. -J., Delahaye F., Kobulia B., Zeymer U., Cokkinos D., Karlocai K., Graham I., Shelley E., Behar S., Maggioni A., Goncalves L., Grabauskiene V., Asmussen I., Deckers J., Stepinska J., Mareev V., Vasiljevic Z., Riecansky I., Kenda M. F., Alonso A., Lopez-Sendon J. L., Rosengren A., Buser P., Okay T., Sychov O., Fox K., Schofield P., Simoons M., Wood D., Battler A., Boersma E., Komajda M., Andresen D., McGregor K., Mulder B., Priori S., Ryden L., Vahanian A., Wijns W., Sanofi-Aventis, Grigoryan S. V., Apetyan I., Aroyan S., Camm A. J., Azarapetyan L., Anvari A., Gottsauner-Wolf M., Pfaffenberger S., Aydinkoc K., Kalla K., Penka M., Drexel H., Langer P., Pierard L. A., Davies W., Legrand V., Blommaert D., Schroeder E., Mancini I., Geelen P., Brugada P., De Zutter M., Vrints C., Vercammen M., Morissens M., Capucci A., Borisov B., Petrov V. A., Marinova M., Assen A., Goudev R., Peychev Y., Stoyanovsky V., Stoynev E., Kranjcevic S., Moutiris J., Ioannides M., Evequoz D., Spacilova J., Novak M., Eisenberger M., Mullerova J., Kautzner J., Riedlbauchova L., Petru` J., Taborsky M., Cappelen H., Sharaf Y. A., Ibrahim B. S. S., Tammam K., Saad A., Elghawaby H., Sherif H. Z., Farouk H., Mielke A., Engelen M., Kirchhof P., Zimmermann P., Aviles F. F., Rubio J., Malpartida F., Corona M., Sanchez L. T., Miguel J., Herrera L., Quesada A., Garcia A. J. M., Gonzalez C. S., Juango M. S. A., Berjon-Reyero J., Alegret J. M., Fernandez J. M. C., Carrascosa C., Romero R. A. F., Lara M. G., Sendon J. L. L., de Diego J. J. G., Martin L. S., Irurita M., Guttierez N. H., Rubio J. R. S., Antorrena I., Paves A. B., Salvador A., Orriach M. D., Garcia A. A., Epelde F., Martinez V. B., Sanchez A. B., Galvez C. P., Rivero R. F., Madrid A. H., Baron-Esquivias G., Peinado R., Guindal J. A. G., Vera T. R., Fernandez E. L., Gayan R., Garcia J., Bodegas A., Lopez J. T., Florez J. M., Cabezas C. L., de Castroviejo E. V. R., Bellido J. M., Ruiz M. E., Savolainen K., Nieminen M., Toivonen L., Syvanne M., Pietila M., Galley D., Beltra C., Gay A., Daubert J. C., Lecocq G., Poulain C., Cleland J. G. F. C., Shelton R., Choudhury A., Abuladze G., Jashi I., Tsiavou A., Giamouzis G., Dagres N., Kostopoulou A., Tsoutsanis D., Stefanadis C., Latsios G., Vogiatzis I., Gotsis A., Bozia P., Karakiriou M., Koulouris S., Parissis J., Kostakis G., Kouris N., Kontogianni D., Athanasios K., Douras A., Tsanakis T., Marketou M., Patsourakos N., Czopf L., Halmosi R., Preda I., Csoti E., Badics A., Strasberg B., Freedberg N. A., Katz A., Zalzstein E., Grosbard A., Goldhammer E., Nahir M., Epstein M., Vider I., Luria D., Mandelzweig L., Aloisi B., Cavallaro A., Antonielli E., Doronzo B., Pancaldo D., Mazzola C., Buontempi L., Calvi V., Giuffrida G., Figlia A., Ippolito F., Gelmini G. -P., Gaibazzi N., Ziacchi V., De Tommasi F., Lombardi F., Fiorentini C., Terranova P., Maiolino P., Albunni M., Pinna-Pintor P., Fumagalli S., Masotti G., Boncinelli L., Rossi D., Santoro G. M., Fioranelli M., Naccarella F., Maranga S. S., Lepera G., Bresciani B., Seragnoli E., Forti M. C., Cortina V., Baciarello G., Cicconetti P., Lax A., Vitali F., Igidbashian D., Scarpino L., Terrazzino S., Tavazzi L., Cantu F., Pentimalli F., Novo S., Coppola G., Zingarini G., Ambrozio G., Moruzzi P., Callegari S., Saccomanno G., Russo P., Carbonieri E., Paino A., Zanetta M., Barducci E., Cemin R., Rauhe W., Pitscheider W., Meloni M., Marchi S. M., Di Gennaro M., Calcagno S., Squaratti P., Quartili F., Bertocchi P., De Martini M., Mantovani G., Komorovsky R., Desideri A., Celegon L., Tarantini L., Catania G., Lucci D., Bianchini F., Puodziukynas A., Kavoliuniene A., Barauskiene V., Aidietis A., Barysiene J., Vysniauskas V., Zukauskiene I., Kazakeviciene N., Georgievska-Ismail L., Poposka L., Vataman E., Grosu A. A., op Reimer W. S., de Swart E., Lenzen M., Jansen C., Brons R., Tebbe H., van Hoogenhuyze D. C. A., Veerhoek M. J., Kamps M., Haan D., van Rijn N., Bootsma A., van den A., Fransen H., Eurlings L., Meeder J., De Boer M. J., Winter J., Broers H., Werter C., Bijl M., Versluis S., Milkowska M., Wozakowska-Kaplon B., Janion M., Lepska L., Swiatecka G., Kokowicz P., Cybulski J., Gorecki A., Szulc M., Rekosz J., Manczak R., Wnuk-Wojnar A. -M., Trusz-Gluza M., Rybicka-Musialik A., Myszor J., Szpajer M., Cymerman K., Sadowski J., Sniezek-Maciejewska M., Ciesla-Dul M., Gorkiewicz-Kot I., Grodzicki T., Rewiuk K., Kubik L., Lewit J., de Sousa J. M. F. R., Ferreira R., Freitas A., Morais J. C. A., Pires R., Gomes M. J. V., Gago P., Candeias R. A. C., Nunes L., Sa J. V. M., Ventura M., de Oliveira M., Alves L. B., Bostaca I., Olariu C. T., Dan G. A., Dan A., Podoleanu C., Frigy A., Georgescu G. I. M., Arsenescu C., Statescu C., Sascau R., Dimitrascu D. L., Rancea R., Shubik Y. V., Duplyakov D., Shalak M., Danielyan M., Galyavich A., Zakirova V., Hatala R., Kaliska G., Kmec J., Zupan I., Tasie` J., Vokac D., Edvardsson N., Poci D., Gamra H., Denguir H., Sepetoglu A., Arat-Ozkan A., Orynchak M., Paliy E., Vakalyuk I., Malidze D., Prog R., Yabluchansky M. I., Makienko N. V., Potpara T., Knezevic S., Randjelovic M., Nieuwlaat R., Prins M.H., Le Heuzey J.-Y., Vardas P.E., Aliot E., Santini M., Cobbe S.M., Widdershoven J.W.M.G., Baur L.H., Levy S., Crijns H.J.G.M., Olsson B., Breithardt G., Manini M., Bramley C., Laforest V., Taylor C., Del Gaiso S., Huber K., De Backer G., Sirakova V., Cerbak R., Thayssen P., Lehto S., Blanc J.-J., Delahaye F., Kobulia B., Zeymer U., Cokkinos D., Karlocai K., Graham I., Shelley E., Behar S., Maggioni A., Goncalves L., Grabauskiene V., Asmussen I., Deckers J., Stepinska J., Mareev V., Vasiljevic Z., Riecansky I., Kenda M.F., Alonso A., Lopez-Sendon J.L., Rosengren A., Buser P., Okay T., Sychov O., Fox K., Schofield P., Simoons M., Wood D., Battler A., Boersma E., Komajda M., Andresen D., McGregor K., Mulder B., Priori S., Ryden L., Vahanian A., Wijns W., Sanofi-Aventi, Grigoryan S.V., Apetyan I., Aroyan S., Camm A.J., Azarapetyan L., Anvari A., Gottsauner-Wolf M., Pfaffenberger S., Aydinkoc K., Kalla K., Penka M., Drexel H., Langer P., Pierard L.A., Davies W., Legrand V., Blommaert D., Schroeder E., Mancini I., Geelen P., Brugada P., De Zutter M., Vrints C., Vercammen M., Morissens M., Capucci A., Borisov B., Petrov V.A., Marinova M., Assen A., Goudev R., Peychev Y., Stoyanovsky V., Stoynev E., Kranjcevic S., Moutiris J., Ioannides M., Evequoz D., Spacilova J., Novak M., Eisenberger M., Mullerova J., Kautzner J., Riedlbauchova L., Petru` J., Taborsky M., Cappelen H., Sharaf Y.A., Ibrahim B.S.S., Tammam K., Saad A., Elghawaby H., Sherif H.Z., Farouk H., Mielke A., Engelen M., Kirchhof P., Zimmermann P., Aviles F.F., Rubio J., Malpartida F., Corona M., Sanchez L.T., Miguel J., Herrera L., Quesada A., Garcia A.J.M., Gonzalez C.S., Juango M.S.A., Berjon-Reyero J., Alegret J.M., Fernandez J.M.C., Carrascosa C., Romero R.A.F., Lara M.G., Sendon J.L.L., de Diego J.J.G., Martin L.S., Irurita M., Guttierez N.H., Rubio J.R.S., Antorrena I., Paves A.B., Salvador A., Orriach M.D., Garcia A.A., Epelde F., Martinez V.B., Sanchez A.B., Galvez C.P., Rivero R.F., Madrid A.H., Baron-Esquivias G., Peinado R., Guindal J.A.G., Vera T.R., Fernandez E.L., Gayan R., Garcia J., Bodegas A., Lopez J.T., Florez J.M., Cabezas C.L., de Castroviejo E.V.R., Bellido J.M., Ruiz M.E., Savolainen K., Nieminen M., Toivonen L., Syvanne M., Pietila M., Galley D., Beltra C., Gay A., Daubert J.C., Lecocq G., Poulain C., Cleland J.G.F.C., Shelton R., Choudhury A., Abuladze G., Jashi I., Tsiavou A., Giamouzis G., Dagres N., Kostopoulou A., Tsoutsanis D., Stefanadis C., Latsios G., Vogiatzis I., Gotsis A., Bozia P., Karakiriou M., Koulouris S., Parissis J., Kostakis G., Kouris N., Kontogianni D., Athanasios K., Douras A., Tsanakis T., Marketou M., Patsourakos N., Czopf L., Halmosi R., Preda I., Csoti E., Badics A., Strasberg B., Freedberg N.A., Katz A., Zalzstein E., Grosbard A., Goldhammer E., Nahir M., Epstein M., Vider I., Luria D., Mandelzweig L., Aloisi B., Cavallaro A., Antonielli E., Doronzo B., Pancaldo D., Mazzola C., Buontempi L., Calvi V., Giuffrida G., Figlia A., Ippolito F., Gelmini G.-P., Gaibazzi N., Ziacchi V., De Tommasi F., Lombardi F., Fiorentini C., Terranova P., Maiolino P., Albunni M., Pinna-Pintor P., Fumagalli S., Masotti G., Boncinelli L., Rossi D., Santoro G.M., Fioranelli M., Naccarella F., Maranga S.S., Lepera G., Bresciani B., Seragnoli E., Forti M.C., Cortina V., Baciarello G., Cicconetti P., Lax A., Vitali F., Igidbashian D., Scarpino L., Terrazzino S., Tavazzi L., Cantu F., Pentimalli F., Novo S., Coppola G., Zingarini G., Ambrozio G., Moruzzi P., Callegari S., Saccomanno G., Russo P., Carbonieri E., Paino A., Zanetta M., Barducci E., Cemin R., Rauhe W., Pitscheider W., Meloni M., Marchi S.M., Di Gennaro M., Calcagno S., Squaratti P., Quartili F., Bertocchi P., De Martini M., Mantovani G., Komorovsky R., Desideri A., Celegon L., Tarantini L., Catania G., Lucci D., Bianchini F., Puodziukynas A., Kavoliuniene A., Barauskiene V., Aidietis A., Barysiene J., Vysniauskas V., Zukauskiene I., Kazakeviciene N., Georgievska-Ismail L., Poposka L., Vataman E., Grosu A.A., op Reimer W.S., de Swart E., Lenzen M., Jansen C., Brons R., Tebbe H., van Hoogenhuyze D.C.A., Veerhoek M.J., Kamps M., Haan D., van Rijn N., Bootsma A., van den A., Fransen H., Eurlings L., Meeder J., De Boer M.J., Winter J., Broers H., Werter C., Bijl M., Versluis S., Milkowska M., Wozakowska-Kaplon B., Janion M., Lepska L., Swiatecka G., Kokowicz P., Cybulski J., Gorecki A., Szulc M., Rekosz J., Manczak R., Wnuk-Wojnar A.-M., Trusz-Gluza M., Rybicka-Musialik A., Myszor J., Szpajer M., Cymerman K., Sadowski J., Sniezek-Maciejewska M., Ciesla-Dul M., Gorkiewicz-Kot I., Grodzicki T., Rewiuk K., Kubik L., Lewit J., de Sousa J.M.F.R., Ferreira R., Freitas A., Morais J.C.A., Pires R., Gomes M.J.V., Gago P., Candeias R.A.C., Nunes L., Sa J.V.M., Ventura M., de Oliveira M., Alves L.B., Bostaca I., Olariu C.T., Dan G.A., Dan A., Podoleanu C., Frigy A., Georgescu G.I.M., Arsenescu C., Statescu C., Sascau R., Dimitrascu D.L., Rancea R., Shubik Y.V., Duplyakov D., Shalak M., Danielyan M., Galyavich A., Zakirova V., Hatala R., Kaliska G., Kmec J., Zupan I., Tasie` J., Vokac D., Edvardsson N., Poci D., Gamra H., Denguir H., Sepetoglu A., Arat-Ozkan A., Orynchak M., Paliy E., Vakalyuk I., Malidze D., Prog R., Yabluchansky M.I., Makienko N.V., Potpara T., Knezevic S., and Randjelovic M.
Subjects: Male, medicine.medical_specialty, Rate control, Heart Diseases, Heart disease, Prognosi, Hemorrhage, Risk Assessment, Anticoagulation, Electrocardiography, Internal medicine, Atrial Fibrillation, Humans, Medicine, Sinus rhythm, Prospective Studies, Mortality, Prospective cohort study, Stroke, Survival rate, Aged, Progression, medicine.diagnostic_test, business.industry, Anticoagulant, Anticoagulants, Atrial fibrillation, Prognosis, medicine.disease, Management, Survival Rate, Prospective Studie, Heart Disease, Treatment Outcome, Heart failure, Disease Progression, Cardiology, Rhythm control, Female, Cardiology and Cardiovascular Medicine, business, Human
Abstract: Aims: To gain insight in the prognosis and treatment of atrial fibrillation (AF) patients during 1-year follow-up in the Euro Heart Survey (EHS) on AF. Methods and results: The EHS enrolled 5333 AF patients in 2003-2004. One-year follow-up data were available for 80%. Of first detected AF patients, 46% did not have a recurrence during 1 year, paroxysmal AF largely remained paroxysmal AF (80%), and 30% of persistent AF progressed to permanent AF. Many treatment changes occurred since baseline. Oral anticoagulation was started in 19% and discontinued in 16% of all patients. Of patients initially on rhythm control 27% did not receive rhythm control during follow-up, whereas 15% of patients initially on rate control received rhythm control. Mortality was highest in permanent AF (8.2%), but also substantial in first detected AF (5.7%). In multivariable analysis, sinus rhythm at baseline was associated with lower mortality, but no significant effect was observed regarding the application of either rhythm or rate control. Conclusion: The EHS on AF provides unique prospective observational data on AF progression, long-term treatment, prognosis, and determinants of adverse outcome of the total clinical spectrum of AF in a European cardiology-based patient cohort. © The Author 2008.
Published: 2008
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35. 0465 Performance of Revised Machine Learning Models for Prediction of Non-Diagnostic Home Sleep Apnea Tests

Author: Constance H. Fung, Armand Ryden, Dennis Hwang, Robert Stretch, Abigail Maller, and Michelle Zeidler
Subjects: Computer science, business.industry, Physiology (medical), medicine, Sleep apnea, Neurology (clinical), Artificial intelligence, medicine.disease, business, Machine learning, computer.software_genre, computer
Published: 2019
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36. 0525 Association of Black Race with Positive Airway Pressure Therapy Adherence Among Veterans with Obstructive Sleep Apnea

Author: Armand Ryden, Michelle Zeidler, Nancy Hsu, and Constance H. Fung
Subjects: Obstructive sleep apnea, medicine.medical_specialty, business.industry, Physiology (medical), Internal medicine, Positive airway pressure, Medicine, Neurology (clinical), Therapy adherence, business, medicine.disease, Association (psychology), Black race
Published: 2019
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37. Antithrombotic treatment in real-life atrial fibrillation patients: a report from the Euro Heart Survey on Atrial Fibrillation

Author: Nieuwlaat R., Capucci A., Lip G. Y. H., Olsson S. B., Prins M. H., Nieman F. H., Lopez-Sendon J., Vardas P. E., Aliot E., Santini M., Crijns H. J. G. M., Andresen D., Camm A. J., Davies W., Levy S., Breithardt G., Cobbe S., Le Heuzey J. -Y., Manini M., Bramley C., Laforest V., Taylor C., Del Gaiso S., Huber K., De Backer G., Sirakova V., Cerbak R., Thayssen P., Lehto S., Blanc J. -J., Delahaye F., Kobulia B., Zeymer U., Cokkinos D., Karlocai K., Graham I., Shelley E., Behar S., Maggioni A., Goncalves L., Grabauskiene V., Asmussen I., Deckers J., Stepinska J., Mareev V., Vasiljevic Z., Riecansky I., Kenda M. F., Alonso A., Rosengren A., Buser P., Okay T., Sychov O., Fox K., Schofield P., Simoons M., Wood D., Battler A., Boersma E., Komajda M., McGregor K., Mulder B., Priori S., Ryden L., Vahanian A., Wijns W., Sanofi-Aventis, Grigoryan S. V., Apetyan I., Aroyan S., Azarapetyan L., Anvari A., Gottsauner-Wolf M., Pfaffenberger S., Aydinkoc K., Kalla K., Penka M., Drexel H., Langer P., Pierard L. A., Legrand V., Blommaert D., Schroeder E., Mancini I., Geelen P., Brugada P., De Zutter M., Vrints C., Vercammen M., Morissens M., Borisov B., Petrov V. A., Marinova M., Assen A., Goudev R., Peychev Y., Stoyanovsky V., Stoynev E., Kranjcevic S., Moutiris J., Ioannides M., Evequoz D., Spacilova J., Novak M., Eisenberger M., Mullerova J., Kautzner J., Riedlbauchova L., Petru` J., Taborsky M., Cappelen H., Sharaf Y. A., Ibrahim B. S. S., Tammam K., Saad A., Elghawaby H., Sherif H. Z., Farouk H., Mielke A., Engelen M., Kirchhof P., Zimmermann P., Aviles F. F., Rubio J., Malpartida F., Corona M., Sanchez L. T., Miguel J., Herrera L., Quesada A., Garcia A. J. M., Gonzalez C. S., Juango M. S. A., Berjon-Reyero J., Alegret J. M., Fernandez J. M. C., Carrascosa C., Romero R. A. F., Lara M. G., Sendon J. L. L., de Diego J. J. G., Martin L. S., Irurita M., Guttierez N. H., Rubio J. R. S., Antorrena I., Paves A. B., Salvador A., Orriach M. D., Garcia A. A., Epelde F., Martinez V. B., Sanchez A. B., Galvez C. P., Rivero R. F., Madrid A. H., Baron-Esquivias G., Peinado R., Guindal J. A. G., Vera T. R., Fernandez E. L., Gayan R., Garcia J., Bodegas A., Lopez J. T., Florez J. M., Cabezas C. L., de Castroviejo E. V. R., Bellido J. M., Ruiz M. E., Savolainen K., Nieminen M., Toivonen L., Syvanne M., Pietila M., Galley D., Beltra C., Gay A., Daubert J. C., Lecocq G., Poulain C., Cleland J. G. F. C., Shelton R., Choudhury A., Abuladze G., Jashi I., Tsiavou A., Giamouzis G., Dagres N., Kostopoulou A., Tsoutsanis D., Stefanadis C., Latsios G., Vogiatzis I., Gotsis A., Bozia P., Karakiriou M., Koulouris S., Parissis J., Kostakis G., Kouris N., Kontogianni D., Athanasios K., Douras A., Tsanakis T., Marketou M., Patsourakos N., Czopf L., Halmosi R., Preda I., Csoti E., Badics A., Strasberg B., Freedberg N. A., Katz A., Zalzstein E., Grosbard A., Goldhammer E., Nahir M., Epstein M., Vider I., Luria D., Mandelzweig L., Aloisi B., Cavallaro A., Antonielli E., Doronzo B., Pancaldo D., Mazzola C., Buontempi L., Calvi V., Giuffrida G., Figlia A., Ippolito F., Gelmini G. -P., Gaibazzi N., Ziacchi V., De Tommasi F., Lombardi F., Fiorentini C., Terranova P., Maiolino P., Albunni M., Pinna-Pintor P., Fumagalli S., Masotti G., Boncinelli L., Rossi D., Santoro G. M., Fioranelli M., Naccarella F., Maranga S. S., Lepera G., Bresciani B., Seragnoli E., Forti M. C., Cortina V., Baciarello G., Cicconetti P., Lax A., Vitali F., Igidbashian D., Scarpino L., Terrazzino S., Tavazzi L., Cantu F., Pentimalli F., Novo S., Coppola G., Zingarini G., Ambrozio G., Moruzzi P., Callegari S., Saccomanno G., Russo P., Carbonieri E., Paino A., Zanetta M., Barducci E., Cemin R., Rauhe W., Pitscheider W., Meloni M., Marchi S. M., Di Gennaro M., Calcagno S., Squaratti P., Quartili F., Bertocchi P., De Martini M., Mantovani G., Komorovsky R., Desideri A., Celegon L., Tarantini L., Catania G., Lucci D., Bianchini F., Puodziukynas A., Kavoliuniene A., Barauskiene V., Aidietis A., Barysiene J., Vysniauskas V., Zukauskiene I., Kazakeviciene N., Georgievska-Ismail L., Poposka L., Vataman E., Grosu A. A., op Reimer W. S., de Swart E., Lenzen M., Jansen C., Brons R., Tebbe H., van Hoogenhuyze D. C. A., Veerhoek M. J., Kamps M., Haan D., van Rijn N., Bootsma A., Baur L., van den A., Fransen H., Eurlings L., Meeder J., De Boer M. J., Winter J., Broers H., Werter C., Bijl M., Versluis S., Milkowska M., Wozakowska-Kaplon B., Janion M., Lepska L., Swiatecka G., Kokowicz P., Cybulski J., Gorecki A., Szulc M., Rekosz J., Manczak R., Wnuk-Wojnar A. -M., Trusz-Gluza M., Rybicka-Musialik A., Myszor J., Szpajer M., Cymerman K., Sadowski J., Sniezek-Maciejewska M., Ciesla-Dul M., Gorkiewicz-Kot I., Grodzicki T., Rewiuk K., Kubik L., Lewit J., de Sousa J. M. F. R., Ferreira R., Freitas A., Morais J. C. A., Pires R., Gomes M. J. V., Gago P., Candeias R. A. C., Nunes L., Sa J. V. M., Ventura M., de Oliveira M., Alves L. B., Bostaca I., Olariu C. T., Dan G. A., Dan A., Podoleanu C., Frigy A., Georgescu G. I. M., Arsenescu C., Statescu C., Sascau R., Dimitrascu D. L., Rancea R., Shubik Y. V., Duplyakov D., Shalak M., Danielyan M., Galyavich A., Zakirova V., Hatala R., Kaliska G., Kmec J., Zupan I., Tasie` J., Vokac D., Edvardsson N., Poci D., Gamra H., Denguir H., Sepetoglu A., Arat-Ozkan A., Orynchak M., Paliy E., Vakalyuk I., Malidze D., Prog R., Yabluchansky M. I., Makienko N. V., Potpara T., Knezevic S., Randjelovic M., Nieuwlaat R., Capucci A., Lip G.Y.H., Olsson S.B., Prins M.H., Nieman F.H., Lopez-Sendon J., Vardas P.E., Aliot E., Santini M., Crijns H.J.G.M., Andresen D., Camm A.J., Davies W., Levy S., Breithardt G., Cobbe S., Le Heuzey J.-Y., Manini M., Bramley C., Laforest V., Taylor C., Del Gaiso S., Huber K., De Backer G., Sirakova V., Cerbak R., Thayssen P., Lehto S., Blanc J.-J., Delahaye F., Kobulia B., Zeymer U., Cokkinos D., Karlocai K., Graham I., Shelley E., Behar S., Maggioni A., Goncalves L., Grabauskiene V., Asmussen I., Deckers J., Stepinska J., Mareev V., Vasiljevic Z., Riecansky I., Kenda M.F., Alonso A., Rosengren A., Buser P., Okay T., Sychov O., Fox K., Schofield P., Simoons M., Wood D., Battler A., Boersma E., Komajda M., McGregor K., Mulder B., Priori S., Ryden L., Vahanian A., Wijns W., Sanofi-Aventi, Grigoryan S.V., Apetyan I., Aroyan S., Azarapetyan L., Anvari A., Gottsauner-Wolf M., Pfaffenberger S., Aydinkoc K., Kalla K., Penka M., Drexel H., Langer P., Pierard L.A., Legrand V., Blommaert D., Schroeder E., Mancini I., Geelen P., Brugada P., De Zutter M., Vrints C., Vercammen M., Morissens M., Borisov B., Petrov V.A., Marinova M., Assen A., Goudev R., Peychev Y., Stoyanovsky V., Stoynev E., Kranjcevic S., Moutiris J., Ioannides M., Evequoz D., Spacilova J., Novak M., Eisenberger M., Mullerova J., Kautzner J., Riedlbauchova L., Petru` J., Taborsky M., Cappelen H., Sharaf Y.A., Ibrahim B.S.S., Tammam K., Saad A., Elghawaby H., Sherif H.Z., Farouk H., Mielke A., Engelen M., Kirchhof P., Zimmermann P., Aviles F.F., Rubio J., Malpartida F., Corona M., Sanchez L.T., Miguel J., Herrera L., Quesada A., Garcia A.J.M., Gonzalez C.S., Juango M.S.A., Berjon-Reyero J., Alegret J.M., Fernandez J.M.C., Carrascosa C., Romero R.A.F., Lara M.G., Sendon J.L.L., de Diego J.J.G., Martin L.S., Irurita M., Guttierez N.H., Rubio J.R.S., Antorrena I., Paves A.B., Salvador A., Orriach M.D., Garcia A.A., Epelde F., Martinez V.B., Sanchez A.B., Galvez C.P., Rivero R.F., Madrid A.H., Baron-Esquivias G., Peinado R., Guindal J.A.G., Vera T.R., Fernandez E.L., Gayan R., Garcia J., Bodegas A., Lopez J.T., Florez J.M., Cabezas C.L., de Castroviejo E.V.R., Bellido J.M., Ruiz M.E., Savolainen K., Nieminen M., Toivonen L., Syvanne M., Pietila M., Galley D., Beltra C., Gay A., Daubert J.C., Lecocq G., Poulain C., Cleland J.G.F.C., Shelton R., Choudhury A., Abuladze G., Jashi I., Tsiavou A., Giamouzis G., Dagres N., Kostopoulou A., Tsoutsanis D., Stefanadis C., Latsios G., Vogiatzis I., Gotsis A., Bozia P., Karakiriou M., Koulouris S., Parissis J., Kostakis G., Kouris N., Kontogianni D., Athanasios K., Douras A., Tsanakis T., Marketou M., Patsourakos N., Czopf L., Halmosi R., Preda I., Csoti E., Badics A., Strasberg B., Freedberg N.A., Katz A., Zalzstein E., Grosbard A., Goldhammer E., Nahir M., Epstein M., Vider I., Luria D., Mandelzweig L., Aloisi B., Cavallaro A., Antonielli E., Doronzo B., Pancaldo D., Mazzola C., Buontempi L., Calvi V., Giuffrida G., Figlia A., Ippolito F., Gelmini G.-P., Gaibazzi N., Ziacchi V., De Tommasi F., Lombardi F., Fiorentini C., Terranova P., Maiolino P., Albunni M., Pinna-Pintor P., Fumagalli S., Masotti G., Boncinelli L., Rossi D., Santoro G.M., Fioranelli M., Naccarella F., Maranga S.S., Lepera G., Bresciani B., Seragnoli E., Forti M.C., Cortina V., Baciarello G., Cicconetti P., Lax A., Vitali F., Igidbashian D., Scarpino L., Terrazzino S., Tavazzi L., Cantu F., Pentimalli F., Novo S., Coppola G., Zingarini G., Ambrozio G., Moruzzi P., Callegari S., Saccomanno G., Russo P., Carbonieri E., Paino A., Zanetta M., Barducci E., Cemin R., Rauhe W., Pitscheider W., Meloni M., Marchi S.M., Di Gennaro M., Calcagno S., Squaratti P., Quartili F., Bertocchi P., De Martini M., Mantovani G., Komorovsky R., Desideri A., Celegon L., Tarantini L., Catania G., Lucci D., Bianchini F., Puodziukynas A., Kavoliuniene A., Barauskiene V., Aidietis A., Barysiene J., Vysniauskas V., Zukauskiene I., Kazakeviciene N., Georgievska-Ismail L., Poposka L., Vataman E., Grosu A.A., op Reimer W.S., de Swart E., Lenzen M., Jansen C., Brons R., Tebbe H., van Hoogenhuyze D.C.A., Veerhoek M.J., Kamps M., Haan D., van Rijn N., Bootsma A., Baur L., van den A., Fransen H., Eurlings L., Meeder J., De Boer M.J., Winter J., Broers H., Werter C., Bijl M., Versluis S., Milkowska M., Wozakowska-Kaplon B., Janion M., Lepska L., Swiatecka G., Kokowicz P., Cybulski J., Gorecki A., Szulc M., Rekosz J., Manczak R., Wnuk-Wojnar A.-M., Trusz-Gluza M., Rybicka-Musialik A., Myszor J., Szpajer M., Cymerman K., Sadowski J., Sniezek-Maciejewska M., Ciesla-Dul M., Gorkiewicz-Kot I., Grodzicki T., Rewiuk K., Kubik L., Lewit J., de Sousa J.M.F.R., Ferreira R., Freitas A., Morais J.C.A., Pires R., Gomes M.J.V., Gago P., Candeias R.A.C., Nunes L., Sa J.V.M., Ventura M., de Oliveira M., Alves L.B., Bostaca I., Olariu C.T., Dan G.A., Dan A., Podoleanu C., Frigy A., Georgescu G.I.M., Arsenescu C., Statescu C., Sascau R., Dimitrascu D.L., Rancea R., Shubik Y.V., Duplyakov D., Shalak M., Danielyan M., Galyavich A., Zakirova V., Hatala R., Kaliska G., Kmec J., Zupan I., Tasie` J., Vokac D., Edvardsson N., Poci D., Gamra H., Denguir H., Sepetoglu A., Arat-Ozkan A., Orynchak M., Paliy E., Vakalyuk I., Malidze D., Prog R., Yabluchansky M.I., Makienko N.V., Potpara T., Knezevic S., and Randjelovic M.
Subjects: Adult, Male, medicine.medical_specialty, Oral anticoagulation, Guideline, Risk Assessment, Electrocardiography, Fibrinolytic Agents, Risk Factors, Drug Combination, Antithrombotic, medicine, Humans, Outpatient clinic, Risk factor, Multivariate Analysi, Stroke, Risk stratification, Aged, Antithrombotic therapy, Fibrinolytic Agent, Framingham Risk Score, business.industry, Risk Factor, Atrial fibrillation, Middle Aged, medicine.disease, Drug Combinations, Multivariate Analysis, Practice Guidelines as Topic, Emergency medicine, Physical therapy, Female, Guideline Adherence, Cardiology and Cardiovascular Medicine, business, Cardioversions, Risk assessment, Human
Abstract: Aims To describe guideline adherence and application of different stroke risk stratification schemes regarding antithrombotic therapy in real-life atrial fibrillation (AF) patients and to assess which factors influence antithrombotic management decisions. Methods and results The Euro Heart Survey enrolled 5333 AF patients in 35 countries, in 2003 and 2004. Prescription of antithrombotic drugs, especially oral anticoagulation (OAC), was hardly tailored to the patient's stroke risk profile as indicated by the joint guidelines of the American College of Cardiology, American Heart Association, and the European Society of Cardiology, ACCP guidelines, or CHADS2 and Framingham risk scores. In multivariable analysis, only a limited number of the well-known stroke risk factors triggered OAC prescription. In contrast, less relevant factors, of which clinical type of AF and availability of an OAC monitoring outpatient clinic were the most marked, played a significant role in OAC prescription. Electrical cardioversions and catheter ablations clearly triggered OAC prescription, whereas pharmacological cardioversions even in the presence of stroke risk factors did not. Conclusion Antithrombotic therapy in AF is hardly tailored to the patient's stroke risk profile. Factors other than well-known stroke risk factors were significantly involved in antithrombotic management decisions. To facilitate this tailored treatment, guideline writers and physician educators should focus on providing one uniform and easy to use stroke risk stratification scheme.
Published: 2006
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38. 1129 Central Sleep Apnea after Hypoglossal Nerve Stimulation

Author: A Mendelsohn, Ravi S. Aysola, Melisa Chang, L C Chan, Armand Ryden, and Michelle Zeidler
Subjects: Central sleep apnea, business.industry, Stimulation, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Anesthesia, medicine, Neurology (clinical), 030223 otorhinolaryngology, business, Hypoglossal nerve, 030217 neurology & neurosurgery
Published: 2018
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39. Systemic effects of a short course of betamethasone compared with high-dose inhaled budesonide in early childhood asthma

Author: J Svedmyr, G Hedlin, and A C Ryden
Subjects: Budesonide, medicine.medical_specialty, Creatinine, Inhalation, medicine.drug_class, business.industry, General Medicine, medicine.disease, chemistry.chemical_compound, Endocrinology, N-terminal telopeptide, chemistry, Oral administration, Internal medicine, Pediatrics, Perinatology and Child Health, medicine, Corticosteroid, Betamethasone, business, medicine.drug, Asthma
Abstract: Forty children aged 1-3 y completed a placebo-controlled study on the effects of 10 d of inhaled budesonide for asthma caused by respiratory tract infection. The effects on symptoms were significantly better in the active than in the placebo group. In 20 of these children the systemic effects of high-dose inhaled budesonide for 10 d and the effect of a 3-d course of oral betamethasone on asthma exacerbation were evaluated. Systemic effects were evaluated by measuring morning cortisol in serum and urine, and the bone markers osteocalcin, ICTP (the C-terminal telopeptide region of type I collagen) and PIIINP (an N-terminal propeptide of type III procollagen) in serum before and at the end (d 7-10) of treatment (1600 microg budesonide d(-1) for 3 d and 800 microg for 7 d). In 9 children, measurements were taken on d 3 of a 3-d course of betamethasone (6, 4 and 2 mg) for asthma exacerbation and 14 d later. There were no signs of systemic effects after 7-10 d of budesonide. After 3 d of betamethasone, serum cortisol decreased from a median of 263 to 26 nmol l(-1), urine cortisol/creatinine from 19.9 to 7.2 nmol l(-1), osteocalcin from 31.4 to 5.5 microg l(-1), ICTP from 19.4 to 8.5 microg l(-1) and PIIINP from 12.3 to 5.9 microg l(-1). Two weeks later, the levels were back to normal. In conclusion, short courses of oral betamethasone have pronounced systemic effects, whereas 10 d of high doses of budesonide do not produce significant systemic effects.
Published: 2007
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40. Serpin treatment suppresses inflammatory vascular lesions in temporal artery implants (TAI) from patients with giant cell arteritis

Author: Erbin Dai, Colin Macaulay, Donghang Zheng, Anthony T. Yachnis, Eric S. Sobel, Mee Y Bartee, Alexandra Lucas, Cornelia M. Weyand, Sally Ryden, Liying Liu, Robert Thoburn, Hazem Samy, Sriram Ambadapadi, Hao Chen, and Jennifer Davids
Subjects: Male, Pathology, medicine.medical_specialty, Giant Cell Arteritis, lcsh:Medicine, Inflammation, Mice, SCID, Mice, Viral Proteins, Mice, Inbred NOD, medicine.artery, Biopsy, medicine, Macrophage, Animals, Humans, Arteritis, IL-2 receptor, lcsh:Science, Serpins, Severe combined immunodeficiency, Aorta, Multidisciplinary, medicine.diagnostic_test, business.industry, lcsh:R, medicine.disease, Takayasu Arteritis, 3. Good health, Temporal Arteries, Giant cell arteritis, Disease Models, Animal, Heterografts, Female, lcsh:Q, medicine.symptom, business, Research Article
Abstract: Giant cell arteritis (GCA) and Takayasu's disease are inflammatory vasculitic syndromes (IVS) causing sudden blindness and widespread arterial obstruction and aneurysm formation. Glucocorticoids and aspirin are mainstays of treatment, predominantly targeting T cells. Serp-1, a Myxomavirus-derived serpin, blocks macrophage and T cells in a wide range of animal models. Serp-1 also reduced markers of myocardial injury in a Phase IIa clinical trial for unstable coronary disease. In recent work, we detected improved survival and decreased arterial inflammation in a mouse Herpesvirus model of IVS. Here we examine Serp-1 treatment of human temporal artery (TA) biopsies from patients with suspected TA GCA arteritis after implant (TAI) into the aorta of immunodeficient SCID (severe combined immunodeficiency) mice. TAI positive for arteritis (GCApos) had significantly increased inflammation and plaque when compared to negative TAI (GCAneg). Serp-1 significantly reduced intimal inflammation and CD11b+ cell infiltrates in TAI, with reduced splenocyte Th1, Th17, and Treg. Splenocytes from mice with GCApos grafts had increased gene expression for interleukin-1 beta (IL-1β), IL-17, and CD25 and decreased Factor II. Serp-1 decreased IL-1β expression. In conclusion, GCApos TAI xenografts in mice provide a viable disease model and have increased intimal inflammation as expected and Serp-1 significantly reduces vascular inflammatory lesions with reduced IL-1β.
Published: 2015

41. Clinical efficacy of computerised cognitive-behavioural therapy for anxiety and depression in primary care: Randomised controlled trial

Author: Anthony Mann, J. Proudfoot, Clash Ryden, Andre Tylee, David A. Shapiro, Isaac M. Marks, David Goldberg, Brian Everitt, and Jeffrey A. Gray
Subjects: Adult, Male, medicine.medical_treatment, Anxiety, law.invention, 03 medical and health sciences, 0302 clinical medicine, Patient satisfaction, Randomized controlled trial, law, medicine, Humans, 030212 general & internal medicine, Depression (differential diagnoses), Aged, Cognitive Behavioral Therapy, Primary Health Care, Depression, Cognition, Middle Aged, medicine.disease, Anxiety Disorders, 030227 psychiatry, Clinical trial, Psychiatry and Mental health, Treatment Outcome, Multimedia, Patient Satisfaction, Therapy, Computer-Assisted, Cognitive therapy, Female, medicine.symptom, Psychology, Anxiety disorder, Clinical psychology
Abstract: BackgroundPreliminary results have demonstrated the clinical efficacy of computerised cognitive-behavioural therapy (CBT) in the treatment of anxiety and depression in primary care.AimsTo determine, in an expanded sample, the dependence of the efficacy of this therapy upon clinical and demographic variables.MethodA sample of 274 patients with anxiety and/or depression were randomly allocated to receive, with or without medication, computerised CBTor treatment as usual, with follow-up assessment at 6 months.ResultsThe computerised therapy improved depression, negative attributional style, work and social adjustment, without interaction with drug treatment, duration of preexisting illness or severity of existing illness. For anxiety and positive attributional style, treatment interacted with severity such that computerised therapy did better than usual treatment for more disturbed patients. Computerised therapy also led to greater satisfaction with treatment.ConclusionsComputer-delivered CBT is a widely applicable treatment for anxiety and/or depression in general practice.
Published: 2004
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42. Efficacy and Safety of Low-Dose Aspirin in Polycythemia Vera

Author: Landolfi, R, Marchioli, R, Kutti, J, Gisslinger, H, Tognoni, G, Patrono, C, Barbui, T, Finazzi, G, Pusterla, S, Falanga, A, Galli, M, Wadenvik, H, Gastl, G, Ludescher, C, Lutz, D, Girschikofsky, M, Michlmayr, G, Rechberger, E, Niessner, H, Ivansich, E, Rain, Jd, Chommienne Thomas, C, Hehlmann, R, Engelich, G, Kohne, E, Kramer, A, Christakis, Ji, Papaioannou, M, Gerotziafas, G, O'Donnell, R, Bennett, M, Lugassy, G, Ellis, M, Eldor, A, Naparstek, E, Marilus, R, Leoni, P, Rupoli, S, Scortechini, Ar, Agostini, V, Volpe, E, Calmieri, F, Volpe, A, Storti, G, Ciampa, A, Dammacco, F, Lauta, Vm, Ranieri, G, Rizzi, R, Orsola, S, Tura, S, Finelli, C, Marino, G, Rossi, G, Almici, C, Capucci, A, Zanetti, F, Giustolisi, R, Cacciola, Rr, Cacciola, E, Peta, A, Magro, D, Frigerio, G, Alberio, F, Beretta, A, Bonferroni, M, Raviolo, A, Ferrini, Prl, Grossi, A, Fabbri, A, Nardelli, S, Centra, A, Musolino, C, Bellomo, G, Trincali, O, Spatari, Giovanna, Foa, P, Gerli, G, Carraro, Mc, Zanella, A, Lurlo, A, Barraco, F, Torelli, G, Marietta, M, Pogliani, E, Miccolis, Ir, La Rocca, A, Puglisi, A, Sardeo, G, Rotoli, B, Martinelli, V, Ciancia, R, Cardarelli, A, Cimino, R, Fasanaro, A, Randi, Ml, Rizzoli, V, Caramatti, C, Gaeta, L, Lazzarino, M, Passamonti, F, Lazzola, M, Malabarba, L, Natale, D, Pulini, S, Davi, G, Gugliotta, L, Ilariucci, F, De Candia, E, Eugenio, S, Amadori, S, Buccisano, F, Mandelli, F, Montefusco, E, Petti, Mc, Spadea, A, Carotenuto, M, Morelli, A, Nobile, M, Longinotti, M, Pardini, Sm, Lauria, F, Buccalossi, A, Gentili, S, Mazza, P, Cervellera, M, Maggi, A, Di Francesco, A, Pasqualoni, E, Chisesi, T, Polacco, A, Capnist, G, Rodeghiero, F, Ruggeri, M, Arrizabalaga, B, Remacha, A, De Mendiguren, Bp, Hernandez Nieto, L, Hernandez Garcia, Mt, Gonzalez Brito, G, Machado, P, Garcia, G, Villegas, A, Pena, A, Fernandez, Ag, Carbonell, F, Del Arco, A, Back, H, Stenke, L, Hansen, S, Larsson, G, Stromblad, G, Lauri, B, Ryden, Bo, Linder, O, Lundholm, Bg, Lannemyr, O, Strandberg, M, Andreasson, B, Stockelberg, D, Pasquariello, F, Tichelli, A, Otremba, B, Hinrichs, Hf, Weber Stadelmann, W, Bareford, D, Oscier, Dg, Bowey, N, Taylor, Pc, de Gaetano, G, Najean, Y, Pearson, Tc, Di Blasio, A, Atashkar, S, Mari, E, Tamayo, D, Borelli, G, Ferri, B, Marfisi, Rm, Olivieri, M, Polidoro, A, Spoltore, R, Levantesi, G, Di Mascio, R, Miceli, G, Sperti, G, Correale, E, Vermjlen, J, and Collins, R.
Subjects: Aspirin, medicine.medical_specialty, business.industry, food and beverages, General Medicine, medicine.disease, Thrombosis, Pulmonary embolism, Venous thrombosis, Polycythemia vera, Relative risk, Internal medicine, Anesthesia, Cardiology, Medicine, Myocardial infarction, business, Contraindication, medicine.drug
Abstract: background The use of aspirin for the prevention of thrombotic complications in polycythemia vera is controversial. methods We enrolled 518 patients with polycythemia vera, no clear indication for aspirin treatment, and no contraindication to such treatment in a double-blind, placebo-controlled, randomized trial to assess the safety and efficacy of prophylaxis with low-dose aspirin (100 mg daily). The two primary end points were the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes. The mean duration of follow-up was about three years. results Treatment with aspirin, as compared with placebo, reduced the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes (relative risk, 0.41; 95 percent confidence interval, 0.15 to 1.15; P=0.09) and the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (relative risk, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.03). Overall mortality and cardiovascular mortality were not reduced significantly. The incidence of major bleeding episodes was not significantly increased in the aspirin group (relative risk, 1.62; 95 percent confidence interval, 0.27 to 9.71). conclusions Low-dose aspirin can safely prevent thrombotic complications in patients with polycythemia vera who have no contraindications to such treatment.
Published: 2004
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43. [PP.08.29] MARKED INSULIN RESISTANCE IN FAT CELLS OF SUBJECTS WITH INCREASED CARDIOVASCULAR RISK

Author: P. Arner and M. Ryden
Subjects: medicine.medical_specialty, Endocrinology, Insulin resistance, Physiology, business.industry, Internal medicine, Internal Medicine, Adipose tissue, Medicine, Cardiology and Cardiovascular Medicine, business, medicine.disease
Published: 2017
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44. 1254 Resolution of persistent nocturnal hypoxia in a patient with treated obstructive sleep apnea after closure of a patent foramen ovale

Author: J Tobis, D Hong, Michelle Zeidler, Armand Ryden, and J Currier
Subjects: medicine.medical_specialty, business.industry, Hypoxia (medical), Nocturnal, medicine.disease, Obstructive sleep apnea, Physiology (medical), Anesthesia, Internal medicine, medicine, Patent foramen ovale, Cardiology, Neurology (clinical), medicine.symptom, business
Published: 2017
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45. Auto-adjusting and advanced positive airway pressure therapeutic modalities

Author: Armand Ryden, Ravi S. Aysola, and Joanne M. Bando
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Sleep Apnea, Obstructive, Modalities, Modality (human–computer interaction), Continuous Positive Airway Pressure, business.industry, Central apnea, medicine.medical_treatment, Sleep apnea, Critical Care and Intensive Care Medicine, medicine.disease, respiratory tract diseases, Obstructive sleep apnea, Positive-Pressure Respiration, Sleep Apnea Syndromes, Positive airway pressure, Breathing, Medicine, Humans, Continuous positive airway pressure, Cheyne-Stokes Respiration, business, Intensive care medicine
Abstract: Continuous positive airway pressure (CPAP) therapy is the first-line treatment for obstructive sleep apnea (OSA). Although the gold standard for the treatment of OSA, CPAP may not be the optimal modality to treat more complex sleep disordered breathing such as Cheyne-Stokes respirations, opioid-induced central apnea, and complex sleep disordered breathing related to chronic hypoventilation syndromes (obesity-hypoventilation syndrome, restrictive thoracic disease due to neuromuscular or thoracic cage disease, chronic obstructive pulmonary disease). Newer generation auto-adjusting PAP devices are increasingly being used to treat OSA. Advanced positive airway pressure modalities have been developed in an effort to improve treatment of the more complex sleep disordered breathing syndromes including automated servo ventilation and volume-targeted pressure-limited ventilation. This article is intended to provide the clinician reader with a description of newer PAP modalities, a review of evidence-supported indications for use, as well as to provide a framework for managing patients with advanced positive airway pressure therapy.
Published: 2014

46. Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells

Author: Arner, E., Forrest, A.R.R., Hideya, K., Michael, R., J Kenneth Baillie, Michiel J, L.D.H., Vanja, H., Timo, L., Ivan, V.K., Marina, L., Masayoshi, I., Robin, A., Christopher, J.M., Terrence, F.M., Sebastian, S., Nicolas, B., Mette, J., Emmanuel, D., Erik, A., Christian, S., Ulf, S., Yulia, A.M., Charles, P., Morana, V., Jessica, S., Colin, A.S., Yuri, I., Margherita, F., Intikhab, A., Davide, A., Gabriel, M.A., John A, C.A., Peter, A., Magda, B., Sarah, B., Piotr, J.B., Anthony, G.B., Swati, P., Judith, A.B., Antje, B., Bodega, B., Alessandro, B., James, B., Frank, B., A Maxwell Burroughs, Andrea, C., Carlo, V.C., Daniel, C., Yun, C., Marco, C., Yari, C., Hans, C.C., Emiliano, D., Carrie, A.D., Michael, D., Alexander, D.D., Taeko, D., Albert S, B.E., Matthias, E., Karl, E., Mitsuhiro, E., Hideki, E., Michela, F., Lynsey, F., Hai, F., Mary, C.F., Geoffrey, J.F., Alexander, V.F., Malcolm, E.F., Martin, C.F., Rie, F., Shiro, F., Cesare, F., Masaaki, F., Jun-ichi, F., Teunis, B.G., Andrew, G., Thomas, G., Daniel, G., Julian, G., Sven, G., Reto, G., Stefano, G., Thomas, J.H., Masahide, H., Mitsuko, H., Matthias, H., Jayson, H., Akira, H., Yuki, H., Takehiro, H., Meenhard, H., Kelly, J.H., Shannan, J.H.S., Oliver, M.H., Ilka, H., Fumi, H., Lukasz, H., Kei, I., Tomokatsu, I., Boris, R.J., Hui, J., Anagha, J., Giuseppe, J., Bogumil, K., Chieko, K., Kaoru, K., Kaiho, A., Kazuhiro, K., Mutsumi, K., Artem, S.K., Takeya, K., Shintaro, K., Sachi, K., Shuji, K., Hiroshi, K., Yuki, I.K., Tsugumi, K., Judith, S.K., Tony, J.K., Juha, K., Levon, M.K., Toshio, K., S Peter Klinken, Alan, J.K., Miki, K., Soichi, K., Naoto, K., Haruhiko, K., Shigeo, K., Sarah, K., Atsutaka, K., Andrew, T.K., Jeroen F, J.L., Weonju, L., Andreas, L., Kang, L., Berit, L., Leonard, L., Alan, M., Ri-ichiroh, M., Jessica, C.M., Benoit, M., Anthony, M., Niklas, M., Alison, M., Yosuke, M., David, A.D.L.M., Hiromasa, M., Mitsuru, M., Kazuyo, M., Efthymios, M., Hozumi, M., Christine, L.M., Mitsuyoshi, M., Sayaka, N., Yutaka, N., Fumio, N., Toshiyuki, N., Yukio, N., Kenichi, N., Erik van Nimwegen, Noriko, N., Hiromi, N., Shohei, N., Tadasuke, N., Soichi, O., Naganari, O., Hiroko, O., Hiroshi, O., Mitsuhiro, O., Mariko, O., Yasushi, O., Valerio, O., Dmitry, A.O., Arnab, P., Robert, P., Margaret, P., Helena, P., Silvano, P., James G, D.P., Owen J, L.R., Jordan, A.R., Mamoon, R., Timothy, R., Patrizia, R., Marco, R., Sugata, R., Morten, B.R., Eri, S., Antti, S., Akiko, S., Shimon, S., Mizuho, S., Hiroki, S., Hironori, S., Suzana, S., Alka, S., Claudio, S., Erik, A.S., Gundula, G.S., Anita, S., Thierry, S., Guojun, S., Hisashi, S., Yishai, S., Jay, W.S., Christophe, S., Daisuke, S., Takaaki, S., Masanori, S., Rolf, K.S., Peter A, C.'.H., Michihira, T., Naoko, T., Jun, T., Hiroshi, T., Hideki, T., Zuotian, T., Mark, T., Hiroo, T., Tetsuro, T., Eivind, V., Marc van de Wetering, Linda, M.V.D.B., Roberto, V., Dipti, V., Ilya, E.V., Wyeth, W.W., Shoko, W., Christine, A.W., Louise, N.W., Ernst, W., Emily, J.W., Yoko, Y., Masayuki, Y., Misako, Y., Yohei, Y., Shigehiro, Y., Suzan, E.Z., Peter, G.Z., Xiaobei, Z., Silvia, Z., Kim, M.S., Harukazu, S., Carsten, O.D., Jun, K., Peter, H., Winston, H., Tom, C.F., Boris, L., Vladimir, B.B., Martin, S.T., Vsevolod, J.M., Albin, S., David, A.H., Piero, C., Yoshihide HayashizakiEhrlund, A., Mejhert, N., Itoh, M., Kawaji, H., Lassmann, T., Laurencikiene, J., Ryden, M., Arner, P., Hubrecht Institute for Developmental Biology and Stem Cell Research, AII - Amsterdam institute for Infection and Immunity, Infectious diseases, and Experimental Immunology
Subjects: Male, Angiogenesis, lcsh:Medicine, Adipose tissue, Gene Expression, Endocrinology, Neoplasms, Molecular Cell Biology, Basic Cancer Research, Databases, Genetic, Medicine and Health Sciences, Adipocytes, lcsh:Science, Multidisciplinary, biology, Cancer Risk Factors, Ceruloplasmin, Genomics, Middle Aged, Genomic Databases, Functional Genomics, Oncology, Adipose Tissue, Female, Transcriptome Analysis, Network Analysis, Research Article, Signal Transduction, Adult, medicine.medical_specialty, Computer and Information Sciences, Adipose tissue macrophages, Adipokine, Settore BIO/11 - Biologia Molecolare, Adipokines, Internal medicine, Cell Line, Tumor, medicine, Genetics, Cancer Genetics, Humans, Obesity, Sweden, business.industry, Gene Expression Profiling, lcsh:R, Cancer, Biology and Life Sciences, Computational Biology, Cell Biology, medicine.disease, Genome Analysis, Signaling Networks, Cell culture, Genetic Loci, Metabolic Disorders, Case-Control Studies, Cancer cell, biology.protein, lcsh:Q, business, Genome Expression Analysis
Abstract: Obesity confers an increased risk of developing specific cancer forms. Although the mechanisms are unclear, increased fat cell secretion of specific proteins (adipokines) may promote/facilitate development of malignant tumors in obesity via cross-talk between adipose tissue(s) and the tissues prone to develop cancer among obese. We searched for novel adipokines that were overexpressed in adipose tissue of obese subjects as well as in tumor cells derived from cancers commonly associated with obesity. For this purpose expression data from human adipose tissue of obese and non-obese as well as from a large panel of human cancer cell lines and corresponding primary cells and tissues were explored. We found expression of ceruloplasmin to be the most enriched in obesity-associated cancer cells. This gene was also significantly up-regulated in adipose tissue of obese subjects. Ceruloplasmin is the body's main copper carrier and is involved in angiogenesis. We demonstrate that ceruloplasmin is a novel adipokine, which is produced and secreted at increased rates in obesity. In the obese state, adipose tissue contributed markedly (up to 22%) to the total circulating protein level. In summary, we have through bioinformatic screening identified ceruloplasmin as a novel adipokine with increased expression in adipose tissue of obese subjects as well as in cells from obesity-associated cancers. Whether there is a causal relationship between adipose overexpression of ceruloplasmin and cancer development in obesity cannot be answered by these cross-sectional comparisons.
Published: 2014

47. Combined Tamoxifen and Luteinizing Hormone-Releasing Hormone (LHRH) Agonist Versus LHRH Agonist Alone in Premenopausal Advanced Breast Cancer: A Meta-Analysis of Four Randomized Trials

Author: Klijn, J. G. M., Blamey, R. W., Boccardo, F., Tominaga, T., Duchateau, L., Sylvester, R., Beex, L. V. A. M., Mauriac, L., Zijl, J. A., Veyret, C., Wildiers, J., Jassem, J., Piccart, M., Burghouts, J., Becqaert, D., Seynaeve, C., Mignolet, F., Namer, M., Julien, J. P., Garcia Conde, J., Dunser, M., Margreiter, R., Tjabbes, T., Roozendaal, K. J., Velden, P. C., Nortier, J. W. R., Blamey, R., Howell, A., Forbes, J., Kaufmann, M., Nordenskjold, B., Kvinnsland, S., Wilson, R. G., Jonat, W., Kleeberg, U. R., Eiermann, W., Hilfrich, J., Weitzel, H. K., Glas, U., Rutqvist, L. E., Rudenstam, C., Sander, S., Ryden, S., Honsson, P., Lonning, P. E., Loven, L., Russell, I. S., Olweny, C., Byrne, J. J., Snyder, R. D., Coates, A. S., Lowenthal, R. M., Jeal, P. N., Dalley, D. N., Janicke, F., Kleine, W., Michel, R. Th, Canobbio, L., Amoroso, D., Rubagotti, A., Bumma, C., D Aprile, M., Matteis, A., Di Carlo, A., Francini, G., Petrioli, R., Folco, U., Calligioni, E., Gallotti, P., Lopez, M., Mesiti, M., Pacini, P., Sassi, M., Sismondi, P., Paolo Zola, Ogita, M., Okazaki, M., Watanabe, T., Satomi, T., Hatazawa, C., Okuyama, N., Koyama, T., Kobayashi, M., Shimizu, T., Tabei, T., Sano, M., Makino, H., Ando, J., Kimura, M., Takeuchi, T., Aoyama, H., Koyama, H., Shin, E., Chou, G., and Medical Oncology
Subjects: Agonist, Oncology, endocrine system, Cancer Research, medicine.medical_specialty, Neoplasms, Hormone-Dependent, Antineoplastic Agents, Hormonal, medicine.drug_class, medicine.medical_treatment, Antineoplastic Agents, Breast Neoplasms, Buserelin, Gonadotropin-Releasing Hormone, Drug Therapy, SDG 3 - Good Health and Well-being, Neoplasms, Internal medicine, medicine, Humans, Neoplasm Metastasis, Hormone-Dependent, Randomized Controlled Trials as Topic, Hormonal, business.industry, Standard treatment, Goserelin, Oophorectomy, Cancer, Antiestrogen, medicine.disease, Survival Analysis, Drug Therapy, Combination, Female, Premenopause, Tamoxifen, Endocrinology, Combination, business, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract: PURPOSE: The logic behind the application of luteinizing hormone-releasing hormone (LHRH) agonists in combination with tamoxifen in premenopausal women is that LHRH agonists on the one hand suppress the tamoxifen-induced stimulation of the pituitary-ovarian function and, on the other hand, seem as effective as surgical castration. This meta-analysis combines all randomized evidence to compare the combined treatment with LHRH agonist alone with respect to overall survival, progression-free survival, and objective response in premenopausal women with advanced breast cancer. PATIENTS AND METHODS: Four clinical trials randomizing a total of 506 premenopausal women with advanced breast cancer to LHRH agonist alone or to the combined treatment of LHRH agonist plus tamoxifen were identified. Meta-analytic techniques were used to analyze individual patient data from these trials. RESULTS: With a median follow-up of 6.8 years, there was a significant survival benefit (stratified log-rank test, P = .02; hazards ratio [HR] = 0.78) and progression-free survival benefit (stratified log-rank test, P = .0003; HR = 0.70) in favor of the combined treatment. The overall response rate was significantly higher on combined endocrine treatment (stratified Mantel Haenszel test, P = .03; odds ratio = 0.67). CONCLUSION: The combination of LHRH agonist plus tamoxifen is superior to LHRH agonist alone in premenopausal women with advanced breast cancer. Therefore, if a premenopausal woman with advanced breast cancer is thought to be suitable for endocrine treatment, it is proposed that the combination of a LHRH agonist plus tamoxifen be considered as the new standard treatment.
Published: 2001
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48. The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial programme. Rationale, design and baseline characteristics including a meta-analysis of the effects of thienopyridines in vascular disease

Author: M. Keltai, Michael Gent, A Sosa Liprandi, T. Wittlinger, Andrzej Budaj, Piotr Szymański, A Avezum, M. Galli, H. De Raedt, M. Sotty, E. G. Hasbani, J. Bouthier, S. Chrolavicius, P. J. Commerford, B. J. Gersh, N. Awan, Bongani M. Mayosi, M. Den Hartoog, F. Zhao, P. Widimsky, S. Kopecky, F. Mauri, P. Commerford, Christophe Gaudin, A. Pipilis, J. Norris, J Pogue, D. C G Basart, J. Wittes, Y. K. Chan, J. Cairns, K Hall, J. Varigos, A. Maggioni, K. Fox, A. A. Fernandez, M. Nieminen, I. Copland, T. Mocceti, J. Renkin, Akbar Panju, S. Ounpuu, P. Montague, R. J. Peters, V. Yacyshyn, J. J. Fuselli, E. Sitkei, H. Rupprecht, J. O. Bono, M. Bertrand, J. Keys, M. Flather, Sonia S. Anand, Dereck L. Hunt, T. Ryan, J. F. Marquis, Madhu K. Natarajan, Jack Hirsh, R. A. Ahuad Guerrero, W. Grossman, Robert G. Hart, P. Auger, T. Hess, C. Rihal, J. Morais, R. Diaz, Matthew J. McQueen, W. Wasek, B. Cracknell, C. Joyner, A. J. Gambarte, J. Garcia-Guerrero, B. Morris, L. Ceremuzynski, G. Tognoni, N. Karatzas, K. Malmberg, A. Caccavo, L. Piegas, C. Wright, Catherine Demers, N. Khurmi, David A. Halon, G. Allende, Vicent Valentin, E. Paolasso, R. Peters, M. A. Ramos-Corrales, M. G. Franzosi, J. Col, L. Ryden, Shamir R. Mehta, G. Wyse, B. S. Lewis, John W. Eikelboom, M. Blumenthal, and Salim Yusuf
Subjects: medicine.medical_specialty, Acute coronary syndrome, Ticlopidine, Klinikai orvostudományok, Angina, Meta-Analysis as Topic, Internal medicine, medicine, Humans, Angina, Unstable, Vascular Diseases, Myocardial infarction, Stroke, Randomized Controlled Trials as Topic, Aspirin, business.industry, Unstable angina, Orvostudományok, medicine.disease, Clopidogrel, Cardiology, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract: Background Other than aspirin, there are few oral antithrombotic treatments with proven efficacy in patients with acute coronary syndrome. In this report, we present the rationale, design and baseline characteristics of the Clopidogrel in Unstable angina to prevent Recurrent ischaemic Events (CURE) trial, which includes a meta-analysis of the effects of thienopyridines in patients with vascular disease. Methods and Results Combined data from randomized trials of thienopyrindines in patients with atherosclerotic disease demonstrated a 29% reduction in vascular events when compared with placebo/control (n=2392) (OR 0.71, 95% CI 0.58-0.86, P=0.0006) and a 10% reduction in vascular events when compared with aspirin (n=22 254) (OR 0.91, 95% Cl 0.84-0.99, P=0.039). Similarly, randomized trials of aspirin plus thienopyridines in patients undergoing intracoronary stenting, demonstrated marked benefit of aspirin plus ticlopidine in reducing death or myocardial infarction compared with aspirin alone (OR 0.23, 95% CI 0.11-0.49, P=0.0001) or aspirin plus warfarin (OR 0.51, 95% CI 0.33-0.78, P=0.002). Whether these benefits extend to the much larger population of patients with acute coronary syndrome is unknown. CURE is an international, randomized, double-blind trial, in which patients with acute coronary syndrome will be randomized to receive either a bolus dose of clopidogrel (300 mg) followed by 75 mg per day for 3-12 months, or matching placebo. Both groups will receive aspirin. The co-primary efficacy end-points of CURE are: (1) the composite of cardiovascular death, myocardial infarction or stroke; and (2) the composite of cardiovascular death, myocardial infarction, stroke or refractory ischaemia. CURE will recruit approximately 12 500 patients with acute coronary syndrome (from 28 countries) and its power to detect moderate treatment benefits will be in the region of 80-90%, while maintaining an overall type I error (a) of 0.05. The baseline characteristics of the study population are consistent with at least a moderate risk group of patients with acute coronary syndrome. Conclusions Randomized trials of thienopyridines in patients with vascular disease demonstrate that thienopyridines are effective in reducing vascular events when compared with placebo/control or aspirin, as well as when used in combination with aspirin in patients undergoing intracoronary stent implantation. The CURE trial is a large international study to determine if acute and longterm treatment with the combination of clopidogrel and aspirin is superior to aspirin alone in patients with acute coronary syndrome. (C) 2000 The European Society of Cardiology.
Published: 2000
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49. The relationship between social interaction and characteristics of aggressive, cognitively impaired nursing home residents

Author: Yu-Ling Chen, Muriel B. Ryden, Kay Savik, and Karen S. Feldt
Subjects: 05 social sciences, 050109 social psychology, medicine.disease, Social relation, 030227 psychiatry, 03 medical and health sciences, 0302 clinical medicine, Neuropsychology and Physiological Psychology, Scale (social sciences), medicine, Community interaction, Dementia, Marital status, 0501 psychology and cognitive sciences, Cognitively impaired, Geriatrics and Gerontology, Psychology, Cognitive impairment, Nursing homes, Clinical psychology
Abstract: The extent of social interaction of aggressive, cognitively impaired nursing home residents and the relationship between social interaction and selected resident characteristics were explored in this study, which was part of a larger experimental study of the effect of dementia education for staff on the aggressive behavior of cognitively impaired residents. Staff rated residents using the Social Interaction Scale (SIS),which has two subscales: Institutional Interaction and Family/Community Interaction. Mean SIS scores were low; institutional interaction scores were higher than family/community scores. Marital status, morale, degree of cognitive impairment, dependency, and sexual aggression were significantly associated with social interaction, but gender and age were not.
Published: 2000
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50. A 3-year prospective study on serum tumor markers used for detecting cholangiocarcinoma in patients with primary sclerosing cholangitis

Author: Ulrika Broomé, Rolf Hultcrantz, Gunnar Järnerot, Lars Lööf, Brita Wahren, Bengt Olof Ryden, Åke Danielsson, and Rolf Olsson
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, CA-19-9 Antigen, Cholangitis, Sclerosing, digestive system, Gastroenterology, Primary sclerosing cholangitis, Cholangiocarcinoma, Liver disease, Carcinoembryonic antigen, Double-Blind Method, Predictive Value of Tests, Risk Factors, Internal medicine, Biomarkers, Tumor, medicine, Humans, Antigens, Tumor-Associated, Carbohydrate, In patient, Prospective Studies, Prospective cohort study, neoplasms, Neoplasm Staging, Hepatology, biology, business.industry, Reproducibility of Results, Middle Aged, medicine.disease, digestive system diseases, Carcinoembryonic Antigen, Clinical trial, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, Predictive value of tests, biology.protein, Colchicine, Complication, business, Follow-Up Studies
Abstract: Patients with primary sclerosing cholangitis (PSC) have an increased risk of developing cholangiocarcinoma (CC), which is notoriously difficult to diagnose since these patients may have increased levels of bilirubin due to benign strictures. To evaluate the validity of different tumor markers as an aid to diagnosing CC, we have carried out serial serum tumor marker analyses in patients with PSC who have been followed for several years.Seventy-five patients with PSC, without any clinical signs of CC were included in the study. They were investigated every 6th months for 3 years, with extensive liver function tests and four tumor serum markers CEA, CA 19-9, CA 50 and CA 242. The patients were then followed for 5 years to exclude the possibility that CC remained unrecognized.Of the 75 patients, two (3%) developed CC during the 3-year period. One of these had normal levels, and one had significantly increased levels of the tumor markers. In the follow-up part of the study two further patients died from CC and one from hepatocellular carcinoma, 3 and 4 years after the 3-year study, respectively. Twenty-one patients had an increase of one of the markers on at least one occasion. Five patients had a transient increase of more than double the upper normal limit of the tumor markers on more than one occasion. There was a good correlation between CA 19-9, CA 50 and CA 242, but not with CEA. Fourteen of the 75 patients had periods of increased bilirubin levels, but none of these showed increased tumor markers.The serum tumor markers CEA, CA 19-9, CA 50 and CA 242 are of limited value for the detection of CC in patients with PSC because of low specificity. However, we found no falsely increased values in patients with hyperbilirubinemia.
Published: 1999
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