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Your search keyword '"Diabetes Mellitus/drug therapy"' showing total 22 results
Start Over Descriptor "Diabetes Mellitus/drug therapy" Topic diabetes mellitus
22 results on '"Diabetes Mellitus/drug therapy"'

1. Intensive monitoring for post-transplant diabetes mellitus and treatment with dipeptidyl peptidase-4 inhibitor therapy.

Author

Thiruvengadam S, Hutchison B, Lim W, Bennett K, Daniels G, Cusack N, Jacques A, Cawley B, Thiruvengadam S, and Chakera A

Subjects
Blood Glucose analysis, Case-Control Studies, Diabetes Mellitus etiology, Female, Follow-Up Studies, Glucose Tolerance Test, Glycated Hemoglobin analysis, Humans, Male, Middle Aged, Postoperative Complications diagnosis, Postoperative Complications etiology, Prognosis, Retrospective Studies, Biomarkers analysis, Diabetes Mellitus diagnosis, Diabetes Mellitus drug therapy, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases therapeutic use, Kidney Failure, Chronic surgery, Kidney Transplantation adverse effects, Postoperative Complications drug therapy
Abstract

Aim: Current monitoring practices fail to diagnose patients with post-transplant hyperglycaemia and tend to delay initiation of treatment, which potentially results in adverse graft and morbidity outcomes. This real-world study set out to assess the impact on insulin resistance indices of a new clinical pathway for diagnosis and treatment of hyperglycaemia following renal transplantation., Methods: A hundred and forty-seven adult renal transplant recipients, without pre-existing diabetes, from a single centre were included. Patients transplanted between January 2008 to September 2015 formed the historical cohort. Patients transplanted between October 2015 and February 2018 were subject to a new clinical pathway - if they had fasting blood sugar levels more than 7 mmol/L or random blood glucose levels more than 11.1 mmol/L, they had early introduction of oral therapy, using the DPP-4 inhibitor linagliptin., Results: In the historical cohort, 19.8% were diagnosed with PTDM, compared to 46.3% in the protocol cohort. Amongst patients with PTDM, there was a significant difference in HOMA-IR (p = 0.02) between the historical cohort (median HOMA-IR 3.33) and the protocol cohort (median HOMA-IR 2.21). There was a significant difference at each time point (0,1,2-h measurements) of blood glucose levels form oral glucose tolerance testing between patients with and without PTDM in the historical cohort (p < 0.001), but no difference between patients in the protocol cohort., Conclusion: Detection of PTDM was higher with the new clinical pathway. Early treatment of hyperglycaemia resulted in better insulin resistance scores. Larger prospective controlled studies focussing on early detection and management of PTDM with linagliptin are warranted., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Published
2019
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2. Risk of diabetes and the impact on preexisting diabetes in patients with lymphoma treated with steroid-containing immunochemotherapy

Author

Joachim Baech, Marianne Tang Severinsen, Andreas K. Øvlisen, Henrik Frederiksen, Peter Vestergaard, Christian Torp-Pedersen, Judit Jørgensen, Michael Roost Clausen, Christian B. Poulsen, Peter Brown, Anne Ortved Gang, Robert Schou Pedersen, Karin Ekström Smedby, Sandra Eloranta, Lasse Hjort Jakobsen, and Tarec Christoffer El-Galaly

Subjects
Lymphoma, Non-Hodgkin, Prednisone/adverse effects, Insulins, Hematology, Diabetes Mellitus/drug therapy, Insulins/therapeutic use, Cohort Studies, Cardiovascular Diseases, hemic and lymphatic diseases, Diabetes Mellitus, Prednisone, Humans, Cardiovascular Diseases/etiology, Lymphoma, Non-Hodgkin/complications
Abstract

First-line treatments for lymphomas often include high doses of prednisolone, but the risks of new-onset diabetes mellitus (DM) or worsening of preexisting DM following treatment with cyclic high dose corticosteroids is unknown. This cohort study matched non-Hodgkin lymphoma (NHL) patients treated with steroid-containing immunochemotherapy (ie, R-CHOP[-like] and R-CVP) between 2002 and 2015 to individuals from the Danish population to investigate the risks of new-onset DM. For patients with preexisting DM, the risks of insulin dependency and anthracycline-associated cardiovascular diseases (CVDs) were assessed. In total, 5672 NHL patients and 28 360 matched comparators were included. Time-varying incidence rate ratios (IRRs) showed increased risk of DM in the first year after treatment compared with matched comparators, with the highest IRR being 2.7. The absolute risks were higher among patients in the first 2 years, but the difference was clinically insignificant. NHL patients with preexisting DM had increased risks of insulin prescriptions with 0.5-, 5-, and 10-year cumulative risk differences of insulin treatment of 15.3, 11.8, and 6.0 percentage units as compared with the DM comparators. In a landmark analysis at 1 year, DM patients with lymphoma had decreased risks of insulin dependency compared with comparators. Time-varying IRRs showed a higher CVD risk for NHL patients with DM as compared with comparators in the first year after treatment. NHL patients treated with steroid-containing immunochemotherapy regimens have a clinically insignificant increased risk of DM in the first year following treatment, and patients with preexisting DM have a temporary increased risk of insulin prescriptions and CVD.

Published
2022
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3. Outcomes After Acute Coronary Syndrome in Patients With Diabetes Mellitus and Peripheral Artery Disease (from the TRACER, TRILOGY-ACS, APPRAISE-2, and PLATO Clinical Trials)

Author

Rubina Attar, Angie Wu, Daniel Wojdyla, Svend Eggert Jensen, Pontus Andell, Kenneth W. Mahaffey, Matthew T. Roe, Stefan K. James, Lars Wallentin, Sreekanth Vemulapalli, John H. Alexander, Renato D. Lopes, E. Magnus Ohman, Adrian F. Hernandez, Manesh R. Patel, and W. Schuyler Jones

Subjects
Peripheral Arterial Disease, Treatment Outcome, Organoplatinum Compounds, Diabetes Mellitus, Myocardial Infarction, Humans, Peripheral Arterial Disease/complications, Acute Coronary Syndrome/complications, Acute Coronary Syndrome, Cardiology and Cardiovascular Medicine, Diabetes Mellitus/drug therapy, Randomized Controlled Trials as Topic
Abstract

Patients with acute coronary syndrome (ACS) are at risk for recurrent adverse events, and multiple reports suggest that this risk is increased in patients with concomitant diabetes mellitus (DM) and peripheral artery disease (PAD). The aim of this article was to investigate cardiovascular outcomes in patients with DM presenting with ACS, stratified by PAD status. Data were derived from 4 randomized post-ACS trials (PLATO [Platelet Inhibition and Patient Outcomes], APPRAISE-2 p Apixaban for Prevention of Acute Ischemic Events 2], TRILOGY [Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage], and TRACER [Thrombin Receptor Agonist for Clinical Event Reduction in Acute Coronary Syndrome]). Using Cox regression analysis, we investigated major adverse cardiovascular events (MACEs), a composite of cardiovascular mortality, myocardial infarction (MI), or stroke and the individual components of MACE and all-cause mortality in patients with DM, presenting with ACS, stratified by PAD status as the risk modifier. This study included 15,387 patients with a diagnosis of DM and ACS, of whom 1,751 had an additional diagnosis of PAD. PAD was associated with more than doubled rates of MACE (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.81 to 2.27), all-cause mortality (HR 2.48, 95% CI 2.14 to 2.87), cardiovascular mortality (HR 2.42, 95% CI 2.04 to 2.86), and MI (HR 2.07, 95% CI 1.79 to 2.38). Patients with both PAD and DM were also more optimally treated with antihypertensive, antidiabetic, and statin medication at baseline. In conclusion, this analysis of 4 major post-ACS trials showed that patients with DM and PAD had a substantially higher risk of MACE, cardiovascular mortality, all-cause mortality, and MI despite being optimally treated with guideline-based therapies.

Published
2022
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4. Health status and quality of life in patients with diabetes in Switzerland

Author

Anne Zanchi, Chantal Arditi, and Isabelle Peytremann-Bridevaux

Subjects
Male, Gerontology, Time Factors, Social Determinants of Health, Cross-sectional study, Health Status, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, 03 medical and health sciences, 0302 clinical medicine, Cost of Illness, Quality of life, Risk Factors, Diabetes mellitus, Diabetes Mellitus, Internal Medicine, Humans, Hypoglycemic Agents, Insulin, Medicine, In patient, 030212 general & internal medicine, Social determinants of health, Lower income, Aged, Nutrition and Dietetics, business.industry, Age Factors, Middle Aged, medicine.disease, Mental health, humanities, Cross-Sectional Studies, Diabetes Mellitus/diagnosis, Diabetes Mellitus/drug therapy, Diabetes Mellitus/physiopathology, Diabetes Mellitus/psychology, Female, Hypoglycemic Agents/adverse effects, Insulin/adverse effects, Mental Health, Quality of Life, Switzerland, ADDQoL, Diabetes, Health status, SF-12, Sex life, Family Practice, business
Abstract

Aims We aimed to assess the health status and quality of life (QoL) of patients with diabetes and explore the associated factors in a French-speaking region of Switzerland. Methods This cross-sectional study analyzed self-reported data from 585 patients with diabetes. We ran univariate and multivariate regressions analyses on health status (Physical and Mental Component Summary scores (PCS, MCS) of the SF-12) and diabetes-specific QoL (ADDQoL score). Results Mean PCS was 43.1 ± 10.4 and mean MCS was 46.7 ± 11.1. The overall ADDQoL score was −1.6 ± 1.6; the life domains of the ADDQoL with the lowest scores were freedom to eat, sex life and freedom to drink. Being older was independently and significantly associated with higher mental health and QoL, while lower income was associated with lower physical health, mental health, and QoL. Having diabetes for over 10 years was associated with lower QoL, while insulin treatment and complications were correlated with lower physical health and QoL. Conclusions This study provides key information on the health status and QoL of patients with diabetes in Switzerland and their associated factors, which can help healthcare providers to identify patients at higher risk of lower health and QoL.

Published
2019
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5. Pharmacological reflection of plants traditionally used to manage diabetes mellitus in Tanzania

Author

Emanuel L. Peter, Crispin Duncan Sesaazi, Naasson Tuyiringire, Efrata Ashuro, Prakash B. Nagendrappa, Anita Kaligirwa, Samson Hilonga, Pharmaceutical and Pharmacological Sciences, and Faculty of Medicine and Pharmacy

Subjects
Tanzania, Diabetes Mellitus/drug therapy, Hypoglycemic Agents/adverse effects, Moringa, 03 medical and health sciences, Pharmacology, Toxicology and Pharmaceutics(all), 0302 clinical medicine, Plants, Medicinal/chemistry, Diabetes mellitus, Drug Discovery, Diabetes Mellitus, Medicine, Animals, Humans, Hypoglycemic Agents, Medicine, Traditional/adverse effects, Medicinal plants, 030304 developmental biology, Pharmacology, 0303 health sciences, Plants, Medicinal, biology, Adiponectin, Momordica, Traditional medicine, business.industry, Plant Preparations/adverse effects, biology.organism_classification, medicine.disease, Caesalpinia bonduc, Phytochemical, 030220 oncology & carcinogenesis, Ethnopharmacology, Medicine, Traditional, Plant Preparations, business
Abstract

Ethnopharmacological relevance The increasing national prevalence of diabetes mellitus (DM) and its complications have overstretched the health care system in Tanzania and influenced patients to use herbal medicines as alternative therapeutic strategies. Therefore, an urgent need exists to validate the safety and efficacy of plants used locally. Aim of the study To identify plants used for the management of DM in Tanzania and analyses their pharmacological, phytochemistry, and safety evidence with a special focus on the mechanism of action. Methods Researchers searched Medline, web of science, and Scopus for published articles. Also, specialized herbarium documents of Muhimbili Institute of traditional medicine were reviewed. Articles were assessed for relevance, quality, and taxonomical accuracy before being critically reviewed. Results We identified 62 plant species used locally for DM management. Moringa oleifera Lam. and Cymbopogon citratus (D.C) stapf were the most mentioned. Fifty-four phytochemicals from 13 species had DM activities. These were mainly; polyphenolics, phytosterols, and triterpenoids. Extracts, fractions, and pure compounds from 18 species had in vitro antidiabetic activities of which 14 had α-glucosidase and α-amylase inhibition effects. The most studied -Momordica charantia L. increased; glucose uptake and adiponectin release in 3T3-L1 adipocytes, insulin secretion, insulin receptor substrate-1 (IRS-1), GLUT-4 translocation, and GLP-1 secretion; and inhibited protein tyrosine phosphatase 1 B (PTP1B). Preclinical studies reported 30 species that lower plasma glucose with molecular targets in the liver, skeletal muscles, adipose tissues, pancreases, and stomach. While three species; Aspilia mossambiscensis (Oliv.) Willd, Caesalpinia bonduc (L.) Roxb, and Phyllanthus amarus Schumach. & Thonn. had mild toxicity in animals, 33 had no report of their efficacy in DM management or toxicity. Conclusion Local communities in Tanzania use herbal medicine for the management of DM. However, only a fraction of such species has scientific evidence. A. mossambiscensis, C. bonduc., and P. amarus had mild toxicity in animals. Together, our findings call for future researches to focus on in vitro, in vivo, and phytochemical investigation of plant species for which their use in DM among the local communities in Tanzania have not been validated.

Published
2020

6. Polypharmacy difference between older people with and without diabetes: Evidence from the English longitudinal study of ageing

Author

Yun-Ting Huang, Andrew Steptoe, Paola Zaninotto, and Li Wei

Subjects
Gerontology, Male, Longitudinal study, Aging, Glycated Hemoglobin A/metabolism, Endocrinology, Diabetes and Metabolism, Prevalence, Hypoglycemic Agents/therapeutic use, 030209 endocrinology & metabolism, Comorbidity, Diabetes Mellitus/drug therapy, Diabetes Complications, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Risk Factors, Diabetes mellitus, Internal Medicine, medicine, Diabetes Mellitus, Humans, Hypoglycemic Agents, 030212 general & internal medicine, Longitudinal Studies, Obesity, England/epidemiology, Risk factor, Aged, Polypharmacy, Aged, 80 and over, Glycated Hemoglobin, business.industry, General Medicine, Pharmacoepidemiology, Middle Aged, medicine.disease, Aging/physiology, Cross-Sectional Studies, England, Relative risk, Diabetes Complications/drug therapy, Female, Obesity/complications, business
Abstract

AIM: To study the association between diabetes and the prevalence of and risk factors for polypharmacy among adults aged 50 and older in England.METHODS: A cross-sectional study (2012-2013) of the English Longitudinal Study of Ageing. Polypharmacy was defined as taking 5-9 long-term medications a day and heightened polypharmacy as 10 or more. Diabetes included diagnosed and undiagnosed cases (glycated haemoglobin ≥ 6.5% (48 mmol/mol)).RESULTS: Of 7729 participants, 1100 people had diabetes and showed higher prevalence rates of polypharmacy (41.1% vs 14.8%) and heightened polypharmacy (5.8% vs 1.7%) than those without diabetes, even when antihyperglycemic medications were excluded. Risk factors for polypharmacy also differed according to diabetes status. Among people with diabetes, risk factors for polypharmacy and heightened polypharmacy were having more long-term conditions (relative risk ratio (RRR) = 1.86; 3.51) and being obese (RRR = 1.68; 3.68), while females were less likely to show polypharmacy (RRR = 0.51) and heightened polypharmacy (RRR = 0.51) than males. Older age (RRR = 1.04) was only related to polypharmacy among people without diabetes.CONCLUSIONS: Adults with diabetes had higher prevalence rates of polypharmacy and heightened polypharmacy than those without diabetes, regardless of including antihyperglycemic drugs. Early detection of polypharmacy among older people with diabetes needs to focus on co-morbidities and obesity.

Published
2020
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7. ‘A necessary evil’: associations with taking medication and their relationship with medication adherence

Author

Mieke Kleppe, J. Lacroix, Jaap Ham, Cjh Cees Midden, and Human Technology Interaction

Subjects
Adult, Male, Health Knowledge, Attitudes, Practice, medicine.medical_specialty, Adolescent, Medication adherence, SDG 3 – Goede gezondheid en welzijn, Affect (psychology), Medication Adherence, Diabetes Mellitus/drug therapy, Association, Young Adult, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Diabetes Mellitus, 80 and over, medicine, Humans, 030212 general & internal medicine, Young adult, Psychiatry, Applied Psychology, Aged, Aged, 80 and over, Practice, 030505 public health, business.industry, Health Knowledge, Cognition, Middle Aged, Taking medication, Affect, Psychiatry and Mental health, Clinical Psychology, Medication Adherence/psychology, Cardiovascular Diseases, Attitudes, Female, Cardiovascular Diseases/drug therapy, 0305 other medical science, business
Abstract

Cognitive factors, like beliefs, have been studied extensively as determinants of medication adherence, while affect associated with taking medicines has been studied much less. In the present study (N = 525), we investigated affect by assessing patients’ first associations with taking their medicines. Results showed that these associations were related to self-reported medication adherence: Patients who associated taking medicines with negative affect were the least adherent, while those associating taking medicines with the need to take medicines were the most adherent. Our results support the idea that affect should be considered an important determinant of adherence.

Published
2017
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8. Medication self-management support for people with diabetes and low health literacy: A needs assessment

Author

Visscher, Boudewijn B, Steunenberg, Bas, Heerdink, Eibert R, Rademakers, Jany, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, RS: CAPHRI - R6 - Promoting Health & Personalised Care, Family Medicine, Afd Pharmacoepi & Clinical Pharmacology, and Pharmacoepidemiology and Clinical Pharmacology

Subjects
Male, Health Knowledge, Attitudes, Practice, Health Literacy/methods, Physiology, Psychological intervention, Social Sciences, Pharmacists, Biochemistry, Diabetes Mellitus/drug therapy, 0302 clinical medicine, Endocrinology, Sociology, Health care, Medicine and Health Sciences, Insulin, Psychology, 030212 general & internal medicine, Medical Personnel, Qualitative Research, Language, Practice, education, Multidisciplinary, Health Knowledge, Communication, Social Communication, Focus Groups, Middle Aged, Blood Sugar, Body Fluids, Professions, Blood, Health Education and Awareness, Needs assessment, Medicine, Female, Anatomy, Needs Assessment, Self-medication, Research Article, Adult, Endocrine Disorders, Science, MEDLINE, 030209 endocrinology & metabolism, Health literacy, Medication Adherence, 03 medical and health sciences, ADHERENCE, Diabetes Mellitus, Humans, interventions, Diabetic Endocrinology, Medical education, business.industry, Self-Management, Cognitive Psychology, Biology and Life Sciences, Focus group, Communications, Hormones, Health Literacy, MODEL, Self Care, Health Care, Medication Adherence/psychology, Attitudes, Metabolic Disorders, People and Places, Self-Management/methods, Cognitive Science, Population Groupings, business, Qualitative research, Neuroscience
Abstract

IntroductionAn adequate level of health literacy is regarded as a prerequisite for adequate medication self-management. Low health literacy skills are relatively more common in people with Diabetes Mellitus type 2. The aim of this study was to explore the needs regarding medication self-management of people with type 2 diabetes and low (functional, communicative and critical) health literacy, and their preferences for medication self-management support.Materials and methodsA two-stage qualitative needs assessment study was performed using in-depth individual interviews and focus groups.ResultsThe participants preferred to be supported with reliable and easily understandable information, adequate interactive communication with health care professionals and fellow people with diabetes and tools for medication self-management support.DiscussionFuture interventions should be created in co-creation with people with low health literacy and fulfill the expressed needs on information, communication and tools to improve self-management.

Published
2019

9. Choice and Outcomes of Rate Control versus Rhythm Control in Elderly Patients with Atrial Fibrillation: A Report from the REPOSI Study

Author

Paciullo, Francesco, Proietti, Marco, Bianconi, Vanessa, Nobili, Alessandro, Pirro, Matteo, Mannucci, Pier Mannuccio, Lip, Gregory Y. H., Lupattelli, Graziana, Tettamanti, Mauro, Pasina, Luca, Franchi, Carlotta, Perticone, Francesco, Salerno, Francesco, Corrao, Salvatore, Marengoni, Alessandra, Licata, Giuseppe, Violi, Francesco, Corazza, Gino Roberto, Marcucci, Maura, Eldin, Tarek Kamal, Di Blanca, Maria Pia Donatella, Lanzo, Giovanna, Astuto, Sarah, Ardoino, Ilaria, Cortesi, Laura, Prisco, Domenico, Silvestri, Elena, Cenci, Caterina, Emmi, Giacomo, Biolo, Gianni, Guarnieri, Gianfranco, Zanetti, Michela, Fernandes, Giovanni, Chiuch, Massimiliano, Vanoli, Massimo, Grignani, Giulia, Casella, Gianluca, Pulixi, Edoardo Alessandro, Bernardi, Mauro, Bassi, Silvia Li, Santi, Luca, Zaccherini, Giacomo, Mannarino, Elmo, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Palazzuoli, Alberto, Salvatore, Teresa, Sasso, Ferdinando Carlo, Girelli, Domenico, Olivieri, Oliviero, Matteazzi, Thomas, Barbagallo, Mario, Plances, Lidia, Alcamo, Roberta, Calvo, Luigi, Valenti, Maria, Zoli, Marco, Arnò, Raffaella, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Bicchi, Maurizio, Palasciano, Giuseppe, Modeo, Maria Ester, Peragine, Maria, Pappagallo, Fabrizio, Pugliese, Stefania, Di Gennaro, Carla, Postiglione, Alfredo, Barbella, Maria Rosaria, de Stefano, Francesco, Cappellini, Maria Domenica, Fabio, Giovanna, Seghezzi, Sonia, de Amicis, Margherita Migone, Mancarella, Marta, Mari, Daniela, Rossi, Paolo Dionigi, Damanti, Sarah, Ottolini, Barbara Brignolo, Bonini, Giulia, Miceli, Emanuela, Lenti, Marco Vincenzo, Padula, Donatella, Murialdo, Giovanni, Marra, Alessio, Cattaneo, Federico, Secchi, Maria Beatrice, Ghelfi, Davide, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Davì, Giovanni, Guagnano, Maria Teresa, Sestili, Simona, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mosè, Meroni, Maria Rachele, Perin, Paolo Cavallo, Lorenzati, Bartolomeo, Gruden, Gabriella, Bruno, Graziella, Amione, Cristina, Fornengo, Paolo, Tassara, Rodolfo, Melis, Deborah, Rebella, Lara, Delitala, Giuseppe, Pretti, Vincenzo, Masala, Maristella Salvatora, Pes, Chiara, Bolondi, Luigi, Rasciti, Leonardo, Serio, Ilaria, Fanelli, Filippo Rossi, Amoroso, Antonio, Molfino, Alessio, Petrillo, Enrico, Zuccalà, Giuseppe, Franceschi, Francesco, de Marco, Guido, Chiara, Cordischi, Marta, Sabbatini, D’Aurizio, Gabriella, Romanelli, Giuseppe, Amolini, Claudia, Chiesa, Deborah, Picardi, Antonio, Gentilucci, Umberto Vespasiani, Gallo, Paolo, Annoni, Giorgio, Corsi, Maurizio, Zazzetta, Sara, Bellelli, Giuseppe, Szabo, Hajnalka, Arturi, Franco, Succurro, Elena, Rubino, Mariangela, Sesti, Giorgio, Loria, Paola, Becchi, Maria Angela, Martucci, Gianfranco, Fantuzzi, Alessandra, Maurantonio, Mauro, Serra, Maria Grazia, Bleve, Maria Antonietta, Gasbarrone, Laura, Sajeva, Maria Rosaria, Brucato, Antonio, Ghidoni, Silvia, Di Corato, Paola, Agnelli, Giancarlo, Marchesini, Emanuela, Fabris, Fabrizio, Carlon, Michela, Turatto, Francesca, Baritusso, Aldo, Amabile, Annalisa, Omenetto, Elisabetta, Scarinzi, Paolo, Manfredini, Roberto, Molino, Christian, Pala, Marco, Fabbian, Fabio, Boari, Benedetta, de Giorgi, Alfredo, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Laieta, Maria Teresa, Rini, Giovanbattista, Mansueto, Pasquale, Pepe, Ilenia, Borghi, Claudio, Strocchi, Enrico, de Sando, Valeria, Pareo, Ilaria, Sabbà, Carlo, Vella, Francesco Saverio, Suppressa, Patrizia, Valerio, Raffaella, Agosti, Pasquale, Fontana, Flavia, Loparco, Francesca, Capobianco, Caterina, Fenoglio, Luigi, Bracco, Christian, Giraudo, Alessia Valentina, Testa, Elisa, Serraino, Cristina, Fargion, Silvia, Bonara, Paola, Periti, Giulia, Porzio, Marianna, Tiraboschi, Slivia, Peyvandi, Flora, Tedeschi, Alberto, Rossio, Raffaella, Ferrari, Barbara, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Magnini, Maria, Conca, Alessio, Gobbo, Giulia, Pallini, Giada, Valenti, Miriam, Balduini, Carlo L., Bertolino, Giampiera, Provini, Stella, Quaglia, Federica, Dallegri, Franco, Ottonello, Luciano, Liberale, Luca, Chin, Wu Sheng, Carassale, Laura, Caporotundo, Silvia, Traisci, Giancarlo, de Feudis, Lucrezia, Di Carlo, Silvia, Liberato, Nicola Lucio, Buratti, Alberto, Tognin, Tiziana, Bianchi, Giovanni Battista, Giaquinto, Sabrina, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Rozzini, Renzo, Falanga, Lina, Spazzini, Elena, Montrucchio, Giuseppe, Greco, Elisabetta, Tizzani, Pietro, Petitti, Paolo, Perciccante, Antonio, Coralli, Alessia, Salmi, Raffaella, Gaudenzi, Piergiorgio, Gamberini, Susanna, Semplicini, Andrea, Gottardo, Lucia, Vendemiale, Gianluigi, Serviddio, Gaetano, Forlano, Roberta, Masala, Cesare, Mammarella, Antonio, Raparelli, Valeria, Basili, Stefania, Perri, Ludovica, Landolfi, Raffaele, Montalto, Massimo, Mirijello, Antonio, Vallone, Carla, Bellusci, Martino, Setti, Donatella, Pedrazzoli, Filippo, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Molaro, Marta, Bertolotti, Marco, Mussi, Chiara, Libbra, Maria Vittoria, Miceli, Andrea, Pellegrini, Elisa, Carulli, Lucia, Veltri, Francesca, Sciacqua, Angela, Quero, Michele, Bagnato, Chiara, Colangelo, Lidia, Falbo, Tania, de Giorgio, Roberto, Serra, Mauro, Grasso, Valentina, Ruggeri, Eugenio, Ilaria, Benzoni, Salvi, Andrea, Leonardi, Roberto, Grassini, Chiara, Mascherona, Ilenia, Minelli, Giorgio, Maltese, Francesca, Damiani, Giampaolo, Capeci, William, Mattioli, Massimo, Martino, Giuseppe Pio, Biondi, Lorenzo, Ormas, Monica, Pettinari, Pietro, Romiti, Roberto, Messina, Silvia, Cavallaro, Federica, Ghio, Riccardi, Favorini, Serena, Col, Anna Dal, Minisola, Salvatore, Colangelo, Luciano, Afeltra, Antonella, Alemanno, Pamela, Marigliano, Benedetta, Pipita, Maria Elena, Castellino, Pietro, Blanco, Julien, Zanoli, Luca, Cattaneo, Marco, Fracasso, Paola, Amoruso, Maria Valentina, Saracco, Valter, Fogliati, Marisa, Bussolino, Carlo, Durante, Vittorio, Eusebi, Giovanna, Tirotta, Daniela, Mete, Francesca, Gino, Miriam, Cittadini, Antonio, Vigorito, Carlo, Arcopinto, Michele, Salzano, Andrea, Bobbio, Emanuele, Marra, Alberto Maria, Sirico, Domenico, Moreo, Guido, Scopelliti, Francesco, Gasparini, Francesca, Cocca, Melissa, Ballestrero, Alberto, Ferrando, Fabio, Berra, Sergio, Dassi, Simonetta, Nava, Maria Cristina, Graziella, Bruno, Baldassarre, Stefano, Fragapani, Salvatore, Galanti, Giorgio, Mascherini, Gabriele, Petri, Cristian, Stefani, Laura, Girino, Margherita, Piccinelli, Valeria, Nasso, Francesco, Gioffrè, Vincenza, Pasquale, Maria, Scattolin, Giuseppe, Martinelli, Sergio, Turrin, Mauro, Sechi, Leonardo, Catena, Cristina, Colussi, Gianluca, Nieves, Ramirez Duque, Alberto, Muela Molinero, Pedro, Abad Requejo, Vanessa, Lopez Pelaez, Lara, Tamargo, Xavier, Corbella Viros, Francesc, Formiga, Jesus, Diez Manglano, Esperanza, Bejarano Tello, Esther, Del Corral Behamonte, Maria, Sevil Puras, Romero, Manuel, Blanca, Pinilla Llorente, Cristina, Lopez Gonzalez-Cobos, Victoria, Villalba Garcia M., Saez, Lopez, Bosco, Juan, Susana, Sanz Baena, Marta, Arroyo Gallego, Concepcion, Gonzalez Becerra, Antonio, Fernandez Moyano, Hernandez, Mercedes Gomez, Borrego, Manuel Poyato, Raquel, Pacheco Cuadros, Florencia, Perez Rojas, Beatriz, Garcia Olid, Sara, Carrascosa Garcia, Alfonso, Gonzalez-Cruz Cervellera, Marta, Peinado Martinez, Garcia, Sara Carrascosa, Alberto, Ruiz Cantero, Antonio, Albarracín Arraigosa, Montserrat, Godoy Guerrero, Ángel, Barón Ramos Miguel, Manuel, Machin Jose, Ignacio, Novo Veleiro, Lucía, Alvela Suarez, Alfonso, Lopez, David, Rubal Bran, Iria, Iñiguez Vazquez, Monica, Rios Prego, Paciullo F., Proietti M., Bianconi V., Nobili A., Pirro M., Mannucci P.M., Lip G.Y.H., Lupattelli G., Tettamanti M., Pasina L., Franchi C., Perticone F., Salerno F., Corrao S., Marengoni A., Licata G., Violi F., Corazza G.R., Marcucci M., Eldin T.K., Di Blanca M.P.D., Lanzo G., Astuto S., Ardoino I., Cortesi L., Prisco D., Silvestri E., Cenci C., Emmi G., Biolo G., Guarnieri G., Zanetti M., Fernandes G., Chiuch M., Vanoli M., Grignani G., Casella G., Pulixi E.A., Bernardi M., Bassi S.L., Santi L., Zaccherini G., Mannarino E., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Salvatore T., Sasso F.C., Girelli D., Olivieri O., Matteazzi T., Barbagallo M., Plances L., Alcamo R., Calvo L., Valenti M., Zoli M., Arno R., Pasini F.L., Capecchi P.L., Bicchi M., Palasciano G., Modeo M.E., Peragine M., Pappagallo F., Pugliese S., Di Gennaro C., Postiglione A., Barbella M.R., De Stefano F., Cappellini M.D., Fabio G., Seghezzi S., De Amicis M.M., Mancarella M., Mari D., Rossi P.D., Damanti S., Ottolini B.B., Bonini G., Miceli E., Lenti M.V., Padula D., Murialdo G., Marra A., Cattaneo F., Secchi M.B., Ghelfi D., Anastasio L., Sofia L., Carbone M., Davi G., Guagnano M.T., Sestili S., Mancuso G., Calipari D., Bartone M., Meroni M.R., Perin P.C., Lorenzati B., Gruden G., Bruno G., Amione C., Fornengo P., Tassara R., Melis D., Rebella L., Delitala G., Pretti V., Masala M.S., Pes C., Bolondi L., Rasciti L., Serio I., Fanelli F.R., Amoroso A., Molfino A., Petrillo E., Zuccala G., Franceschi F., De Marco G., Chiara C., Marta S., D'Aurizio G., Romanelli G., Amolini C., Chiesa D., Picardi A., Gentilucci U.V., Gallo P., Annoni G., Corsi M., Zazzetta S., Bellelli G., Szabo H., Arturi F., Succurro E., Rubino M., Sesti G., Loria P., Becchi M.A., Martucci G., Fantuzzi A., Maurantonio M., Serra M.G., Bleve M.A., Gasbarrone L., Sajeva M.R., Brucato A., Ghidoni S., Di Corato P., Agnelli G., Marchesini E., Fabris F., Carlon M., Turatto F., Baritusso A., Amabile A., Omenetto E., Scarinzi P., Manfredini R., Molino C., Pala M., Fabbian F., Boari B., De Giorgi A., Paolisso G., Rizzo M.R., Laieta M.T., Rini G., Mansueto P., Pepe I., Borghi C., Strocchi E., De Sando V., Pareo I., Sabba C., Vella F.S., Suppressa P., Valerio R., Agosti P., Fontana F., Loparco F., Capobianco C., Fenoglio L., Bracco C., Giraudo A.V., Testa E., Serraino C., Fargion S., Bonara P., Periti G., Porzio M., Tiraboschi S., Peyvandi F., Tedeschi A., Rossio R., Ferrari B., Monzani V., Savojardo V., Folli C., Magnini M., Conca A., Gobbo G., Pallini G., Balduini C.L., Bertolino G., Provini S., Quaglia F., Dallegri F., Ottonello L., Liberale L., Chin W.S., Carassale L., Caporotundo S., Traisci G., De Feudis L., Di Carlo S., Liberato N.L., Buratti A., Tognin T., Bianchi G.B., Giaquinto S., Purrello F., Di Pino A., Piro S., Rozzini R., Falanga L., Spazzini E., Montrucchio G., Greco E., Tizzani P., Petitti P., Perciccante A., Coralli A., Salmi R., Gaudenzi P., Gamberini S., Semplicini A., Gottardo L., Vendemiale G., Serviddio G., Forlano R., Masala C., Mammarella A., Raparelli V., Basili S., Perri L., Landolfi R., Montalto M., Mirijello A., Vallone C., Bellusci M., Setti D., Pedrazzoli F., Guasti L., Castiglioni L., Maresca A., Squizzato A., Molaro M., Bertolotti M., Mussi C., Libbra M.V., Miceli A., Pellegrini E., Carulli L., Veltri F., Sciacqua A., Quero M., Bagnato C., Colangelo L., Falbo T., De Giorgio R., Serra M., Grasso V., Ruggeri E., Ilaria B., Salvi A., Leonardi R., Grassini C., Mascherona I., Minelli G., Maltese F., Damiani G., Capeci W., Mattioli M., Martino G.P., Biondi L., Ormas M., Pettinari P., Romiti R., Messina S., Cavallaro F., Ghio R., Favorini S., Col A.D., Minisola S., Afeltra A., Alemanno P., Marigliano B., Pipita M.E., Castellino P., Blanco J., Zanoli L., Cattaneo M., Fracasso P., Amoruso M.V., Saracco V., Fogliati M., Bussolino C., Durante V., Eusebi G., Tirotta D., Mete F., Gino M., Cittadini A., Vigorito C., Arcopinto M., Salzano A., Bobbio E., Marra A.M., Sirico D., Moreo G., Scopelliti F., Gasparini F., Cocca M., Ballestrero A., Ferrando F., Berra S., Dassi S., Nava M.C., Graziella B., Baldassarre S., Fragapani S., Galanti G., Mascherini G., Petri C., Stefani L., Girino M., Piccinelli V., Nasso F., Gioffre V., Pasquale M., Scattolin G., Martinelli S., Turrin M., Sechi L., Catena C., Colussi G., Nieves R.D., Alberto M.M., Pedro A.R., Vanessa L.P., Lara T., Xavier C.V., Francesc F., Jesus D.M., Esperanza B.T., Esther D.C.B., Maria S.P., Romero M., Blanca P.L., Cristina L.G.-C., Victoria V.G.M., Saez L., Bosco J., Susana S.B., Marta A.G., Concepcion G.B., Antonio F.M., Hernandez M.G., Borrego M.P., Raquel P.C., Florencia P.R., Beatriz G.O., Sara C.G., Alfonso G.-C.C., Marta P.M., Garcia S.C., Alberto R.C., Antonio A.A., Montserrat G.G., Angel B.R.M., Manuel M.J., Ignacio N.V., Lucia A.S., Alfonso L., David R.B., Iria I.V., Monica R.P., Paciullo, Francesco, Proietti, Marco, Bianconi, Vanessa, Nobili, Alessandro, Pirro, Matteo, Mannucci, Pier Mannuccio, Lip, Gregory Y. H., Lupattelli, Graziana, Tettamanti, Mauro, Pasina, Luca, Franchi, Carlotta, Perticone, Francesco, Salerno, Francesco, Corrao, Salvatore, Marengoni, Alessandra, Licata, Giuseppe, Violi, Francesco, Corazza, Gino Roberto, Marcucci, Maura, Eldin, Tarek Kamal, Di Blanca, Maria Pia Donatella, Lanzo, Giovanna, Astuto, Sarah, Ardoino, Ilaria, Cortesi, Laura, Prisco, Domenico, Silvestri, Elena, Cenci, Caterina, Emmi, Giacomo, Biolo, Gianni, Guarnieri, Gianfranco, Zanetti, Michela, Fernandes, Giovanni, Chiuch, Massimiliano, Vanoli, Massimo, Grignani, Giulia, Casella, Gianluca, Pulixi, Edoardo Alessandro, Bernardi, Mauro, Bassi, Silvia Li, Santi, Luca, Zaccherini, Giacomo, Mannarino, Elmo, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Palazzuoli, Alberto, Salvatore, Teresa, Sasso, Ferdinando Carlo, Girelli, Domenico, Olivieri, Oliviero, Matteazzi, Thoma, Barbagallo, Mario, Plances, Lidia, Alcamo, Roberta, Calvo, Luigi, Valenti, Maria, Zoli, Marco, Arnò, Raffaella, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Bicchi, Maurizio, Palasciano, Giuseppe, Modeo, Maria Ester, Peragine, Maria, Pappagallo, Fabrizio, Pugliese, Stefania, Di Gennaro, Carla, Postiglione, Alfredo, Barbella, Maria Rosaria, de Stefano, Francesco, Cappellini, Maria Domenica, Fabio, Giovanna, Seghezzi, Sonia, de Amicis, Margherita Migone, Mancarella, Marta, Mari, Daniela, Rossi, Paolo Dionigi, Damanti, Sarah, Ottolini, Barbara Brignolo, Bonini, Giulia, Miceli, Emanuela, Lenti, Marco Vincenzo, Padula, Donatella, Murialdo, Giovanni, Marra, Alessio, Cattaneo, Federico, Secchi, Maria Beatrice, Ghelfi, Davide, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Davì, Giovanni, Guagnano, Maria Teresa, Sestili, Simona, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mosè, Meroni, Maria Rachele, Perin, Paolo Cavallo, Lorenzati, Bartolomeo, Gruden, Gabriella, Bruno, Graziella, Amione, Cristina, Fornengo, Paolo, Tassara, Rodolfo, Melis, Deborah, Rebella, Lara, Delitala, Giuseppe, Pretti, Vincenzo, Masala, Maristella Salvatora, Pes, Chiara, Bolondi, Luigi, Rasciti, Leonardo, Serio, Ilaria, Fanelli, Filippo Rossi, Amoroso, Antonio, Molfino, Alessio, Petrillo, Enrico, Zuccalà, Giuseppe, Franceschi, Francesco, de Marco, Guido, Chiara, Cordischi, Marta, Sabbatini, D’Aurizio, Gabriella, Romanelli, Giuseppe, Amolini, Claudia, Chiesa, Deborah, Picardi, Antonio, Gentilucci, Umberto Vespasiani, Gallo, Paolo, Annoni, Giorgio, Corsi, Maurizio, Zazzetta, Sara, Bellelli, Giuseppe, Szabo, Hajnalka, Arturi, Franco, Succurro, Elena, Rubino, Mariangela, Sesti, Giorgio, Loria, Paola, Becchi, Maria Angela, Martucci, Gianfranco, Fantuzzi, Alessandra, Maurantonio, Mauro, Serra, Maria Grazia, Bleve, Maria Antonietta, Gasbarrone, Laura, Sajeva, Maria Rosaria, Brucato, Antonio, Ghidoni, Silvia, Di Corato, Paola, Agnelli, Giancarlo, Marchesini, Emanuela, Fabris, Fabrizio, Carlon, Michela, Turatto, Francesca, Baritusso, Aldo, Amabile, Annalisa, Omenetto, Elisabetta, Scarinzi, Paolo, Manfredini, Roberto, Molino, Christian, Pala, Marco, Fabbian, Fabio, Boari, Benedetta, de Giorgi, Alfredo, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Laieta, Maria Teresa, Rini, Giovanbattista, Mansueto, Pasquale, Pepe, Ilenia, Borghi, Claudio, Strocchi, Enrico, de Sando, Valeria, Pareo, Ilaria, Sabbà, Carlo, Vella, Francesco Saverio, Suppressa, Patrizia, Valerio, Raffaella, Agosti, Pasquale, Fontana, Flavia, Loparco, Francesca, Capobianco, Caterina, Fenoglio, Luigi, Bracco, Christian, Giraudo, Alessia Valentina, Testa, Elisa, Serraino, Cristina, Fargion, Silvia, Bonara, Paola, Periti, Giulia, Porzio, Marianna, Tiraboschi, Slivia, Peyvandi, Flora, Tedeschi, Alberto, Rossio, Raffaella, Ferrari, Barbara, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Magnini, Maria, Conca, Alessio, Gobbo, Giulia, Pallini, Giada, Valenti, Miriam, Balduini, Carlo L., Bertolino, Giampiera, Provini, Stella, Quaglia, Federica, Dallegri, Franco, Ottonello, Luciano, Liberale, Luca, Chin, Wu Sheng, Carassale, Laura, Caporotundo, Silvia, Traisci, Giancarlo, de Feudis, Lucrezia, Di Carlo, Silvia, Liberato, Nicola Lucio, Buratti, Alberto, Tognin, Tiziana, Bianchi, Giovanni Battista, Giaquinto, Sabrina, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Rozzini, Renzo, Falanga, Lina, Spazzini, Elena, Montrucchio, Giuseppe, Greco, Elisabetta, Tizzani, Pietro, Petitti, Paolo, Perciccante, Antonio, Coralli, Alessia, Salmi, Raffaella, Gaudenzi, Piergiorgio, Gamberini, Susanna, Semplicini, Andrea, Gottardo, Lucia, Vendemiale, Gianluigi, Serviddio, Gaetano, Forlano, Roberta, Masala, Cesare, Mammarella, Antonio, Raparelli, Valeria, Basili, Stefania, Perri, Ludovica, Landolfi, Raffaele, Montalto, Massimo, Mirijello, Antonio, Vallone, Carla, Bellusci, Martino, Setti, Donatella, Pedrazzoli, Filippo, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Molaro, Marta, Bertolotti, Marco, Mussi, Chiara, Libbra, Maria Vittoria, Miceli, Andrea, Pellegrini, Elisa, Carulli, Lucia, Veltri, Francesca, Sciacqua, Angela, Quero, Michele, Bagnato, Chiara, Colangelo, Lidia, Falbo, Tania, de Giorgio, Roberto, Serra, Mauro, Grasso, Valentina, Ruggeri, Eugenio, Ilaria, Benzoni, Salvi, Andrea, Leonardi, Roberto, Grassini, Chiara, Mascherona, Ilenia, Minelli, Giorgio, Maltese, Francesca, Damiani, Giampaolo, Capeci, William, Mattioli, Massimo, Martino, Giuseppe Pio, Biondi, Lorenzo, Ormas, Monica, Pettinari, Pietro, Romiti, Roberto, Messina, Silvia, Cavallaro, Federica, Ghio, Riccardi, Favorini, Serena, Col, Anna Dal, Minisola, Salvatore, Colangelo, Luciano, Afeltra, Antonella, Alemanno, Pamela, Marigliano, Benedetta, Pipita, Maria Elena, Castellino, Pietro, Blanco, Julien, Zanoli, Luca, Cattaneo, Marco, Fracasso, Paola, Amoruso, Maria Valentina, Saracco, Valter, Fogliati, Marisa, Bussolino, Carlo, Durante, Vittorio, Eusebi, Giovanna, Tirotta, Daniela, Mete, Francesca, Gino, Miriam, Cittadini, Antonio, Vigorito, Carlo, Arcopinto, Michele, Salzano, Andrea, Bobbio, Emanuele, Marra, Alberto Maria, Sirico, Domenico, Moreo, Guido, Scopelliti, Francesco, Gasparini, Francesca, Cocca, Melissa, Ballestrero, Alberto, Ferrando, Fabio, Berra, Sergio, Dassi, Simonetta, Nava, Maria Cristina, Graziella, Bruno, Baldassarre, Stefano, Fragapani, Salvatore, Galanti, Giorgio, Mascherini, Gabriele, Petri, Cristian, Stefani, Laura, Girino, Margherita, Piccinelli, Valeria, Nasso, Francesco, Gioffrè, Vincenza, Pasquale, Maria, Scattolin, Giuseppe, Martinelli, Sergio, Turrin, Mauro, Sechi, Leonardo, Catena, Cristina, Colussi, Gianluca, Nieves, Ramirez Duque, Alberto, Muela Molinero, Pedro, Abad Requejo, Vanessa, Lopez Pelaez, Lara, Tamargo, Xavier, Corbella Viro, Francesc, Formiga, Jesus, Diez Manglano, Esperanza, Bejarano Tello, Esther, Del Corral Behamonte, Maria, Sevil Pura, Romero, Manuel, Blanca, Pinilla Llorente, Cristina, Lopez Gonzalez-Cobo, Victoria, Villalba Garcia M., Saez, Lopez, Bosco, Juan, Susana, Sanz Baena, Marta, Arroyo Gallego, Concepcion, Gonzalez Becerra, Antonio, Fernandez Moyano, Hernandez, Mercedes Gomez, Borrego, Manuel Poyato, Raquel, Pacheco Cuadro, Florencia, Perez Roja, Beatriz, Garcia Olid, Sara, Carrascosa Garcia, Alfonso, Gonzalez-Cruz Cervellera, Marta, Peinado Martinez, Garcia, Sara Carrascosa, Alberto, Ruiz Cantero, Antonio, Albarracín Arraigosa, Montserrat, Godoy Guerrero, Ángel, Barón Ramos Miguel, Manuel, Machin Jose, Ignacio, Novo Veleiro, Lucía, Alvela Suarez, Alfonso, Lopez, David, Rubal Bran, Iria, Iñiguez Vazquez, Monica, Rios Prego, De Stefano, Francesco, De Amicis, Margherita Migone, De Marco, Guido, De Giorgi, Alfredo, De Sando, Valeria, De Feudis, Lucrezia, De Giorgio, Roberto, Mannucci, Pm, Nobili, A, Tettamanti, M, Pasina, L, Franchi, C, Perticone, F, Salerno, F, Corrao, S, Marengoni, A, Licata, G, Violi, F, Corazza, Gr, Marcucci, M, Eldin, Tk, Di Blanca, Mpd, Lanzo, G, Astuto, S, Ardoino, I, Cortesi, L, Prisco, D, Silvestri, E, Cenci, C, Emmi, G, Biolo, G, Guarnieri, G, Zanetti, M, Fernandes, G, Chiuch, M, Vanoli, M, Grignani, G, Casella, G, Pulixi, Ea, Bernardi, M, Bassi, Sl, Santi, L, Zaccherini, G, Mannarino, E, Lupattelli, G, Bianconi, V, Paciullo, F, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Salvatore, T, Sasso, Fc, Girelli, D, Olivieri, O, Matteazzi, T, Barbagallo, M, Plances, L, Alcamo, R, Calvo, L, Valenti, M, Zoli, M, Arnò, R, Pasini, Fl, Capecchi, Pl, Bicchi, M, Palasciano, G, Modeo, Me, Peragine, M, Pappagallo, F, Pugliese, S, Di Gennaro, C, Postiglione, A, Barbella, Mr, De Stefano, F, Cappellini, Md, Fabio, G, Seghezzi, S, De Amicis, Mm, Mancarella, M, Mari, D, Rossi, Pd, Damanti, S, Ottolini, Bb, Bonini, G, Miceli, E, Lenti, Mv, Padula, D, Murialdo, G, Marra, A, Cattaneo, F, Secchi, Mb, Ghelfi, D, Anastasio, L, Sofia, L, Carbone, M, Davì, G, Guagnano, Mt, Sestili, S, Mancuso, G, Calipari, D, Bartone, M, Meroni, Mr, Perin, Pc, Lorenzati, B, Gruden, G, Bruno, G, Amione, C, Fornengo, P, Tassara, R, Melis, D, Rebella, L, Delitala, G, Pretti, V, Masala, M, Pes, C, Bolondi, L, Rasciti, L, Serio, I, Fanelli, Fr, Amoroso, A, Molfino, A, Petrillo, E, Zuccalà, G, Franceschi, F, De Marco, G, Chiara, C, Marta, S, D'Aurizio, G, Romanelli, G, Amolini, C, Chiesa, D, Picardi, A, Gentilucci, Uv, Gallo, P, Annoni, G, Corsi, M, Zazzetta, S, Bellelli, G, Szabo, H, Arturi, F, Succurro, E, Rubino, M, Sesti, G, Loria, P, Becchi, Ma, Martucci, G, Fantuzzi, A, Maurantonio, M, Serra, Mg, Bleve, Ma, Gasbarrone, L, Sajeva, Mr, Brucato, A, Ghidoni, S, Di Corato, P, Agnelli, G, Marchesini, E, Fabris, F, Carlon, M, Turatto, F, Baritusso, A, Amabile, A, Omenetto, E, Scarinzi, P, Manfredini, R, Molino, C, Pala, M, Fabbian, F, Boari, B, De Giorgi, A, Paolisso, G, Rizzo, Mr, Laieta, Mt, Rini, G, Mansueto, P, Pepe, I, Borghi, C, Strocchi, E, De Sando, V, Pareo, I, Sabbà, C, Vella, F, Suppressa, P, Valerio, R, Agosti, P, Fontana, F, Loparco, F, Capobianco, C, Fenoglio, L, Bracco, C, Giraudo, Av, Testa, E, Serraino, C, Fargion, S, Bonara, P, Periti, G, Porzio, M, Tiraboschi, S, Peyvandi, F, Tedeschi, A, Rossio, R, Ferrari, B, Monzani, V, Savojardo, V, Folli, C, Magnini, M, Conca, A, Gobbo, G, Pallini, G, Balduini, Cl, Bertolino, G, Provini, S, Quaglia, F, Dallegri, F, Ottonello, L, Liberale, L, Chin, W, Carassale, L, Caporotundo, S, Traisci, G, De Feudis, L, Di Carlo, S, Liberato, Nl, Buratti, A, Tognin, T, Bianchi, Gb, Giaquinto, S, Purrello, F, Di Pino, A, Piro, S, Rozzini, R, Falanga, L, Spazzini, E, Montrucchio, G, Greco, E, Tizzani, P, Petitti, P, Perciccante, A, Coralli, A, Salmi, R, Gaudenzi, P, Gamberini, S, Semplicini, A, Gottardo, L, Vendemiale, G, Serviddio, G, Forlano, R, Masala, C, Mammarella, A, Raparelli, V, Basili, S, Perri, L, Landolfi, R, Montalto, M, Mirijello, A, Vallone, C, Bellusci, M, Setti, D, Pedrazzoli, F, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Molaro, M, Bertolotti, M, Mussi, C, Libbra, Mv, Miceli, A, Pellegrini, E, Carulli, L, Veltri, F, Sciacqua, A, Quero, M, Bagnato, C, Colangelo, L, Falbo, T, De Giorgio, R, Serra, M, Grasso, V, Ruggeri, E, Ilaria, B, Salvi, A, Leonardi, R, Grassini, C, Mascherona, I, Minelli, G, Maltese, F, Damiani, G, Capeci, W, Mattioli, M, Martino, Gp, Biondi, L, Ormas, M, Pettinari, P, Romiti, R, Messina, S, Cavallaro, F, Ghio, R, Favorini, S, Col, Ad, Minisola, S, Afeltra, A, Alemanno, P, Marigliano, B, Pipita, Me, Castellino, P, Blanco, J, Zanoli, L, Cattaneo, M, Fracasso, P, Amoruso, Mv, Saracco, V, Fogliati, M, Bussolino, C, Durante, V, Eusebi, G, Tirotta, D, Mete, F, Gino, M, Cittadini, A, Vigorito, C, Arcopinto, M, Salzano, A, Bobbio, E, Marra, Am, Sirico, D, Moreo, G, Scopelliti, F, Gasparini, F, Cocca, M, Ballestrero, A, Ferrando, F, Berra, S, Dassi, S, Nava, Mc, Graziella, B, Baldassarre, S, Fragapani, S, Galanti, G, Mascherini, G, Petri, C, Stefani, L, Girino, M, Piccinelli, V, Nasso, F, Gioffrè, V, Pasquale, M, Scattolin, G, Martinelli, S, Turrin, M, Sechi, L, Catena, C, Colussi, G, Nieves, Rd, Alberto, Mm, Pedro, Ar, Vanessa, Lp, Lara, T, Xavier, Cv, Francesc, F, Jesus, Dm, Esperanza, Bt, Esther, Dcb, Maria, Sp, Romero, M, Blanca, Pl, Cristina, Lg, Victoria, Vgm, Saez, L, Bosco, J, Susana, Sb, Marta, Ag, Concepcion, Gb, Antonio, Fm, Hernandez, Mg, Borrego, Mp, Raquel, Pc, Florencia, Pr, Beatriz, Go, Sara, Cg, Alfonso, Gc, Marta, Pm, Garcia, Sc, Alberto, Rc, Antonio, Aa, Montserrat, Gg, Ángel, Brm, Manuel, Mj, Ignacio, Nv, Lucía, A, Alfonso, L, David, Rb, Iria, Iv, Monica, Rp., Paciullo, F., Proietti, M., Bianconi, V., Nobili, A., Pirro, M., Mannucci, P. M., Lip, G. Y. H., Lupattelli, G., Tettamanti, M., Pasina, L., Franchi, C., Perticone, F., Salerno, F., Corrao, S., Marengoni, A., Licata, G., Violi, F., Corazza, G. R., Marcucci, M., Eldin, T. K., Di Blanca, M. P. D., Lanzo, G., Astuto, S., Ardoino, I., Cortesi, L., Prisco, D., Silvestri, E., Cenci, C., Emmi, G., Biolo, G., Guarnieri, G., Zanetti, M., Fernandes, G., Chiuch, M., Vanoli, M., Grignani, G., Casella, G., Pulixi, E. A., Bernardi, M., Bassi, S. L., Santi, L., Zaccherini, G., Mannarino, E., Nuti, R., Valenti, R., Ruvio, M., Cappelli, S., Palazzuoli, A., Salvatore, T., Sasso, F. C., Girelli, D., Olivieri, O., Matteazzi, T., Barbagallo, M., Plances, L., Alcamo, R., Calvo, L., Valenti, M., Zoli, M., Arno, R., Pasini, F. L., Capecchi, P. L., Bicchi, M., Palasciano, G., Modeo, M. E., Peragine, M., Pappagallo, F., Pugliese, S., Di Gennaro, C., Postiglione, A., Barbella, M. R., De Stefano, F., Cappellini, M. D., Fabio, G., Seghezzi, S., De Amicis, M. M., Mancarella, M., Mari, D., Rossi, P. D., Damanti, S., Ottolini, B. B., Bonini, G., Miceli, E., Lenti, M. V., Padula, D., Murialdo, G., Marra, A., Cattaneo, F., Secchi, M. B., Ghelfi, D., Anastasio, L., Sofia, L., Carbone, M., Davi, G., Guagnano, M. T., Sestili, S., Mancuso, G., Calipari, D., Bartone, M., Meroni, M. R., Perin, P. C., Lorenzati, B., Gruden, G., Bruno, G., Amione, C., Fornengo, P., Tassara, R., Melis, D., Rebella, L., Delitala, G., Pretti, V., Masala, M. S., Pes, C., Bolondi, L., Rasciti, L., Serio, I., Fanelli, F. R., Amoroso, A., Molfino, A., Petrillo, E., Zuccala, G., Franceschi, F., De Marco, G., Chiara, C., Marta, S., D'Aurizio, G., Romanelli, G., Amolini, C., Chiesa, D., Picardi, A., Gentilucci, U. V., Gallo, P., Annoni, G., Corsi, M., Zazzetta, S., Bellelli, G., Szabo, H., Arturi, F., Succurro, E., Rubino, M., Sesti, G., Loria, P., Becchi, M. A., Martucci, G., Fantuzzi, A., Maurantonio, M., Serra, M. G., Bleve, M. A., Gasbarrone, L., Sajeva, M. R., Brucato, A., Ghidoni, S., Di Corato, P., Agnelli, G., Marchesini, E., Fabris, F., Carlon, M., Turatto, F., Baritusso, A., Amabile, A., Omenetto, E., Scarinzi, P., Manfredini, R., Molino, C., Pala, M., Fabbian, F., Boari, B., De Giorgi, A., Paolisso, G., Rizzo, M. R., Laieta, M. T., Rini, G., Mansueto, P., Pepe, I., Borghi, C., Strocchi, E., De Sando, V., Pareo, I., Sabba, C., Vella, F. S., Suppressa, P., Valerio, R., Agosti, P., Fontana, F., Loparco, F., Capobianco, C., Fenoglio, L., Bracco, C., Giraudo, A. V., Testa, E., Serraino, C., Fargion, S., Bonara, P., Periti, G., Porzio, M., Tiraboschi, S., Peyvandi, F., Tedeschi, A., Rossio, R., Ferrari, B., Monzani, V., Savojardo, V., Folli, C., Magnini, M., Conca, A., Gobbo, G., Pallini, G., Balduini, C. L., Bertolino, G., Provini, S., Quaglia, F., Dallegri, F., Ottonello, L., Liberale, L., Chin, W. S., Carassale, L., Caporotundo, S., Traisci, G., De Feudis, L., Di Carlo, S., Liberato, N. L., Buratti, A., Tognin, T., Bianchi, G. B., Giaquinto, S., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Spazzini, E., Montrucchio, G., Greco, E., Tizzani, P., Petitti, P., Perciccante, A., Coralli, A., Salmi, R., Gaudenzi, P., Gamberini, S., Semplicini, A., Gottardo, L., Vendemiale, G., Serviddio, G., Forlano, R., Masala, C., Mammarella, A., Raparelli, V., Basili, S., Perri, L., Landolfi, R., Montalto, M., Mirijello, A., Vallone, C., Bellusci, M., Setti, D., Pedrazzoli, F., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Molaro, M., Bertolotti, M., Mussi, C., Libbra, M. V., Miceli, A., Pellegrini, E., Carulli, L., Veltri, F., Sciacqua, A., Quero, M., Bagnato, C., Colangelo, L., Falbo, T., De Giorgio, R., Serra, M., Grasso, V., Ruggeri, E., Ilaria, B., Salvi, A., Leonardi, R., Grassini, C., Mascherona, I., Minelli, G., Maltese, F., Damiani, G., Capeci, W., Mattioli, M., Martino, G. P., Biondi, L., Ormas, M., Pettinari, P., Romiti, R., Messina, S., Cavallaro, F., Ghio, R., Favorini, S., Col, A. D., Minisola, S., Afeltra, A., Alemanno, P., Marigliano, B., Pipita, M. E., Castellino, P., Blanco, J., Zanoli, L., Cattaneo, M., Fracasso, P., Amoruso, M. V., Saracco, V., Fogliati, M., Bussolino, C., Durante, V., Eusebi, G., Tirotta, D., Mete, F., Gino, M., Cittadini, A., Vigorito, C., Arcopinto, M., Salzano, A., Bobbio, E., Marra, A. M., Sirico, D., Moreo, G., Scopelliti, F., Gasparini, F., Cocca, M., Ballestrero, A., Ferrando, F., Berra, S., Dassi, S., Nava, M. C., Graziella, B., Baldassarre, S., Fragapani, S., Galanti, G., Mascherini, G., Petri, C., Stefani, L., Girino, M., Piccinelli, V., Nasso, F., Gioffre, V., Pasquale, M., Scattolin, G., Martinelli, S., Turrin, M., Sechi, L., Catena, C., Colussi, G., Nieves, R. D., Alberto, M. M., Pedro, A. R., Vanessa, L. P., Lara, T., Xavier, C. V., Francesc, F., Jesus, D. M., Esperanza, B. T., Esther, D. C. B., Maria, S. P., Romero, M., Blanca, P. L., Cristina, L. G. -C., Victoria, V. G. M., Saez, L., Bosco, J., Susana, S. B., Marta, A. G., Concepcion, G. B., Antonio, F. M., Hernandez, M. G., Borrego, M. P., Raquel, P. C., Florencia, P. R., Beatriz, G. O., Sara, C. G., Alfonso, G. -C. C., Marta, P. M., Garcia, S. C., Alberto, R. C., Antonio, A. A., Montserrat, G. G., Angel, B. R. M., Manuel, M. J., Ignacio, N. V., Lucia, A. S., Alfonso, L., David, R. B., Iria, I. V., Monica, R. P., Proietti, M, Pirro, M, Mannucci, P, Lip, G, Corazza, G, Eldin, T, Di Blanca, M, Pulixi, E, Bassi, S, Sasso, F, Pasini, F, Capecchi, P, Modeo, M, Barbella, M, de Stefano, F, Cappellini, M, de Amicis, M, Rossi, P, Ottolini, B, Lenti, M, Secchi, M, Guagnano, M, Meroni, M, Perin, P, Fanelli, F, de Marco, G, D’Aurizio, G, Gentilucci, U, Becchi, M, Bleve, M, Sajeva, M, de Giorgi, A, Rizzo, M, Laieta, M, de Sando, V, Giraudo, A, Balduini, C, de Feudis, L, Liberato, N, Bianchi, G, Libbra, M, de Giorgio, R, Martino, G, Col, A, Pipita, M, Amoruso, M, Nava, M, Nieves, R, Alberto, M, Pedro, A, Vanessa, L, Xavier, C, Jesus, D, Esperanza, B, Esther, D, Maria, S, Blanca, P, Cristina, L, Victoria, V, Susana, S, Marta, A, Concepcion, G, Antonio, F, Hernandez, M, Borrego, M, Raquel, P, Florencia, P, Beatriz, G, Sara, C, Alfonso, G, Marta, P, Garcia, S, Alberto, R, Antonio, A, Montserrat, G, Ángel, B, Manuel, M, Ignacio, N, David, R, Iria, I, and Monica, R

Subjects
Male, Anti-Arrhythmia Agents/therapeutic use, antiarrhythmic agent, Comorbidity, Aged, Aged, 80 and over, Anti-Arrhythmia Agents, Atrial Fibrillation, Diabetes Mellitus, Female, Heart Failure, Heart Rate, Hospitalization, Humans, Odds Ratio, Polypharmacy, Prevalence, Geriatrics and Gerontology, Pharmacology (medical), 030204 cardiovascular system & hematology, anticoagulant agent, Diabetes Mellitus/drug therapy, 0302 clinical medicine, 80 and over, 030212 general & internal medicine, LS4_4, antiarrhythmic agent, anticoagulant agent, antithrombocytic agent, calcium channel blocking agent, digoxin, Heart Rate/drug effects, Diabetes Mellitu, Atrial fibrillation, antithrombocytic agent, digoxin, Anti-Arrhythmia Agent, Human, medicine.medical_specialty, Socio-culturale, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Heart rate, calcium channel blocking agent, medicine, business.industry, Atrial Fibrillation/drug therapy, Odds ratio, medicine.disease, Heart Failure/drug therapy, Confidence interval, Heart failure, business
Abstract

Background: Among rate-control or rhythm-control strategies, there is conflicting evidence as to which is the best management approach for non-valvular atrial fibrillation (AF) in elderly patients. Design: We performed an ancillary analysis from the ‘Registro Politerapie SIMI’ study, enrolling elderly inpatients from internal medicine and geriatric wards. Methods: We considered patients enrolled from 2008 to 2014 with an AF diagnosis at admission, treated with a rate-control-only or rhythm-control-only strategy. Results: Among 1114 patients, 241 (21.6%) were managed with observation only and 122 (11%) were managed with both the rate- and rhythm-control approaches. Of the remaining 751 patients, 626 (83.4%) were managed with a rate-control-only strategy and 125 (16.6%) were managed with a rhythm-control-only strategy. Rate-control-managed patients were older (p=0.002), had a higher Short Blessed Test (SBT; p=0.022) and a lower Barthel Index (p=0.047). Polypharmacy (p=0.001), heart failure (p=0.005) and diabetes (p=0.016) were more prevalent among these patients. Median CHA2DS2-VASc score was higher among rate-control-managed patients (p=0.001). SBT [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94–1.00, p=0.037], diabetes (OR 0.48, 95% CI 0.26–0.87, p=0.016) and polypharmacy (OR 0.58, 95% CI 0.34–0.99, p=0.045) were negatively associated with a rhythm-control strategy. At follow-up, no difference was found between rate- and rhythm-control strategies for cardiovascular (CV) and all-cause deaths (6.1 vs. 5.6%, p=0.89; and 15.9 vs. 14.1%, p=0.70, respectively). Conclusion: A rate-control strategy is the most widely used among elderly AF patients with multiple comorbidities and polypharmacy. No differences were evident in CV death and all-cause death at follow-up.

Published
2018
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10. Determinants of change in polypharmacy status in Switzerland: the population-based CoLaus study

Author

Pedro Marques-Vidal, Julien Castioni, Gérard Waeber, Peter Vollenweider, and Nazanin Abolhassani

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Population, Population based, 030204 cardiovascular system & hematology, Overweight, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Diabetes mellitus, medicine, Diabetes Mellitus, Prevalence, Humans, Hypoglycemic Agents, Pharmacology (medical), 030212 general & internal medicine, education, Life Style, Aged, Dyslipidemias, Pharmacology, Polypharmacy, education.field_of_study, Analgesics, Psychotropic Drugs, business.industry, Smoking, Cardiovascular Agents, General Medicine, Middle Aged, medicine.disease, Analgesics/therapeutic use, Cardiovascular Agents/therapeutic use, Diabetes Mellitus/drug therapy, Diabetes Mellitus/epidemiology, Dyslipidemias/drug therapy, Dyslipidemias/epidemiology, Female, Hypertension/drug therapy, Hypertension/epidemiology, Hypoglycemic Agents/therapeutic use, Overweight/drug therapy, Overweight/epidemiology, Psychotropic Drugs/therapeutic use, Smoking/drug therapy, Smoking/epidemiology, Switzerland/epidemiology, Determinants, General population, Switzerland, Trends, Obesity, Cardiovascular agent, Hypertension, medicine.symptom, business, Dyslipidemia, Demography
Abstract

This study aimed to assess the prevalence, the change, and the determinants of change in polypharmacy in a population-based sample. Baseline (2003–2006) and follow-up (2009–2012) data are from 4679 participants aged between 35 and 75 years (53.5% women, mean age 52.6 ± 10.6 years) from the population of Lausanne, Switzerland. Polypharmacy was defined by the regular use of ≥5 drugs. Four categories of change were defined: never (no polypharmacy at baseline and follow-up), initiating (no polypharmacy at baseline but at follow-up), maintaining, or quitting. Polypharmacy increased from 7.7% at baseline to 15.3% at follow-up. Cardiovascular drugs were the most prescribed medicines at baseline and follow-up. Gender, age, obesity, smoking, previously diagnosed hypertension, or diabetes or dyslipidemia were significantly and independently associated with initiating and maintaining polypharmacy. In a population-based sample, prevalence of polypharmacy doubled over a 5.6-year period. The main determinants of initiating polypharmacy were age, overweight and obesity, smoking status, and previously diagnosed cardiovascular risk factors.

Published
2017

11. Design and rationale of a large, international, prospective cohort study to evaluate the occurrence of malformations and perinatal/neonatal death using insulin detemir in pregnant women with diabetes in comparison with other long-acting insulins

Author

Sofia I. I. Kring, Henning F. Andersen, Peter Damm, and Elisabeth R. Mathiesen

Subjects
Adult, medicine.medical_specialty, medicine.medical_treatment, Perinatal Death, Insulin Detemir/adverse effects, Pregnancy in Diabetics, 030209 endocrinology & metabolism, Type 2 diabetes, Diabetes Mellitus/drug therapy, Hypoglycemic Agents/adverse effects, Pregnancy in Diabetics/drug therapy, 03 medical and health sciences, Study Protocol, 0302 clinical medicine, Insulin Detemir, Pregnancy, Diabetes mellitus, Obstetrics and Gynaecology, medicine, Diabetes Mellitus, Abnormalities, Drug-Induced/epidemiology, Humans, Hypoglycemic Agents, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Insulin detemir, Obstetrics, business.industry, Insulin, Diabetes, Infant, Newborn, Obstetrics and Gynecology, Abnormalities, Drug-Induced, medicine.disease, Basal (medicine), Research Design, Perinatal Death/etiology, Female, business, Cohort study, medicine.drug
Abstract

Background There are a lack of data regarding the effect of basal insulin analogues on rates of events like congenital malformation and perinatal mortality in diabetic pregnancy. Methods The present study is a prospective, non-interventional, multicentre cohort study conducted in seven countries, designed to assess the safety of insulin detemir during pregnancy, and to monitor the health status of resulting infants (exposed in utero) up to 1 year of age. The study population includes women with type 1 or type 2 diabetes, who are pregnant and being treated with insulin. Data will be collected in the context of routine practice. The primary endpoint is the proportion of pregnancies in women treated with insulin detemir, compared with other basal insulin regimens, which do not result in any of the following events: major congenital malformations, perinatal death or neonatal death. A sample size of 3075 pregnancies was calculated to provide an 80% power to detect a difference of 3.5% between groups in the primary endpoint at a 5% level. Discussion The study will also examine other important maternal endpoints (e.g., incidences of severe hypoglycaemia and pre-eclampsia) and perinatal outcomes such as overweight neonates, as well as infant outcomes at 1 year of age. It has a fixed recruitment period from 2013 to 2018, enrolling all eligible patients, and is expected to inform future prescribing with basal insulins in diabetic pregnancy. Trial registration ClinicalTrials.gov: NCT01892319 (date registered: 27.06.2013). Electronic supplementary material The online version of this article (doi:10.1186/s12884-016-1177-4) contains supplementary material, which is available to authorized users.

Published
2017
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12. Artemisinins Target GABA A Receptor Signaling and Impair α Cell Identity

Author

Sara Sdelci, Tibor Harkany, Keiryn L. Bennett, Kilian Huber, Patrick Collombat, Christian Honoré, Florian M. Pauler, Matthias Farlik, Ekaterine Berishvili, Monica Courtney, Igor Baburin, Stefan Kubicek, Nicole Schmitner, Jin Li, Steffen Hering, Peter Májek, Jacob Hecksher-Sørensen, Thierry Sulpice, Martin Distel, Robin A. Kimmel, Charles-Hugues Lardeau, Manuela Gridling, Johanna Klughammer, Camilla Ingvorsen, Alexey Stukalov, Christoph Bock, Andhira Vieira, François Briand, Giulio Superti-Furga, Roman A. Romanov, Thomas Frogne, Dirk Meyer, Caterina Sturtzel, Thomas Penz, Fabio Avolio, Katja Parapatics, Jacques Colinge, Andreas Spittler, Charlotte Barbieux, Tamara Casteels, Harbin Engineering University (HRBEU), Research Center for Molecular Medicine of the Austrian Academy of Sciences [Vienna, Austria] (CeMM ), Austrian Academy of Sciences (OeAW), CeMM Research Center for Molecular Medicine [Vienna, Austria], Novo Nordisk A/S , Danemark, Novo Nordisk, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institute for Research on Cancer and Aging, Nice (IRCAN), INSERM, U1081, CNRS UMR 7284, Nice, Innsbruck Medical University [Austria] (IMU), Leopold Franzens Universität Innsbruck - University of Innsbruck, Medizinische Universität Wien = Medical University of Vienna, Karolinska Institutet [Stockholm], Tumor Immunology [Vienna, Austria] (Children’s Cancer Research Institute), St. Anna Kinderkrebsforschung e.V. [Vienna, Austria], CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria, Physiological Chemistry, Biocenter, Am Hubland, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), IBM PSSC Montpellier - Innovation Lab., IBM PSSC Montpellier, Physiogenex, University of Geneva [Switzerland], Geneva University Hospital (HUG), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Children’s Cancer Research Institute [Vienna, Austria], University of Vienna [Vienna], Cancer Center Karolinska [Karolinska Institutet] (CCK), Directors's Laboratory, Novo Nordisk Foundation Center for Biosustainability, and Technical University of Denmark [Lyngby] (DTU)

Subjects
0301 basic medicine, insulin secretion, Artemisinins/administration & dosage/pharmacology, β cell, Carrier Proteins/metabolism, Diabetes Mellitus/drug therapy, Mice, Single-cell analysis, Insulin-Secreting Cells, GABA-receptor signaling, Insulin, artemisinins, gamma-Aminobutyric Acid/metabolism, Cells, Cultured, Zebrafish, gamma-Aminobutyric Acid, pancreatic endocrine transdifferentiation, ddc:617, biology, diabetes, Protein Stability, Receptors, GABA-A/metabolism, Transdifferentiation, Diabetes Mellitus, Type 1/drug therapy/pathology, 3. Good health, Cell biology, medicine.anatomical_structure, Biochemistry, ARX translocation, Artemether, MESH: Animals, Disease models, animal, Insulin/Genetics, Signal transduction, Artemisinins/Pharmacology, Single-Cell Analysis, Signal Transduction, Cell type, regenerative medicine, chemical biology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Transdifferentiation/drug effects, Article, General Biochemistry, Genetics and Molecular Biology, Diabetes Mellitus, Experimental, Islets of Langerhans, 03 medical and health sciences, Genetic model, Protein Stability/drug effects, Diabetes Mellitus, medicine, Homeodomain Proteins/metabolism, Regeneration, Animals, Humans, Transcription Factors/metabolism, Transcription factor, Homeodomain Proteins, Insulin/genetics/metabolism, Gephyrin, Biochemistry, Genetics and Molecular Biology(all), Gene Expression Profiling, Pancreatic islets, Membrane Proteins, Islets of Langerhans/drug effects, Receptors, GABA-A, gephyrin, Rats, Disease Models, Animal, Diabetes Mellitus, Type 1, 030104 developmental biology, Cell Transdifferentiation, biology.protein, Membrane Proteins/metabolism, Carrier Proteins, Transcription Factors
Abstract

Summary Type 1 diabetes is characterized by the destruction of pancreatic β cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types, including glucagon-producing α cells. In a genetic model, loss of the master regulatory transcription factor Arx is sufficient to induce the conversion of α cells to functional β-like cells. Here, we identify artemisinins as small molecules that functionally repress Arx by causing its translocation to the cytoplasm. We show that the protein gephyrin is the mammalian target of these antimalarial drugs and that the mechanism of action of these molecules depends on the enhancement of GABAA receptor signaling. Our results in zebrafish, rodents, and primary human pancreatic islets identify gephyrin as a druggable target for the regeneration of pancreatic β cell mass from α cells., Graphical Abstract, Highlights • Artemisinins inhibit ARX function and impair α cell identity • Compounds act by stabilizing gephyrin, thus enhancing GABAA receptor signaling • Artemisinins increase β cell mass in zebrafish and rodent models • Functional and transcriptional data indicate a conserved phenotype in human islets, The anti-malarial drug Artemisinin can drive the in vivo conversion of pancreatic α cells into functional β-like cells through enhanced GABA signaling and may have potential as a therapeutic for diabetes.

Published
2017
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13. Polypharmacy and specific comorbidities in university primary care settings

Author

Carole E. Aubert, Bruno R. da Costa, Sven Streit, Jacques Cornuz, Nicolas Rodondi, Drahomir Aujesky, Tinh-Hai Collet, Jean-Michel Gaspoz, and Doug C. Bauer

Subjects
Male, Pediatrics, Databases, Factual, Cross-sectional study, Inappropriate Prescribing, Comorbidity, 030204 cardiovascular system & hematology, Diabetes Mellitus/drug therapy, Hospitals, University, 0302 clinical medicine, 80 and over, Renal Insufficiency, 030212 general & internal medicine, Aged, 80 and over, Hypertension/drug therapy, Pharmacoepidemiology, Middle Aged, Hospitals, 3. Good health, Cardiovascular Diseases, Hypertension, symbols, Female, Switzerland, medicine.medical_specialty, Chronic/drug therapy, Aged, Cardiovascular Diseases/drug therapy, Cross-Sectional Studies, Humans, Inappropriate Prescribing/statistics & numerical data, Logistic Models, Multivariate Analysis, Polypharmacy, Primary Health Care, Renal Insufficiency, Chronic/drug therapy, Comorbidities, Inappropriate prescribing, Multimorbidity, Databases, 03 medical and health sciences, symbols.namesake, Internal medicine, mental disorders, Internal Medicine, medicine, Diabetes Mellitus, Poisson regression, Renal Insufficiency, Chronic, Factual, ddc:613, University, business.industry, Odds ratio, medicine.disease, business, Body mass index, Kidney disease
Abstract

Aims Polypharmacy is associated with adverse events and multimorbidity, but data are limited on its association with specific comorbidities in primary care settings. We measured the prevalence of polypharmacy and inappropriate prescribing, and assessed the association of polypharmacy with specific comorbidities. Methods We did a cross-sectional analysis of 1002 patients aged 50–80 years followed in Swiss university primary care settings. We defined polypharmacy as ≥ 5 long-term prescribed drugs and multimorbidity as ≥ 2 comorbidities. We used logistic mixed-effects regression to assess the association of polypharmacy with the number of comorbidities, multimorbidity, specific sets of comorbidities, potentially inappropriate prescribing (PIP) and potential prescribing omission (PPO). We used multilevel mixed-effects Poisson regression to assess the association of the number of drugs with the same parameters. Results Patients (mean age 63.5 years, 67.5% ≥ 2 comorbidities, 37.0% ≥ 5 drugs) had a mean of 3.9 (range 0–17) drugs. Age, BMI, multimorbidity, hypertension, diabetes mellitus, chronic kidney disease, and cardiovascular diseases were independently associated with polypharmacy. The association was particularly strong for hypertension (OR 8.49, 95%CI 5.25–13.73), multimorbidity (OR 6.14, 95%CI 4.16–9.08), and oldest age (75–80 years: OR 4.73, 95%CI 2.46–9.10 vs.50–54 years). The prevalence of PPO was 32.2% and PIP was more frequent among participants with polypharmacy (9.3% vs. 3.2%, p Conclusions Polypharmacy is common in university primary care settings, is strongly associated with hypertension, diabetes mellitus, chronic kidney disease and cardiovascular diseases, and increases potentially inappropriate prescribing. Multimorbid patients should be included in further trials for developing adapted guidelines and avoiding inappropriate prescribing.

Published
2016

14. Use of metformin and survival of diabetic women with breast cancer

Author

Paul J.H.L. Peeters, Marloes T Bazelier, Marjanka K. Schmidt, Frank de Vries, Hubert G. M. Leufkens, Peter Vestergaard, and Marie L. De Bruin

Subjects
Research design, Survival, type 2 diabetes mellitus, Denmark, Comorbidity, Toxicology, Diabetes Mellitus/drug therapy, Cohort Studies, Breast cancer, 0302 clinical medicine, Risk Factors, 80 and over, Pharmacology (medical), Registries, Young adult, Cause of death, Aged, 80 and over, 0303 health sciences, Middle Aged, Metformin, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Cohort study, medicine.drug, Adult, medicine.medical_specialty, Breast Neoplasms/complications, Adolescent, Breast Neoplasms, Hypoglycemic Agents/therapeutic use, Article, Young Adult, 03 medical and health sciences, Internal medicine, Diabetes Mellitus, medicine, Hypoglycemic Agents, Humans, Metformin/therapeutic use, Aged, 030304 developmental biology, Pharmacology, Gynecology, business.industry, medicine.disease, mortality, Denmark/epidemiology, Discontinuation, business, Follow-Up Studies
Abstract

OBJECTIVE: This study was set out to determine whether metformin use influences survival in breast cancer patients treated with antidiabetic drugs as compared to non-users.RESEARCH DESIGN AND METHODS: We used data from the Danish national registries (1996-2008) to identify adult female patients diagnosed with breast cancer who were prescribed antidiabetic medication. We performed multivariate Coxproportional hazard regression to assess all-cause and breast cancer-specific mortality risks associated with metformin exposure. In a secondary analysis, we stratified use of metformin according to the cumulative number of prescriptions.RESULTS: Of the 1058 breast cancer patients 349 died during follow-up, with breast cancer listed as the primary cause of death for 152 cases. Compared to non-use, current metformin treatment was associated with a significant reduction in overall mortality (adjusted HR 0.74, 95% CI, 0.58-0.96). For breast cancer-specific mortality, a non-significant risk reduction (adjusted HR 0.88, 95% CI, 0.59-1.29) was observed, which became significant after stratification according to cumulative number of prescriptions. An increased risk of both overall and breast cancer-specific mortality was observed in the first 12 months after discontinuation of metformin.CONCLUSIONS: We observed a nonsignificant reduction in breast cancer-specific mortality associated with metformin exposure among breast cancer patients treated with antidiabetic drugs. However, our findings suggest that long-term metformin use may have a beneficial effect on survival in patients with breast cancer. Further confirmation of these findings is needed.

Published
2013
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15. Endothelial small-conductance and intermediate-conductance KCa channels:An Update on Their Pharmacology and Usefulness as Cardiovascular Targets

Author

Heike Wulff and Ralf Köhler

Subjects
Endothelium, Vascular/drug effects, Ataxia, Vascular smooth muscle, Small-Conductance Calcium-Activated Potassium Channels, Biological Factors/metabolism, Pharmacology, Biology, Apamin, KCa3.1, KCa2.3, Article, Diabetes Mellitus/drug therapy, Bursting, chemistry.chemical_compound, Biological Factors, action potential, medicine, Diabetes Mellitus, endothelium-derived hyperpolarization, Humans, Animals, Molecular Targeted Therapy, B cell, lymphocyte activation, small/intermediate-conductance calcium-activated K+ channel, blood pressure, Afterhyperpolarization, Hyperpolarization (biology), Small-Conductance Calcium-Activated Potassium Channels/drug effects, Intermediate-Conductance Calcium-Activated Potassium Channels, Intermediate-Conductance Calcium-Activated Potassium Channels/drug effects, gating modulation, medicine.anatomical_structure, chemistry, Cardiovascular Diseases, Drug Design, afterhyperpolarizatin, Neuron, Endothelium, Vascular, medicine.symptom, Cardiovascular Diseases/drug therapy, Cardiology and Cardiovascular Medicine
Abstract

Most cardiovascular researchers are familiar with intermediate-conductance KCa3.1 and small-conductance KCa2.3 channels because of their contribution to endothelium-derived hyperpolarization. However, to immunologists and neuroscientists, these channels are primarily known for their role in lymphocyte activation and neuronal excitability. KCa3.1 is involved in the proliferation and migration of T cells, B cells, mast cells, macrophages, fibroblasts, and dedifferentiated vascular smooth muscle cells and is, therefore, being pursued as a potential target for use in asthma, immunosuppression, and fibroproliferative disorders. In contrast, the 3 KCa2 channels (KCa2.1, KCa2.2, and KCa2.3) contribute to the neuronal medium afterhyperpolarization and, depending on the type of neuron, are involved in determining firing rates and frequencies or in regulating bursting. KCa2 activators are accordingly being studied as potential therapeutics for ataxia and epilepsy, whereas KCa2 channel inhibitors like apamin have long been known to improve learning and memory in rodents. Given this background, we review the recent discoveries of novel KCa3.1 and KCa2.3 modulators and critically assess the potential of KCa activators for the treatment of diabetes and cardiovascular diseases by improving endothelium-derived hyperpolarizations.

Published
2013
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16. Prednisolone-induced beta cell dysfunction is associated with impaired endoplasmic reticulum homeostasis in INS-1E cells

Author

Gerard C.M. van der Zon, Michaela Diamant, Wim H. A. Dokter, D. Margriet Ouwens, Margot M. Linssen, Daniël H. van Raalte, Bruno Guigas, Erik J M Toonen, Wynand Alkema, Data Sciences for Life Science & Health, Internal medicine, EMGO - Lifestyle, overweight and diabetes, and ICaR - Ischemia and repair

Subjects
insulin secretion, medicine.medical_treatment, Eukaryotic Initiation Factor-2, receptors, Apoptosis, Endoplasmic Reticulum, prednisolone/adverse effects, eIF-2 Kinase, Glucocorticoid receptor, homeostasis/drug effects, Insulin-Secreting Cells, endoplasmic reticulum/drug effects, Homeostasis, Insulin, Phosphorylation, biology, Calpain, protein-serine-threonine kinases/genetics, Health aging / healthy living Pathogenesis and modulation of inflammation [IGMD 5], insulin/metabolism, phosphorylation/drug effects, signal transduction/drug effects, genetica, Glucocorticoids Prednisolone Beta cells ER stress Insulin Apoptosis unfolded protein response glucocorticoid-receptor insulin-biosynthesis glucose-homeostasis messenger-rnas er stress activation dexamethasone eif2ak3 kinase, animals, mifepristone/pharmacology, Mifepristone, trans-activators/genetics, Signal Transduction, medicine.medical_specialty, insulin-secreting cells/cytology, XBP1, diabetes mellitus/drug therapy, Prednisolone, eukaryotic initiation factor-2/genetics, Protein Serine-Threonine Kinases, apoptosis/drug effects, Cell Line, Receptors, Glucocorticoid, Downregulation and upregulation, glucocorticoid/antagonists & inhibitors, Internal medicine, Diabetes Mellitus, medicine, Humans, Homeodomain Proteins, membrane proteins/genetics, ATF6, Endoplasmic reticulum, calpain/genetics, Membrane Proteins, Cell Biology, Activating Transcription Factor 6, activating transcription factor 6/genetics, rats, Glucose, Endocrinology, gene expression regulation/drug effects, Gene Expression Regulation, homeodomain proteins/genetics, glucose/metabolism, receptors, glucocorticoid/antagonists & inhibitors, Trans-Activators, Unfolded Protein Response, biology.protein, Unfolded protein response
Abstract

Item does not contain fulltext Glucocorticoids (GCs), such as prednisolone (PRED), are widely prescribed anti-inflammatory drugs, but their use may induce glucose intolerance and diabetes. GC-induced beta cell dysfunction contributes to these diabetogenic effects through mechanisms that remain to be elucidated. In this study, we hypothesized that activation of the unfolded protein response (UPR) following endoplasmic reticulum (ER) stress could be one of the underlying mechanisms involved in GC-induced beta cell dysfunction. We report here that PRED did not affect basal insulin release but time-dependently inhibited glucose-stimulated insulin secretion in INS-1E cells. PRED treatment also decreased both PDX1 and insulin expression, leading to a marked reduction in cellular insulin content. These PRED-induced detrimental effects were found to be prevented by prior treatment with the glucocorticoid receptor (GR) antagonist RU486 and associated with activation of two of the three branches of the UPR. Indeed, PRED induced a GR-mediated activation of both ATF6 and IRE1/XBP1 pathways but was found to reduce the phosphorylation of PERK and its downstream substrate eIF2alpha. These modulations of ER stress pathways were accompanied by upregulation of calpain 10 and increased cleaved caspase 3, indicating that long term exposure to PRED ultimately promotes apoptosis. Taken together, our data suggest that the inhibition of insulin biosynthesis by PRED in the insulin-secreting INS-1E cells results, at least in part, from a GR-mediated impairment in ER homeostasis which may lead to apoptotic cell death. 01 november 2011

Published
2011
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17. Opposing actions of rosiglitazone and resveratrol on mineralization in human vascular smooth muscle cells

Author

Johannes P.T.M. van Leeuwen, Marijke Koedam, Hideki Chiba, Claudia Bruedigam, Marco Eijken, and Internal Medicine

Subjects
Vascular smooth muscle, Apoptosis, Resveratrol, medicine.disease_cause, Muscle, Smooth, Vascular, Diabetes Mellitus/drug therapy, Hypoglycemic Agents/adverse effects, chemistry.chemical_compound, Signal Transduction/drug effects, Stilbenes, Thiazolidinedione, Receptor, Cells, Cultured, Thiazolidinediones/adverse effects, Cell Differentiation, Up-Regulation, Muscle, Smooth, Vascular/cytology, Caspases, Cardiology and Cardiovascular Medicine, Rosiglitazone, medicine.drug, Signal Transduction, medicine.medical_specialty, Caspases/genetics, medicine.drug_class, Myocytes, Smooth Muscle, Oxidative Stress/drug effects, Myocytes, Smooth Muscle/cytology, Biology, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Diabetes Mellitus, Humans, Hypoglycemic Agents, Molecular Biology, Caloric restriction mimetic, Apoptosis/drug effects, Atherosclerosis/drug therapy, Atherosclerosis, Oxidative Stress, Endocrinology, chemistry, Cell Differentiation/drug effects, Stilbenes/pharmacology, Thiazolidinediones, Oxidative stress
Abstract

Arteriosclerotic vascular disease is a major cardiac health problem in westernized countries and the primary cause of mortality in diabetic patients. Recent data have raised serious safety concerns with the antidiabetic rosiglitazone, a thiazolidinedione with peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonistic activity, in regard to cardiovascular risks. A common feature of atherosclerosis is vascular mineralization. The latter is formed by vascular smooth muscle cells (VSMC) through complex processes that are similar to mineralization in bone. The aim of the current study was to investigate the effect of rosiglitazone on mineralization in cultured human VSMCs. We found that rosiglitazone stimulated mineralization by, at least in part, induction of caspase-dependent apoptosis. Furthermore, rosiglitazone-induced oxidative stress was correlated with stimulated osteoblast-like differentiation of VSMCs. Treatment of rosiglitazone-supplemented VSMC cultures with the caloric restriction mimetic and antioxidant resveratrol diminished rosiglitazone-induced oxidative stress, osteoblast-like differentiation and mineralization. In conclusion, this study reveals novel insights into the relationship of rosiglitazone and cardiovascular events by providing a model that links rosiglitazone-induced osteoblast-like differentiation, oxidative stress and apoptosis with mineralization in VSMCs. In addition, we position resveratrol in this model acting to reduce rosiglitazone-induced oxidative stress, osteoblast-like VSMC differentiation and mineralization. (C) 2011 Elsevier Ltd. All rights reserved.

Published
2011
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18. Trends in self-reported prevalence and management of hypertension, hypercholesterolemia and diabetes in Swiss adults, 1997-2007

Author

Peter Vollenweider, Fred Paccaud, Pedro Marques-Vidal, and Daniel Estoppey

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, Cross-sectional study, Population, Hypercholesterolemia, Aged, Cross-Sectional Studies, Diabetes Mellitus/drug therapy, Diabetes Mellitus/epidemiology, Female, Humans, Hypercholesterolemia/drug therapy, Hypercholesterolemia/epidemiology, Hypertension/drug therapy, Hypertension/epidemiology, Mass Screening/statistics & numerical data, Middle Aged, Self Care, Switzerland/epidemiology, Young Adult, Diabetes mellitus, Epidemiology, medicine, Diabetes Mellitus, Mass Screening, Young adult, education, Mass screening, education.field_of_study, business.industry, Mortality rate, lcsh:Public aspects of medicine, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, medicine.disease, Hypertension, Biostatistics, business, Switzerland, Research Article
Abstract

Background Switzerland has a low mortality rate from cardiovascular diseases, but little is known regarding prevalence and management of cardiovascular risk factors (CV RFs: hypertension, hypercholesterolemia and diabetes) in the general population. In this study, we assessed 10-year trends in self-reported prevalence and management of cardiovascular risk factors in Switzerland. Methods data from three national health interview surveys conducted between 1997 and 2007 in representative samples of the Swiss adult population (49,261 subjects overall). Self-reported CV RFs prevalence, treatment and control levels were computed. The sample was weighted to match the sex - and age distribution, geographical location and nationality of the entire adult population of Switzerland. Results self-reported prevalence of hypertension, hypercholesterolemia and diabetes increased from 22.1%, 11.9% and 3.3% in 1997 to 24.1%, 17.4% and 4.8% in 2007, respectively. Prevalence of self-reported treatment among subjects with CV RFs also increased from 52.1%, 18.5% and 50.0% in 1997 to 60.4%, 38.8% and 53.3% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Self-reported control levels increased from 56.4%, 52.9% and 50.0% in 1997 to 80.6%, 75.1% and 53.3% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Finally, screening during the last 12 months increased from 84.5%, 86.5% and 87.4% in 1997 to 94.0%, 94.6% and 94.1% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Conclusion in Switzerland, the prevalences of self-reported hypertension, hypercholesterolemia and diabetes have increased between 1997 and 2007. Management and screening have improved, but further improvements can still be achieved as over one third of subjects with reported CV RFs are not treated.

Published
2011

19. Drug consumption in elderly diabetics

Author

Else Marie Damsgaard and J. Gram

Subjects
Drug, medicine.medical_specialty, Danish population, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, media_common.quotation_subject, Hypoglycemic Agents/therapeutic use, Nonprescription Drugs, Self Administration, Self Medication, Pharmacology, Diabetes Mellitus/drug therapy, Endocrinology, Pharmacotherapy, Reference Values, Diabetes mellitus, Internal medicine, Surveys and Questionnaires, Internal Medicine, medicine, Diabetes Mellitus, Hypoglycemic Agents, Aged/psychology, Humans, media_common, Aged, Pharmaceutical Preparations/administration & dosage, business.industry, Insulin, Antidiabetic treatment, General Medicine, Middle Aged, medicine.disease, Control subjects, Pharmaceutical Preparations, Drug consumption, business
Abstract

The drug use in 228 persons with diabetes was studied and compared with that of sex- and age-matched non-diabetic controls--all of whom were found by the screening of a well-defined Danish population aged 60-74 years. Ninety per cent of the diabetics had non-insulin-dependent diabetes mellitus (NIDDM), as evaluated by a glucagon-C-peptide test. Information on daily use of prescribed and non-prescribed drugs was obtained by questionnaires and interviews. More than 80% of the diabetics used drugs daily, compared to 55% of control subjects (P less than 0.00001). Among subjects using drugs diabetics, on average, used 70% more defined daily doses (DDD) than controls, even when antidiabetics were excluded. There was no difference in the number of drug users among subgroups of diabetics when divided according to antidiabetic treatment but tablet-treated diabetics, on average, used 20% fewer DDD than other diabetics. Cardiovascular drugs were the most commonly used drugs. Diabetics in all antidiabetic treatment groups used significantly more cardiovascular drugs than non-diabetics. Diabetics treated with oral antidiabetics used fewer cardiovascular drugs than insulin- and diet-treated diabetics. The estimated cost of drug therapy was more than 2.5 times higher for diabetics than for the control group. Our results reflect the increased morbidity among elderly diabetics and emphasise, together with other aspects of costs of diabetes in the elderly, the need for allocating resources for the prevention of NIDDM instead of the treatment of its complications.

Published
1989

20. Use of insulin and insulin analogs and risk of cancer - systematic review and meta-analysis of observational studies

Author

Morten Andersen, Jari Haukka, Jacob Starup-Linde, Anssi Auvinen, Peter Vestergaard, Øystein Karlstad, Marloes T Bazelier, Kari Furu, Marie L. De Bruin, Marjanka K. Schmidt, Frank de Vries, and Vidar Hjellvik

Subjects
Oncology, Colorectal cancer, medicine.medical_treatment, Insulin Glargine, VDP::Medisinske fag: 700::Helsefag: 800::Epidemiologi medisinsk og odontologisk statistikk: 803, Toxicology, Diabetes Mellitus/drug therapy, Hypoglycemic Agents/adverse effects, Cohort Studies, Cancer risk, 0302 clinical medicine, Neoplasms, Insulin, Pharmacology (medical), Registries, Breast Neoplasms/chemically induced, 2. Zero hunger, 3. Good health, Insulin, Long-Acting, Insulin/adverse effects, Observational Studies as Topic, Research Design, 030220 oncology & carcinogenesis, Meta-analysis, diabetes mellitus, Female, VDP::Midical sciences: 700::Health sciences: 800::Epidemiology, medical and dental statistics: 803, systematic review, Colorectal Neoplasms, medicine.drug, medicine.medical_specialty, Breast Neoplasms, Long-Acting/adverse effects, 030209 endocrinology & metabolism, Article, 03 medical and health sciences, Breast cancer, Colorectal Neoplasms/chemically induced, Internal medicine, Diabetes mellitus, medicine, Hypoglycemic Agents, Humans, Pharmacology, business.industry, Insulin glargine, Case-control study, Cancer, medicine.disease, meta-analysis, Endocrinology, Case-Control Studies, business, Neoplasms/epidemiology, Publication Bias, neoplasm
Abstract

Background: An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified. Objective: To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes. Data Sources: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. Study Eligibility Criteria (PICOS): Population: diabetes patients. Exposure: Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs. Outcome: Any incident cancer. Study Design: Cohort and case-control studies. Results: 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer. Limitations: Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders. Conclusions: Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk.

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21. Health systems research for policy change: lessons from the implementation of rapid assessment protocols for diabetes in low- and middle-income settings

Author

David Beran, María Kathia Cárdenas, Maryam Bigdeli, and J. Jaime Miranda

Subjects
Program evaluation, Asia, International Cooperation, Decision Making, Developing country, Context (language use), Nicaragua, Computer-assisted web interviewing, Health systems research, World Health Organization, Trust, Health Services Accessibility, Health administration, Diabetes Mellitus/drug therapy, Health Services Research/methods, Health systems, Nursing, purl.org/pe-repo/ocde/ford#3.03.02 [https], Surveys and Questionnaires, Credibility, Diabetes Mellitus, Insulin, Medicine, Humans, Cooperative Behavior, Policy Making, Developing Countries, Health policy, ddc:613, business.industry, Research, Health Policy, Diabetes, Health services research, Administrative Personnel, Public relations, Policy, Attitude, Insulin/therapeutic use, Africa, Income, Health Services Research, business, Program Evaluation
Abstract

BACKGROUND: As many challenges exist for access to diabetes care in developing countries, the International Insulin Foundation developed a Rapid Assessment tool and implemented this approach to identify barriers to care and propose concrete recommendations for decision makers. The objective of this paper is to identify the factors that contributed to informing and influencing policymakers with regards to this work. METHODS: A documentary review comprised Stage 1. Stage 2 used an online questionnaire to gain insight from users of the Rapid Assessment results. Based on Stages 1 and 2, Stage 3 comprised in-depth interviews with a total of nine individuals (one individual each from the six participating countries; two individuals from the World Health Organization; one "Global Diabetes Advocate"). Interviews were analyzed based on a list of themes developed from Stage 2. RESULTS: Stage 1 led to the identification of various types of documents referring to the results. The online questionnaire had a response rate of 33%. Respondents directly involved in the assessment had a "Good" or "Very Good" appreciation of most aspects and scored these higher than those not directly involved. From the interviews, formalized methods and close collaboration between the international team and local partners were strengths. Trust and a relationship with local partners were also seen as assets. All stakeholders valued the results and the credibility of the data generated. Local partners felt that more could have been done for dissemination. CONCLUSION: This study shows the importance of specific results from the different assessments. In addressing complex issues having external experts involved was seen as an advantage. The uptake of results was due to the credibility of the research which was influenced by a mix of the people involved, past assessments, trusted local partners, and the use of the results by knowledge brokers, such as the World Health Organization. Through these brokers, others gained ownership of the data. The methods used and the fact that this data was grounded in a local context also reinforced its value. Despite limitations, this study offers a unique perspective where a similar research approach was taken in six countries.

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22. CARING (CAncer Risk and INsulin analoGues): The association of diabetes mellitus and cancer risk with focus on possible determinants - a systematic review and a meta-analysis

Author

Peter Vestergaard, Morten Andersen, Anthonius de Boer, Kari Furu, Frank de Vries, Jakob Starup-Linde, Vidar Hjellvik, Marloes T Bazelier, Øystein Karlstad, Anssi Auvinen, Stine Aistrup Eriksen, Jari Haukka, Heleen K Bronsveld, and Marie L. De Bruin

Subjects
Cochrane Library, Diabetes Complications/epidemiology, Toxicology, Diabetes Mellitus/drug therapy, Hypoglycemic Agents/adverse effects, Cancer risk, 0302 clinical medicine, systematic review, Neoplasms, 80 and over, Insulin, Pharmacology (medical), 030212 general & internal medicine, Young adult, Child, 2. Zero hunger, Aged, 80 and over, education.field_of_study, Middle Aged, 3. Good health, Insulin/adverse effects, 030220 oncology & carcinogenesis, Meta-analysis, Child, Preschool, diabetes mellitus, Regression Analysis, Adult, Risk, medicine.medical_specialty, Adolescent, Population, Article, Diabetes Complications, 03 medical and health sciences, Young Adult, Internal medicine, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, education, Preschool, Aged, Pharmacology, business.industry, Cancer, Infant, Publication bias, medicine.disease, Surgery, meta-analysis, business, Body mass index, Neoplasms/epidemiology, Publication Bias, neoplasm
Abstract

Background: Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se. Objective: To examine the association between DM and cancers by a systematic review and meta-analysis according to the PRISMA guidelines. Data Sources: The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane library, Web of Science and SveMed+ with the search terms: “Diabetes mellitus”, “Neoplasms”, and “Risk of cancer”. Study Eligibility Criteria: The included studies compared the risk of cancer in diabetic patients versus non-diabetic patients. All types of observational study designs were included. Results: Diabetes patients were at a substantially increased risk of liver (RR=2.1), and pancreas (RR=2.2) cancer. Modestly elevated significant risks were also found for ovary (RR=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index, and possible effect modification of age, gender, with some influence of study characteristics (population source, cancer- and diabetes ascertainment). Limitations: Publication bias seemed to be present. Only published data were used in the analyses. Conclusions: The systematic review and meta-analysis confirm the previous results of increased cancer risk in diabetes and extend this to additional cancer sites. Physicians in contact with patients with diabetes should be aware that diabetes patients are at an increased risk of cancer.

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