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903 results on '"Jb, A."'

1. Comparison of Ambulatory Tonometric and Oscillometric Blood Pressure Monitoring in Hypertensive Patients

Author

Hornstrup BG, Rosenbæk JB, and Bech JN

Subjects
ambulatory blood pressure monitoring, oscillometric, tonometric, Internal medicine, RC31-1245
Abstract

Bodil Gade Hornstrup, Jeppe Bakkestrøm Rosenbæk, Jesper Nørgaard Bech University Clinic in Nephrology and Hypertension, Regional Hospital West Jutland and Aarhus University, Holstebro, DenmarkCorrespondence: Bodil Gade HornstrupUniversity Clinic in Nephrology and Hypertension, Regional Hospital West Jutland and Aarhus University, Holstebro, DenmarkEmail bodil.hornstrup@rm.dkAim: Correct measurement of blood pressure (BP) is important for optimal diagnosis and treatment of patients with hypertension. The aim of this study was to compare a wrist-worn device using tonometric measurements of BP to a conventional device using oscillometric measurements of 24 h BP, diagnosing of hypertension, and non-dipping.Methods: One-hundred patients in the Renal Outpatient Clinic had 24 h ambulatory BP monitoring performed with a tonometric device, BPro, and an oscillometric device, A&D, simultaneously.Results: Twenty-four-hour and daytime systolic BP was significantly lower using tonometric monitoring compared to oscillometric (7 and 6 mmHg, respectively, p< 0.001). In the population of patients diagnosed with hypertension, the tonometric device diagnosed 90% of patients with uncontrolled hypertension correctly (positive predictive value), whereas 49% of patients classified as normotensive were uncontrolled hypertensive (negative predictive value). The mean difference between relative nocturnal BP decrease between tonometric and oscillometric was 2± 8% (p< 0.01), and 33% of patients classified as dippers were non-dippers (negative predictive value).Conclusion: Using the BPro device for tonometric monitoring of BP and classification of hypertension and non-dipping in patients diagnosed with hypertension leads to misclassification of patients. Therefore, the BPro device is not suitable for clinical practice in hypertensive patients from a Renal Outpatient Clinic.Keywords: ambulatory blood pressure monitoring, oscillometric, tonometric

Published
2020

2. 47 FNAC & Post Operative Histopathology in Thyroid

Author

Asef A Wani, Raphella Khan, Ayaz Rehman, Masood H Kirmam, JB Singh, and Afiya Shafi

Subjects
Thyroid masses, FNAC, Histopathology, Non-neoplastic, Neoplastic, Medicine (General), R5-920, Internal medicine, RC31-1245
Abstract

Introduction: To evaluate a case of thyroid mass multitude of diagnostic tests like ultrasound, FNAC etc are available.Final diagnosis always requires morphological examination of lesions for which FNAC and histopathological examination (HPE) become mandatory. Methods: Study was conducted on 195 patients with thyroid masses who had undergone pre-operative FNAC which was compared with the histopathology and conclusions were drawn after statistical analysis.Results: In 92.8% patients FNAC and histopathology correlated very well. In 7.2 % patients FNAC and Histopathology did not correlate. 9 patients diagnosed as colloid goitre / cyst on FNAC, subsequently on HPE proved as Follicular adenoma in 5 patients and Papillary carcinoma in 4 patients, thus false negative results on FNAC were seen in 9 patients . 5 patients diagnosed as Follicular Neoplasm on FNAC turned out to be Colloid Goitre/cyst on histopathology,thus false positive diagnosis on FNAC was seen in 5 patients . Sensitivity, specificity, positive predictive value , negative predictive value and efficacy of FNAC in predicting neoplastic lesions were 90.4%, 95.04%, 94.4%, 91.4% and 92.8% respectively. Conclusion: Benign FNAC diagnosis should be viewed with caution as false negative results do occur and these patients should be followed up for any clinical suspicion of malignancy.

Published
2022

3. Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay

Author

Wiegand, Martin, Halsall, David J, Cowan, Sarah L, Taylor, Kevin, Goudie, Robert JB, Preller, Jacobus, Gurnell, Mark, Wiegand, Martin [0000-0003-0276-658X], Cowan, Sarah L [0000-0001-9149-3530], Goudie, Robert JB [0000-0001-9554-1499], Preller, Jacobus [0000-0001-5706-816X], Gurnell, Mark [0000-0001-5745-6832], and Apollo - University of Cambridge Repository

Subjects
renin-angiotensin-aldosterone system, Endocrinology, SARS-CoV-2, Endocrinology, Diabetes and Metabolism, Internal Medicine, COVID-19
Abstract

Objective Previous studies have reported conflicting findings regarding aldosterone levels in patients hospitalised with COVID-19. We therefore used the gold-standard technique of liquid chromatography–tandem mass spectrometry (LCMSMS) to address this uncertainty. Design All patients admitted to Cambridge University Hospitals with COVID-19 between 10 March 2020 and 13 May 2021, and in whom a stored blood sample was available for analysis, were eligible for inclusion. Methods Aldosterone was measured by LCMSMS and by immunoassay; cortisol and renin were determined by immunoassay. Results Using LCMSMS, aldosterone was below the limit of detection ( 744 nmol/L (P = 0.005). Conclusion When measured by LCMSMS, aldosterone was found to be profoundly low in a significant proportion of patients with COVID-19 at the time of hospital admission. This has likely not been detected previously due to high levels of interference with immunoassays in patients with COVID-19, and this merits further prospective investigation.

Published
2022
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4. Personalized medicine and treatment approaches in hypertension: current perspectives

Author

Byrd JB

Subjects
Hypertension, blood pressure, personalized medicine, Internal medicine, RC31-1245
Abstract

James Brian Byrd Division of Cardiovascular Medicine, Department of Medicine, University of Michigan, Ann Arbor, MI, USA Abstract: In the US, hypertension affects one in three adults. Current guideline-based treatment of hypertension involves little diagnostic testing. A more personalized approach to the treatment of hypertension might be of use. Several methods of personalized treatment have been proposed and vetted to varying degrees. The purpose of this narrative review is to discuss the rationale for personalized therapy in hypertension, barriers to its development and implementation, some influential examples of proposed personalization measures, and a view of future efforts. Keywords: hypertension, blood pressure, personalized medicine

Published
2016

5. Predicting Out-of-Office Blood Pressure in a Diverse US Population

Author

Bellows, BK, Xu, J, Sheppard, JP, Schwartz, JE, Shimbo, D, Muntner, P, McManus, RJ, Moran, AE, Bryant, KB, Cohen, LP, Bress, AP, King, JB, Shikany, JM, Green, BB, Yano, Y, Clark Iii, D, and Zhang, Y

Subjects
Adult, Male, Hypertension, Internal Medicine, Humans, Blood Pressure, Blood Pressure Determination, Female, Blood Pressure Monitoring, Ambulatory, Middle Aged, Nutrition Surveys, Antihypertensive Agents, United States
Abstract

BACKGROUND The PRedicting Out-of-OFfice Blood Pressure (PROOF-BP) algorithm accurately predicted out-of-office blood pressure (BP) among adults with suspected high BP in the United Kingdom and Canada. We tested the accuracy of PROOF-BP in a diverse US population and evaluated a newly developed US-specific algorithm (PROOF-BP-US). METHODS Adults with ≥2 office BP readings and ≥10 awake BP readings on 24-hour ambulatory BP monitoring from 4 pooled US studies were included. We compared mean awake BP with predicted out-of-office BP using PROOF-BP and PROOF-BP-US. Our primary outcomes were hypertensive out-of-office systolic BP (SBP) ≥130 mm Hg and diastolic BP (DBP) ≥80 mm Hg. RESULTS We included 3,058 adults, mean (SD) age was 52.0 (11.9) years, 38% were male, and 54% were Black. The area under the receiver-operator characteristic (AUROC) curve (95% confidence interval) for hypertensive out-of-office SBP was 0.81 (0.79–0.82) and DBP was 0.76 (0.74–0.78) for PROOF-BP. For PROOF-BP-US, the AUROC curve for hypertensive out-of-office SBP was 0.82 (0.81–0.83) and for DBP was 0.81 (0.79–0.83). The optimal predicted out-of-office BP ranges for out-of-office BP measurement referral were 120–134/75–84 mm Hg for PROOF-BP and 125–134/75–84 mm Hg for PROOF-BP-US. The 2017 American College of Cardiology/American Heart Association BP guideline (referral range 130–159/80–99 mm Hg) would refer 93.1% of adults not taking antihypertensive medications with office BP ≥130/80 mm Hg in the National Health and Nutrition Examination Survey for out-of-office BP measurement, compared with 53.1% using PROOF-BP and 46.8% using PROOF-BP-US. CONCLUSIONS PROOF-BP and PROOF-BP-US accurately predicted out-of-office hypertension in a diverse sample of US adults.

Published
2022
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6. Evaluation methods and objectives for neuromuscular and hemodynamic responses subsequent to different rest intervals in resistance training: a systematic review

Author

RA Moreira Nunes, R Gomes de Souza Vale, JB da Silva, V Pinheiro Lima, D Braga de Mello, G Casimiro Lopes, and L de Lima e Silva

Subjects
medicine.medical_specialty, Blood pressure, business.industry, Internal medicine, Heart rate, Evaluation methods, Resistance training, medicine, Cardiology, Hemodynamics, Physical Therapy, Sports Therapy and Rehabilitation, Orthopedics and Sports Medicine, business
Abstract

Introduction: The training routine planned, and performed correctly results in exercises that, systematically organized, influence the levels of strength, and muscle hypertrophy. However, the magnitudes of these gains vary considerably. To optimize these gains, it is important to underst, and the interaction between training variables such as external load, volume, number of exercises, number of repetitions, duration of repetitions, the order of exercises, number of series, recovery interval between series, and the exercises, as well as the time under tension. The influence of the recovery interval on the response following exercise on neuromuscular components is very important. However, different objectives, and instruments are used to evaluate these responses. Objective: The purpose of this study is to conduct a systematic review of the assessment methods, and objectives for responses after different recovery intervals in strength training. METHODS: The present study is characterized by a systematic review study. Articles found in the following databases were considered for the systematic review: Scopus, PubMed / MEDLINE, Web of Science, Cochrane Library. The following descriptors, and their respective synonyms according to the terms MeSH were used in the databases, both singular, and plural: “Resistance Training”, “Rest Interval”, and “Bech Press”. As filters were used: a) species (humans), and type of study (original). Results: Seven studies were analyzed that met the established criteria. Conclusion: The studies presented have verified the influence of different recovery intervals on muscle, and hemodynamic responses. Evaluating image measurements such as ultrasound, and resonance, blood measurements such as GH, Testosterone, IGF-1, and Lactate, number of repetitions for performance, and fatigue, as well as heart rate, and blood pressure.

Published
2021
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7. C-Reactive Protein as A Fungal Infection Marker in Acute Leukemia Patients

Author

Brigitte Rina Aninda Sidharta, Avanti Fitri Astuti, and Jb. Suparyatmo

Subjects
medicine.medical_specialty, Acute leukemia, Clinical pathology, biology, business.industry, C-reactive protein, Cancer, Neutropenia, medicine.disease, Gastroenterology, Likelihood ratios in diagnostic testing, Leukemia, Liver disease, Internal medicine, medicine, biology.protein, General Earth and Planetary Sciences, business, General Environmental Science
Abstract

Invasive Fungal Infections (IFIs) can cause serious problems in cancer patients and may result in high morbidity andmortality. C-reactive protein levels increase in response to injury, infection, and inflammation. C-reactive protein increasesin bacterial infections (mean of 32 mg/L) and in fungal infections (mean of 9 mg/L). This study aimed to determineC-Reactive Protein (CRP) as a marker of fungal infections in patients with acute leukemia by establishing cut-off values ofCRP. This study was an observational analytical study with a cross-sectional approach and was carried out at the Departmentof Clinical Pathology and Microbiology of Dr. Moewardi Hospital in Surakarta from May until August 2019. The inclusioncriteria were patients with acute leukemia who were willing to participate in this study, while exclusion criteria were patientswith liver disease. There were 61 samples consisting of 30 male and 31 female patients with ages ranging from 1 to 70 years.Fifty-four patients (88.5%) were diagnosed with Acute Lymphoblastic Leukemia (ALL) and 30 (49.18%) were in themaintenance phase. The risk factors found in those patients were neutropenia 50-1500 μL (23.8%), use of intravenous line(22%), and corticosteroid therapy for more than one week (20.9%). The median of CRP in the group of patients with positiveculture results was 11.20 mg/L (11.20-26.23 mg/L) and negative culture results in 0.38 mg/L (0.01-18.63 mg/L). The cut-offvalue of CRP using the Receiver Operating Curve (ROC) was 9.54 mg/L (area under curve 0.996 and p. 0.026), with a sensitivityof 100%, specificity of 93.2%, Positive Predictive Value (PPV) of 33.3%, Negative Predictive Value (PPV) of 100%, PositiveLikelihood Ratio (PLR) of 1.08, Negative Likelihood Ratio (NLR) of 0 and accuracy of 93.4%. C-reactive protein can be used asa screening marker for fungal infections in patients with acute leukemia.

Published
2021
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8. The Budget Impact of Monoclonal Antibodies Used to Treat Metastatic Colorectal Cancer in Minas Gerais, Brazil

Author

Mariângela Leal Cherchiglia, Marcos Andre Portella, Francisco de Assis Acurcio, Konrad Maruszczyk, Brian Godman, Wânia Cristina da Silva, Agner Pereira Lana, JB Izidoro, Orozimbo Henriques Campos Neto, Antony P. Martin, and Eli Iola Gurgel Andrade

Subjects
Oncology, Economics and Econometrics, medicine.medical_specialty, Bevacizumab, Colorectal cancer, medicine.drug_class, Cost-Benefit Analysis, medicine.disease_cause, Monoclonal antibody, RS, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, Panitumumab, 030212 general & internal medicine, health care economics and organizations, Cetuximab, business.industry, 030503 health policy & services, Health Policy, Antibodies, Monoclonal, Cancer, Health Care Costs, General Medicine, Budget impact, medicine.disease, digestive system diseases, KRAS, Colorectal Neoplasms, 0305 other medical science, business, Brazil, medicine.drug
Abstract

Introduction: Biological medicines have increased the cost of cancer treatments, which also raises concerns about sustainability. In Brazil, three monoclonal antibodies (mAbs)—bevacizumab, cetuximab, and panitumumab—are indicated for the treatment of metastatic colorectal cancer (mCRC) but not currently funded by the Unified Health System (SUS). However, successful litigation has led to funding in some cases. Objective: Our objective was to evaluate the budgetary impact of including the mAbs bevacizumab, cetuximab, and panitumumab in standard chemotherapy for the treatment of mCRC within the SUS of Minas Gerais (MG), Brazil. Method: A budget impact analysis of incorporating mAbs as first-line treatment of mCRC in MG was explored. The perspective taken was that of the Brazilian SUS, and a 5-year time horizon was applied. Data were collected from lawsuits undertaken between January 2009 and December 2016, and the model was populated with data from national databases and published sources. Costs are expressed in $US. Results: In total, 351 lawsuits resulted in funding for first-line treatment with mAbs for mCRC. The three alternative scenarios analyzed resulted in cost increases of 348–395% compared with the reference scenario. The use of panitumumab had a budgetary impact of $US103,360,980 compared with the reference scenario over a 5-year time horizon, and bevacizumab and cetuximab had budgetary impacts of $US111,334,890 and 113,772,870, respectively. The use of the anti-epidermal growth factor receptor (EGFR) mAbs (cetuximab and panitumumab) is restricted to the approximately 41% of patients with KRAS mutations, so the best cost alternative for incorporation would be the combination of panitumumab and bevacizumab, with a cost of approximately $US106 million. Conclusion: These results highlight the appreciable costs for incorporating bevacizumab, cetuximab, and panitumumab into the SUS. Appreciable discounts are likely to be necessary before incorporation of these mAbs is approved.

Published
2021
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9. Association of overweight/obesity with the severity of periodontitis using BPE code in an iraqi population

Author

Ali A. Abdulkareem, Sarhang S. Gul, Nada K. Imran, and Ali Jb. Al-Sharqi

Subjects
Microbiology (medical), medicine.medical_specialty, Gingival and periodontal pocket, Epidemiology, Periodontal examination, Population, Overweight, Severe periodontitis, Severity, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, 030212 general & internal medicine, Periodontitis, education, Body mass index, BPE code, education.field_of_study, 030219 obstetrics & reproductive medicine, business.industry, Public Health, Environmental and Occupational Health, medicine.disease, Obesity, Infectious Diseases, Public aspects of medicine, RA1-1270, medicine.symptom, business
Abstract

Objective Periodontitis is a chronic inflammatory disease driven by bacteria and risk factors. The aim of this study is to assess the effect of obesity on the severity of periodontitis using the basic periodontal examination (BPE) index. Methods Age, gender and smoking status were collected from 258 periodontitis subjects with code 3 (shallow periodontal pocket) and 4 (deep periodontal pocket) of BPE. Periodontal status was examined using BPE criteria, detailed probing pocket depth (PPD) in sextant with BPE code 3 and full mouth PPD with BPE code 4 were recorded, plaque index and gingival index with WHO probe. Body mass index (BMI) was used to assess obesity. The relation with the severity of periodontitis was assessed using chi square and ANOVA tests. Results Among recruited patients, 77 were normal weight, 97 were overweight and 84 were obese, and those with shallow PPD, deep PPD and with furcation numbered 121,101 and 36, respectively. The BMI levels were higher in the smoker and older patients (>45 years) than in non-smoker and younger (≤45 years) patients and the differences were statistically significant (p = 0.004, 0.035, respectively). Average BMI levels in patients with deep PPD (28.4 ± 4.9) were higher than in those with shallow PPD (26.5 ± 5.1). Patients with obesity and overweight exhibited statistically significantly higher average PPD (5.3 ± 1.1 mm, 5.2 ± 0.9 mm, respectively) than normal weight (4.7 ± 0.3 mm) patients. Obesity status and severity of periodontitis were shown to have statistically significant association (p = 0.017). Conclusions This study suggests individuals with overweight and obesity experience more severe periodontitis than normal weight individuals in an Iraqi population.

Published
2021
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10. A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study

Author

John Jb, Duraisamy, Ramesh Krishnan, Suresh Kumar Vasaviah, and Gainneos Pd

Subjects
Aging, medicine.medical_specialty, education.field_of_study, business.industry, Cross-sectional study, Population, Human immunodeficiency virus (HIV), medicine.disease_cause, Health Professions (miscellaneous), Biochemistry, Genetics and Molecular Biology (miscellaneous), General Biochemistry, Genetics and Molecular Biology, Comparative evaluation, Salivary iga, Internal medicine, General Health Professions, medicine, Dentistry (miscellaneous), business, education, General Dentistry
Published
2021
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11. Use of salivary liver function markers for the prognosis of deaddiction in alcohol dependent non-smokers and smokers: A before and after study

Author

SS Avinash, John P Mathai, Arnadi Ramachandrayya Shivashankara, JB Honnamurthy, and M Malathi

Subjects
medicine.medical_specialty, Saliva, biology, Aspartate transaminase, Alcohol, digestive system, γ glutamyl transferase, Gastroenterology, digestive system diseases, respiratory tract diseases, stomatognathic diseases, chemistry.chemical_compound, chemistry, Alanine transaminase, Internal medicine, behavior and behavior mechanisms, biology.protein, medicine, Before and after study, Liver function, Total protein
Abstract

Alcohol deaddiction improves the liver function markers in blood as well as saliva in both smokers and non-smokers. The study was conducted to observe the changes in liver function markers after deaddiction in both blood as well as saliva. The study included 83 alcohol dependent subjects, among whom 45 were smokers and 38 were non-smokers. They were followed up after deaddiction for 19-21 days. The liver function markers GGT- γ glutamyl transferase, AST- Aspartate transaminase, ALT- Alanine transaminase, TP- Total protein, and Alb-Albumin were measured spectrophotometrically before and after deaddiction in saliva as well as blood. Paired‘t’ test was done to analyse the significance of their changes in before and after deaddiction. There was no difference in NR (normalization rate) of GGT, AST and ALT between alcohol dependent smokers and non-smokers in saliva as well as blood. NR of TP and Alb was better in non-smokers compared to smokers. GGT (p

Published
2020
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12. The Correlation between Serum Growth Differentiation Factor-15 Levels and Post-Acute Myocardial Infarction Acute Heart

Author

Jb. Suparyatmo, Dian Ariningrum, and Kenny Mayavani

Subjects
medicine.medical_specialty, Proportional hazards model, business.industry, Incidence (epidemiology), Hazard ratio, medicine.disease, Internal medicine, Heart failure, Cardiology, medicine, General Earth and Planetary Sciences, Myocardial infarction, GDF15, Prospective cohort study, business, Complication, General Environmental Science
Abstract

Acute Heart Failure (AHF) is a common rapid complication of Acute Myocardial Infarction (AMI). Myocardial dysfunction leads to pathologic remodeling of the heart, which causes AHF. Growth differentiation factor-15 (GDF-15) is expressed by cardiomyocytes and upregulated due to injury and cardiomyocyte damage. Thus, it can be used as a predictor of severe heart damage. This study aimed to determine the correlation between GDF-15 levels and the incidence rate of post-AMI AHF. This prospective cohort study was performed in patients with AMI treated in Dr. Moewardi Hospital from August to September 2019. The Kolmogorov-Smirnov normality test was used. Bivariate analysis was applied for Hazard Ratio (HR) with 95% CI. The GDF-15 cut-off used the ROC curve. The Cox Regression Proportional Hazard Model was used for multivariable analysis. The significance value was p

Published
2020
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13. Serum Copeptin as the Predictor for Acute Heart Failure Complication of Acute Myocardial Infarction in Patients with ST-Segment Elevation

Author

Jb. Suparyatmo, Dian Ariningrum, and Ardi Putranto Ari Supomo

Subjects
medicine.medical_specialty, Heart disease, business.industry, 030204 cardiovascular system & hematology, medicine.disease, Confidence interval, 03 medical and health sciences, 0302 clinical medicine, Copeptin, Internal medicine, Heart failure, medicine, Cardiology, General Earth and Planetary Sciences, ST segment, 030211 gastroenterology & hepatology, cardiovascular diseases, Myocardial infarction, Complication, Prospective cohort study, business, General Environmental Science
Abstract

Acute Myocardial Infarction (AMI) is necrotic cardiac muscle cells due to unstable ischemic syndrome. Therapy monitoring is needed because various complications may occur (Heart Failure/HF). ST-Segment Elevation Myocardial Infarction (STEMI) can develop to Acute Heart Failure (AHF) due to myocardial dysfunction, transmural heart disease, pathological cardiac remodeling. Copeptin is an antidiuretic hormone which increases in the cardiac event. It can be used as a predictor of a further cardiac event. This study aimed to determine the role of serum copeptin level as a predictor of AHF complication in STEMI patients. A prospective cohort study was performed in 85 adult STEMI patients admitted to The Clinical Pathology Installation of Dr. Moewardi Hospital, Surakarta. Data with normal and abnormal distribution were presented in mean±Standard Deviation (SD) and median (min-max), respectively. Statistical analysis was performed using Kolmogorov-Smirnov, bivariate, and multivariate analysis for RR with Confidence Interval (CI) of 95% and p < 0.05 was considered significant. The copeptin cut-off point was determined using the ROC curve. Bivariate and multivariate analysis showed a higher copeptin level in STEMI patients with AHF compared to that of non-AHF (RR=5.172, CI 95% 1.795-14.902, p=0.002 and RR=1.889, CI 95% 1.156-3.086, p=0.001; respectively). The STEMI patients with an elevated level of copeptin showed an increased risk of AHF (STEMI with elevated copeptin level vs STEMI with normal copeptin level; 28.74% vs. 88.91%). Copeptin level is significantly related to AHF complication in STEMI patient, the higher level of copeptin led to the higher the risk of AHF.

Published
2020
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14. Shape of the OGTT glucose response curve: relationship with β-cell function and differences by sex, race, and BMI in adults with early type 2 diabetes treated with metformin

Author

C Wright, C Sanders, C Wilson, L Tucker, S Jones, S Douglass, C Patel, A Kumar, S Smith, C Adams, R Hill, D Martin, M Lee, J Cook, M Jackson, G Riera, E González, J Park, S Yang, A Carlson, C Martin, A Krol, A Sood, J Martinez, C DeSouza, M Johnson, L Estrada, A Jackson, K Martin, SA Khan, J Craig, A Kuhn, Deborah J Wexler, R Chatterjee, J Kerr, W Taylor, R Henry, R Fraser, Kieren J Mather, M Larkin, E King, E Diaz, J Marks, A Ross, M Khalid, J Barzilay, B Chambers, G Montes, C Jensen, J McConnell, R Nelson, S Morton, M Curtis, P Wilson, L Young, M Fürst, C Newman, S Kuo, N Rasouli, A Werner, A Ghazi, F Ismail-Beigi, P Kringas, C Baker, E Ellis, Philip Raskin, A Cherian, L Holloway, M Madden, B Hollis, G Fuller, B Steiner, K Stokes, T Lowe, K Chu, S Durán, A Alfred, John M Lachin, T Hamilton, J Costello, E Burgess, R Garg, C Stevens, T Tran, M Hurtado, H Schneier, R Lorch, M Mullen, J Bantle, K Arnold, D Wexler, Neda Rasouli, D Howard, J Tejada, S Hernandez, E Schroeder, S Kunkel, G Lord, A Smiley, E Debnam, H Petrovitch, B Kauffman, V Jenkins, B Cramer, Kristina M Utzschneider, Naji Younes, Joshua I Barzilay, Mary Ann Banerji, Robert M Cohen, Erica V Gonzalez, Faramarz Ismail-Beigi, Steven E Kahn, JP Crandall, MD McKee, S Behringer-Massera, J Brown-Friday, E Xhori, K Ballentine-Cargill, H Estrella, S Gonzalez de la torre, J Lukin, LS Phillips, D Olson, M Rhee, TS Raines, J Boers, C Gullett, M Maher-Albertelli, R Mungara, L Savoye, CA White, F Morehead, S Person, M Sibymon, S Tanukonda, A Balasubramanyam, R Gaba, P Hollander, E Roe, P Burt, K Chionh, C Falck-Ytter, L Sayyed Kassem, M Tiktin, T Kulow, KA Stancil, J Iacoboni, MV Kononets, G McPhee AMaxwell, L Colosimo, R Goland, J Pring, L Alfano, C Hausheer, K Gumpel, A Kirpitch, JB Green, H AbouAssi, MN Feinglos, J English Jones, RP Zimmer, BM Satterwhite, K Evans Kreider, CR Thacker, CN Mariash, KJ Mather, A Lteif, V Pirics, D Aguillar, S Hurt, R Bergenstal, T Martens, J Hyatt, H Willis, W Konerza, K Kleeberger, R Passi, S Fortmann, M Herson, K Mularski, H Glauber, J Prihoda, B Ash, C Carlson, PA Ramey, E Schield, B Torgrimson-Ojerio, E Panos, S Sahnow, K Bays, K Berame, D Ghioni, J Gluth, K Schell, J Criscola, C Friason, S Nazarov, N Rassouli, R Puttnam, B Ojoawo, C Sanders-Jones, Z El-Haqq, A Kolli, J Meigs, A Dushkin, G Rocchio, M Yepes, H Dulin, M Cayford, A DeManbey, M Hillard, N Thangthaeng, L Gurry, R Kochis, E Raymond, V Ripley, V Aroda, Ann Ressing, A Loveland, M Hamm, F Mofor, HJ Florez, WM Valencia, S Casula, L Oropesa-Gonzalez, L Hue, AK Riccio Veliz, R Nieto-Martinez, M Gutt, A Ahmann, D Aby-Daniel, F Joarder, V Morimoto, C Sprague, D Yamashita, N Cady, N Rivera-Eschright, P Kirchhoff, B Morales Gomez, J Adducci, A Goncharova, SH Hox, M Matwichyna, NO Bermudez, L Broadwater, RR Ishii, DS Hsia, WT Cefalu, FL Greenway, C Waguespack, N Haynes, A Thomassie, B Bourgeois, C Hazlett, S Mudaliar, S Boeder, J Pettus, D Garcia-Acosta, S Maggs, C DeLue, E Castro, J Krakoff, JM Curtis, T Killean, E Joshevama, K Tsingine, T Karshner, J Albu, FX Pi-Sunyer, S Frances, C Maggio, J Bastawrose, X Gong, MA Banerji, D Lorber, NM Brown, DH Josephson, LL Thomas, M Tsovian, MH Jacobson, MM Mishko, MS Kirkman, JB Buse, J Dostou, K Bergamo, A Goley, JF Largay, S Guarda, J Cuffee, D Culmer, H Almeida, S Coffer, L Kiker, K Josey, WT Garvey, A Cherrington, D Golson, MC Robertson, A Agne, S McCullars, RM Cohen, MC Rogge, K Kersey, S Lipp, MB Vonder Meulen, C Underkofler, S Steiner, W Sivitz, E Cline, L Knosp, WH Herman, R Pop-Busui, MH Tan, A Waltje, A Katona, L Goodhall, R Eggleston, K Whitley, S Bule, N Kessler, E LaSalle, ER Seaquist, A Bantle, T Harindhanavudhi, B Redmon, M Coe, M Mech, A Taddese, L Lesne, L Kuechenmeister, V Shivaswamy, AL Morales, K Seipel, J Eggert, R Tillson, DS Schade, A Adolphe, M Burge, E Duran-Valdez, P August, MG Rodriguez, JB Kimpel, and O Griffith

Subjects
Adult, Male, medicine.medical_specialty, insulin, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Type 2 diabetes, Lower risk, Diseases of the endocrine glands. Clinical endocrinology, Body Mass Index, chemistry.chemical_compound, Internal medicine, Diabetes mellitus, medicine, OGTT, Humans, Glycemic, C-peptide, business.industry, Insulin, Glucose Tolerance Test, RC648-665, medicine.disease, Metformin, Endocrinology, Cross-Sectional Studies, Glucose, Metabolism, chemistry, Diabetes Mellitus, Type 2, type 2, diabetes mellitus, Female, business, Body mass index, medicine.drug
Abstract

IntroductionThe shape of the glucose curve during an oral glucose tolerance test (OGTT) reflects β-cell function in populations without diabetes but has not been as well studied in those with diabetes. A monophasic shape has been associated with higher risk of diabetes, while a biphasic pattern has been associated with lower risk. We sought to determine if phenotypic or metabolic characteristics were associated with glucose response curve shape in adults with type 2 diabetes treated with metformin alone.Research design and methodsThis is a cross-sectional analysis of 3108 metformin-treated adults with type 2 diabetes diagnosed ResultsThe monophasic profile was the most common (67.8% monophasic, 5.5% biphasic, 26.7% continuous rise). The monophasic subgroup was younger, more likely male and white, and had higher body mass index (BMI), while the continuous rise subgroup was more likely female and African American/black. HOMA2-S and fasting glucose did not differ among the subgroups. The biphasic subgroup had the highest early, late, and total insulin and C peptide responses (all pConclusionsBased on the large multiethnic GRADE cohort, sex, race, age, and BMI were found to be important determinants of the shape of the glucose response curve. A pattern of a continuously rising glucose at 2 hours reflected reduced β-cell function and may portend increased glycemic failure rates.Trial registration numberNCT01794143.

Published
2021

15. Empagliflozin in the treatment of heart failure with reduced ejection fraction in addition to background therapies and therapeutic combinations (EMPEROR-Reduced): a post-hoc analysis of a randomised, double-blind trial

Author

Subodh Verma, Nitish K Dhingra, Javed Butler, Stefan D Anker, Joao Pedro Ferreira, Gerasimos Filippatos, James L Januzzi, Carolyn S P Lam, Naveed Sattar, Barbara Peil, Matias Nordaby, Martina Brueckmann, Stuart J Pocock, Faiez Zannad, Milton Packer, M Packer, S Anker, J Butler, G Filippatos, S Pocock, F Zannad, JP Ferreira, M Brueckmann, J George, W Jamal, FK Welty, M Palmer, T Clayton, KG Parhofer, TR Pedersen, B Greenberg, MA Konstam, KR Lees, P Carson, W Doehner, A Miller, M Haas, S Pehrson, M Komajda, I Anand, J Teerlink, A Rabinstein, T Steiner, H Kamel, G Tsivgoulis, J Lewis, J Freston, N Kaplowitz, J Mann, J Petrie, S Perrone, S Nicholls, S Janssens, E Bocchi, N Giannetti, S Verma, J Zhang, J Spinar, M-F Seronde, M Boehm, B Merkely, V Chopra, M Senni, S Taddi, H Tsutsui, D-J Choi, E Chuquiure, HPB La Rocca, P Ponikowski, JRG Juanatey, I Squire, J Januzzi, I Pina, R Bernstein, A Cheung, J Green, S Kaul, C Lam, G Lip, N Marx, P McCullough, C Mehta, J Rosenstock, N Sattar, B Scirica, S Shah, C Wanner, D Aizenberg, L Cartasegna, F Colombo Berra, H Colombo, M Fernandez Moutin, J Glenny, C Alvarez Lorio, D Anauch, R Campos, A Facta, A Fernandez, R Ahuad Guerrero, L Lobo Márquez, RA Leon de la Fuente, M Mansilla, M Hominal, E Hasbani, M Najenson, G Moises Azize, H Luquez, L Guzman, H Sessa, M Amuchástegui, O Salomone, E Perna, D Piskorz, M Sicer, D Perez de Arenaza, C Zaidman, S Nani, C Poy, J Resk, R Villarreal, C Majul, T Smith Casabella, S Sassone, A Liberman, G Carnero, A Caccavo, M Berli, N Budassi, J Bono, A Alvarisqueta, J Amerena, K Kostner, A Hamilton, A Begg, J Beltrame, D Colquhoun, G Gordon, A Sverdlov, G Vaddadi, J Wong, J Coller, D Prior, A Friart, A Leone, G Vervoort, P Timmermans, P Troisfontaines, C Franssen, T Sarens, H Vandekerckhove, P Van De Borne, F Chenot, J De Sutter, E De Vuyst, P Debonnaire, M Dupont, O Pereira Dutra, LH Canani, MdC Vieira Moreira, W de Souza, LM Backes, L Maia, B De Souza Paolino, ER Manenti, W Saporito, F Villaça Guimarães Filho, T Franco Hirakawa, LA Saliba, FC Neuenschwander, CA de Freitas Zerbini, G Gonçalves, Y Gonçalves Mello, J Ascenção de Souza, L Beck da Silva Neto, EA Bocchi, J Da Silveira, JB de Moura Xavier Moraes Junior, JD de Souza Neto, M Hernandes, HC Finimundi, CR Sampaio, E Vasconcellos, FJ Neves Mancuso, MM Noya Rabelo, M Rodrigues Bacci, F Santos, M Vidotti, MV Simões, FL Gomes, C Vieira Nascimento, D Precoma, FA Helfenstein Fonseca, JA Ribas Fortes, PE Leães, D Campos de Albuquerque, JF Kerr Saraiva, S Rassi, FA Alves da Costa, G Reis, S Zieroth, D Dion, D Savard, R Bourgeois, C Constance, K Anderson, M-H Leblanc, D Yung, E Swiggum, L Pliamm, Y Pesant, B Tyrrell, T Huynh, J Spiegelman, J-P Lavoie, M Hartleib, R Bhargava, L Straatman, S Virani, A Costa-Vitali, L Hill, M Heffernan, Y Khaykin, J Ricci, M Senaratne, A Zhai, B Lubelsky, M Toma, L Yao, R McKelvie, L Noronha, M Babapulle, A Pandey, G Curnew, A Lavoie, J Berlingieri, S Kouz, E Lonn, R Chehayeb, Y Zheng, Y Sun, H 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Escarcega, J, Velasco Sanchez, R, Al - Windy, N, van Heerebeek, L, Bellersen, L, Brunner-La Rocca, H, Post, J, Linssen, G, van de Wetering, M, Peters, R, van Stralen, R, Groutars, R, Smits, P, Yilmaz, A, Kok, W, Van der Meer, P, Dijkmans, P, Troquay, R, van Alem, A, Van de Wal, R, Handoko, L, Westendorp, I, van Bergen, P, Rensing, B, Hoogslag, P, Kietselaer, B, Kragten, J, den Hartog, F, Alings, A, Danilowicz-Szymanowicz, L, Raczak, G, Piesiewicz, W, Zmuda, W, Kus, W, Podolec, P, Musial, W, Drelich, G, Kania, G, Miekus, P, Mazur, S, Janik, A, Spyra, J, Peruga, J, Balsam, P, Krakowiak, B, Szachniewicz, J, Ginel, M, Grzybowski, J, Chrustowski, W, Wojewoda, P, Kalinka, A, Zurakowski, A, Koc, R, Debinski, M, Fil, W, Kujawiak, M, Forys, J, Kasprzak, M, Krol, M, Michalski, P, Mirek-Bryniarska, E, Radwan, K, Skonieczny, G, Stania, K, Skoczylas, G, Madej, A, Jurowiecki, J, Firek, B, Wozakowska-Kaplon, B, Cymerman, K, Neutel, J, Adams, K, Balfour, P, Deswal, A, Djamson, A, Duncan, P, Hong, M, Murray, C, Rinde-Hoffman, D, Woodhouse, S, Macnevin, R, Rama, B, Broome-Webster, C, Kindsvater, S, Abramov, D, Barettella, M, Pinney, S, Herre, J, Cohen, A, Vora, K, Challappa, K, West, S, Baum, S, Cox, J, Jani, S, Karim, A, Akhtar, A, Quintana, O, Paukman, L, Goldberg, R, Bhatti, Z, Budoff, M, Bush, E, Potler, A, Delgado, R, Ellis, B, Dy, J, Fialkow, J, Sangrigoli, R, Ferdinand, K, East, C, Falkowski, S, Donahoe, S, Ebrahimi, R, Kline, G, Harris, B, Khouzam, R, Jaffrani, N, Jarmukli, N, Kazemi, N, Koren, M, Friedman, K, Herzog, W, Silva Enciso, J, Cheung, D, Grover-McKay, M, Hauptman, P, Mikhalkova, D, Hegde, V, Hodsden, J, Khouri, S, Mcgrew, F, Littlefield, R, Bradley, P, Mclaurin, B, Lupovitch, S, Labin, I, Rao, V, Leithe, M, Lesko, M, Lewis, N, Lombardo, D, Mahal, S, Malhotra, V, Dauber, I, Banerjee, A, Needell, J, Miller, G, Paladino, L, Munuswamy, K, Nanna, M, Mcmillan, E, Mumma, M, Napoli, M, Nelson, W, O'Brien, T, Adlakha, A, Onwuanyi, A, Serota, H, Schmedtje, J, Paraschos, A, Potu, R, Sai-Sudhakar, C, Saltzberg, M, Sauer, A, Shah, P, Skopicki, H, Bui, H, Carr, K, Stevens, G, Tahirkheli, N, Tallaj, J, Yousuf, K, Trichon, B, Welker, J, Tolerico, P, Vest, A, Vivo, R, Wang, X, Abadier, R, Dunlap, S, Weintraub, N, Malik, A, Kotha, P, Zaha, V, Kim, G, Uriel, N, Greene, T, Salacata, A, Arora, R, Gazmuri, R, Kobayashi, J, Iteld, B, Vijayakrishnan, R, Dab, R, Mirza, Z, Marques, V, Nallasivan, M, Bensimhon, D, Peart, B, Saint-Jacques, H, Barringhaus, K, Contreras, J, Gupta, A, Koneru, S, Nguyen, V, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Male, medicine.medical_specialty, Angiotensin receptor, Glucoside, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Placebo, 03 medical and health sciences, Angiotensin Receptor Antagonists, 0302 clinical medicine, Endocrinology, Mineralocorticoid receptor, Glucosides, Double-Blind Method, Internal medicine, Post-hoc analysis, Internal Medicine, medicine, Empagliflozin, Humans, 030212 general & internal medicine, Benzhydryl Compounds, ComputingMilieux_MISCELLANEOUS, Aged, Benzhydryl Compound, Heart Failure, Ejection fraction, business.industry, Angiotensin Receptor Antagonist, Adrenergic beta-Antagonist, Angiotensin-Converting Enzyme Inhibitor, Stroke Volume, medicine.disease, 3. Good health, Heart failure, ACE inhibitor, Female, Hypotension, business, medicine.drug, Human
Abstract

Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

Published
2022
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16. Ataluren delays loss of ambulation and respiratory decline in nonsense mutation Duchenne muscular dystrophy patients

Author

Craig M McDonald, Francesco Muntoni, Vinay Penematsa, Joel Jiang, Allan Kristensen, Francesco Bibbiani, Elizabeth Goodwin, Heather Gordish-Dressman, Lauren Morgenroth, Christian Werner, James Li, Richard Able, Panayiota Trifillis, Már Tulinius, M Ryan, K Jones, N Goemans, C Campbell, JK Mah, K Selby, B Chabrol, Y Pereon, T Voit, T Gidaro, U Schara, JB Kirschner, Y Nevo, GP Comi, E Bertini, E Mercuri, J Colomer, A Nascimento, JJ Vilchez, M Tulinius, T Sejersen, F Muntoni, K Bushby, and M Guglieri

Subjects
medicine.medical_specialty, Vital capacity, nonsense mutation Duchenne muscular dystrophy, Duchenne muscular dystrophy, Nonsense mutation, efficacy, Walking, dystrophin, chemistry.chemical_compound, respiratory function, Internal medicine, loss of ambulation, medicine, Humans, Respiratory function, Respiratory system, Oxadiazoles, business.industry, Health Policy, ataluren, medicine.disease, Ataluren, Muscular Dystrophy, Duchenne, chemistry, Codon, Nonsense, Propensity score matching, Ambulatory, Study 019, business, Research Article
Abstract

Aim: We investigated the effect of ataluren plus standard of care (SoC) on age at loss of ambulation (LoA) and respiratory decline in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) versus patients with DMD on SoC alone. Patients & methods: Study 019 was a long-term Phase III study of ataluren safety in nmDMD patients with a history of ataluren exposure. Propensity score matching identified Study 019 and CINRG DNHS patients similar in disease progression predictors. Results & conclusion: Ataluren plus SoC was associated with a 2.2-year delay in age at LoA (p = 0.0006), and a 3.0-year delay in decline of predicted forced vital capacity to ClinicalTrials.gov registration : NCT01557400 .

Published
2021

17. RHOA MUTATION IS A POTENTIAL BIOMARKER ASSOCIATED WITH ADVERSE PROGNOSIS AND HIGH- TUMOR BURDEN IN PATIENTS WITH NODAL PERIPHERAL LYMPHOMAS WITH T-HELPER FOLLICULAR PHENOTYPE (NPTCL-THF): DATA FROM A BRAZILIAN RETROSPECTIVE COHORT OF NPTCL

Author

Vanderson Rocha, Lbo Alves, Luciana Nardinelli, Israel Bendit, GC Barreto, JB Cavalcanti, Hebert Fabricio Culler, Lapc Lage, and Juliana Pereira

Subjects
Oncology, Mutation, medicine.medical_specialty, education.field_of_study, RHOA, biology, business.industry, Population, Retrospective cohort study, Hematology, Gene mutation, medicine.disease_cause, IDH2, Internal medicine, Cohort, medicine, biology.protein, Immunology and Allergy, Diseases of the blood and blood-forming organs, Epigenetics, RC633-647.5, business, education
Abstract

Introduction: Nodal-PTCL constitute a rare group of aggressive malignancies with heterogeneous clinical-biological presentation and outcomes. Recently its pathophysiological knowledge has been highly improved, with descriptions of gene mutations associated with epigenetic phenomena and of the RHOA G17V mutation playing a fundamental role in the lymphomagenesis. However, the prognostic impact of these alterations is still controversial, and particularly, in the case of the RHOA mutation, it has never been previously accessed in the literature. The aim of this study was to evaluate the frequency and prognostic impact of mutations in the IDH2, TET2, DNMT3 and RHOA genes in Brazilian patients with nPTCL. Methods: In this observational, retrospective and unicentric study, we analyzed the clinical-epidemiological characteristics, outcomes and mutational profile of 59 Brazilian patients with nPTCL treated at the HC-FMUSP, from January 2000 to December 2017. All cases were submitted to centralized histopathological review and were classified according to the criteria proposed by WHO-2016. FFPE tumor samples from patients with PTCL/NOS, AITL, ALK+/ALCL and ALK-/ALCL were deparaffinized and submitted to DNA extraction using QIAmp DNA FFPE kit. For amplification of specific products of target-genes primers flanking the hot spots regions were designed. After this step, the PCR products were submitted to first generation sequencing. Absolute and relative frequencies of mutations were accessed for the total cohort and its pathological subtypes. OS and PFS curves were constructed using the Kaplan-Meier method. Log-rank test was used to estimate the prognostic impact of mutations in the studied population. Results: With a median follow-up of 3.70 years, the estimated 2-years OS and PFS were 59.1% and 47.2%, respectively. ORR was 55.9%, with early relapse rate (< 12 months) of 14.3% and global death rate of 52.5%. In the total cohort, we found a mutation frequency of 3.4% (2/59) for the IDH2 gene, 62.7% (37/59) for DNMT3A, 23.7% (14/59) for RHOA and 50.8% (30/59) for TET2. There was no statistically significant difference in the frequency distribution of IDH2, DNMT3A and TET2 mutations between the different histological subtypes of nPTCL. However, there was a statistical trend towards a higher occurrence of the RHOA mutation in the AITL and nPTCL-Thf subtypes (3/9–33.3% and 7/16-43.7%, respectively; p = 0.07). So, the mutation RHOA was predominantly found in THf cell-derived neoplasms in our cohort. The mutational status of DNMT3A, RHOA and TET2 genes had no prognostic impact on OS, with p = 0.85, p = 0.13 and p = 0.95, respectively. The same was observed in relation to PFS for the DNMT3A (p = 0.70) and TET2 (p = 0.52) mutations. However, the presence of the RHOA mutation was associated with the unfavorable PFS in our cohort (HR:1.98, p = 0.05). We observed 2-year PFS of 28.6% (95% CI: 8.8-52.4%) for mutated-RHOA cases versus 52.9% (95% CI: 37.3-66.3%) for wild-type-RHOA patients (p = 0.05). We also demonstrated that the presence of the RHOA mutation was a predictor of lower ORR to first-line therapy (p = 0.01) and was associated with high tumor burden (p = 0.03). Conclusion: For the first time we demonstrated the unfavorable prognostic impact of the RHOA mutation in patients with nPTCL with THf-phenotype, making it a potential molecular biomarker predictor of poor-PFS, associated with resistance to primary therapy and with high tumor burden.

Published
2021

18. Diagnostic evaluation of IgM ELISA and IgM Immunofluorescence assay for the diagnosis of Acute Scrub Typhus in central Nepal

Author

John Stenos, Sherchand Jb, Keshab Parajuli, Tshokey Tshokey, and Rajendra Gautam

Subjects
Adult, Male, medicine.medical_specialty, Orientia tsutsugamushi, Endemic Diseases, Prevalence, Fluorescent Antibody Technique, Enzyme-Linked Immunosorbent Assay, Scrub typhus, Gastroenterology, Likelihood ratios in diagnostic testing, Sensitivity and Specificity, lcsh:Infectious and parasitic diseases, Nepal, Internal medicine, medicine, Humans, lcsh:RC109-216, Prospective Studies, biology, business.industry, Diagnostic Tests, Routine, Gold standard (test), medicine.disease, biology.organism_classification, bacterial infections and mycoses, Orientia, Antibodies, Bacterial, Infectious Diseases, Immunoglobulin M, biology.protein, Female, ELISA, Antibody, business, Research Article
Abstract

Introduction Scrub typhus is an acute febrile illness caused by the obligate intracellular bacterium,Orientia tsutsugamushi. Given their affordability and ease of use, antibody based diagnostic assays can be important diagnostic tools for early detection of scrub typhus fever in resource poor countries like Nepal. Immunochromatography (ICT) and IgM ELISA are two of the routinely employed antibody based assays for diagnosis of Scrub typhus fever in Nepal, although the recommended gold standard diagnostic test is IgM Immunofluorescence assay (IFA). This study evaluated the InBios Scrub Typhus Detect™ Immunoglobulin M (IgM) ELISA and IgM Immunofluorescence assays in single serum sample at the time of admission. Methodology Study participants (1585 suspected cases), were enrolled based on acute febrile illness with suspected scrub typhus cases in central Nepal from April 2017 to March 2018. Blood sample was collected from the suspected patients of scrub typhus, presenting with acute febrile illness. IgM antibody to Orientia tsusugamushi was detected by using Scrub Typhus Detect™ Kit (In Bios International, USA) and an in-house IgM IFA (Australian Rickettsial Reference Laboratory, Geelong, Australia. The IFA assay was performed with the Gilliam, Karp, Kato strains and O. chuto antigens following the ARRL protocol. Result Statistical analysis of ELISA IgM results when compared to reference test, IgM IFA results demonstrated the following characteristics, sensitivity 84.0% (95%CI: 79.73%-87.68%), specificity 94.82% (95% CI: 93.43%-95.99%), positive likelihood ratio 16.21% (95% CI: 12.71%-20.67%), negative likelihood ratio 0.17% (95% CI: 0.13-0.21%), disease prevalence 22.08% (95% CI: 20.06%-24.21%), positive predictive value 82.12% (95% CI: 78.28-85.42%) and negative predictive value 95.44% (95% CI: 94.27%-96.38%) respectively. Conclusion The study indicated that the IgM ELISA has the sensitivity 84.0% (95% CI: 79.73%-87.68%) and specificity 94.82% (95% CI: 93.43%-95.99%). Although IgM IFA is considered the gold standard test for the diagnosis of scrub typhus cases, it is relatively expensive, requires trained personal and a microscope with fluorescence filters. Scrub typhus IgM ELISA with appropriate OD cut–off values may be the best alternative test and possible viable option for resource limited endemic countries like Nepal.

Published
2020

19. Hematological prediction study of peritonitis following laparotomy in goats

Author

Shakirat Omolara Adediran, Abdullahi Aliyu, Waliyullahi Folorunsho Abdulwahab, JB Adeyanju, Salman Zubairu Abdulkadir, Hameedat Olayinka Uthman, Olawale Alimi Alimi, Abdullateef Ajadi, F. M. Lawal, Sadudeen Adetayo Amid, and Mashood Bolaji

Subjects
Male, medicine.medical_specialty, Exploratory laparotomy, medicine.medical_treatment, Peritonitis, Abdominal wall, Xylazine, Postoperative Complications, Peritoneum, Laparotomy, Internal medicine, medicine, Animals, Goat Diseases, Hematology, Full Paper, General Veterinary, hematology, West African Dwarf, business.industry, Goats, goat, medicine.disease, medicine.anatomical_structure, Anesthesia, Female, Surgery, business, medicine.drug, Abdominal surgery
Abstract

Surgical trauma to the abdominal wall and peritoneum during celiotomy is expected to cause postoperative inflammation. However, complications after abdominal surgery are hardly detected in the early stage. Hematological analysis of blood has been considered beneficial in disease diagnosis and prognosis. This study aimed to evaluate the hematological parameters predicting peritonitis in goats and to determine the post-surgery day that hematology is significant. Six apparently healthy West African Dwarf goats were included in this study. After 2 weeks of acclimatization, blood samples were obtained daily for 3 days for hematological analyses, which served as the baseline data. The right flanks of the animals were aseptically prepared routinely for exploratory laparotomy. Restraint and anesthesia were achieved using xylazine and lignocaine using an inverted “L” block technique. Laparotomy was performed, and the incision was left for 20 min and then closed routinely. Blood samples were collected for hemogram 24 hr postoperatively and daily for 7 days. Based on the post-surgery hematology results, relative neutrophil (P=0.015) and lymphocyte (P=0.006) counts significantly increased and decreased on day 5 respectively. Significant differences were also observed for red blood cell count, hemoglobin concentration, and packed cell volume on days 5, 6, and 7 respectively. It could therefore be concluded that the diagnostic result for hematology post-laparotomy can be obtained on the fifth and sixth day.

Published
2020
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21. Deflazacort vs prednisone treatment for Duchenne muscular dystrophy: A meta‐analysis of disease progression rates in recent multicenter clinical trials

Author

McDonald CM, A238., Sajeev, G, Yao, Z, Mcdonnell, E, Elfring, G, Souza, M, Peltz, Sw, Darras, Bt, Shieh, Pb, Cox, Da, Landry, J, Signorovitch, J, Campbell, C, Torricelli, Re, Finkel, Rs, Flanigan, Km, Goemans, N, Heydemann, P, Kaminska, A, Kirschner, J, Muntoni, F, Osorio, An, Schara, U, Sejersen, T, Sweeney, Hl, Topaloglu, H, Tulinius, M, Vilchez, Jj, Voit, T, Wong, B, Alfano, Ln, Eagle, M, James, Mk, Lowes, L, Mayhew, A, Mazzone, Es, Nelson, L, Rose, Kj, Abdel-Hamid, Hz, Apkon, Sd, Barohn, Rj, Bertini, E, Bloetzer, C, de Vaud LC, Butterfield, Rj, Chabrol, B, Chae, Jh, Jongno-Gu, Dr, Comi, Gp, Dastgir, J, Desguerre, I, Escobar, Rg, Finanger, E, Guglieri, M, Hughes, I, Iannaccone, St, Jones, Kj, Karachunski, P, Kudr, M, Lotze, T, Mah, Jk, Mathews, K, Nevo, Y, Parsons, J, Péréon, Y, de Queiroz Campos Araujo AP, Renfroe, Jb, de Mbd, R, Ryan, M, Selby, K, Tennekoon, G, Vita, G, Abdel-Hamid, H, Apkon, S, Barohn, R, Belousova, E, Brandsema, J, Bruno, C, Burnette, W, Butterfield, R, Byrne, B, Carlo, J, Chandratre, S, Comi, G, Connolly, A, De Groot, I, Deconinck, N, Dooley, J, Dubrovsky, A, Durigneux, J, Finkel, R, Frank, Lm, Harper, A, Hattori, A, Herguner, O, Iannaccone, S, Janas, J, Jong, Yj, Komaki, H, Kuntz, N, Lee, Wt, Leung, E, Mah, J, Cm, M, Mercuri, E, Mcmillan, H, Mueller-Felber, W, Lopez de Munain, A, Nakamura, A, Niks, E, Ogata, K, Pascual, S, Pegoraro, E, Pereon, Y, Renfroe, B, Sanka, Rb, Schallner, J, Sendra, Ii, Servais, L, Smith, E, Sparks, S, Victor, R, Wicklund, M, Wilichoswki, E, and Wong, B.

Subjects
Male, Duchenne muscular dystrophy, 0301 basic medicine, medicine.medical_specialty, Physiology, medicine.drug_class, Prednisolone, Anti-Inflammatory Agents, Walking, 030105 genetics & heredity, Placebo, prednisone/prednisolone, ambulatory function, deflazacort, meta-analysis, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Pregnenediones, Prednisone, Physiology (medical), Internal medicine, Humans, Multicenter Studies as Topic, Medicine, Child, Clinical Research Articles, Randomized Controlled Trials as Topic, Clinical Research Article, business.industry, medicine.disease, Confidence interval, Muscular Dystrophy, Duchenne, Deflazacort, Treatment Outcome, meta‐analysis, Ambulatory, Disease Progression, Corticosteroid, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Introduction In this study we characterized disease progression over 48 weeks among boys receiving deflazacort vs prednisone/prednisolone placebo arm treatment in two recent Duchenne muscular dystrophy (DMD) clinical trials. Methods Ambulatory boys with DMD receiving placebo in the phase 3 ataluren (N = 115) and tadalafil (N = 116) trials were included. The trials required at least 6 months of prior corticosteroid use and stable baseline dosing. Associations between corticosteroid use and 48‐week changes in ambulatory function were estimated using mixed models. Adjusted differences between corticosteroid groups were pooled in a meta‐analysis. Results In the meta‐analysis, deflazacort‐treated patients vs prednisone/prednisolone‐treated patients experienced, on average, lower declines of 28.3 meters on 6‐minute walk distance (95% confidence interval [CI], 5.7, 50.9; 2.9 seconds on rise from supine [95% CI, 0.9, 4.9 seconds]; 2.3 seconds on 4‐stair climb [95% CI, 0.5, 4.1 seconds]; and 2.9 [95% CI, 0.1, 5.8] points on the North Star Ambulatory Assessment linearized score). Discussion Deflazacort‐treated patients experienced significantly lower functional decline over 48 weeks.

Published
2019
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22. Chlamydia psittaci infection as a cause of respiratory disease in neonatal foals

Author

Catherine Russell, Shane Raidal, JB Carrick, Kristopher Hughes, Lucy Cudmore, Sarah Gough, Sharanne Raidal, NM Collins, and S. Keane

Subjects
medicine.medical_specialty, Systemic disease, 040301 veterinary sciences, animal diseases, urologic and male genital diseases, digestive system, 0403 veterinary science, Internal medicine, parasitic diseases, medicine, Chlamydia psittaci, Lung, biology, Critically ill, business.industry, Respiratory disease, 0402 animal and dairy science, Horse, 04 agricultural and veterinary sciences, General Medicine, medicine.disease, biology.organism_classification, 040201 dairy & animal science, female genital diseases and pregnancy complications, medicine.anatomical_structure, Atypical pneumonia, Differential diagnosis, business
Abstract

Background During 2016-2018, 15 critically ill neonatal foals with acute respiratory distress associated with Chlamydia psittaci infection were presented to three referral hospitals in New South Wales. Chlamydia psittaci has not previously been associated with the development of neonatal respiratory disease. Objectives To investigate and describe the clinical features and outcome of C. psittaci infection in neonatal foals. Study design Multicentre retrospective case series. Methods The clinical, clinicopathological, necropsy and histological features of 15 foals with confirmed C. psittaci infection were reviewed and reported. Results Thirteen foals with C. psittaci infection died or were subjected to euthanasia within 36 h of hospitalisation and two foals survived to discharge. Findings during post-mortem examination of nonsurviving foals included bronchopneumonia, pulmonary congestion, hepatic congestion and hepatic inflammation. Detection of C. psittaci was achieved using polymerase chain reaction (PCR) testing of swabs of nasal secretions (4/6) and rectal mucosa (5/7) from live foals, lung tissues of foals at necropsy (11/14) and foetal membranes (4/5). Main limitations Small numbers of confirmed cases of neonatal C. psittaci infection and inconsistent sampling methods. Conclusions Chlamydia psittaci should be considered a differential diagnosis for neonatal foals with signs of severe systemic disease, including equine neonatal acute respiratory distress syndrome (EqNARDS). Chlamydia psittaci is a zoonotic pathogen and a personal protective equipment (PPE) should be worn for the management of foals with suspected or confirmed infection.

Published
2019
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23. Long‐term efficacy and safety of combined insulin and glucagon‐like peptide‐1 therapy: Evidence from the LEADER trial

Author

Tack, CJ, Jacob, S, Desouza, C, Bain, SC, Buse, JB, Nauck, MA, Petrie, JR, Poulter, NR, Pratley, RE, Stegmann, HVBK, Bosch-Traberg, H, Startseva, E, Zinman, B, and LEADER Publication Committee on behalf of the LEADER Trial Investigators

Subjects
Male, Agonist, medicine.medical_specialty, Combination therapy, medicine.drug_class, insulin analogues, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, glucagon‐like peptide‐1 analogue, Type 2 diabetes, Disease, 030204 cardiovascular system & hematology, glucagon-like peptide-1 analogue, Placebo, Glucagon-Like Peptide-1 Receptor, Endocrinology & Metabolism, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, LEADER Publication Committee on behalf of the LEADER Trial Investigators, Internal medicine, Internal Medicine, Humans, Hypoglycemic Agents, Insulin, Medicine, Aged, Glycated Hemoglobin, liraglutide, business.industry, Liraglutide, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], 1103 Clinical Sciences, Original Articles, Middle Aged, medicine.disease, Glucagon-like peptide-1, 3. Good health, Diabetes Mellitus, Type 2, insulin therapy, Female, Original Article, type 2 diabetes, business, medicine.drug
Abstract

Contains fulltext : 215463.pdf (Publisher’s version ) (Open Access) AIM: Glucagon-like peptide-1 receptor agonist (GLP-1RA) and insulin combination therapy is an effective treatment option for type 2 diabetes, but long-term data are lacking. The aim was to assess the long-term efficacy of the GLP-1RA liraglutide in subgroups by insulin use in the LEADER trial. MATERIALS AND METHODS: LEADER assessed cardiovascular (CV) safety and efficacy of liraglutide (1.8 mg) versus placebo (plus standard of care therapy) in 9340 patients with type 2 diabetes and high risk of CV disease, for up to 5 years. We analyzed CV events, metabolic parameters and hypoglycaemia post hoc in three subgroups by baseline insulin use (basal-only insulin, other insulin or no insulin). Insulin was a non-random treatment allocation as part of standard of care therapy. RESULTS: At baseline, 5171 (55%) patients were not receiving insulin, 3159 (34%) were receiving basal-only insulin and 1010 (11%) other insulins. Insulin users had a longer diabetes duration and slightly worse glycaemic control (HbA1c) than the no-insulin subgroup. Liraglutide reduced HbA1c and weight versus placebo in all three subgroups (P < .001), and severe hypoglycaemia rate in the basal-only insulin subgroup. The need for insulin was less with liraglutide. CV risk reduction with liraglutide was similar to the main trial results in the basal-only and no-insulin subgroups. CONCLUSIONS: In patients on insulin, liraglutide improved glycaemic control, weight and need for insulin versus placebo, for at least 36 months with no increased risk of severe hypoglycaemia, while maintaining CV safety/efficacy, supporting the combination of liraglutide and insulin for management of type 2 diabetes.

Published
2019
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24. Combined immunoglobulin free light chains are novel predictors of cardiovascular events in patients with abdominal aortic aneurysm

Author

Luis Miguel Blanco-Colio, C. Vegas-Dominguez, E. Nuñez, Michel Jb, J.L. Martin-Ventura, Jesús Vázquez, Carmen Gomez-Guerrero, L. Ortega-Villanueva, Jes S. Lindholt, I. Cerro-Pardo, R.R. Montero, Ministerio de Economía, Innovación y Competitividad (España), Fundación La Caixa, Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), and Comunidad de Madrid (España)

Subjects
medicine.medical_specialty, biology, business.industry, Immunoglobulin light chain, medicine.disease, Prognosis, Abdominal aortic aneurysm, Logistic Models, Risk Factors, Internal medicine, Cardiology, biology.protein, Medicine, Humans, In patient, Surgery, Immunoglobulin Light Chains, Antibody, business, Cardiology and Cardiovascular Medicine, Biomarkers, Aortic Aneurysm, Abdominal
Abstract

Abdominal aortic aneurysm (AAA) is characterised by the presence of B cells and immunoglobulins in the aortic wall, mainly in the adventitia. Kappa (κ) and lambda (λ) free light chains (FLCs) are produced from B cells during immunoglobulin synthesis. This study investigated the presence and prognostic value of combined FLCs (cFLCs or summed κ and λ) in patients with AAA. cFLCs were analysed by a turbidimetric specific assay in tissue conditioned media from AAA samples (n = 34) compared with healthy aortas (n = 34) from France and in plasma samples from patients with AAA (n = 434) and age matched controls (n = 104) selected from the Viborg Vascular (VIVA) AAA screening trial in Denmark. t test, logistic regression, and Cox regression were used to test whether plasma cFLCs serve as a marker for AAA presence and whether cFLCs were predictive of death, major adverse cardiovascular events (MACE), or major adverse lower limb events (MALE). Increased cFLC levels were detected in the AAA adventitial layer compared with the AAA medial layer and healthy media layer (13.65 ± 3.17 vs. 6.57 ± 1.01 vs. 0.49 ± 0.09 mg/L, respectively, p < .050). The upper tertile of plasma cFLCs was independently associated with AAA presence after correcting for confounders (odds ratio [OR] 7.596, 95% confidence intervals [CI] 3.117 - 18.513; p < .001). Of 434 patients with AAA, 89 (20.5%) died, 104 (24.0%) suffered MACE, and 63 (14.5%) suffered MALE, during a five year follow up. In univariable analysis, the cFLC upper tertile was associated with a higher risk of death, MACE, and MALE (p < .001 for all). After adjustment for confounders, cFLCs remained an independent predictor of all cause mortality (hazard ratio [HR] 4.310, 95% CI 2.157 - 8.609; p < .001), MACE (HR 2.153, 95% CI 1.218 - 3.804; p = .008), or MALE (HR 3.442, 95% CI 1.548 - 7.652; p = .002) for those in the upper tertile. Increased cFLCs are observed in adventitial tissue of patients with AAA, indicating local activation of B cells. Plasma cFLC levels are an independent predictor of death, MACE, and MALE in patients with AAA. This study was funded by the Spanish MINECO (PID2019- 106814RB-I00 and PGC2018-097019-B-I00), la Caixa Foundation (HR17-00247), CAM (S2017/BMD-3673), and Fondo de Investigaciones Sanitarias ISCiii-FEDER (PI19/ 00128). Sí

Published
2021
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25. Are His bundle pacing or His bundle plus coronary sinus pacing superior to conventional cardiac resynchronization therapy in improving heart failure? Results from a controlled study

Author

JS Senes, TG Grimaldi, NB Bottoni, Giovanni Coluccia, Paolo Donateo, CM Calogero, Enrico Puggioni, JB Bertolozzi, MB Brignole, Giuseppe Mascia, and Daniele Oddone

Subjects
medicine.medical_specialty, Ejection fraction, Intention-to-treat analysis, business.industry, Surrogate endpoint, medicine.medical_treatment, Cardiac resynchronization therapy, medicine.disease, Bundle of His, medicine.anatomical_structure, Physiology (medical), Internal medicine, Heart failure, Bundle, medicine, Cardiology, Cardiology and Cardiovascular Medicine, business, Coronary sinus
Abstract

Funding Acknowledgements Type of funding sources: None. BACKGROUND His bundle pacing (HBP), alone or optimized in association with coronary sinus pacing (HBP + LV) has recently been proposed as an alternative to conventional cardiac resynchronization therapy (CRT). However, there is lack of controlled studies that assessed clinical outcome. METHODS We did a single-centre, propensity-score matched, case-control study of comparison of HBP and HBP + LV versus conventional CRT in patients with heart failure (HF) and standard indications for CRT. The study group patients (n = 27) were consecutively enrolled in the years 2019. The control group patients (n = 27) were selected, by propensity score matching, among those CRT implantations performed, in the years 2015-2018. RESULTS In the active group, HBP alone was preferred in 12 (44%) patients, HBP + LV pacing in 12 (44%) patients and HBP failed in 3 (11%) patients. In the control group, conventional CRT was achieved in 26 (96%) patients and failed in one. Paced QRS width was shorter in the active than in the control group (128 ± 18 ms vs 148 ± 27 ms, p = 0.004). During a mean of 9.6 months of follow-up, in the intention-to-treat analysis, a composite clinical outcome of death, hospitalization for HF or worsening HF occurred in 3 (11%) in the active group and in 4 (15%) in the control group, p = 0.58. No difference was also observed with softer endpoints: NYHA class (1.9 ± 0.7 versus 2.1 ± 0.7), subjective improvement (74% versus 74%) and LV ejection fraction (40.7% versus 40.7%). CONCLUSION Compared with standard CRT, a shorter QRS width can be obtained with HBP alone or HBP + LV but we were unable to show a better clinical outcome. There is urgent need for large, randomized trials. Results by intention-to-treat analysisVariableActive groupN = 27Control groupN = 27PFollow-up, months9.7 ± 4.89.5 ± 4.50.90QRS width, ms128 ± 18148 ± 270.004Combined primary endpoint3 (11%)4 (15%)0.58• Death for HF10• Hospitalization for HF24• Worsening HF-1Subjective improvement20 (74%)20 (74%)1.24NYHA class1.9 ± 0.72.1 ± 0.70.15LV ejection fraction (%)40.7 ± 11.540.7 ± 12.21.00HF = heart failure; NYHA = New York Heart Association; LV = left ventricleAbstract Figure. Flow of active group patients

Published
2021
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26. Lower perception of pharmacological treatment increases risk of non-adherence to medication

Author

Sam Riahi, Mogens Lytken Larsen, Teresa Holmberg, JB Valentin, Christina Boesgaard Graversen, Line Zinckernagel, and Søren Paaske Johnsen

Subjects
medicine.medical_specialty, Epidemiology, business.industry, Perception, media_common.quotation_subject, Internal medicine, medicine, Cardiology and Cardiovascular Medicine, business, Non adherence, Pharmacological treatment, media_common
Abstract

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation Background A large proportion of patients fail to reach optimal adherence to medication following incident ischemic heart disease (IHD) despite amble evidence of the beneficial effect of medication. Non-adherence to medication increases risk of disease-related adverse outcomes but none has explored how perception about pharmacological treatment detail on non-adherence using register-based follow-up data. Purpose To investigate the association between patients’ perception of pharmacological treatment and risk of non-initiation and non-adherence to medication in a population with incident IHD. Methods This cohort study followed 871 patients until 365 days after incident IHD. The study combined patient-reported survey data on perception about pharmacological treatment (categorised by ‘To a high level’, ‘To some level’, and ‘To a lesser level’) with register-based data on reimbursed prescription of cardiovascular medication (antithrombotics, statins, ACE-inhibitors/angiotensin receptor blockers, and β-blockers). Non-initiation was defined as no pick-up of medication in the first 180 days following incident IHD and analysed by Poisson regression. Two different measures evaluated non-adherence in patients initiating treatment: 1) proportion of days covered (PDC) analysed by Poisson regression, and 2) risk of discontinuation analysed by Cox proportional hazard regression. All analyses were adjusted for confounding variables (age, sex, ethnicity, income, educational level, civil status, occupation, charlson comorbidity index, supportive relatives, and individual consultation in medication) identified by directed acyclic graph and obtained from national registers and the survey. Item non-response was handled by multiple imputation and item consistency was evaluated by McDonalds omega. Results Lower perceptions about pharmacological treatment was associated with increased risk of non-initiation and non-adherence to medication irrespectively of drug class and adherence measure in the multiple adjusted analyses (please see figure illustrating results on antithrombotics). A dose-response relationship was observed both at 180- and 365-days of follow-up, but the steepest decline in adherence differed when comparing the two adherence measures (results not shown). Moderate internal consistency was found for the summed measure of perception (McDonalds omega = 0.67). Conclusion Lower perception of pharmacological treatment was associated with subsequent non-initiation and non-adherence to medication, irrespectively of measurement method and drug class. Abstract Figure. Figre: Multiple adjusted analyses

Published
2021
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27. Early treatment with nitazoxanide prevents worsening of mild and moderate COVID-19 and subsequent hospitalization

Author

Bréchot C, Rossignol J, Mogelnicki D, Matthew Cb, Bostick Bg, Fulgencio J, Vora Kn, and Oaks Jb

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Nitazoxanide, Placebo, Multicenter study, Internal medicine, Sustained response, medicine, business, Extended release tablets, Viral load, medicine.drug
Abstract

BackgroundThere is an urgent need for treatments to prevent the progression to severe COVID-19 and hospitalization.MethodsA randomized double-blind placebo-controlled clinical trial in 36 centers in the U.S. and Puerto Rico investigated the safety and effectiveness of oral nitazoxanide 600 mg twice daily for 5 days in outpatients with symptoms of mild or moderate COVID-19 enrolled within 72 hours of symptom onset. Key objectives were reduction of duration of symptoms (primary) and progression to severe illness (key secondary).Results1,092 subjects were enrolled, and 379 with laboratory-confirmed SARS-CoV-2 infection were analyzed. Overall, times to sustained clinical recovery were similar for the two arms. Nitazoxanide treatment was associated with an 85% reduction in the progression to severe COVID-19 (1/184, [0.5%] vs. 7/195, [3.6%], p=0.07) and 82% reduction in the rate of hospitalization, emergency room visit or death (1/184 [0.5%] vs. 6/195 [3.1%], p=0.12). In subjects with mild illness at baseline, treatment was also associated with a 3.1-day reduction in median time to sustained clinical recovery and a 5.2-day reduction in time to return to usual health. Nitazoxanide was safe and well tolerated.ConclusionsTreatment of mild or moderate COVID-19 with a five-day course of oral nitazoxanide was safe and well tolerated and was associated with an 85% reduction in the progression to severe illness and a 3- to 5-day reduction of the duration of mild illness.

Published
2021
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28. Cardiac Tamponade - A Hypothyroidism Associated Emergency: A Report of 2 Cases

Author

Khichar S, Garg Mk, Tripathi S, Vijayvergia P, and Sharma Jb

Subjects
endocrine system, medicine.medical_specialty, endocrine system diseases, business.industry, Cardiac tamponade, Internal medicine, medicine, Cardiology, General Medicine, medicine.disease, business, hormones, hormone substitutes, and hormone antagonists
Abstract

Pericardial effusion in commonly seen in-patient with hypothyroidism but effusion large enough to cause cardiac tamponade is not a common presenting feature whereas myxedema coma is a commonly defined medical emergency in-patient with hypothyroidism. We report 2 cases of hypothyroid associated medical emergencies. First case is a young female with history of recurrent pericardial effusion presenting to the emergency department with cardiac tamponade and later on diagnosed as having hypothyroidism. The second patient is a known case of hypothyroidism non-compliant to thyroid supplement and presented with lethargy, fatigue, decreased talking and breathlessness who was later diagnosed as having myxedema coma and impending cardiac tamponade. Both the patient required percutaneous pericardiocentesis and improved with medical management.

Published
2021
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29. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes

Author

Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Peterson ED, Holman RR, Josse RG, Califf RM, Goldstein BJ, Shapiro DR, Silverman R, Bethel A, Green J, Hayden S, Hannan K, Quintero K, Rorick T, Berdan L, Leloudis D, Califf S, Wilson M, McFarron D, Trollinger K, Pesarchick J, Eskenazi L, Campbell C, Townes O, Tolsma D, Keenan J, Milton J, Athwal R, Darbyshire J, Doran Z, Kennedy I, Gregory V, Lokhnygina Y, Prather K, Wolfley A, Usman M, Tajjar A, Gray R, Pfeffer MA, Gerstein HC, Groop L, McMurray JJ, Pocock SJ, Clayton T, Sinay I, Brieger D, Stranks S, Scheen A, Lopes R, Tankova T, Hramiak I, Grado CR, Wenying Y, Ge J, Aschner P, Skrha J, Ambos A, Strandberg T, Travert F, Hanefeld M, Riefflin A, Chan JC, Ofner P, Reddy NK, Christopher J, Mathur A, Arambam P, Mittal S, Manchanda M, Wainstein J, Ambrosio G, Pirags V, Jakuboniene N, Mohamed M, Scott R, White H, Cornel J, Halvorsen S, Tykarski A, Veresiu IA, Dreval AV, Misinkova I, Tai E, Krahulec B, Distiller L, Park Y, Rovira A, Alversson M, Chuang LM, Delibasi T, Adler A, Rodbard HW, Marre M, Goff D, Chacra A, DeVore A, Beaven A, Shah B, Hirsch B, Batch B, Bushnell C, Patel C, Melloni C, Henshaw C, Kong D, Bernecki G, Tillman H, Kang HJ, Hawes J, Strickler J, Piccini J, Wilder J, Alexander K, Mahaffey K, Patel K, Hyland K, Newby K, Jackson L, Cooper L, Armaganijan L, Szczeh L, Koshizaka M, Roe M, Morse M, Guimaraes P, Hess P, Tricoci P, Mehta R, Mathews R, Kociol R, Harrison R, Mentz R, Pokorney S, Leblanc T, Lazzarini V, Eapen Z, Truffa A, Fosbol E, Brito F, Katz M, Bahit M, Santos M, Barros P, Bernardez S, Alvarisqueta AF, Arias P, Cagide AL, Calella PR, Cantero MC, Canella JP, Cipullo MA, de Loredo L, Gelersztein ES, Gorban de Lapertosa SB, Klyver MI, Maffei LE, Maldonado N, Oviedo AI, Piskorz DL, Ridruejo MC, Saavedra SS, Sessa HA, Sinay IR, Sposetti GD, Ulla MR, Vico ML, Waitman JN, Binnekamp M, Carroll P, Cheung W, Colman P, Davis T, De Looze F, dEmden M, Fulcher G, Gerstman M, Hamilton A, Lehman S, Moses R, Proietto J, Roberts A, Shaw J, Simpson R, Sinha A, Tan Y, Topliss D, Vora P, Waites J, Crenier L, Descamps O, Keymeulen B, Mathieu C, Nobels F, Van den Bruel A, Van Gaal L, Borges JL, Costa e Forti A, Eliaschewitz FG, Felício JS, Griz LH, Hissa MN, Leite S, Panarotto D, Pimentel Filho P, Rassi N, Saraiva JK, Sgarbi JA, Silva RP, Tambascia M, Weber Silva DM, Bobeva R, Bostandzhieva R, Cinlikov I, Georgieva M, Iliev D, Ilieva E, Kovacheva S, Liubenova L, Nikitov Z, SHeinikova G, Slavcheva A, Spasova V, Temelkova-Kurktschiev T, Velichka D, Yakov A, Carpentier A, Chiasson JL, Constance C, Dumas R, Filteau P, Garceau C, Huynh T, Kaiser S, Kornder J, Leiter L, Mereu L, Miller D, Pandey S, Punthakee Z, Rabasa-Lhoret R, Robitaille Y, Saunders K, Sigal R, Sigalas J, Vizel S, Weisnagel S, Woo V, Yale JF, Yared K, Zinman B, Bunster Balocchi LB, Escobar Cerda EE, Garces Flores EE, Lanas Zanetti FT, Larrazabal Miranda Adel P, Morales Alvarado JM, Olivares Cañon CM, Potthoff Cárdenas SH, Raffo Grado CA, Rodriguez Venegas ME, Saavedra Gajardo VA, Westerberg Maldonado BH, Chen LL, Dong J, Guo X, Li QM, Shi B, Tang XL, Yang T, Yang WY, Zheng SX, Aschner Montoya P, Botero Lopez R, Coronel Arroyo JA, Cure CA, Gómez Medina AM, Molina DI, Perez Amador GA, Reyes Rincon A, Urina Triana MA, Valenzuela Rincon A, Vélez Pelaez S, Yupanqui Lozno H, Brabec T, Brychta T, Hasalova Zapletalova J, Havelkova J, Hejnicova K, Hola O, Hornackova M, Hrdina T, Kafkova D, Kellnerova I, Krystl T, Kutejova V, Mikulkova I, Nevrla J, Pantlikova C, Petr M, Racicka E, Sarbochova R, Smolenakova K, Turcinek R, Urbancova K, Vejvodova J, Vondrakova M, Zachoval R, Alt I, Kaasik Ü, Kiiroja K, Lanno R, Märtsin K, Past M, Vides H, Viitas L, Kantola I, Nieminen S, Perhonen M, Strand J, Valle T, Clergeot A, Couffinhal T, Courreges JP, Gouet D, Moulin P, Ziegler O, Badenhoop K, Behnke T, Bender G, Braun M, Dshabrailov J, Hamann A, Himpel-Boenninghoff A, Kamke W, Kasperk C, Luedemann J, Mayr P, Merkel M, Oerter EM, Ohlow MA, Ott P, Overhoff U, Paschen B, Remppis R, Rose L, Schumm-Draeger PM, Segiet T, Strotmann HJ, Stuchlik G, Stürmer W, Thinesse-Mallwitz M, Tytko A, Wendisch U, Wurziger J, Ho AY, Kam G, Kong AP, Lam YY, Lau EY, Lee S, Siu SC, Tomlinson B, Tsang CC, Yeung VT, Dezső E, Dudás M, Földesi I, Fülöp T, Késmárki N, Koranyi L, Nagy K, Oroszlán T, Pécsvárady Z, Ples Z, Taller A, Agarwal P, Ambulkar S, Aravind S, Balaji V, Kalra S, Kesavadev J, Kudalkar H, Kumar A, Misra A, Mithal A, Mohan V, Pitale S, Ramu M, Reddy N, Shah S, Shamanna P, Sharda A, Sharma A, Shunmugavelu M, Srikanta S, Suryaprakash G, Abramov G, Adawi F, Bashkin A, Darawsha M, Fuchs S, Harman-Boehm I, Hayek T, Jaffe A, Knobler H, Minuchin O, Mosseri M, Shechter M, Shimon I, Stern N, Tsur A, Vishlitzky V, Alfonsi F, Cavalot F, Del Vecchio L, Frisinghelli A, Gambardella S, Lauro D, Lembo G, Leotta S, Mondillo S, Novo S, Pedrinelli R, Piatti P, Salvioni A, Tritto I, Zavaroni DZ, Ahn KJ, Choi KM, Chung C, Han SJ, Kim DM, Kim IJ, Kim MH, Lee IK, Nam M, Park IeB, Park KS, Park TS, Rhee EJ, Yoo SJ, Andersone I, Balode A, Eglite R, Gersamija A, Kakurina N, Jegere B, Leitane I, Pastare S, Stalte V, Teterovska D, Baltramonaitiene K, Barsiene L, Ceponis J, Lasiene J, Levinger A, Sirutaviciene A, Sulskiene M, Urbanaviciene L, Valius L, Varanauskiene E, Velickiene D, Mahendran KA, Abu Hassan MR, Aziz NA, Hussein Z, Ismail IS, Kamaruddin NA, Nordin Z, Nayar SK, Ramanathan GR, Sothiratnam R, Beijerbacht H, Breedveld R, Cornel JH, Den Hartog F, Hermans W, Kietselaer B, Kooy A, Lenderink T, Nierop P, Remmen J, Rojas Lingan G, Ronner E, Van der Heijden R, Van Hessen M, van Kempen W, Voors-Pette C, Westendorp I, Baker J, Benatar J, Cutfield R, Krebs J, Leikis R, Lunt H, Manning P, Williams M, Birkeland K, Claudi T, Istad H, Karlsson T, Ossum Gronert J, Arciszewska M, Artemiuk E, Blach E, Blicharski T, Cypryk K, Dabrowska M, Górny G, Górska M, Jakubowska I, Jazwinska-Tarnawska E, Karczmarczyk A, Kitowska-Koterla J, Koltowski L, Krzyzagorska E, Pasternak D, Pentela-Nowicka J, Piesiewicz W, Przekwas-Jaruchowska M, Rajzer M, Salamon-Ferenc A, Sawicki A, Skowron T, Śmiałowski A, Albota A, Alexandru C, Crisan C, Dumitrescu A, Ferariu IE, Lupusoru DA, Munteanu M, Negru D, Nicolau A, Pintiliei E, Popescu A, Serban G, Voitec M, Babenko A, Barbarash O, Bondar I, Chizhov P, Demin A, Dora S, Dreval A, Ershova O, Gratsiansky N, Ketova G, Kotelnikov M, Levashov S, Morugova T, Mustafina S, Pekarskiy S, Raskina T, Rechkova E, Samoylova Y, Sazonova O, Sherenkov A, Shilkina N, Stetsyuk O, Tretyakova T, Turova E, Valeeva F, Zadionchenko V, Dalan R, Tan RS, Tay L, Buganova I, Fabry J, Jan C, Toserova E, Zak R, Zimanova J, Badat A, Bester F, Burgess L, De Jong D, Ellis G, Fouche L, Govender P, Govind U, Naidoo V, Nieuwoudt G, Nortje H, Rheeder P, Robertson L, Siddique N, Stapelberg AM, Trinder Y, Van Der Merwe A, Van Zyl L, Viljoen M, Wilhase A, Botella M, Civeira Murillo F, de Teresa L, Del Cañizo FJ, Extremera BG, Gimeno EJ, Martin-Hidalgo A, Morales C, Nubiola A, Tinahones Madueño F, Tranche S, Trescolí Serrano C, Alvarsson M, Eizyk E, Gillblad A, Johansson P, Löndahl M, Ohlsson-Önerud Å, Rautio A, Sundström U, Torstensson I, Chen JF, Chou CW, Ho LT, Hsieh IC, Huang BH, Huang CL, Huang CN, Lai WT, Lo PH, Pei D, Sheu WH, Wang SY, Araz M, Bakiner O, Comlekci A, Guler S, Sahin I, Sarac F, Tarkun I, Ukinc K, Yilmaz M, Abdulhakim E, Abraham P, Adamson K, Blagden M, Bundy C, Daly M, Davies M, Deshpande M, Gillings S, Harvey P, Horvathova V, Hristova D, Jaap A, Johnson A, Jones H, Kerrane J, Kilvert A, Ko T, Kumar J, Lindsay R, Litchfield J, McCrimmon R, McKnight J, Millward B, Oyesile B, Purewal T, Ravikumar C, Robinson A, Sathyapalan T, Simpson H, Thomas H, Turner W, Weaver J, Wilding J, Wiles P, Adkins K, Akpunonu B, Albu J, Anagnostis G, Anastasi L, Argoud G, Aroda V, Azizad M, Banerji MA, Bartkowiak A Jr, Bays H, Behn P, Bergenstal R, Bhargava A, Bias D, Bolster E, Buchanan P, Busch R, Chadha C, Chang M, Cheng C, Cohen A, Cohen J, Cole B, Connery L, Cooperman M, Cushman W, DAgostino R, Dayamani P, De Lemos J, De Meireles M, Dean J, DeHart D, Detweiler R, Donovan D, Dugano-Daphnis P, Dulin M, Dunn F, Eaton C, Erickson B, Estevez R, Feinglos M, Fonseca V, Force R, Forker A, Fox D, Gabriel J, Garcia R, Garvey T, Gaudiani L, Getaneh A, Goldberg A, Goldman S, Hairston K, Harris R, Haught W, Hidalgo H Jr, Higgins A, Houchin V, Ison R, Jacobs G, Jaffrani N, Jafry B, Kapsner P, Kaye W, Labroo A, Levinson L, Lewis S, Lillestol M, Luttrell L, Madu I, McNeill R, Merrick B, Metzger F, Nadar V, Nagelberg S, Nash S, Oparil S, Osei K, Papademetriou V, Patel N, Pedley C, Prentiss A, Radbill M, Raisinghani A, Rassouli N, Reddy R, Rees P, Rendell M, Robbins D, Rodbard H, Rohlf J, Roseman H, Rudolph L, Sadler L, Schnall A, Schramm R, Schubart U, Seneviratne T, Shanik M, Snyder H, Sorli C, Stich M, Sweeney ME, Tsao J, Ukwade P, Viswanath D, Vo A, Vogel C, Voyce S, Weintraub H, White J, Wood M, Wu P, Wysham C, Zimmerman R, Pathology/molecular and cellular medicine, Diabetes Pathology & Therapy, and Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Peterson ED, Holman RR, Holman RR, Peterson ED, Holman RR, Peterson ED, Armstrong PW, Buse JB, Josse RG, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Engel SS, Califf RM, Goldstein BJ, Shapiro DR, Silverman R, Bethel A, Green J, Hayden S, Hannan K, Quintero K, Rorick T, Berdan L, Leloudis D, Califf S, Wilson M, McFarron D, Trollinger K, Pesarchick J, Eskenazi L, Campbell C, Townes O, Tolsma D, Keenan J, Milton J, Athwal R, Darbyshire J, Doran Z, Kennedy I, Gregory V, Garg J, Lokhnygina Y, Prather K, Wolfley A, Usman M, Tajjar A, Gray R, Pfeffer MA, Gerstein HC, Groop L, McMurray JJ, Pocock SJ, Clayton T, Sinay I, Brieger D, Stranks S, Scheen A, Lopes R, Tankova T, Hramiak I, Grado CR, Wenying Y, Ge J, Aschner P, Skrha J, Ambos A, Strandberg T, Travert F, Hanefeld M, Riefflin A, Chan JC, Ofner P, Reddy NK, Christopher J, Mathur A, Arambam P, Mittal S, Manchanda M, Wainstein J, Ambrosio G, Pirags V, Jakuboniene N, Mohamed M, Scott R, White H, Cornel J, Halvorsen S, Tykarski A, Veresiu IA, Dreval AV, Misinkova I, Tai E, Krahulec B, Distiller L, Park Y, Rovira A, Alversson M, Chuang LM, Delibasi T, Adler A, Rodbard HW, Marre M, Goff D, Chacra A, DeVore A, Beaven A, Shah B, Hirsch B, Batch B, Bushnell C, Patel C, Melloni C, Henshaw C, Kong D, McFarron D, Bernecki G, Tillman H, Kang HJ, Green J, Hawes J, Strickler J, Piccini J, Wilder J, Alexander K, Mahaffey K, Patel K, Hyland K, Newby K, Jackson L, Cooper L, Armaganijan L, Szczeh L, Koshizaka M, Roe M, Morse M, Guimaraes P, Hess P, Tricoci P, Mehta R, Lopes R, Mathews R, Kociol R, Harrison R, Mentz R, Pokorney S, Leblanc T, Lazzarini V, Eapen Z, Truffa A, Fosbol E, Brito F, Katz M, Bahit M, Santos M, Barros P, Bernardez S, Alvarisqueta AF, Arias P, Cagide AL, Calella PR, Cantero MC, Canella JP, Cipullo MA, de Loredo L, Gelersztein ES, Gorban de Lapertosa SB, Klyver MI, Maffei LE, Maldonado N, Oviedo AI, Piskorz DL, Ridruejo MC, Saavedra SS, Sessa HA, Sinay IR, Sposetti GD, Ulla MR, Vico ML, Waitman JN, Binnekamp M, Carroll P, Cheung W, Colman P, Davis T, De Looze F, dEmden M, Fulcher G, Gerstman M, Hamilton A, Lehman S, Moses R, Proietto J, Roberts A, Shaw J, Simpson R, Sinha A, Stranks S, Tan Y, Topliss D, Vora P, Waites J, Crenier L, Descamps O, Keymeulen B, Mathieu C, Nobels F, Scheen A, Van den Bruel A, Van Gaal L, Borges JL, Costa e Forti A, Eliaschewitz FG, Felício JS, Griz LH, Hissa MN, Leite S, Panarotto D, Pimentel Filho P, Rassi N, Saraiva JK, Sgarbi JA, Silva RP, Tambascia M, Weber Silva DM, Bobeva R, 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Subjects
Oral, medicine.medical_specialty, Heart diseases, Glycosylated, Administration, Oral, heart failure, Type 2 diabetes, Dipeptidyl peptidase-4 inhibitor, Kaplan-Meier Estimate, Placebo, Sitagliptin Phosphate, Sitagliptin, Cardiovascular Outcomes, chemistry.chemical_compound, Drug Therapy, Double-Blind Method, Internal medicine, Diabetes Mellitus, medicine, Humans, Hypoglycemic Agents, Glycated Hemoglobin, Hemoglobin A, Glycosylated, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Follow-Up Studies, Heart Diseases, Heart Failure, Hospitalization, Pyrazines, Triazoles, Medicine (all), business.industry, Semaglutide, Hemoglobin A, General Medicine, ta3121, medicine.disease, Surgery, Cardiovascular diseases, chemistry, Sitagliptin, Administration, Combination, Glycated hemoglobin, business, Type 2, Alogliptin, medicine.drug
Abstract

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to-0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P

Published
2015
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30. Baseline Characteristics and Risk Profiles of Participants in the ISCHEMIA Randomized Clinical Trial

Author

Hochman, JS, Reynolds, HR, Bangalore, S, O'Brien, SM, Alexander, KP, Senior, R, Boden, WE, Stone, GW, Goodman, SG, Lopes, RD, Lopez-Sendon, J, White, HD, Maggioni, AP, Shaw, LJ, Min, JK, Picard, MH, Berman, DS, Chaitman, BR, Mark, DB, Spertus, JA, Cyr, DD, Bhargava, B, Ruzyllo, W, Wander, GS, Chernyavskiy, AM, Rosenberg, YD, Maron, DJ, Mavromatis, K, Miller, T, Banerjee, S, Abdul-Nour, K, Stone, PH, Jang, JJ, Weitz, S, Arnold, S, Shapiro, MD, El-Hajjar, M, McFalls, EO, Khouri, MG, Goldberg, JL, Goldweit, R, Cohen, RA, Winchester, DE, Kronenberg, M, Heitner, JF, Dauber, IM, Cannan, C, Sudarshan, S, Mehta, PK, Hedgepeth, CM, Sahul, Z, Booth, D, Setty, S, Barua, RS, Hage, F, Dajani, K, Arif, I, Trejo (Gutierrez), JF, Gemignani, A, Meadows, JL, Call, JT, Hannan, J, Martin, ET, Vorobiof, G, Moorman, A, Kinlay, S, Rayos, G, Seedhom, A, Kumkumian, G, Sedlis, SP, Tamis-Holland, JE, Saba, S, Badami, U, Marzo, K, Robbins, IH, Hamroff, GS, Little, RW, Lui, CY, Hu, B, Labovitz, AJ, Rodriguez, F, Deedwania, P, Sweeny, J, Spizzieri, C, Hochberg, CP, Salerno, WD, Wyman, R, Zarka, A, Haldis, T, Kohn, JA, Girotra, S, Almousalli, O, Krishnam, MS, Coram, R, Thomas, S, El Shahawy, M, Stafford, J, Abernethy, WB, Zurick, A, Meyer, TM, Rutkin, B, Bokhari, S, Sokol, SI, Hamzeh, I, Turner, MC, Good, AP, Shammas, NW, Chilton, R, Nguyen, PK, Jezior, M, Gordon, PC, Stenberg, R, Pedalino, RP, Wiesel, J, Juang, GJ, Al-Amoodi, M, Wohns, D, Lader, EW, Mumma, M, Dharmarajan, L, McGarvey, JFX, Downes, TR, Cheong, B, Potluri, S, Mastouri, RA, Li, D, Giedd, K, Old, W, Burt, F, Sokhon, K, Gopal, D, Valeti, US, Kobashigawa, J, Govindan, SC, Manjunath, CN, Pandit, N, Dwivedi, SK, Mathew, A, Gadkari, MA, Satheesh, S, Mathur, A, Christopher, J, Oomman, A, Naik, S, Grant, P, Kachru, R, Kumar, A, Kaul, U, Gamma, RA, De Belder, MA, Nageh, T, Lindsay, SJ, Hoye, A, Donnelly, P, Chauhan, A, Barr, C, Alfakih, K, Henriksen, P, Okane, P, De Silva, R, Conway, DSG, Sirker, AA, Hoole, SP, Witherow, FN, Johnston, N, Luckie, M, Sobolewska, J, Jeetley, P, Travill, C, Braganza, D, Henderson, R, Berry, C, Moriarty, AJ, Glover, JD, Mikhail, G, Gosselin, G, Diaz, A, Phaneuf, DC, Garg, P, Chow, BJW, Bainey, KR, Cheema, AN, Cha, J, Howarth, AG, Wong, G, Uxa, A, Galiwango, P, Lam, A, Mehta, S, Udell, J, Genereux, P, Hameed, A, Daba, L, Hueb, W, Smanio, PEP, De Quadros, AS, Vitola, JV, Marin-Neto, JA, Polanczyk, CA, Carvalho, AC, Alves Junior, AR, Dracoulakis, MDA, Figueiredo, E, Caramori, PR, Tumelero, R, Dall'Orto, F, Mesquita, CT, Ribeiro da Silva, EE, Saraiva, JF, Costantini, C, Demkow, M, Mazurek, T, Drozdz, J, Szwed, H, Witkowski, A, Gajos, G, Pruszczyk, P, Loboz-Grudzien, K, Lesiak, M, Reczuch, KW, Kalarus, Z, Musial, WJ, Bockeria, L, Bershtein, LL, Demchenko, EA, Lopez-Sendon, JL, Peteiro, J, Gonzalez Juanatey, JR, Sionis, A, Miro, V, Ortuno, FM, Blancas, MG, Luena, JEC, Fernandez-Aviles, F, Chen, J, Wu, Y, Ma, Y, Ji, Z, Yang, X, Lin, W, Zeng, H, Fu, X, Yang, B, Wang, S, Cheng, G, Zhao, Y, Fang, X, Zeng, Q, Su, X, Li, Q, Nie, S-P, Yu, Q, Wang, J, Zhang, S, Perna, GP, Provasoli, S, Monti, L, Di Chiara, A, Mortara, A, Galvani, M, Sicuro, M, Calabro, P, Tarantini, G, Racca, E, Briguori, C, Amati, R, Russo, A, Poh, K-K, Foo, D, Chua, T, Doerr, R, Sechtem, U, Schulze, PC, Nickenig, G, Schuchlenz, H, Lang, IM, Huber, K, Vertes, A, Varga, A, Fontos, G, Merkely, B, Kerecsen, G, Hinic, S, Beleslin, BD, Cemerlic-Adjic, N, Davidovic, G, Dekleva, MN, Stankovic, G, Apostolovic, S, Escobedo, J, Rosas, EA, Selvanayagam, JB, Thambar, ST, Beltrame, JF, Hillis, GS, Thuaire, C, Steg, P-G, Slama, MS, El Mahmoud, R, Nicollet, E, Barone-Rochette, G, Furber, A, Laucevicius, A, Kedhi, E, Riezebos, RK, Suryapranata, H, Ramos, R, Pinto, FJ, Ferreira, N, Guzman, L, Figal, JC, Alvarez, C, Courtis, J, Schiavi, L, Rubio, M, Devlin, GP, Stewart, RAH, Kedev, S, Held, C, Aspberg, J, Sharir, T, Kerner, A, Fukuda, K, Yasuda, S, Nishimura, S, Goetschalckx, K, Hung, C-L, Ntsekhe, M, Moccetti, T, Abdelhamid, M, Pop, 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JA, Cyr DD, Bhargava B, Ruzyllo W, Wander GS, Chernyavskiy AM, Rosenberg YD, Maron DJ, Mavromatis K, Miller T, Banerjee S, Abdul-Nour K, Stone PH, Jang JJ, Weitz S, Arnold S, Shapiro MD, El-Hajjar M, McFalls EO, Khouri MG, Goldberg JL, Goldweit R, Cohen RA, Winchester DE, Kronenberg M, Heitner JF, Dauber IM, Cannan C, Sudarshan S, Mehta PK, Hedgepeth CM, Sahul Z, Booth D, Setty S, Barua RS, Hage F, Dajani K, El-Hajjar M, Arif I, Trejo JF, Gemignani A, Meadows JL, Call JT, Hannan J, Martin ET, Vorobiof G, Moorman A, Kinlay S, Rayos G, Seedhom A, Kumkumian G, Sedlis SP, Tamis-Holland JE, Saba S, Badami U, Marzo K, Robbins IH, Hamroff GS, Little RW, Lui CY, Booth D, Hu B, Labovitz AJ, Maron DJ, Rodriguez F, Deedwania P, Sweeny J, Spizzieri C, Hochberg CP, Salerno WD, Wyman R, Zarka A, Haldis T, Kohn JA, Girotra S, Almousalli O, Krishnam MS, Coram R, Thomas S, El Shahawy M, Stafford J, Abernethy WB, Zurick A, Meyer TM, Rutkin B, Bokhari S, Sokol SI, Hamzeh I, Turner MC, Good AP, Shammas 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PEP, de Quadros AS, Vitola JV, Marin-Neto JA, Polanczyk CA, Carvalho AC, Alves AR, Dracoulakis MDA, Figueiredo E, Caramori PR, Tumelero R, Dall'Orto F, Mesquita CT, da Silva EER, Saraiva JF, Costantini C, Demkow M, Mazurek T, Drozdz J, Szwed H, Witkowski A, Gajos G, Pruszczyk P, Loboz-Grudzien K, Lesiak M, Reczuch KW, Kalarus Z, Musial WJ, Bockeria L, Chernyavskiy AM, Bershtein LL, Demchenko EA, Lopez-Sendon JL, Peteiro J, Juanatey JRG, Sionis A, Miro V, Ortuno FM, Blancas MG, Luena JEC, Fernandez-Aviles F, Chen JY, Wu YJ, Ma YT, Ji Z, Yang XC, Lin WH, Zeng HS, Fu, X, Yang B, Wang ST, Cheng G, Zhao YL, Fang XH, Zeng QT, Su X, Li QX, Nie SP, Yu Q, Wang JA, Zhang SY, Perna GP, Provasoli S, Monti L, Di Chiara A, Mortara A, Galvani M, Sicuro M, Calabro P, Tarantini G, Racca E , Briguori C, Amati R, Russo A, Poh KK, Foo D, Chua, Doerr R, Sechtem U, Schulze PC, Nickenig G, Schuchlenz H, Lang IM, Huber K, Vertes A, Varga A, Fontos G, Merkely B, Kerecsen G, Hinic S, Beleslin BD, Cemerlic-Adjic 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Subjects
medicine.medical_specialty, Cardiac & Cardiovascular Systems, IMPACT, medicine.medical_treatment, Population, 030204 cardiovascular system & hematology, Revascularization, law.invention, MEDICAL THERAPY, ISCHEMIA Research Group, Angina, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Severity of illness, SCORE, medicine, BENEFIT, 030212 general & internal medicine, cardiovascular diseases, education, education.field_of_study, OUTCOMES, Science & Technology, business.industry, PCI, medicine.disease, Clinical trial, PROGNOSTIC VALUE, Stenosis, Cardiology, Cardiovascular System & Cardiology, CORONARY-ARTERY-DISEASE, REVASCULARIZATION, Cardiology and Cardiovascular Medicine, business, ECHOCARDIOGRAPHY, Life Sciences & Biomedicine
Abstract

Importance It is unknown whether coronary revascularization, when added to optimal medical therapy, improves prognosis in patients with stable ischemic heart disease (SIHD) at increased risk of cardiovascular events owing to moderate or severe ischemia. Objective To describe baseline characteristics of participants enrolled and randomized in the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial and to evaluate whether qualification by stress imaging or nonimaging exercise tolerance test (ETT) influenced risk profiles. Design, Setting, and Participants The ISCHEMIA trial recruited patients with SIHD with moderate or severe ischemia on stress testing. Blinded coronary computed tomography angiography was performed in most participants and reviewed by a core laboratory to exclude left main stenosis of at least 50% or no obstructive coronary artery disease (CAD) (

Published
2019

31. Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

Author

Lincoff, A. Michael, Nicholls, Stephen J., Riesmeyer, Jeffrey S., Barter, Philip J., Brewer, H. Bryan, Fox, Keith A. A., Gibson, C. Michael, Granger, Christopher, Menon, Venu, Montalescot, Gilles, Rader, Daniel, Tall, Alan R., McErlean, Ellen, Wolski, Kathy, Ruotolo, Giacomo, Vangerow, Burkhard, Weerakkody, Govinda, Goodman, Shaun G., Conde, Diego, McGuire, Darren K., Nicolau, Jose C., Leiva-Pons, Jose L., Pesant, Yves, Li, Weimin, Kandath, David, Kouz, Simon, Tahirkheli, Naeem, Mason, Denise, Nissen, Steven E. Del Valle M, Finnell JB, Standley J, Poi K, Croaning J, Tong YC, Guerra JL, Guasparini G, Hubert C, Ardissino D, Betteridge J, Borghi C, Bruckert E, Chiang CE, Cinteza M, Dalby AJ, Erlinge D, Fernandez-Ortiz A, Ge J, Gottlieb S, Goudev A, Gratsiansky N, Huber K, Ilavská A, Jeong MH, Jukema JW, Katus H, Keltai M, Krum H, Nielsen H, Ogawa H, Ongen Z, Parkhomenko A, Raugaliene R, Renkin J, Rynkiewicz A, Steinhubl S, White H, Widimsky P, Zhu J, Armstrong P, Ridker P, Mahaffey K, Steg G, Wittes J, Bhargava A, Chenier M, Coleman C, Cremer P, Jellis C, Lahoud R, Lappe J, Min D, Monteleone P, Newton D, Stegman B, Senn T, Katzan I, Sharma J, Uchino K, Vora N, Brown K, Fabec D, Piper P, Preston S, Colombo T, Pagel-Langenickel I, Penev P, Maixing A, Crowley K, Sarkar S, Torosyan N, Castano L, Tran D, Dena V, Blain L, Keenan G, Slade K, Quinlan E, Edwards R, Ren H, Glenny J, Maffei L, Albisu Di Gennaro J, Caccavo A, Prado A, Colombo H, Luquez H, Lobo Marquez L, Hammett C, Blombery P, Colquhoun D, Amerena J, Howes L, Cooke D, Simpson R, Horowitz J, Sullivan D, Proietto J, Yeo W, Hirschl M, Hanusch U, Drexel H, Brodmann M, Wollaert B, De Wolf L, Delforge M, Vanwelden J, Peeters A, Siqueira Bodart J, Montenegro R, Franken M, Eliaschewitz F, Parvanova Z, Raev D, Mincheva V, Kichukov K, Stoyanov M, Apostolova E, Tzekova M, Dimov B, Lazov P, Devedzhiev T, Dion D, Poirier P, Lavoie JP, Lonn E, Shukla D, Chehayeb R, Nault P, Gaudet D, Tardif JC, Beaudry Y, Bakbak A, Wong B, St-Maurice F, Labonte R, Polasek P, Sweet M, Bhargava R, Nawaz S, Pandey S, Tishler S, Peterson S, O’Keefe D, Genest J, Syan R, Leiter L, Li H, Ma W, Ma C, Xu D, Li X, Hala T, Machova V, Smejkalova O, Vodnansky P, Reichert P, Velimsky T, Matuska J, Machkova M, Jerabek O, Kuchar J, Rasmussen T, Lindgren L, Alexandersen P, Bang L, Brønnum-Schou J, Valter I, Soots M, Lanno R, Rosenthal S, Cottin Y, Elbaz M, Lafitte S, Silvain J, Coste P, Rangé G, Gosse P, Morel O, Berrouschot J, Bourhaial H, Toursarkissian N, Appel KF, 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Hranai, M, Gergel, V, Dzupina, A, Uhliar, R, Vinanska, D, Fazekas, F, Bugan, W, Saaiman, J, Nortje, H, Theron, H, Bernhardi, D, Ramlachan, P, Van-Zyl, L, Basson, M, Venter, T, Kim, D, Han, S, Park, G, Hwang, K, Rhee, M, Cho, B, Jeong, J, Hong, B, Chang, K, Garcia Puig, J, Fuentes Jiménez, F, Nieto Iglesias LJ, Pintó Sala, X, Gamez, Jm, Sánchez Álvarez, J, Hernandez García JM, Olsson, A, Mooe, T, Tengmark, Bo, Lindholm, Cj, Hansen, O, Tyden, P, Moccetti, T, Binder, R, Ueng, K, Lai, W, Shyu, K, Hsieh, I, Sheu, W, Chen, J, Altunkeser, B, Erkan, A, Karpenko, O, Kaydashev, I, Yagensky, A, Kovalenko, V, Brunskill, J, Barr, C, Cecil, J, Cahill, T, A Gorog D, Bakhai, A, Coulson, W, Gorog, D, Loftus, I, Haddad, T, Hotchkiss, D, Isserman, S, Janik, M, Weinstein, D, Wilson, S, Butman, S, Hearne, S, Khan, F, Nadar, V, Zelman, R, R, Benton, E, Flore, Kahn, B, Soni, A, Asbill, B, Singal, D, Dy, J, Foucauld, J, Crenshaw, B, Rogers, W, Aslam, A, Lieber, I, Shah, P, Durr, S, Spencer, R, Mahal, S, Cheng, S, Abadier, R, Gilmore, R, Staniloae, C, Miller, G, Seals, A, Jetty, P, Mathis, C, Henry, S, Murray, A, Felten, W, Navas, J, Gudipati, R, Singh, N, West, S, Sabatino, K, Crater, T, Amin, J, Dosh, K, Earl, J, Z Jafar M, Gelernt, M, Kutner, M, J, Salazar, Krantzler, J, El-Ahdab, F, Lader, E, Zakhary, B, Miller, S, Madder, R, Khan, T, Khan, M, Collis, W, Evans, J, Prodafikas, J, Panchal, V, Cohen, K, Weiss, R, Dietrich, D, Vogel, C, Mascarenhas, V, Seaworth, J, Teklinski, A, Davalos, J, Dehning, M, Herzog, W, Snyder, H, Talano, J, Donahoe, S, Hunter, J, Sandoval, J, Batchelor, W, Brautigam, D, Moriarty, K, Siachos, A, Kereiakes, D, Traboulssi, M, Arif, I, Kosinski, E, Quadrel, M, Dehart, D, Miller, M, Poock, J, Loh, I, van Cleeff, M, Georgeson, S, Suryanarayana, P, Cohn, J, Schmedtje, J, Lamas, G, Desantis, J, Stahl, L, Prashad, R, Schuchard, T, Schramm, E, Rao, V, Deen, C, Soufer, J, Gurbel, P, Vazquez-Tanus, J, Srivastava, S, Ballantyne, C, Lotun, K, Younis, L, Gupta, D, Yeoman, G, Zebrack, J, Knutson, T, Whitaker, J, Appel, M, Koren, M, Muneer, B, Fairlamb, J, Aviles, R, Kozlowski, L, Rees, A, Stephens, M, Mays, M, Downey, H, Almassi, H, Peichert, D, Rocco, M, French, W, Bhatia, P, Hoch, J, Peart, B, Carmichael, P, Acheatel, R, Vo, A, Kirtane, A, Bhagwat, R, Gilchrist, I, Labroo, A, Pollock, S, Bacon, J, Karunaratne, H, Moursi, M, Doshi, A, Sethi, P, Treasure, C, Marple, R, Goodwin, T, Zayas-Torres, C, Loussararian, A, Korn, D, Paster, R, Albirini, A, Moretto, T, Guarnieri, T, White, L, Kramer, J, Shortal, B, Maynard, K, Raikhel, M, Rohatgi, A, Melucci, M, Masri, B, Krichmar, P, Morris, F, Canto, J, Wali, A, Comerota, A, Ellison, W, Degregorio, M, Chandrika Parameswaran, A, Goldscher, D, George, W, Mulkay, A, Maynard, R, Ziada, K, Strain, J, Hermiller, J, Ennis, B, Desai, V, Al-Joundi, B, Azocar, J, Claudio, J, Perez Vargas, E, Loy, J, Albert, M, Chandler, G, Maislos, F, Graf, R, Rama, P, Studeny, M, Gimple, L, Pytlewski, G, Simon, H, Islam, A, Dillon, W, Shah, S, Geohas, C., Lincoff, A. Michael, Nicholls, Stephen J., Riesmeyer, Jeffrey S., Barter, Philip J., Brewer, H. Bryan, Fox, Keith A. A., Gibson, C. Michael, Granger, Christopher, Menon, Venu, Montalescot, Gille, Rader, Daniel, Tall, Alan R., Mcerlean, Ellen, Wolski, Kathy, Ruotolo, Giacomo, Vangerow, Burkhard, Weerakkody, Govinda, Goodman, Shaun G., Conde, Diego, Mcguire, Darren K., Nicolau, Jose C., Leiva-Pons, Jose L., Pesant, Yve, Li, Weimin, Kandath, David, Kouz, Simon, Tahirkheli, Naeem, Mason, Denise, Nissen, Steven E., Del Valle M, Young, C, Nieto Iglesias, Lj, Hernandez García, Jm, A Gorog, D, Benton, R, Flores, E, Z Jafar, M, and Salazar, J

Subjects
Male, 0301 basic medicine, Cardiovascular Outcome, Cholesterol Ester Transfer Protein, Myocardial Ischemia, 030204 cardiovascular system & hematology, Coronary artery disease, cholesteryl ester transfer protein inhibitor, Benzodiazepines, chemistry.chemical_compound, 0302 clinical medicine, Cardiovascular Disease, Anticholesteremic Agent, Intracranial Arteriosclerosi, Treatment Failure, Evacetrapib, Peripheral Vascular Diseases, Benzodiazepine, biology, Medicine (all), Anticholesteremic Agents, Diabetes Mellitu, General Medicine, Middle Aged, Intracranial Arteriosclerosis, High-Risk Vascular Disease, Editorial, Cardiovascular Diseases, Cardiology, Female, lipids (amino acids, peptides, and proteins), Human, Risk, medicine.medical_specialty, Acute coronary syndrome, 03 medical and health sciences, Double-Blind Method, Internal medicine, Diabetes mellitus, Cholesterylester transfer protein, Diabetes Mellitus, Journal Article, medicine, Humans, Aged, Cholesterol, Vascular disease, business.industry, Cholesterol, HDL, Biomarker, Cholesterol, LDL, medicine.disease, Cholesterol Ester Transfer Proteins, Surgery, 030104 developmental biology, Peripheral Vascular Disease, chemistry, biology.protein, business, Biomarkers, Lipoprotein
Abstract

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .).

Published
2017
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32. The Application of Zonisamide to Patients Suffering from Dementia with Lewy Bodies: Emerging Clinical Data

Author

Babak Tousi and James Jb Leverenz

Subjects
0301 basic medicine, Lewy Body Disease, medicine.medical_specialty, Pharmaceutical Science, Zonisamide, Review, Neuropsychiatry, Placebo, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Drug Discovery, mental disorders, medicine, Dementia, Humans, parkinsonism, Pharmacology, Lewy body, Dementia with Lewy bodies, business.industry, Parkinsonism, clinical trial, medicine.disease, nervous system diseases, Clinical trial, 030104 developmental biology, Clinical Trials, Phase III as Topic, 030220 oncology & carcinogenesis, business, dementia with Lewy bodies, medicine.drug
Abstract

Zonisamide is an anti-epileptic medication with multiple mechanisms of action and a favorable safety profile. Zonisamide may interact with Lewy body dementia pathophysiology through a mechanism unrelated to its original indication. Zonisamide has shown efficacy as adjunct therapy for the management of motor symptoms in patients with Parkinson’s disease (PD). Given that dementia with Lewy bodies (DLB) and PD are considered subtypes of a Lewy body disease spectrum, zonisamide was investigated for the treatment of parkinsonism in DLB. Phase II and phase III clinical trials were conducted in patients with DLB in Japan. In both studies, participants were randomized to receive 12 weeks of zonisamide 25 or 50 mg/day or placebo. Zonisamide significantly improved the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) without affecting the Mini-Mental State Examination (MMSE) or Neuropsychiatry Inventory-10 (NPI-10) scores at week 12. In 2018, zonisamide received Japanese regulatory approval for the additional indication of parkinsonism in DLB. This review discusses the emerging clinical data on zonisamide in the field of DLB.

Published
2021

33. Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease

Author

Bhatt, Dl, Szarek, M, Pitt, B, Cannon, Cp, Leiter, La, Mcguire, Dk, Lewis, Jb, Riddle, Mc, Inzucchi, Se, Kosiborod, Mn, Cherney, Dzi, Dwyer, Jp, Scirica, Bm, Bailey, Cj, Díaz, R, Ray, Kk, Udell, Ja, Lopes, Rd, Lapuerta, P, Steg, Gabriel, P, and Lauro, D

Subjects
Male, SAXAGLIPTIN, 030204 cardiovascular system & hematology, Saxagliptin, MELLITUS, chemistry.chemical_compound, 0302 clinical medicine, Settore MED/13, Glycosides, 030212 general & internal medicine, 11 Medical and Health Sciences, RISK, SGLT2 INHIBITOR, OUTCOMES, Kidney, EMPAGLIFLOZIN, General Medicine, Middle Aged, Hospitalization, medicine.anatomical_structure, Cardiovascular Diseases, HEART-FAILURE, Diarrhea/chemically induced, Female, OUTPATIENTS, Life Sciences & Biomedicine, Diarrhea, medicine.medical_specialty, SCORED Investigators, Mycoses/etiology, Diabetic ketoacidosis, Renal Insufficiency, Chronic/complications, Glycosides/adverse effects, Diabetic Ketoacidosis, 03 medical and health sciences, Medicine, General & Internal, Sodium-Glucose Transporter 1, Double-Blind Method, General & Internal Medicine, Internal medicine, Diabetes mellitus, medicine, Empagliflozin, Humans, Renal Insufficiency, Chronic, Sodium-Glucose Transporter 2 Inhibitors, Aged, Hospitalization/statistics & numerical data, Science & Technology, Diabetic Ketoacidosis/chemically induced, urogenital system, business.industry, MORTALITY, Cardiovascular Diseases/epidemiology, Diabetes Mellitus, Type 2/complications, Sodium-Glucose Transporter 2 Inhibitors/adverse effects, medicine.disease, CARDIOVASCULAR EVENT RATES, Clinical trial, Mycoses, chemistry, Diabetes Mellitus, Type 2, Sodium-Glucose Transporter 1/antagonists & inhibitors, Heart failure, business, Kidney disease
Abstract

In a trial involving 10,584 patients with diabetes and chronic kidney disease, sotagliflozin resulted in fewer total deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure than placebo. Diarrhea, mycotic infections, and diabetic ketoacidosis occurred with sotagliflozin. Background The efficacy and safety of sodium-glucose cotransporter 2 inhibitors such as sotagliflozin in preventing cardiovascular events in patients with diabetes with chronic kidney disease with or without albuminuria have not been well studied. Methods We conducted a multicenter, double-blind trial in which patients with type 2 diabetes mellitus (glycated hemoglobin level, >= 7%), chronic kidney disease (estimated glomerular filtration rate, 25 to 60 ml per minute per 1.73 m(2) of body-surface area), and risks for cardiovascular disease were randomly assigned in a 1:1 ratio to receive sotagliflozin or placebo. The primary end point was changed during the trial to the composite of the total number of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure. The trial ended early owing to loss of funding. Results Of 19,188 patients screened, 10,584 were enrolled, with 5292 assigned to the sotagliflozin group and 5292 assigned to the placebo group, and followed for a median of 16 months. The rate of primary end-point events was 5.6 events per 100 patient-years in the sotagliflozin group and 7.5 events per 100 patient-years in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.63 to 0.88; P

Published
2021
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34. Influenza vaccination and prognosis of COVID ‐19 in hospitalized patients with diabetes: Results from the CORONADO study

Author

Diallo, A, Pichelin, Matthieu, Wargny, Matthieu, Gourdy, Pierre, Bonnet, JB, Hadjadj, Samy, Cariou, Bertrand, Sultan, Ariane, Galtier, Florence, Mahot, Pascale, Fournier‐Guilloux, Anne‐Laure, Mauduit, Nicolas, Bigot‐corbel, Edith, Boureau, Anne‐Sophie, Dekcer, Laure, Ernould, Audrey, Primot, Claire, Seguin, Anne, Joliveau, Marielle, Pouvreau, Sonia, FOURNIER, Chloé, Thureau, Jeremy, Fonteneau, Edith, Hublain, Pamela, Nantes, Chu, Agasse, Carole, Kergaradec, Mathilde DE, Minville, Vincent, Vardon‐Bounes, Fanny, Martin‐Blondel, Guillaume, Tramunt, Blandine, Turnin, Marie‐Christine, Hanaire, Hélène, Mansuy, Jean‐Michel, Fabre, Didier, Arhainx, Marie‐Blanche, Cazals, Laurent, Combes, Laure, Lami, Emmanuelle, Cianferani, Mallory, Megarbane, Bruno, Leroy, Pierre, Gautier, Jean‐François, Vidal‐Trecan, Tiphaine, Riveline, Jean‐Pierre, Laplanche, Jean‐Louis, Mouly, Stéphane, Potier, Louis, Roussel, Ronan, Taher, Malak, Abouleka, Yawa, Yaker, Fetta, Carlier, Aurelie, Boutten, Anne, Hallot‐Feron, Marilyne, Mourah, Fadila, Thivolet, Charles, Blond, Emilie, Rolland, Muriel, Mendez, Josep Verdecho, Alexandre, Marine, Pottecher, Julien, Richer, Emilie, Meyer, Laurent, Luca, Florina, Lessinger, Jean‐Marc, Bahougne, Thibault, Guerci, Bruno, Ludwig, Lisa, Benzirar, Siham, Malaplate, Catherine, Matton, Thierry, Poissy, Julien, Faure, Karine, Fontaine, Pierre, Baudoux, Florence, Vambergue, Anne, Pekar, Jean David, Lambert, Marc, Yelnik, Cécile, Bruandet, Amélie, Petit, Laurent, Neau, Didier, Rigalleau, Vincent, Berard, Annie, Galioot, Amandine, Coudroy, Remy, Thille, Arnaud, Robert, René, Roblot‐Cazenave, France, Rammaert, Blandine, Saulnier, Pierre Jean, Piguel, Xavier, Benhenda, Nesrine, Husson, Camille, Olivier, Celine, Torremocha, Florence, Fraty, Mathilde, d'assigny, Marie Flamen, Miot, Aurelie, Bossard, Valentin, Klouche, Kada, Makinson, Alain, Bonnet, Jean‐Baptiste, Foulongne, Vincent, Aubron, Cécile, Ansart, Séverine, Kerlan, Véronique, Quiniou, Pascale, Carre, Jean‐Luc, Quesnot, Stéphane, Laviolle, Bruno, Schwebel, Carole, Epaulard, Olivier, Benhamou, Pierre‐Yves, Betry, Cécile, Borel, Anne‐Laure, Lablanche, Sandrine, Guergour, Dorra, Duclos, Catherine, Cosson, Emmanuel, Guyot, Erwan, Deniau, Aurore, Nguyen, Phucthutrang, Reznik, Yves, Joubert, Michael, Allouche, Stéphane, Guittet, Lydia, Grange, Steven, Etienne, Manuel, Prévost, Gaëtan, Brunel, Valéry, Lagier, Jean‐Christophe, Raoult, Didier, Dutour, Anne, Gaborit, Bénédicte, Boulllu, Sandrine, Darmon, Patrice, Lasbleiz, Adèle, Cerino, Mathieu, Romain, Fanny, Houssays, Marie, Quenot, Jean Pierre, Piroth, Lionel, Vergès, Bruno, Duvillard, Laurence, Bonnotte, Bernard, Mercat, Alain, Dubee, Vincent, Allix, Ingrid, Rodien, Patrice, Dhersin, Robin, Lebeault, Maylis, Trzepizur, Wojciech, Loison, Jocelyne, Brangier, Antoine, Asfar, Pierre, Reynier, Pascal, Larcher, Françoise, Joubaud, Françoise, Andreu, Marie‐Rita, Urbanski, Geoffrey, Hubert, Laurent, Annweiler, Cedric, Dellamonica, Jean, Courjon, Johan, Chevalier, Nicolas, Chinetti, Giulia, Chafai, Magda, Mourvillier, Bruno, Bani‐Sadr, Firouze, Barraud, Sarra, Delemer, Brigitte, Gillery, Philippe, Labedade, Pascale, Chabrol, Amélie, Penfornis, Alfred, Petit, Catherine, Amadou, Coralie, Adler, Maxime, Dubost, Clément, Conan, Pierre‐Louis, Bordier, Lyse, Ceppa, Franck, Garcia, Cyril, Sollier, Mathilde, Dupuy, Olivier, Laplance, Sophie, Billuart, Olivier, Aroulanda, Marie Joseph, Olivier, Frédérique, Ayon, Florence, Wilhelm, Nathalie, Epelboin, Loic, Sabbah, Nadia, Charpin, Aurelie, Squara, Pierre, Belliard, Olivier, Dubois, Claude, Marre, Michel, Auchabie, Johann, Courtois, Roxane, Duriez, Thierry, Mergey, Tiphaine, Vallee, Laura, Seguin, Laetitia, Al‐Salameh, Abdallah, Lanoix, Jean‐Philippe, Soriot‐Thomas, Sandrine, Bourgeois‐Descouls, Anne‐Marie, Desailloud, Rachel, Germain, Natacha, Galusca, Bogdan, Belleton, Gwenaelle, Marouani, Nesrine, Palaghiu, Delia, Hammour, Amira, Berdaguer, Fernando, Klopfenstein, Thimothée, Zayet, Hajer, Winiszewski, Patrice, Zanusso, Marie, Garnier, Pauline, Julier, Ingrid, Hamzaoui, Karim, Marty‐Gres, Sophie, Sadki, Tarik, Cadot, Lucile, Dubost, Jean‐Louis, Gonfroy, Céline, Campinos, Catherine, Martres, Pascale, Coulhon, Marie Pierre, Allou, Nicolas, Bachir, Marwa, Hoang, Stella, Kembellec, Candice, Suply, Olivia, Kharcha, Fatima, Devouge, Anne‐Claire, Flaus‐Furmanuk, Anna, Madeline, Isabelle, Ehinger, Vincent, Bastard, Sophie, Raffray, Loic, Renou, Frederic, Bojarski, Aude, Paul, Caroline, Borsu, Karine, Gorlin, Angelique, Bernardo, Servane, Ut, Carole Truong, Renaud, Stephane, Vignoles, Antoine, Foch, Emilie, Masse, Laurie, Grand, Hubert, Ferrand, Helene, Raffaitin‐Cardin, Christelle, Zellagui, Hadjer, Castang‐Brachet, Celine, Boury, Frederique, Tena, Ana Alvarez, Moura, Isabelle, Kalfon, Pierre, Darasteanu, Juliana, Monier, Arnaud, Foucault, Pascal, Depuille, Alexandra, Laugier‐Robiolle, Stéphanie, Caneiro, Patrick, Basso, Maud, Larger, Etienne, Bouam, Samir, Benzenati, Wahiba, Bachir, Leila Ait, Pillegand, Camille Cussac, Vasse, Marc, Michard, Christophe, Montanier, Nathanaëlle, Millot, Luc, Crepet, Françoise, Ratsimba, Danielle, Bouiller, Kevin, Borot, Sophie, Bruckert, Isabelle, Clergeot, Annie, Schillo, Franck, Vignes, Dorothée, Bourgeon‐Ghittori, Muriel, Lachgar, Hamoud, Cursay, Claire Lambert DE, Levante, Stéphane, Auregan, Jean Charles, Merlet, Antoine, Zaragoza, Cécile, Arnault, Gwénaëlle, Loupp, Anne‐Gaëlle, Lesieur, Olivier, Roncato‐Saberan, Mariam, Gouet, Didier, Lemarie, Romain, Allano, Hong_an, Vivier, Emmanuel, Pariset, Caroline, Luyton, Cédric, Marchand, Lucien, Doroszewski, Fanny, Pecquet, Matthieu, Perard, Laurent, Vuillermoz‐Blas, Sylvie, Kacki, Nicolas, Charrier, Patricia, Ducet‐Boiffard, Amélie, Roure, Françoise Desroys, Bourron, Olivier, Bonnefont‐Rousselot, Dominique, Laroche, Suzanne, Phan, Franck, Hartemann, Agnès, CAUSSY, Cyrielle, Disse, Emmanuel, Guerin, Claude, Perpoint, Thomas, Moulin, Philippe, CARTIER, RÉGINE, Hariri, Geoffroy, Chopin, Dorothée, Vatier, Camille, Bourcigaux, Nathalie, Chaigneau, Emmanuelle, Christin‐Maitre, Sophie, Donadille, Bruno, Feve, Bruno, Lamothe, Sophie, Sarfati, Julie, Pernet, Pascal, Chambon, Anne, Demarsy, Delphine, Campagne, Hugo, Latil‐Plat, Françoise, Berne, Monica, Grinand, Marilyne, Touzet, Marion, Zabulon, Aydrey, Craspag, Jocelyne, Ledoux, Catherine, Contaret, Cedric, Janand‐Delenne, Blandine, Giraud, Anaïs, Lacrimini, Marie Lou, Arrivie, Joëlle, Ancelle, Deborah, Guillois, Carine, Fremy, Bénédicte, Chaalal, Amina, Barrande, Gaëlle, Dorange, Anne, Rouanet, Eglantine, Seret‐Begue, Dominique, Saoud, Audrey, Guedj, Anne‐Marie, Bedos, Nathalie, Velayoudom, Fritz‐Line, Dumas, Marie, Gonda, Benoite, Coffin, Christine, Gibiat, Stéphanie, Lungo, Myriam, Bully, Chantal, Serusclat, Pierre, Bully, Stella, Carre, Patricia, Leberre, Jean‐Philippe, Elkhoury, Carlos, THIEUX, Marine, Paradisi‐Prieur, Laetitia, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Hospitalized patients, Influenza vaccine, Endocrinology, Diabetes and Metabolism, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Diabetes mellitus, Influenza, Human, Internal Medicine, Diabetes Mellitus, Research Letter, Medicine, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, business.industry, SARS-CoV-2, Vaccination, COVID-19, medicine.disease, Prognosis, Research Letters, 3. Good health, Hospitalization, Propensity score matching, business
Abstract

International audience

Published
2021
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35. Vaccines to Prevent COVID-19: A Living Systematic Review With Trial Sequential Analysis and Network Meta-Analysis of Randomised Controlled Trials

Author

Ong G, Bardach A, Siddiqui F, Janus Christian Jakobsen, Ngalamika O, Klingenberg S, Korang Sk, Sophie Juul, Ciapponi A, Christian Gluud, Legart C, Lehana Thabane, Allan Randrup Thomsen, Feinberg Jb, Areti Angeliki Veroniki, Emil Eik Nielsen, Maagaard M, Kokogho A, Rohden Ev, and Petersen Jj

Subjects
Clinical trial, medicine.medical_specialty, business.industry, Internal medicine, Meta-analysis, Relative risk, medicine, MEDLINE, Disease, Adverse effect, Vaccine efficacy, business, Confidence interval
Abstract

Background: COVID-19 is a rapidly spreading disease that is causing extensive burdens across the world. Effective vaccines to prevent COVID-19 are urgently needed. Several vaccines have been accepted by regulatory authorities, but their individual and relative efficacy and adverse effects remain unclear. Methods: We conducted a systematic review of randomised clinical trials with network meta-analysis and Trial Sequential Analysis (TSA). Searches were made in CENTRAL, MEDLINE, Embase, and other sources from inception to May 12, 2021 for randomised clinical trials, assessing vaccines for COVID-19 . At least two independent reviewers screened studies, extracted data, and assessed the risk of bias. Our primary outcomes included all-cause mortality, vaccine efficacy, and serious adverse events. Findings We identified 22 trials; 19 trials randomising 144 434 participants were included in our analyses. mRNA vaccines (efficacy 95%, 95% confidence interval (CI) 92% to 97%; 69 285 participants; 2 trials; GRADE: moderate certainty) and viral vector vaccines (efficacy 68%, 95% CI 61% to 74%; 71 401 participants; 5 trials; GRADE: low certainty) prevented COVID-19. Viral vector vaccines decreased mortality (risk ratio (RR) 0·25, 95% CI 0·09 to 0·67; 67 563 participants; 3 trials, GRADE: low certainty), but data on mRNA vaccines are still imprecise. None of the vaccines showed evidence of a difference on serious adverse events, but observational evidence indicated rare serious adverse events. mRNA and viral vector vaccines increased the risk of non-serious adverse events. Interpretation The evidence suggests that mRNA vaccines and viral vector vaccines are effective in preventing COVID-19. mRNA vaccines seem most effective in preventing COVID-19, but viral vector vaccines seem most effective in reducing mortality. mRNA vaccines and viral vector vaccines increase the risks of rare serious adverse events according to observational evidence. Further trials and longer follow-up are necessary to provide better insight into the safety profile of these vaccines. Registration Information: PROSPERO CRD42020196492. Funding Information: The Copenhagen Trial Unit funded the wages for the authors affiliated with the Copenhagen Trial Unit. None of the authors received any specific funding related to the review. Declaration of Interests: The authors declare that they have no known competing interests.

Published
2021
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36. Comparative clinical prognosis of massive and non-massive pulmonary embolism: A registry-based cohort study

Author

Marc Blondon, David Jimenez, Helia Robert‐Ebadi, Jorge Del Toro, Luciano Lopez‐Jimenez, Conxita Falga, Andris Skride, Llorenç Font, Fernando Javier Vazquez, Henri Bounameaux, Manuel Monreal, Paolo Prandoni, Benjamin Brenner, Dominique Farge‐Bancel, Raquel Barba, Pierpaolo Di Micco, Laurent Bertoletti, Sebastian Schellong, Inna Tzoran, Abilio Reis, Marijan Bosevski, Radovan Malý, Peter Verhamme, Joseph A Caprini, Hanh My Bui, MD Adarraga, M Agud, J Aibar, MA Aibar, J Alfonso, C Amado, JI Arcelus, C Baeza, A Ballaz, R Barba, C Barbagelata, M Barrón, B Barrón‐Andrés, A Blanco‐Molina, E Botella, AM Camon, J Castro, MA Caudevilla, P Cerdà, L Chasco, J Criado, C de Ancos, J de Miguel, P Demelo‐Rodríguez, JA Díaz‐Peromingo, J Díez‐Sierra, R Díaz‐Simón, IM Domínguez, M Encabo, JC Escribano, C Falgá, AI Farfán, C Fernández‐Capitán, JL Fernández‐Reyes, MA Fidalgo, K Flores, C Font, I Francisco, C Gabara, F Galeano‐Valle, MA García, F García‐Bragado, MM García‐Mullor, O Gavín‐Blanco, O Gavín‐Sebastián, A Gil‐Díaz, C Gómez‐Cuervo, J González‐Martínez, E Grau, L Guirado, J Gutiérrez, L Hernández‐Blasco, L Jara‐Palomares, MJ Jaras, D Jiménez, MD Joya, I Jou, B Lacruz, R Lecumberri, J Lima, JL Lobo, H López‐Brull, L López‐Jiménez, P López‐Miguel, JJ López‐Núñez, R López‐Reyes, JB López‐Sáez, MA Lorente, A Lorenzo, M Loring, O Madridano, A Maestre, PJ Marchena, M Martín del Pozo, F Martín‐Martos, C Martínez‐Baquerizo, C Mella, M Mellado, MI Mercado, J Moisés, MV Morales, A Muñoz‐Blanco, D Muñoz‐Guglielmetti, N Muñoz‐Rivas, E Nart, JA Nieto, MJ Núñez, MC Olivares, C Ortega‐Michel, MD Ortega‐Recio, J Osorio, S Otalora, R Otero, P Parra, V Parra, JM Pedrajas, G Pellejero, A Pérez‐Jacoiste, ML Peris, D Pesántez, JA Porras, J Portillo, L Reig, A Riera‐Mestre, A Rivas, A Rodríguez‐Cobo, C Rodríguez‐Matute, J Rogado, V Rosa, CM Rubio, P Ruiz‐Artacho, N Ruiz‐Giménez, J Ruiz‐Ruiz, P Ruiz‐Sada, JC Sahuquillo, G Salgueiro, A Sampériz, JF Sánchez‐Muñoz‐Torrero, T Sancho, P Sigüenza, M Sirisi, S Soler, S Suárez, JM Suriñach, G Tiberio, MI Torres, C Tolosa, J Trujillo‐Santos, F Uresandi, E Usandizaga, R Valle, JR Vela, G Vidal, C Vilar, P Villares, C Zamora, P Gutiérrez, FJ Vázquez, T Vanassche, C Vandenbriele, P Verhamme, J Hirmerova, R Malý, E Salgado, I Benzidia, L Bertoletti, A Bura‐Riviere, B Crichi, P Debourdeau, O Espitia, D Farge‐Bancel, H Helfer, I Mahé, F Moustafa, G Poenou, S Schellong, A Braester, B Brenner, I Tzoran, M Amitrano, F Bilora, C Bortoluzzi, B Brandolin, M Ciammaichella, D Colaizzo, F Dentali, P Di Micco, E Giammarino, E Grandone, S Mangiacapra, D Mastroiacovo, R Maida, N Mumoli, F Pace, R Pesavento, F Pomero, P Prandoni, R Quintavalla, A Rocci, C Siniscalchi, A Tufano, A Visonà, N Vo Hong, B Zalunardo, RV Kalejs, K Maķe, M Ferreira, S Fonseca, F Martins, J Meireles, M Bosevski, M Zdraveska, L Mazzolai, JA Caprini, AJ Tafur, I Weinberg, H Wilkins, HM Bui, Blondon, M., Jimenez, D., Robert-Ebadi, H., Del Toro, J., Lopez-Jimenez, L., Falga, C., Skride, A., Font, L., Vazquez, F. J., Bounameaux, H., Monreal, M., Prandoni, P., Brenner, B., Farge-Bancel, D., Barba, R., Di Micco, P., Bertoletti, L., Schellong, S., Tzoran, I., Reis, A., Bosevski, M., Maly, R., Verhamme, P., Caprini, J. A., My Bui, H., Adarraga, M. D., Agud, M., Aibar, J., Aibar, M. A., Alfonso, J., Amado, C., Arcelus, J. I., Baeza, C., Ballaz, A., Barbagelata, C., Barron, M., Barron-Andres, B., Blanco-Molina, A., Botella, E., Camon, A. M., Castro, J., Caudevilla, M. A., Cerda, P., Chasco, L., Criado, J., de Ancos, C., de Miguel, J., Demelo-Rodriguez, P., Diaz-Peromingo, J. A., Diez-Sierra, J., Diaz-Simon, R., Dominguez, I. M., Encabo, M., Escribano, J. C., Farfan, A. I., Fernandez-Capitan, C., Fernandez-Reyes, J. L., Fidalgo, M. A., Flores, K., Font, C., Francisco, I., Gabara, C., Galeano-Valle, F., Garcia, M. A., Garcia-Bragado, F., Garcia-Mullor, M. M., Gavin-Blanco, O., Gavin-Sebastian, O., Gil-Diaz, A., Gomez-Cuervo, C., Gonzalez-Martinez, J., Grau, E., Guirado, L., Gutierrez, J., Hernandez-Blasco, L., Jara-Palomares, L., Jaras, M. J., Joya, M. D., Jou, I., Lacruz, B., Lecumberri, R., Lima, J., Lobo, J. L., Lopez-Brull, H., Lopez-Miguel, P., Lopez-Nunez, J. J., Lopez-Reyes, R., Lopez-Saez, J. B., Lorente, M. A., Lorenzo, A., Loring, M., Madridano, O., Maestre, A., Marchena, P. J., Martin del Pozo, M., Martin-Martos, F., Martinez-Baquerizo, C., Mella, C., Mellado, M., Mercado, M. I., Moises, J., Morales, M. V., Munoz-Blanco, A., Munoz-Guglielmetti, D., Munoz-Rivas, N., Nart, E., Nieto, J. A., Nunez, M. J., Olivares, M. C., Ortega-Michel, C., Ortega-Recio, M. D., Osorio, J., Otalora, S., Otero, R., Parra, P., Parra, V., Pedrajas, J. M., Pellejero, G., Perez-Jacoiste, A., Peris, M. L., Pesantez, D., Porras, J. A., Portillo, J., Reig, L., Riera-Mestre, A., Rivas, A., Rodriguez-Cobo, A., Rodriguez-Matute, C., Rogado, J., Rosa, V., Rubio, C. M., Ruiz-Artacho, P., Ruiz-Gimenez, N., Ruiz-Ruiz, J., Ruiz-Sada, P., Sahuquillo, J. C., Salgueiro, G., Samperiz, A., Sanchez-Munoz-Torrero, J. F., Sancho, T., Siguenza, P., Sirisi, M., Soler, S., Suarez, S., Surinach, J. M., Tiberio, G., Torres, M. I., Tolosa, C., Trujillo-Santos, J., Uresandi, F., Usandizaga, E., Valle, R., Vela, J. R., Vidal, G., Vilar, C., Villares, P., Zamora, C., Gutierrez, P., Vanassche, T., Vandenbriele, C., Hirmerova, J., Salgado, E., Benzidia, I., Bura-Riviere, A., Crichi, B., Debourdeau, P., Espitia, O., Helfer, H., Mahe, I., Moustafa, F., Poenou, G., Braester, A., Amitrano, M., Bilora, F., Bortoluzzi, C., Brandolin, B., Ciammaichella, M., Colaizzo, D., Dentali, F., Giammarino, E., Grandone, E., Mangiacapra, S., Mastroiacovo, D., Maida, R., Mumoli, N., Pace, F., Pesavento, R., Pomero, F., Quintavalla, R., Rocci, A., Siniscalchi, C., Tufano, A., Visona, A., Vo Hong, N., Zalunardo, B., Kalejs, R. V., Maie, K., Ferreira, M., Fonseca, S., Martins, F., Meireles, J., Zdraveska, M., Mazzolai, L., Tafur, A. J., Weinberg, I., Wilkins, H., and Bui, H. M.

Subjects
Registrie, medicine.medical_specialty, pulmonary embolism, Prognosi, Hemodynamics, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, Clinical prognosis, 0302 clinical medicine, Recurrence, Internal medicine, Case fatality rate, medicine, Humans, hemorrhage, mortality, prognosis, thrombolytic therapy, Registries, cardiovascular diseases, business.industry, Anticoagulant, Anticoagulants, Hematology, Venous Thromboembolism, Prognosis, medicine.disease, Confidence interval, Pulmonary embolism, Discontinuation, Cohort Studie, business, Venous thromboembolism, Cohort study, Human
Abstract

Aims Little is known about the prognosis of patients with massive pulmonary embolism (PE) and its risk of recurrent venous thromboembolism (VTE) compared with non-massive PE, which may inform clinical decisions. Our aim was to compare the risk of recurrent VTE, bleeding, and mortality after massive and non-massive PE during anticoagulation and after its discontinuation. Methods and results We included all participants in the RIETE registry who suffered a symptomatic, objectively confirmed segmental or more central PE. Massive PE was defined by a systolic hypotension at clinical presentation (

Published
2021

37. Arginine-vasopressin mediates counter-regulatory glucagon release and is diminished in type 1 diabetes

Author

Caroline Miranda, Lisa Mellander, Filip K. Knop, Patrick E. MacDonald, Thomas Hill, Victoria Salem, Lina Abdul-Kadir, Patrik Rorsman, Ingrid Wernstedt Asterholm, Linford Jb Briant, Joseph C. Madara, Yanling Wu, Kinga Suba, Bradford B. Lowell, Anna Benrick, Tim James, Angela Kim, Jakob G. Knudsen, Tina Visboll, Mikkel Christensen, Haopeng Lin, Joely A. Kellard, Tore Magnussen, Aliya F. Spigelman, and Diabetes UK

Subjects
Life Sciences & Biomedicine - Other Topics, Male, Vasopressin, Mouse, vasopressin, 0601 Biochemistry and Cell Biology, GLUCOSE, Mice, 0302 clinical medicine, DELTA-CELLS, Insulin, Biology (General), islets, 0303 health sciences, Chemistry, General Neuroscience, Glucagon secretion, General Medicine, COPEPTIN, medicine.anatomical_structure, Medicine, SECRETION, Female, Life Sciences & Biomedicine, ROSTRAL VENTROLATERAL MEDULLA, POTASSIUM CHANNELS, hormones, hormone substitutes, and hormone antagonists, Research Article, Human, Adult, medicine.medical_specialty, brain glucose sensing, endocrine system, QH301-705.5, DEPENDENT INSULINOTROPIC POLYPEPTIDE, Science, 030209 endocrinology & metabolism, Hypoglycemia, Glucagon, General Biochemistry, Genetics and Molecular Biology, HYPOGLYCEMIA, 03 medical and health sciences, Young Adult, BETA-CELLS, Copeptin, Posterior pituitary, Internal medicine, medicine, Animals, Humans, Biology, 030304 developmental biology, Science & Technology, General Immunology and Microbiology, Pancreatic islets, Cell Biology, medicine.disease, ALPHA, Arginine Vasopressin, Endocrinology, Diabetes Mellitus, Type 1, nervous system, Glucagon-Secreting Cells, counter-regulation, Glucagon receptor, Neuroscience
Abstract

Insulin-induced hypoglycemia is a major barrier to the treatment of type-1 diabetes (T1D). Accordingly, it is important that we understand the mechanisms regulating the circulating levels of glucagon – the body’s principal blood glucose-elevating hormone which is secreted from alpha-cells of the pancreatic islets. Varying glucose over the range of concentrations that occur physiologically between the fed and fuel-deprived states (from 8 to 4 mM) has no significant effect on glucagon secretion in the perfused mouse pancreas or in isolated mouse islets (in vitro) and yet associates with dramatic changes in plasma glucagon in vivo. The identity of the systemic factor(s) that stimulates glucagon secretion remains unknown. Here, we show that arginine-vasopressin (AVP), secreted from the posterior pituitary, stimulates glucagon secretion. Glucagon-secreting alpha-cells express high levels of the vasopressin 1b receptor gene (Avpr1b). Activation of AVP neurons in vivo increased circulating copeptin (the C-terminal segment of the AVP precursor peptide, a stable surrogate marker of AVP) and increased blood glucose; effects blocked by pharmacological antagonism of either the glucagon receptor or vasopressin 1b receptor. AVP also mediates the stimulatory effects of hypoglycemia produced by exogenous insulin and 2-deoxy-D-glucose on glucagon secretion. We show that the A1/C1 neurons of the medulla oblongata drive AVP neuron activation in response to insulin-induced hypoglycemia. Exogenous injection of AVP in vivo increased cytoplasmic Ca2+ in alpha-cells (implanted into the anterior chamber of the eye) and glucagon release. Hypoglycemia also increases circulating levels of AVP in humans and this hormone stimulates glucagon secretion from isolated human islets. In patients with T1D, hypoglycemia failed to increase both plasma copeptin and glucagon levels. These findings suggest that AVP is a physiological systemic regulator of glucagon secretion and that this mechanism becomes impaired in T1D.

Published
2021
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38. Association of Variants in the SPTLC1 Gene with Juvenile Amyotrophic Lateral Sclerosis

Author

Johnson, JO, Chia, R, Miller, DE, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, AE, Topp, SD, Gibbs, JR, Cookson, MR, Sabir, MS, Dalgard, CL, Troakes, C, Jones, AR, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, IP, Dobson-Stone, C, Kwok, JB, Bonkowski, ES, Palvadeau, R, Tienari, PJ, Morrison, KE, Shaw, PJ, Al-Chalabi, A, Brown, RH, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, IJ, Perlman, SJ, Glass, I, Scott, AI, Shaw, CE, Basak, AN, Landers, JE, Chiò, A, Crawford, TO, Smith, BN, Traynor, BJ, Fallini, C, Gkazi, AS, Scotter, EL, Kenna, KP, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, ten Asbroek, ALMA, McKenna-Yasek, D, McLaughlin, RL, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D’Alfonso, S, Mazzini, L, Comi, GP, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, KL, Nicholson, GA, Leblond-Manry, C, Rouleau, GA, Hardiman, O, Veldink, JH, van den Berg, LH, Pall, H, Turner, MR, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, JD, Ratti, A, Adeleye, A, Soltis, AR, Alba, C, Viollet, C, Bacikova, D, Hupalo, DN, Sukumar, G, Pollard, HB, Wilkerson, MD, Martinez, EM, Ahmed, S, Arepalli, S, Baloh, RH, Bowser, R, Brady, CB, Brice, A, Broach, J, Campbell, RH, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, VE, Dunckley, TL, Eicher, JD, England, BK, Faghri, F, Feldman, E, Floeter, MK, Fratta, P, Geiger, JT, Gerhard, G, Gibson, SB, Hardy, J, Harms, MB, Heiman-Patterson, TD, Hernandez, DG, Jansson, L, Kirby, J, Kowall, NW, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, MacGowan, DJL, Maragakis, NJ, Mouzat, K, Murphy, NA, Myllykangas, L, Nalls, MA, Orrell, RW, Ostrow, LW, Pamphlett, R, Pickering-Brown, S, Pioro, EP, Pletnikova, O, Pliner, HA, Pulst, SM, Ravits, JM, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, JD, Scholz, SW, Sendtner, M, Sidle, KC, Simmons, Z, Singleton, AB, Smith, N, Stone, DJ, Troncoso, JC, Valori, M, Van Damme, P, Van Deerlin, VM, Van Den Bosch, L, Zinman, L, Angelocola, SM, Ausiello, FP, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, TA, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, FL, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D’Errico, E, DeMarco, G, Dubbioso, R, Ferrarese, C, Ferraro, PM, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, FO, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, MG, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, MR, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, Johnson J.O., Chia R., Miller D.E., Li R., Kumaran R., Abramzon Y., Alahmady N., Renton A.E., Topp S.D., Gibbs J.R., Cookson M.R., Sabir M.S., Dalgard C.L., Troakes C., Jones A.R., Shatunov A., Iacoangeli A., Al Khleifat A., Ticozzi N., Silani V., Gellera C., Blair I.P., Dobson-Stone C., Kwok J.B., Bonkowski E.S., Palvadeau R., Tienari P.J., Morrison K.E., Shaw P.J., Al-Chalabi A., Brown R.H., Calvo A., Mora G., Al-Saif H., Gotkine M., Leigh F., Chang I.J., Perlman S.J., Glass I., Scott A.I., Shaw C.E., Basak A.N., Landers J.E., Chio A., Crawford T.O., Smith B.N., Traynor B.J., Fallini C., Gkazi A.S., Scotter E.L., Kenna K.P., Keagle P., Tiloca C., Vance C., Colombrita C., King A., Pensato V., Castellotti B., Baas F., Ten Asbroek A.L.M.A., McKenna-Yasek D., McLaughlin R.L., Polak M., Asress S., Esteban-Perez J., Stevic Z., D'Alfonso S., Mazzini L., Comi G.P., Del Bo R., Ceroni M., Gagliardi S., Querin G., Bertolin C., Van Rheenen W., Rademakers R., Van Blitterswijk M., Lauria G., Duga S., Corti S., Cereda C., Corrado L., Soraru G., Williams K.L., Nicholson G.A., Leblond-Manry C., Rouleau G.A., Hardiman O., Veldink J.H., Van Den Berg L.H., Pall H., Turner M.R., Talbot K., Taroni F., Garcia-Redondo A., Wu Z., Glass J.D., Ratti A., Adeleye A., Soltis A.R., Alba C., Viollet C., Bacikova D., Hupalo D.N., Sukumar G., Pollard H.B., Wilkerson M.D., Martinez E.M., Ahmed S., Arepalli S., Baloh R.H., Bowser R., Brady C.B., Brice A., Broach J., Campbell R.H., Camu W., Cooper-Knock J., Ding J., Drepper C., Drory V.E., Dunckley T.L., Eicher J.D., England B.K., Faghri F., Feldman E., Floeter M.K., Fratta P., Geiger J.T., Gerhard G., Gibson S.B., Hardy J., Harms M.B., Heiman-Patterson T.D., Hernandez D.G., Jansson L., Kirby J., Kowall N.W., Laaksovirta H., Landeck N., Landi F., Le Ber I., Lumbroso S., Macgowan D.J.L., Maragakis N.J., Mouzat K., Murphy N.A., Myllykangas L., Nalls M.A., Orrell R.W., Ostrow L.W., Pamphlett R., Pickering-Brown S., Pioro E.P., Pletnikova O., Pliner H.A., Pulst S.M., Ravits J.M., Rivera A., Robberecht W., Rogaeva E., Rollinson S., Rothstein J.D., Scholz S.W., Sendtner M., Sidle K.C., Simmons Z., Singleton A.B., Smith N., Stone D.J., Troncoso J.C., Valori M., Van Damme P., Van Deerlin V.M., Van Den Bosch L., Zinman L., Angelocola S.M., Ausiello F.P., Barberis M., Bartolomei I., Battistini S., Bersano E., Bisogni G., Borghero G., Brunetti M., Cabona C., Canale F., Canosa A., Cantisani T.A., Capasso M., Caponnetto C., Cardinali P., Carrera P., Casale F., Colletti T., Conforti F.L., Conte A., Conti E., Corbo M., Cuccu S., Dalla Bella E., D'Errico E., Demarco G., Dubbioso R., Ferrarese C., Ferraro P.M., Filippi M., Fini N., Floris G., Fuda G., Gallone S., Gianferrari G., Giannini F., Grassano M., Greco L., Iazzolino B., Introna A., La Bella V., Lattante S., Liguori R., Logroscino G., Logullo F.O., Lunetta C., Mandich P., Mandrioli J., Manera U., Manganelli F., Marangi G., Marinou K., Marrosu M.G., Martinelli I., Messina S., Moglia C., Mosca L., Murru M.R., Origone P., Passaniti C., Petrelli C., Petrucci A., Pozzi S., Pugliatti M., Quattrini A., Ricci C., Riolo G., Riva N., Russo M., Sabatelli M., Salamone P., Salivetto M., Salvi F., Santarelli M., Sbaiz L., Sideri R., Simone I., Simonini C., Spataro R., Tanel R., Tedeschi G., Ticca A., Torriello A., Tranquilli S., Tremolizzo L., Trojsi F., Vasta R., Vacchiano V., Vita G., Volanti P., Zollino M., Zucchi E., Johnson, J. O., Chia, R., Miller, D. E., Li, R., Kumaran, R., Abramzon, Y., Alahmady, N., Renton, A. E., Topp, S. D., Gibbs, J. R., Cookson, M. R., Sabir, M. S., Dalgard, C. L., Troakes, C., Jones, A. R., Shatunov, A., Iacoangeli, A., Al Khleifat, A., Ticozzi, N., Silani, V., Gellera, C., Blair, I. P., Dobson-Stone, C., Kwok, J. B., Bonkowski, E. S., Palvadeau, R., Tienari, P. J., Morrison, K. E., Shaw, P. J., Al-Chalabi, A., Brown, R. H., Calvo, A., Mora, G., Al-Saif, H., Gotkine, M., Leigh, F., Chang, I. J., Perlman, S. J., Glass, I., Scott, A. I., Shaw, C. E., Basak, A. N., Landers, J. E., Chio, A., Crawford, T. O., Smith, B. N., Traynor, B. J., Fallini, C., Gkazi, A. S., Scotter, E. L., Kenna, K. P., Keagle, P., Tiloca, C., Vance, C., Colombrita, C., King, A., Pensato, V., Castellotti, B., Baas, F., Ten Asbroek, A. L. M. A., McKenna-Yasek, D., Mclaughlin, R. L., Polak, M., Asress, S., Esteban-Perez, J., Stevic, Z., D'Alfonso, S., Mazzini, L., Comi, G. P., Del Bo, R., Ceroni, M., Gagliardi, S., Querin, G., Bertolin, C., Van Rheenen, W., Rademakers, R., Van Blitterswijk, M., Lauria, G., Duga, S., Corti, S., Cereda, C., Corrado, L., Soraru, G., Williams, K. L., Nicholson, G. A., Leblond-Manry, C., Rouleau, G. A., Hardiman, O., Veldink, J. H., Van Den Berg, L. H., Pall, H., Turner, M. R., Talbot, K., Taroni, F., Garcia-Redondo, A., Wu, Z., Glass, J. D., Ratti, A., Adeleye, A., Soltis, A. R., Alba, C., Viollet, C., Bacikova, D., Hupalo, D. N., Sukumar, G., Pollard, H. B., Wilkerson, M. D., Martinez, E. M., Ahmed, S., Arepalli, S., Baloh, R. H., Bowser, R., Brady, C. B., Brice, A., Broach, J., Campbell, R. H., Camu, W., Cooper-Knock, J., Ding, J., Drepper, C., Drory, V. E., Dunckley, T. L., Eicher, J. D., England, B. K., Faghri, F., Feldman, E., Floeter, M. K., Fratta, P., Geiger, J. T., Gerhard, G., Gibson, S. B., Hardy, J., Harms, M. B., Heiman-Patterson, T. D., Hernandez, D. G., Jansson, L., Kirby, J., Kowall, N. W., Laaksovirta, H., Landeck, N., Landi, F., Le Ber, I., Lumbroso, S., Macgowan, D. J. L., Maragakis, N. J., Mouzat, K., Murphy, N. A., Myllykangas, L., Nalls, M. A., Orrell, R. W., Ostrow, L. W., Pamphlett, R., Pickering-Brown, S., Pioro, E. P., Pletnikova, O., Pliner, H. A., Pulst, S. M., Ravits, J. M., Rivera, A., Robberecht, W., Rogaeva, E., Rollinson, S., Rothstein, J. D., Scholz, S. W., Sendtner, M., Sidle, K. C., Simmons, Z., Singleton, A. B., Smith, N., Stone, D. J., Troncoso, J. C., Valori, M., Van Damme, P., Van Deerlin, V. M., Van Den Bosch, L., Zinman, L., Angelocola, S. M., Ausiello, F. P., Barberis, M., Bartolomei, I., Battistini, S., Bersano, E., Bisogni, G., Borghero, G., Brunetti, M., Cabona, C., Canale, F., Canosa, A., Cantisani, T. A., Capasso, M., Caponnetto, C., Cardinali, P., Carrera, P., Casale, F., Colletti, T., Conforti, F. L., Conte, A., Conti, E., Corbo, M., Cuccu, S., Dalla Bella, E., D'Errico, E., Demarco, G., Dubbioso, R., Ferrarese, C., Ferraro, P. M., Filippi, M., Fini, N., Floris, G., Fuda, G., Gallone, S., Gianferrari, G., Giannini, F., Grassano, M., Greco, L., Iazzolino, B., Introna, A., La Bella, V., Lattante, S., Liguori, R., Logroscino, G., Logullo, F. O., Lunetta, C., Mandich, P., Mandrioli, J., Manera, U., Manganelli, F., Marangi, G., Marinou, K., Marrosu, M. G., Martinelli, I., Messina, S., Moglia, C., Mosca, L., Murru, M. R., Origone, P., Passaniti, C., Petrelli, C., Petrucci, A., Pozzi, S., Pugliatti, M., Quattrini, A., Ricci, C., Riolo, G., Riva, N., Russo, M., Sabatelli, M., Salamone, P., Salivetto, M., Salvi, F., Santarelli, M., Sbaiz, L., Sideri, R., Simone, I., Simonini, C., Spataro, R., Tanel, R., Tedeschi, G., Ticca, A., Torriello, A., Tranquilli, S., Tremolizzo, L., Trojsi, F., Vasta, R., Vacchiano, V., Vita, G., Volanti, P., Zollino, M., Zucchi, E., Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), Palvadeau, Robin, Johnson, Janel O., Chia, Ruth, Miller, Danny E., Li, Rachel, Kumaran, Ravindran, Abramzon, Yevgeniya, Alahmady, Nada, Renton, Alan E., Topp, Simon D., Gibbs, J. Raphael, Cookson, Mark R., Sabir, Marya S., Dalgard, Clifton L., Troakes, Claire, Jones, Ashley R., Shatunov, Aleksey, Lacoangeli, Alfredo, Al Khleifat, Ahmad, Ticozzi, Nicola, Silani, Vincenzo, Gellera, Cinzia, Blair, Ian P., Dobson-Stone, Carol, Kwok, John B., Bonkowski, Emily S., Tienari, Pentti J., Morrison, Karen E., Shaw, Pamela J., Al-Chalabi, Ammar, Jr, Robert H. Brown, Calvo, Andrea, Mora, Gabriele, Al-Saif, Hind, Gotkine, Marc, Leigh, Fawn, Chang, Irene J., Perlman, Seth J., Glass, Ian, Scott, Anna, I., Landers, John E., Chio, Adriano, Crawford, Thomas O., Smith, Bradley N., Traynor, Bryan J., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Johnson, J, Chia, R, Miller, D, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, A, Topp, S, Gibbs, J, Cookson, M, Sabir, M, Dalgard, C, Troakes, C, Jones, A, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, I, Dobson-Stone, C, Kwok, J, Bonkowski, E, Palvadeau, R, Tienari, P, Morrison, K, Shaw, P, Al-Chalabi, A, Brown, R, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, I, Perlman, S, Glass, I, Scott, A, Shaw, C, Basak, A, Landers, J, Chiò, A, Crawford, T, Smith, B, Traynor, B, Fallini, C, Gkazi, A, Scotter, E, Kenna, K, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, Ten Asbroek, A, McKenna-Yasek, D, Mclaughlin, R, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D'Alfonso, S, Mazzini, L, Comi, G, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, K, Nicholson, G, Leblond-Manry, C, Rouleau, G, Hardiman, O, Veldink, J, van den Berg, L, Pall, H, Turner, M, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, J, Ratti, A, Adeleye, A, Soltis, A, Alba, C, Viollet, C, Bacikova, D, Hupalo, D, Sukumar, G, Pollard, H, Wilkerson, M, Martinez, E, Ahmed, S, Arepalli, S, Baloh, R, Bowser, R, Brady, C, Brice, A, Broach, J, Campbell, R, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, V, Dunckley, T, Eicher, J, England, B, Faghri, F, Feldman, E, Floeter, M, Fratta, P, Geiger, J, Gerhard, G, Gibson, S, Hardy, J, Harms, M, Heiman-Patterson, T, Hernandez, D, Jansson, L, Kirby, J, Kowall, N, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, Macgowan, D, Maragakis, N, Mouzat, K, Murphy, N, Myllykangas, L, Nalls, M, Orrell, R, Ostrow, L, Pamphlett, R, Pickering-Brown, S, Pioro, E, Pletnikova, O, Pliner, H, Pulst, S, Ravits, J, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, J, Scholz, S, Sendtner, M, Sidle, K, Simmons, Z, Singleton, A, Smith, N, Stone, D, Troncoso, J, Valori, M, Van Damme, P, Van Deerlin, V, Van Den Bosch, L, Zinman, L, Angelocola, S, Ausiello, F, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, T, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, F, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D'Errico, E, Demarco, G, Dubbioso, R, Ferrarese, C, Ferraro, P, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, F, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, M, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, M, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, HUS Neurocenter, Department of Neurosciences, Clinicum, Neurologian yksikkö, TRIMM - Translational Immunology Research Program, Pentti Tienari / Principal Investigator, Human Genetics, ARD - Amsterdam Reproduction and Development, ANS - Complex Trait Genetics, Johnson, Janel O, Miller, Danny E, Renton, Alan E, Topp, Simon D, Gibbs, J Raphael, Cookson, Mark R, Sabir, Marya S, Dalgard, Clifton L, Jones, Ashley R, Iacoangeli, Alfredo, Blair, Ian P, Kwok, John B, Bonkowski, Emily S, Tienari, Pentti J, Morrison, Karen E, Shaw, Pamela J, Brown, Robert H, Chang, Irene J, Perlman, Seth J, Scott, Anna I, Shaw, Christopher E, Basak, A Nazli, Landers, John E, Chiò, Adriano, Crawford, Thomas O, Smith, Bradley N, Traynor, Bryan J, Fallini, Claudia, Gkazi, Athina Soragia, Scotter, Emma L, Kenna, Kevin P, Keagle, Pamela, Tiloca, Cinzia, Vance, Caroline, Colombrita, Claudia, King, Andrew, Pensato, Viviana, Castellotti, Barbara, Baas, Frank, Ten Asbroek, Anneloor L M A, McKenna-Yasek, Diane, Mclaughlin, Russell L, Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesú, Stevic, Zorica, D'Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P, Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, van Rheenen, Wouter, Rademakers, Rosa, van Blitterswijk, Marka, Lauria, Giuseppe, Duga, Stefano, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Sorarù, Gianni, Williams, Kelly L, Nicholson, Garth A, Leblond-Manry, Claire, Rouleau, Guy A, Hardiman, Orla, Veldink, Jan H, van den Berg, Leonard H, Pall, Hardev, Turner, Martin R, Talbot, Kevin, Taroni, Franco, García-Redondo, Alberto, Wu, Zheyang, Glass, Jonathan D, Ratti, Antonia, Adeleye, Adelani, Soltis, Anthony R, Alba, Camille, Viollet, Coralie, Bacikova, Dagmar, Hupalo, Daniel N, Sukumar, Gauthaman, Pollard, Harvey B, Wilkerson, Matthew D, Martinez, Elisa McGrath, Ahmed, Sarah, Arepalli, Sampath, Baloh, Robert H, Bowser, Robert, Brady, Christopher B, Brice, Alexi, Broach, Jame, Campbell, Roy H, Camu, William, Cooper-Knock, John, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E, Dunckley, Travis L, Eicher, John D, England, Bryce K, Faghri, Faraz, Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Geiger, Joshua T, Gerhard, Glenn, Gibson, Summer B, Hardy, John, Harms, Matthew B, Heiman-Patterson, Terry D, Hernandez, Dena G, Jansson, Lilja, Kirby, Janine, Kowall, Neil W, Laaksovirta, Hannu, Landeck, Natalie, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, Macgowan, Daniel J L, Maragakis, Nicholas J, Mouzat, Kevin, Murphy, Natalie A, Myllykangas, Liisa, Nalls, Mike A, Orrell, Richard W, Ostrow, Lyle W, Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik P, Pletnikova, Olga, Pliner, Hannah A, Pulst, Stefan M, Ravits, John M, Rivera, Alberto, Robberecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D, Scholz, Sonja W, Sendtner, Michael, Sidle, Katie C, Simmons, Zachary, Singleton, Andrew B, Smith, Nathan, Stone, David J, Troncoso, Juan C, Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M, Van Den Bosch, Ludo, Zinman, Lorne, Angelocola, Stefania M, Ausiello, Francesco P, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Bersano, Enrica, Bisogni, Giulia, Borghero, Giuseppe, Brunetti, Maura, Cabona, Corrado, Canale, Fabrizio, Canosa, Antonio, Cantisani, Teresa A, Capasso, Margherita, Caponnetto, Claudia, Cardinali, Patrizio, Carrera, Paola, Casale, Federico, Colletti, Tiziana, Conforti, Francesca L, Conte, Amelia, Conti, Elisa, Corbo, Massimo, Cuccu, Stefania, Dalla Bella, Eleonora, D'Errico, Eustachio, Demarco, Giovanni, Dubbioso, Raffaele, Ferrarese, Carlo, Ferraro, Pilar M, Filippi, Massimo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Gallone, Salvatore, Gianferrari, Giulia, Giannini, Fabio, Grassano, Maurizio, Greco, Lucia, Iazzolino, Barbara, Introna, Alessandro, La Bella, Vincenzo, Lattante, Serena, Liguori, Rocco, Logroscino, Giancarlo, Logullo, Francesco O, Lunetta, Christian, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Manganelli, Fiore, Marangi, Giuseppe, Marinou, Kalliopi, Marrosu, Maria Giovanna, Martinelli, Ilaria, Messina, Sonia, Moglia, Cristina, Mosca, Lorena, Murru, Maria R, Origone, Paola, Passaniti, Carla, Petrelli, Cristina, Petrucci, Antonio, Pozzi, Susanna, Pugliatti, Maura, Quattrini, Angelo, Ricci, Claudia, Riolo, Giulia, Riva, Nilo, Russo, Massimo, Sabatelli, Mario, Salamone, Paolina, Salivetto, Marco, Salvi, Fabrizio, Santarelli, Marialuisa, Sbaiz, Luca, Sideri, Riccardo, Simone, Isabella, Simonini, Cecilia, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Ticca, Anna, Torriello, Antonella, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Vasta, Rosario, Vacchiano, Veria, Vita, Giuseppe, Volanti, Paolo, Zollino, Marcella, and Zucchi, Elisabetta

Subjects
Hereditary sensory neuropathy, L-serine, Mutations, Deoxysphingolipids, Accumulation, Enzyme complex, Juvenile amyotrophic lateral sclerosis, Serine C-Palmitoyltransferase, Whole Exome Sequencing, 0302 clinical medicine, Medicine, Family history, Amyotrophic lateral sclerosis, Child, Index case, Exome sequencing, Original Investigation, 0303 health sciences, Neurosciences and neurology, 3. Good health, Child, Preschool, Failure to thrive, Female, medicine.symptom, Life Sciences & Biomedicine, L-SERINE, Comments, Human, Adult, medicine.medical_specialty, Adolescent, Amyotrophic Lateral Sclerosis, Genetic Predisposition to Disease, Humans, Mutation, Young Adult, Clinical Neurology, NO, 03 medical and health sciences, DEOXYSPHINGOLIPIDS, Internal medicine, Exome Sequencing, Online First, Juvenile, Preschool, 030304 developmental biology, ACCUMULATION, Science & Technology, SPTLC1, business.industry, MUTATIONS, Research, 3112 Neurosciences, medicine.disease, HEREDITARY SENSORY NEUROPATHY, juvenile, 3111 Biomedicine, Neurology (clinical), Neurosciences & Neurology, ALS, genetic, business, 030217 neurology & neurosurgery, Amyotrophic Lateral Sclerosi
Abstract

Key Points Question What genetic variants are associated with juvenile amyotrophic lateral sclerosis (ALS)? Findings In this family-based genetic study, exome sequencing was performed in 3 patients diagnosed with juvenile ALS and failure to thrive; this identified de novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient). Variants in SPTLC1 are a known cause of hereditary sensory and autonomic neuropathy, type 1A, and these data extend the phenotype associated with this gene. Meaning De novo variants in the SPTLC1 gene are associated with juvenile ALS, a fatal neurological disorder., This genetic association study identifies genetic variants associated with juvenile amyotrophic lateral sclerosis., Importance Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective To identify the genetic variants associated with juvenile ALS. Design, Setting, and Participants In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main Outcomes and Measures De novo variants present only in the index case and not in unaffected family members. Results Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway. Conclusions and Relevance These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.

Published
2021
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39. Risk factors for kidney disorders in patients with type 2 diabetes at high cardiovascular risk: An exploratory analysis (DEVOTE 12)

Author

Amod, A, Buse, JB, McGuire, DK, Pieber, TR, Pop-Busui, R, Pratley, RE, Zinman, B, Hansen, MB, Jia, T, Mark, T, Poulter, NR, and DEVOTE Study Group

Subjects
Male, medicine.medical_specialty, Time Factors, type 2 diabetes mellitus, Endocrinology, Diabetes and Metabolism, insulin analogues, DEVOTE Study Group, Insulin Glargine, Type 2 diabetes, urologic and male genital diseases, Cardiovascular, Kidney, Risk Assessment, CVOT, Endocrinology & Metabolism, Double-Blind Method, chronic renal failure, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, Hypoglycemic Agents, In patient, Renal Insufficiency, Chronic, business.industry, Type 2 Diabetes Mellitus, 1103 Clinical Sciences, Exploratory analysis, Acute Kidney Injury, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, diabetic kidney disease, Insulin, Long-Acting, Treatment Outcome, Diabetes Mellitus, Type 2, Heart Disease Risk Factors, 1116 Medical Physiology, Chronic renal failure, Original Article, Female, Kidney disorder, 1115 Pharmacology and Pharmaceutical Sciences, Cardiology and Cardiovascular Medicine, business, Cardiovascular outcomes, Glomerular Filtration Rate
Abstract

Aim: To investigate risk factors associated with kidney disorders in patients with type 2 diabetes (T2D) at high cardiovascular (CV) risk. Methods: In DEVOTE, a cardiovascular outcomes trial, 7637 patients were randomised to insulin degludec (degludec) or insulin glargine 100 units/mL (glargine U100), with standard of care. In these exploratory post hoc analyses, serious adverse event reports were searched using Standardised MedDRA® Queries related to chronic kidney disease (CKD) or acute kidney injury (AKI). Baseline predictors of CKD, AKI and change in estimated glomerular filtration rate (eGFR) were identified using stepwise selection and Cox or linear regression. Results: Over 2 years, eGFR (mL/min/1.73 m2) decline was small and similar between treatments (degludec: 2.70; glargine U100: 2.92). Overall, 97 and 208 patients experienced CKD and AKI events, respectively. A history of heart failure was a risk factor for CKD (hazard ratio [HR] 1.97 [95% confidence interval [CI] 1.41; 2.75]) and AKI (HR 2.28 [95% CI 1.64; 3.17]). A history of hepatic impairment was a significant predictor of CKD (HR 3.28 [95% CI 2.12; 5.07]) and change in eGFR (estimate: −8.59 [95% CI −10.20; −7.00]). Conclusion: Our findings indicate that traditional, non-modifiable risk factors for kidney disorders apply to insulin-treated patients with T2D at high CV risk. Trial registration: NCT01959529 (ClinicalTrials.gov).

Published
2020

40. Improving sensitivity of the connective tissue disease screening questionnaire: A comparative study of various scoring methods

Author

Mihir Gandhi, Julian Thumboo, Elenore Jb Uy, Xiaohui Xin, Elizabeth W. Karlson, Ying Ying Leung, Jeffrey A. Sparks, Andrea Hsiu Ling Low, Warren Fong, and Ling Xiang

Subjects
Adult, Male, medicine.medical_specialty, China, Sensitivity and Specificity, High morbidity, Young Adult, Rheumatology, Internal medicine, Rheumatic Diseases, Surveys and Questionnaires, medicine, Humans, Connective Tissue Diseases, Aged, Aged, 80 and over, Window of opportunity, business.industry, Scoring methods, Middle Aged, medicine.disease, Connective tissue disease, Screening questionnaire, Rheumatoid arthritis, Female, Population screening, business
Abstract

Objectives Early detection of autoimmune rheumatic diseases is crucial given their high morbidity and mortality and short window of opportunity to improve patient outcomes. Self-administered screening questionnaires such as the connective tissue disease screening questionnaire (CSQ) have been shown to promote early detection of autoimmune rheumatic diseases. However, optimal scoring of screening questionnaires may differ with prevalence of clinical features and changes in classification criteria. We compared the performance of 3 scoring methods for the CSQ for early detection of autoimmune rheumatic diseases in a multi-ethnic Asian population. Methods Patients who were newly referred for evaluation of possible autoimmune rheumatic diseases were invited to answer the cross-culturally adapted CSQ. Detection of autoimmune rheumatic diseases using 1) the original CSQ scoring, 2) a modified CSQ scoring and 3) a scoring based on current classification criteria, were compared to classification of autoimmune rheumatic diseases by classification criteria. Results Of 819 participants, 85 were classified as having autoimmune rheumatic diseases screened for by the adapted CSQ. The original CSQ scoring yielded relatively lower sensitivities in detecting both any and individual autoimmune rheumatic diseases (67% and 20-57%, respectively) compared to the modified CSQ scoring (81% and 60-73%, respectively) and the scoring based on current classification criteria (89% and 50-88%, respectively). Conclusion The adapted CSQ with the classification criteria-based scoring achieved relatively high sensitivities in detecting autoimmune rheumatic diseases, suggesting this could be employed as the first step in population screening.

Published
2020

41. Development of a hypoglycaemia risk score to identify high-risk individuals with advanced type 2 diabetes in DEVOTE

Author

Heller, S, Lingvay, I, Marso, SP, Philis-Tsimikas, A, Pieber, TR, Poulter, NR, Pratley, RE, Hachmann-Nielsen, E, Kvist, K, Lange, M, Moses, AC, Trock Andresen, M, Buse, JB, and DEVOTE Study Group

Subjects
Pediatrics, medicine.medical_specialty, Glycated Hemoglobin A, Endocrinology, Diabetes and Metabolism, DEVOTE Study Group, Insulin Glargine, 030209 endocrinology & metabolism, Type 2 diabetes, Disease, 030204 cardiovascular system & hematology, risk score, Lower risk, 03 medical and health sciences, Endocrinology & Metabolism, 0302 clinical medicine, Endocrinology, Risk Factors, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Generalizability theory, Glycated haemoglobin, Glycated Hemoglobin, Framingham Risk Score, business.industry, Area under the curve, 1103 Clinical Sciences, Original Articles, Stepwise regression, medicine.disease, severe hypoglycaemia, Hypoglycemia, Diabetes Mellitus, Type 2, Original Article, type 2 diabetes, business
Abstract

Aims The ability to differentiate patient populations with type 2 diabetes at high risk of severe hypoglycaemia could impact clinical decision making. The aim of this study was to develop a risk score, using patient characteristics, that could differentiate between populations with higher and lower 2‐year risk of severe hypoglycaemia among individuals at increased risk of cardiovascular disease. Materials and methods Two models were developed for the risk score based on data from the DEVOTE cardiovascular outcomes trials. The first, a data‐driven machine‐learning model, used stepwise regression with bidirectional elimination to identify risk factors for severe hypoglycaemia. The second, a risk score based on known clinical risk factors accessible in clinical practice identified from the data‐driven model, included: insulin treatment regimen; diabetes duration; sex; age; and glycated haemoglobin, all at baseline. Both the data‐driven model and simple risk score were evaluated for discrimination, calibration and generalizability using data from DEVOTE, and were validated against the external LEADER cardiovascular outcomes trial dataset. Results Both the data‐driven model and the simple risk score discriminated between patients at higher and lower hypoglycaemia risk, and performed similarly well based on the time‐dependent area under the curve index (0.63 and 0.66, respectively) over a 2‐year time horizon. Conclusions Both the data‐driven model and the simple hypoglycaemia risk score were able to discriminate between patients at higher and lower risk of severe hypoglycaemia, the latter doing so using easily accessible clinical data. The implementation of such a tool (http://www.hyporiskscore.com/) may facilitate improved recognition of, and education about, severe hypoglycaemia risk, potentially improving patient care.

Published
2020

42. ACE-inhibitors and Angiotensin-2 Receptor Blockers are not associated with severe SARS-COVID19 infection in a multi-site UK acute Hospital Trust

Author

Daniel M Bean, Zeljko Kraljevic, Thomas Searle, Rebecca Bendayan, Kevin O’Gallagher, Andrew Pickles, Amos Folarin, Lukasz Roguski, Kawsar Noor, Anthony Shek, Rosita Zakeri, Ajay M Shah, James TH Teo, and Richard JB Dobson

Subjects
0303 health sciences, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Severe disease, Disease, 030204 cardiovascular system & hematology, medicine.disease, Intensive care unit, 3. Good health, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Diabetes mellitus, Heart failure, Internal medicine, Cohort, medicine, Clinical endpoint, cardiovascular diseases, business, hormones, hormone substitutes, and hormone antagonists, 030304 developmental biology
Abstract

AimsThe SARS-Cov2 virus binds to the ACE2 receptor for cell entry. It has been suggested that ACE-inhibitors (ACEi) and Angiotensin-2 Blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise ACE2 levels, could increase the risk of severe COVID19 infection.Methods and ResultsWe evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID19 at two hospitals with a multi-ethnic catchment population in London (UK). The mean age was 68±17 years (57% male) and 74% of patients had at least 1 comorbidity. 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21-days of symptom onset. 399 patients (33.3 %) were taking ACEi or ARB. Patients on ACEi/ARB were significantly older and had more comorbidities. The odds ratio (OR) for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co-morbidities, was 0.63 (CI 0.47-0.84, pConclusionsThere was no evidence for increased severity of COVID19 disease in hospitalised patients on chronic treatment with ACEi or ARB. A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta-analyses and randomised clinical trials.

Published
2020
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43. Risk of severe hypoglycaemia and its impact in type 2 diabetes in DEVOTE

Author

Heller, S, Lingvay, I, Marso, SP, Philis-Tsimikas, A, Pieber, TR, Poulter, NR, Pratley, RE, Hachmann-Nielsen, E, Kvist, K, Lange, M, Moses, AC, Andresen, MT, Buse, JB, and DEVOTE Study Group

Subjects
Insulin degludec, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Population, DEVOTE Study Group, Insulin Glargine, 030209 endocrinology & metabolism, MACE, 030204 cardiovascular system & hematology, 03 medical and health sciences, Endocrinology & Metabolism, 0302 clinical medicine, Endocrinology, Internal medicine, Internal Medicine, medicine, Humans, Hypoglycemic Agents, cardiovascular diseases, Risk factor, education, education.field_of_study, Framingham Risk Score, Insulin glargine, business.industry, Incidence (epidemiology), 1103 Clinical Sciences, Original Articles, Hypoglycemia, severe hypoglycaemia, Insulin, Long-Acting, all‐cause mortality, Quartile, Diabetes Mellitus, Type 2, all-cause mortality, Original Article, type 2 diabetes, business, Mace, medicine.drug
Abstract

Aims To undertake a post‐hoc analysis, utilizing a hypoglycaemia risk score based on DEVOTE trial data, to investigate if a high risk of severe hypoglycaemia was associated with an increased risk of cardiovascular events, and whether reduced rates of severe hypoglycaemia in patients identified as having the highest risk affected the risk of cardiovascular outcomes. Materials and Methods The DEVOTE population was divided into quartiles according to patients' individual hypoglycaemia risk scores. For each quartile, the observed incidence and rate of severe hypoglycaemia, major adverse cardiovascular event (MACE) and all‐cause mortality were determined to investigate whether those with the highest risk of hypoglycaemia were also at the greatest risk of MACE and all‐cause mortality. In addition, treatment differences within each risk quartile [insulin degludec (degludec) vs. insulin glargine 100 units/mL (glargine U100)] in terms of severe hypoglycaemia, MACE and all‐cause mortality were investigated. Results Patients with the highest risk scores had the highest rates of severe hypoglycaemia, MACE and all‐cause mortality. Treatment ratios between degludec and glargine U100 in the highest risk quartile were 95% confidence interval (CI) 0.56 (0.39; 0.80) (severe hypoglycaemia), 95% CI 0.76 (0.58; 0.99) (MACE) and 95% CI 0.77 (0.55; 1.07) (all‐cause mortality). Conclusions The risk score demonstrated that a high risk of severe hypoglycaemia was associated with a high incidence of MACE and all‐cause mortality and that, in this high‐risk group, those treated with degludec had a lower incidence of MACE. These observations support the hypothesis that hypoglycaemia is a risk factor for cardiovascular events.

Published
2020

44. 4CPS-176 Electrolyte disturbances in premature infants with intrauterine growth restriction receiving parenteral nutrition

Author

S Clemente-Bautista, L Gómez-Ganda, M Linés-Palazón, F Castillo-Salinas, CJ Parramón-Teixidó, Albert Blanco-Grau, JB Montoro-Ronsano, and B Garcia-Palop

Subjects
medicine.medical_specialty, Hypercalcaemia, business.industry, Phosphorus, Albumin, Intrauterine growth restriction, Gestational age, chemistry.chemical_element, Calcium, medicine.disease, Phosphate, chemistry.chemical_compound, Endocrinology, Parenteral nutrition, chemistry, Internal medicine, medicine, business
Abstract

Background and importance Intrauterine growth restriction (IUGR) in neonates can promote the occurrence of electrolyte disturbances. Therefore, some authors propose a modification of parenteral nutrition (PN) in these patients which allows for correcting electrolyte disturbances. Aim and objectives To evaluate the association between IUGR and the occurrence of calcium and phosphate disturbances in a cohort of premature infants receiving PN. Material and methods An observational retrospective study was conducted at a third level children’s hospital between January and December 2016. Neonates with a gestational age (GA) We analysed ionised calcium levels because it does not depend on albumin levels. The infants were divided into two groups: IUGR and non-IUGR. Hypophosphataemia was defined as plasma phosphate levels 1.3 mmol/L. Associations between calcium and phosphate, and IUGR were analysed by logistic regression using SPSS V.15.0 (SPSS Inc, Chicago, Illinois, USA) software package. Results In the IUGR group (n=52, 33 female), GA was 29.39±2.82 weeks and BW was 1047.13±297.41 g. PN composition: 93.20±16.31 mL/kg/day; 59.00±8.61 kcal/kg/day; amino acids 2.96±0.44 g/kg/day; calcium 1.45±0.28 mEq/kg/day; and phosphorus 0.68±0.13 mmol/kg/day. Plasma levels of phosphate were 1.36±0.34 mmol/L and plasma levels of calcium ion were 1.20±0.30 mmol/L; hypophosphataemia 85.48%; hypercalcaemia 34.62%. In the non-IUGR group (n=62, 32 female), GA was 27.77±2.10 weeks and BW was 1087.42±260.13 g. PN composition: 94.78±18.94 mL/kg/day; 58.56±7.89 kcal/kg/day; amino acids 2.91±0.34 g/kg/day; calcium 1.47±0.19 mEq/kg/day; and phosphorus 0.66±0.14 mmol/kg/day. Plasma levels of phosphate were 1.64±0.34 mmol/L and plasma levels of calcium ion were 1.21±0.25 mmol/L; hypophosphataemia 78.85%; hypercalcaemia 19.35%. There was no statistically significant difference between the groups with respect to age, GA, BW, PN composition or phosphate and calcium plasma levels. Logistical regression showed a statistically significant relationship between IUGR and hypercalcaemia events (p=0.047). Only weight was associated with hypophosphataemia events (p=0.019). Conclusion and relevance We found that the IUGR group presented more hypercalcaemia events compared with the non-IUGR group. These results suggest that modification of electrolyte content of the PN in the IUGR group may be a strategy to avoid calcium disturbances. References and/or acknowledgements No conflict of interest.

Published
2020
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45. 4CPS-033 Off-label use of nebulised aztreonam lysine in patients with chronic gram negative bacterial lung colonisation

Author

C Alonso Martinez, M Larrosa García, JB Montoro Ronsano, S Garcia Garcia, I. Cardona Pascual, E Revilla López, J Vidal Otero, L Cantos Gil, C Alerany Pardo, Gomez Domingo, and P Granollers Rabal

Subjects
education.field_of_study, medicine.medical_specialty, Bronchiectasis, business.industry, Population, medicine.disease, FEV1/FVC ratio, Internal medicine, medicine, Colistin, Tobramycin, Sputum, Respiratory function, medicine.symptom, education, business, Adverse effect, medicine.drug
Abstract

Background and importance Aztreonam lysine inhalation solution (AZLI) is approved for nebulised treatment (nebT) of pulmonary Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF). The clinical benefit of nebulised AZLI in non-CF, such as bronchiectasis (BC) or lung transplant (LT) patients with chronic gram negative infection, has not been clearly established. Aim and objectives To assess the safety and effectiveness of AZLI for nebT in patients with non-CF BC or LT colonised by gram negative chronic bacteria. Material and methods This was an observational retrospective study in patients with non-CF BC or LT affected by chronic gram negative bacterial infection who started AZLI in 2013–2019. Clinical data were collected from the hospital medical records: hospital admissions, infective bacteria, previous nebT, safety and effectiveness date of AZLI. Mean (SD) respiratory function tests (FVC, FEV1, FEF25–75) were analysed for each patient, along with AZLI treatment. To evaluate treatment effects (time=0 vs follow-up data), variance analysis (ANOVA) was applied (SPSS). Results The study included 15 patients (aged >18 years) previously treated with alternative nebT. Reasons for stopping previous treatment were: tobramycin/colistin intolerance (n=6, 40%), tobramycin/colistin resistance (n=7, 46.7%) and no clinical improvement (n=2, 13.3%). Patients were classified by diagnosis: BC (n=7; 28.6% men) and LT (n=8; 50.0% men). AZLI was administered in ‘on/off’ cycles in combination with other nebT or in monotherapy (BC, n=1 (14.3%); LT, n=3 (37.5%)). Bacteria causing chronic infection was P aeruginosa in BC (n=7;100%), and in LT, P aeruginosa (n=6; 75%) and Proteus mirabilis (n=2; 25%). AZLI treatment duration was 20.6±14.2 months (BC) and 10.1±9.7 months (LT). Respiratory function tests during AZLI (mean values of the population) are shown in table 1. Comparing BC with LT, a statistically significant improvement was observed in FVC (p=0.011) and FEF25–75 (p=0.005) but this was not clinically relevant. BC annual emergency admissions were 0.07 before and 0.42 during AZLI; annual rates of hospital admissions were 0.44 and 0.55, respectively. Remission data (negative results in sputum burdens) were: BC (n=2, 28.6%) and LT (n=1, 12.5%). The most commonly reported treatment emergent adverse effects (AE) were dyspnoea, bronchospasm and arthralgias in BC (n=3; 42,9%). There were no AE in LT and no deaths in either group. Conclusion and relevance The results suggest that off-label use of AZLI in complicated chronic infected patients could control gram negative infection and neutralise sputum burdens in some cases, while maintaining lung function and decreasing accelerated clinical deterioration. References and/or acknowledgements No conflict of interest.

Published
2020
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46. 4CPS-119 ‘Real world’ experience of tofacitinib and baricitinib in the treatment of rheumatoid arthritis: effectiveness and safety evaluation

Author

R Caparros Ruiz, M Larrosa García, S Garcia Garcia, C Alonso Martinez, I. Cardona Pascual, C Alerany Pardo, J Vidal Otero, JB Montoro Ronsano, Gomez Domingo, and S Gamarra Calvo

Subjects
medicine.medical_specialty, Tofacitinib, business.industry, Hydroxychloroquine, Retrospective cohort study, medicine.disease, Discontinuation, Clinical trial, Rheumatoid arthritis, Internal medicine, medicine, business, Adverse effect, Leflunomide, medicine.drug
Abstract

Background and importance Tofacitinib and baricitinib are oral Janus kinase inhibitors (JKi) approved for the treatment of rheumatoid arthritis (RA), offering an alternative in patients who have not responded or tolerated previous treatment lines because of adverse effects, complications or other reasons. In pivotal clinical trials, patients had higher DAS28-ESR than our patients and were less pretreated with biologic disease modifying antirheumatic drugs (bDMARDs). Lower effectiveness in real world compared with clinical trials has been reported. We conducted a retrospective study to evaluate effectiveness in our patients. Aim and objectives To assess the effectiveness and safety of JKi in patients with RA in a clinical setting. Material and methods This observational retrospective study included patients with RA in a third level hospital, from 2016 to 2019. Clinical data were collected from the hospital medical records and ‘patient and treatments registry programme’ of our local government: demographic, indications, previous and current treatments, discontinuity of treatment and reasons, effectiveness and safety data. Clinical disease impact, defined by the disease activity score, DAS28-ESR, was evaluated during patient monitoring. Mean (SD) DAS28-ESR at baseline and at follow-up after JKi treatment were analysed. Variance analysis (ANOVA) and the χ2 test were applied (SPSS) to evaluate treatment effect (time=0 vs follow-up data). Results Fifty-three patients were included with a mean age of 63.9±13.3 years and 46 (86.8%) were women. Previous non-bDMARDs treatments were: methotrexate (n=39, 73.6%), leflunomide (n=34, 64.2), hydroxychloroquine (n=15, 28.3%) and sulfasalazine (n=9, 17.0%). Disease activity was categorised as: remission (DAS28-ESR 5.1). At the beginning of the study, one patient had DAS28-ESR Patients were classified by treatment received: tofacitinib group (TofG (n=44, 83.0%)) and baricitinib group (BarG (n=9, 17.0%)). Number of bDMARDs used before JKi: -TofG: 0 (n=7, 15.9%), 0–3 (n=22, 50.0%), >3 (n=15, 34.1%). -BarG: 0 (n=2, 22.2%), 0–3 (n=3, 33.3%), >3 (n=4, 44.4%). At follow-up, mean DAS28-ESR decreased: TofG, 0.64±1.44 (9.3±32.0%) and BarG, 0.98±1.44 (15.6±23.0%). Twelve patients discontinued JKi: baricitinib (n=3, 33.3%) and tofacitinib (n=9, 20.5%). Reasons for discontinuation, baricitinib and tofacitinib, respectively, were due to: -lack of effectiveness (n=2, 22.2%) and (n=5, 9.4%); -lack of adherence (n=1, 11.1%) and (n=2, 3.8%); -adverse effects (n=0, 0%) and (n=1, 1.9% oedema and dyspnoea); and -patient´s choice (n=0, 0%) and (n=1, 1.9%). Conclusion and relevance Our study suggests that JKi could be effective in real world settings after switching from other multiple bDMARDs. The results showed a modest benefit of JKi in complicated and over treated patients with diverse backgrounds, as found in daily practice. References and/or acknowledgements No conflict of interest.

Published
2020
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47. CALCIUM REQUIREMENT AFTER PARATHYROIDECTOMY (PTX) IN SECONDARY HYPERPARATHYROIDISM (2° HPT)

Author

YJ Kwon, BH Kang, SY Bae, JH Seo, JY Kim, EA Lee, JK Wang, YM Lee, KJ Go, HJ Pyo, and JB Lee

Subjects
Internal medicine, RC31-1245, Specialties of internal medicine, RC581-951
Abstract

After PTX in 2°HPT, appropriate calcium and calcitriol was supplied to prevent hungry bone syndrome. Duration of admission was variable according to multiple causes. We hypothesized the admission duration was mainly affected by calcium requirement. The aims of this study were to evaluate PTX in 2°HPT in single center and to make equation for calcium requirement. We evaluated 91 patients with 94 PTX from Nov. 2003 to Dec.2011 in Korea Univ. Guro Hospital. We retrieved demographic details including sex, age, body weight, DM, hypertension, mode of renal replacement therapy, duration of dialysis, duration of admission, mode of PTX, method of anesthetics, number of glands removed, the largest gland length, the heaviest gland, and histologic profile of removed gland. We also gathered preoperative and postoperative (12 hrs and 48 hrs after PTX, discharge, 3 mo, 6 mo, 1 yr after PTX) laboratory data such as calcium, phosphorus, iPTH, ALP, albumin, and Hb. We summated oral and intravenous calcium supplement during hospitalization after PTX. We prescribed oral calcitriol 2.0 μg/day after PTX. Statistical analysis was performed with SPSS ver. 12.0.1. We could find log(calcium total supplement during admission) is correlated with preoperative ALP (p=0.000), preoperative iPTH (p+0.037), and Δ phosphorus 48 hrs after PTX (p=0.000) by multiple linear regression. Log (calcium total supplement during admission) = 2.576 + 0.001 X preoperative ALP + 3.575 X 10-5 X preoperative iPTH + 0.06 X Δphosphorus 48 hrs after PTX. We believe this equation would be helpful to estimate calcium requirements after 48 hrs PTX and to give a clue about length of hospitalization. We also would evaluate whether this equation is predictable in our patients in the future.

Published
2012
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48. A novel predictive approach for GVHD after allogeneic SCT based on clinical variables and cytokine gene polymorphisms

Author

Martínez-Laperche C, Buces E, Aguilera-Morillo MC, Picornell A, González-Rivera M, Lillo R, Santos N, Martín-Antonio B, Guillem V, Nieto JB, González M, de la Cámara R, Brunet S, Jiménez-Velasco A, Espigado I, Vallejo C, Sampol A, Bellón JM, Serrano D, Kwon M, Gayoso J, Balsalobre P, Urbano-Izpizua Á, Solano C, Gallardo D, Díez-Martín JL, Romo J, Buño I, and GVHD/Immunotherapy Committee of the Spanish Group for Hematopoietic Transplantat

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Multivariate analysis, Adolescent, Graft vs Host Disease, Single-nucleotide polymorphism, Disease, 03 medical and health sciences, 0302 clinical medicine, Lasso (statistics), immune system diseases, hemic and lymphatic diseases, Internal medicine, Linear regression, medicine, Humans, Child, Bone Marrow Transplantation, Aged, Retrospective Studies, Transplantation, Polymorphism, Genetic, Framingham Risk Score, Models, Genetic, business.industry, Hematopoietic Stem Cell Transplantation, Infant, Newborn, Infant, Retrospective cohort study, Hematology, Middle Aged, Allografts, Clinical trial, surgical procedures, operative, Child, Preschool, Hematologic Neoplasms, 030220 oncology & carcinogenesis, Commentary, Cytokines, Female, business, Follow-Up Studies, Stem Cell Transplantation, 030215 immunology
Abstract

Despite considerable advances in our understanding of the pathophysiology of graft-versus-host disease (GVHD), its prediction remains unresolved and depends mainly on clinical data. The aim of this study is to build a predictive model based on clinical variables and cytokine gene polymorphism for predicting acute GVHD (aGVHD) and chronic GVHD (cGVHD) from the analysis of a large cohort of HLA-identical sibling donor allogeneic stem cell transplant (allo-SCT) patients. A total of 25 SNPs in 12 cytokine genes were evaluated in 509 patients. Data were analyzed using a linear regression model and the least absolute shrinkage and selection operator (LASSO). The statistical model was constructed by randomly selecting 85% of cases (training set), and the predictive ability was confirmed based on the remaining 15% of cases (test set). Models including clinical and genetic variables (CG-M) predicted severe aGVHD significantly better than models including only clinical variables (C-M) or only genetic variables (G-M). For grades 3-4 aGVHD, the correct classification rates (CCR1) were: 100% for CG-M, 88% for G-M, and 50% for C-M. On the other hand, CG-M and G-M predicted extensive cGVHD better than C-M (CCR1: 80% vs. 66.7%, respectively). A risk score was calculated based on LASSO multivariate analyses. It was able to correctly stratify patients who developed grades 3-4 aGVHD (P < .001) and extensive cGVHD (P < .001). The novel predictive models proposed here improve the prediction of severe GVHD after allo-SCT. This approach could facilitate personalized risk-adapted clinical management of patients undergoing allo-SCT.

Published
2018
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49. Liraglutide and Renal Outcomes in Type 2 Diabetes

Author

Mann JFE, Ørsted DD, Brown-Frandsen K, Marso SP, Poulter NR, Rasmussen S, Tornøe K, Zinman B, Buse JB, LEADER Steering Committee and Investigators. Bergenstal R, Daniels G, Moses AC, Nauck M, Nissen S, Pocock S, Steinberg W, Stockner M, Kristensen P, Ravn LS, Zychma M, Flyvbjerg A, Ford I, Kloos RT, Schactman MJ, Sleight P, Swedberg K, Tenner SM, Akalın S, Arechavaleta R, Bain S, Babkowski MC, Benroubi M, Berard L, Comlekci A, Czupryniak L, Eliasson B, Eriksson M, Fonseca V, Franek E, Gross J, Hafidh K, Haluzik M, Hayes F, Huang YY, Jacob S, Kaddaha G, Khalil A, Kilhovd B, Laakso M, Leiter L, Lalic N, Ji L, Luedemann J, Mannucci E, Marre M, Masmiquel L, Mota M, Omar M, O’Shea D, Pan C, Petrie J, Pieber T, Pratley R, Raz I, Rea R, Rutten G, Satman I, Shestakova M, Simpson R, Smith D, Tack C, Tarnow L, Thomas N, Van Gaal L, Travert F, Vidal J, Warren M, Yoon KH, Tuttle RM, Sheerman SI, Hegedüs L, Baerwald H, Bergenstal M, Celik S, Dias C, Eder M, Fitzgibbons S, Irvhage L, Kloluckova J, Kriulianski R, McDuffie R, Moen S, Paster A, Saalfeld RM, Sankar K, Shehaj E, Swierzewska P, Tiktin M, Tovey S, Gibson CM, Chakrabarti AK, Dashe JF, Hinchey J, Leary MC, Pride Y, Wiviott S, Allen S, Mehr AP, Mutter WP, Parikh S, Ray S, Cheifetz A, Leffler D, Sheth S, Alexander E, Gaglia JL, Goessling W, Mitzner LD, Rosenberg C, Snow KJ, Wagner A, Piazza G, Abell S, Davis T, D'Emden M, Ding SA, Gilfillan C, Greenaway T, Gunawan F, Ho J, Jackson R, Kalra B, Lau SL, Lin J, MacIsaac R, Makepeace A, Malabu U, Marjason J, McCallum R, McLean M, Moin N, Petersons C, Price S, Roberts A, Roberts D, Sangla K, Stranks S, Tan Y, Thynne T, Walters J, Ward G, Wen W, Zhang J, Brix J, Feder A, Höbaus C, Höllerl F, Höller V, Kotter T, Kratz E, Krzizek EC, Leb-Stoeger U, Mader J, Mras N, Novak E, Obendorf F, Peric S, Pesau G, Prager R, Ribitsch A, Schnack C, Schernthaner G, Wascher T, Batens AH, Benhalima K, De Block C, Ernest P, Fouckova A, Jandrain B, Lapauw B, Letiexhe M, Mathieu C, Neven S, Peiffer F, Ruige J, Scheen A, Taes Y, Van Boxelaer I, Vandistel G, Van Durme Y, Verhaegen A, Alencar E, Alencar R, Almeida AC, Alves B, Alves E, Alves G, Alves J, Araujo L, Arruda V, Augusto GA, Baggentoss R, Balestrassi L, Barbosa M, Barcelos I, Belem L, de Bem A, Betti RT, Bona R, Bosco A, Branda J, Bronstein M, Bueno T, Bulcão T, Caiado F, Camazzola F, Cambréa MF, Campos S, Canani L, Carra MK, Caruso S, Carvalho N, Casillo A, Castro D, Cavalcanti T, Cavichioli V, Cercato C, Chacra A, Challela W, Charchar HS, Chaves C, Chrisman C, Correia-Deur J, da Costa A Jr, Costa M, Costi B, Coutinho P, Coutinho W, Cunha MR, Daher J Jr, Davini E, Democh D Jr, Eliaschewitz F, Esmanhoto Facin G, Farias F, Felício J, Fernandes V, Filho CS, Filho FF, Filho M, Fontan D, Fontenele AP, Forti A, Franco D, Freire K, Fusaro A, Genestreti P, Gerchman F, Godi A, Gomes KF, Gonçalves P, Gonçalves R, Griz L, Grossman M, Gurgel MH, Vasconcellos Haddad AW, Halpern A, Hissa M, Inuy A, Jaime J, Jonasson T, Jorge JC, Malucelli FJ, Kohara S, Kramer C, Lacerda C, Ladeira S, Lana J, Lastebasse F, Leitão A, Leite S, Lerário AC, Lima D, Lima M, Lippi V, Lunardi M, Machado E, Maia F, Maia J, Maia KP, Mañas N, Marchisotti F, Marinho C, Martins C, Figueiredo de Medeiros F, Melo A, Melo F, Mendonca E, Mendonça P, Filho RM, Miguel M, Miléo K, Miyahara M, Montenegro AP, Moraes A, Moreira A, Ítalo Mota J, Mothe FS, Murro A, Nakatani V, Napoli TF, Neto BG, Neto OQ, Niclewicz E, Ohe LN, Oliveira F, Oliveira M, Panarotto D, Parente E, Parolin S, Pechmann L, Costa da Penha P, Perlamagna L, Perotta B, Pimentel L, Pinto M, Poço C, Ponte C, Prazeres P, Quintao E, Raduan R, Rassi DT, Rassi N, Reck L, Montenegro R Jr, Ribeiro R, Rodovalho S, Silveira Rodrigues G, Rollin G, Rossi S, Sabino C, Sales AP, Salles J, Sampaio CR, Santana L, Sato V, da Silva Santos M, Santos NL, Santos R, Saraiva J, Sartori C, Sena R, Sevilha M, Sgarbi J, Silva D, D'albuquerque Silva L, Silva ME, Siqueira K, Soares S, Sobreira W, Sousa B, Souza AC, Souza B, Tambascia M, Tarantino R, Tenor F, Tomarchio M, Triches C, Tristão LJ, Valenti A, Vasques E, Vencio S, Vianna A, Munhoz Vidotto T, Vieira S, Villar H, Visconti G, Volaco A, Wajchenberg B, Zanatta L, Zimmerman L, Abbott EC, Abu-Bakare A, Advani A, Allison R, Bishara P, Bowering CK, Cheng A, Chouinard S, Clayton D, Conway J, D'Amours M, de Tugwell B, DeYoung P, D'Ignazio G, Dube F, Ekoe JM, Fagan S, Garceau C, Gottesman I, Hanna A, Harris S, Hramiak IM, Hurd C, Imran S, Josse R, Joyce C, Kaiser S, Khan F, Kirouac I, Kovacs C, Labonte I, Langlois WJ, Levac MF, Liutkus J, McDonald C, Milosevic V, Nyomba BL, Paul T, Raby K, Ransom T, Reichert SM, Retnakaran R, Rabasa-Lhoret R, Raff E, Shaikholeslami R, Sigalas J, Yip CE, Weisnagel SJ, Woo V, Bao Y, Cai X, Chen J, Chen K, Chen M, Chen X, Chen Y, Ji Y, Lei J, Li H, Liu P, Mu Y, Ren M, Ren Y, Shi Y, Wang D, Wang F, Wang J, Wang Y, Yan L, Yang G, Yang J, Yu X, Yuan G, Xu M, Zhao X, Zheng J, Zhou L, Anderlová K, Brožová J, Haluzík M, Hanušová V, Kosák M, Křížová J, Mráz M, Owen K, Rušavý Z, Tomešová J, Trachta P, Žourek M, Andersen PH, Boesgaard T, Christensen S, Gram J, Gregersen S, Henriksen JE, Hermansen K, Jakobsen PE, Jensen J, Krogsaa A, Larsen M, Lervang HH, Madsbad S, Mortensen L, Olesen T, Pietraszek A, Ridderstråle M, Safai N, Schioldan AG, Schmidt C, Snorgaard O, Stidsen J, Cederberg H, Haapamäki H, Hukkanen J, Jauhiainen R, Kujari ML, Lahtela J, Laine M, Mäkelä J, Miilunpohja M, Savolainen M, Taurio J, Vänttinen M, Creton C, Cosma NV, Dillinger J, Jacques JL, Guedj AM, Moulla M, Petit C, Ratsianoharana V, Richter D, Rodier M, Roussel R, Hinz A, Politz E, Esser M, Deuse U, Mittag D, Hagenow A, Jacob F, Jordan R, Gantke D, Venschott-Jordan U, Löhr C, Klausmann G, Eschenbrücher K, Karakas M, Jahrsdörfer B, Kunze MR, Wöhrle J, König W, Spielhagen H, Kilimnik A, Lüdemann HP, Lüdemann J, Mölle A, Mölle M, Müller J, Appelt S, Sauter A, Sauter J, Hartmann U, Löw A, Krötz F, Sohn HY, von Schacky C, Klauss V, Braun D, Segner A, Degtyareva E, Kreutzmann K, Paschmionka R, Hauck N, Sihal O, Busch AK, Maus O, Stübler P, Füllgraf-Horst S, Vietzke A, Müller C, Tosch-Sisting R, Lengsfeld B, Thaler J, Schaum T, Steindorf J, Steindorf S, König A, Reitschuster S, Schlott D, Clever HU, Witzel P, Kempe HP, Stemler L, Benis A, Diakoumopoulou E, Kazakos K, Kypraios N, Liatis S, Pagkalos E, Siami E, Tentolouris N, Alur VC, Agrawal M, Ali M, Asirvatham A, Asirvatham E, Bandgar TR, Balaji M, Bardoloi N, Baruah M, Bekur R, Bhansali A, Bhatia S, Bhonsley S, Bhuyan S, Borah B, Bright N, Ambrish C, Chaudhury T, Choudhury S, Chellan G, Das M, Dharmalingam M, Dutta P, Erugu A, Vinutha FP, Gunasekaran P, Das Gupta R, Iqbal A, Jagadish P, Jain S, Jebasingh H, John A, John M, Kalra S, Kasaragod P, Kesavadev J, Kumar H, Kumar P, Lakshmanan V, Lila AR, Mathew T, Miyen H, Mohan T, Motha A, Murthy C, Shivashankara N, Nanaiah A, Ommen T, Pani K, Pandey K, Paramesh S, Paramesh V, Pillai B, Prabhu M, Kalki RC, Ramachandran S, Ramu M, Rao Y, Reddy S, Saikia P, Saravu K, Selvam K, Sethi B, Shankar A, Sharma A, Shah N, Shankar P, Shetty R, Shivane V, Srivalli S, Thaseen 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Sutton T, Tabbah I, Talsania M, Tang R, Tapia J, Taylor K, Taylor-Hancher R, Teator R, Tekateka M, Temple B, Temple K, Teodori M, Tharp P, Thethi T, Theuma P, Thomas S, Thottan A, Thrasher J, Thrasher L, Tiemeyer M, Tinney I, Tobin T, Toma S, Tovar M, Townsend J, Trantow C, Traylor H, Trevino M, Troy M, Trumper D, Tryggestad J, Tucker C, Turner J, Turney R, Tuten C, Tyzack J, Ullo L, Underkofler C, Unger J, Urdanetta R, Valdivia V, Valenti S, Vanderheiden A, Vanderlinde-Wood M, Varma C, Vasquez E, Vazquez M, Vickery D, Villafuerte B, Villegas C, Vivar J, Vivekananthan K, Vo G, Vukojicic K, Wachter A, Wahl D, Waitmann J, Walker D, Walsh J, Walsh K, Walton A, Wang A, Wardell K, Watkins S, Watkinson J, Watts M, Watwe V, Weaver N, Weber R, Wedick C, Weeks D, Weeks L, Weindorff K, Weinstein R, Weiss S, Wenger K, Wentworth M, Werner A, West M, Whelan S, White B, White J, Whitmire M, Whittington R, Wical J, Wigley C, Wilkins F, Will K, Williams A, Wilson LE, Wince M, Wine S, Winkle P, Winner C, Wise J, Witte M, Wittenmyer J, Wood C, Wood R, Woodruff C, Worthington B, Wynn D, Wysham C, Xavier P, Yela S, Yenoby L, Young L, Younus N, Yourell V, Zaid M, Zubair I., Mann, Jfe, Ørsted, Dd, Brown-Frandsen, K, Marso, Sp, Poulter, Nr, Rasmussen, S, Tornøe, K, Zinman, B, Buse, Jb, Bergenstal R, LEADER Steering Committee and Investigators., Daniels, G, Moses, Ac, Nauck, M, Nissen, S, Pocock, S, Steinberg, W, Stockner, M, Kristensen, P, Ravn, L, Zychma, M, Flyvbjerg, A, Ford, I, Kloos, Rt, Schactman, Mj, Sleight, P, Swedberg, K, Tenner, Sm, Akalın, S, Arechavaleta, R, Bain, S, Babkowski, Mc, Benroubi, M, Berard, L, Comlekci, A, Czupryniak, L, Eliasson, B, Eriksson, M, Fonseca, V, Franek, E, Gross, J, Hafidh, K, Haluzik, M, Hayes, F, Huang, Yy, Jacob, S, Kaddaha, G, Khalil, A, Kilhovd, B, Laakso, M, Leiter, L, Lalic, N, Ji, L, Luedemann, J, Mannucci, E, Marre, M, Masmiquel, L, Mota, M, Omar, M, O’Shea, D, Pan, C, Petrie, J, Pieber, T, Pratley, R, Raz, I, Rea, R, Rutten, G, Satman, I, 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S, Pechmann, L, Costa da Penha, P, Perlamagna, L, Perotta, B, Pimentel, L, Pinto, M, Poço, C, Ponte, C, Prazeres, P, Quintao, E, Raduan, R, Rassi, Dt, Rassi, N, Reck, L, Montenegro, R Jr, Ribeiro, R, Rodovalho, S, Silveira Rodrigues, G, Rollin, G, Rossi, S, Sabino, C, Sales, Ap, Salles, J, Sampaio, Cr, Santana, L, Sato, V, da Silva Santos, M, Santos, Nl, Santos, R, Saraiva, J, Sartori, C, Sena, R, Sevilha, M, Sgarbi, J, Silva, D, D'albuquerque Silva, L, Silva, Me, Siqueira, K, Soares, S, Sobreira, W, Sousa, B, Souza, Ac, Souza, B, Tambascia, M, Tarantino, R, Tenor, F, Tomarchio, M, Triches, C, Tristão, Lj, Valenti, A, Vasques, E, Vencio, S, Vianna, A, Munhoz Vidotto, T, Vieira, S, Villar, H, Visconti, G, Volaco, A, Wajchenberg, B, Zanatta, L, Zimmerman, L, Abbott, Ec, Abu-Bakare, A, Advani, A, Allison, R, Bishara, P, Bowering, Ck, Cheng, A, Chouinard, S, Clayton, D, Conway, J, D'Amours, M, de Tugwell, B, Deyoung, P, D'Ignazio, G, Dube, F, Ekoe, Jm, Fagan, S, Garceau, C, Gottesman, I, 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Subjects
Male, Settore MED/09 - Medicina Interna, Acute Kidney Injury, Aged, Albuminuria, Creatinine, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Double-Blind Method, Female, Follow-Up Studies, Glomerular Filtration Rate, Glucagon-Like Peptide 1, Humans, Hypoglycemic Agents, Intention to Treat Analysis, Kidney Failure, Chronic, Liraglutide, Middle Aged, Type 2 diabetes, 030204 cardiovascular system & hematology, urologic and male genital diseases, GLOMERULAR-FILTRATION-RATE, KIDNEY-FUNCTION, DISEASE, law.invention, Kidney Failure, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Medicine, Settore MED/49 - Scienze Tecniche Dietetiche Applicate, Chronic, RISK, Kidney, Acute kidney injury, 11 Medical And Health Sciences, General Medicine, medicine.anatomical_structure, TRIAL, liraglutide, randomized controlled trial, type 2 diabetes, renal outcomes, Life Sciences & Biomedicine, Type 2, medicine.drug, medicine.medical_specialty, Renal function, 030209 endocrinology & metabolism, CARDIOVASCULAR OUTCOMES, Follow-Up Studie, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, Diabetes mellitus, Internal medicine, Diabetes Mellitus, Intensive care medicine, Science & Technology, business.industry, MORTALITY, medicine.disease, INTENSIVE GLUCOSE CONTROL, INDIVIDUALS, chemistry, Diabetic Nephropathie, LEADER Steering Committee and Investigators, business
Abstract

BACKGROUND: In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown. METHODS: We report the prespecified secondary renal outcomes of that randomized, controlled trial in which patients were assigned to receive liraglutide or placebo. The secondary renal outcome was a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease. The risk of renal outcomes was determined with the use of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rate and albuminuria were also analyzed. RESULTS: A total of 9340 patients underwent randomization, and the median follow-up of the patients was 3.84 years. The renal outcome occurred in fewer participants in the liraglutide group than in the placebo group (268 of 4668 patients vs. 337 of 4672; hazard ratio, 0.78; 95% confidence interval [CI], 0.67 to 0.92; P=0.003). This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P=0.004). The rates of renal adverse events were similar in the liraglutide group and the placebo group (15.1 events and 16.5 events per 1000 patient-years), including the rate of acute kidney injury (7.1 and 6.2 events per 1000 patient-years, respectively). CONCLUSIONS: This prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of diabetic kidney disease than placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .).

Published
2017

50. Effects of Alirocumab on Cardiovascular Events After Coronary Bypass Surgery

Author

Szarek, M, Bhatt, DL, Bittner, VA, Diaz, R, Edelberg, JM, Hanotin, C, Harrington, RA, Jukema, JW, Letierce, A, Moryusef, A, Pordy, R, Lopez, GAR, Roe, MT, White, HD, Zeiher, AM, Steg, PG, Schwartz, GG, Aylward, PE, Drexel, H, Sinnaeve, P, Dilic, M, Goodman, SG, Prieto, JC, Yong, H, Lopez-Jaramillo, P, Pecin, I, Reiner, Z, Ostadal, P, Poulsen, SH, Viigimaa, M, Nieminen, MS, Danchin, N, Chumburidze, V, Tse, HF, Xavier, D, Zahger, D, Valgimigli, M, Kimura, T, Kim, HS, Kim, SH, Erglis, A, Laucevicius, A, Kedev, S, Yusoff, K, Alings, M, Halvorsen, S, Flores, RMC, Sy, RG, Budaj, A, Morais, J, Dorobantu, M, Karpov, Y, Ristic, AD, Chua, T, Murin, J, Fras, Z, Tunon, J, de Silva, HA, Muller, C, Ray, KK, Vogel, R, Chaitman, B, Kelsey, SF, Olsson, AG, Rouleau, JL, Simoons, ML, Alexander, K, Meloni, C, Rosenson, R, Sijbrands, EJG, Alexander, JH, Armaganijan, L, Bagai, A, Bahit, MC, Brennan, JM, Clifton, S, DeVore, AD, Deloatch, S, Dickey, S, Dombrowski, K, Ducrocq, G, Eapen, Z, Endsley, P, Eppinger, A, Hess, CN, Hlatky, MA, Jordan, JD, Knowles, JW, Kolls, BJ, Kong, DF, Leonardi, S, Lillis, L, Maron, DJ, Marcus, J, Mathews, R, Mehta, RH, Mentz, RJ, Moreira, HG, Patel, CB, Pereira, SB, Perkins, L, Povsic, TJ, Puymirat, E, Jones, WS, Shah, BR, Sherwood, MW, Stringfellow, K, Sujjavanich, D, Toma, M, Trotter, C, van Diepen, SFP, Wilson, MD, Yan, ATK, Schiavi, LB, Garrido, M, Alvarisqueta, AF, Sassone, SA, Bordonava, AP, De Lima, AEA, Schmidberg, JM, Duronto, EA, Caruso, OC, Novaretto, LP, Hominal, MA, Montana, OR, Caccavo, A, Vilamajo, OAG, Lorenzatti, AJ, Cartasegna, LR, Paterlini, GA, Mackinnon, IJ, Caime, GD, Amuchastegui, M, Codutti, OR, Jure, HO, Bono, JOE, Hrabar, AD, Vallejos, JA, Rodolfo, AAG, Novoa, F, Patocchi, CA, Zaidman, CJ, Giuliano, ME, Dran, RD, Vico, ML, Carnero, GS, Guzman, PN, Allende, JCM, Brasca, DFG, Labarta, MHB, Nani, S, Blumberg, EDS, Colombo, HR, Liberman, A, Luciardi, HL, Waisman, GD, Berli, MA, Duran, ROG, Cestari, HG, Luquez, HA, Giordano, JA, Saavedra, SS, Waites, JH, Collins, N, Soward, A, Hii, CLS, Shaw, J, Arstall, MA, Horowitz, J, Rogers, JF, Colquhoun, D, Flores, REO, Roberts-Thomson, P, Raffel, O, Lehman, SJ, Coverdale, SGM, Garrahy, PJ, Starmer, G, Sader, M, Carroll, PA, Zweiker, R, Hoppe, U, Huber, K, Berger, R, Weidinger, F, Faes, D, Hermans, K, Pirenne, B, Leone, A, Hoffer, E, Vrolix, MCM, De Wolf, L, Wollaert, B, Castadot, M, Dujardin, K, Beauloye, C, Vervoort, G, Striekwold, H, Convens, C, Roosen, J, Barbato, E, Claeys, M, Cools, F, Terzic, I, Barakovic, F, Midzic, Z, Pojskic, B, Fazlibegovic, E, Durak-Nalbantic, A, Vulic, D, Muslibegovic, A, Reis, G, Sousa, L, Nicolau, JC, Giorgeto, FE, Silva, RP, Maia, LN, Rech, R, Rossi, PRF, Cerqueira, MJAG, Duda, N, Kalil, R, Kormann, A, Abrantes, JAM, Pimentel, P, Soggia, AP, de Santos, MON, Neuenschwander, F, Bodanese, LC, Michalaros, YL, Eliaschewitz, FG, Vidotti, MH, Leaes, PE, Botelho, RV, Kaiser, S, Manenti, ERFF, Precoma, DB, Jorge, JCM, Silva, PGMD, Silveira, JA, Saporito, W, Marin, JA, Feitosa, GS, Ritt, LEF, de Souza, JA, Costa, F, Souza, WKSB, Reis, HJL, Lopes, RD, Machado, L, Ayoub, JCA, Todorov, GV, Nikolov, FP, Velcheva, ES, Tzekova, ML, Benov, HO, Petranov, SL, Tumbev, HS, Shehova-Yankova, NS, Markov, DT, Raev, DH, Mollov, MN, Kichukov, KN, Ilieva-Pandeva, KA, Gotcheva, NN, Ivanova, R, Mincheva, VM, Lazov, PV, Dimov, BI, Senaratne, M, Stone, J, Kornder, J, Pearce, S, Dion, D, Savard, D, Pesant, Y, Pandey, A, Robinson, S, Gosselin, G, Vizel, S, Hoag, G, Bourgeois, R, Morisset, A, Sabbah, E, Sussex, B, Kouz, S, MacDonald, P, Diaz, A, Michaud, N, Fell, D, Leung, R, Vuurmans, T, Lai, C, Nigro, F, Davies, R, Nogareda, G, Vijayaraghavan, R, Ducas, J, Lepage, S, Mehta, S, Cha, J, Dupuis, R, Fong, P, Rodes-Cabau, J, Fadlallah, H, Cleveland, D, Huynh, T, Bata, I, Hameed, A, Pincetti, C, Potthoff, S, Acevedo, M, Aguirre, A, Vejar, M, Yanez, M, Araneda, G, Fernandez, M, Perez, L, Varleta, P, Florenzano, F, Huidobro, L, Raffo, CA, Olivares, C, Chen, JY, Dong, YG, Huang, WJ, Wang, JZ, Huang, SA, Yao, ZH, Cui, L, Lin, WH, Sun, YM, Wang, JF, Li, JP, Zhang, XL, Zhu, H, Chen, DD, Huang, L, Dong, SH, Su, GH, Xu, B, Su, X, Cheng, XS, Lin, JX, Zong, WX, Li, HM, Feng, Y, Xu, DL, Yang, XC, Ke, YN, Lin, XF, Zhang, Z, Zheng, ZQ, Luo, ZR, Chen, YD, Ding, CH, Zheng, Y, Li, XD, Peng, DQ, Li, Y, Wei, M, Liu, SW, Yu, YH, Qu, BM, Jiang, WH, Zhou, YJ, Zhao, XS, Yuan, ZY, Guo, Y, Xu, XP, Shi, XB, Ge, JB, Fu, GS, Bai, F, Fang, WY, Shou, XL, Yang, XJ, Wang, JA, Jaramillo, N, Vallejo, GS, Botia, DCL, Lopez, RB, De Salazar, DIM, Bonfanti, AJC, Higuera, JD, Silva, SIB, Lozada, HJG, Arroyo, JAC, Mendoza, JLA, Ruiz, RLF, Fernandez, AM, Jatin, FGM, Herazo, AS, Parada, JC, Triana, MAU, Spinar, J, Horak, D, Stasek, J, Alan, D, Machova, V, Linhart, A, Novotny, V, Kaucak, V, Rokyta, R, Naplava, R, Coufal, Z, Adamkova, V, Podpera, I, Zizka, J, Motovska, Z, Marusincova, I, Svab, P, Heinc, P, Kuchar, J, Povolny, P, Raungaard, B, Clemmensen, P, Bang, LE, May, O, Bottcher, M, Hove, JD, Frost, L, Gislason, G, Larsen, J, Johansen, PB, Hald, F, Jeppesen, J, Nielsen, T, Kristensen, KS, Walichiewicz, PM, Lomholdt, JD, Klausen, IC, Nielsen, PK, Davidsen, F, Videbaek, L, Soots, M, Vahula, V, Hedman, A, Soopold, U, Martsin, K, Taskinen, MR, Porthan, K, Airaksinen, JK, Juonala, M, Kiviniemi, T, Vikman, S, Posio, P, Taurio, J, Huikuri, H, Kaikkonen, K, Coste, P, Ferrari, E, Morel, O, Montalescot, G, Barone-Rochette, G, Mansourati, J, Cottin, Y, Leclercq, F, Belhassane, A, Delarche, N, Boccara, F, Paganelli, F, Clerc, J, Schiele, F, Aboyans, V, Probst, V, Berland, J, Lefevre, T, Khintibidze, I, Shaburishvili, T, Pagava, Z, Ghlonti, R, Lominadze, Z, Khabeishvili, G, Hemetsberger, R, Rauch-Krohnert, U, Stratmann, M, Appel, KF, Schmidt, E, Omran, H, Stellbrink, C, Dorsel, T, Lianopoulos, E, Marx, R, Zirlik, A, Schellenberg, D, Heitzer, T, Laufs, U, Marx, N, Gielen, S, Winkelmann, B, Behrens, S, Sydow, K, Simonis, G, Muenzel, T, Werner, N, Leggewie, S, Bocker, D, Braun-Dullaeus, R, Toursarkissian, N, Jeserich, M, Weissbrodt, M, Schaeufele, T, Weil, J, Voller, H, Waltenberger, J, Natour, M, Steiner, S, Heidenreich, L, Gremmler, U, Killat, H, Patsilinakos, S, Kartalis, A, Manolis, A, Sionis, D, Liberopoulos, E, Skoumas, I, Athyros, V, Parthenakis, PIF, Hahalis, PIG, Lekakis, J, Xatzitolios, A, Ovando, SRF, Valdovinos, PCM, Benecke, JLA, De Leon, ERR, Yan, BPY, Siu, DCW, Turi, T, Merkely, B, Kiss, RG, Ungi, I, Lupkovics, G, Nagy, L, Katona, A, Edes, I, Muller, G, Horvath, I, Kapin, T, Falukozy, J, Kumbla, M, Sandhu, M, Annam, S, Proddutur, NR, Premchand, RK, Mahajan, A, Abhyanakar, AD, Kerkar, P, Govinda, RA, Oomman, A, Sinha, D, Patil, SN, Kahali, D, Sawhney, J, Joshi, AB, Chaudhary, S, Harkut, P, Guha, S, Porwal, S, Jujjuru, S, Pothineni, RB, Monteiro, MR, Khan, A, Iyengar, SS, Grewal, JS, Chopda, M, Fulwani, MC, Patange, A, Chopra, VK, Goyal, NK, Shinde, R, Manakshe, GV, Patki, N, Sethi, S, Munusamy, V, Karna, S, Adhyapak, S, Pandurangi, U, Mathur, R, Kalashetti, S, Bhagwat, A, Raghuraman, B, Yerra, SK, Bhansali, P, Borse, R, Das, S, Abdullakutty, J, Saathe, S, Palimkar, P, Atar, S, Shechter, M, Mosseri, M, Arbel, Y, Lotan, C, Rosenschein, U, Katz, A, Henkin, Y, Francis, A, Klutstein, M, Nikolsky, E, Turgeman, Y, Halabi, M, Kornowski, R, Jonas, M, Amir, O, Rozenman, Y, Fuchs, S, Hussein, O, Gavish, D, Vered, Z, Caraco, Y, Elias, M, Tov, N, Piovaccari, G, De Pellegrin, A, Guardigli, G, Licciardello, G, Auguadro, C, Cuccia, C, Salvioni, A, Musumeci, G, Calabro, P, Novo, S, Faggiano, P, De Cesare, NB, Berti, S, Cavallini, C, Puccioni, E, Galvani, M, Tespili, M, Piatti, P, Palvarini, M, De Luca, G, Violini, R, De Leo, A, Filardi, PP, Ferratini, M, Dai, K, Kamiya, H, Ando, K, Takeda, Y, Morino, Y, Hata, Y, Kimura, K, Kishi, K, Michishita, I, Uehara, H, Higashikata, T, Hirayama, A, Hirooka, K, Sakagami, S, Taguchi, S, Koike, A, Fujinaga, H, Koba, S, Kozuma, K, Kawasaki, T, Ono, Y, Shimizu, M, Katsuda, Y, Wada, A, Shinke, T, Ako, J, Fujii, K, Takahashi, T, Sakamoto, T, Furukawa, Y, Sugino, H, Mano, T, Utsu, N, Ito, K, Haraguchi, T, Ueda, Y, Nishibe, A, Fujimoto, K, Yoon, JH, Park, HS, Chae, IH, Kim, MH, Jeong, MH, Rha, S, Kim, C, Hong, T, Busmane, A, Pontaga, N, Strelnieks, A, Mintale, I, Sime, I, Petrulioniene, Z, Kavaliauskiene, R, Jurgaitiene, R, Sakalyte, G, Slapikas, R, Norkiene, S, Misonis, N, Kibarskis, A, Kubilius, R, Bojovski, S, Lozance, N, Kjovkaroski, A, Doncovska, S, Ong, TK, Kasim, S, Maskon, O, Kandasamy, B, Liew, HB, Mohamed, WMIW, Castillo, AG, Calvillo, JC, Campos, PF, Fragoso, JCN, Llamas, EAB, Gamba, MAA, Madrigal, JC, Salas, LGG, Rosas, EL, Diaz, BG, Vazquez, ES, Ackar, AN, Esperon, GAL, Sanchez, CRM, De Leon, MG, Otero, RS, Salmon, GF, Rios, JAP, Ruiz, JAG, Breedveld, RW, Hoogslag, PAM, Suryapranata, H, Oomen, A, Wiersma, JJ, Van Der Wal, RMA, Van Huysduynen-Monraats, PSH, Karalis, I, Verdel, GJE, Brueren, BRG, Troquay, RPT, Viergever, EP, Al-Windy, NYY, Bartels, GL, Cornel, JH, Hermans, WRM, Herrman, JPR, Bos, RJ, Groutars, RGEJ, Van Der Zwaan, CC, Kaplan, R, Ronner, E, Groenemeijer, BE, Bronzwaer, PNA, Liem, AAH, Rensing, BJWM, Bokern, MJJA, Nijmeijer, R, Hersbach, FMRJ, Willems, FF, Gosselink, ATM, Elliott, J, Wilkins, G, Fisher, R, Scott, D, Hart, H, Stewart, R, Harding, S, Ternouth, I, Fisher, N, Aitken, D, Anscombe, R, Tomala, T, Nygard, O, Sparby, JA, Andersen, K, Gullestad, L, Jortveit, J, Munk, PS, Hurtig, U, Ticona, JRC, Velasquez, JRD, Miguel, SAN, Perez, ESS, Chambilla, JMC, Ayala, CAC, Leon, RPC, Gonzales, RJV, Zuniga, JDH, Cosavalente, LAC, Mannucci, JEB, Navarro, NCL, Concha, YMR, Chavez, VER, Hernandez, HAA, Nunez, CAZ, Ferrolino, A, Sy, RAG, Tirador, L, Matiga, G, Coching, RM, Bernan, A, Rogelio, G, Morales, DD, Tan, E, Wlodarczak, A, Jaworska, K, Skonieczny, G, Pawlowicz, L, Wojewoda, P, Busz-Papiez, B, Bednarski, J, Goch, A, Staneta, P, Dulak, E, Saminski, K, Krasowski, W, Sudnik, W, Zurakowski, A, Skorski, M, Lysek, R, Miklaszewicz, B, Kubica, J, Lipko, JA, Kostarska-Srokosz, E, Piepiorka, M, Drzewiecka, A, Sciborski, R, Stasiewski, A, Blicharski, T, Bystryk, L, Szpajer, M, Korol, M, Czerski, T, Mirek-Bryniarska, E, Gniot, J, Lubinski, A, Gorny, J, Franek, E, Monteiro, P, Bastos, JM, Pereira, HH, Martins, D, Seixo, F, Mendonca, C, Botelho, A, Minescu, B, Istratoaie, O, Tesloianu, DN, Cristian, G, Podoleanu, CGC, Constantinescu, MCA, Bengus, CM, Militaru, C, Rosu, D, Parepa, IR, Matei, AV, Alexandru, TM, Shvarts, Y, Orlikova, O, Kobalava, Z, Barbarash, OL, Markov, V, Lyamina, N, Gordienko, A, Zrazhevsky, K, Vishnevsky, AY, Gurevich, V, Stryuk, R, Lomakin, NV, Bokarev, I, Shalaev, S, Khaisheva, L, Chizhov, P, Viktorova, I, Osokina, N, Akatova, E, Chumakova, G, Libov, I, Voevoda, MI, Tretyakova, TV, Baranov, E, Shustov, S, Yakushin, S, Gordeev, I, Khasanov, N, Reshetko, O, Sotnikova, T, Molchanova, O, Nikolaev, K, Gapon, L, Baranova, E, Shogenov, Z, Kosmachova, E, Povzun, A, Egorova, L, Tyrenko, VV, Ivanov, IG, Simic, D, Ivanovic, N, Davidovic, G, Tasic, N, Asanin, MR, Stojic, S, Apostolovic, SR, Ilic, S, Putnikovic, B, Stankovic, A, Arandjelovic, A, Radovanovic, S, Balinovac, J, Dincic, DV, Seferovic, P, Dodic, S, Dimkovic, S, Poh, KK, Ong, HY, Micko, K, Nociar, J, Pella, D, Fulop, P, Hranai, M, Palka, J, Mazur, J, Majercak, I, Dzupina, A, Fazekas, F, Gonsorcik, J, Bugan, V, Selecky, J, Kamensky, G, Strbova, J, Smik, R, Dukat, A, Zuran, I, Oklukar, J, Suligoj, NC, Cevc, M, Lipar, L, Cyster, HP, Ranjith, N, Corbett, C, Bayat, J, Makotoko, EM, Kapp, IE, Basson, MMD, Lottering, H, Van Zyl, LJ, Sebastian, PJ, Pillay, T, Saaiman, JA, Commerford, PJ, Cassimjee, S, Ebrahim, IO, Sarvan, M, Mynhardt, JH, Dalby, AJ, Reuter, H, Moodley, R, Vida, M, Fillat, ARC, Peris, VB, Jimenez, FF, Marin, F, Fernandez, JMC, Gil-Extremera, B, Diz, FW, Garcia-Dorado, D, Iniguez, A, Fernandez, JT, Gonzalez-Juanatey, JR, Portales, JF, Murillo, FC, Pericas, LM, Zamorano, JL, Martin, MD, Cortada, JB, Martin, JJA, Fernandez, JRD, Fernandez, JFD, Lledo, JAG, Sales, JC, Rodriguez, JB, Tragant, GG, Benedicto, A, Gonzalez-Juanatey, C, Potau, MC, Perez, IP, De La Tassa, CM, Rincon, PLO, Recena, JB, Escudier, JM, Constantine, G, Haniffa, R, Tissera, N, Amarasekera, S, Fernando, N, Jayawardena, J, Santharaj, W, Ekanayaka, R, Mendis, S, Senaratne, V, Mayurathan, G, Sirisena, T, Rajapaksha, A, Herath, JI, Amarasena, N, Berglund, S, Rasmanis, G, Hagstrom, E, Witt, N, Mourtzinis, G, Nicol, P, Hansen, O, Romeo, S, Torstensson, I, Jensen, SA, Ahremark, U, Sundelin, T, Moccetti, T, Mach, F, Binder, R, Chiang, CE, Tsai, WC, Ueng, KC, Lai, WT, Liu, ME, Hwang, JJ, Yin, WH, Hsieh, IC, Kuo, JY, Huang, TY, Fang, CY, Kaewsuwanna, P, Soonfuang, W, Jintapakorn, W, Sukonthasarn, A, Sritara, P, Wongpraparut, N, Sastravaha, K, Sansanayudh, N, Kehasukcharoen, W, Piyayotai, D, Camsari, A, Kultursay, H, Guneri, S, Mutlu, B, Ersanli, M, Demirtas, M, Kirma, C, Ural, E, Koldas, L, Karpenko, O, Prokhorov, A, Vakaluyk, I, Myshanych, H, Reshotko, D, Batushkin, V, Rudenko, L, Kovalskyi, I, Kushnir, M, Tseluyko, V, Mostovoy, Y, Stanislavchuk, M, Kyiak, Y, Karpenko, Y, Malynovsky, Y, Klantsa, A, Kutniy, O, Amosova, E, Tashchuk, V, Leshchuk, O, Parkhomenko, A, Rishko, M, Kopytsya, M, Yagensky, A, Vatutin, M, Bagriy, A, Barna, OM, Ushakov, O, Dzyak, G, Goloborodko, B, Rudenko, A, Trevelyan, J, Zaman, A, Lee, K, Moriarty, A, Aggarwal, RK, Clifford, P, Wong, YK, Iqbal, SMR, Subkovas, E, Braganza, D, Sarkar, D, Storey, R, Griffiths, H, Mcclure, S, Muthusamy, R, Kurian, J, Levy, T, Barr, C, Kadr, H, Gerber, R, Simaitis, A, Soran, H, Mathur, A, Brodison, A, Oliver, R, Mudawi, T, Reynolds, T, Sharman, D, Butler, R, Wilkinson, P, Lip, GYH, Halcox, J, Vardi, G, Baldari, D, Brabham, D, Treasure, C, Dahl, C, Palmer, B, Wiseman, A, Puri, S, Mohart, AE, Ince, C, Flores, E, Wright, S, Cheng, SC, Rosenberg, M, Rogers, W, Kosinski, E, Forgosh, L, Waltman, J, Khan, M, Shoukfeh, M, Dagher, G, Lieber, I, Kumar, P, East, C, Krichmar, P, White, L, Knickelbine, T, Haldis, T, Gillespie, E, Suh, D, Arif, I, Akhter, F, Carlson, E, D'Urso, M, El-Ahdab, F, Nelson, W, Harris, B, Cohen, S, Carter, L, Sabatino, K, Haddad, T, Malik, A, Rao, S, Mulkay, A, Jovin, I, Klancke, K, Malhotra, V, Devarapalli, SK, Koren, M, Chandna, H, Dodds, G, Janik, M, Moran, J, Sumner, A, Kobayashi, J, Davis, W, Yazdani, S, Pasquini, J, Thakkar, M, Vedere, A, Leimbach, W, Rider, J, Singh, N, Shah, AV, Moriarty, PM, Janosik, D, Pepine, C, Berman, B, Gelormini, J, Daniels, C, Keating, F, Kondo, NI, Shetty, S, Waider, W, Takata, T, Abu-Fadel, M, Shah, V, Aggarwal, R, Izzo, M, Kumar, A, Hattler, B, Link, C, Bortnick, A, Kinzfogl, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, WW, Thew, S, Abbas, J, White, M, Ranadive, N, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, MM, Schmalfuss, C, Picone, M, Herzog, W, Lindsey, J, Nowins, R, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, May, W, Galski, T, Chu, A, Mody, F, Hodes, Z, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, King, M, Carey, C, Gerber, J, Younis, L, Park, H, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Kimmelstiel, C, Silver, K, Foster, M, Tonnessen, G, Amlani, M, Wali, A, Malozzi, C, Wattanakit, K, O'Donnell, PJ, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Akyea-Djamson, A, Labroo, A, Marais, HJ, Claxton, E, Berk, M, Rossi, P, Joshi, P, Khaira, AS, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Farrar, M, Pollock, S, French, WJ, Diamantis, S, Gimple, L, Schwartz, S, Pereira, E, Spriggs, D, Strain, J, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, FM, Nahhas, A, Pope, T, Nager, P, Vohra, R, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, PS, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Gilbert, JM, Chalavarya, G, Eaton, C, Schmedtje, JF, Christenson, S, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Akright, L, Schifferdecker, B, Krawczyk, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, İÜC, and Ege Üniversitesi

Subjects
Male, medicine.medical_specialty, Acute coronary syndrome, alirocumab, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, lipids, PCSK9, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Double-Blind Method, coronary artery bypass graft, Internal medicine, medicine, Humans, Cardiac and Cardiovascular Systems, 030212 general & internal medicine, Myocardial infarction, cardiovascular diseases, Acute Coronary Syndrome, Coronary Artery Bypass, Alirocumab, Aged, Kardiologi, business.industry, Unstable angina, Hazard ratio, cholesterol, Middle Aged, medicine.disease, surgical procedures, operative, Bypass surgery, Cardiovascular Diseases, Cardiology, Drug Therapy, Combination, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business, Mace
Abstract

Sherwood, Matthew/0000-0002-4305-5883; Taskinen, Marja-Riitta/0000-0002-6229-3588; Leonardi, Sergio/0000-0002-4800-6132; Raffel, Owen C/0000-0001-5470-7050; Muenzel, Thomas/0000-0001-5503-4150; Ersanli, Murat/0000-0003-1847-3087; Gislason, Gunnar H/0000-0002-0548-402X; bastos, jose/0000-0002-9526-3123; Abbate, Antonio/0000-0002-1930-785X; Chumakova, Galina A/0000-0002-2810-6531; Nikolaev, Konstantin/0000-0003-4601-6203; Tse, Hung Fat/0000-0002-9578-7808; Keskin, Kudret/0000-0002-9049-1530; Reshetko, Olga/0000-0003-3107-7636; Podoleanu, Cristian/0000-0001-9987-2519; Aylward, Philip/0000-0002-5358-8552; LETIERCE, Alexia/0000-0001-6679-5772, WOS: 000483334800002, PubMed: 31466614, BACKGROUND Patients with acute coronary syndrome (ACS) and history of coronary artery bypass grafting (CABG) are at high risk for recurrent cardiovascular events and death. OBJECTIVES This study sought to determine the clinical benefit of adding alirocumab to statins in ACS patients with prior CABG in a pre-specified analysis of ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab). METHODS Patients (n = 18,924) 1 to 12 months post-ACS with elevated atherogenic lipoprotein levels despite high-intensity statin therapy were randomized to alirocumab or placebo subcutaneously every 2 weeks. Median follow-up was 2.8 years. the primary composite endpoint of major adverse cardiovascular events (MACE) comprised coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Patients were categorized by CABG status: no CABG (n = 16,896); index CABG after qualifying ACS, but before randomization (n = 1,025); or CABG before the qualifying ACS (n = 1,003). RESULTS in each CABG category, hazard ratios (95% confidence intervals) for MACE (no CABG 0.86 [0.78 to 0.95], index CABG 0.85 [0.54 to 1.35], prior CABG 0.77 [0.61 to 0.98]) and death (0.88 [ 0.75 to 1.03], 0.85 [0.46 to 1.59], 0.67 [0.44 to 1.01], respectively) were consistent with the overall trial results (0.85 [ 0.78 to 0.93] and 0.85 [0.73 to 0.98], respectively). Absolute risk reductions (95% confidence intervals) differed across CABG categories for MACE (no CABG 1.3% [0.5% to 2.2%], index CABG 0.9% [-2.3% to 4.0%], prior CABG 6.4% [0.9% to 12.0%]) and for death (0.4% [-0.1% to 1.0%], 0.5% [-1.9% to 2.9%], and 3.6% [0.0% to 7.2%]). CONCLUSIONS Among patients with recent ACS and elevated atherogenic lipoproteins despite intensive statin therapy, alirocumab was associated with large absolute reductions in MACE and death in those with CABG preceding the ACS event. (ODYSSEY OUTCOMES: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402) (C) 2019 by the American College of Cardiology Foundation., Fondation Assistance Publique-Hopitaux de Paris, Paris, France, The authors thank the patients, study coordinators, and investigators who participated in this trial. Sophie Rushton-Smith, PhD (MedLink Healthcare Communications, London) provided editorial assistance in the preparation of the manuscript (limited to editing for style, referencing, and figure and table editing) and was funded by Fondation Assistance Publique-Hopitaux de Paris, Paris, France.

Published
2019
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