The complex phenotype of Diabetic Cardiomyopathy: clinical indicators and novel treatment targets

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Publisher : Frontiers Media SA
ISBN 13 : 283255542X
Total Pages : 106 pages
Book Rating : 4.8/5 (325 download)

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Book Synopsis The complex phenotype of Diabetic Cardiomyopathy: clinical indicators and novel treatment targets by : Ramoji Kosuru

Download or read book The complex phenotype of Diabetic Cardiomyopathy: clinical indicators and novel treatment targets written by Ramoji Kosuru and published by Frontiers Media SA. This book was released on 2024-10-09 with total page 106 pages. Available in PDF, EPUB and Kindle. Book excerpt: Diabetic cardiomyopathy is a clinical condition of heart dysfunction that develops in the absence of hypertension and coronary atherosclerosis in diabetic patients. The main characteristics of diabetic cardiomyopathy are myocardial fibrosis, cardiac stiffness, left ventricular hypertrophy and decreased left ventricular compliance. This eventually progresses to clinical heart failure with reduced ejection fraction. To detect changes in cardiac structure and function, such as fibrosis, several noninvasive techniques have been used. These include echocardiography, cinematic magnetic resonance imaging, and computed tomography. From a mechanistic perspective; oxidative stress, inflammation, enhanced production and deposition of advanced glycation end products (AGEs), mitochondrial dysfunction, impaired mitochondrial Ca2+ handling and function, and endoplasmic reticulum stress are observed. Furthermore activation of the sympathetic nervous system and renin-angiotensin system, microvascular dysfunction, and cardiac metabolic disorders are involved in the pathophysiology of this condition. Numerous proteins and signaling pathways, such as AMPK, FOXO1, SERCA2A, NF-kB, Nrf2, HO-1, MAPK, PKC, and PPARs, may be implicated in the development of diabetic cardiomyopathy. Additionally, increased levels of O-linked N-acetylglucosamine (O-GlcNAc), C-reactive protein, atrial natriuretic peptide, and, brain natriuretic peptide, among others, may also serve as clinical biomarkers to identify diabetic cardiomyopathy. Lifestyle modifications including aerobic exercise, maintaining a healthy weight, and smoking cessation are beneficial treatment measures to avoid diabetic cardiomyopathy. It is significant to note that in people with diabetes mellitus; high blood glucose and systemic and cardiac insulin resistance, are independently correlated to the development and progression of cardiac dysfunction and heart failure. The prevalence of diabetic cardiomyopathy declines with sustained glycemic management. However, a formal definition for diabetic cardiomyopathy as a distinct clinical entity remains poorly defined due to a lack of accepted diagnostic criteria and knowledge of subclinical cardiovascular diseases at the early stages of diabetes mellitus. There is currently no distinct histological features, biochemical markers, or clinical manifestation that can be used to make a definitive diagnosis of diabetic cardiomyopathy. Additionally, there are no prospective clinical trials to back up the claim that high insulin or blood sugar levels alone, without additional risk factors like obesity, coronary heart disease, or high blood pressure, increase the likelihood of developing diabetic cardiomyopathy. To decipher the precise mechanisms behind the onset and progression of diabetic cardiomyopathy, and to develop novel strategies for reducing the risk of heart failure in people with diabetes, further research is necessary. Hence, more clinical observational studies are required to comprehend the unknown factors underlying diabetic cardiomyopathy, and to further investigate novel biomarkers that can be used for risk assessment, screening, and diagnosis. Early detection and early intervention are essential for preventing diabetic cardiomyopathy, which drives ongoing research to better understand and treat this condition.

Diagnosis and Management of Hypertrophic Cardiomyopathy

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Publisher : John Wiley & Sons
ISBN 13 : 140514615X
Total Pages : 527 pages
Book Rating : 4.4/5 (51 download)

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Book Synopsis Diagnosis and Management of Hypertrophic Cardiomyopathy by : Barry J. Maron

Download or read book Diagnosis and Management of Hypertrophic Cardiomyopathy written by Barry J. Maron and published by John Wiley & Sons. This book was released on 2008-04-15 with total page 527 pages. Available in PDF, EPUB and Kindle. Book excerpt: Diagnosis and Management of Hypertrophic Cardiomyopathy is aunique, multi-authored compendium of information regarding thecomplexities of clinical and genetic diagnosis, natural history,and management of hypertrophic cardiomyopathy (HCM)—the mostcommon and important of the genetic cardiovasculardiseases—as well as related issues impacting the health oftrained athletes. Edited by Dr. Barry J. Maron, a world authority on HCM, and withmajor contributions from all of the international experts in thisfield, this book provides a single comprehensive source ofinformation concerning HCM. Recent advances in the field arediscussed, including the importance of left ventricular outflowtract obstruction, the use of implantable defibrillators for theprevention of sudden death in young people, definition of thegenetic basis for HCM and its role in clinical diagnosis and riskstratification, the development of more precise strategies forassessing the level of risk for sudden death among all patientswith HCM, and the evolution of invasive interventions for heartfailure symptoms, such as surgical management and its alternatives(alcohol septal ablation and dual-chamber pacing). Key Features: Contributions from all experts in the field,representing diverse viewpoints regarding this heterogeneousdisease and related issues in athletes Information to dispel misunderstandings regarding issuesassociated with HCM and cardiovascular disease in athletes The only comprehensive source of information available on thetopic

The Breathless Heart

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Publisher : Springer
ISBN 13 : 3319263544
Total Pages : 288 pages
Book Rating : 4.3/5 (192 download)

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Book Synopsis The Breathless Heart by : Michele Emdin

Download or read book The Breathless Heart written by Michele Emdin and published by Springer. This book was released on 2016-11-25 with total page 288 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book systematically focuses on central sleep apneas, analyzing their relationship especially with heart failure and discussing recent research results and emerging treatment strategies based on feedback modulation. The opening chapters present historical background information on Cheyne-Stokes respiration (CSR), clarify terminology, and explain the mechanics and chemistry of respiration. Following a description of the physiology of respiration, the pathophysiology underlying central apneas in different disorders and particularly in heart failure is discussed. The similarities and differences of obstructive and central apneas are then considered. The book looks beyond the concept of sleep apnea to daytime CSR and periodic breathing during effort and contrasts the opposing views of CSR as a compensatory phenomenon or as detrimental to the failing heart. The diagnostic tools currently in use for the detection of CSR are thoroughly reviewed, with guidance on interpretation of findings. The book concludes by describing the various forms of treatment that are available for CSR and by explaining how to select patients for treatment.

Acute Heart Failure

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Publisher : Springer Science & Business Media
ISBN 13 : 1846287820
Total Pages : 922 pages
Book Rating : 4.8/5 (462 download)

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Book Synopsis Acute Heart Failure by : Alexandre Mebazaa

Download or read book Acute Heart Failure written by Alexandre Mebazaa and published by Springer Science & Business Media. This book was released on 2009-12-24 with total page 922 pages. Available in PDF, EPUB and Kindle. Book excerpt: For many years, there has been a great deal of work done on chronic congestive heart failure while acute heart failure has been considered a difficult to handle and hopeless syndrome. However, in recent years acute heart failure has become a growing area of study and this is the first book to cover extensively the diagnosis and management of this complex condition. The book reflects the considerable amounts of new data reported and many new concepts which have been proposed in the last 3-4 years looking at the epidemiology, diagnostic and treatment of acute heart failure.

Management of Genetic Syndromes

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Publisher : John Wiley & Sons
ISBN 13 : 1118210670
Total Pages : 1678 pages
Book Rating : 4.1/5 (182 download)

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Book Synopsis Management of Genetic Syndromes by : Suzanne B. Cassidy

Download or read book Management of Genetic Syndromes written by Suzanne B. Cassidy and published by John Wiley & Sons. This book was released on 2011-09-20 with total page 1678 pages. Available in PDF, EPUB and Kindle. Book excerpt: The bestselling guide to the medical management of common genetic syndromes —now fully revised and expanded A review in the American Journal of Medical Genetics heralded the first edition of Management of Genetic Syndromes as an "unparalleled collection of knowledge." Since publication of the first edition, improvements in the molecular diagnostic testing of genetic conditions have greatly facilitated the identification of affected individuals. This thorough revision of the critically acclaimed bestseller offers original insights into the medical management of sixty common genetic syndromes seen in children and adults, and incorporates new research findings and the latest advances in diagnosis and treatment of these disorders. Expanded to cover five new syndromes, this comprehensive new edition also features updates of chapters from the previous editions. Each chapter is written by an expert with extensive direct professional experience with that disorder and incorporates thoroughly updated material on new genetic findings, consensus diagnostic criteria, and management strategies. Edited by two of the field's most highly esteemed experts, this landmark volume provides: A precise reference of the physical manifestations of common genetic syndromes, clearly written for professionals and families Extensive updates, particularly in sections on diagnostic criteria and diagnostic testing, pathogenesis, and management A tried-and-tested, user-friendly format, with each chapter including information on incidence, etiology and pathogenesis, diagnostic criteria and testing, and differential diagnosis Up-to-date and well-written summaries of the manifestations followed by comprehensive management guidelines, with specific advice on evaluation and treatment for each system affected, including references to original studies and reviews A list of family support organizations and resources for professionals and families Management of Genetic Syndromes, Third Edition is a premier source to guide family physicians, pediatricians, internists, medical geneticists, and genetic counselors in the clinical evaluation and treatment of syndromes. It is also the reference of choice for ancillary health professionals, educators, and families of affected individuals looking to understand appropriate guidelines for the management of these disorders. From a review of the first edition: "An unparalleled collection of knowledge . . . unique, offering a gold mine of information." —American Journal of Medical Genetics

Adrenal Disorders

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Publisher : Springer Science & Business Media
ISBN 13 : 1592591019
Total Pages : 420 pages
Book Rating : 4.5/5 (925 download)

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Book Synopsis Adrenal Disorders by : Andrew N. Margioris

Download or read book Adrenal Disorders written by Andrew N. Margioris and published by Springer Science & Business Media. This book was released on 2001-04-20 with total page 420 pages. Available in PDF, EPUB and Kindle. Book excerpt: In Adrenal Disorders, a panel of distinguished physicians and researchers select the most relevant new findings and integrate them into the existing body of clinical knowledge on adrenal pathologies. The book includes important reviews of disturbances in cortisol homeostasis, and new concepts regarding adrenal tumors and hereditary adrenal diseases. Also discussed are mineralocorticoids and the syndromes of mineralocortoid excess and aldosterone synthase deficiency. Authoritative and insightful, Adrenal Disorders provides physicians and scientists with a comprehensive, state-of-the-art practical guide to the devastating diseases of the adrenals that are so often difficult to diagnose and treat.

The Chromosome 22q11.2 Deletion Syndrome

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Publisher : Academic Press
ISBN 13 : 0128160489
Total Pages : 526 pages
Book Rating : 4.1/5 (281 download)

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Book Synopsis The Chromosome 22q11.2 Deletion Syndrome by : Donna M. McDonald-McGinn

Download or read book The Chromosome 22q11.2 Deletion Syndrome written by Donna M. McDonald-McGinn and published by Academic Press. This book was released on 2022-08-19 with total page 526 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Chromosome 22q11.2 Deletion Syndrome: A Multidisciplinary Approach to Diagnosis and Treatment serves as the first comprehensive, user-friendly resource on the etiology, prognosis, and recurrence risk associated with the chromosome 22q11.2 deletion syndrome. Leading international contributors cover the background, genetics, testing methods, and pathophysiology of 22q11.2DS, placing emphasis on a strong foundation for multidisciplinary treatment strategies. Written by specialists in every applicable subspecialty, such as, cardiology, immunology, endocrinology, gastroenterology, hematology, ophthalmology, neurology, and psychiatry, among other fields. This book presents an authoritative resource with full color images that enhance concept illustration and aid in real-time decision-making. As 22q11.2 deletion syndrome has become a model for understanding rare and frequent anomalies, numerous medical issues, cognitive and behavioral phenotypes, and later onset conditions, this text will become the go to resource for clinicians, researchers, trainees, and motivated family members, in gaining a full understanding of this complex chromosomal disorder. - Provides a complete description of 22q11.2 deletion syndrome for healthcare professionals, researchers, trainees, and families affected by this common condition - Presents diagnostic and treatment strategies to help tackle this complex and often undiagnosed and therefore undertreated condition - Covered in a user-friendly, practical format that emphasizes evidence-based evaluation and treatment derived from the latest clinical experience and research in the field - Features leading international contributors in numerous sub-specialties, representing the multisystem nature of this condition - Includes full color figures, flow charts, tables, and patient images to guide real-time decision-making

Prevention and Treatment of Atherosclerosis

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Author :
Publisher : Springer Nature
ISBN 13 : 3030860760
Total Pages : 537 pages
Book Rating : 4.0/5 (38 download)

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Book Synopsis Prevention and Treatment of Atherosclerosis by : Arnold von Eckardstein

Download or read book Prevention and Treatment of Atherosclerosis written by Arnold von Eckardstein and published by Springer Nature. This book was released on 2022 with total page 537 pages. Available in PDF, EPUB and Kindle. Book excerpt: This open access book is supported by the European Atherosclerosis Society Association (EAS). This follow-up edition of the well-received Handbook volume 'Atherosclerosis: Diet and Drugs' reflects the state-of-the-art and most recent developments in atherosclerosis research. Outstanding international experts give a comprehensive overview of the field covering topics, such as improving the treatment focusing on established targets, novel drug developments addressing pre-defined targets, hypothesis-based and hypothesis-free approaches to unravel novel targets.

Novel Perspectives For The Therapy And Prevention Of Heart Failure

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Publisher : Frontiers Media SA
ISBN 13 : 288976849X
Total Pages : 231 pages
Book Rating : 4.8/5 (897 download)

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Book Synopsis Novel Perspectives For The Therapy And Prevention Of Heart Failure by : Eliot Ohlstein

Download or read book Novel Perspectives For The Therapy And Prevention Of Heart Failure written by Eliot Ohlstein and published by Frontiers Media SA. This book was released on 2022-08-26 with total page 231 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Cardiomyopathy

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Publisher :
ISBN 13 : 9781789852240
Total Pages : 0 pages
Book Rating : 4.8/5 (522 download)

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Book Synopsis Cardiomyopathy by : Gustav Mattsson

Download or read book Cardiomyopathy written by Gustav Mattsson and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cardiomyopathies are diseases of the heart muscle with diverse etiologies ranging from myocarditis to gene mutations. They are classified according to morphology and function, and then further categorized based on whether they are familial or non-familial and based on specific etiologies. This book examines the various cardiomyopathies, including arrhythmogenic cardiomyopathy, hypertrophic cardiomyopathy, and dilated cardiomyopathy, as well as their genetic basis.

A Practical Guide to Diabetes Mellitus

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Publisher : JAYPEE BROTHERS PUBLISHERS
ISBN 13 : 9350905973
Total Pages : 467 pages
Book Rating : 4.3/5 (59 download)

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Book Synopsis A Practical Guide to Diabetes Mellitus by : Nihal Thomas

Download or read book A Practical Guide to Diabetes Mellitus written by Nihal Thomas and published by JAYPEE BROTHERS PUBLISHERS. This book was released on 2012-12-15 with total page 467 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Sixth Edition of A Practical Guide to Diabetes Mellitus offers a unique combination of rigorous pathophysiology with very practical approaches to diabetes prevention and control. This outstanding textbook will equip a cadre of doctors and other health care professionals to deliver high quality care to vulnerable populations around India and far beyond. Based on research as well as clinical practice, the text describes diabetes in relation to physiology, ocular, cardiovascular, neuropathy, pregnancy, emergencies, childhood diabetes, etc. Each chapter beings with a brief outline of the disease concerned followed by introduction, definition/terminology, classification, treatment, conclusion and ending with set of question for self-assessment. Covers step wise images describes insulin administration in subcutaneous and using pen devices in the chapter: Insulin therapy: practical aspects. Feet, Footcare and Neuroarthropathy chapter deals with etiology and pathophysiology and is divided into three parts: Ulceration, Neuroarthropathy and Peripheral Artery Occlusive(PAD) diseases. Infection in diabetes chapter focuses on infection related to head and neck, genitourinary, skin and soft tissue, pulmonology and abdominal. Recent advances includes application of new drugs like Taspoglutide, Albiglutide, Lixisenatide, Newer DPP-IV inhibitors, along with new insulin receptor activators, PPAR agonists, new hepatic targets for glycemic control in diabetes. This book contains more than 300 coloured images and illustrations, 40 clinical cases, 50 questions for quick revision along with answers to the self-assessments question given at the end of book."

Advances of Endocrine and Metabolic Cardiovascular Outcomes: From Basic to Clinical Science

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Publisher : Frontiers Media SA
ISBN 13 : 2832506569
Total Pages : 149 pages
Book Rating : 4.8/5 (325 download)

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Book Synopsis Advances of Endocrine and Metabolic Cardiovascular Outcomes: From Basic to Clinical Science by : Si Jin

Download or read book Advances of Endocrine and Metabolic Cardiovascular Outcomes: From Basic to Clinical Science written by Si Jin and published by Frontiers Media SA. This book was released on 2023-03-02 with total page 149 pages. Available in PDF, EPUB and Kindle. Book excerpt: Renin-angiotensin-aldosterone system (RAAS) dependent hypertension, diabetes featured by hyperglycemia, hyperlipidemia, hyperuricemia, hyperhomocysteinemia, overweight or obesity etc., represent the major types of endocrine and metabolic disorders which contribute most to the development of atherosclerosis-based cardiovascular diseases. In clinical studies, these diseases comprise nonfatal myocardial infarction, nonfatal cerebral infarction, or even cardiovascular death, termed 3 major adverse cardiovascular events (3p MACE). On one side, these endocrine or metabolic dysfunctions are the upstream risk factors of cardiovascular diseases. Meanwhile, more and more antidiabetic drugs, e.g., glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose transporter-2 inhibitors (SGLT2i) etc., are reported to have not only blood glucose lowering effects, but also have direct cardiovascular protective effects independent of the glucose lowering effects. Regarding the close relationship between endocrine or metabolic disorders and downstream cardiovascular outcomes, a call for a new subspeciality in internal medicine, cardiometabolic medicine, was proposed in Am J Med, 2019. Recently, many basic or clinical studies focused on endocrine and metabolic cardiovascular outcomes. The goal of this Research Topic is to compile recent advances concentrating in this area, both in terms of basic and clinical aspects, to further value the cardiovascular outcomes in treating endocrine and metabolic diseases.

Genomic Applications in Pathology

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Publisher : Springer
ISBN 13 : 3319968300
Total Pages : 631 pages
Book Rating : 4.3/5 (199 download)

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Book Synopsis Genomic Applications in Pathology by : George Jabboure Netto

Download or read book Genomic Applications in Pathology written by George Jabboure Netto and published by Springer. This book was released on 2018-12-10 with total page 631 pages. Available in PDF, EPUB and Kindle. Book excerpt: ​The recent advances in genomics are continuing to reshape our approach to diagnostics, prognostics and therapeutics in oncologic and other disorders. A paradigm shift in pharmacogenomics and in the diagnosis of genetic inherited diseases and infectious diseases is unfolding as the result of implementation of next generation genomic technologies. With rapidly growing knowledge and applications driving this revolution, along with significant technologic and cost changes, genomic approaches are becoming the primary methods in many laboratories and for many diseases. As a result, a plethora of clinical genomic applications have been implemented in diagnostic pathology laboratories, and the applications and demands continue to evolve rapidly. This has created a tremendous need for a comprehensive resource on genomic applications in clinical and anatomic pathology. We believe that our current textbook provides such a resource to practicing molecular pathologists, hematopathologists and other subspecialized pathologists, general pathologists, pathology and other trainees, oncologists, geneticists and a growing spectrum of other clinicians. With periodic updates and a sufficiently rapid time from submission to publication, this textbook will be the resource of choice for many professionals and teaching programs. Its focus on genomics parallels the evolution of these technologies as primary methods in the clinical lab. The rapid evolution of genomics and its applications in medicine necessitates the (frequent) updating of this publication. This text will provide a state-of-the art review of the scientific principles underlying next generation genomic technologies and the required bioinformatics approaches to analyses of the daunting amount of data generated by current and emerging genomic technologies. Implementation roadmaps for various clinical assays such as single gene, gene panels, whole exome and whole genome assays will be discussed together with issues related to reporting and the pathologist’s role in interpretation and clinical integration of genomic tests results. Genomic applications for site-specific solid tumors and hematologic neoplasms will be detailed. Genomic applications in pharmacogenomics, inherited genetic diseases and infectious diseases will also be discussed. The latest iteration of practice recommendations or guidelines in genomic testing put forth by stakeholder professional organizations such as the College of American Pathology and the Association for Molecular Pathology, will be discussed as well as regulatory issues and laboratory accreditation related to genomic testing. All chapters will be written by experts in their fields and will include the most up to date scientific and clinical information.

Registries for Evaluating Patient Outcomes

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Publisher : Government Printing Office
ISBN 13 : 1587634333
Total Pages : 385 pages
Book Rating : 4.5/5 (876 download)

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Book Synopsis Registries for Evaluating Patient Outcomes by : Agency for Healthcare Research and Quality/AHRQ

Download or read book Registries for Evaluating Patient Outcomes written by Agency for Healthcare Research and Quality/AHRQ and published by Government Printing Office. This book was released on 2014-04-01 with total page 385 pages. Available in PDF, EPUB and Kindle. Book excerpt: This User’s Guide is intended to support the design, implementation, analysis, interpretation, and quality evaluation of registries created to increase understanding of patient outcomes. For the purposes of this guide, a patient registry is an organized system that uses observational study methods to collect uniform data (clinical and other) to evaluate specified outcomes for a population defined by a particular disease, condition, or exposure, and that serves one or more predetermined scientific, clinical, or policy purposes. A registry database is a file (or files) derived from the registry. Although registries can serve many purposes, this guide focuses on registries created for one or more of the following purposes: to describe the natural history of disease, to determine clinical effectiveness or cost-effectiveness of health care products and services, to measure or monitor safety and harm, and/or to measure quality of care. Registries are classified according to how their populations are defined. For example, product registries include patients who have been exposed to biopharmaceutical products or medical devices. Health services registries consist of patients who have had a common procedure, clinical encounter, or hospitalization. Disease or condition registries are defined by patients having the same diagnosis, such as cystic fibrosis or heart failure. The User’s Guide was created by researchers affiliated with AHRQ’s Effective Health Care Program, particularly those who participated in AHRQ’s DEcIDE (Developing Evidence to Inform Decisions About Effectiveness) program. Chapters were subject to multiple internal and external independent reviews.

The Practical Guide

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Author :
Publisher :
ISBN 13 :
Total Pages : 94 pages
Book Rating : 4.:/5 (319 download)

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Book Synopsis The Practical Guide by :

Download or read book The Practical Guide written by and published by . This book was released on 2002 with total page 94 pages. Available in PDF, EPUB and Kindle. Book excerpt:

The Diabetic Neuropathies

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Publisher :
ISBN 13 :
Total Pages : 12 pages
Book Rating : 4.:/5 (3 download)

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Book Synopsis The Diabetic Neuropathies by : National Institute of Neurological and Communicative Disorders and Stroke. Office of Scientific and Health Reports

Download or read book The Diabetic Neuropathies written by National Institute of Neurological and Communicative Disorders and Stroke. Office of Scientific and Health Reports and published by . This book was released on 1978 with total page 12 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Severe Asthma

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Publisher : European Respiratory Society
ISBN 13 : 1849841047
Total Pages : 365 pages
Book Rating : 4.8/5 (498 download)

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Book Synopsis Severe Asthma by : Kian Fan Chung

Download or read book Severe Asthma written by Kian Fan Chung and published by European Respiratory Society. This book was released on 2019-06-01 with total page 365 pages. Available in PDF, EPUB and Kindle. Book excerpt: Severe asthma is a form of asthma that responds poorly to currently available medication, and its patients represent those with greatest unmet needs. In the last 10 years, substantial progress has been made in terms of understanding some of the mechanisms that drive severe asthma; there have also been concomitant advances in the recognition of specific molecular phenotypes. This ERS Monograph covers all aspects of severe asthma – epidemiology, diagnosis, mechanisms, treatment and management – but has a particular focus on recent understanding of mechanistic heterogeneity based on an analytic approach using various ‘omics platforms applied to clinically well-defined asthma cohorts. How these advances have led to improved management targets is also emphasised. This book brings together the clinical and scientific expertise of those from around the world who are collaborating to solve the problem of severe asthma.