Monocytes and macrophages are innate immune cells that reside and accumulate in atherosclerotic lesions but also in the healthy and injured heart and brain. The cells and their subsets pursue distinct functions in steady state and disease, and their tenure may range between hours to months. Some subsets are highly inflammatory, while others support tissue repair.
Dr. Matthias Nahrendorf discusses current concepts of cell supply by the hematopoietic system, lineage relationships and systems’ cross talk, highlights open questions, and describes imaging tools for studying monocytes, macrophages and their progenitors.
Key Topics Include:
- Resident versus bone marrow derived macrophages
- Roles and phenotypes of heart leukocytes
- Hematopoiesis and the bone marrow in cardiovascular disease
Update on the 18th International Conference on Co-morbidities and Adverse Drug Reactions in HIV
Daniel Lee, M.D.
January 20th, 2017
UCSD HIV & Global Health Rounds
Cardiac Inflammation and Repair Following Myocardial InfarctionInsideScientific
Join Dr. Merry Lindsey as she discusses her research involving the physiology of recovery from cardiac events.
Age plays a pivotal role in the deterioration of cardiovascular functionality, resulting in an increased risk of cardiovascular disease in older adults. The prevalence of cardiovascular disease has also been shown to increase with age, in both men and women, including the prevalence of atherosclerosis, stroke and, myocardial infarction.
Following myocardial infarction (MI), the left ventricle (LV) undergoes a series of cardiac wound healing responses that involve both the stimulation of robust inflammation to clear necrotic myocytes and tissue debris and the induction of extracellular matrix (ECM) protein synthesis to generate an infarct scar. Collectively, this process in known as LV remodeling. Matrix metalloproteinase-9 (MMP-9) is a key regulator of LV remodeling post-MI, through direct effects on ECM turnover as well as indirect effects on the regulation of the major cell types that coordinate cardiac wound healing- namely the infiltrating leukocytes and the cardiac fibroblasts. We will discuss recent research that has expanded our understanding of MI LV remodeling, including recent proteomic advances focused on the ECM compartment to provide novel functional and translational insights. In summary, this webinar will provide an overview of how cardiac ECM research has evolved over the last decade and will provide insight into future directions that will drive further understanding of MMP directed cardiac ECM turnover after MI.
"Mechanisms of nitric oxide synthase uncoupling in endotoxin-induced acute lung injury: role of asymmetric dimethylarginine" appeared in a 2010 issue of Vascular Pharmacology and summarized Stephen M. Black's research into acute lung injury/sepsis.
Monocytes and macrophages are innate immune cells that reside and accumulate in atherosclerotic lesions but also in the healthy and injured heart and brain. The cells and their subsets pursue distinct functions in steady state and disease, and their tenure may range between hours to months. Some subsets are highly inflammatory, while others support tissue repair.
Dr. Matthias Nahrendorf discusses current concepts of cell supply by the hematopoietic system, lineage relationships and systems’ cross talk, highlights open questions, and describes imaging tools for studying monocytes, macrophages and their progenitors.
Key Topics Include:
- Resident versus bone marrow derived macrophages
- Roles and phenotypes of heart leukocytes
- Hematopoiesis and the bone marrow in cardiovascular disease
Update on the 18th International Conference on Co-morbidities and Adverse Drug Reactions in HIV
Daniel Lee, M.D.
January 20th, 2017
UCSD HIV & Global Health Rounds
Cardiac Inflammation and Repair Following Myocardial InfarctionInsideScientific
Join Dr. Merry Lindsey as she discusses her research involving the physiology of recovery from cardiac events.
Age plays a pivotal role in the deterioration of cardiovascular functionality, resulting in an increased risk of cardiovascular disease in older adults. The prevalence of cardiovascular disease has also been shown to increase with age, in both men and women, including the prevalence of atherosclerosis, stroke and, myocardial infarction.
Following myocardial infarction (MI), the left ventricle (LV) undergoes a series of cardiac wound healing responses that involve both the stimulation of robust inflammation to clear necrotic myocytes and tissue debris and the induction of extracellular matrix (ECM) protein synthesis to generate an infarct scar. Collectively, this process in known as LV remodeling. Matrix metalloproteinase-9 (MMP-9) is a key regulator of LV remodeling post-MI, through direct effects on ECM turnover as well as indirect effects on the regulation of the major cell types that coordinate cardiac wound healing- namely the infiltrating leukocytes and the cardiac fibroblasts. We will discuss recent research that has expanded our understanding of MI LV remodeling, including recent proteomic advances focused on the ECM compartment to provide novel functional and translational insights. In summary, this webinar will provide an overview of how cardiac ECM research has evolved over the last decade and will provide insight into future directions that will drive further understanding of MMP directed cardiac ECM turnover after MI.
"Mechanisms of nitric oxide synthase uncoupling in endotoxin-induced acute lung injury: role of asymmetric dimethylarginine" appeared in a 2010 issue of Vascular Pharmacology and summarized Stephen M. Black's research into acute lung injury/sepsis.
"Glutathione supplementation attenuates lipopolysaccharide-induced mitochondrial dysfunction and apoptosis in a mouse model of acute lung injury" appeared in a 2012 issue of 'Physiology' and summarized the research Stephen M. Black and his team conducted into acute lung injury.
Learn more about his research on his blog: http://stephenmblack.com/blog/
Dr.Ameet Dravid has made a significant contribution in Research & Treatment of HIV and AIDS medicine.Dr. Dravidis expert in successfully treating Diseases like: HIV,AIDS.He has treated & cured more than 25+ patient! Best practices in HIV at the district, international levels.
Fine Tuning Nutrient Intake Timing for Cardiac HealthInsideScientific
Cardiovascular function changes on a daily basis with potential implications for risk of heart attack and sudden cardiac death. In this webinar, Martin Young, DPhil, will discuss these cardiovascular changes and the potential mechanisms that govern these 24-hour rhythms with a particular focus on circadian clocks. These studies highlight that circadian clocks modulate processes that are critical for normal cardiovascular function, including metabolism. Daily rhythms in metabolism, in turn, influence the manner with which organs (such as the heart) respond to nutrient intake. Dr. Young illustrates the concept that the time of day at which specific macronutrients (such as lipids and proteins) are consumed dramatically impacts the heart. Dr. Young showcases the relevance of these basic science findings to human population studies.
"Glutathione supplementation attenuates lipopolysaccharide-induced mitochondrial dysfunction and apoptosis in a mouse model of acute lung injury" appeared in a 2012 issue of 'Physiology' and summarized the research Stephen M. Black and his team conducted into acute lung injury.
Learn more about his research on his blog: http://stephenmblack.com/blog/
Dr.Ameet Dravid has made a significant contribution in Research & Treatment of HIV and AIDS medicine.Dr. Dravidis expert in successfully treating Diseases like: HIV,AIDS.He has treated & cured more than 25+ patient! Best practices in HIV at the district, international levels.
Fine Tuning Nutrient Intake Timing for Cardiac HealthInsideScientific
Cardiovascular function changes on a daily basis with potential implications for risk of heart attack and sudden cardiac death. In this webinar, Martin Young, DPhil, will discuss these cardiovascular changes and the potential mechanisms that govern these 24-hour rhythms with a particular focus on circadian clocks. These studies highlight that circadian clocks modulate processes that are critical for normal cardiovascular function, including metabolism. Daily rhythms in metabolism, in turn, influence the manner with which organs (such as the heart) respond to nutrient intake. Dr. Young illustrates the concept that the time of day at which specific macronutrients (such as lipids and proteins) are consumed dramatically impacts the heart. Dr. Young showcases the relevance of these basic science findings to human population studies.
Mechanical Ventilation of Patient with COPD ExacerbationDr.Mahmoud Abbas
Mechanical Ventilation of Patient with COPD Exacerbation lecture presented by Dr Andres Esteban at the Egyptian Critical care Summit 2015 held at Cairo, egypt.
The Egyptian Critical Care Summit is the leading medical event and exhibition for Intensive Care Medicine in Egypt.
BRIEF OBSERVATION
All-cause Mortality Associated with
TNF-a Inhibitors in Rheumatoid Arthritis:
A Meta-Analysis of Randomized Controlled Trials
Lucile Poiroux, MD, Yannick Allanore, MD, PhD, André Kahan, MD, PhD, Jérôme Avouac, MD, PhD
Paris Descartes University, Sorbonne Paris Cité, Rheumatology A Department, Cochin Hospital, Paris, France
Funding: This
Conflict of In
Authorship: A
conception, design
Requests for re
Université Paris D
rue du Faubourg S
E-mail address
0002-9343/$ -see
http://dx.doi.org/1
ABSTRACT
OBJECTIVE: To compare mortality data obtained from randomized controlled trials for the 5 tumor necrosis
factor-a (TNF-a) inhibitors used in the treatment of rheumatoid arthritis.
METHODS: A systematic review of articles published up to November 2014 was performed using electronic
databases. We included randomized, controlled trials, with a follow-up period of at least 24 weeks,
comparing TNF-a inhibitors to placebo or disease-modifying antirheumatic drugs. The primary outcome
was the occurrence of all-cause mortality.
RESULTS: Twenty-three studies were selected. These articles included 6525 patients in the anti-TNF-a
group and 3523 in the control group. The duration of patient follow-up ranged from 24 to 104 weeks. The
risk of all-cause mortality in patients receiving TNF-a inhibitors was not significantly different from those
receiving the comparator (odds ratio 1.32; 95% confidence interval, 0.76-2.29). Subgroup analyses with
respect to the molecule used, the dose received, the use of TNF-a inhibitors as monotherapy or combination
therapy, or the quality of the trial did not modify the findings.
CONCLUSION: This meta-analysis performed on a large number of patients and including the 5 TNF-a
inhibitors currently available shows no increased risk of medium-term all-cause mortality in patients with
rheumatoid arthritis.
� 2015 Elsevier Inc. All rights reserved. � The American Journal of Medicine (2015) -, ---
KEYWORDS: Meta-analysis; Mortality; Rheumatoid arthritis; TNF-a inhibitors
Tumor necrosis factor-a (TNF-a) inhibitors are the most
widely used first-line biologic therapy for the treatment of
rheumatoid arthritis. Much has been written on the concern
that TNF-a inhibitors may increase the risk of malignancy,
infections, and other serious adverse events.1,2 However,
studies of the potential risks of this drug class on the “hard
endpoint” mortality are scarce and have provided conflicting
results.3 A previous meta-analysis reported no evidence of
increased mortality associated with any TNF-a inhibitor in
rheumatoid arthritis. However, the analysis was limited to
research received no funding.
terest: None.
ll authors had access to the data and participated in the
, writing, editing, and final approval of the manuscript.
prints should be addressed to Jérôme Avouac, MD, PhD,
escartes, Service de Rhumatologie A, Hôpital Cochin, 27
aint-Jacques, Paris 75014, France.
: [email protected]
front matter � 2015 Elsevier Inc. All right ...
Dr. Roberto Machado from the University of Illinois at Chicago presented an update on PAH at a Patient Education Conference on March 15, 2014 hosted by the Scleroderma Foundation, Greater Chicago Chapter.
Presented by D.Niall Ferguson at 9th Pulmonary Medicine Update Course held at Cairo, Egypt.
This course is the leading Pulmonary Critical Care event in Egypt. The course is organized by Scribe (www.scribeofegypt.com)
The Changing Role of the Coronary Care Cardiologist & The Emerging Role of Ca...Dr.Mahmoud Abbas
The Changing Role of the Coronary Care Cardiologist
&
The Emerging Role of Cardiac Intensive Care Specialists lecture presented by Dr Sherif Mokhtar, President ECCCP at the Egyptian Spanish Critical care Symposium held at Cairo, Egypt on 11 May 2023
Drug induced Kidney Injury in the ICU. Presentation by Dr Sandra Kane Gill , President Society of Critical Care Medicine (SCCM) , USA at the Egyptian Critical care Summit 2022 conference , organized by the Egyptian College of Critical care Physicians (ECCCP) , Egypt
Using Novel Kidney Biomarkers to Guide Drug Therapy.pdfDr.Mahmoud Abbas
Using Novel Kidney Biomarkers to Guide Drug Therapy: Presentation by Dr Sandra Gill , President SCCM at the Egyptian Critical Care Summit 2022 held at Cairo, Egypt and organized by the Egyptian College of Critical care Physicians (ECCCP)
Presentation by Dr Marwa Atef , National Research Center, Cairo, Egypt . Presented at Cairo Textile Week 2021 , the leading textiles conference in Egypt
Cairo Textile Week 2021 Conference -Egypt Textiles & Home Textiles Export Cou...Dr.Mahmoud Abbas
Egyptian Textiles Export
Opportunities & Requirements
Presentation by Engineer Hany Salam, CEO Salam Textiles, Board member Egypt Textiles & Home Textiles
Export Council (THTEC)
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
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We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
How to Give Better Lectures: Some Tips for Doctors
C O P D :State of the Art
1. COPD State-of-the-Art Richard K. Albert, M.D. Chief of Medicine Denver Health Professor of Medicine University of Colorado Adjunct Professor of Engineering and Computer Science University of Denver 8 th Pulmonary Medicine Update February 6, 2008 Denver Health
4. Changes in Definition of COPD ATS/ERS Guidelines COPD has systemic consequences - Systemic inflammation - Weight loss - Skeletal muscles - Cardiac disease and death (Huiart, Chest 2005) > 5648 receiving “1 st Rx for COPD” > HF most common cause of hospitalization > More hospitalizations for CV disease than COPD > CVD more common cause of death than COPD Denver Health
5. COPD Epidemiology Prevalence: 12.4 - 24 million in US Morbidity: 2004: 461,000 hospitalizations (4 th most common) 1.5 million ED visits Mortality: 120,000 deaths in 2001 (6 th most common - 3 rd by 2020) 1 death/4 min (14 during this lecture) Only cause of death in top 10 that is Cost: $6.5 billion Denver Health
6. COPD Epidemiology: Gender Discrepancy in Mortality Machado, AJRCCM 2006 Mortality for women on O 2 Denver Health
7. COPD Phenotyping Correlates with FEV 1 Health status Resource utilization AECOPD Mortality Small airway wall thickness - Inflammatory cell infiltration - Smooth muscle - Subepithelial fibrosis Does Not Correlate with FEV 1 Emphysema Hyperinflation BMI Peripheral muscle fxn Dyspnea Exercise tolerance Denver Health
8. COPD Phenotyping (courtesy John Riley, B & W) FEV 1 : 105% DL CO : 50% FEV 1 : 95% DL CO : 70% FEV 1 : 40% DL CO : 70% Denver Health
9. COPD Phenotyping: Predictors of Mortality (Multivariate Analysis) 609 pts, NETT, medical Rx Martinez, AJRCCM 2006 Denver Health 1.36 DL CO < 22 1.38 Hemoglobin < 13.4 1.48 Modified BODE 1.40 O 2 use 1.48 Maximum work 1.53 Perfusion ratio 1.56 RV (% predicted) 1.72 Age > 70 1.80 % Upper lobe emphysema Hazard Ratio Predictor
10. COPD Phenotyping: CRP Predicts Hospitalization and Prognosis Hospitalization Death Dahl, AJRCCM 2006 Denver Health
11. COPD Phenotyping: BNP Predicts PHT and Prognosis 176 pts “scheduled for RH cath” BNP Predicts PHT PHT predicts survival BNP predicts survival 85% sensitivity 88% specificity (5% with Ppa > 40 torr) Leuchte, AJRCCM 2006 Denver Health
12. COPD Genetics Candidate Gene Abns SERPINA 1 ( -1-AT) MMP-9 (C-1562 SNP promotor activity) ADAM-33 (adhesion, signaling, proteolysis) Elastin (Gly Asp in terminal exon) Secretory PLA 2 , Group IID CCL1 SNP ( AECOPD x 2 yr) Denver Health
22. AECOPD: Biomarkers Hurst, 2006 Purpose? Dx AECOPD Assess severity Dx other problem Pathobiology Etiology Denver Health
23. AECOPD: Left Heart Dysfunction Abroug, AJRCCM 2006 148 consecutive pts with AECOPD - 55 (37%) on mechanical ventilation All got ECHO, BNP, Troponins Excluded pneumonia, PE, CPA, inotropes ARF, nonechogenic LVF and RVF diagnosed by 4 MDs - Definite, Possible, Unlikely - Clinical data (not BNP or Troponins) Denver Health
24. AECOPD: Left Heart Dysfunction 75 (51%) with LV dysfunction 17 (23%) systolic dysfunction 48 (64%) diastolic dysfunction 10 (13%) both 41 (31%) 20 (14%) 82 (55%) BNP > 1000 94% Sensitive 77% Specific (Abroug, AJRCCM 2006) Denver Health
25. AECOPD: Pulmonary Embolism Spiral CT & US 211 consecutive pts with “unexplained” AECOPD - Not requiring mechanical ventilation - No acute bronchitis, pneumonia, PTX - Disparity between CXR and ABGs 49/197 (25%) positive for PE - 43 by CT (19 of whom had + US) - 6 by US Associations: - Previous PE, malignancy, 5 torr PaCO 2 (Tillie-Leblond, 2006) Denver Health
26. COPD Rx: Steroid Resistance Limited effect of steroids in stable disease Cells, cytokines, proteases in BAL Histology of biopsies IL-8, TNF suppression AM cytokine production Oxidative/nitrative stress inhibits HDAC fxn Denver Health
33. COPD Rx: Long-Acting Bronchodilators GOLD Guidelines Regular treatment with long-acting bronchodilators is more effective and convenient than treatment with short-acting agents Regular use of a long-acting bronchodilator… improves health status Treatment with a long-acting bronchodilator reduces the rate of AECOPD Denver Health
34. COPD Rx: Do LABAs AECOPD? (Sin, JAMA 2003) Denver Health
35. COPD Rx: Does Tiotropium AECOPD? (Sin, JAMA 2003) Denver Health
36. COPD Rx: ICS GOLD Guidelines Regular treatment with ICS is appropriate for symptomatic patients with COPD with an FEV 1 < 50% predicted (stages III and IV) and repeated AECOPD (e.g., 3/3 yr) (Evidence A). This treatment has been shown to reduce AECOPD and thus improve health status (Evidence A) Withdrawal from treatment can lead to AECOPD in some patients. Denver Health
37. COPD Rx: Do ICS AECOPD? Sin, JAMA 2003 Denver Health
38. Effect of Rx on AECOPD (Suissa, AJRCCM 2006) Methods of Analysis Unweighted (individual pt data) (Bad) - AEs for each pt/time of f/u for each pt - Each pt contributes equally regardless of f/u time - Exaggerates Rx effect Weighted (pooled data) (Better) - Total AE for all pts/total time of f/u for all pts - Weights each pt’s AE rate by their f/u time - Produces correct and best estimate (i.e., maximum likelihood estimate) of AE rate (not biased by short f/u) Denver Health
39. Effect of Rx on AECOPD (Suissa, AJRCCM 2006) Analysis of weighted data Assume Poisson distribution for AEs (Bad) - AEs can occur repeatedly, randomly, independently - Ignores that some pts may have frequent AEs and some may have none Estimate variability and use “overdispersion parameter” (Better) - p value and CI based on within- and between- subject variability Denver Health
40. COPD Rx: Quality of the Data Cited supporting references Many used unweighted analyses None used an overdispersion parameter Some analyzed adjusted data One QOL just exceeded “clinically significant” (e.g., 5 vs 4) Many included Pharma employees as authors with analyses performed in-house Some actually reported NO beneficial effects Denver Health
42. COPD Rx: Do ICS AECOPD? Berge (+ Glaxo), BMJ 2000 (ISOLDE) ICS, LABA, ICS + LABA, placebo Analyzed by Glaxo Reported median exacerbation rate # AEs/# Rx days extrapolated to #/yr Unweighted analysis (overestimates effect) Denver Health
43. COPD Rx: Do ICS AECOPD? Van der Valk, AJRCCM 2003 Routine Rx + ICS x 4 M, continue ICS vs P Primary outcome measures - First and second AE - Rapid recurrent AEs - HRQL 21% crossovers 1.3 1.5 vs 1.3 1.6 AEs/yr - 48% had no AEs Time to first AE different (“adjusted for smoking status”) Denver Health
44. COPD Rx: Does Tiotropium AECOPD? Niewoehner, AIM 2005 1829 pts (Mod-Severe) Tiotropium vs usual Rx AECOPD (1 yr): Tiotropium: 28% Placebo: 32% P < 0.05 “ These treatment effects were small to modest, and their overall clinical importance must be weighed against other considerations, including cost” Denver Health
45. COPD Rx: Do ICS AECOPD? Szafranski, ERJ 2003 (126) ICS, LABA, ICS + LABA, placebo Poisson regression, dispersion adjustment Corresponding author @ Astra-Zeneca No correction for multiple comparisons (P < 0.016) Denver Health NS LABA vs Placebo P value Rx NS ICS vs Placebo 0.043 ICS + LABA vs LABA NS ICS + LABA vs ICS 0.035 ICS + LABA vs Placebo
46. COPD Rx: Do ICS Mortality? TORCH study (NEJM 2007) 6100 pts, FEV1 ~ 1.2 L (44%) - Salmeterol - Salmeterol/fluticasone - Fluticasone - Placebo Endpoints: - Death (Primary) - Frequency of AECOPD - QOL (SGRQ) - Lung function Calverley, 2007 Denver Health
47. COPD Rx: Do ICS Mortality? 3-yr mortality: Placebo: 15.2% Combination: 12.6% 17.5% relative P = 0.052 LaVecchia & Fabbri Salmeterol vs not 13 vs 15.6% (P = 0.004) Fluticasone vs not 14.3 vs 14.3% (P = 0.99) Calverley, 2007 Denver Health
48. COPD Rx: Do ICS Mortality? 3-yr COPD mortality: Placebo: 6.0% Combination: 4.7% 21.7% relative P = 0.11 Fluticasone: 6.9% Combination: 4.7% 31.8% relative P = 0.008 LABA vs Combo: NS Calverley,NEJM 2007 Denver Health
49. COPD Rx: Do ICS Mortality? FEV 1 (ml) SGRQ (units) Calverley, NEJM 2007 Denver Health
50. COPD Rx: Do ICS Mortality? Problems: 40% drop out in placebo group (P < 0.05) All pts had indications for Rx Pts with more severe disease might not have enrolled Pneumonia - Placebo: 12.3% - Combination: 19.6% (P < 0.001) - Ernst, AJRCCM 2007: RR 1.70 (1.63-1.77) Rabe, NEJM 2007 Denver Health
51. COPD Rx: Do ICS Mortality? “ All trials are a gamble, and the TORCH investigators came close to winning, but did not win” “ LABA was a winner, ICS was a clear loser” Combination Rx better - Health status - Use of oral steroids - AECOPD - in FEV 1 Combination Rx: severe disease &/or AECOPD (same as GOLD recommendations) More pneumonia in combination Rx Rabe, NEJM 2007 Denver Health