The document discusses approaches to rheumatic diseases, including criteria, biomarkers, and classification systems. It summarizes the 1977 ACR criteria for gout, the 2014 Nijmegen diagnostic rule, and the 2015 ACR/EULAR gout classification criteria. It also summarizes the 1997 ACR, 2012 SLICC, and 2015 ACR/SLICC revised criteria for systemic lupus erythematosus. Various biomarkers for osteoarthritis and rheumatoid arthritis are discussed for purposes like diagnosis, prognosis, monitoring disease activity and treatment response.
Dr. Swamy Venuturupalli talks about Rheumatoid Arthritis, Early Diagnosis and Treatment at the James R. Klinenberg symposium on Rheumatic diseases in Pasadena, CA.
Crystal arthropathies gout & pseudogoutShinjan Patra
Gout is one of the most dangerous underrated acute emergency in rheumatological diseases. CPPD disease is an another entity which is very much under-diagnosed in respect t OA
Dr. Swamy Venuturupalli talks about Rheumatoid Arthritis, Early Diagnosis and Treatment at the James R. Klinenberg symposium on Rheumatic diseases in Pasadena, CA.
Crystal arthropathies gout & pseudogoutShinjan Patra
Gout is one of the most dangerous underrated acute emergency in rheumatological diseases. CPPD disease is an another entity which is very much under-diagnosed in respect t OA
Remote Ischaemic Conditioning: A Paper Review & Uses in Paramedic Practicebgander23
A 2 part presentation. Part 1 reviews a paper on the long-term clinical outcomes of STEMI patients undergoing remote ischaemic perconditioning prior to primary percutaneous coronary intervention. The 2nd part looks at how this technique can be used in Paramedic practice.
Important Trials of the Day & Basics of Biostatistics | IACTS SCORE 2020IACTSWeb
This presentation emphasizes on the importance of biostatistics in the interpretation, analysis and design of studies and trials in the daily life of an academic surgeon. It also sheds light on some important clinical trials of the present milieu that are playing a vital role in the course that cardiothoracic surgery is taking.
Courtesy of Dr. Prasanna Simha Mohan Rao, MS, MCh, DNB, PGDHHM. He presently serves as Professor and Unit Chief of Cardiothoracic and Vascular Surgery at Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru.
This presentation accompanies a video that is part of the lecture series of IACTS SCORE 2020 held at the SSSIHMS Whitefield, Bengaluru between 7th and 8th March, 2020.
“8th National Biennial Conference on Medical Informatics 2012”Ashu Ash
“8th National Biennial Conference on Medical Informatics 2012” at Jawaharlal Nehru Auditorium, AIIMS New Delhi on 5th Feb 2012,
The organizing committee consisting of Mr. S.K. Meher (Organizing Secretary), Major (Dr.) Anil Kuthiala (Jt. Organizing Secretary) and Ashu (Assistant to the Organizing Secretariat) worked hard and toiled to make the conference a grand success.
The scientific committee comprising of Dr. S.B Gogia, Prof. Khalid Moidu, Prof Arindam Basu, Dr. S Bhatia, Dr. Thanga Prabhu, Dr. Karanvir Singh, Tina Malaviya, Dr. Kamal Kishore, Dr. Vivek Sahi, Spriha Gogia, Dr. Supten Sarbhadhikari, Dr.Sanjay Bedi, Mr. Sushil Kumar Meher actively reviewed all papers for the various scientific sessions.
Two different use cases to obtain best response using recist 11 sdtm and a ...Kevin Lee
Each therapeutic area has its own unique data collection and analysis. Especially, Oncology has a unique way to collect and analyze the data and one of unique data points in oncology study is best response. The paper will be based on Solid Tumor and RECIST 1.1, and it will show use cases on how best response will be collected in SDTM domains and derived in ADaM datasets using RECIST 1.1 in solid tumor oncology study.
The paper will provide the brief introduction of RECIST 1.1 such as legions type (i.e., target, non-target and new) and their selection criteria(e.g., size and number). The paper will provide the practical application on how tumor measurements for target and non-target lesions are collected in TR domain, how those measurement are assessed according to RECIST 1.1, and eventually how responses are represented in RS domain based on the assessment from tumor measurements.
We will also put in prospective a pictorial road map on which way we choose to derive responses to give a prospective to the user and the process to get from beginning to end objective. This paper will also discuss a use case where the visit level response are been derived programmatically in ADaM and perform a sensitive analysis in comparison to investigator provides visit level response to SDTM RS domain. This case study will help user identify the differences between both the methodologies and help answer any anomalies from investigator inference prospective vs analytical calculations by the programmer.
Back to the Bedside: Internal Medicine Bedside Ultrasound ProgramAllina Health
David Tierney, MD. How bedside ultrasound is changing the practice of medicine and how Abbott Northwestern Hospital has become a national leader in integrating bedside ultrasound in its Internal Medicine Residency Program. "As internal medicine physicians, we are finding that everything we do with our hands, eyes and stethoscopes can be done a little better with ultrasound. That means our physical exam, which we consider our bread and butter, has more sensitivity and specificity. This gives us better diagnostic ability and results in earlier and more appropriate treatment."
Welcomed the challenge to give updates in Rheumatology under 10 minutes during the 2024 PCP Annual Convention.
The QR code to the compilation of references didn't work so here's the link https://drive.google.com/drive/folders/1cZUPyvey-lutM3jgslCrq-5oHakbM5Aw?usp=sharing
This was a review of different guidelines on lupus nephritis from ACR, EULAR, and KDIGO. Goal is appreciate similarities and differences between the different guidelines.
Feeling the chapter on gout in HPIM didn't sufficiently capture the essence of managing gout, I felt the need to come up with a presentation discussing how best to manage the disease and cover some related topics such as allopurinol adverse events, diet and genetic testing prior to allopurinol use. This is my talk on gout which I gave to my IM residents last April 2019
To Treat or Not to Treat.
This is a frequent question we encounter in practice. Here's looking into the latest studies on whether treating patients with Asymptomatic Hyperuricemia with urate lowering therapy helps improves cardiovascular outcomes.
Managing CV risk in Inflammatory Arthritis (Focusing on Gout)Sidney Erwin Manahan
Presentation made during the 1st Inter-Hospital Rheumatology Fellows' Case Discussion on 9 June 2018 at the Speaker Feliciano Belmonte Auditorium, 7/F East Avenue Medical Center. Presentation highlights the needs to recognize gout as one of the rheumatic conditions that put patients at risk for developing CV disease.
Was recently asked to discuss whether there is evidence to support the use of B vitamins in managing different aches and pains. Here's my talk delivered last 16 Sept 2016 at the 12th Post Graduate Course of the East Avenue Medical Center Department of Internal Medicine.
I was asked by the organizers to review updates on the management of gout. I compared guideline recommendations from the 2008 Philippine CPG to the 2012 ACR Recommendations and the 2014 3E Initiative.
In the presentation, I discussed new concepts in OA pathogenesis and identified possible targets of treatment. This was followed by a review of new treatment options for osteoarthritis. Presented during the Joint RA OA SIG Symposium at the F1 Hotel last 28 November 2014.
I was asked to present something on Fibromyalgia during a Pain Summit. I ended up describing what we know so far about clinical features, evolution of diagnostic criteria and synthesized some recent guidelines.
I was asked to discuss recently the latest guidelines with the fellows. Here's my work. I also included some slides on how to apply for support via Phil Charity Sweepstakes Office.
It's challenging to treat patients with gout who also have chronic kidney disease. Here's a review of literature on how to proceed. This happens to be my second PRA convention presentation.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
- 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
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the 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 lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
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. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
2. DISCLOSURE
• Part of the speakers bureau for Pfizer
(Celebrex, Lyrica)
• Previously part of the speakers bureau
for Ajanta Pharma (Atenurix) and
Menarini (Ketesse)
• Received honoraria for previous
participation in clinical trials from
Roche, Wyeth and Parexel
• Received education support from
Pfizer
4. 1977 ACR Criteria for
Acute Arthritis of GOUT
• >1 attack of acute arthritis
• Max inflammation within 24 hrs
• Attack of monoarthritis
• Joint redness
• Painful or swollen MTP1
• Unilateral attack involving the
tarsal jt
• Suspected tophus
• Hyperuricemia
• Assymmetric swelling within a
joint (XR)
• Subcortical cyst without erosions
(XR)
• Negative SF culture aspirated
during an acute episode of
arthritis
URATE CRYSTALS in joint fluid or from a tophus
OR
Any SIX (6) of the following criteria:
5. 2014 Diagnostic Rule for GOUT
(NIJMEGEN SCORE)
FEATURES Score
Male Sex 2
Previous arthritis attack (patient reported) 2
Onset within 1 day 0.5
Joint Redness 1
Involvement of the 1st MTP (podagra) 2.5
Hypertension or >1 CV disease 1.5
Serum uric acid >5.88mg/dl 3.5
< 4 points
NON-GOUT
>4 and <8 points
UNCERTAIN
> 8 points
GOUT
Kienhorst LB, Janssens HJ, Fransen J, et al. Rheumatology (Oxford) 2014; 16 Epub.
6. 2015 GOUT Classification Criteria
( AC R/ E U L AR )
• Joint Involvement
• Characteristics
• Typical Episodes
• Evidence of Tophus
• Serum Uric Acid
• Synovial Fluid Urate
• Imaging
• Radiographs
Neogi T, Jansen TLTA, Dalbeth N, et al. Ann Rheum Dis 2015; 74: 1789-98.
7. 2015 GOUT Classification Criteria
( AC R/ E U L AR )
• JOINT INVOLVEMENT
• Characteristics
• Typical Episodes
• Evidence of Tophus
• Serum Uric Acid
• Synovial Fluid Urate
• Imaging
• Radiographs
• MTP1 (2)
• Ankle/ midfoot (1)
• Other joints (0)
Neogi T, Jansen TLTA, Dalbeth N, et al. Ann Rheum Dis 2015; 74: 1789-98.
8. 2015 GOUT Classification Criteria
( AC R/ E U L AR )
• Joint Involvement
• CHARACTERISTICS
• Typical Episodes
• Evidence of Tophus
• Serum Uric Acid
• Synovial Fluid Urate
• Imaging
• Radiographs
DURING THE ACUTE
ATTACK
• Great difficulty using the joint
• Can’t bear touch or pressure
• Erythema
• All 3 are present (3)
• Only 2 are present (2)
• Only 1 is present (1)
• None are present (0)
Neogi T, Jansen TLTA, Dalbeth N, et al. Ann Rheum Dis 2015; 74: 1789-98.
9. 2015 GOUT Classification Criteria
( AC R/ E U L AR )
• Joint Involvement
• Characteristics
• TYPICAL EPISODES
• Evidence of Tophus
• Serum Uric Acid
• Synovial Fluid Urate
• Imaging
• Radiographs
THE TYPICAL GOUT ATTACK
• Maximal pain <24h
• Resolution <14 days
• Asymptomatic in between
• Recurrent attacks (2)
• One typical attack (1)
• No typical attack (0)
Neogi T, Jansen TLTA, Dalbeth N, et al. Ann Rheum Dis 2015; 74: 1789-98.
10. 2015 GOUT Classification Criteria
( AC R/ E U L AR )
• Joint Involvement
• Characteristics
• Typical Episodes
• EVIDENCE OF TOPHUS
• Serum Uric Acid
• Synovial Fluid Urate
• Imaging
• Radiographs
TOPHUS
• Present (4)
• Absent (0)
Neogi T, Jansen TLTA, Dalbeth N, et al. Ann Rheum Dis 2015; 74: 1789-98.
11. 2015 GOUT Classification Criteria
( AC R/ E U L AR )
• Joint Involvement
• Characteristics
• Typical Episodes
• Evidence of Tophus
• SERUM URIC ACID
• Synovial Fluid Urate
• Imaging
• Radiographs
URATE LEVELS (mg/dl)*
• <4 (-4)
• 4 - <6 (0)
• 6 - <8 (2)
• 8- <10 (3)
• >10 (4)
* Highest measurement, OFF urate
lowering therapy, >4 weeks from
an episode
Neogi T, Jansen TLTA, Dalbeth N, et al. Ann Rheum Dis 2015; 74: 1789-98.
12. 2015 GOUT Classification Criteria
( AC R/ E U L AR )
• Joint Involvement
• Characteristics
• Typical Episodes
• Evidence of Tophus
• Serum Uric Acid
• SYNOVIAL FLUID
URATE
• Imaging
• Radiographs
• NEGATIVE for MSU (-4)
• NOT DONE (0)
• POSITIVE for MSU
(SUFFICIENT CRITERION)
Neogi T, Jansen TLTA, Dalbeth N, et al. Ann Rheum Dis 2015; 74: 1789-98.
13. 2015 GOUT Classification Criteria
( AC R/ E U L AR )
• Joint Involvement
• Characteristics
• Typical Episodes
• Evidence of Tophus
• Serum Uric Acid
• Synovial Fluid Urate
• IMAGING
• Radiographs
IMAGING CRITERIA
• Double contour sign on US OR
urate deposition on DECT in an
affected joint
• Present (4)
• Absent / Not Done (0)
Neogi T, Jansen TLTA, Dalbeth N, et al. Ann Rheum Dis 2015; 74: 1789-98.
14. 2015 GOUT Classification Criteria
( AC R/ E U L AR )
• Joint Involvement
• Characteristics
• Typical Episodes
• Evidence of Tophus
• Serum Uric Acid
• Synovial Fluid Urate
• Imaging
• RADIOGRAPHS
GOUT EROSION
• Cortical break with
sclerotic margin and
overhanging edge on
hands or feet images
• Present (4)
• Absent (0)
Neogi T, Jansen TLTA, Dalbeth N, et al. Ann Rheum Dis 2015; 74: 1789-98.
15. 2015 GOUT Classification Criteria
( AC R/ E U L AR )
ENTRY CRITERIA
• >1 episode of joint or
bursal swelling, pain or
tenderness
SUFFICIENT CRITERIA
• Demonstration of MSU
crystals in synovial fluid or
tophus
THRESHOLD SCORE
• >8 classifies a patient as
having gout
Neogi T, Jansen TLTA, Dalbeth N, et al. Ann Rheum Dis 2015; 74: 1789-98.
16. CRITERIA SET SENSITIVITY SPECIFICITY
ACR / EULAR 0.92 0.89
ACR/ EULAR (Clinical) 0.85 0.78
ACR 1977 (survey) 0.84 0.62
Rome 0.97 0.78
New York 1.00 0.78
Neogi T, Jansen TLTA, Dalbeth N, et al. Ann Rheum Dis 2015; 74: 1789-98.
Comparison of
Criteria for GOUT
19. 2012 SLICC CLASSIFICATION CRITERIA FOR
SYSTEMIC LUPUS ERYTHEMATOSUS
• Acute cutaneous LE
• Chronic cutaneous LE
• Oral ulcer
• Alopecia
• Synovitis
• Serositis
• Renal
• Neurologic
• Hemolytic anemia
• Leucopenia/ lymphopenia
• Thrombocytopenia
• ANA
• Anti-dsDNA
• Anti-Sm
• aPL antibodies
• Low complement
• Direct Coomb’s test
CLINICAL IMMUNOLOGIC
Petri M, Orbai AM, Alarcon GS, et al. Arth & Rheum 2012; 64 (8): 2677-86.
AT LEAST 4 CRITERIA
(1 Needs to be IMMUNOLOGIC)
Biopsy proven LUPUS NEPHRITIS and ANA or anti-DNA
20. 2015 ACR/ SLICC Revised Criteria for
SYSTEMIC LUPUS ERYTHEMATOSUS
• ACUTE CUTANEOUS LE
– Malar rash (2)
– SCLE rash (1)
– Urticarial vasculitis (1)
– Photosensitivity (1)
• DISCOID LE (1)
• ALOPECIA (1)
• ORAL ULCERS (1)
• JOINT DISEASE (1)
• SEROSITIS (1)
• PSYCHOSIS OR SEIZURES OR
ACUTE CONFUSION STATE (1)
• KIDNEY
– Proteinuria or casts (1)
– Biopsy proven LN (2)
• HEMOLYTIC ANEMIA (1)
• THROMBOCYTOPENIA (1)
• LEUCOPENIA/ LYMPHOPENIA
(1)
• LOW TITER ANA (1)
• HIGH TITER ANA – homo/ rim
(2)
• Positive ANTI-DSDNA (2)
• Positive ANTI-SM (2)
• APL antibodies (1)
• LOW COMPLEMENT (1)
?
Salehi-Abari I. Autoimmune Dis Ther Approaches Open Access 2015; 2:114
21. 2015 ACR/ SLICC Revised Criteria for
SYSTEMIC LUPUS ERYTHEMATOSUS
HOW WERE THE CRITERIA CREATED?
?
“You should know that after many years of
visiting the patients with SLE and studying the
literatures and evaluating of the classification
criteria of SLE in every each one of the
patients who have had a diagnosis of SLE
upon clinical/ laboratory judgement, this new
criteria can easily be created.”
Salehi-Abari I. Autoimmune Dis Ther Approaches Open Access 2015; 2:114
22. BIOMARKERS
in Rheumatic Diseases
DRUG DEVELOPMENT
• Identify responders
• Assess patient response
Bay-Jensen AC, Reker D, Kjelgaard-Petersen CF, et al. Osteoarth and Cart 2016; 24: 9-20. Karsdal MA, Henriksen K, Leeming DJ, et al.
Biomarkers 2009; 14: 181-202. Bauer DC, Hunter DJ, Abramson SB, et al. Osteoarth and Cart 2006; 14: 723-7.
DIAGNOSIS
PROGNOSIS MONITORING
23. BIPED Classification of OA Biomarkers
Burden of Disease ADAMTS4
ADAMTS5
ARGS
Autotaxin
C Col 10*
CCL3
CCL4
CD14*
CGRP
COMP*
CRPM
FGF21*
MMP1/3
Sclerostin
TNF-
Investigative C2C* CD14*
Prognosis
Predictive
CD163* hmwAPN* Leptin*
Efficacy
Diagnostic BDNF* Fib3-2*
Bay-Jensen AC, Reker D, Kjelgaard-Petersen CF, et al. Osteoarth and Cart 2016; 24: 9-20.
28. Does Remission ENSURE
Better Outcomes?
Patients who meet established
criteria for CLINICAL
REMISSION may experience
progressive structural damage.
Brown AK, Conaghan PG, Karim Z, et al. Ann Rheum Dis 2008; 58: 2958-67
Brown AK, Quinn MA, Karim Z, et al. Ann Rheum Dis 2006; 54: 3761-73
Cohen G, Gossec L., Dougados M, et al. Ann Rheum Dis 2007; 66: 358-363
Lillegraven S, Prince FH, Shadick NA, et al. Ann Rheum Dis 2012; 71:861-6
Molenaar ET, Voskuyl AE, Dirant HS, et al. Arthritis and Rheum 2004: 36-42
29. Developing the BIOMARKERS
Study Biomarker Patients Samples Objectives
SCREEN 130 20 20 Candidate identification
I 113 128 128 Prioritization
II 75 320 320 Prioritization
III 65 85 255 Prioritization
IV 16 119 119
New marker evaluation,
prioritization
Pilot >25 24 107 Assessment of capabilities
Training 25 708 708
Analytical validation,
development of algorithm
Centola M, Cavet G, Shen Y, et al. PLoS ONE 2013; 8(4): e60635
30. Biomarkers in Rheumatoid Arthritis
IL-6 Leptin
TNF R1 VEGF-A
EGF VCAM-1
SAA
YKL-40
MMP-1
MMP-3
Resistin
CRP
31. Biomarkers in Rheumatoid Arthritis
IL-6 Leptin
TNF R1 VEGF-A
EGF VCAM-1
SAA
YKL-40
Predicted
TJC
MMP-1
MMP-3
Resistin
CRP
37. Validation of the MBDA Score
Biomarker
Measure
Clinical Measure
Pearson’s
Correlation
P-value N
SEROPOSITIVE
MBDA Score SDAI 0.55 <0.001 148
CDAI 0.48 <0.001 148
RAPID3 0.47 <0.001 92
SERONEGATIVE
MBDA Score SDAI 0.29 <0.001 139
CDAI 0.21 0.02 139
RAPID3 0.26 0.003 127
Curtis JR, van der Helm-van Mil AH, Knevel R, et al. Arthritis Care & Res 2012; 64 (12): 1794-1803.
38. Monitoring with the MBDA Score
Clinical Outcome Δ MBDA Score
Change in disease activity (Spearman’s)
Baseline to FinalVisit
Δ DAS28 CRP 0.51 (P<0.001)
ACR-N ResponseCriteria 0.45 (P=0.002)
Discrimination of clinically defined response (AUROC)
Baseline to FinalVisit
Δ DAS28 CRP 0.77 (P=0.002)
ACR50 ResponseCriteria 0.69 (P=0.03)
Baseline toWeek 2
Δ DAS28 CRP 0.72 (P=0.02)
ACR-N ResponseCriteria 0.65 (P=0.11)
Curtis JR, van der Helm-van Mil AH, Knevel R, et al. Arthritis Care & Res 2012; 64 (12): 1794-1803.
39. How the MBDA Score Compares
% with Good Radiographic Outcome (ΔSHS <3)
Test for Remission Remission Non-Remission P-value
DAS28 CRP<2.32 80 (66/83) 71 (134/188) 0.18
MBDA<25 93 (40/43) 70 (160/228) 0.001
ACR/ EULAR 83 (25/30) 73 (175/241) 0.27
Van der Helm-van Mil AHM, Knevel R, Cavet G, et al. Rheumatology 2013; 52: 839-46.
40. Which was better at predicting
RADIOGRAPHIC PROGRESSION?
7
20
15
27
18
24
43
37
0
5
10
15
20
25
30
35
40
45
50
MBDA DAS28 CRP
RiskofRadiographicProgression
Remission
Low
Moderate
High
Van der Helm-van Mil AHM, Knevel R, Cavet G, et al. Rheumatology 2013; 52: 839-46.
RR 6.1
RR 1.8
P<0.05
41. When MBDA and DAS28 DIFFER
58
20
11
87
47
33
0
10
20
30
40
50
60
70
80
90
100
ΔSHS>0 ΔSHS>3 ΔSHS>5
RiskofRadiographicProgression
DAS28 CRP Remission
DAS 28 CRP Remission, High MBDA
Van der Helm-van Mil AHM, Knevel R, Cavet G, et al. Rheumatology 2013; 52: 839-46.
RR 1.5
(1.16, 1.85)
RR 2.28
(1.13, 3.68)
RR 3.07
(1.08, 5.47)
42. MBDA Score in the CAMERA Study
MBDA
Score
DAS28 CRP
Baseline At 6 Months
Low Moderate High Low Moderate High
Low 0 1 4 9 3 2
Moderate 0 8 5 7 7 4
High 0 15 40 2 4 10
K (95% CI) 0.23 (-0.03, 0.48) 0.32 (0.11, 0.53)
Weighted K 0.20 (0.01, 0.39) 0.39 (0.02, 0.76)
Pearson Correlation (r) = 0.72 (p <0.001)
AUROC = 0.86 (p <0.001)
Bakker MF, Cavet G, Jacobs JWG, et al. Ann Rheum Dis 2012; 71: 1692-97.
Baseline = 66%
AT 6 MONTHS = 54%
43. MBDA Score in the SWEFOT Trial
Baseline
MBDA
Score
Baseline DAS28 ESR
Low
<3.2
Moderate
>3.2-5.1
High
>5.1
TOTAL
Low
(<30)
0 0/3 0/2 0/5
Moderate
(30-44)
0 1/14 0/15 1/29
High
(>44)
0 9/51 33/150 42/201
TOTAL 0 10/68 33/167 43/235
Hambardzumyan K, Bolce R, Saevasdottir S, et al. Ann Rheum Dis 2015; 74:1102-09.
NUMERATORS – no of patients with radiographic progression (change in SHS >5)
DENOMINATORS – no o f patients meeting MBDA and DAS Scores
15% 20%
3%
21%
44. MBDA Score in the SWEFOT Trial
The MBDA Score at baseline was a strong predictor of radiographic
progression at 1 year among patients with early RA
Hambardzumyan K, Bolce R, Saevasdottir S, et al. Ann Rheum Dis 2015; 74:1102-09.
80
20
0
66
14
3
46
33
21
0
10
20
30
40
50
60
70
80
90
No Change in SHS Change in SHS >3 Change in SHS >5
%ofPatients
Low (<30) Moderate (30-44) High (>44)
45. RADIOGRAPHIC PROGRESSION:
DAS28 CRP x MBDA Score
7
16
0
20
22
7
44
28
50
0
10
20
30
40
50
60
<2.6 >2.6-<4.1 >4.1
RiskofRadiographicProgression
(ΔSHS>3)
DAS 28 CRP
Low
Moderate
High
MBDA Score
Wanying L, Sasso EH, van der Helm-can Mil AHM, et al. Rheumatology 2016; 55:357-366
47. Using MBDA Score in Undiff Arthritis
100
80
60
40
20
MBDAScore
RA-RA
n=81
UA-RA
n=16
UA-UA
n=29
p=0.001 p=0.132
Maijer K, Wanying L, Sasso EH, et al. Ann Rheum Dis 2015; 74 (11): 2097-99
48. MBDA Score in JIA
Patients 31 children with JIA with mean duration of 5
years (RF+ / RF- /oligoarticular)
Comparison MBDA vs JADAS
Methodology Cross sectional observational study
Results • Moderate correlation between MBDA and
JADAS (r=0.68)
• Similar biomarker profile between those
with CID and controls
• Difference between CID/ controls and
active disease seen in SAA, CRP, IL6 and
MMP3
Ringold S, Lu L, Wallace CA, et al. Arthritis Rheum 2014l 66 (S3): S10-S11.
49. Tailoring First Line Biologic Therapy
from the Italian BiologicsTherapy (ITABIO) Board
“Any biologic may be used in the
absence of driving factors in RA.”
High Infection Risk or +LTBI
Abatacept
Tocilizumab
Etanercept
High ACPA or RF
Tocilizumab
Abatacept
High CV Risk
Etanercept
Anti-TNF inhibitors
Cost Effectivess
Etanercept
bs Infliximab
Cantini F, Nannini C, Cassara E, et al. Semin Arthritis Rheum 2015; S0049-0172.
50. Tailoring First Line Biologic Therapy
from the Italian BiologicsTherapy (ITABIO) Board
Anterior Uveitis / IBD
Mabs Anti-TNF
Inhibitors
High Infection Rate or +TB
Ustekinumab
Etanercept
Enthesitis, Dactylitis, Severe Skin
or Joint Symptoms
Anti-TNF inhibitors
Ustekinumab
Metabolic Syndrome or
High CV Disease Risk
Etanercept
Cantini F, Nannini C, Cassara E, et al. Semin Arthritis Rheum 2015; S0049-0172.
Spondyloarthritis / Psoriatic Arthritis
51. SUMMARY
• Reviewed the latest criteria on gout
and lupus
• Describe the state of biomarker
studies in OA
• Discuss the use of MBDA in RA
• Enumerated recommendations from
the ITABIO Board on tailoring first line
biologic therapy in RA/ SpA/ PsA
52. SLIDES would be made available
(for viewing) SOON at
RheumatologyWebsite (rheumatology.org.ph)
PersonalWebsite (phrheumajr.wordpress.com)
Editor's Notes
<=4 NOT GOUT in 95%
>=8 GOUT in 87%
>4-<8 UNCERTAIN
Draining OR chalk-like subcutaneous nodule under transparent skin, often with overlying vascularity over joints, ears, olecranon bursae, finger pads, tendons
In order to make a diagnosis of knee OA – we look into the patient’s background risks for developing the condition, we look for signs and symptoms suggesting the diagnosis and request for radiographs to looks for features supporting the diagnosis of OA. Past criteria for OA have focused on a constellation of symptoms, PE findings and radiographic changes in order to make a diagnosis.
The 2010 EULAR Criteria is different in that it focuses on risk factors and clinical features to make the diagnosis.
How do we diagnose then?
In adults >45 complaining of knee pain, a diagnosis of knee osteoarthritis can be made with 99% probability if all symptoms and signs are present
In adults > 40 years with knee pains, a diagnosis of knee OA can be confidently made if all symptoms AND at least one physical examination finding is present
ALSO, a confident diagnosis of knee OA can be made even without radiographic evaluation (which can still be ordered but whose purpose will be for anatomic evaluation) and even if an ordered radiograph turns out normal.
The 2010 EULAR Criteria is different in that it focuses on risk factors and clinical features to make the diagnosis.
How do we diagnose then?
In adults >45 complaining of knee pain, a diagnosis of knee osteoarthritis can be made with 99% probability if all symptoms and signs are present
In adults > 40 years with knee pains, a diagnosis of knee OA can be confidently made if all symptoms AND at least one physical examination finding is present
ALSO, a confident diagnosis of knee OA can be made even without radiographic evaluation (which can still be ordered but whose purpose will be for anatomic evaluation) and even if an ordered radiograph turns out normal.
The US FDA and EMA have recently published guidelines recommending a higher level of integration of biomarkers in development and testing of new drugs – to advance decision making on dosing, time, treatment effect, risk/ benefit analysis and personalized medicine.
Why biomarkers in drug development?
To identify a subpopulation of responsive subjects that will provide the best evidence for rejecting the null hypothesis of no treatment effect and thereby demonstrate the efficacy and safety of a drug candidate.
To assess individual patient’s response to treatment – clinicians will be able to conclude whether treatment has the desired effect or not.
For 2014/ 2015, most biomarkers in OA studied were either biomarkers of joint tissue turnover and biomarkers of the inflammatory status. But more than the nature of biomarkers, most investigators were interested in the utility of these tests and their potential impact in influencing management.
BIPED Classification - evaluation and qualification of the utility of biomarkers. (* tested in large studies)
S ADAMTS4 – found in early OA > intermediate and late OA while S ADAMTS5 was higher in intermediate and late OA than early OA and controls. SF ARGS in acute knee injury. S/ SF were increased following knee injury. C2C P/ SF Autotaxin – severity of RKOA and WOMAC scores. S C Col 10 – elevated in KL 2 vs KL 0 and those with above normal hsCRP. CCL 3 severity of KOA. CCL 4 associated with severity of RKOA. CRGP – correlated with KL score, total WOMAC. S COMP increased in severity of hand OA but no correlation with RHOA. CRPM – correlated with degree of central sensitization. S FGF21 – correlated with radiographic bone loss. MMP1 and MMP3 correlated with intermediate and late OA but not with early OA and controls. Sclerostin – negative correlation with RKOA. Increased SF TNF alpha, SPARC and IL-8 were associated with osteochondral fractures.
P/ SF CD14 – associated with JSN and osteophytosis and osteophyte progression. Also seen to correlate with severity of knee pain. CD163 – osteophyte progression. S HMWAPN associated with progression of RHOA.
Leptin (Elderly Boston Study Population), high leptin level were associated with increased risk for OA – suggesting that part of the BMI risk factor is mediated through leptin concentrations.
BDNF – correlated with RKOA and WOMAC severity. Fib3-2 (in the PROOF study), high levels of Fibulin 3 epitopes were highly associated with clinical KOA among middle aged and obese women.
Not all assessments use the same set of paramters
Some assessments like RAPID emphasize patient reported outcomes (PROs)
Others use a combination of patient reported outcomes, physician assessments and laboratory tests
OBVIOUSLY, not included are imaging modalities
There are concerns about inter- and intra- observer variation. Some problems are observed. The joint counts for example – may pose a challenge – swollen – obesity OR tender points OR swelling in OA OR fibrous thickening
ACR – reflects visit to visit changes in disease activity
DAIs – represents single point in time assessment
ACR 20/50/70, DAS 28 and Health Assessment Questionnaires are required by regulatory and licensing agencies for product approval in the US
The target in treating RA is remission. No cure is available. Remission offers the possibility of better QOL and minimal disability
Staged approach used in biomarker discovery and prioritization and algorithm development
The target in treating RA is remission. No cure is available. Remission offers the possibility of better QOL and minimal disability
MBDA had significant correlation with DAS28 CRP in distinguishing low/ remission disease activity vs moderate/ high disease activity. It was an independent predictor of disease activity measures. MBDA scores went down from 53 (SD 18) to 39 (SD 16). MBDA scores in the intensive treatment group went down from 53 (17) to 35 (14) while the usual care group it went down from 55 (20) to 56 (19).
Numerators = number of patients with radiographic progression
Denominators = no of patients meeting MBDA and DAS scores
Agreement between MBDA Score and DAS28 ESR seen in 70% of cases
The target in treating RA is remission. No cure is available. Remission offers the possibility of better QOL and minimal disability
Systematic review of the literature to identify English-language articles on the variables influencing the first-line biologic choice, including the efficacy and safety of the drug, the route of administration, the availability of response predictorbiomarkers, the need of monotherapy, the patient socio-economic status, lifestyle, cultural level, personality, fertility and childbearing potential in women, the presence of comorbidities, the host-related risk factors for infection and latent tuberculosis infection (LTBI) reactivation, the cardiovascular (CV) risk, and costs