This document discusses challenges in developing drugs to treat osteoarthritis (OA) by modifying disease structure. OA is a complex disease involving multiple joint structures. Clinical trials must demonstrate that changes in structural endpoints, like cartilage thickness, reliably predict improvements in how patients feel and function. However, there is a lack of standard definitions for structural progression and uncertainty if structural changes translate to clinical benefits. Large trials are needed to concurrently assess structural and symptomatic effects. Biomarkers may help link structural and clinical outcomes if changes reasonably reflect patient benefits. Developing drugs targeting specific joint structures like cartilage or subchondral bone remains difficult given OA's complexity.
Presentation given by Dr Adnan Saithna, Professor of Orthopedic Surgery at AAOS 2020, on factors influencing outcomes of a validated return to sports test battery after ACL reconstruction
Functional Independence Measure (FIM)
Is an 18-item, 7-level ordinal scale
Is designed to assess areas of dysfunction in activities that commonly occur
The scale has few cognitive, behavioral, and communication-related functional items
Is not specific for spinal cord injuries but is designed to assess neurological, musculoskeletal, and other disorders.
Presentation given by Dr Adnan Saithna, Professor of Orthopedic Surgery at AAOS 2020, on factors influencing outcomes of a validated return to sports test battery after ACL reconstruction
Functional Independence Measure (FIM)
Is an 18-item, 7-level ordinal scale
Is designed to assess areas of dysfunction in activities that commonly occur
The scale has few cognitive, behavioral, and communication-related functional items
Is not specific for spinal cord injuries but is designed to assess neurological, musculoskeletal, and other disorders.
Clinical prediction rule in spinal painNityal Kumar
This lecture is on spinal pain and the clinical methods used in treating the pain. Clinical prediction rules is a research method done systematically describing when to use which method of treatment approach
Clinical prediction rule in spinal painNityal Kumar
This lecture is on spinal pain and the clinical methods used in treating the pain. Clinical prediction rules is a research method done systematically describing when to use which method of treatment approach
The Challenges of Sarcopenia: Definition, Underlying Mechanisms, Intervention...InsideScientific
During this webinar, Drs. Peterson and Guralnik will discuss sarcopenia, the physiological mechanisms underlying the disease, and the current avenues of treatment and assessment that are being researched and developed for patients.
Sarcopenia is the age-related loss of muscle that causes decreased strength and functional limitations. Muscle loss occurs universally in people as we age, but some people lose muscle at an accelerated rate compared to others. While chronic disease can cause sarcopenia, it can also result from a sedentary lifestyle, hospitalizations and extended bed rest due to other conditions.
A gradual decline in muscle mass and strength begins around 30 years of age with this condition, and annual losses get larger throughout life. The self-reporting of functional difficulties to health care providers may give an indication that sarcopenia is present, but a more precise definition is needed for research and clinical use.
Efforts made in Europe and the US have used grip strength, gait speed and lean mass to define sarcopenia, but these definitions lead to large differences in prevalence rate and discordance in who is labelled as “sarcopenic”. To assess this condition, lean mass as measured by dual x-ray absorptiometry (DXA) may not accurately reflect actual muscle mass, but a new technique using dilution of deuterium-labelled creatine may prove to be superior in clinically diagnosing sarcopenia. Currently, a consensus has not been reached on the clinical outcome assessments that can be used by regulatory agencies to judge the effectiveness of drugs for sarcopenia.
A number of potential interventions are being explored to treat sarcopenia in older people, but no drugs are currently approved for this condition. The antidiabetic drug metformin shows promise in preventing many age-associated conditions, but appears to blunt the benefits of exercise on muscle. Senolytic drugs, which clear senescent cells, may improve muscle repair following injury preferentially in older individuals.
Evidence based management of osteoarthritis in primary care - Dr Jonathan Quickepcsciences
Dr Jonathan Quicke is an NIHR Academic Clinical Lecturer in Physiotherapy (Keele University). Dr Quicke presented at the 2017 Musculoskeletal Education Day, where he discussed how we can ensure that best practice can be implemented within general practice for patients suffering with osteoarthritis
PCHAlliance conducted a systematic review of published literature to gather the available data on health outcome measures, reviewing over 1,450 citations. Fifty-three randomized controlled studies and trials were selected for analysis, on topics related to mobile technologies, remote patient monitoring, web-based counseling and other personal connected health technologies. This publication aims to set an initial baseline for the current body of evidence in personal connected health in key areas, namely behavior change and self-care, remote patient monitoring, remote counseling and mental health, as well as more broadly through key condition-specific studies.
Download the paper here: http://www.pchalliance.org/personal-connected-health-state-evidence-and-call-action
The Chiro Hub is at the forefront of providing advanced treatment in the field of balance, dizziness and postural disorders. Physiosensing, using unparalleled accuracy in obtaining objective measures, is superior when it comes to the management of conditions such as concussion, whiplash, neurologic and orthopaedic conditions.
> Why HEOR?
> Costs, Consequences and Perspectives
> Key Stakeholders in HEOR
> What is Health Economics and Pharmaco-economic Research?
> Economic Evaluations
> Incremental Cost Effectiveness Ratio (ICER)
> Concept of HRQoL
> Comparative Effectiveness Research (CER)
> Pragmatic Clinical Trials
> Observational Studies
> Systematic Reviews and Meta-Analysis
> Application of CER
> Health Technology Assessment (HTA)
> Real World Evidence (RWE)
> Patient Reported Outcomes (PROs)
> Patient Focused Drug Development (PFDD)
> Application of Health Economic Evaluations
> Challenges and Barriers
This primer is intended for the non-clinician. After reading it, hopefully you will have a slightly better understanding of the complexities of clinical trials.
Similar to Approval of Therapeutics for Osteoarthritis in 2019 (20)
Real-life examples of manuscript reviews Comparison and contrast of useful ...OARSI
Aileen Davis, PhD
Senior Scientist and Division Head,
Health Care and Outcomes Research,
Krembil Research Institute,
University Health Network and
Professor, University of Toronto
Real-life examples of manuscript reviews Comparison and contrast of useful ...OARSI
Aileen Davis, PhD
Senior Scientist and Division Head,
Health Care and Outcomes Research,
Krembil Research Institute,
University Health Network and
Professor, University of Toronto
How to write an effective review (and help editors and authors)OARSI
Rik Lories, MD PhD Professor of Experimental Rheumatology
Director of the Laboratory of Tissue Homeostasis and Disease
KU Leuven, Skeletal Biology and Engineering Research Centre and University Hospitals Leuven, Division of Rheumatology
Joel A Block, MD
The Willard L Wood MD Professor, and
Director, Division of Rheumatology, Rush University Medical Center
Editor in Chief, Osteoarthritis and Cartilage
Real-life examples of manuscript reviews Comparison and contrast of useful ...OARSI
Senior Scientist and Division Head,
Health Care and Outcomes Research, Krembil Research Institute,
University Health Network and
Professor, University of Toronto
Professor of Radiology and Medicine
Vice Chair, Academic Affairs
Assistant Dean of Diversity
Director, Quantitative Imaging Center (QIC)
Boston University School of Medicine, Boston, MA
Nuts & Bolts of Systematic Reviews, Meta-analyses & Network Meta-analysesOARSI
Director, Applied Health Research Centre (AHRC)
Li Ka Shing Knowledge Institute, St. Michael’s Hospital
Professor, Department of Medicine & IHPME, University of Toronto
Tier 1 Canada Research Chair in Clinical Epidemiology of Chronic Diseases
Structural Targets for Prevention of Post Traumatic OAOARSI
David Hunter MBBS, PhD, FRACP
Florance and Cope Chair of Rheumatology, Professor of Medicine
University of Sydney and Royal North Shore Hospital
Chair, Institute of Bone and Joint Research
Chair, Musculoskeletal, Sydney Medical Program
Consultant Rheumatologist, North Sydney Orthopedic and Sports Medicine
Building a translational team for impacting public policy Pre-Congress Worksh...OARSI
David Hunter MBBS, PhD, FRACP
Florance and Cope Chair of Rheumatology, Professor of Medicine
University of Sydney and Royal North Shore Hospital
Chair, Institute of Bone and Joint Research
Consultant Rheumatologist, North Sydney Orthopedic and Sports Medicine
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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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
3. What is Needed For Approval: In General
• Non clinical data performed in terms of GLP
• Manufacturing practices performed in terms of GMP
• Clinical data performed in terms of GCP
– Two replicate adequate and well controlled trials
– One if the p < 0.001 (robust p value)
5. What Are Potential Measurable Outcomes?
CLINICAL OUTCOMES
Biomarkers Performance
Clinician-
Reported
Observational
Patient-
Reported
• Walking
time/distance
• Range of
motion
• Muscle strength
• Global
impression of
severity
• Joint
replacement
• Quantity of
rescue
medication
used for pain
• Pain
• Function
• Distress
• Biochemical
(urinary CTXII)
• Imaging (MRI
cartilage
thickness;
radiographic
joint space
narrowing)
SURVIVAL
Adapted from Patrick et al. 2014
Figure 3
6. Problems with OA Development
• Typical Development program
– Signs and symptoms
• Pain
• Function
• Patient global
• Structural Development Program
– Structural benefit must be linked in some manner with symptomatic
benefit
– Assess benefit to entire joint
• Halt progression of damage
• Reverse damage
7. Why is this so?
• OA is multifactorial in cause, with an unpredictable
progression and has a complex etiopathogenesis
– Is it a progressive disease of the whole joint: subchondral bone
followed by effects on cartilage, with consequent increase in low
grade inflammation
– Is it a progressive disease of cartilage subsequently having impact
on subchondral bone and consequent increase in low grade
inflammation
• Is it a progressive disease of abnormal cartilage sustaining normal load or
normal cartilage being subjected to abnormal loading
– All of the above?
9. Why is This So?
• In assessing OA there is a recognized discordance between
structural changes and signs, symptoms and function
• There is a lack of standard definitions of disease progression by
xray or other imaging techniques
• There is an absence of measured endpoints to reliably assess the
ability of a product to alter OA disease progression
10. These Issues Then Lead to
• Because of the complex and variable pathologic changes through which OA impairs
function and leads to long-term disability and/or joint replacement,
– It is unclear what magnitude of change in structural endpoints would translate to a
clinically meaningful benefit to patients
• i.e., reliably predict both reduced pain and increased function or prolonged time to end-stage
disease
• To accept structural endpoints as valid outcome measures for accelerated approval,
there should be substantial confidence that an effect on the candidate structural
endpoint will reliably predict an effect on the clinical outcomes
– Based on empirical evidence from randomized, controlled comparisons from clinical trials
– Based on a comprehensive understanding of the disease process and product
mechanism of action,
11. Goals of a Structure Modifying
Development Program
• The ultimate goal of treatments related to alteration of structural
damage (targeting the underlying pathophysiology associated with
OA) is to avoid or significantly delay the complications of joint
failure and the need for joint replacement
• An equally important goal would be reduce the deterioration of
function and worsening of pain
• Either might be considered important clinically relevant outcomes
12. Structural Development
Program
• If there is an identified method of measuring change in the
joint structure, is that change correlated with how a patient
feels, functions or survives?
• Currently all of these measures must be concurrent
– What ever benefit is demonstrated, the powering of the clinical trial
must be able to provide measure of benefit both in terms of structure
and symptoms
13. An Example of a Structure Modifying Trial
• Risedronate in the treatment of OA
• 23,000 patients screened with 2300 recruited into trial for
2 years
• Signs and symptoms and flouroscopically positioned
specialized xray with central reading
• Post hoc small number of patients who were determined
to be rapid progressors evidenced structural modification
but not able to be identified at start of trial and not linked
to symptom benefit
Bingham CO III, 2006; Arthritis Rheum 54: 3494-3507
14. Biomarker and Surrogate Endpoints
Definitions
Biomarker: biological marker or imaging marker is a
characteristic that is measured and evaluated as an
indicator of normal biologic processes, pathogenic
processes, or pharmacologic responses to a
therapeutic intervention.
Clinical endpoint- A characteristic or variable that
measures how a patient feels, functions or survives
Surrogate endpoint- A marker intended to substitute
for a clinical endpoint
15. Surrogates as Drug Approval
Measures
A surrogate endpoint of a clinical trial is a laboratory measurement,
imaging measure, or a physical sign used as a substitute for a clinically
meaningful endpoint that measures directly how a patient feels,
functions, or survives.
Changes induced by a therapy on a surrogate endpoint are expected to
reasonably likely reflect changes in a clinically meaningful endpoint.
18. Conclusions
• OA has significant patient impact causing pain, loss of function, increased
disability and significant risk of increased mortality, in some patients
• OA affects a large population
• Developing drugs to alter the complex structures involved in the joint will be
difficult
– Target cartilage?
• Decrease loss?
• Stimulate new cartilage growth?
– Target subchondral bone? And show what?
– Both? And do changes link to how a patient feels, functions or survives
