Examples of Traditional vs. Precision Therapies
1) James Kennedy, Centre for Addiction and Mental Health
2) Niya Chari, CBCN
3) Michael Duong, Roche
4) Linsay Davis, AveXis
5) Josh Silvertown, Bayer Canada
Sex- and Age-specific Increases in Suicide Attempts by Self-Poisoning in the ...Δρ. Γιώργος K. Κασάπης
There was a more than twofold increase in the rate of suspected self-poisoning suicide cases between 2011 and 2018, according to a new study that looked at more than 1.6 million such cases.
Here’s what else you need to know:
•Overall trends: Cases of suicide attempts by self-poisoning doubled in those aged 10-18 between 2011 and 2018, rising from around 39,000 to more than 78,000.
•Gender: More girls than boys attempted suicide by self-poisoning. The rate of intentional attempts among girls 10-18 also steadily increased from 2011-2018.
•Outcomes: The number of serious outcomes — including death and hospitalizations — as a result of the poisoning increased 235% between 2000 and 2018, and more than 1,400 children died.
Sex- and Age-specific Increases in Suicide Attempts by Self-Poisoning in the ...Δρ. Γιώργος K. Κασάπης
There was a more than twofold increase in the rate of suspected self-poisoning suicide cases between 2011 and 2018, according to a new study that looked at more than 1.6 million such cases.
Here’s what else you need to know:
•Overall trends: Cases of suicide attempts by self-poisoning doubled in those aged 10-18 between 2011 and 2018, rising from around 39,000 to more than 78,000.
•Gender: More girls than boys attempted suicide by self-poisoning. The rate of intentional attempts among girls 10-18 also steadily increased from 2011-2018.
•Outcomes: The number of serious outcomes — including death and hospitalizations — as a result of the poisoning increased 235% between 2000 and 2018, and more than 1,400 children died.
Contemporary Management of HIV. New Data From IDWeek 2018 and Other Fall 2018...hivlifeinfo
Contemporary Management of HIV. New Data From IDWeek 2018 and Other Fall 2018 HIV Conferences
Format: Microsoft PowerPoint (.ppt)
File Size: 690 KB
Released: December 5, 2018
20180202 3 j. lombard genomind milan relazione part 2 to pub.pptxRoberto Scarafia
https://www.linkedin.com/pulse/simposio-toma-implementazione-della-farmacogenetica-nel-scarafia/
https://www.linkedin.com/pulse/malattie-psichiatriche-e-neurologiche-arriva-toma-il-test-scarafia/
2 febbraio 2018, Sala Congressi Laboratorio TOMA
Relatori: Dr. J. Lombard, Dr.ssa F.R. Grati, Dr.ssa S. De Toffol
BREVE PREMESSA
La farmacogenetica studia l’influenza dei fattori genetici sull’attività di un farmaco, la sua assimilazione e il suo metabolismo allo scopo di massimizzarne l’efficacia terapeutica e minimizzare gli effetti avversi. I fattori genetici possono giustificare fino al 95% della variabilità interpersonale nella risposta e nelle reazioni avverse a determinati trattamenti farmacologici. Finora la diagnosi ed il trattamento farmacologico in psichiatria si sono basati principalmente sul un protocollo ‘trial and error’ tramite colloquio, osservazione clinica e analisi di laboratorio costituivano esclusivamente un complemento per valutare possibili effetti collaterali o i livelli plasmatici di alcuni farmaci. L’introduzione di test di farmacogenetica consente di fornire al clinico informazioni costitutive dell’individuo relativamente al metabolismo di molti farmaci e la potenziale risposta in determinati contesti clinici al fine di ridurre i tempi ottenimento del trattamento efficace personalizzato e arricchire con le più recenti informazioni genetiche la gestione terapeutica dei pazienti.
OBIETTIVI FORMATIVI
Introdurre i principi scientifici alla base del test genetico che si presenterà durante il corso, il significato, la funzione e la rilevanza clinica per la salute mentale di ciascun gene indagato dal test;
L’utilità clinica del test Genecept: presentare come vengono riportati i risultati del test e come meglio interpretarli;
Presentare alcuni casi clinici reali per discutere circa l’utilità di un trattamento farmacologico guidato dai risultati del test genetico rispetto all’approccio tradizionale ‘trial and error’
Audio and slides for this presentation are available on YouTube: http://youtu.be/49JdPPPRFNw
Cognitive effects of cancer and cancer treatment -- also known as chemobrain -- are widely recognized. Dr. Fremonta Meyer from Dana-Farber Cancer Institute, talks about what chemobrain is, research into its effects, and how to manage and/or treat it.
For more information, watch our YouTube video on chemobrain here:
http://www.youtube.com/watch?v=iK1UqTnD5GI
This is a presentation explaining a brief background of Opioid Use Disorder, the methods of National Survey on Drug Use and Health, data analysis of selected risk factors to OUD, and possible solutions.
Pharmacology for Physiotherapy Book By Padmaja Udaykumar Second Edition.Khalid Ghaznavi
Pharmacology for Physiotherapy Book
By Padmaja Udaykumar Second Edition.
This consists of a complete book version. I hope this will be helpful for you.
Alex's Lemonade Stand Foundation holds an annual Childhood Cancer Symposium in Philadelphia. It is designed to be an educational resource, providing families with the opportunity to learn about issues and topics of treatment and beyond, while meeting other families in a group setting. Registration is free and is open to all those touched by childhood cancer, including patients and their siblings.
Hear from speaker Rochelle Bagatell, MD of Children's Hospital of Philadelphia as she discusses clinical trials and experimental treatments in childhood cancer cases.
For more information on Alex's Lemonade Stand Foundation's childhood cancer resources, click here: http://www.AlexsLemonade.org
Personalized medicine involves the prescription of specific therapeutics best suited for an individual based on their genetic or proteomic profile. This talk discusses current approaches in drug discovery/development, the role of genetics in drug metabolism, and lawful/ethical issues surrounding the deployment of new health technology. I highlight some bioinformatic roles in the drug discovery process, and discuss the use of semantic web technologies for data integration and knowledge discovery..
iCAAD London 2019 - Antonio Metastasio - PERSONALISED MEDICINE IN THE TREATM...iCAADEvents
Personalised medicine is considered the next frontier of health care. The role of genetic testing in psychiatry and in addictions medicine, however, has been recently critically reviewed. Are genetic tests helpful in assessing and managing these conditions?
2015 04-13 Pharma Nutrition 2015 Philadelphia Alain van GoolAlain van Gool
Keynote lecture at the Pharma-Nutrition 2015 conference, outline global paradigm shifts and activities in pharma, personalized healthcare and pharmanutrition combination therapies.
Contemporary Management of HIV. New Data From IDWeek 2018 and Other Fall 2018...hivlifeinfo
Contemporary Management of HIV. New Data From IDWeek 2018 and Other Fall 2018 HIV Conferences
Format: Microsoft PowerPoint (.ppt)
File Size: 690 KB
Released: December 5, 2018
20180202 3 j. lombard genomind milan relazione part 2 to pub.pptxRoberto Scarafia
https://www.linkedin.com/pulse/simposio-toma-implementazione-della-farmacogenetica-nel-scarafia/
https://www.linkedin.com/pulse/malattie-psichiatriche-e-neurologiche-arriva-toma-il-test-scarafia/
2 febbraio 2018, Sala Congressi Laboratorio TOMA
Relatori: Dr. J. Lombard, Dr.ssa F.R. Grati, Dr.ssa S. De Toffol
BREVE PREMESSA
La farmacogenetica studia l’influenza dei fattori genetici sull’attività di un farmaco, la sua assimilazione e il suo metabolismo allo scopo di massimizzarne l’efficacia terapeutica e minimizzare gli effetti avversi. I fattori genetici possono giustificare fino al 95% della variabilità interpersonale nella risposta e nelle reazioni avverse a determinati trattamenti farmacologici. Finora la diagnosi ed il trattamento farmacologico in psichiatria si sono basati principalmente sul un protocollo ‘trial and error’ tramite colloquio, osservazione clinica e analisi di laboratorio costituivano esclusivamente un complemento per valutare possibili effetti collaterali o i livelli plasmatici di alcuni farmaci. L’introduzione di test di farmacogenetica consente di fornire al clinico informazioni costitutive dell’individuo relativamente al metabolismo di molti farmaci e la potenziale risposta in determinati contesti clinici al fine di ridurre i tempi ottenimento del trattamento efficace personalizzato e arricchire con le più recenti informazioni genetiche la gestione terapeutica dei pazienti.
OBIETTIVI FORMATIVI
Introdurre i principi scientifici alla base del test genetico che si presenterà durante il corso, il significato, la funzione e la rilevanza clinica per la salute mentale di ciascun gene indagato dal test;
L’utilità clinica del test Genecept: presentare come vengono riportati i risultati del test e come meglio interpretarli;
Presentare alcuni casi clinici reali per discutere circa l’utilità di un trattamento farmacologico guidato dai risultati del test genetico rispetto all’approccio tradizionale ‘trial and error’
Audio and slides for this presentation are available on YouTube: http://youtu.be/49JdPPPRFNw
Cognitive effects of cancer and cancer treatment -- also known as chemobrain -- are widely recognized. Dr. Fremonta Meyer from Dana-Farber Cancer Institute, talks about what chemobrain is, research into its effects, and how to manage and/or treat it.
For more information, watch our YouTube video on chemobrain here:
http://www.youtube.com/watch?v=iK1UqTnD5GI
This is a presentation explaining a brief background of Opioid Use Disorder, the methods of National Survey on Drug Use and Health, data analysis of selected risk factors to OUD, and possible solutions.
Pharmacology for Physiotherapy Book By Padmaja Udaykumar Second Edition.Khalid Ghaznavi
Pharmacology for Physiotherapy Book
By Padmaja Udaykumar Second Edition.
This consists of a complete book version. I hope this will be helpful for you.
Alex's Lemonade Stand Foundation holds an annual Childhood Cancer Symposium in Philadelphia. It is designed to be an educational resource, providing families with the opportunity to learn about issues and topics of treatment and beyond, while meeting other families in a group setting. Registration is free and is open to all those touched by childhood cancer, including patients and their siblings.
Hear from speaker Rochelle Bagatell, MD of Children's Hospital of Philadelphia as she discusses clinical trials and experimental treatments in childhood cancer cases.
For more information on Alex's Lemonade Stand Foundation's childhood cancer resources, click here: http://www.AlexsLemonade.org
Personalized medicine involves the prescription of specific therapeutics best suited for an individual based on their genetic or proteomic profile. This talk discusses current approaches in drug discovery/development, the role of genetics in drug metabolism, and lawful/ethical issues surrounding the deployment of new health technology. I highlight some bioinformatic roles in the drug discovery process, and discuss the use of semantic web technologies for data integration and knowledge discovery..
iCAAD London 2019 - Antonio Metastasio - PERSONALISED MEDICINE IN THE TREATM...iCAADEvents
Personalised medicine is considered the next frontier of health care. The role of genetic testing in psychiatry and in addictions medicine, however, has been recently critically reviewed. Are genetic tests helpful in assessing and managing these conditions?
2015 04-13 Pharma Nutrition 2015 Philadelphia Alain van GoolAlain van Gool
Keynote lecture at the Pharma-Nutrition 2015 conference, outline global paradigm shifts and activities in pharma, personalized healthcare and pharmanutrition combination therapies.
For this Discussion, review the case Learning Resources and the .docxevonnehoggarth79783
For this Discussion, review the case Learning Resources and the case study excerpt presented. Reflect on the case study excerpt and consider the therapy approaches you might take to assess, diagnose, and treat the patient’s health needs.
Case: An elderly widow who just lost her spouse.
Subjective: A patient presents to your primary care office today with chief complaint of insomnia. Patient is 75 YO with PMH of DM, HTN, and MDD. Her husband of 41 years passed away 10 months ago. Since then, she states her depression has gotten worse as well as her sleep habits. The patient has no previous history of depression prior to her husband’s death. She is awake, alert, and oriented x3. Patient normally sees PCP once or twice a year. Patient denies any suicidal ideations. Patient arrived at the office today by private vehicle. Patient currently takes the following medications:
•
Metformin 500mg BID
•
Januvia 100mg daily
•
Losartan 100mg daily
•
HCTZ 25mg daily
•
Sertraline 100mg daily
Current weight: 88 kg
Current height: 64 inches
Temp: 98.6 degrees F
BP: 132/86
By Day 3 of Week 7
Post
a response to each of the following:
• List three questions you might ask the patient if she were in your office. Provide a rationale for why you might ask these questions.
• Identify people in the patient’s life you would need to speak to or get feedback from to further assess the patient’s situation. Include specific questions you might ask these people and why.
• Explain what, if any, physical exams, and diagnostic tests would be appropriate for the patient and how the results would be used.
• List a differential diagnosis for the patient. Identify the one that you think is most likely and explain why.
• List two pharmacologic agents and their dosing that would be appropriate for the patient’s antidepressant therapy based on pharmacokinetics and pharmacodynamics. From a mechanism of action perspective, provide a rationale for why you might choose one agent over the other.
• For the drug therapy you select, identify any contraindications to use or alterations in dosing that may need to be considered based on the client’s ethnicity. Discuss why the contraindication/alteration you identify exists. That is, what would be problematic with the use of this drug in individuals of other ethnicities?
• Include any “check points” (i.e., follow-up data at Week 4, 8, 12, etc.), and indicate any therapeutic changes that you might make based on possible outcomes that may happen given your treatment options chosen.
Respond to the these discussions. All questions need to be addressed.
Discussion 2 Me
Treatment of a Patient with Insomnia
The case presented this week, is that of a 75-year-old widow who just lost her spouse 10-months ago. Th patient presents with chief complaints of insomnia. Past medical history of DM, HTN, and MDD is reported. Since the passing of her husband, she states her depression has gotten worse .
Similar to Day 1: 1:00pm- 2:30pm Panel Slides (Nov 18) Access to Innovation Conference 2019 3 views (20)
On this webinar, we’ll hear from experts on the issue and invite an open conversation with stakeholders. We need discussion, shared questions and answers and a review of case studies, which is why we are hosting this session.
Panelist:
Neil Palmer, Principal Consultant, WN Palmer & Co. and former PMPRB staff
Michael Dietrich, Executive Director, Policy, Innovative Medicines Canada
Laurene Redding, Global Head, Strategic Pricing (ex-China), BeiGene
Durhane Wong-Rieger, President & CEO, CORD
Moderator: Bill Dempster, CEO, 3Sixty Public Affairs
CORD Rare Drug Conference: June 8-9, 2022
Registries and Real-World Data
INFORM RARE: Beth Potter, Alexandra Wyatt, Pranesh Chakraborty,
Monica Lamoureux, John Adams, Kim Angel
CORD Rare Drug Conference: June 8-9, 2022
Registries and Real-World Data
INFORM RARE: Beth Potter, Alexandra Wyatt, Pranesh Chakraborty,
Monica Lamoureux, John Adams, Kim Angel Opportunities and Challenges for Data Management
CORD Rare Drug Conference June 8-9, 2022
Global, International, and National Rare Disease Networks
Rare Disease Research Network and National Children’s Hospital - Marshall
Summar, Rare Disease Institute
CORD Rare Drug Conference: June 8-9, 2022
Global, International, and National Rare Disease Networks
WHO-RDI Global Rare Disease Network - Matt Bolz-Johnson, EURORDIS
CORD Rare Drug Conference: June 8-9, 2022
Global, International, and National Rare Disease Networks
Canadian Network of Rare Disease Centres of Excellence - Paula Robeson, Children’s Healthcare Canada
CORD Rare Drug Conference: June 8 - 9, 2022
The Ottawa Pediatric Bone Health Research Group and The Canadian Consortium for Children’s Bone Health/Canadian Alliance for Rare Disorders of the Skeleton - Leanne Ward, CHEO
More from Canadian Organization for Rare Disorders (20)
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!
- 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
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
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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.
Day 1: 1:00pm- 2:30pm Panel Slides (Nov 18) Access to Innovation Conference 2019 3 views
1. Development and Application of
Pharmacogenetic Testing
James L. Kennedy MD, FRCPC, FRSC.
Director, Molecular Brain Science Dept,
Centre for Addiction and Mental Health;
Professor & Co-Head, Division of Brain & Therapeutics
Dept of Psychiatry, University of Toronto.
Fellow of the Royal Society of Canada.
& DJ Mueller, C Zai, A Tiwari, G Zai, Vanessa Goncalves.
CORD Conference Panel, Nov 18, 2019
Univ of Toronto
Disclosures: CAMH is 15% co-
owner of Myriad Canada Ltd;
JLK is Myriad USA SAB
member (unpaid); author on
patents
2. The CAMH Pharmacogenetics Study
(`IMPACT`)
■ Assessment of six liver enzyme genes and two
serotonin system genes
■ Testing feasibility and acceptance by psychiatrists
and by primary care physicians
■ In-hospital genetic panel assay
■ Interpretation of results is given to physician
■ Patient follow-up & Physician survey
www.IM-PACT.ca
www.pharmacogenetics.ca
3. Response & side effects
Additional
factors
CYP450 Dopamine
Serotonin
etc.
PharmacodynamicsPharmacokinetics
Smoking
Ethnicity
NutritionGender
Fitness
Compliance
Age
4.
5. 0
1
2
3
4
5
6
7
8
9
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
2012 2013 2014 2015 2016 2017
Participants (Thousands)
Participants
IMPACT Pharmacogenetics: Publications, Physicians & Patients
11,400
patients
3,200
doctors
178
publications First patient enrolled
through Pharmacists
Personalized Medicine
Experts (PRIME) study
Launch of online
registration
process
IMPACT gene
test becomes
available for
family physicians
First patient
consents
Mobile lab collects
first samples from
rural communities
7. ž Caucasian female of Ashkenazi Jewish descent
¡ Anorexia, severe OCD, depression
¡ Previous meds failed (quetiapine -900mg, & citalopram 20
mg
¡ fluoxetine – 80mg per day x 3 mo – no response
1) genetic test resultsà ultra-rapid CYP2D6 metabolizer
2) Incr fluoxetine to 120mg/d - some response, no side
effects
3) Prozac 160 mg per day!!
§ all her OCD, anxiety and mood symptoms improved
§ She returned to college full time; family very happy
10. Amer J Med Genetics. 2019;180B:46–54
Enrichment of pathogenic variants in genes associated with
inborn errors of metabolism in psychiatric populations
V Sriretnakumar 1, R Harripaul1, JB. Vincent1,4, JL Kennedy1,4, J So1,5.
1. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health; 2.
Department of Psychiatry, University of Toronto; 3 The Fred A. Litwin Family Centre in Genetic Medicine,
University Health Network and Mount Sinai Hospital; Toronto, Ontario, Canada.
Abstract: Many genetic conditions can mimic mental health disorders, with psychiatric symptoms
that are difficult to treat with standard psychotropic medications. We tested the hypothesis that
psychiatric populations are enriched for pathogenic variants associated with inborn errors of
metabolism (IEMs). Using next-gen sequencing, 2046 psychiatric patients were screened for
pathogenic variants in genes associated with: Niemann-Pick disease type C (NPC), Wilson disease
(WD), homocystinuria (HOM), and acute intermittent porphyria (AIP). Among the 2046 cases, carrier
rates of 0.83, 0.98, and 0.20%, for NPC, WD and HOM, and affected rates of 0.10 and 0.24% for
NPC and AIP were seen, respectively. An enrichment of NPC and AIP pathogenic variants was
found in the psychiatric cohort, especially in schizophrenia patients. Thus we find pathogenic
variants in genes associated with IEMs are over-represented in psychiatric populations. Underlying
undiagnosed IEMs could account for the psychiatric symptomatology in a subset of psychiatric
patients. Carriers for IEMs may have an increased risk for psychiatric disorders, particularly in the
context of poor treatment response.
11. Sriretnakumar et al (con’t):
Niemann-Pick C & Porphyria variants are 100x
more frequent in psychiatric populations
Two patients (0.10%) with schizophrenia were found to
have homozygous N931I likely pathogenic variant for
Niemann-Pick C, thus a predicted significant increase vs
0.001% in the general population (p = 2.4×10-4).
Five patients had pathogenic variants in the HMBS gene,
thus a predicted significantly increased rate of Acute
Intermittent Porphyria in the psychiatric cohort (0.24%) vs
0.003 in general population (p = 1.031×10-10).
13. Benefits to Patients and Society
Matching the right drug at the right dosage may
mean that we stand to increase our ability to:
■ Treat patients right the first time
■ Minimize the risk of dangerous side effects
■ Reduce the risk of suicide
■ Give family doctors tools they can use - increasing
their ability to manage patients in the community
■ Save 100s of millions of dollars in prescriptions
that are ineffective or harmful
■ Evidence-based biomedical test reduces stigma
against people with mental illness
15. Forest plot of random-effects meta-analyses of five prospective, randomized
controlled trials of Pharmacogenetic guided therapy on remission in major
depressive disorder.
Meta-Analysis of 5 Pharmacogenetic Guided
Therapy for Depression RCTs Bousman et al, (Dec, 2018)
16. Examples of Traditional vs Precision Therapies: The
Patient Perspective
Niya Chari, Canadian Breast Cancer Network
November 18th-CORD Access to Innovation Conference
19. Clinical Development in a Personalized World
Michael Duong, Ph.D.
Head of Personalized Healthcare
Hoffmann-La Roche Ltd.
20. Source: 1) Health Policy Brief: The Relative Contribution of Multiple Determinants of Health Outcomes, Health Affairs,
August 21, 2014, http://www.healthaffairs.org/healthpolicybriefs/
2) Nature 539, 467-468 (24 November 2016)
Exogenous determinants
(behaviour, socio-economic,
environment, etc.)60%
1,100 terabytesgenerated per lifetime of a person
6 terabytesGenetic
determinants30% generated per lifetime of a patient
Medical/clinical
determinants10% 0.4 terabytes
generated per lifetime of a patient
Determinants of Health Outcomes
Realizing the true potential of personalized healthcare
21. THE PERSONALIZED HEALTHCARE PARADIGM
TREAT THE DISEASE
TREAT THE PATIENT
TREAT THE PERSON
10%
40%
100%
Medical and clinical determinants of health
only allow us to understand the biology of
the disease. Treatment decisions based on
disease information can only capture up to
10% of health outcomes.
Genomic information and multi-omic
information in combination with disease
information has the potential to capture up
to 40% of health outcomes for patients.
Only when we understand the person,
including all their exogenous factors can we
capture up to 100% of health outcomes. To
achieve this, we must collect data on the social
determinants of health – data which are only
available in the real world.
PHC shifts the paradigm from treating the disease to treating the
person. This means that we not only need to understand the
complexities of the disease but also the complexities of the person
and the environment from which they come.
26. a v ex is. com
UNDERSTANDING GENE
REPLACEMENT THERAPY
US-UNB-18-0126 09/18
27. AVEXIS.COM • 2
The AveXis Commitment
We Are: A clinical-stage gene therapy company
relentlessly focused on bringing gene therapies out of
the lab and into the clinical setting for patients and
families who desperately need them.
Our Mission: We are dedicated to harnessing the
potential of gene replacement therapy as an effective
treatment for rare and life-threatening genetic diseases
that affect the nervous system.
28. a v e xi s.c o m
3
CONFIDENTIAL
DISCOVER THEGENETIC EVOLUTION
Although the l ogic be h i nd GRT is simple, the s c i e nc e be h i nd it h a s remained elusive for years. 1
The field of genetics h a s a d v a n c e d significantly from Mendel’s early discoveries. With e m e r g i ng g e n e
therapy approvals a n d others currently b e i n g developed, a new era of ge ne t i c s c i e nc e h a s emerged. 1 - 4
1860s
1953
1984
-
2000
1999
-
2002
2018
Gregor Mendel’ s p e a plant studies help
to establish the rules of
g enetic inheritance. 5
The structure of D N A is
characterized. 2 , 6
Scientists successfully
s e q u e n c e the h u m a n g en ome. 7
A number of individual g e n e therapy c as es result
in complications . A d e ath in a clinical trial sets b a c
k research. 4
C h i n a approves
2003 the first g e n e
therapy in the world.8
2017
FDA approves the
first g e n e therapy
for use in the US.9
es
With numerous
promising c a n d i d a t
in the pipeline, a
Science publication
declares “ G e n e
Therapy C o m e s
of Age.”1
References: 1. Dunbar CE, et al. Science. 2018;359(6372):eaan4672. 2. Gayon J. C RBiol. 2016;339(7-8):225-230. 3. Boudes PF. Eur J Intern Med. 2014;25(1):31-36. 4. Keeler
AM,et al. Clin Transl Sci. 2017;10(4):242-248. 5. Gregor Mendel: the father of modern genetics. May 22, 2013. https://history.nih.gov/exhibits/nirenberg/HS1_mendel.htm. 6. The
Nobel Prize in physiology or medicine 1962. https://www.nobelprize.org/nobel_prizes/medicine/laureates/1962. 7. Hood L & Rowen L. Genome Med. 2013;5(9):79. 8. Zhang WW,
et al. Hum Gen Ther. 2018;29(2):160-179. 9. FDAapproval brings first gene therapy tothe United States. August 30, 2017. https://www.fda.gov/NewsEvents/Newsroom/
PressAnnouncements/ucm574058.htm.
31. Genes are small sections of DNA.
DNA is inherited from your parents
and carries instructions that tell
the body how to function properly.
Specific genes tell the body how
to make specific proteins.
GENE
32. Proteins play important roles
in the body, like helping your
cells to function properly or
acting as the building blocks
of your body.
PROTEIN
33. If a gene has an error, and the
body can’t make a specific
protein, it can be damaging to a
person’s health.
ERROR
34. GENETIC DISEASE
A genetic disease or disorder is the result of an errorin
one or more of a person’s genes.
The disease a person has depends on which gene inhis
or her DNA has the error. Depending on the disease or
disorder, the gene can be inherited from one or both
parents.
Or, sometimes it’s a change that just happens randomly.
A genetic disease caused by a single gene that isfaulty
or missing is called a monogenic disease.
GENETIC DISEASE
35. a v e xi s.c o m
1
1
CONFIDENTIAL
NEWPOSSIBILITIESFOR MONOGENIC DISEASES
M o n o g e n i c diseases are ideal targets for GRT b e c a u s e they c a n result from the loss or malfunction of a single g e n
e . Examples include 1 - 5 :
• Cystic fibrosis ( C F )
• D u c h e n n e muscular dystrophy ( D MD )
• Hemophilia
• Spinal muscular atrophy ( S MA)
• Rett syndrome
• S o m e forms of amyotrophic lateral sclerosis ( ALS)
• S o m e forms of Parkinson’s d i s e a se
References: 1. Saraiva J, et al. J Control Release. 2016;241:94-109. 2. Boudes PF. Eur J Intern Med. 2014;25(1):31-36. 3. Lisowski L, et al. Curr Opin Pharmacol.
2015; 24:59-67. 4. Prakash V,et al. Mol Ther. 2016;24(3);465-474. 5. Klein C & Westenberger A. Cold Spring Harb Perspect Med. 2012;2(1):a008888. 6. Wang CH, et
al.
J Child Neurol. 2007;22(8):1027-1049. 7. Lin CW, et al. Pediatr Neurol. 2015;53(4):293-300.
38. GOAL OF GENE REPLACEMENT THERAPY
Gene replacement
therapy attempts to
give the body a new,
working copy of the
missing or faulty
gene that can make
a particular protein
the body needs.
GOAL OF GENE REPLACEMENT THERAPY
39. HOW GENE
THERAPY WORKS
In the lab, a new, working
copy of a specific gene
is made.
Then the new gene is placed
inside a vector. A vectoracts
like an envelope or a delivery
vehicle. It carries the new
gene to cells throughout the
body.
40. Gene Replacement Therapy Delivery Routes
Collins M & Thrasher A. Proc Biol Sci 2015;282(1821).
FOR MEDICAL EDUCATION ONLY
43. CONSIDERATIONS OF
GENE REPLACEMENT THERAPY
Supportive therapies will continue to be important for patients treated
with gene replacement therapy.
Gene replacement therapy may not be right for all patients.
The safety and efficacy of all gene replacement therapies being studied
are specific to the vector and the disease targeted.
Especially in gene therapy models with gene placement into the cell’s
DNA, risks of undesired effects may occur and are being studied.
Data continues to emerge about the lasting effects of gene replacement
therapy.
Gene replacement therapy may halt progression of disease but does not
reverse the damage that happened before treatment.
CONSIDERATIONS OF
GENE REPLACEMENT THERAPY
46. I am an employee of Bayer Inc.
Bayer has provided an unrestricted sponsorship to support the CORD meeting.
This presentation may contain information regarding indications and/or instructions which differ from the
approved use of products available in Canada.
For complete information on Bayer products, please refer to the respective product monograph:
https://www.bayer.ca/omr/online/vitrakvi-pm-en.pdf
Disclaimers
Presentation to CORD; Nov 18, 2019
Page 2
47. From traditional to precision oncology
Precision Medicine: Innovation in Oncology Clinical Development
Positive predictive
biomarkers
Molecular
profiling
“Conventional
treatment” (eg, systemic
chemotherapy)
Molecular-
driven
therapy
Markers predictive
of resistance or
adverse events
3
48. TRK fusion cancer:
Identified in >24 histologies and counting
Cancers enriched
For TRK fusions
Frequency >75%
Cancers harbouring TRK
Fusions at lower frequencies
5% to 25%
<5%
Adapted from Cocco et al. NTRK fusion-positive cancers and TRK
inhibitor therapy. Nat Rev Clin Oncol. 2018 (ePub ahead of print)
4
49. Larotrectinib’s clinical development program overcame
traditional hurdles in drug development
1. Hyman DM, et al. J Clin Oncol. 2017;35:LBA2501.
2. Drilon A, et al. N Engl J Med. 2018;378:731-739.
3. https://www.bayer.ca/en/media/news/?dt=TlRRPQ==&st=1
First drug to be simultaneously investigated in adult and
pediatric populations1,2.
First drug to be approved by Health Canada with a tumour
agnostic indication.
Presentation to CORD; Nov 18, 2019
50. New ways of treating rare cancer requires new trial
designs
Need for
modification
of clinical
trial design
Increase in
number of
potentially
actionable
mutation targets
Limited number
to recruit into
rare cancer
clinical studies
Existing
evidence for
rare cancer
treatments is
poor
Pediatric
population is
underserved
6
Presentation to CORD; Nov 18, 2019
51. 7
Basket Design –
Biomarker Specific, Histology-Agnostic Cohorts
Tao, Jessica J., Alison M. Schram, and David M. Hyman. "Basket studies: Redefining clinical
trials in the era of genome-driven oncology." Annual review of medicine 69 (2018): 319-331.
Melanoma Thyroid cancer Colorectal cancer Lung cancer
Increase access to
therapy
Small cohorts lead to
faster results
Establishment of standard
of care in rare diseases
Drug activity can depend
on tumour histology
Patient heterogeneity can
impact validity
Challenging to define
controls
Comparison issues due to
excessive testing of
subgroups
Presentation to CORD; Nov 18, 2019
52. 8
Pooling Biomarker-Positive Patients for a Rare
Disease
Hyman et al, 2019. Durability of response with larotrectinib in adult and pediatric patients with TRK fusion cancer. Presented at ESMO 2019. Barcelona, Spain. (445PD)
53. 9
Hyman et al, 2019. Durability of response with larotrectinib in adult and pediatric patients with TRK fusion cancer. Presented at ESMO 2019. Barcelona, Spain. (445PD)
Balancing the challenge (and expectations) of
heterogeneity among rare diseases
54. 10
What is a pragmatic approach to measure efficacy
in basket trials?
Hyman et al, 2019. Durability of response with larotrectinib in adult and pediatric patients with TRK fusion cancer. Presented at ESMO 2019. Barcelona, Spain. (445PD)
Presentation to CORD; Nov 18, 2019
55. 11
Take-home messages
Unique challenges exist in oncology
drug development for tumor agnostic
drugs but can be addressed with
appropriate and innovative trial designs.
Basket trial designs are effective and
feasible in studying treatments for a rare
disease (i.e. pediatric cancers, TRK
fusion cancer).