Longevity Metrics

Lecture Summary
mRNA, or messenger RNA, tells biological cells how to construct proteins from the code (genes) contained in our DNA.  Using synthetic mRNA, multiple organizations have created vaccines that are very effective against COVID19 infection and very safe. The pace of progress has been extraordinary. Join me in learning about this new incredible technology as well as the results of two pandemic-breaking phase 3 clinical trials.

Key Points
-       On January 12, 2020 the Chinese CDC released the genome sequence of the SARs CoV-2 virus.
-       The spike protein on the outside of the Covid viral particle was already identified as a good potential vaccination target from the SARs CoV-1 epidemic (Severe Acute Respiratory Syndrome 1).
-       The COVID19 pandemic declared March 11, 2020 by the WHO, 9 months later we are getting vaccinated.
-       57 vaccine candidate where either in or finished with clinical trials as of Dec, 2020
-       Since the 1990s, mRNA vaccines have been on the drawing board
-       The first successful mRNA vaccines have now been produced and are being used against SARs CoV2 with 95% efficacy. The mRNA is contained in lipid nanoparticles.
-       Side effects have been minimal
-       The phase 3 clinical trials from the BNT162b2 (Pfizer) and mRNA-1273 will be discussed.
-       Normally vaccines take 10 to 15 years to develop. New vaccines in < 1 year, using brand new technology is an insane accomplishment!
-       Honor this extraordinary scientific work by getting the vaccine, stopping the pandemic, and resuming normal life.

References
-       Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Pérez Marc G, Moreira ED, Zerbini C, Bailey R, Swanson KA, Roychoudhury S, Koury K, Li P, Kalina WV, Cooper D, Frenck RW Jr, Hammitt LL, Türeci Ö, Nell H, Schaefer A, Ünal S, Tresnan DB, Mather S, Dormitzer PR, Şahin U, Jansen KU, Gruber WC; C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 Dec 31;383(27):2603-2615.
-       Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Kehtan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2020 Dec 30.
-       https://www.fda.gov/media/142749/download
-       WHO BNT162b2 Info. WHO-2019-nCoV-vaccines-SAGE_evaluation-BNT162b2-2020.1-eng.pdf
-       Huang, Y., Yang, C., Xu, Xf. et al. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin 41, 1141–1149 (2020)
-       Wikipedia. Transcription, translation, Asian Palm Civet, SARs CoV-1, Bell’s Palsy,
-       https://www.cdc.gov/sars/about/faq.html
-       NIH. Clinical Research Trials and You. https://www.nih.gov/health-information/nih-clinical-research-trials-you/basics
-       https://www.fda.gov/patients/drug-development-process/step-3-clinical-research

Lecture Summary

Vaccines are biological tools used to educate our acquired immune system. They have allowed for the prevention of numerous infectious diseases within populations throughout the world.  Additionally, they have made it possible to eradicate diseases on a global scale. I believe that vaccines are the greatest clinical medicine advancement ever made. We depend on these biological tools for a modern life. Sadly, they are currently under attack, mostly from loud voices making scientifically baseless claims. Currently available vaccines prevent millions of deaths and hundreds of millions from suffering every single year.

Key Points 

-       In 2020, there are vaccines available for the prevention of 27 infectious diseases in the United States. Most are highly efficacious.

-       Worldwide there are vaccines available for the prevention of an additional 5 or so diseases. Namely malaria, ebola, dengue, tick-borne encephalitis, and hepatitis E. 

-       Vaccines against at least 30 additional diseases are currently in the pipeline for development.

-       While some vaccines (eg Anthrax) can be dangerous and have common side effects, all vaccines currently recommended for routine use in children and adults are exceptionally safe.

-       Vaccines come in different forms. These include inactivated whole organisms, live-attenuated, subunit (single or multiple antigens), subunit-conjugated, toxoid, heterotypic, mRNA, and other experimental designs.

-       Vaccines prevent infection in individuals. When enough people in a population are vaccinated, communicable diseases cannot effectively spread, thereby offering what is called “herd immunity”.

-       There are very few contraindications to routine vaccinations.

-       A history of severe allergic reaction to any vaccine or component within a vaccine is the most common (exceedingly rare) contraindication.

-       Live attenuated vaccines are contraindicated in pregnancy and certain types of immunodeficiency.

-       Titers are a good way to check for immunity if vaccination status is unknown.

-       Everybody needs to get back on board with vaccines. They are essential for modern life and will be needed to save us from current and future pandemics.

References

-       CDC. Vaccines schedules: https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html; 

-       CDC. Vaccine Information Statements. https://www.cdc.gov/vaccines/hcp/vis/index.html

-       CDC. Diarrhea global killer. https://www.cdc.gov/healthywater/pdf/global/programs/Globaldiarrhea508c.pdf

-       WHO. Vaccine recommendations by country: https://apps.who.int/immunization_monitoring/globalsummary

-       WHO. Individual vaccine pages. Eg. https://www.who.int/news-room/q-a-detail/poliomyelitis-vaccine-derived-polio

-       Wikipedia.org – Vaccines, pages for diseases prevented by vaccines, pages for individual vaccines.

-       Uptodate.com – Childhood vaccines, Adult vaccines, Pages for individual vaccines.

Lecture Summary
The goal of the medical community is the eradication of communicable infectious diseases. Vaccines have given us the tools necessary to create such a disease-free future.  Following complete eradication, vaccinations actually become unnecessary, as with smallpox.  However new human diseases are a constant threat. In fact, this threat has never been greater. More pandemics will come that may be more deadly than COVID-19. We need to be ready and be on the lookout constantly.

 Key Points
-       Smallpox virus (Variola major) formerly killed about 30% of people infected and is thought to have killed 500 million people in its last 100 years of existence, before eradication in 1977.
-       Emerging infectious disease are broadly defined as diseases that have recently increased in prevalence or possibly could in the near future.
-       Completely new, previously unknown disease are also considered emerging.
-       Most new disease come from animal reservoirs 
-       Diseases that infect humans from animal reservoirs can be dangerous as humans often lack immunity. Our bodies are caught off guard and lack defenses.
-       When pathogens obtain mutations, that allow them to spread from human to human, epidemics and even pandemics can occur. This is a dangerous cascade of mutations.
-       The prevalence of humans on earth along with our constant encroachment into the natural world, make the possibility of new diseases more likely than ever.
-       Feeding our large populations with meat has also led to increased animal production. Chickens, pigs, cattle, and other livestock can harbor disease, become infected with diseases from wild animal populations, that may then potentially spread to humans.
-       Many of our most intelligent minds were aware of the danger of truly novel infectious diseases prior to the COVID19 pandemic.
-       Many of these scientists had been sounding alarm bells for years.
-       The new mRNA vaccines used to combat COVID19 were first conceptualized in the 1990s. Such vaccines were meant to speed up the novel vaccine production pipeline, in anticipation of future epidemics and pandemics. 
-       Scientists and public health officials are being attacked right now. These individuals will save us from much more devastating pandemics in the future. This attack on science needs to stop, or we will pay dearly in the future!

 References
- Vourc'h, G., Bridges, V. E., Gibbens, J., De Groot, B. D., McIntyre, L., Poland, R....Barnouin, J. (2006). Detecting Emerging Diseases in Farm Animals through Clinical Observations. Emerging Infectious Diseases, 12(2), 204-210.
- USDA. National H5/H7 Avian Influenza Surveillance Plan. Available at: https://www.aphis.usda.gov/animal_health/downloads/animal_diseases/ai/surveillance-plan.pdf
- CDC. Understanding and Explaining mRNA COVID-19  Vaccines. Available at: https://www.cdc.gov/vaccines/covid-19/hcp/mrna-vaccine-basics.html
- McArthur DB. Emerging Infectious Diseases. Nurs Clin North Am. 2019 Jun;54(2):297-311. doi: 10.1016/j.cnur.2019.02.006. Epub 2019 
- Moore ZS, Seward JF, Lane JM. Smallpox. Lancet. 2006 Feb 4;367(9508):425-35.
- Wikipedia. Smallpox, Emerging Infectious Disease, Eradications of Infectious Diseases, Rinderpest, influenza.
- Wolfe ND, Dunavan CP, Diamond J. Origins of major human infectious diseases. Nature. 2007 May 17;447(7142):279-83. 

Lecture Summary

The basic reproduction number, R0 (R zero or R naught) is a measurement used in epidemiology focused on the infectivity of a given pathogen. It attempts to predict how many people will become infected by one infected person in the absence of any immunity within a given population. It is not a biological constant and can be affected by human behavior, societal infrastructure, geography, and climate.

Key Points

-       The basic reproduction number is not a constant, It depends on time, location, and can change based on the particular mathematical model used for calculation.

-       R0 is not based on time in anyway. An individual infected with HIV has their entire life to spread the virus. On the contrary, someone with COVID19 has only about a week.

-       The most important number regarding R0 is 1. If the R0 is above 1, the infection will spread. If R0 is below one, the infection will eventually die off.

-       Humans can alter the R0 of an infection with behavior, the goal is almost always to lower the number to < 1.

-       Infections are spread in different ways. Examples include aerosol generation, respiratory droplets, contact with body fluids, and the fecal to oral route.

-       Various infection control measures are utilized in the healthcare setting to combat these including masks, gloves, gowns, and other barrier protections.

-       Many of the infections with the highest R0 values have effectively been vaccinated out of our populations. Examples include measles, chickenpox, mumps, rubella, pertussis, and smallpox. We have forgotten the morbidity and mortality associated with these infections in a matter of decades.

-       Let’s compare Measles, HIV/AIDs, and SARs CoV-2 with regard to basic reproduction number. Listen to the show for this!

-       This is the first of a 4 part series, that will also cover smallpox, emerging infectious diseases, basic vaccine design, and the new messenger RNA. Saddle up!

References

-       van den Driessche P. Reproduction numbers of infectious disease models. Infect Dis Model. 2017;2(3):288-303. Published 2017 Jun 29. doi:10.1016/j.idm.2017.06.002

-       Delamater PL, Street EJ, Leslie TF, et al. Complexity of the Basic Reproduction Number (R0). Emerging Infectious Diseases. 2019;25(1):1-4. doi:10.3201/eid2501.171901.

-       Katul GG, Mrad A, Bonetti S, Manoli G, Parolari AJ (2020) Global convergence of COVID-19 basic reproduction number and estimation from early-time SIR dynamics. PLOS ONE 15(9): e0239800. https://doi.org/10.1371/journal.pone.0239800

-       Wikipedia, Basic Reproduction Number, Measles, COVID19, HIV

-       CDC, transmission based precautions. Available at: https://www.cdc.gov/infectioncontrol/basics/transmission-based-precautions.html

-       Tanne Janice Hopkins. Measles cases and deaths are increasing worldwide, warn health agencies BMJ 2020; 371 :m4450

Lecture Summary
Pneumoconioses are fibrotic interstitial lung diseases caused by the inhalation of inorganic mineral dusts. Occupational exposure to asbestos, silica, and coal over many years are the most common causes. Sadly, this preventable disease is on the rise world-wide and no targeted treatments exist.

 Key Points
-       Lung diseases are very common in the workplace and include occupational asthma, COPD, Metal-induced lung injury, acute inhalation injuries, bronchiolitis obliterans, hypersensitivity pneumonitis, tumor formation, as well as other diseases.
-       Pneumoconiosis is caused by the inhalation of inorganic mineral dusts, often over many years.
-       Those effected develop a fibrotic interstitial lung disease that is progressive.
-       Pneumoconiosis is increasing worldwide, particularly in developing nations. It is thought to kill approximately 250,000 people every year.
-       Crystalized silica, asbestos, coal, graphite, kaolin, diatomatious earth, aluminum oxide, nylon floc, talc, and mica are all known culprits.
-       Silicosis is the most common cause. Silicon dioxide makes up 60% of earth’s crust.
-       Generally, disease takes years to develop, but can occur more acutely over months to years.
-       Dry cough and progressive shortness of breath are the most common symptoms
-       Chest xray are often used for surveillance of disease in workers. The International Labor Organization has published standards to guide readers. CTs are more sensitive for disease and should be pursued following any diagnosis.
-       Prevention with engineering and environmental controls, personal protective equipment, and medical surveillance is key.
-       No treatment exists in 2020. Treatment is supportive with oxygen, improved physical fitness, and lung transplant in severe cases. Research is being done on antifibrotic medications.
-       Workers should be educated about the dangers of working with respirable minerals as well as the additive negative effects of smoking tobacco.

References
-       Shi P, Xing X, Xi S, Jing H, Yuan J, Fu Z, Zhao H. Trends in global, regional and national incidence of pneumoconiosis caused by different aetiologies: an analysis from the Global Burden of Disease Study 2017. Occup Environ Med. 2020 Jun;77(6):407-414.
-       Drbeen Medical Lectures – Pneumoconiosis. Available at: https://www.youtube.com/watch?v=DVQP4wKN7RQ
-       Pulmonary Fibrosis Foundation – Pneumoconiosis: Pulmonary Fibrosis Caused by Occupational Lung Exposures. Available at: https://www.youtube.com/watch?v=k3AQyx3_ElU&t=2739s
-       Wikipedia – Pneumoconiosis
-       Ladou and Harrison. Occupational & Environmental Medicine: Current Diagnosis and Treatment, 5th Editiona. Balmes. Occupational Lung Diseases. 378 – 382. McGraw Hill. 2007
-       Asbestos Contractor/Supervisor Manual. OSHA and EPA. 2015
-       NIOSH/CDC B Reader Online Training. https://www.cdc.gov/niosh/learning/b-reader/radiograph/subset2/4.html
-       ILO Standard Radiograms 2011
-       DeLight and Sachs. Pneumoconiosis. Stat Pearls. 2020. https://www.ncbi.nlm.nih.gov/books/NBK555902/ 

Lecture Summary
Pneumoconioses are fibrotic interstitial lung diseases caused by the inhalation of inorganic mineral dusts. Occupational exposure to asbestos, silica, and coal over many years are the most common causes. Sadly, this preventable disease is on the rise world-wide and no targeted treatments exist.

 Key Points
-       Lung diseases are very common in the workplace and include occupational asthma, COPD, Metal-induced lung injury, acute inhalation injuries, bronchiolitis obliterans, hypersensitivity pneumonitis, tumor formation, as well as other diseases.
-       Pneumoconiosis is caused by the inhalation of inorganic mineral dusts, often over many years.
-       Those effected develop a fibrotic interstitial lung disease that is progressive.
-       Pneumoconiosis is increasing worldwide, particularly in developing nations. It is thought to kill approximately 250,000 people every year.
-       Crystalized silica, asbestos, coal, graphite, kaolin, diatomatious earth, aluminum oxide, nylon floc, talc, and mica are all known culprits.
-       Silicosis is the most common cause. Silicon dioxide makes up 60% of earth’s crust.
-       Generally, disease takes years to develop, but can occur more acutely over months to years.
-       Dry cough and progressive shortness of breath are the most common symptoms
-       Chest xray are often used for surveillance of disease in workers. The International Labor Organization has published standards to guide readers. CTs are more sensitive for disease and should be pursued following any diagnosis.
-       Prevention with engineering and environmental controls, personal protective equipment, and medical surveillance is key.
-       No treatment exists in 2020. Treatment is supportive with oxygen, improved physical fitness, and lung transplant in severe cases. Research is being done on antifibrotic medications.
-       Workers should be educated about the dangers of working with respirable minerals as well as the additive negative effects of smoking tobacco.

References
-       Shi P, Xing X, Xi S, Jing H, Yuan J, Fu Z, Zhao H. Trends in global, regional and national incidence of pneumoconiosis caused by different aetiologies: an analysis from the Global Burden of Disease Study 2017. Occup Environ Med. 2020 Jun;77(6):407-414.
-       Drbeen Medical Lectures – Pneumoconiosis. Available at: https://www.youtube.com/watch?v=DVQP4wKN7RQ
-       Pulmonary Fibrosis Foundation – Pneumoconiosis: Pulmonary Fibrosis Caused by Occupational Lung Exposures. Available at: https://www.youtube.com/watch?v=k3AQyx3_ElU&t=2739s
-       Wikipedia – Pneumoconiosis
-       Ladou and Harrison. Occupational & Environmental Medicine: Current Diagnosis and Treatment, 5th Editiona. Balmes. Occupational Lung Diseases. 378 – 382. McGraw Hill. 2007
-       Asbestos Contractor/Supervisor Manual. OSHA and EPA. 2015
-       NIOSH/CDC B Reader Online Training. https://www.cdc.gov/niosh/learning/b-reader/radiograph/subset2/4.html
-       ILO Standard Radiograms 2011
-       DeLight and Sachs. Pneumoconiosis. Stat Pearls. 2020. https://www.ncbi.nlm.nih.gov/books/NBK555902/ 

Lecture Summary

Ketamine is a small molecule that works mainly through inhibition of the NMDA receptor in brain and nerve tissue.  It has varying effects at different doses and can be used for a number of medical indications including depression, suicidal ideation, acute and chronic pain, sedation, and anesthesia. Ketamine is a very safe drug when used intermittently and appropriately. However, it can cause both harm and addiction. Many clinicians fear ketamine. This fear is misplaced as ketamine is very forgiving in the clinical setting and safer than other alternatives like opiates.

Key Points

-       Ketamine is a derivative of phencyclidine (PCP) and because it causes much less agitation, aggressive behavior, and sympathomimetic symptoms, it has enjoyed wide-spread and sustained clinical use.

-       Ketamine primarily acts as an inhibitor of the NMDA receptor. However, it has effects at a number of other targets including multiple opioid receptors. Ketamine also inhibits the reuptake of multiple neurotransmitters including serotonin, norepinephrine, and dopamine.

-       Ketamine can be used at lower doses for mental health conditions like depression, anxiety, OCD, and suicidal ideation.

-       NMDA receptors modulate neuronal development, plasticity, and connectivity. The author hypothesizes that acute plasticity afforded by ketamine allows individuals with mental health issues a unique opportunity to leave negative thought patterns and view themselves from a different level of consciousness.

-       Ketamine’s effectiveness in treating both acute and chronic pain makes it very desirable. 

-       At higher doses, ketamine causes sedation with preserved respiratory function. This makes it ideal for resource limited settings.

-       Ketamine can cause a number of side effects. Most notably an emergence reaction some people experience when waking up from dissociative or sedative doses of ketamine.

-       This emergence reaction can be effectively treated by limiting sensory stimulation and administration of benzodiazepines like lorazepam. Alpha antagonists like clonidine and antihistamines like hydroxyzine may also be helpful. Avoiding antipsychotics in this setting is recommended by some due to the risks of dystonic reactions.

-       Ketamine can also cause hematuria, bladder, and urinary tract dysfunction. Particularly with frequent illicit use.

-       Memory impairment and depressive symptoms also can occur with chronic use.

-       Fatalities from ketamine toxicity are almost unheard of. The LD50 in mice was 600 mg/kg. However, accidents can certainly occur and be fatal in recreational use.

-       There is a lot of controversy regarding a number of Ketamine’s effects. For instance, is ketamine neuroprotective in trauma? What is its effect on seizures at lower doses? Does Ketamine raise intercranial pressure? Ketamine can cause hypotension, hypertension, tachycardia, and bradycardia. Its action at multiple receptors, dose dependent effects, and the heterogeneity of human subjects likely explains a lot of this controversy.

-       Ketamine’s proven safety record, low cost, unique clinical properties, multiple uses, as well as its ability to provide full anesthesia without significant respiratory depression, make it an absolute must have, in resource poor settings.

References
See Part 2 Notes

Lecture Summary

Ketamine is a small molecule that works mainly through inhibition of the NMDA receptor in brain and nerve tissue.  It has varying effects at different doses and can be used for a number of medical indications including depression, suicidal ideation, acute and chronic pain, sedation, and anesthesia. Ketamine is a very safe drug when used intermittently and appropriately. However, it can cause both harm and addiction. Many clinicians fear ketamine. This fear is misplaced as ketamine is very forgiving in the clinical setting and safer than other alternatives like opiates.

References
-       Olson KR et al. Poisoning and drug Overdose, 6th ed. Arminian P. Phencyclidine and Ketamin. 2012. McGraw Hill. 325-327
-       Nelson LS et al. GoldFrank’s Toxicological Emergencies, 11th ed. Olmedo RE. Phencyclidine and Ketamin, chapter 83. 2019. McGraw Hill. 1210-1221. (NMDA receptor information from other chapters as well)
-       George D et al. Pilot randomized controlled trial of titrated subcutaneous ketamine in older patients with treatment-resistant depression. Am J Geriatr Pscychiatry. 2017; 25(11): 1199-1209.
-       Murrough JW et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013; 170(100): 1134-1142.
-       Rodriguez CI et al. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology. 2013; 38:2475-2483.
-       Michelet D et al. Ketamine for chronic non-cancer pain: A meta-analysis and trial sequential analysis of randomized control trials. Eur J Pain. 2018; 22:632-646.
-       Price RB et al. Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression. Depress Anxiety. 2014; 31(4): 335-343.
-       Lapidus KAB et al. A randomized controlled trial of intrasal ketamine in major depressive disorder. Biol Pscyhiatry. 2014; 76(12): 970-976.
-       Zanos P, Gould TD. Mechanisms of Ketamine Action as an Antidepressant. Mol Psychiatry. 2018; 23(4): 801-811.
-       Orhurhu VJ et al. Ketamine Toxicity. StatPearls. 2020. Available at: https://www.ncbi.nlm.nih.gov/books/NBK541087/
-       Wikipedia – Ketamine, Enantiomers, NMDA, etc.

Lecture Summary
Ketamine is a small molecule that works mainly through inhibition of the NMDA receptor in brain and nerve tissue.  It has varying effects at different doses and can be used for a number of medical indications including depression, suicidal ideation, acute and chronic pain, sedation, and anesthesia. Ketamine is a very safe drug when used intermittently and appropriately. However, it can cause both harm and addiction. Many clinicians fear ketamine. This fear is misplaced as ketamine is very forgiving in the clinical setting and safer than other alternatives like opiates.

Key Points
-       Ketamine is a derivative of phencyclidine (PCP) and because it causes much less agitation, aggressive behavior, and sympathomimetic symptoms, it has enjoyed wide-spread and sustained clinical use.
-       Ketamine primarily acts as an inhibitor of the NMDA receptor. However, it has effects at a number of other targets including multiple opioid receptors. Ketamine also inhibits the reuptake of multiple neurotransmitters including serotonin, norepinephrine, and dopamine.
-       Ketamine can be used at lower doses for mental health conditions like depression, anxiety, OCD, and suicidal ideation.
-       NMDA receptors modulate neuronal development, plasticity, and connectivity. The author hypothesizes that acute plasticity afforded by ketamine allows individuals with mental health issues a unique opportunity to leave negative thought patterns and view themselves from a different level of consciousness.
-       Ketamine’s effectiveness in treating both acute and chronic pain makes it very desirable. 
-       At higher doses, ketamine causes sedation with preserved respiratory function. This makes it ideal for resource limited settings.
-       Ketamine can cause a number of side effects. Most notably an emergence reaction some people experience when waking up from dissociative or sedative doses of ketamine.
-       This emergence reaction can be effectively treated by limiting sensory stimulation and administration of benzodiazepines like lorazepam. Alpha antagonists like clonidine and antihistamines like hydroxyzine may also be helpful. Avoiding antipsychotics in this setting is recommended by some due to the risks of dystonic reactions.
-       Ketamine can also cause hematuria, bladder, and urinary tract dysfunction. Particularly with frequent illicit use.
-       Memory impairment and depressive symptoms also can occur with chronic use.
-       Fatalities from ketamine toxicity are almost unheard of. The LD50 in mice was 600 mg/kg. However, accidents can certainly occur and be fatal in recreational use.
-       There is a lot of controversy regarding a number of Ketamine’s effects. For instance, is ketamine neuroprotective in trauma? What is its effect on seizures at lower doses? Does Ketamine raise intercranial pressure? Ketamine can cause hypotension, hypertension, tachycardia, and bradycardia. Its action at multiple receptors, dose dependent effects, and the heterogeneity of human subjects likely explains a lot of this controversy.
-       Ketamine’s proven safety record, low cost, unique clinical properties, multiple uses, as well as its ability to provide full anesthesia without significant respiratory depression, make it an absolute must have, in resource poor settings.

See References In Part 2 Notes

Lecture Summary
This podcast talks about disaster preparedness, how to prepare, the initial assessment, and the importance of reflection for constant improvement.

Key Points
- We are not prepared for disasters and emergencies. COVID19 made this very clear.
- Preparing requires thinking through possible emergency scenarios, developing algorithms, training, gathering supplies, and periodically re-training.
- The initial assessment represents an algorithm which can be used when responding to any emergency involving human casualties.
- Having a written initial assessment and practicing its use is highly encouraged.
- The acronym SAD LAB CATS describes the algorithm I use in my initial assessment.
- It stands for scene safety, additional resources, disease protection, level of consciousness, airway, breathing, circulation, arterial bleeds, temperature, and spine.
- Reflection following any emergency or disaster is key to improving outcomes in the future.

References
I have learned so much about this topic through wilderness first aid/responder courses, my emergency medical technician training and work, advanced wilderness life support, as well as my work in the hospital setting. I have read numerous sources including but not limited to The American Red Cross Wilderness and Remote First Aid Handbook, Auerbach's Wilderness Medicine, Wilkerson's Medicine for Mountaineering, Prehospital Care textbook through St. Louis Community College, and so many other books on the subject I have read throughout the years. However, most of this podcasts comes from personal experience.