COVID-19, Chloroquine, Clinical Trials….

World Corona Virus Cases
https://www.worldometers.info/coronavirus/
FYI: Current as of 2020\03\31 @8:18, at 802,556 cases and 39,012 deaths.

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DISCLAIMER: A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed.
https://en.wikipedia.org/wiki/Prescription_drug

Chloroquine and Hydroxychloroquine ARE “prescription drugs”, and are intended to be taken under the administration and guidance of medical professionals (doctors and pharmacists) in order to maximize safety. (Translation, if you take a prescription drug, you do so at your own risk, and often at extreme risk of receiving a nomination for a Darwin Award.)

My providing information regarding Chloroquine and other treaments is NOT medical advice, it is merely providing a clearing-house of related information in a singular place.  And I fervently advise against the stupidity of taking any prescription medicine, over-the-counter drug, herbal supplement, or vitamin for which you lack understanding of the risks entailed, the dosage requirements, safety precautions, etc. Particularly, when we have the availability of medical practitioners. You’re not living in Mad Max Thunderdome. The COVID-19 pandemic is NOT the end of the world.  Don’t act like it. Use common sense. Understand that for some SARS-CoV-2 (the virus that leads to the COVID-19 disease) is likely to affect no more than a sniffle, while others it can pose a life threatening situation.  Young, healthy, no existing conditions, are at lower risk (& potentially can be silent carriers) while as older, overweight, less healthy individuals are at far greater risk.

Be wiser and prudent, particularly as the holidays (Easter, Passover, etc.) approach.  It may be better to skip having the large yearly traditional family gathering, and miss out on seeing loved ones and family for one year, than to risk not having a loved one in future years, because one individual was an asymptomatic carrier and another family member at high risk. For many, this may be nothing more than a typical cold or flu, but please do not dismiss the danger to others who are at high risk. I have already had to comfort one friend who lost their younger brother (age 35 – https://www.rep-am.com/local/localnews/2020/03/26/wolcott-man-dies-at-35-from-coronavirus/) to the virus.  And while some may point to his weight, blood pressure, etc. as contributing factors to his succumbing to COVID-19 at only 35, recognize that most Americans (myself included) are out-of-shape, overweight, pre-diabetic, etc. Thus the majority of us are at higher risk than we should be for our ages.

 

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https://www.mediterranee-infection.com/wp-content/uploads/2020/03/Hydroxychloroquine_final_DOI_IJAA.pdf

https://www.the-scientist.com/news-opinion/is-hype-over-chloroquine-as-a-potential-covid-19-therapy-justified–673

Second study released
https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-IHU-2-1.pdf

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Chloroquine shown to inhibit the original SARS,
https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-2-69

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Pre-print, pending peer review randomized clinical trial
https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v1

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NY Times releases their Coronavirus Case Data for every U.S. County on GitHub.
Article https://www.nytimes.com/article/coronavirus-county-data-us.html
GitHub https://github.com/nytimes/covid-19-data
Besides being interesting from a Corona data standpoint, this is the first time I have seen a major news agency release data thru GitHub.

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FDA, Chloroquine, and COVID-19

CDC Info on Therapeutic options for COVID-19
https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html

The purpose of this document is to provide information on two of the approved drugs (chloroquine and hydroxychloroquine) and one of the investigational agents (remdesivir) currently in use in the United States.

CHLOROQUINE- chloroquine phosphate tablet
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9b585ad5-ae86-4403-b83f-8d8363d43da5

Searchable Clinical Trials Site
https://clinicaltrials.gov/

Studies on Chloroquine as an anti-viral for HIV patients.
https://aidsinfo.nih.gov/drugs/569/chloroquine/0/patient

Request for Authorization of Emergency Use of Hydrochloroquine
https://www.fda.gov/media/136534/download

https://www.npr.org/sections/coronavirus-live-updates/2020/03/30/823987540/fda-oks-addition-to-stockpile-of-malaria-drugs-for-covid-19

Fact Sheet …Emergency Use Authorization (EUA) of Hydroxychloroquine for COVID-19
https://www.fda.gov/media/136538/download

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A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19
https://www.sciencedirect.com/science/article/pii/S0883944120303907

• COVERS: Six articles (one narrative letter, one in-vitro study, one editorial, expert consensus paper, two national guideline documents) and 23 ongoing clinical trials in China. Chloroquine seems to be effective in limiting the replication of SARS-CoV-2 (virus causing COVID-19) in vitro.
• Chloroquine has been used worldwide for more than 70 years, and it is part of the World Health Organization (WHO) model list of essential medicines.

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COVID-19 Drug Therapy – Potential Options
https://www.elsevier.com/__data/assets/pdf_file/0007/988648/COVID-19-Drug-Therapy_Mar-2020.pdf

• Chloroquine – In vitro and limited clinical data suggest potential benefit.
• Hydroxychloroquine – In vitro and limited clinical data suggest potential benefit.
• Lopinavir; Ritonavir – Role in the treatment of COVID-19 is unclear. Preclinical data suggested potential benefit; however, more recent data has failed to confirm.
• Remdesivir – Investigational and available only through expanded access and study protocols; several large clinical trials are underway.
• Azithromycin – Used in some protocols based on theoretical mechanism and limited preliminary data as adjunct therapy.
• Tocilizumab – Immunomodulating agent used in some protocols based on theoretical mechanism and limited preliminary data as adjunct therapy.
• COVID-19 convalescent plasma – Investigational use is being studied.

Recently, I’ve seen mention of Melatonin

• https://www.sciencedirect.com/science/article/pii/S0024320520303313

Which of these have robust clinical trials showing efficacy for treatment of COVID-19? NONE!! And no treatment will, because clinical trials usually take years. Even a single study is likely to take months, and for it to pass muster there must be randomizing, placebo testing, etc. Not something you do in the midst of the worst pandemic crisis in a 100 years!

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CLINICAL TRIALS

The Clinical Trial Model Is Up for Review: Time, Expense, and Quality of Results Are at Issue, As Is the Relationship to Drug Pricing (published in 2014)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189694/

• Gilead’s Harvoni, a fixed-dose combination therapy for hepatitis C, was the fastest program in the anti-infectives therapy area with a 20 month clinical duration, and one of the fastest overall. It was also faster than any anti-infectives in the 2014 study.
• ^ KEY POINT, fastest = 20 months. Do you really want to wait 20 months with COVID-19 running amok?

 

How fast are clinical trial? (Basically many many months to years.)https://www.clinicaltrialsandme.com/resources/how-long-do-clinical-trials-take.html

Future role of AI in Clinical Trials
https://www.cbinsights.com/research/clinical-trials-ai-tech-disruption/

Fastest drug developers and their practices
https://www.centerwatch.com/articles/13284

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Planquenil (brand name) Dosing
https://www.drugs.com/dosage/plaquenil.html

• Malaria Prophylaxis (preventative) Dose = Adults: 400 mg (310 mg base) once weekly on the same day of each week starting 2 weeks prior to exposure, and continued for 4 weeks after leaving the endemic area. NOTE: This is NOT the dose to treat Malaria, just the dose prescribed to take weekly if entering an area with a high risk of Malaria contraction.
• Malaria Treatment Dose = Adults: 800 mg (620 mg base) followed by 400 mg (310 mg base) at 6 hours, 24 hours and 48 hours after the initial dose (total 2000 mg hydroxychloroquine sulfate or 1550 mg base). Weight based dosage in adults and pediatric patients: 13 mg/kg (10 mg/kg base), not to exceed 800 mg (620 mg base) followed by 6.5 mg/kg (5 mg/kg base), not to exceed 400 mg (310 mg base), at 6 hours, 24 hours and 48 hours after the initial dose.
• Lupus Dose = Adults, 200 to 400 mg (155 to 310 mg base) daily, administered as a single daily dose or in two divided doses. Doses above 400 mg a day are not recommended. à The incidence of retinopathy has been reported to be higher when this maintenance dose is exceeded.
• Rheumatoid Arthritis (Initial) Dose = Initial adult dosage: 400 mg to 600 mg (310 to 465 mg base) daily, administered as a single daily dose or in two divided doses. In a small percentage of patients, side effects may require temporary reduction of the initial dosage.
• Rheumatoid Arthritis (Maintenance) Dose = Maintenance adult dosage: When a good response is obtained, the dosage may be reduced by 50 percent and continued at a maintenance level of 200 mg to 400 mg (155 to 310 mg base) daily, administered as a single daily dose or in two divided doses. Do not exceed 600 mg or 6.5 mg/kg (5 mg/kg base) per day, whichever is lower, as the incidence of retinopathy has been reported to be higher when this maintenance dose is exceeded.

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Amesh Adalja, MD, of the Johns Hopkins University Center for Health Security, said hydroxychloroquine has been well-studied, and has both antiviral and anti-inflammatory properties.
http://www.cidrap.umn.edu/news-perspective/2020/03/trump-says-fda-fast-track-approve-covid-19-drugs

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German Metrics
https://www.rki.de/DE/Content/InfAZ/N/Neuartiges_Coronavirus/Situationsberichte/2020-03-20-en.pdf?__blob=publicationFile

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NOTE: The that in this case, the “regular care” entailed the use of other anti-virals, namely lopinavir and ritonavir. Chloroquine is an older med, easily manufactured cheaply.

Malaria Drug Chloroquine No Better Than Regular Coronavirus Care, Study Finds: In the Chinese study, which was conducted by researchers from the department of infection and immunity at the Shanghai Public Health Clinical Center, the 15 patients who didn’t get hydroxychloroquine were treated with conventional care.

This includes bed rest, oxgen inhalation, and the use of anti-viral drugs recommended in China’s treatment guidelines like lopinavir and ritonavir, and antibiotics when necessary.
https://www.bloomberg.com/news/articles/2020-03-25/hydroxychloroquine-no-better-than-regular-covid-19-care-in-study

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“It’s an important tool we have to study and make sure we get good data on good coronavirus patients and what the impact is,” he told CIDRAP News. But he cautioned that there is limited availability of the drug, and many patients with rheumatoid arthritis rely on it. He also worried the sudden interest in the drug could cause supply chain issues.
https://www.the-scientist.com/news-opinion/is-hype-over-chloroquine-as-a-potential-covid-19-therapy-justified–67301

Continues to Facilitate Development of Treatments
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-continues-facilitate-development-treatments

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Wiki – Hydroxychlorquin
https://en.wikipedia.org/wiki/Hydroxychloroquine#cite_note-Cor2020-3

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Can we please stop the foolishness and political-infusion into this pandemic.  All options that show any potential merit for treatment need to be explored and utilized. People are dying.

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Three questions to ask when hiring supervisory positions

I was recently asked by a friend for advice regarding three questions to ask when interviewing a prospective candidate for a supervisory or managerial role. These are the three I suggested for her scenario, however, I think these are fairly good questions to ask in general for any mid-level management interview.

1. What techniques do you use to motivate your employees/team while avoiding the increase of conflict or negative impacts on morale?
   
   Ensuring employees are motivated to be productive in the performance of their tasks is the sacred blood flow of a company. Unless your industry can magically print money, you need productive workers. Unmotivated employees lead to poor productivity levels, inefficiency, and a loss of corporate competitiveness. This is the lifeblood of any company. If circulation slows and stops, the company will fail.  So what ensures your employees are motivated and productive?
   
   It’s been said, employees do not leave companies, they leave managers. While not wholly accurate, it conveys a very strong point. An employee that has a great manager, will usually continue working productively, even if they are employed at a lousy company.  Where as, even an employee of a top company, will leave, if they have a horrible manager. 
   
   Being a supervisor or manager brings a certain amount of authority. However, the rod can only motivate to a degree, abuse of authority is a common cause for employee churn. Leadership, accomplishes the same goal, with far better outcomes of increased productivity and reduced employee churn.   With this question, we want to access the candidate’s leadership abilities.
   
   
2. How do you facilitate bi-directional knowledge sharing, including the encouragement of idea sharing from those you lead? How do you go about evaluating, implementing, and determining the profitable feasibility of said ideas and innovations?
   
   Here we want to ensure the candidate is inclined to share knowledge and processes with those under their direction, rather than holding knowledge for themselves and becoming a single point of failure.  We do not want a supervisor to be a “locked gateway”.  Nor do we want a culture in which ideas and innovations are suppressed. In this day and age, innovative ideas differentiate Amazon and Sears, Tesla and Chrysler. That said, not every idea is good. A manager needs to foster an environment that encourages innovation while simultaneously implementing a framework that evaluates both the immediate impact and the effect over time to ensure that any new process enacted, affects the organization positively.
   
   We want to ensure the candidate is a facilitator who enables their team to be productive and fosters their growth. Does the candidate micro manage, is their way the only way, or are open to change and accepting of suggestions and input from underlings?
   
   
3. How do you handle conflict and failure? Both in regards to those under your supervision and more importantly, your own? When in-over-your-head or too heavily invested, what actions do you take to ensure the situation does not reach a level that puts the well being of the greater whole in jeopardy or at risk? (project, team, business, well being of personnel) What external resources beyond yourself and your team, do you utilize or reach out to in order to ensure that you, your team, and the venture as a whole continue to be successful?
   
   What are we looking for here? Primarily, an ability to look outside one’s self and to ensure stakeholders are notified in an appropriate timeframe when issues arise.  Simple answers can include: “I google the problem.” “Seek input from a peer/colleague.” “Reach out to stakeholders.” 
   
   We want to ensure that the candidate is not going to attempt to put out a fire alone, without activating alarms to notify the appropriate response teams. That their ego will not prevent them from reaching out for assistance when the situation warrants doing so.  As a stakeholder, we do not want to discover one of our business’ buildings burned down because we were never alerted to the fire.
   

How are those three? Yes, they are a bit long. But really they cover the primary issues I see in supervisory/team dynamics.

I. Motivation of the team.
II. Empowering the team.
III. Mitigating risks – particularly those with the potential to negatively impact the smooth operation of the project.

If able, be sure to ask follow-up questions. If not, then I suggest prefacing your three questions with the following statement. “For each question, please elaborate and provide an example from two of your listed past employments. Express how each required and necessitated different approaches.”

Thoughts? What are some questions you’ve found useful in weeding out good leaders and supervisors from bad ones?

 

 

The Future of Collegiate Education

Why every student will be able to go to an Ivy League school….
I’ve said it for years, others are saying, the collegiate school bubble is going to bust. Here’s the main reasons why:

– cost of a collegiate degree is excessive
– value of a collegiate degree has declined
– availability and access to knowledge has expanded by orders of magnitude
– practical value of the knowledge delivered by universities has little to no real-world value
– the collegiate system is one of the most heavily tax payer subisidized industries in the world

I’ve said that in 20 years, probably half the colleges and universities present today will be no more. Here is how and why it that will come to be.  In the future, you will have community colleges and Ivy Leagues and top tier schools, the middle ground of collegiate education will cease to be.

First off, if you had a choice of graduating from the University of York Pennsylvania or Dartmouth, which would you choose? Oh, but you can’t get into Dartmouth nor afford it – right now.

But realize that online learning, which is just in it’s infancy, will begin to mature. Already most top tier universities offer free courses: Stamford, Harvard, MIT, etc.  And while you cannot currently, and never likely, will be able to get a free degree from these establishments. You can already LEARN from them.

How long until Stanford says, why should we only have 15,000 clients. Sure, that’s a whopping $750 million per year. But there are ~20 million college students in the U.S., if Stanford offered online degrees for $5,000/year tuition and enrolled a 150,000 students.  They would double their $750 million revenue. But they would do so at an extremely low overhead. No building to build, far less professors needed per student, etc. The amount of that revenue which would be profit would be exceedingly high.

90% of collegiate learning can be done via online courses. Courses could even be taught live with thousands in digital attendance. But what about interaction? Simple, the delivery app would allow students to ask questions. Moderators would see these questions, the professors would not. The moderators would then be able to post popular questions to the professor. So if dozens of students ask a question, the moderators would gain a sense of its need for clarity. Then a single moderator would raise the question to the professor. “Professor, a number of students have asked about what happens when….blah blah blah.” And the professor responds live to the classrooms needs.

The quality of learning would in fact exceed most classroom environments. Because the schools would select the best professors.  We all had them in college, those professors who made it all click. Those professors who conveyed the material with understanding that other instructors failed to posess.  Well guess what, all those sub-par tenured professors will go bye-bye. Time to find new jobs.  Top tier professors will become akin to sports stars.  Stamford, Harvard, MIT, etc. will hire the absolute best teachers in fields, not just in knowledge but in teaching ability. These professors may earn over $500K/year, maybe even a million a year.  But they’ll be worth it…

The gap will be in those fields that require labs – chemistry, biology, physics, etc.  Here is why community colleges will stick around. You see, you will do your labs at your local community and regional state colleges. You might even do a lot of your basic courses there such as reading, math, etc.

Furthermore, I expect that a National Online University will be established as well. This will offer tuition free degrees. The degrees will be limited to handful of basic degree options:  bio/chem/pre-med, math/engineering, computer science, english/education, history/education, business, nursing, psychology, political science, economics/accounting, etc.

But what about college campuses? Will those go away? Yes, and no. For the thousands of colleges and universities that will disappear entirely, yes. But for the top tier, Ivy Leagues, MIT, etc.  No…these will continue but in a far different way.  Only the privileged few will get invited to the campus. Tuition for these will likely be free. The actual campuses will be far more focused on research.  Professors will handpick high school graduate applicants and select individuals who excel in the online program their first year or two may also be invited to participate on campus.