Naked Medicine

Let's Face It: Medicine is Business

How Antibiotics Work

Antibiotics work according to the mechanism of action (what the drug “targets” in microbes or how the drug “works” in the microbe) that is driven by the drug’s distinguishing chemical structure.

Chemical structures also define the “classification” of antibiotics. If you hear doctors talk about “macrolides” versus “quinolones”, they are talking about families of drugs (not “one” specific drug) and they are referring to the way each family of drugs targets microbes.

When you hear about “generations” of an antibiotic, this means the chemical structure of the current drug has been modified (changed) somehow. These changes are designed to improve the action of the drug, especially when the bacteria have evolved to resist the original drug.

A well known example is Penicillin resistance. Overuse of penicillin resulted in widespread bacterial resistance to this drug. If I went to the doctor today and the doctor decided that a beta-lactam based antibiotic was appropriate, the doctor may prescribe amoxicillin or one of the newer generation cephalosporins versus the original penicillin. That’s because the doctor is thinking the bacteria in my body will probably laugh at penicillin and a “newer” penicillin (like amoxicillin) may be needed.

Why We must complete the ENTIRE course of antibiotic therapy

One of the biggest problems in antibiotic resistance, besides antibiotics being over-prescribed, is patients stopping their medication as soon as they start feeling better instead of finishing their entire course (taking ALL pills prescribed by the doctor).

Imagine your body is a kingdom and your immune system as a fortress/defense system. Your kingdom has undergone an invasion. Taking antibiotics is similar to giving your immune system a much needed weapon to defeat the invaders.

A full course of antibiotic therapy aims to kill off as many invaders that have infiltrated your kingdom within as short amount of time as possible, so that your defense system can take care of the rest, and to ensure that ALL the invaders are killed.

People sometimes stop taking the antibiotic when they start feeling better (“Oh, I’m already feeling better”) or for another reason (“hey, maybe I should save these couple of pills, just in case, for next time”). The problem is that there may be a few invaders that have thus far evaded the antibiotic response, and these will be the invaders who will come back with a vengeance, literally.

Your feeling better has do to with most of the invaders being killed off, but the few that have escaped being killed are buying time to adapt and evolve… to become smarter against your defenses.

Antibiotic resistance arises from the ones that have been allowed to escape because the host (you) decided “All is well, call off the troops!” and giving the invaders time to learn how to better take you down the next time there is an opportunity.

Based on the way each antibiotic family targets microbes, the drugs in that antibiotic family may either kill (bactericidal) or stall the growth of (bacteriostatic) microbes.

This is where we get into the specifics of “how” an antibiotic works. Antibiotics aim to kill by:

  • Targeting a specific feature of bacteria
  • Targeting the reproductive process of bacteria
  • Targeting a critical chemical pathway in bacteria (especially protein synthesis)
  • Overcoming bacteria’s evolved mechanisms of resistance (for example, bacteria that have evolved pumps in their membranes to “pump out” drugs)

Targeting a Specific Feature of Bacteria, Reproduction, or critical process (typically making proteins or “protein synthesis)

Antibiotics that target gram positive bacteria will disrupt the chemical process critical to making the thick peptidoglycan wall (the thick wall is what holds the “gram stain” that allows us to visually identify the “gram positive” bacterial strain).

However, if the bacteria has a thin peptidoglycan wall (this then won’t show up as bright violet stains on the gram stain, making this bacteria a “gram negative” type), then an antibiotic that targets that wall won’t do much damage.

Instead, you’d need an antibiotic that targets a specific feature of gram negative bacteria or target a critical process like protein synthesis. For example, the antibiotic can cross the gram negative bacteria’s cell wall (but are blocked by gram positive bacteria’s peptidoglycan layer) to stop protein synthesis, which stops many critical machinery in bacteria.

Antibiotics that target the bacterial reproduction prevents new bacteria from being produced. This gives your body a fighting chance to go over the existing microbes.

Theranos’ Elizabeth Holmes is Not a Liar

(Via Quora’s Is Elizabeth Holmes a liar?)

The Theranos story has gone from bad to worse, first from the Wall Street Journal “expose” that Holmes during a live blogging event equated to “tabloid” journalism, then from a series of very public disengagements with partner corporations, and now — complying with a Herculean FDA request. This is causing some in the public to ask whether Holmes is a mastermind in a fairytale of scientific triumph.

No. Holmes is not a liar.

Holmes made bad business decisions and painted herself into a corner.

Holmes is in the class of executives that are technologist founders, which combines subject matter STEM expertise with the vision and strategy typical of C-level executives. The challenge with this class of executives is that they often do not excel in all aspects required in each role. There are incredible business chiefs that cannot do the job of their company’s top subject matter experts (SME). There are genius technologists who can rapidly run businesses of any size to the ground. It is rare to combine both SME and business acumen at the highest levels in one person.

In the case of Theranos, she was extremely effective in the beginning, when she needed to create excitement and inspire others to support her vision. She fulfilled an important role for a chief executive. She brought the technology into development, which fulfilled an important role for a technical subject matter expert, although I am less “sold” on how cutting edge her technology is given the lack of data, thus I hold her less credible on the SME role compared with the CEO role.

Companies must exist beyond initial honeymoons, and especially must weather and survive crises that are part of business cycle/life. Add to this, the “healthcare business”, where we now involve the quality and quantity of people’s lives, and we can see the level of shit-storms that can happen. In the healthcare business, I have come to believe that the question is never about “if” a shit-storm will happen to a life science company, but “when” and “how bad” a shit-storm will happen.

This is where Holmes began making a series of bad calls that snowballed into bad decisions, which became bad publicity that she made worse by more bad decisions. Now we’re at the point where we may want to believe but we harbor more doubt because of Holmes’ cumulative actions resulting from the original points of doubt.

But has Holmes fared worse in her CEO actions than other CEOs who have been embroiled in scandals? Has she behaved in a way that shows greater opacity or concealment than other CEOs under fire from public scrutiny?

I don’t think so. Holmes is acting exactly as other CEOs had to act in this situation: as directed by company lawyers, to ensure her actions are in the best interest of Theranos at this point. Even if she was the one who caused great harm the credibility and public image of the venture that has become her entire identity.

The Theranos Problem in One WSJ Graphic

Now that Theranos is allegedly/denying-trying to raise money, speculations continue as to whether it could survive the Wall Street Journal article, Hot Startup Theranos Has Struggled With Its Blood-Test Technology, or whether a big industry player may swoop down to acquire the company.

In terms of “who would be audacious (to use a polite word) enough to possibly merge/acquire Theranos”, I think a diagnostic company would be more a likely candidate… you know, one of the big players that Theranos was meant to “disrupt” the business of.

The short sighted assumption from many people thus far, is that Theranos was the only company that had the “foresight” to reduce sample volume required for blood based assays.

Can we actually believe that NONE of the big players NEVER considered the competitive advantage of reducing sample volume required from patients and human subjects? Are we saying that all these years no one had ever realized how many people hated needles, and the kind market leadership position one may gain if one creates an assay method that enables accurate sampling of mere drops of blood versus vials of blood?

When we look at Theranos’s “accuracy” compared with hospital results, most scientists familiar with the assay process can deduce the magnitude of what needs disrupting:

The best performance in the graphic from Theranos in terms of “accuracy” compared with a hospital result “standard”, is the glucose test.

This is nothing to be impressed about: getting the glucose reading right is no newer than the finger prick glucose draw available from today’s diabetes management devices. It only shows Theranos got their tech as right as what is already available in terms of a finger prick blood sugar test.

Perhaps someone can use current glucose monitoring technology, modify it so it could assay for Herpes (simplex type1), and see if the same “tech” transfers readily to accurately test for Herpes. This would offer an interesting data point to show just how novel the “Edison portfolio of technology” is.

This one graphic sums up the Theranos problem: the most accurate comparison is in a variable for which cheap and accessible diagnostic is available (glucose), and not for any variables for which wide clinical use are expected (liver function tests, which are critical for a variety of medications affecting liver function).

Theranos’s results are consistently “false positive” compared with hospital standard: if a clinician believes in the Theranos result, the clinician may order the patient to stop taking medications that the patient needed and was doing well on, but should no longer be taking because the results show that liver was being negatively affected, or the clinician could switch to another less effective medication for the patient out of concern for liver function. Either case, if the Theranos test was inaccurate, this would cause harm to the patient by unnecessarily disrupting treatment regimen that was otherwise appropriate.

This is not the kind of “disruption” healthcare providers want.

From a business perspective, Theranos’s FDA approved use for its product has a very narrow indication (Herpes), yet the test is commercially available without authorization from a licensed healthcare practitioner. This is great for the company’s bottom line, because the (federal) agency will have a tough time identifying which kits have been purchased for “approved” use and which kits are actually used “off-label”. The pricing advantage allows Theranos to reduce dependence on CMS reimbursement, by going straight to consumers. Liability becomes a matter of personal injury, which may be skirted when the consumers assume entire risk by “inappropriately using” the kit.

However, this is not great from a consumer protection standpoint.

We may subscribe to a conspiracy theory about major diagnostic and device companies colluding to keep an oligopoly on expensive assay machines and profit margins for assay kits, but from a business competition standpoint, the market dominance/leadership would be too attractive for a major player to ignore in the name of market oligopoly.

Biotechnology Stock Price Drivers

The following may be happening that can affect the stock price:

  • Presentations or buzz occurring at key scientific and medical meetings; for oncology from which many biotechs sprout, we have ASCO, ASH, AACR, to name a few key meetings.
  • Clinical trial results are closely pending or just released. Typically companies dealing with the same or similar technology/pathway are affected by a peer company’s clinical trial results.
  • FDA decisions pending or released.
  • FDA holds on a clinical trial either imposed or lifted (as with $GERN).
  • Management taking the “poison pill” strategy against possible hostile bids (as with $ARIA 2 years ago)
  • Earnings are reported (usually at a loss unless there is already a commercial drug).
  • Merger & acquisition activity (Drama around $VRX hostile bid for $AGN).
  • Licensing announced including upfront/milestone payments.
  • Orphan drug designation announced (as with $ISIS recently).
  • Key management (C-level for biotech) changes.
  • Major insider buys/sells (like when $INO’s CEO bought a ton of company stock as a show of confidence when stock dropped last year because a blogger made unfavorable comments about the company’s drug, or $OPK’s founder buying a ton of his company’s stock last year when $IBB went through a bloodbath.)
  • Major shareholder (usually investment firms or hedge fund managers) buys/sells.

For the most part, biotech stocks should be viewed either as a speculative investment and/or truly for the long term. Those who bought $MDVN or $PCYC when these were in double digit prices and held through 2015 has seen their investment double or triple in value. There are those who daytrade and really speculate the sector for its volatility, but that’s a pretty stressful “day job” in my personal opinion.

What You Need to Know about Your 401K Plan

Before entering your employer’s 401K plan, you need to decide:

  • Percent of pre-tax contributions
  • Percent of post-tax contributions
  • Percent of employer match

At the very minimum you want to contribute whatever % your employer matches, this way you can get the $ that your employer sets aside for your 401K.

Preferably you will maximize % of pre- and post-tax contributions regardless of employer match.

Percent of pre-tax contributions are useful for reducing your AGI (adjusted gross income). Percent of post-tax contributions are useful for building up your retirement nest egg in a way that is automated (out of sight, out of mind, therefore out of impulsive spending if you have those habits).

The only time when you may consider reducing (never eliminating!) your pre-tax contributions is when you have a significant loan term that has a less favorable % return than if you take that percent of your paycheck to pay down the loan. Even then, calculate carefully whether your investment returns in your 401K may fare better. Example: you have a mortgage loan at 6%. You may calculate the probability that you’d do better paying this down sooner versus building up a nest egg 401K that compounds interest over time.

Part of the investment election process includes:

  • Choice of funds
  • Expense ratios (cost)
  • Redemption fees
  • Your investment plan or strategy

Employers often offer both passive index (mutual) funds AND actively managed funds. Employees are able to choose what products they want their contribution to go toward.

Basically the options are in broad categories of “Bonds, Stocks/equities, and Target Retirement”.

Bond funds are just that — made of bond products, although you’d want to look at what are actually in those bond products. Sometimes these include treasury (US dollars) and other mortgage backed securities, some of these riskier than others.

Stock funds are made up of all or selection of stocks in the stock market that is supposed to represent “the market”.

Target retirement funds tend to be actively managed (more expensive) but is promoted as “you don’t have to do anything, we’ll do it for you” products. These are sometimes called Life cycle fund or similar name. It’s supposed to shift the allocation of lower-risk (usually bonds & cash) versus higher-risk (usually stocks) products as you age, so that you won’t be exposed to too much risk as you near retirement age. I don’t buy these since I can click buttons and enter % of allocation for bonds:stocks based on risk tolerance and overall retirement portfolio (important if the household has dual working partners so you are dealing with 2 retirement portfolios not one).

My rule is to ALWAYS GO FOR PASSIVE INDICES. In other words, products that are a version of “S&P500 index”, “Total stock market index”, “Total bond market index”, “Total international stock market index”, and “Russell 2000 index”. This is because the cost of owning these (expense ratio) makes a huge difference over time as you leverage compounding interest, without paying the 401K management company a higher cost to buy other funds. In 401K these actively managed funds tend to be ‘sector based’, such as ‘healthcare’ or ‘technology’. I ignore those, since I can buy sector mutual or ETF funds for way cheaper at Vanguard’s retirement account.

‘s an example of a Russell 2000 index fund expense ratio (cost) at a major employer’s 401K fund selection:

Same employer’s sector-based (science/tech) actively managed fund:

Granted, the “Morning Star” boxes are not identical because the science/tech fund is more Large Cap-Growth (big companies) while Russell 2000 focuses on smaller companies (high risk and high reward Small Cap-Blend), but if you want to focus on big companies then you might as well go for the total stock market index fund (cheaper Large Cap-Blend) which costs:

Finally, investment strategy is based on where you want your money contributed when it is automatically entered into your 401K account, and how often you want to move your money based on market conditions (although you will never move it while incurring any redemption/short-term trading) fees. Moving money isn’t taking it out (distribution — a No-No) — it’s simply transferring monies in a particular fund into another particular fund to match your (“household”/family) overall portfolio’s target asset allocation.

For example, if the S&P index fund has done well but is looking over priced, I will move all/a percent of money out of this into another fund that is pulling back (looks cheaper). Usually I have enough time to plan because I can’t move money between accounts without incurring redemption fees, so I may start watching a particular index that appears to be heading to lower prices and wait until I can “sell high” (fund that’s doing well and moving money out of” to “buy low” (fund that’s cheaper).

Disclaimer: Not a CPA, not a Financial Advisor, Not affiliated with FINRA. Just an individual who has taken time to educate myself on money management and I usually read Prospectus(es).

What to Do If You Lose Your Wallet

Some time ago, I lost my wallet, and within the hour that I realized my wallet had been lost, I was able to do the most important “damage control” tasks like:

  • notifying credit card companies to cancel existing cards and issue new card numbers
  • downloading a duplicate health insurance card
  • figure out how to replace driver license
  • putting a “freeze” on opening new lines of credit

Other than knowing an exciting day of waiting at the DMV (Department of Motor Vehicles) is in my future, I am glad I haven’t lost anything I cannot replace.

Since my credit card transactions all come with email alerts, if anyone had tried to buy anything with the cards, I’d be notified immediately via email.

In terms of lines of credit being opened, this is where putting a “credit freeze” is critical. In the U.S. the 3 major credit reporting agencies will get a record “pull” anytime when anyone inquires about your credit or someone (hopefully yourself) is trying to open up a line of credit: maybe this is applying for a new credit card, or apply for a store card, trying to buy a car, trying to inquire about a mortgage or line of equity loan etc…. by putting on a “freeze” it forces the inquirer to call a number before any data can be pulled. This way you will know if someone is trying to use your identity and take a loan in your name.

The “credit freeze” is new for me this time around when I lost my wallet, but I’m not actually worried about my credit cards being used in appropriately because of the email alerts and also because I acted extremely quickly, and have online access to all my credit card transactions.

While it’s very disturbing to have lost my wallet — I forget to appreciate how much having a method of identification factors into daily financial transactions — I also appreciate how technology lets me minimize financial damage in a quick and timely manner. Of course I’m still hoping a kind-hearted person will turn in my wallet to the police and I have filed a police report.

Do you have a “lost wallet” action plan?

Value of Money

Depending on situation, money buys:

  • stability
  • security
  • choices
  • freedom
  • influence

I am under no delusion that most of what I enjoy today in my life: stability, security, choices (to work or not to work, to do certain types of work, to work only certain hours), and freedom (being able to immigrate and stay in this country) were supported by a level of financial means.

Read some personal accounts on Quora of why people have to go to “cash advance” gouge-level interest services or why they have to line up to renew food stamps, and I appreciate all the more how “money-supported stability” makes the difference between maintaining life in the middle class versus becoming a member of the working poor.

Thus, I can’t in my good conscience talk down money like I’m holier than needing a currency. All the other stuff like bartering and in-kind services are simply other currencies that “money” represents as the de-facto symbol.

Antibiotic Resistance: Cultural Issue not Medical Science

We must tackle a cultural problem around overuse of antibiotics.

It doesn’t matter whether we keep coming up with antibiotics: we simply breed for the most drug resistant pathogens by increasing the selective pressure in bacteria. We do this by over-prescribing antibiotics.

But wait. This isn’t necessarily about getting doctors to stop over-prescribing antibiotics. If it were that simple….

When a patient comes in complaining of what a physician judge to be “a cold”, the physician may very well tell the patient, “Go home, sip lots of hot tea and chicken soup, get plenty of rest, and take some decongestant for the symptoms.”

Then that patient says, “But I waited in your damn office for 45 minutes! You’d better get me SOMETHING.”

In other words, the patient EXPECTS the doctor to write a prescription for what the patient perceives to be “more than just” a cold.

If that doctor tries to educate the patient on the broader consequences of antibiotic overuse, the patient may very well continue to demand (DEMAND!) that the doctor write a prescription for an antibiotic (yes, here in the U.S. many patients aren’t afraid to tell doctor what they want prescriptions for). If that doctor refuses, the patient simply goes to another doctor, who is willing to write the prescription.

So I don’t care if we come up with nth generation macrolide / cephalosporin or we engineer a quinolone that won’t cause such serious adverse events that half of the drugs in that class has been pulled off the shelf…

I don’t care if we start ‘designing’ antibiotics that overcome a microbe’s awesome drug-effluxing receptors…

it is only a matter of time that we create enough selective pressure for a bug to breed and mutate into a superbug that not only will clip whatever enzyme an antibiotic uses to disable the superbug’s replication system but will pump and dump that antibiotic faster than you can say “vancomycin”.

The most important thing we can do is to curb society’s demand for antibiotics for conditions that does not warrant antibiotics, and hope that pharmaceutical sciences can catch up with the superbugs.

Behavioral Economics in Personal Finance: How to Stop Over-Spending

Step 1: Control Your Purchasing Impulse By Removing Your Purchasing Ability.

Stop using all credit cards and use only cash. When you run out of cash, you don’t have money to buy anything anymore. You can be a major shopaholic: shop only in cash.

There are behavioral economics studies that have been done about what happens when your money is too far removed from cash. As soon as you abstract actual cash into a different form like tokens (as close to cash as you can get short of the actual coins) and then credit cards, your willingness to spend on impulse increases.

I’m not saying you shouldn’t use credit cards ever, but until you are disciplined enough to buy only what you can afford and you can pay off your entire credit balance every month for at least 6+ months… then cash-only will build the kind of habit that can help you manage your personal finances better. How about trying cash-only system for 1 month? It’s only 30 days but is incredibly powerful at showing you what you can actually afford and how expensive the “cheap little purchases” begin to add up.

A preferable behavioral outcome of Step 1 is for you to look for creative ways to cut costs where you can, such as buying used items, shopping for bargain items, and selling items you no longer use.

Step 2. Track Every Single Dollar into and out of Your accounts to Maximize “Pain of Paying” Reminders

I don’t use fancy programs — a simple Excel spreadsheet works for me. You can use online sites like Mint.com and Bundle.com to track your bank accounts and credit card spends once you know you have the discipline to spend only within your means, or if you are absolutely unwilling to go all-cash-only for the next 30 days.

Being able to see and track every single purchase will continue to create “salience” of every dollar that is leaving your bank account, or every dollar you are borrowing at astronomical interests rates from credit card companies. I have my credit card email me every single time a charge over $1 is registered to my account. This means I will be reminded again of what amount I spent when I check my email, and it puts “the pain of paying” at the forefront of my mind. I also have the kind of credit card that requires full-balance payoff, so I can never hold a credit card balance that incurs any interest.

Step 3. Create Budget Projections for Next Quarter Spending.

Once you have 3 months worth of data, you start tracking trends. At this point I only track certain budget items (utilities mainly) on a monthly basis because I’m so familiar with the “typical” spending caps that any abnormal fluctuations will catch my attention. Having a budget will make you feel empowered. Since I’ve been doing this for a while, I begin to make adjustments based on major life events, such as how the household utility budget will change when we moved from an apartment to a house, and new costs that having a child will incur.

All this stuff may be a pain in the butt to make habitual early on, but once you do this and get used to it, you will make use of this every year for the rest of your life.

Part of Step 3 is also the Creation of, and Insurance for, a Financial Buffer. Some people call this an emergency fund, and it is basically a pad of financial security you save up for yourself for emergency situations to prevent yourself from spiraling into (too much) debt.

In order for this to work, you need to make sure that you insure yourself against events that will put you into debt. In the U.S. these costs tend to be accidents and medical/healthcare, which means people in the U.S. must insure their healthcare costs as well as insure against certain accidents or liabilities relating to their property or their lives (especially if they have dependents).

How do you set spending limits to ensure you save toward your future?

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