Thoughts from the Front Lines

(by whizbang) Feb 04 2016

Clean-Up Guide

Remember, no matter what you must clean up, you have earned that drink or candy or other treat. Enjoy!

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Before and After

(by whizbang) Jan 27 2016

Life contains a number of events that define turning points. "Before graduation", "after I had kids", and "once I got promoted", for example.

Last week now stands as one of those events. My husband developed a major mental status change. Within 24 hours we diagnosed his brain tumor and had it out the next day. He is much better now mentally, but we have a long road ahead of us.

In those first days, adrenaline kept me going. I had to notify family and get through the immediate issues. (By the way, 140 character twitter updates are the perfect length for anyone in a surgery waiting room. Cute animal photos also make a nice break in the tension.) Post-op, he was sitting up in the ICU talking to us again. Every time I saw him over the next 5 days he was more fluent and seemed more like himself.

Now the relatives have gone and the bouquets are fading. He manages his own medications again. He does not yet feel like he should drive (and he is grounded till his neurosurgery follow-up in 2 weeks), but he wants to use our OKC Thunder tickets this Friday. His progress is not as fast, but we both hope it will continue.

We no longer have any idea what our future holds. For now, we are dealing with stuff as it happens. Be warned - this blog will likely feature some intense introspective naval-gazing in the coming weeks and months.

Welcome to After.

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Why We Can't Do a Cancer Moonshot

(by whizbang) Jan 15 2016

The moment was beautiful, Obama announcing that Biden would direct our next public effort, a moonshot, to cure cancer. Of course, this will not happen with cancer or any other disease that comes to mind.

First, cancer is more than one disease. It affects multiple organs in multiple ways through multiple mechanisms. Most diseases that kill in the US right now could be described this way. Even diabetes, mostly driven by obesity, probably results from a variety of genetic and environmental mechanisms. If we are talking about a single, well-characterized disorder with a single cause, we might be able to do something in a 12-year window.

The bigger problem is we do not know enough about this stuff. When Sputnik launched, we had the same knowledge base as the Soviets. We understood rocketry and astroscience enough to make a moon landing happen. Sputnik pushed the resources to the project. The basic science and technology was available; it was an incremental, if huge, project.

We are not there with most forms of cancer. We do not understand the basic biology well enough yet.

After discovering insulin, Banting turned to cancer research. He made no inroads there. I can remember Nixon declaring war on cancer shortly after the moon landing. We have come a long way since then, but the battles still rage on.

If we really want to cure diseases, we need to fund a wide variety of research ranging from the most basic sciences to clinical studies. We can never predict what finding will provide the key to a breakthrough, no matter how good we believe our peer-review system may be. It may be in a seemingly unrelated field.

We need sustainable growth of the budgets for the NIH and NSF. That will, someday, help us overcome the multitude of cancers and other disorders that we face.

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Reflections in a Cracked Mirror

(by whizbang) Jan 13 2016

In the past 6 months, my feeds brought me numerous articles in the medical education literature about incorporating humanism and reflection. Medical educators encourage students to ask open-ended questions and let patients tell their stories. These techniques should help create thorough, empathetic physicians who can really connect with their patients.

Of course, we then take these idealistic young things and feed them into a grinder that demands a certain level of "production." Patient visits can only last a few minutes, or we cannot generate enough revenue to keep the enterprise humming and the lights on. Increasing efficiency and productivity has worked well in industries. In healthcare, it may be counterproductive, especially when the average patient has multiple chronic conditions to be addressed at each visit.

Physicians also receive instruction now to "negotiate a treatment plan" with each patient. Instead of delivering "the cure from on high" we should take into account each individual's desires, perhaps increasing their buy-in and adherence to the plan. We can help each patient get better, even though we may fall short of the ideal outcome. Of course, the insurers actually paying for the care will grade us and base what we are paid on patient perceptions and our alignment with evidence-based guidelines. A patient may be happy with their plan of care, but it falls short of the prescribed goal of oversight groups. Will the insurer pay me based on the patient's happiness or on adherence to standards?

Is it any wonder that physicians are angry and burned out? Every day I encounter the insolvable problems of the current system. I may see a child that has a trivial lab value in my clinic. That "waste and inefficiency" in the system makes my employer very happy since it's more revenue. Of course, part of this is due to time pressures on primary care physicians. Researching stuff after a visit is unpaid work. If you make the wrong decision, you can get sued. Making that referral is fast, costs you almost nothing, and covers your ass for the future.

I have no answers, of course. This post is merely my reflection on the conflicts I see between what we teach our preclinical students and what our reality is. Think of it as my own bandage for burnout.

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Urine Science as Promised: Microalbuminuria in Toddlers

(by whizbang) Jan 08 2016

So-called microalbuminuria first gained attention as a predictor or marker of diabetic kidney disease. We now know that it is not as good as we thought for that condition, but it is associated with renal and cardiovascular disease risk in adults. Is shedding extra albumin in the urine a risk marker or, perhaps, does it contribute to the development of these conditions? After all, these are major causes of morbidity and mortality.

Could it be that microalbuminuria precedes any of the other stuff? Are we born this way?

The first question to answer is the prevalence of microalbuminuria in children. A group in The Netherlands organized a cohort study over the first two years of life in its general population, the Groningen Expert Center for Kids with Obesity (GECKO). All children born in Drenthe, a northern Dutch province, were eligible for enrollment From April 2006 through April 2007. The primary goal of this study was to identify factors associated with overweight. Data included pregnancy complications, birth weight, placenta weight, and longitudinal anthropomorphic measurements through 5 years of age. Lifestyle and environment factors were assessed by questionnaires beginning in the last trimester of pregnancy. Over the 2-year enrollment period 4778 eligible births were recorded. For this study, a urinary albumin measurement had to be performed; 1352 children did this and were included in their analysis. Children with urine studies did not differ from the overall population for any variable studied.

Their method of urine collection sparks some controversy. Two-year-olds usually do not pee in a cup on command. Sticking a plastic baggy on the perineum requires some skill so that it hangs on long enough for the collection but does not get contaminated by stool. The investigators gave the parents a cotton wool pad to place in the diaper and mail back into the center within 24 hrs. They compared this method to voided urines and found acceptable performance for their method with bias -14 mg/dL albumin, precision 31.3 mg/L, and accuracy 48.1%. Contact with cotton is known to decrease albumin levels within 15 minutes by an average of 40% with high variability.  A nice review of issues with pediatric urine collection can be found at another link.

The standard clinical measurement of microalbuminuria is the albumin:creatinine ratio to correct for the amount of hydration. The median ratio in this study was 14.0 mg/g creatinine. The 75th percentile was 25.6 and the 95th percentile 89.3 mg/g, respectively. Based on the current criteria for microalbuminuria (ratio > 30 mg/g), 23.4% of their kids had microalbuminuria. However, this normal range comes from adult data. Toddlers often have lower creatinine levels because of their lower muscle mass. More study will be needed to determine a level of risk in this population.


Fig 3. doi: 10.1093/ndt/gfv407

The authors had data from another regional adult study (PREVEND) for comparisons, although it used concentration of albumin rather than the ratio. Using albumin concentrations, 6.9% of toddlers met criteria for microalbuminuria, similar to levels seen in healthy adults overall (Fig 3, right). This is especially true for young adults (Fig 4, below).

Fig 4. doi:  10.1093/ndt/gfv407

Fig 4. doi: 10.1093/ndt/gfv407

Effects of prenatal and early life factors to promote disease later in life have been proposed for years, most famously by Barker in the relationship between low birth weight and later cardiovascular risk.  No association could be demonstrated with birthweight, gestation age, impaired placental growth, gestational hypertension, or smoking during pregnancy, providing no support for the Barker hypothesis.

Other issues include the use of a single specimen for determination of albuminuria. A variety of factors can cause transient urinary abnormalities. Repeated elevations over weeks to months are required for clinical use at this time.

While not definitive, this study provides valuable information on microalbuminuria in toddlers. Might we be born with differences in endothelial function, or in other kidney structures, that make our kidneys leaky and predispose us to later cardiovascular disease? Only time, and further study, will tell.

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I Beg To Differ: My Avocado Slicer

(by whizbang) Jan 04 2016

Just before Christmas gift exchange, I heard Alton Brown discouraging the use and gifting of single-use kitchen tools. I also used to pooh-pooh such things, and some of the items discussed in his interview his interview truly perplex me (a square hard-boiled egg?). However, one such tool has a permanent place in my gadget drawer:

The main blade is all plastic. While it easily slices the skin and flesh of the fruit, you would be hard pressed to scratch yourself with it. The only metal pieces are within a cupped area. They are not sharp enough to cut skin, yet they grip the pit and easily twist it out. Finally, the plastic blades in the slicer easily cut through ripe fruit, but I cannot imagine anyone hurting themselves with it.

I used to dismiss these things as nonsense; I could use a chef's knife! Then, I cut myself pitting an avocado and ended up in the emergency room. My payment for that visit (not to mention the subsequent infection) would buy more than 45 of these tools. One of my nurses suffered a very similar injury this fall, also while pitting the fearsome green fruit. I gave her one of these devices.

We are worth it.

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Happy Holidays

(by whizbang) Dec 22 2015

RedcupJoin me in raising a plain red cup to the winter solstice and its celebrations in all cultures and communities.

To my friends and acquaintances in the southern hemisphere, fear not. You will get your winter in 6 months.

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Gifting Adventure, Steampunk Geek Girl Style

(by whizbang) Dec 11 2015

Click to order

Click to order

Looking for a great gift for a tween/teen girl? Or even someone a bit older (hey, I'm over 50)? Look no further.

I just finished Gail Carringer's Finishing School series. As noted in the first book:

It's one thing to learn to curtsy properly. It's quite another to learn to curtsy and throw a knife at the same time.

Set in a steampunk version of Victorian England, the stories focus on Sophronia, a 14-year-old girl who would rather take things apart than flirt with boys. She gets sent to Mademoiselle Geraldine's Finishing Academy for Young Ladies of Quality (always pronounced quali-tay), a school set in interconnected dirigibles so it floats above the moors. It rapidly becomes apparent that this is more than an etiquette academy. Soon Sophronia has learned how to use a well-timed faint to her advantage. She excels at fighting with a fan tipped with steel blades.

This being a steampunk world, homes and school have tracks laid for mechanical servants to roll about and do their jobs. These same servants in the school can help enforce curfews as well. In addition, the world is inhabited by immortals, including werewolves and vampires. The latter live in hives, with mortal human drones who provide a food source for the vampires. Werewolves also tend to run in packs and cannot float, so a werewolf cannot board the school. Becoming an immortal is not as straightforward as in the usual literature; transition to either species is difficult and often not survived.

In addition to the mechanical slaves, there have to be human servants. For the school, the giant steam engines run through the efforts of sooties, black youth who shovel coal and fix the riggings. One of these young men, Soap, becomes acquainted with Sophronia as she galavants about the blimp against all the rules. Can you see the forbidden love interest from here?

Conflict occurs and drives adventures through 4 books. The Picklemen want to rid the world of immortals by taking control of the mechanicals that serve society. Of course, Sophronia and her entourage save England from an ugly fate. Her colleagues include immortals, a girl who lives as a boy, and a mechanical steam dog.

These books provide a lively romp through an alternate history. I just love imagining all these proper young ladies learning the feminine arts while doing very untraditional things. I also greatly appreciate that Sophronia chooses a nontraditional lifestyle in the end, rather than the politically influential marriage that most of the spy-maids enter. I won't spoil the ending, but it is worth every moment.

These four books seem to close the saga. I really wish they didn't and we could go on with Sophronia's adult adventures.

I also believe that this series could be the next big YA movie franchise. Are you listening, Hollywood?


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Learning from the Pharmacy

(by whizbang) Dec 07 2015

PharmacyA morning news show included an interview with folks amazed that the San Bernardino shooters had accumulated so much ammunition, explosives, etc. How did no one notice them accumulating this deadly stuff?

We had this problem a few years back with people buying large quantities of pseudoephedrine to cook meth. Now quantities of cold medicines including this drug get dispensed from behind the pharmacy counter. You must show identification to purchase, and your purchase gets logged in a database to keep you from going store to store. Other cold medications also require ID at checkout, even though they are not sequestered behind the counter (and I am not certain how you would make them into a drug with street value).

We could do something similar with ammunition. Yes, the vast number of bullets are sold to law-abiding citizens who would then be subject to government scrutiny. Of course, the same is true of pseudoephedrine, but we are willing to take a chance with a bit of liberty for the public good.

I'm up for it for bullets.

I'm sure that this idea will get as far as extended background checks for gun purchases and banning those on the no-fly list from gun ownership (really? people can't get on a plane, but it's safe for them to have a firearm?!?).

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Calling Biochemists

(by whizbang) Dec 01 2015



For ten minutes every morning I entertain myself with fashion magazines while my hair gets dry. The December issue of In Style greeted me with the advice to the right.

It has been a few years since doctor school, but metabolism of ethanol does not seem to have changed much (discussion here). I have seen a number of theories on hangovers through the years, with most focusing on volume loss and intermediaries of the metabolic process.

Downing a cup of water between overindulging and sleeping it off might help with dehydration. I am at a loss to explain how a tablespoon of vinegar or a drop of raw honey would be of value here.

Here is a link to Nikki Ostrower's integrative nutrition center.

While this concoction certainly will do no harm, I am not conviced that it would prove superior to just chugging water or other fluid. I would also love to see evidence that it facilitates alcohol metabolism.

Your turn, biochemists. Educate me!

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