Links for Tuesday, November 21, 2017: more on the new HTN guideline, Gymnastics coaches throwing robot shade, the last iron lungs, Germany bans smartwatches, and Raymond Chandler hated US healthcare

Thoughtful post on the new HTN guideline by Dr. Allen Brett

Representative quote: "Consider, for example, a healthy white 65-year-old male nonsmoker with a BP of 130/80 mm Hg, total cholesterol level of 160 mg/dL, HDL cholesterol of 60 mg/dL, LDL cholesterol of 80 mg/dL, and fasting blood glucose of 80 mg/dL — all favorable numbers. The calculator estimates his 10-year CV risk to be 10.1%, making him eligible for BP-lowering medication under the new guideline. To my knowledge, no compelling evidence exists to support drug therapy for this person."

A gymnastics coach says the Boston Dynamics robot flip was a 3.5/5.0

'In a back salto, says Mazloum, “you want to be able to go as high as you can, and you want to be able to land as close to where you take off as possible.” To do that, the gymnast has to squat, throw her arms up by her ears so her body is a straight line (in gymnast-speak, opening the shoulder angle and the hip), then contract into a “closed” position again. By these standards, Atlas’ trick is “not the cleanest flip,” explains Mazloum.

Here’s Mazloum’s critique: Atlas didn’t quite get to that open position, “so it didn’t really get the full vertical that we look for. That’s why it went backwards a little bit.”'

The last of the iron lungs

Get your kids vaccinated for polio, folks.

Germany has banned smartwatches for kids

If I understand this correctly, it is not because smartwatches cause kids to be distracted monsters (although I don't doubt that that statement is at least a little bit true). The decision stems from the capability of bad guys to hack in and monitor the location of little Dick and Jane:

You have to wonder who thought attaching a low-cost, internet-enabled microphone and a GPS tracker to a kid would be a good idea in the first place. Almost none of the companies offering these “toys” implement reasonable security standards, nor do they typically promise that the data they collect—from your children—won’t be used be used for marketing purposes. If there ever was a time to actually sit down and read the terms and conditions, this was it.
Get your shit together, parents.

Asking parents to destroy them might be a bit of an overreaction, though.

Raymond Chandler paints a dark picture of American healthcare in a newly-discovered story

The title, "It’s All Right – He Only Died," sounds like the title of a video residencies would show interns to convince them that quality improvement and patient safety are part of their job.

The doctor who turned away the patient, Chandler writes, had “disgrace[d] himself as a person, as a healer, as a saviour of life, as a man required by his profession never to turn aside from anyone his long-acquired skill might help or save”.

 

Links for Wednesday, November 15, 2017: the new definition of hypertension, preventing bike accidents by driving, podcast brain-fry, and webside manner

Your new definition of hypertension is....130/90 mmHg

I remember an anthropologist in college making fun of an economist, saying the economists never changed the questions on tests, only the answers. This seems like that. But the guideline includes more organizations than I can shake a stick at:

orgs.PNG

So it has consensus going for it, I guess. And I like that it makes HTN treatment more like cholesterol treatment: initiation and targets are linked to 10-year vascular disease risk, which can be calculated here.

With a risk >/=10%, you get drugs if your BP is 130/80 mmHg or above. With a risk <10%, and you get lifestyle management alone. Everyone gets drugs at 140/90 mmHg:

HTN algorithm.PNG

"90 percent of bike accidents could be prevented by buying a car like a normal person."

I LOL'ed. 

Are podcasts frying my brain? Are they worse than silence?

I'm on board for recommendations on sleep. If we could get by with less sleep than ~7-8 hours, I figure Mother Nature would have mutated the need out of us long ago. But even though I'm a social media skeptic, I just can't quite bring myself to think that podcasts are bad for me. Maybe I love them too much. But humans are social animals, and in many cases we're put in situations where social interaction just isn't practical. Podcasts fill some of that gap for me. And I agree that the reason podcasts light up people's brains on fMRI is because fMRI is so boring to begin with:

“One of the problems you have in MRI experiments is oftentimes they are very boring,” Gallant said on Freakonomics. “If you put somebody in an MRI scanner, which is a very uncomfortable place to be, and then you flash a word at them every five seconds for an hour, they get bored out of their skull.”

To me, an apt, potentially enlightening, comparison is podcast listening versus phone calls. We know that even hands-free phone calls for drivers radically decrease the quality of driving. Listening to music is associated with no such risk, and neither is talking to a passenger in the car. So is driving while podcasting (DWP) more like hands-free driving, or is it more like driving with music? If you're futzing around with your device trying to find a podcast you like, it's clearly dangerous. That's one reason I absolutely despise Apple's new podcast app, which won't just play podcasts in series like the old app did. I have to pull over to start a new podcast if I'm in the gas-powered wheelchair. But if you don't need to touch your device to play the sound, it seems more like music. On the other hand, podcasts can't shut up when the traffic gets bad or warn you you're about to hit somebody like a passenger can. Sigh. I don't know if I'm talking myself into something or out of something at this point. 

We need to teach medical students "webside" manner

I've done a fair amount of telemedicine, all with Vigilias. (I think I was the first doc to ever see a patient on their platform). The practice is closer to in-person medicine than you think. But there are some tricks, as the article points out:

"It sounds strange, but when you're on camera all your actions are magnified," Krupinski says. Sitting six feet away from your doctor, in person, you might not mind or notice her slouching, fidgeting, or gesticulating. But a webcam's intimate vantage point augments these actions in ways that patients can find distracting or off-putting. "You take a sip of coffee and your mug takes up the whole screen, and all they hear is the sound of you slurping," she says. "Or you turn away to make a note, and now all your patient sees is your shoulder. Maybe you disappear from the frame entirely."

And this one is the hardest to get used to:

To appear as though they're making eye contact, clinicians are taught to look not at the patient on their screen, but directly into their device's webcam.

I had other little quirks in my telemedicine days: I had to move my studio to the basement because of complaints about the neighbor's dog barking in the background. And at the beginning I only "dressed" from the waist up, since patients would never see me below the waist. But I found that it made me self-conscious. I needed to have some kind of uniform on to feel like a doctor. 

Should young, healthy people with type 1 diabetes take statins?

I encountered this question a couple months ago in a consult and intended to blog about it then, but relatively little trial data was available. I would have essentially been giving my own off-the-cuff opinion. That's very unsatisfying to me, and probably to the reader.

As background: we tend to think of type 1 diabetes as more a need for hormone replacement (insulin) than as a disease state requiring the complex management that type 2 diabetes requires. That is to say that type 1 diabetes, for all the unpleasantness it causes for people, is easier on the blood vessels as a general rule than type 2 diabetes. The ADA has a statement in its guideline that "For patients with diabetes aged <40 years with additional atherosclerotic cardiovascular disease risk factors, consider using moderate-intensity or high-intensity statin and lifestyle therapy." It's a category C recommendation, meaning it's mostly opinion and has a less-than-spectacular evidence base. It also doesn't differentiate between type 1 and type 2 diabetes. Similarly, a joint statement by the ADA and the AHA states that "Adults with T1DM who have abnormal lipids and additional risk factors for CVD (eg, hypertension, obesity, or smoking) who have not developed CVD should be treated with statins." Both statements argue against the routine use of statins in young healthy type 1 diabetics.

But a recent study from the New England Journal helps us with the question of statins in kids, and throws in ACE inhibitors for good measure. Investigators led by M. Loredana Marcovecchio and Scott T. Chiesa randomized 443 kids between 10 and 16 years with type 1 diabetes and urine albumin-to-creatinine ratios in the upper third of "normal" to some combination of ACE inhibitor, statin, and placebo. Creatinine is a consistently excreted product of muscle metabolism that serves as a nice comparator for other things the kidney excretes. So even if you drink a lot of water and dilute the amount of albumin in your urine, we can look at it compared to the similarly diluted creatinine and see if you're excreting too much.

Anyway: the investigators used a 2 x 2 trial design, meaning that there were ultimately four groups: placebo-placebo, placebo-ACEi, placebo-statin, and ACEi-statin. The statin was atorvastatin 10 mg daily, and the ACEi was quinapril 10 mg daily (after titration). They were most interested in the change in albumin excretion (that is, how much protein spilled through the kidneys into the urine). They assessed this according to that same measure, the albumin-to-creatinine ratio in the urine, from three early-morning urine samples obtained every 6 months over about two and a half years. They also looked at secondary outcomes like the new development of microalbuminuria (that is, the new appearance of protein in the urine), worsening of eye disease, changes in kidney function, blood lipid levels, and measures of cardiovascular risk. For the cardiovascular risk, they did ultrasounds of the carotids to measure the thickness of the vessels (carotid intima–media thickness) and measured levels of high-sensitivity C-reactive protein and asymmetric dimethylarginine in the blood. Both of these are generic markers of vascular risk.

After an average of 2.6 years, no benefits were found within the ACEi group, the statin group, or the ACEi+statin group compared to placebo. Unsurprisingly, the ACEi group had a much lower incidence of new microalbuminuria, but "in the context of negative findings for the primary outcome and statistical analysis plan, this lower incidence was not considered significant (hazard ratio, 0.57; 95% confidence interval, 0.35 to 0.94)." Also unsurprisingly, the use of statins resulted in lower cholesterol levels (including, unfortunately, HDL). But neither drug had significant effects on carotid intima–media thickness, C-reactive protein, kidney function, or progression of eye disease.

So we can take away from this small-ish study that, at least in a short amount of time in pretty healthy twelve-year-olds (the subjects were excluded if they had genetically bad lipid levels; the participants' average A1c was ~8.3% and their average blood pressure was 116/65 mmHg), there was no benefit to statins or ace inhibitors. This study will influence my recommendations to patients and other docs in the future. The kicker, naturally, is that many young people with type 1 diabetes have imperfect blood sugar control. What about those who can't get their diabetes controlled? It's a tougher call in that case, and this study didn't address it. 

Links for Tuesday, November 7, 2017: hacking the genome, ammonia in the NFL, and community health workers for hypertension

Body hacker Josiah Zayner wants us all to use CRISPR to modify our bodies

And give ourselves cancer. I think he forgot the cancer part. From author Rowan Jacobsen:

"Let’s be clear: don’t try this at home! Although hundreds of gene-therapy trials are under way, and many experts believe they will eventually transform almost every aspect of human health, few have been proven safe. When you start scrambling your DNA, very bad things can happen. You can get cancer. Your immune system can attack the unfamiliar DNA, as happened when an 18-year-old with a rare metabolic disorder died during a University of Pennsylvania gene-therapy trial in 1999."

You may recall a link I posted to this guy giving himself a DIY fecal transplant. I'll give him an A+ for marketing. You can't beat the name Gut Hack:

NFL players have decided (not recently, it seems) that inhaling ammonia is performance-enhancing

Instead of something sinister, though, what the widespread use of smelling salts really reveals is the increasingly bizarre culture created by the NFL's (win-at-all-costs pressure cooker. Extreme parity, the minuscule margin of error, the constant threat of injury and million-dollar stakes all push players to exploit any shortcut, no matter how weird, gross or pitiful. More than a century ago in major league baseball, players like Hall of Fame pitcher Pud Galvin thought consuming ground-up monkey testicles was the answer (seriously). A decade ago, football found deer antler spray. Now it's smelling salts.

Not coke, but smelling salts in a cup. I think I would actually prefer ground-up monkey testicles.

More evidence that community health workers improve the care of certain patient populations

(paywall, but the abstract is free)

The proportion of patients with controlled hypertension increased from 17.0% at baseline to 72.9% at 18 months in the intervention group and from 17.6% to 52.2% in the usual care group; the difference in the increase was 20.6% (95% CI, 15.4%-25.9%; P < .001).

 

The Gingerbread Man: an iStory

“You should go as the Gingerbread Man,” she said. “I'll be the fox!”

“It's kind of played out, isn't it? Women as foxes?” I replied.

She glanced at my leg. “Well, I could go as the old lady or the farmer. But you have to be the Gingerbread Man.”

“You could be Little Red Riding Hood and I could be the Big Bad Wolf,” I offered.

“Meh. It just wouldn't be the same. Don't you think this would be fun? You never want to have any fun with this. Shouldn't we take advantage?” She looked down at me again.

I didn't bother to offer Hansel and Gretel.

On Halloween I wore a brown shirt and pinned up the right leg of my brown pants. I left my prosthetic leg at home. I left my crutches home, too, so I leaned on her all night. When we got home, I was just under a quarter gone.

What do we do with a free testosterone?

Put another way: what's the free testosterone cutoff we should use for initiating treatment in potentially hypogonadal men?

Spoiler alert: maybe 70 pg/mL?

Background: a new paper from Anna Goldman, Shalender Bhasin, Frederick Wu, Meenakshi Krishna, Alvin M Matsumoto, and Ravi Jasuja lays out their thoughts on the state of the science in free testosterone measurement. This is important because we currently operate under a theory of "bioavailable testosterone." That is, we think that only testosterone that is unbound by proteins, the most important one called "Sex Hormone Binding Globulin," or SHBG, has any effect on the testosterone receptor. All the testosterone that's floating around attached to SHBG or other proteins is inert.

But like any other hormone, testosterone's binding to SHBG or other proteins is affected by myriad causes, like obesity, other hormonal disorders, and other conditions or medications. Even the temperature at which it's measured. So guidelines from the Endocrine Society suggest measuring free testosterone levels in men whose total testosterone concentrations are low-ish and in men with conditions or medications that make total testosterone measurements less reliable (like obesity). But those same guidelines rely almost entirely on the total testosterone to determine who needs testosterone therapy. From their 2010 guideline:

The panelists disagreed on serum testosterone levels below which testosterone therapy should be offered to older men with symptoms. Depending on the severity of clinical manifestations, some panelists favored treating symptomatic older men with a testosterone level below the lower limit of normal for healthy young men [280–300 ng/dl (9.7–10.4 nmol/liter)]; others favored a level less than 200 ng/dl (6.9 nmol/liter). The panelists who favored treating men who had values less than 300 ng/dl were more influenced by the observation that men who have values below that level often have symptoms that might be attributable to low testosterone. The panelists who favored not treating unless the serum testosterone was as low as 200 ng/dl were more influenced by the lack of testosterone treatment effects in randomized clinical trials when subjects had pretreatment values of 300 ng/dl but suggestions of beneficial effects when the pretreatment values were closer to 200 ng/dl. The lack of definitive studies precludes an unequivocal recommendation and emphasizes the need for additional research. [emphasis mine]

No mention of the free testosterone in there. More research needed, they say. Well, Goldman et al have delivered it, in a way. They didn't do any new investigation, so far as I can tell, but they did review the existing literature pretty thoroughly and come up with a series of conjectures. The most important of these clinically is this (my words, not theirs):

 

Without a harmonized, replicable normal range between laboratories and methods, we cannot set a clinical threshold for free testosterone levels at which we should initiate treatment.

 

The authors point out that in a study by Le et al, only about a quarter of labs performing free testosterone assays would even confirm that they had performed validation studies on their assay. But seeking a clinically relevant answer, they go on to point out that In the Framingham Heart Study, the lower limit of the normal range for the calculated free testosterone for men between 19 and 40 (defined as the 2.5th %ile) was 70 pg/mL (242.7 pmol/L). They do not endorse this as a threshold. But given the lack of other published thresholds, I think it is at least a start. 

One more point before I wrap up: whatever value you or your doctor use, whether it's free testosterone, bioavailable, or total, the number is only one piece of data. A free testosterone of 70 pg/mL in a young man with normal body hair, normal muscles, and a normal libido would not cause me to treat him. That same level in a man with a known pituitary issue, enlarging breasts, and fatigue would definitely cause me to treat him. And I tend not to recommend checks of testosterone in elderly men, even those with fatigue, unless they have other compelling evidence of hypogonadism. And my opinion is generally in line with that of the Endocrine Society:

We recommend against a general policy of offering testosterone therapy to all older men with low testosterone levels. (1|⊕○○○)

We suggest that clinicians consider offering testosterone therapy on an individualized basis to older men with low testosterone levels on more than one occasion and clinically significant symptoms of androgen deficiency, after explicit discussion of the uncertainty about the risks and benefits of testosterone therapy. (2|⊕○○○)

Why else do I hesitate to give testosterone? In a series of trials in JAMA and JAMA internal Medicine earlier this year, men aged 65 and older with a total testosterone level <275 ng/dL plus either sexual or physical dysfunction or reduced "vitality" were randomized to get either testosterone gel (lotion that absorbs through the skin) or placebo for 1 year. The men who got testosterone developed more coronary plaque than the men on placebo. (This may or may not mean anything; in other observational studies, the rate of heart problems was lower in men prescribed testosterone than in untreated men). 

Importantly for the men who tend to come to me with suspected androgen deficiency, though, the men in these studies had no improvement in memory or other measures of brain function.

Testosterone did slightly improve bone density and bone strength compared with placebo. And testosterone seems to have improved the hemoglobin level (the weight of the oxygen-carrying protein in our blood) in anemic men by 1 g/dl more often than placebo did.

If all that sounds confusing, it's because it is. When I was an endocrine fellow, one of my faculty told me that in almost every case, if you don't know what to do, the correct path is to do nothing. So that's the direction I lean in borderline androgen deficiency cases, whether determined by total or free testosterone levels. I lean toward withholding therapy.