A Country Doctor Writes:

I scribbled my signature on a pharmaceutical rep’s iPad today for some samples of Jardiance, a diabetes drug that now has expanded indications according to the Food and Drug Administration. This drug lowers blood sugar (reduces HbA1c by less than 1 point) but also reduces diabetes related kidney damage, heart attacks, strokes and now also admission rates for heart failure (from 4.1% to 2.7% if I remember correctly – a significant relative risk reduction but not a big absolute one; the Number Needed to Treat is about 70, so 69 out of 70 patients would take it in vain for the heart failure indication. The NNT for cardiovascular death is around 38 over a three year period – over a hundred patient years for one patient saved). There are already other diabetes drugs that can reduce cardiovascular risk and I see cardiologists prescribing them for non-diabetics.

It’s a bit of a head scratcher and it makes me think of the recently re-emerged interest in the notion of a “Polypill” with several ingredients that together reduce heat attack risk. The tested Polypill formulations are all very inexpensive, which is a big part of their attraction. Jardiance, on the other hand, costs about $400 per month.

The “rep” asked whether this medication would be something I’d be likely to discuss with my diabetic patients.

“Well, you know I’ve only got fifteen minutes…” dampened his expectations. But I told him about the Polypill studies. I think patients are still not ready to make the distinction between on the one hand medications that treat a more or less quantifiable problem like blood sugar levels, blood pressure or the much less straightforward lipid levels and on the other hand ones that only change statistical outcomes. Most of my patients have trouble wrapping their head around taking a $400 a month pill that doesn’t make them feel better or score a whole lot better on their lab test but only changes the odds of something most people think will never happen to them anyway.

I’m a simple minded person in some ways, I guess, but it helps me in my patient interactions to distinguish between what we know with decent certainty and what we think is a good probability and also between what tangible benefit a treatment can be expected to offer as opposed to just some statistical advantage that means nothing if you draw the shorter straw.

It almost makes sense to think of a two tiered approach to healthcare: some people truly want every statistical advantage and pharmaceutical intervention possible while others just want to treat what they can see or measure, and I think we have to figure out where each patient falls on the spectrum between those opposites, or we will overwhelm and lose patients and see them give up on everything we might have to offer.

Whichever approach patients take requires their commitment and determination and we need to listen carefully for clues about their beliefs and willingness to treat. There’s no point in prescribing anything in a half hearted way, because treatment adherence isn’t likely to be very good then. And doing a hard sell to a disinclined patient in fifteen minutes along with many other things we need to cover is a pipe dream and a guaranteed turnoff.

So, and this is a thought I’ve developed working with horses: Doctors shouldn’t be horse whisperers, nor should horse people. People have looked at this from the wrong vantage point. You don’t whisper to the horse so it will do what you want – you must first listen to the horse, and then, once you know how the horse feels about things, you can whisper your suggestion. And because the horse trusts you and knows you’d never suggest anything that is completely against its nature, the horse is likely to follow your low key, “whispered” suggestion better than a harsh command.

But listening comes before whispering, in horsemanship and in healthcare.

We knew that the most powerful way to provide substance abuse treatment is in a group setting. Group members can offer support to each other and call out each other’s self deceptions and public excuses, oftentimes more effectively than the clinicians. They share stories and insights, car rides and job leads, and they form a community that stays connected between sessions.

Participants with more experience and life skills may say things in group that we clinicians might hesitate saying, like “Now you’re whining” and “Time to put on your big boy pants”. They can become role models by being further along in their recovery and by at the same time revealing their own fear or respect for the threat of relapse.

What has also happened in our clinic, entirely unplanned, was that after an informational meeting where we explained the group model and had a national expert physician speak about opioid recovery, several parents raised their hand and said there should be a group for families, too.

We listened and within a few months we started such a group and now, a year and a half into it, the group is co-led by a few of our patients, who naturally had become leaders of the patient group earlier.

There is magic in having these more experienced patients explain to our sometimes bewildered parents and family members how the addicted and recovering mind works, not from having seen it a hundred times, like the clinicians, but by actually having lived it.

The positive feedback and appreciation of this, our “Friends and Family” group has elevated these experienced patients to a mentor role now also for the families trying to be the most help for their loved ones in recovery.

Our biweekly conversations are turning the spotlight on the small and large victories that come with recovery and have put the challenges in perspective through stories of the ultimate successes these mentors have had themselves.

This week, my Tuesday patient group and the Friday Friends and Family group will be held without the two clinicians who usually run the groups and also without our medical assistant, who herself plays a crucial role as both confidant and voice of the program. A stand-in clinician and a covering medical assistant will be there and I will be there virtually as usual through video conferencing.

The glue that will hold everything together will be our informal peer counselors, and I have no doubt the groups will continue as if nothing had changed because of the momentum these folks have brought to our endeavors.

They know how much they mean to all of us. By sharing the experience of their own recovery, they have breathed irreplaceable life into these groups to sustain them even if some of the facilitators are on vacation.

The Swedish word for physician is läkare, which literally means healer. That seems a lot more glamorous than the American word physician, which is derived from physic, the old fashioned laxatives that were thought to rid the body of poisons and impurities. But we are actually the healers a lot less often than we think.

The more we learn about how the body works, the more we have to admit that rather than us doctors, it is each patient that heals themself with at most some guidance from us.

We may recommend a change in diet, but we aren’t there to watch what our patients make of the advice we give them. We may prescribe a medication, but we know that many of the standard treatments in our armamentarium are only marginally better than placebo, and we now understand a little bit about psychoneuroimmunology, so we have to admit that patient expectations greatly influence the efficacy of treatments, even surgical procedures. We have learned this from sham knee operations for meniscal problems, for example. Imagine that, placebo surgery, not just pills.

This goes all the way back to the words of Hippocrates: “Let food be thy medicine and medicine be thy food”, “Walking is man’s best medicine” and “The natural healing force within each of us is the greatest force in getting well”. These quotes seem especially relevant in our struggle with the chronic diseases of the times we now live and practice in – heart disease, diabetes, arthritis; all of them at least in part autoimmune in their pathophysiology. If he body can attack and destroy itself, it also has the potential to do the opposite, to heal.

Our job, then, is to provide basic medical care AND to inspire, empower or whatever one calls awakening the self healing potential that a good diet, physical activity, good sleep, healthy relationships, care of one’s emotional needs and a good measure of faith, trust and optimism can ultimately bring about.

The chest CT report was a bit worrisome. Henry had “pleural based masses” that had grown since his previous scan, which had been ordered by another doctor for unrelated reasons. But as Henry’s PCP, it had become my job to follow up on an emergency room doctor’s incidental finding. The radiologist recommended a PET scan to see if there was increased metabolic activity, which would mean the spots were likely cancerous.

So the head of radiology says this is needed. But I am the treating physician, so I have to put the order in. In my clunky EMR I search for an appropriate diagnostic code in situations like this. This software (Greenway) is not like Google; if you don’t search for exactly what the bureaucratic term is, but use clinical terms instead, it doesn’t suggest alternatives (unrelated everyday example – what a doctor calls a laceration is “open wound” in insurance speak but the computer doesn’t know they’re the same thing).

So here I am, trying to find the appropriate ICD-10 code to buy Henry a PET scan. Why can’t I find the diagnosis code I used to get the recent CT order in when I placed it, months ago? I cruise down the list of diagnoses in his EMR “chart”. There, I find every diagnosis that was ever entered. They are not listed alphabetically or chronologically. The list appears totally random, although perhaps the list is organized alphanumerically by ICD-10, although they are not not displayed in my search box, but that wouldn’t do me any good anyway since I don’t have more than five ICD-10 codes memorized.

Patients are waiting, I’m behind, the usual time pressure in healthcare.

Can’t find a previously used diagnosis. Search for “nonspecific finding on chest X-ray” and multiple variations thereof.

I see R93.89 – “abnormal finding on diagnostic imaging of other body structures”. Close enough, use it, type in exactly what the chief of radiology had said in his report. Move on. Next patient.

Several days later I get a printout of that order in my inbox with a memo that the diagnosis doesn’t justify payment for a PET scan. Attached to that is a multi page list of diagnoses that would work.

Frustrated, I go through the list. It’s another day, other patients are waiting. Eventually I come across R91.8 “other nonspecific finding of lung field” – not exactly pleura, but what the heck, close enough, let’s use that one.

Why is this – me hurriedly choosing the next best thing on a multipage printout, while my other patients are waiting – any more practical, accurate or fraud proof than having me describe in appropriate CLINICAL language what the patient needs and letting SOMEONE ELSE look for the darn code?

Here I am, trying to order what a radiologist told me to order, without having the tools to do it.

Next thing you know, Henry’s insurance will probably have some third party radiologist deny coverage because he disagrees with my radiologist, and I’ll be stuck in the middle…

Not quite what I thought I’d be doing. Who works for whom in healthcare?

Several news media (I first saw it on BBC’s website) recently published the picture of an insect, invaded by a fungus, compelled to climb high, then killed off only to become a means for airborne spread of fungal spores.

I had also read in The New York Times about how massospora live inside cicadas and spread between them like an STD and stimulate mating behaviors to promote its spread, even though the cicadas become grotesquely altered by the fungus (see the yellow fungal “plug” in its rear). This behavior is caused by the release of Psilocybin, a mind altering controlled substance that eases depression and anxiety in cancer patients, and cathinone, a powerful stimulant.

Interesting that one life form can alter another’s behavior, but does anything like this apply to mammals, or humans? Certainly – maybe not for fungi, but definitely other parasitic (or symbiotic) organisms and viruses. Just consider the behaviors caused by rabies infection:

This seemingly improbable concept that specific microbes influence the behavior and neurological function of their hosts had, in fact, already been established. One prime example of “microbial mind control” is the development of aggression and hydrophobia in mammals infected with the rabies virus (Driver, 2014). Another well-known example of behavior modification occurs by Toxoplasma gondii, which alters the host rodents’ fear response. Infected rodents lose their defensive behavior in the presence of feline predators, and instead actually become sexually attracted to feline odors (House et al., 2011). This results in infected rodents being preyed upon more readily by cats, and allows Toxoplasma to continue its lifecycle in the feline host (House et al., 2011). Further, a variety of parasitic microbes are capable of altering the locomotive behavior and environmental preferences of their hosts to the benefit of the microbe. For instance, the Spinochordodes tellinii parasite causes infected grasshopper hosts to not only jump more frequently, but also seek an aquatic environment where the parasite emerges to mate and produce eggs (Biron et al., 2005). Temperature preference of the host can even be altered, such as observed during infection of stickleback fish by Schistocephalus solidus, which changes the hosts’ preference from cooler waters to warmer waters where the parasite can grow more readily (Macnab and Barber, 2012). Other microbes can even alter host behavior to seek higher elevations, believed to allow the infected host to be noticed more easily by predators or to eventually fall and disperse onto susceptible hosts below (Maitland, 1994). More coercively still, microbes can influence the social behavior of their hosts, causing insects, such as ants, to become more or less social to the benefit of the parasite (Hughes, 2005). In fact, the sexually transmitted virus IIV-6/CrIV causes its cricket host (Gryllus texensis) to increase its desire to mate, causing its rate of mating to be significantly elevated and allowing for transmission between individual hosts (Adamo et al., 2014).
— Read on www.ncbi.nlm.nih.gov/pmc/articles/PMC4442490/

There is, of course, now more and more interest in the role our microbiome plays in seemingly every aspect of our lives – from mood to metabolism to immunity. The more I read about this, the more humblingly (is that a word?) fascinated I become.

The well referenced review article quoted above illustrates several already known ways our microbiome affects us, and I highly recommend reading it. I’ll zero in on how our behaviors are influenced, leaving cancer, allergies and other aspects of their influence for another post. Here are some highlights:

Germ Feee (GF) mice tend to be anxious and socially impaired. These behaviors normalize when normal gut flora is introduced.

GF mice have an increased permeability of the blood brain barrier both during fetal development and in adulthood. Some strains of clostridium and bacteroides and also the short chain fatty acid butyrate can restore normal blood brain barrier function.

Probiotics (L. Helveticus and B.longum) caused decreased self reported anxiety and decreased urine cortisol levels in humans.

Microbiota metabolize fermentable complex carbohydrate/fiber into short chain fatty acids (SCFAs) such as acetate, butyrate and propionate, which cross the blood brain barrier. Acetate influences the hypothalamus’ regulation of glutamate, glutamine and GABA. It also increases anorectic neuropeptide, which suppresses appetite.

Probiotics from fermented dairy do not alter the composition of gut microbiome, but they alter the transcriptional state and metabolic activity of the microbiota.

Autism spectrum disorder (ASD) patients have an increased incidence of constipation, increased intestinal permeability and altered intestinal microbiome. Mice with ASD like behaviors have a similar overrepresentation of gastrointestinal abnormalities. Introduction of B. fragilis has normalized intestinal permeability and reduced stereotypical behaviors, communication deficits and anxiety behaviors.

“It is becoming increasingly recognized that other psychiatric and neurological illnesses are also often co-morbid with gastrointestinal (GI) pathology (Vandvik et al., 2004), including schizophrenia, neurodegenerative diseases and depression.“

“The enteric nervous system (ENS) is directly connected to the central nervous system (CNS) through the vagus nerve, providing a direct neurochemical pathway for microbial-promoted signaling in the GI tract to be propagated to the brain on mood and behavior, including depression, anxiety, social behavior, and mate choice.“

Bifidiobacterium infantis can normalize depression-like behavior in mice to a degree similar to the antidepressant citalopram.

Finally, I got the impression in medical school that the vagus nerve was unidirectional. Now I understand that it is very much bidirectional, as quoted above. Here is a quote from another article I ran into about that:

The bidirectional communication between the brain and the gastrointestinal tract, the so-called “brain–gut axis,” is based on a complex system, including the vagus nerve, but also sympathetic (e.g., via the prevertebral ganglia), endocrine, immune, and humoral links as well as the influence of gut microbiota in order to regulate gastrointestinal homeostasis and to connect emotional and cognitive areas of the brain with gut functions (1). The ENS produces more than 30 neurotransmitters and has more neurons than the spine. Hormones and peptides that the ENS releases into the blood circulation cross the blood–brain barrier (e.g., ghrelin) and can act synergistically with the vagus nerve, for example to regulate food intake and appetite (2). The brain–gut axis is becoming increasingly important as a therapeutic target for gastrointestinal and psychiatric disorders, such as inflammatory bowel disease (IBD) (3), depression (4), and posttraumatic stress disorder (PTSD) (5). The gut is an important control center of the immune system and the vagus nerve has immunomodulatory properties (6). As a result, this nerve plays important roles in the relationship between the gut, the brain, and inflammation. There are new treatment options for modulating the brain–gut axis, for example, vagus nerve stimulation (VNS) and meditation techniques. These treatments have been shown to be beneficial in mood and anxiety disorders (7–9), but also in other conditions associated with increased inflammation (10). In particular, gut-directed hypnotherapy was shown to be effective in both, irritable bowel syndrome and IBD (11, 12). Finally, the vagus nerve also represents an important link between nutrition and psychiatric, neurological and inflammatory diseases.
— Read on www.frontiersin.org/articles/10.3389/fpsyt.2018.00044/full