Occum’s razor and Hickam’s dictum: Strange new diseases or something much more interesting?

I have an unusual fascination with the concept of medicine as both an art and a science. Superficially, the two disciplines have little to do with each other – Where medicine is sterile, factual, statistical, and specific, art is paradoxically relaxed, fluid, and imaginative. The role for creativity in the mind of a doctor is limited. We are thinkers and memorizers of minutia. Artists are thoughtful and philosophical. The proverbial war of the left versus right-brained prevails.

The ancient Greek physician Hippocrates is credited with being the first to truly separate medical science from religion and philosophy, based on his belief that disease was not a punishment inflicted by the gods but rather the product of environmental factors, diet, and living habits. For this, he is touted as being the “father of medicine.”

Fast-forward a thousand years, and we meet a lesser known, but equally influential ancient physician, named Claudius Galenus. Galenus studied Hippocrates’s understanding of pathology, but was also heavily influenced by the writings of the great Greek and Roman thinkers like Plato and Aristotle. He recognized medicine as an interdisciplinary field that was best practiced by utilizing theory, observation, and experimentation in conjunction.

One of Galenus’ most famous writings is the treaty entitled “That the best physician is also a philosopher”, which called for a melding of rationalist and empiric medicine sects. Galenus believed the best doctors were the best because they really thought about what they did.

My obsession with medical philosophy introduced me to the interesting and opposing theories called Occam’s razor and Hickam’s dictum. No, these strange-sounding terms do not refer to unusual diseases, but rather to two important, yet contradictory fundamental philosophical ideals of medicine, with specifics regarding the approach to the diagnosis of disease.

Occam’s razor refers to the idea of “diagnostic parsimony”, which means when diagnosing a given injury, ailment, illness, or disease, a doctor should strive to look for the fewest possible causes that will account for all the symptoms.

Hickam’s dictum counterbalances Occam’s razor by stating more often, it’s statistically more likely that a patient has several common diseases, rather than having a single, rare disease that explains a myriad of symptoms.

In veterinary school, we learn when that we hear hoofbeats, we should look for horses, not zebras. The adage refers to more than just the sounds made by the limbs of our patients. Essentially, we’re trained to think more like Occam, and base a diagnosis on the idea that “common things happen commonly”.

An unvaccinated puppy with vomiting, bloody diarrhea, and a fever likely has parvovirus. An older cat with vomiting, weight loss, a rough hair coat, and a lump on its throat likely has hyperthyroidism. In other words, keep it simple, explain things in the most uncomplicated way, and you will have your answer.

There are times, as a veterinary oncologist, I find Occam’s razor to be a bit cumbersome. Don’t get me wrong – I’m a huge fan of giving my patients as few problems as possible and I’m happy to leave Hickam’s mentality to my internist friends who love to come up with dozens of differential diagnoses for each and every one of a patient’s clinical signs. But I can’t ignore the innumerable instances where I’ve seen Occam’s line of thinking not only to be wrong, but also downright dangerous for my patients.

Perhaps the worst “Occam offense” occurs when a veterinarian concludes a pet’s most likely diagnosis is cancer based solely on demographic characteristics such as their age or breed, in lieu of performing diagnostics designed to verify their suspicion.

I understand owners are reluctant to spend money on expensive tests when the outlook for their beloved companion may be poor, and vets are often expected to offer their professional opinion as to a diagnosis prior to having the evidence they need to be sure. This doesn’t excuse a doctor from their responsibility for knowing and stating their limitations and their obligation to divulge an inability to predict an outcome off of limited information.

Occam’s razor also fails owners when we “blame” cancer, or anti-cancer treatments, for a pet’s adverse signs, behavior changes, or lab work alterations that actually result from a completely separate illness or condition. Cancer most commonly strikes older to geriatric pets, a population of animals predisposed to a wide variety of chronic, progressive diseases.

Sometimes a cat with lymphoma isn’t eating well because they have worsening kidney disease unrelated to their cancer. Sometimes dogs have diarrhea because they’re fed a remarkable amount of table scraps and it has nothing to do with their chemotherapy.

I don’t think it’s an end all be all West Side Story type of analogy where a veterinarian must choose whether they’re an Occam or a Hickam. That’s an oversimplification of the point I’m trying to make.

The more important issue is how we need to open up some of the tunnel vision that blinds us to the bigger picture of what’s really going on with our patients. We’re obligated to treat the whole animal, and their entire family, with equal parts respect and knowledge. Occum’s razor isn’t an excuse for laziness or ineptitude.

If we sway too far towards diagnostic parsimony, we could easily miss important signs of other diseases or conditions that are unrelated to our primary concern. Likewise, it’s possible to knit pick each and every detail of a pet’s case to the point where we are blinded by the possibilities of their pathology.

Finally, pet owners should keep an open mind when it comes to their veterinarian’s recommendations for further testing when a definitive diagnosis has not yet been achieved. Opinions and experience account for a great deal of the art of medicine, but there’s also tremendous amount of data garnered from the plain old science part of the discipline as well.

Maybe the hoofbeats are zebras more often than we think.

Maybe I sound a bit too philosophical for a doctor.

Maybe they said the same thing about Galenus…

 

 

 

 

 

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What’s the one side effect of cancer treatment I can never control?

We’re familiar with the more common side effects associated with chemotherapy treatments: nausea, vomiting, lethargy, and hair loss. We all too easily relate to such signs, whether a result of our own personal experience, or those of friends/loved ones, or even through different media outlets.

In veterinary oncology, every precaution is taken to limit such side effects. We accept a much lower rate of toxicity in dogs and cats, so our initial drug doses tend to be lower than our human counterparts. If side effects do occur, we are quick to reduce future dosages or delay treatments, keeping our patient’s safety at the forefront of concern. We want our patients to remain happy and healthy while enduring their protocols and to remain oblivious to the potentially negative repercussions of such serious remedies.

There’s one side effect from chemotherapy that both veterinary and human oncologists remain persistently unable to adequately control. No matter how much effort we put in to preventing it, we are at the mercy of this most disturbing of adverse treatment-related injury. The concern we are speaking of is called financial toxicity.

Financial toxicity, a term first coined by researchers in a study published in The Oncologist in 2013, describes how the “out-of-pocket expenses” of cancer treatment further drain the already stretched emotional and personal reserves of cancer patients, ultimately causing a significant decline in their overall quality of life and, in its most severe form, becoming an actual, palpable adverse side-event of treatment, leading to cessation of treatment.

In the aforementioned study, researchers compared the results of surveys evaluating the impact of health care costs on well-being and treatment of cancer patients who contacted a national copayment assistance foundation with those from patients treated at an academic medical center. The results are staggering.

Among 254 participants, 75% applied for drug copayment assistance. Forty-two percent of participants reported a significant or catastrophic subjective financial burden; 68% cut back on leisure activities, 46% reduced spending on food and clothing, and 46% used savings to defray out-of-pocket expenses.

To save money, 20% took less than the prescribed amount of medication, 19% partially filled prescriptions, and 24% avoided filling prescriptions altogether.

Copayment assistance applicants were more likely than non-applicants to employ at least one of these strategies to defray costs (98% vs. 78%).

One conclusion from the study is that financial toxicity has both an objective side (a true enumeration of the burden the treatment places on the affected individual) as well as a subjective side (the less tangible distress the burden of treatment places on the patient).

Another conclusion was that the consequences of financial toxicity reach far beyond the checkbook and extend into influencing important demographic information including response rates and survival statistics. Patients may actually stop taking medications, or even stop treatment entirely, because of the rising costs of their own healthcare and the burden this places on their lives.

Not surprisingly, though financial toxicity isn’t typically discussed as an “actual” side effect in veterinary medicine, money plays a huge role in the oncological care for companion animals. Having worked directly in the trenches for so long, I would even venture that veterinarians deal with financial toxicity far more frequently than our human doctor counterparts.

When cancer strikes a beloved pet, in addition to the emotional toll, the majority of owners must, at some point, consider the monetary impact of the diagnosis. Unlike humans diagnosed with cancer, our pets typically lack comprehensive healthcare to cover even routine costs, let along oncological care.

A long-standing joke in veterinary medicine is to be wary of the owner who states “money isn’t an issue,” as most often it’s not an issue because they don’t have any. Cancer generally always imparts a sense of urgency, and I’ve witnessed many times where owners will make decisions regarding their pet’s care without full consideration of finances. In all seriousness, I have no way of knowing whether an owner who is giving me free reign to move forward with diagnostics and/or treatments is really able to afford things, or if they are making decisions based on emotions.

I’ve seen many reactions to the cost of chemotherapy for pets. Most owners are well prepared by their primary care veterinarians for estimates of what different treatment plans could cost. There are definitely cases of complete “sticker shock,” where the numbers I discuss are not at all on par with what the owners were anticipating. Other times the reaction is the polar opposite, where there’s great surprise and the treatment is considered inexpensive.

There’s not much I can do to control the cost of veterinary oncology care. Unfortunately, pricing schemes are complex; dictated by factors well beyond my professional “jurisdiction.” But it’s not enough for me to discuss only the physical signs associated with treatment when talking about side effects with owners. I’m equally responsible for attempting to prevent financial toxicity when I can.

As is true for so many aspects of veterinary medicine (and life in general), clear communication is essential to ensuring everyone is on the same page. Your veterinarian should never judge you for deciding to put finances first when considering how to proceed with your pet’s care. And you should never judge your doctor for talking candidly about prices, estimates, costs, and expectations. I’ve been placed in that situation more times than I’d care to admit, and it’s unpleasant for all parties.

We may not be able to eliminate financial toxicity from our treatment regimen, but veterinarians and owners both have a responsibility for making sure we pay close attention to even the subtlest signs of this important side effect. If we treat it as urgently and effectively as we do the more obvious signs, we’re guaranteed to reduce its impact and to further ensure that we maintain our patient’s quality of life, both in and out of the veterinary clinic.

Metronomic chemotherapy – is it the right choice for your pet?

In order for tumor cells to multiple and spread, they must develop their own blood supply through a process called angiogenesis. Angiogenesis inhibitor chemotherapy drugs work to stop or slow down this process, thereby controlling tumor growth. Metronomic chemotherapy is one example of angiogenesis inhibition treatment, which is becoming a popular treatment option for pets with cancer.

 

The definition of metronomic chemotherapy is variable, but usually refers to the continuous administration of low doses of oral chemotherapy drugs designed to target the endothelial cells lining the blood vessels supplying tumor cells.

 

When traditional cytotoxic chemotherapy is administered at maximally tolerated doses (MTD – see previous blog article entitled “Is the remedy for cancer worth the cure?”), death of the endothelial cells lining the blood vessels of tumor cells occurs first, followed by the death of the tumor cells. When we administer chemotherapy in this manner, we typically need to give our patients a rest period between subsequent treatments so healthy cells can repair and regenerate. This delay, necessary to prevent excessive side effects, unfortunately allows damaged tumor blood vessels to recover as well, and may lessen the overall efficacy of the treatment.

 

Metronomic chemotherapy entails the chronic administration of low-dosages of chemotherapy, so theoretically the inhibitory impact on the tumor blood vessel growth is maintained, but the dose is insufficient to cause damage to healthy cells.

 

Historically, metronomic chemotherapy in veterinary medicine consisted of the combination of low doses of oral cyclophosphamide with a non-steroidal anti-inflammatory drug (Feldene/Piroxicam ®), and in some cases, an antibiotic (Doxycycline).

 

Since it’s inception, several other drugs have been examined as metronomic therapy including veterinary approved non-steroidal anti-inflammatory drugs (e.g. Metacam) and other chemotherapeutic drugs (e.g. Lomustine (CeeNu®) and chlorambucil (Leukeran ®))

 

My opinion of metronomic chemotherapy is it’s utilized most effectively in patients where we suspect microscopic cancer cells are present, but at levels where we are unable to detect them. There are two studies I feel are good examples of using metronomic chemotherapy in this exact setting. One looked at dogs with splenic hemangiosarcoma and one looked at dogs with soft tissue sarcomas.

 

Splenic hemangiosarcoma is a very aggressive type of cancer in dogs, and even when the primary tumor is removed via splenectomy and there is no evidence of spread at the time of surgery, most dogs will go on to develop metastases within just a few short weeks to months. Soft tissue sarcomas typically present us with the exact opposite challenge. They are extremely difficult to remove completely with surgery, but usually have a low chance of spread. Though not perfect in their design, in those studies, dogs that underwent treatment with metronomic treatment survived longer and had longer time to tumor regrowth when compared with dogs treated with surgery alone.

 

Metronomic chemotherapy is used to treat a variety of cancers in veterinary patients, other than those listed above. I feel metronomic therapy is most effective in cases where the primary tumor is adequately controlled (e.g. with surgery and/or radiation therapy) and there is no evidence of spread AND that patient has undergone the current standard of care of treatment. For me, the best example would be a dog with appendicular osteosarcoma, which underwent limb amputation and full course injectable cyctotoxic chemotherapy. We know that even with such aggressive treatment, most of those dogs will still go on to develop spread later on and succumb to their disease within 6 months of stopping treatment. I recommend metronomic treatment in those cases. For most cases this will be once injectable chemotherapy is complete, but I am becoming more and more comfortable combining metronomic treatment with injectable chemotherapy.

 

I will also use metronomic chemotherapy in cases where the pet isn’t a good candidate for conventional chemotherapy, or when owners simply can not travel to the hospital to see me as frequently as would be required for other protocols.

 

I’ve used metronomic treatment in cases where visible tumors are detected (e.g. metastases) and the pets are still feeling well. Those are the most challenging cases to treat with chemotherapy, and the major limitation to using metronomic chemotherapy in this setting is once you can detect a tumor, it probably has grown a very decent blood supply of it’s own, and your chance of slowing that down is going to be less (but not impossible). In such cases, owners must be willing to monitor their pets very closely so we can be sure the treatment isn’t causing harm, and to be sure we are truly seeing a benefit from the treatment.

 

A very important aspect of treating cases with metronomic chemotherapy is making sure owners understand this is chronic therapy that requires constant monitoring. Since this form of treatment is relatively new for veterinarians, we don’t really know what adverse effects are possible, so it’s important to watch patients carefully and recognize early signs of drug intolerance before the animals are showing adverse effects. We are usually seeing patients on a monthly basis and performing tests to look for tumor progression and/or spread every few months.

 

Metronomic chemotherapy is a promising new treatment option for veterinary cancer patients and I’m excited to see where research is headed in the future. I enjoy being able to provide owners with cutting edge treatment options, and many owners feel empowered by my ability to expand my own knowledge from information I gain from their pet.

 

In this respect, metronomic treatment certainly brings truth to the statement “Less is more”, as we’ve learned a great deal about how low dose chemotherapy brings a great deal of information on how to control cancer, and in many cases, additional survival time with a great quality of life for our patients.

Do Veterinarians Owe Owners Anything After A Pet’s Death?

Several years ago, an owner scheduled an appointment with me about a week after I’d euthanized their pet. It was an unusual request, seeing as though their pet was no longer alive and in need of my services. I urged the owner to call me or email me with any outstanding questions or concerns. It was explained that if they were to schedule a specific time to see me, not only would it take a spot away from another pet in need of treatment, but that I was required to charge them for the appointment spot, while it would not cost anything to talk on the phone or via email.

 

The owner elected to keep the appointment. We met and talked about their pet and its disease and how it had progressed over time. We didn’t spend a great deal of time together, but it was a significant moment for both of us. As per the policy of the hospital, and our prior discussion, an appointment fee was generated.

 

Several days later, I received a letter from the owner criticizing the fee on the grounds it was unethical for me to charge a visit after all they’d been through. An additional suggestion was made that I should provide follow-up appointments, free of charge, to owners who’d recently euthanized their pets as a means for them to obtain closure and to provide a forum where they could process their feelings and/or frustrations.

 

As I read the letter, a complex mixture of emotions rose within my mind. Empathy, sadness, resentment, and confusion – I felt it all. But my overriding sentiments regarding the words were, “Why had I not accurately prepared this owner for their pet’s death, leading to their compulsive need to talk with me afterwards?” and “Why should I be obligated to give my time for free when a human physician would never face this expectation?” I didn’t feel particularly good about my thoughts, but I’m being honest in my description.

 

Discussing end of life care is something I’m entrusted with nearly every time I enter a new appointment. Invariably owners want to know what to look for to indicate their pet has reached the end stage of their disease. It’s never easy to consider concepts such as death and dying, planning for end of life care, advanced directives, or euthanasia. But experience tells me it’s much better to talk about these topics before we’re in the midst of an emotionally charged situation.

 

In human medicine, dialogue centered on end of life care is frequently entrusted to social workers or hospice providers. Though well-trained in these difficult topics, it’s a patient’s doctor who is best equipped to do so. They possess the medical knowledge about the specifics of what actually occurs physiologically within the body during measures such as cardiopulmonary resuscitation, or in response to treatment of disease, and how to prepare owners for what lies ahead.

 

The results of a pilot study presented this year at the annual Quality of Care and Outcomes Research Scientific Sessions showed physicians were reluctant to discuss end of life issues with their patients because they perceived their patients or their families were not ready to discuss it, they were uncomfortable discussing it, they were afraid of destroying their patient’s sense of hope, or they didn’t have the time to engage in those conversations. The latter example tells us, if a doctor isn’t going to be paid for the time it takes to have an end of life discussion, it’s not going to happen. Period.

 

The good news is more and more private insurance companies now offer reimbursement to doctors for conversations related to advanced care planning. The American Medical Association (AMA), the country’s largest association of physicians and medical students, recently urged Medicare to follow suit, indicating doctors are not only committed to the cause, but recognize they are the ones best equipped for the job.

 

Unfortunately, insurance companies offer lower reimbursement rates to doctors for the time spent talking to people compared to performing medical procedures. If we’re simply sitting around talking, we can’t be ordering tests or administering drugs or performing surgeries, and, ultimately, we’re not making any money. Even when doctors try to do the right thing, it seems we manage to be penalized.

 

It is incredibly sad that innocent animals develop debilitating diseases.   I recognize how fortunate I am to work with owners who have the time and resources to treat their pets. And I understand the loss of a pet is an intensely painful process. None of this changes the fact that being a veterinary oncologist is my job and my source of income. I too, must earn a living, pay bills and loans, and support myself.

 

Was if wrong of me to charge for an end of life/closure discussion? Did this represent detraction from my reservoir of compassion? Worse yet, did it make me a bad doctor? My answer to each of those questions is a resounding, “No!”

 

Years later, I still think about that owner and their letter, and something deeper than being labeled good or bad, compassionate or unethical, or right or wrong continues to weigh on my mind. By gaining a sense of closure and peace for themselves, this owner ironically created a sense of uneasiness in my soul.

 

Sometimes the toughest cases for veterinarians have nothing at all to do with actual animals we are treating. Sometimes the price we pay for the stress can’t be quantitated in dollars or cents.

 

And sometimes this is why we so often work for free, even when we know we shouldn’t, because we hope it will somehow save us from the unyielding pressure of charging adequately for doing our jobs.