The Search For Effective Alzheimer's Therapies: A Work In Progress by Bor (2014)

I opened up the latest copy of Health Affairs today-- and it is an entire issue dedicated to Alzheimer's. I've been thinking one of my goals this summer is to spend a week or two (or three) on each organ system, and learn a little bit about the anatomy/ physiology, as well as common pathologies, and current areas for research. 

Here's my wikipedia list of organ systems:

• Circulatory system: pumping and channeling blood to and from the body and lungs with heart, blood and blood vessels.
• Integumentary system: skin, hair, fat, and nails.
• Skeletal system: structural support and protection with bones, cartilage, ligaments and tendons.
• Reproductive system: the sex organs, such as ovaries, fallopian tubes, uterus, vagina, mammary glands, testes, vas deferens, seminal vesicles and prostate
• Digestive system: digestion and processing food with salivary glands, esophagus, stomach, liver, gallbladder, pancreas, intestines,rectum and anus.
• Urinary system: kidneys, ureters, bladder and urethra involved in fluid balance, electrolyte balance and excretion of urine.
• Respiratory system: the organs used for breathing, the pharynx, larynx, bronchi, lungs and diaphragm.
• Endocrine system: communication within the body using hormones made by endocrine glands such as the hypothalamus, pituitarygland, pineal body or pineal gland, thyroid, parathyroid and adrenals, i.e., adrenal glands.
• Lymphatic system: structures involved in the transfer of lymph between tissues and the blood stream; includes the lymph and the nodes and vessels. The lymphatic system includes functions including immune responses and development of antibodies.
• Muscular system: allows for manipulation of the environment, provides locomotion, maintains posture, and produces heat. Includes skeletal muscles, smooth muscles and cardiac muscle.
• Nervous system: collecting, transferring and processing information with brain, spinal cord and peripheral nervous system.

I'm starting with the nervous system... I'm skipping the anatomy/ physiology part for right now (I'll come back to it) because I found this cool article to read instead.

Article: The Search For Effective Alzheimer's Therapies: A Work In Progress (Bor, 2014-- Health Affairs)

• Basically Alzheimer's sucks. It strips away the elements of life that make life meaningful-- memories, ability to take care of oneself, ability to carry-on a conversation with someone-- but it does so pretty slowly. 
• Places a large burden on caretakers, who are often family-members, creating additional pain and suffering for both the patient and caretaker
• About 5 million people have Alzheimer's in the US, prevalence is expected to increase as more people age (to the tune of tripling the # of people with Alzheimer's)
• Costs: In 2010 the average annual cost of caring for a patient with dementia was estimated to be $41,000–$56,000, for a total cost of $157–$215 billion each year in the United States.
• The goal is to manage Alzheimer's like any other chronic disease (diabetes, HIV/AIDs)-- where, if you adhere to the medication/ lifestyle protocol, you will delay the onset of further complications 
• We aren't there yet... HHS set of moon-shot goal saying we should get there by 2025.. but but I'm not sure we're going to meet that goal
• Two types
• Early onset-- can happen as early as 30s-- usually end stage by 40s
• Late onset-- happens at age 60+
• This quote from the article gives a great description of Alzheimer's brain compared to a healthy brain:
• We're not sure what causes Alzheimer's...
• Two proteins are the focus of much of the research. They are present in both healthy brain function, and in patient's with Alzheimer's:
• Beta amyloid-- form "plaques" on the brain
• Tau-- form "tangles" in brain cells 
• Research-- we haven't cracked the code yet... still searching
• Some drug trials have been conducted to address the build-up of plaque (targeting amyloid) (drug: bapineuzumab)-- while it reduced plaque, it didn't reduce clinical symptoms of Alzheimer's-- IE-- people took the drugs, but they didn't get noticeably better
• Assessment of National Institute on Aging: 
  • “The interventions did not work, which in concept means that amyloid is not an appropriate target, that it wasn’t appropriately targeted by these interventions, or that the time of intervention when symptomatic disease had already developed was too late in the course of cell damage to have an impact.”
• The thinking is now that treatments will need to target both plaque and tangles-- and will need to be delivered as early as possible (maybe even before symptoms start)
• We're still looking for the perfect biomarker-- the thing that identifies you're either going to get Alzheimer's-- or you're at a higher risk for contracting it. 
• Some promising prospects from
• John's Hopkins--cerebrospinal fluid (spinal tap) showing 
• Georgetown-- blood test
• Prospective trial going on with 1000 asymptomatic patients 
• Current treatment options:
• 5 Drugs exist right now to treat the symptoms of Alzheimer's but do nothing to address the actual disease process (like taking a pain killer after surgery-- it dulls the symptom of pain... but it doesn't close up the surgical incision to stop the pain permanently). 
• Aricept, Cognex, Razadyne, Namenda, and Exelon
• No evidence exists directly linking lifestyle factors (diet/ exercise) to Alzheimer's... sure there are "brain-healthy" diets-- but we can't say at this time that poor diet = Alzheimer's.
• How we're treating the disease right now:
• 5 drugs above
• Aware that patients with dementia are more likely to admit to the hospital with ambulatory-sensitive conditions
• Opportunity to have a clinic for these people? Are these frequent-flyers in the ED? Do they affect the 30-day readmissions rates? Why do they keep coming into the ED for things that can be treated in a PCPs office?
• Treat neuropsychiatric/ behavioral symptoms (agitation, depression, etc.)
• Be in communication with/ support family members or caregivers:
• If you can educate them and make sure they can get the patient to the doctor as needed, adhere to the medication schedule, and have safe living arrangement that can delay the need to have the patient in a nursing home for up to 9 months.

Big Data, Big Challenge

I just finished up a 3-day Lean Six Sigma course at work. One of the primary things we discussed was actually looking at the outcomes of the process in question. For most industries, checking out your data probably isn't too hard, but for health care.... it's a different story. A lot of hospitals don't have the infrastructure to report all of their quality outcomes (perhaps only a selected few that are mandated for certain populations). So, it can be the case there is essentially very little data to look at, with any amount of ease. The persistent use of paper charts, capital investments required to coordinate clinical data in one place, and the skill and buy-in needed from all involved prevent hospitals and health systems from being able to meaningfully look inside their data. However, some organizations are finding ways to overcome those hurdles.

Cleveland Clinic publishes "Outcome Books" for each of their institutes. (Described here: From: The Healthcare Blog: Five Lessons in Transparency from Cleveland Clinic CEO Toby Cosgrove). Inside you will find statistics regarding frequency of diseases and procedures, comparative data (over time), as well as written descriptions and analyses. Now, ideally, every hospital would publish the same set of data and consumers would be able to make an educated decision about where to obtain their specific medical treatment... however, this is not the case.

Take a look: Outcome Books

Imagine the incredible success an organization would have if it was able to peer inside it's data, pair this with a blameless culture that focuses on fixing failing processes, and fix what isn't working. Everyone wins. The patient wins because they are getting the best possible treatment. Employees win because they are empowered to make changes, and they aren't afraid of getting blamed when a process they are involved in fails. The industry wins because best practices can be identified, and shared. Move over Charlie Sheen, because we just redefined #winning.

As we all sit around our dinner tables and talk about how to fix health care, I suggest we start with an examination of our current outcomes. How can healthcare organizations expect to improve if they don't even fully understand what is happening in their ORs, or recovery rooms, or their patient's homes. Understanding the 30-day readmission rate is one thing, but understanding a patient's 5-year survival rate after X procedure is another challenge altogether.With registries, we can achieve that-- and we can finally give patients the information they want when making critical life decisions (ie: what is my life going to look like after X procedure?). There is so much value that can be tapped if we just get all of our information in one place, with one reporting structure on top of it.

Childhood obesity- Using BMI percentiles as a diagnostic tool

Childhood obesity has become an extremely exigent issue in public health. Approximately 20% of children are considered obese (JAMA article). Screenings for overweight/ obesity are relatively simple-- but the cure for obesity (weight reduction) is less simple.

I came across a JAMA article recently about weight loss strategies specifically for adolescents. The article has a case-study of a 14 year old girl with obesity, and then follows with more general recommendations (diet, physical activity, and behavioral strategies).

The first step to solving the obesity epidemic is recognizing that there is a problem. Calculating and plotting a child's BMI is a HEDIS 2012 guideline (as well as giving the appropriate nutrition/ activity counseling). In my experience, I have found that calculating and plotting the BMI is not commonplace in pediatric primary care. Often times, even IF BMI is calcualted it may not be plotted, or it is evaluated based on the adult BMI scale.

 

(CDC BMI Percentile example for children aged 2+)

There are sometimes red flags that are raised when using BMI as a diagnosis tool because it is not a perfect measure of body fat. The Body Mass Index (BMI) is regarded as a proxy for body fat-- not a perfect substitution. "Body mass index higher than the 85th percentile or showing a persistent upward trend warrants attention, and BMI at or above the 95th percentile requires full evaluation." (JAMA article). 

Recognizing and diagnosing a child as overweight or obese early on can help the child and their family, along with their physician, correct the problem before other (bigger) problems occur (Diabetes, fatty liver, etc.) which, everyone can agree, is preferable. 

There are many barriers to overcome when it comes to diagnosing overweight/ obesity in children. First of all, practices may or may not be using BMI percentiles as a screening tool. Without this, there is no way to diagnose a weight category. Another major barrier may be the social stigma of an overweight/ obesity diagnosis-- especially for children. Finding a way to gently share the BMI percentile with the child and parent is difficult, as people may become defensive, or may see the diagnosis as a personal attack or judgement. Lastly, there may be providers not paying much attention to BMI percentiles because they do not believe that sharing this information with patients (or their parents) will help anything-- ie: telling the patient to watch what they eat, and increase exercise may not result in weight loss, so why waste time in a busy well-visit with discussing this. This last point is a sticky one. As more information becomes available about strategies for weightloss in adolescents, like that provided in the JAMA article becomes available, this issue may be somewhat alleviated. However, patient compliance is always an issue-- and just because we're not confident that the patient will comply does not mean we should forgo giving them appropriate screenings and guidance. Obesity is linked to so many other health problems, that it is truly worth addressing, even though it may be difficult for everyone in the exam room. 

* Ludwig, David. "Weight Loss Strategies for Adolscents" JAMA (2/1/12). Clinician's Corner.

School Lunches: The only place where a tater tot is the equivalent of a green, leafy vegetable

School lunches have never had a good reputation. Decrypting the true identity of "mystery meat", eating applesauce that is more reminiscent of paste than apples, or chewing green beans that have a questionably squishy texture... complaining about school lunches is a rite of passage for a lot of people. However, the complaint at this point in time isn't about texture or taste-- it's about nutritional content and the obesity epidemic that is occurring in the youngest populations.

Congress has been asked to make legislation that improves the quality of food that school children eat to make it more nutritious. Foods like pizza, french fries, and chicken nuggets appear regularly on school lunch menus and comprise a large part of the average American child's diet. This is problematic as these foods are correlated with higher body mass indexes (BMI)--which is also correlated with health problems in childhood, as well as in their later adult years. Cost has been the primary barrier to providing more healthful food--as it costs more to provide healthy foods than it does to provide less healthy foods (EX: fresh vegetables cost more than tater tots). Also- special interest groups (namely potato and salt industry) have a vested interest in making sure kids continue to eat their current school lunches which are often very high in white potatoes, white flour, and sugar (think: flavored milk). As of now, Congress has backed down on improving the quality of school lunches--and is remaining with the status quo.

The question is-- is this within the realm of what Congress should be doing? (Not that Congress always spends it's time on worthy things-- I remember them getting involved in some of the business with the baseball players who used steroids, and then lied about their usage...just saying). If the answer is yes-- then I think Congress should re-visit the cost-benefit analysis here.

What is the monetary benefit of improving the quality of school lunches? I'm not sure it's possible to determine how school lunches directly effect childhood obesity, but common sense tells me, if a child receives zero healthy meals per day, giving them 1 healthy meal per day at school would be an improvement. Also- this would expose them to healthy foods, which they may discover are actually pretty tasty--thus increasing the likelihood that the child will request mom or dad purchase these types of foods in the future.

Even if having more healthy foods results in very little weight loss in overweight or obese children-- it would still be a WIN on a population level. Imagine all children are on a standard deviation curve where the heaviest are in the right tail and the lowest weight children are in the left tail. If we shift those children in the right tail down the curve 1-2 pounds worth-- that results in less children in the overweight/ obese category (where there are well-known health risks that are very costly). Not having those kids suffer with the chronic conditions that occur due to excessive weight would obviously be good for the kids themselves--but would also be good for society from a cost perspective (and the reward would keep giving overtime--since overweight kids with health problems often turn into overweight adults with even more health problems).

In sum- it would be useful to know the relationship (or elasticity, in Economics-speak),between dollars spent on increasing healthy food for school lunches, and the percent reduction in children above the 85th BMI percentile (IE: the kids who are overweight or obese, by CDC standards). What an awesome experiment this would make! Obviously there would be lots of measurement challenges, and like any observational study, the results would show correlation-- not causation (if they show anything at all)... but it would still be a useful piece of information for Congress, schools, and the food industry to have.

Until then, if you have the resources, brown-bag lunches are looking like a pretty good option!

No cost birth control

An expert panel for the Institute of Medicine has recommended a number of medical services be given at no cost-- one of which is birth control. This raised concern (outrage?) in the pro-life and Catholic communities. Women's right's groups are ecstatic.

What we do know is that about half of all pregnancies are unintended. Women who do not want to be pregnant are less likely to get proper prenatal care and are more likely to have complications later on (low birth weight, delayed development/ development problems). So, we can deduce that for some women who do not want to be pregnant, it can have a distinctly negative impact on the resulting child.

Many women choose not to use birth control due to cost. By the law of demand, lowering the cost (to zero) of birth control more women can afford to take birth control-- thus we can reduce the number of unplanned pregnancies (and unhealthy pregnancies/ births).

Cost-Effectiveness of Meningitis Vaccine

Generally preventative medicines have a good shot at being cost-effective. They prevent hospitalizations, medical/ surgical procedures, additional medicines, etc. The trade-off is that vaccines need to be given to everyone who can get the vaccine for it to be effective. Like the flu vaccine ads say,"don't get it for you-- get it for ___ (insert name here)___" highlighting how getting a vaccine not only protects the person who gets it-- but also the all of the people who that person comes in comes in contact with.

What we don't want to see is the resources a vaccines saves in illness care for the small number of people who are infected, get made up for in the quantity of people having to get the vaccine (albeit, the vaccine is much less expensive than the medical treatment treating the disease). This is the case when the vaccine is very expensive and the disease the immunization protects against is relatively rare.

As a recent NPR piece highlighted, the bacterial meningitis may be in the position discussed. At first the vaccine was only given once and cost $100. Now ACIP (Advistory Committee on Immunization Practices) is recommending a booster-- which raises the cost to $189. NPR states that this would cost the government $387 million annually. All of this is estimated to prevent only 23 deaths per year. Is that okay? If all 23 deaths were people covered by government health care-- that would be more than $16 million per life saved. If you included what other non-government entities were spending on the vaccine- the cost would be even higher--since there are still only 23 deaths per year. Is that an acceptable amount to pay to save a life given the fact that there are budgetary constraints?

From the article:

....experts can't solve the fundamental problem of how to put a dollar value on preventing death or disease, says Mark Pauly, a health economist at the University of Pennsylvania.

"You do have a rough idea that if it's $1.98 per life saved that sounds like a good thing to do and if it's $198 million per life saved, that sounds like not a good thing to do," he says. "But where to draw the line is the part that any sensible person will run away screaming from trying to answer that question."

Excess spending on end of life care

Chris sent me this article- and it was pretty interesting!

This describes a problem well-known to those who know anything about health care expenditures. I remember a vague statistic from my Health Economics course-- it was something like a third of all personal health care expenditures are spent at the end of life, on average (don't quote me on that). While it may not be a third, I think we can safely say it's a disproportionate amount of money...

Given that I have a degree in the dismal science, I'm about to get all dismal on you-- but just think about this without thinking about the morbidity of it:

When you think about how you want to die, you probably don't envision your death dragging out over months and months while you whither away. However, by spending ourselves into the ground (or under it?) we do just that-- we pay for treatments that keep us alive for a marginal amount of time while we suffer.

As you're probably already thinking-- this is pretty tricky. Ideally you would know which disease would be your final, and you would know not to pursue any additional treatments that would prove to be fruitless-- as they would only drag out your suffering (which, it is assumed, is not your goal). Anyway- you would know to just stop, and enjoy your time on Earth doing the things you like to do and spending time with the people you love.

As far as spending goes-- yes, we'd like to reduce end-of-life expenditures (we'd like to reduce all types of expenditures really)... but the problem is that you never know when the "end" really is. This really just adds fuel to the cost-effectiveness fire- and makes it even more of an important and critical type of research. If we're not wasting time or resources of treatments that are just not effective or worth spending money on, we can theoretically give the best reasonable care, while still being fiscally responsible.