Pancreatic Exocrine Insufficiency

How Long Does It Take for Pancreatic Enzyme Replacement Therapy (PERT) to Start Working for People With Exocrine Pancreatic Insufficiency (EPI / PEI)?

by Dana Lewis

How long does it take for pancreatic enzyme replacement therapy to start working? A blog from Dana M. Lewis on DIYPS.orgIf you have been prescribed pancreatic enzyme replacement therapy (PERT), aka enzymes for exocrine pancreatic insufficiency (EPI or PEI), you may be wondering how long it will take before you start to feel better or it starts to work. This is a common question, and the answer depends on several factors, including the dosage, meal composition, and how well your body uses the enzymes. Some improvements can be seen within a single meal, while other benefits take longer to manifest. It also depends on whether you have EPI, or if you have EPI in concert with other types of gastrointestinal conditions, because some of your symptoms may be coming from other conditions.

Immediate Effects of PERT

PERT should start working with your very first meal, if your dose is in the ballpark of being ideal for you and your food intake. The enzymes help break down fats, proteins, and carbohydrates so your body can absorb nutrients more effectively. If you are taking somewhere in the ballpark of the right dose, you may notice immediate improvements in digestion, such as:

  • Less bloating or cramping after eating
  • Reduced gas
  • A decrease in diarrhea or greasy, foul-smelling stools

These improvements should occur on a per-meal basis. If you take PERT with one meal but not another, you may notice a stark difference in symptoms after each of those meals. This is a good indicator that the enzymes are working when you do take them.

Why Some People Don’t See Immediate Improvement With PERT

While PERT can provide relief after a meal or noticeable effects within a day or so, many people do not take a sufficient dose initially. Under-dosing is common, which means you may still experience symptoms as you fine-tune your enzyme intake.

Here are some reasons why you might not see immediate results:

  • Not taking enough enzymes: Many people are prescribed a starting dose well below the standard guidelines, and this may not be enough for their specific needs. This is because your body is unique, and what you eat varies from what other people eat. The combination of these two factors means that your dose is not going to be the same as someone else’s, regardless of which “category” of EPI you fall into or even with an identical fecal elastase test result. If you still experience symptoms, you may need to increase your dose of enzymes.
  • Miscalculating enzyme dosing: If you eat a small salad with a few bites of chicken, this is likely a lower fat and lower protein meal, when you compare it to a large hamburger with bacon and cheese and a side of french fries. These meals likely need different doses of enzymes. The dose you start with may work for some of your existing meals, but don’t be surprised if you have symptoms with meals with more protein or more fat than your lower quantity meals. Some people can use the same, fixed dose for all their meals…but that usually means their meals don’t vary a lot. Other people like me can have a wide range of meal quantities, so we adjust our dosing for every meal. (It gets easier over time!)
  • Enzyme timing may be wrong: PERT needs to be taken with the first few bites of a meal, and sometimes additional enzymes are needed if the meal is prolonged. It’s ok if you get halfway through a meal and haven’t taken your enzymes – start taking them then. But don’t take them well before you eat or well after. The point is to get them into your system at the same time that you are eating (or drinking any drink with fat/protein). If you have a 5 course meal at a restaurant that lasts 2 hours, you will need to take more enzymes even if your usual dose would normally cover the total quantity of what you consumed. The fact that it’s so spread out matters. Rule of thumb most people use is 20-30 minutes, so if you’re eating longer than that, you likely need another pill (or more than one more).
  • Other gastrointestinal conditions: Some people have additional digestive issues such as SIBO or other conditions like pancreatitis that have their own symptoms, and it can be challenging to tell what are EPI-specific symptoms due to enzyme dosing or timing issues as opposed to symptoms of these other conditions.

Here are some example scenarios where you might not see the improvements right away:

  • If you eat a hamburger with fries as your first meal, but your prescription is for two pills of 10,000 lipase of PERT. This is unlikely to be enough for the meal, as the standard dose for regular meals is 40-50,000 units; many people need more than that; and this type of meal is higher in fat and protein than a standard meal. Thus, symptoms.
  • If you take your PERT 30 minutes before you eat, even if the dose matches your food perfectly, the timing is off and the enzymes won’t be where they need to be to help digest your food. Thus, symptoms.

Short-Term vs. Long-Term Improvements

Short-Term (Days to Weeks)

Once you find the right PERT dosage, the most noticeable and immediate improvements should occur within your first several meals and across a few days, including:

  • Reduction in diarrhea or loose stools
  • Less bloating and discomfort after eating
  • Improved stool consistency
  • Decreased urgency to use the bathroom

If you are still experiencing symptoms after a few days of consistent PERT use, consider adjusting your dose, especially in the context of looking at what quantity is in your meal. (You’ll find some other tips here walking you through how to look at what’s in your food and how to track it, including tools like PERT Pilot for tracking it on your phone over time.)

Long-Term (Weeks to Months)

While digestion-related symptoms can improve within days, some longer-term health effects take weeks or months to resolve or notice improvements. These include:

  • Nutritional deficiencies: If you have been malabsorbing fats and nutrients for a long time, it may take months of improved digestion to correct deficiencies in fat-soluble vitamins (A, D, E, K), iron, or B12.
  • Weight stabilization: Weight gain or stabilization may occur over weeks to months. (Not everyone gains weight, but if you’re looking for weight gain to occur after you improve digestion with enzymes, it will take some time).
  • Improved energy levels: Once your body starts absorbing nutrients more efficiently, you may notice a gradual increase in energy.

Do some people see improvement on these and other symptoms sooner? Yes! However, it’s different for everyone, so don’t expect every single symptom to magically get better after your first few days on PERT.

How to Know If PERT Is Working for You

The key to determining if PERT is effective lies in tracking your symptoms and adjusting accordingly. Signs that your PERT is working include:

  • Well-formed stools without oiliness or a greasy appearance
  • Normal bowel movement frequency (not too frequent or urgent)
  • Reduction in gas, bloating, and stomach discomfort
  • Gradual improvements in weight and energy levels over time, if those were bothersome to you before

Note a key factor that does NOT tell you if PERT is working for you, which is that changes in fecal elastase score do not tell you anything about whether your enzymes are working for you. Elastase is not affected directly by your enzymes, meaning the elastase test measures human elastase (and enzymes are not human elastase, so they’re not measured by the elastase test). Elastase can naturally fluctuate a bit over time; test precision is not perfect; and for a lot of reasons it’s common to see different numbers in elastase. Read this blog post for a lot more detail, but a change from 23 to 84, or from 154 to 137, or from 58 to 101 are not meaningful changes and do not change the diagnosis of EPI. The categorization of EPI as ‘moderate’ or ‘severe’ does not matter for either diagnosis overall (EPI is EPI) and does not matter for whether or not enzymes are effective because elastase can’t answer that question.

When to Adjust or Reassess Enzyme Dosing

If you do not see some improvements within a few meals or a few days, it may indicate that your dose is too low or not properly timed or you are eating different size meals and need to pay attention to your dose size relative to what you are eating. Work with your healthcare provider to fine-tune your dosage (note that they may not be aware of the guidelines for starting doses or aware that dose ranges vary person to person), and consider tracking your meals and symptoms to identify patterns. Once you’ve ruled that out, say by tracking your meals and increasing your doses and eating consistently sized meals, you may want to investigate other conditions contributing to symptoms.

For most people, PERT should start showing effects within a single meal if the dose is in the ballpark of being correct, even if it’s not fully covering your meal. However, because under-dosing is common, it may take days or weeks of adjustments to see consistent improvement or to improve or eliminate all symptoms.

Immediate symptoms like bloating, diarrhea, and gas should improve quickly (days to weeks), while long-term nutritional recovery (if you had any nutritional deficiencies) may take longer (weeks to months).
A gif showing a square moving along a spectrum from "too little" to "too much enzyme". Too little enzyme and you have symptoms, not enough and you reduce but don't eliminate symptoms. Enough enzymes and you eliminate symptoms. Too much risks constipation.

Other posts you may find helpful:

Beware “too much” and “too little” advice in Exocrine Pancreatic Insufficiency (EPI / PEI)

by Dana Lewis

If I had a nickel every time I saw conflicting advice for people with EPI, I could buy (more) pancreatic enzyme replacement therapy. (PERT is expensive, so it’s significant that there’s so much conflicting advice).

One rule of thumb I find handy is to pause any time I see the words “too much” or “too little”.

This comes up in a lot of categories. For example, someone saying not to eat “too much” fat or fiber, and that a low-fat diet is better. The first part of the sentence should warrant a pause (red flag words – “too much”), and that should put a lot of skepticism on any advice that follows.

Specifically on the “low fat diet” – this is not true. A lot of outdated advice about EPI comes from historical research that no longer reflects modern treatment. In the past, low-fat diets were recommended because early enzyme formulations were not encapsulated or as effective, so people in the 1990s struggled to digest fat because the enzymes weren’t correctly working at the right time in their body. The “bandaid” fix was to eat less fat. Now that enzyme formulations are significantly improved (starting in the early 2000s, enzymes are now encapsulated so they get to the right place in our digestive system at the right time to work on the food we eat or drink), medical experts no longer recommend low-fat diets. Instead, people should eat a regular diet and adjust their enzyme intake accordingly to match that food intake, rather than the other way around (source: see section 4.6).

Think replacement of enzymes, rather than restriction of dietary intake: the “R” in PERT literally stands for replacement!

If you’re reading advice as a person with EPI (PEI), you need to have math in the back of your mind. (Sorry if you don’t like math, I’ll talk about some tools to help).

Any time people use words to indicate amounts of things, whether that’s amounts of enzymes or amounts of food (fat, protein, carbs, fiber), you need to think of specific numbers to go with these words.

And, you need to remember that everyone’s body is different, which means your body is different.

Turning words into math for pill count and enzymes for EPI

Enzyme intake should not be compared without considering multiple factors.

The first reason is because enzyme pills are not all the same size. Some prescription pancreatic enzyme replacement therapy (PERT) pills can be as small as 3,000 units of lipase or as large as 60,000 units of lipase. (They also contain thousands or hundreds of thousands of units of protease and amylase, to support protein and carbohydrate digestion. For this example I’ll stick to lipase, for fat digestion.)

If a person takes two enzyme pills per meal, that number alone tells us nothing. Or rather, it tells us only half of the equation!

The size of the pills matters. Someone taking two 10,000-lipase pills consumes 20,000 units per meal, while another person taking two 40,000-lipase pills is consuming 80,000 units per meal.

That is a big difference! Comparing the two total amounts of enzymes (80,000 units of lipase or 20,000 units of lipase) is a 4x difference.

And I hate to tell you this, but that’s still not the entire equation to consider. Hold on to your hat for a little more math, because…

The amount of fat consumed also matters.

Remember, enzymes are used to digest food. It’s not a magic pill where one (or two) pills will perfectly cover all food. It’s similar to insulin, where different people can need different amounts of insulin for the same amount of carbohydrates. Enzymes work the same way, where different people need different amounts of enzymes for the same amount of fat, protein, or carbohydrates.

And, people consume different amounts and types of food! Breakfast is a good example. Some people will eat cereal with milk – often that’s more carbs, a little bit of protein, and some fat. Some people will eat eggs and bacon – that’s very little carbs, a good amount of protein, and a larger amount of fat.

Let’s say you eat cereal with milk one day, and eggs and bacon the next day. Taking “two pills” might work for your cereal and milk, but not your eggs and bacon, if you’re the person with 10,000 units of lipase in your pill. However, taking “two pills” of 40,000 units of lipase might work for both meals. Or not: you may need more for the meal with higher amounts of fat and protein.

If someone eats the same quantity of fat and protein and carbs across all 3 meals, every day, they may be able to always consume the same number of pills. But for most of us, our food choices vary, and the protein and fat varies meal to meal, so it’s common to need different amounts at different meals. (If you want more details on how to figure out how much you need, given what you eat, check out this blog post with example meals and a lot more detail.)

You need to understand your baseline before making any comparisons

Everyone’s body is different, and enzyme needs vary widely depending on the amount of fat and protein consumed. What is “too much” for one person might be exactly the right amount for another, even when comparing the same exact food quantity. This variability makes it essential to understand your own baseline rather than following generic guidance. The key is finding what works for your specific needs rather than focusing on an arbitrary notion of “too much”, because “too much” needs to be compared to specific numbers that can be compared as apples to apples.

A useful analogy is heart rate. Some people have naturally higher or lower resting heart rates. If someone tells you (that’s not a doctor giving you direct medical advice) that your heart rate is too high, it’s like – what can you do about it? It’s not like you can grow your heart two sizes (like the Grinch). While fitness and activity can influence heart rate slightly, individual baseline differences remain significant. If you find yourself saying “duh, of course I’m not going to try to compare my heart rate to my spouse’s, our bodies are different”, that’s a GREAT frame of mind that you should apply to EPI, too.

(Another example is respiratory rate, where it varies person to person. If someone is having trouble breathing, the solution is not as simple as “breathe more” or “breathe less”—it depends on their normal range and underlying causes, and it takes understanding their normal range to figure out if they are breathing more or less than their normal, because their normal is what matters.)

If you have EPI, fiber (and anything else) also needs numbers

Fiber also follows this pattern. Some people caution against consuming “too much” fiber, but a baseline level is essential. “Too little” fiber can mimic EPI symptoms, leading to soft, messy stools. Finding the right amount of fiber is just as crucial as balancing fat and protein intake.

If you find yourself observing or hearing comments that you likely consume “too much” fiber – red flag check for “too much!” Similar to if you hear/see about ‘low fiber’. Low meaning what number?

You should get an estimate for how much you are consuming and contextualize it against the typical recommendations overall, evaluate whether fiber is contributing to your issues, and only then consider experimenting with it.

(For what it’s worth, you may need to adjust enzyme intake for fat/protein first before you play around with fiber, if you have EPI. Many people are given PERT prescriptions below standard guidelines, so it is common to need to increase dosing.)

For example, if you’re consuming 5 grams of fiber in a day, and the typical guidance is often for 25-30 grams (source, varies by age, gender and country so this is a ballpark)…. you are consuming less than the average person and the average recommendation.

In contrast, if you’re consuming 50+ grams of fiber? You’re consuming more than the average person/recommendation.

Understanding where you are (around the recommendation, quite a bit below, or above?) will then help you determine whether advice for ‘more’ or ‘less’ is actually appropriate in your case. Most people have no idea what you’re eating – and honestly, you may not either – so any advice for “too much”, “too little”, or “more” or “less” is completely unhelpful without these numbers in mind.

You don’t have to tell people these numbers, but you can and should know them if you want to consider evaluating whether YOU think you need more/less compared to your previous baseline.

How do you get numbers for fiber, fat, protein, and carbohydrates?

Instead of following vague “more” or “less” advice, first track your intake and outcomes.

If you don’t have a good way to estimate the amount of fat, protein, carbohydrates, and/or fiber, here’s a tool you can use – this is a Custom GPT that is designed to give you back estimates of fat, protein, carbohydrates, and fiber.

You can give it a meal, or a day’s worth of meals, or several days, and have it generate estimates for you. (It’s not perfect but it’s probably better than guessing, if you’re not familiar with estimating these macronutrients).

If you don’t like or can’t access ChatGPT (it works with free accounts, if you log in), you can also take this prompt, adjust it how you like, and give it to any free LLM tool you like (Gemini, Claude, etc.):

You are a dietitian with expertise in estimating the grams of fat, protein, carbohydrate, and fiber based on a plain language meal description. For every meal description given by the user, reply with structured text for grams of fat, protein, carbohydrates, and fiber. Your response should be four numbers and their labels. Reply only with this structure: “Fat: X; Protein: Y; Carbohydrates: Z; Fiber; A”. (Replace the X, Y, Z, and A with your estimates for these macronutrients.). If there is a decimal, round to the nearest whole number. If there are no grams of any of the macronutrients, mark them as 0 rather than nil. If the result is 0 for all four variables, please reply to the user: “I am unable to parse this meal description. Please try again.”

If you are asked by the user to then summarize a day’s worth of meals that you have estimated, you are able to do so. (Or a week’s worth). Perform the basic sum calculation needed to do this addition of each macronutrient for the time period requested, based on the estimates you provided for individual meals.

Another option is using an app like PERT Pilot. PERT Pilot is a free app for iOS for people with EPI that requires no login or user account information, and you can put in plain language descriptions of meals (“macaroni and cheese” or “spaghetti with meatballs”) and get back the estimates of fat, protein, and carbohydrates, and record how much enzymes you took so you can track your outcomes over time. (Android users – email me at Dana+PERTPilot@OpenAPS.org if you’d like to test the forthcoming Android version!) Note that PERT Pilot doesn’t estimate fiber, but if you want to start with fat/protein estimates, PERT Pilot is another way to get started with seeing what you typically consume. (For people without EPI, you can use Carb Pilot, another free iOS app that similarly gives estimates of macronutrients.)

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Beware advice of "more" or "less" that is vague and non-numeric (not a number) unless you know your baseline numbers in exocrine pancreatic insufficiency. A blog by Dana M. Lewis from DIYPS.orgTL;DR: Instead of arbitrarily lowering or increasing fat or fiber in the diet, measure and estimate what you are consuming first. If you have EPI, assess fat digestion first by adjusting enzyme intake to minimize symptoms. (And then protein, especially for low fat / high protein meals, such as chicken or fish.) Only then consider fiber intake—some people may actually need more fiber rather than less than what they were consuming before if they experience mushy stools. Remember the importance of putting “more” or “less” into context with your own baseline numbers. Estimating current consumption is crucial because an already low-fiber diet may be contributing to the problem, and reducing fiber further could make things worse. Understanding your own baseline is the key.

How Medical Research Literature Evolves Over Time Like A Game of Telephone

by Dana Lewis

Have you ever searched for or through medical research on a specific topic, only to find different studies saying seemingly contradictory things? Or you find something that doesn’t seem to make sense?

You may experience this, whether you’re a doctor, a researcher, or a patient.

I have found it helpful to consider that medical literature is like a game of telephone, where a fact or statement is passed from one research paper to another, which means that sometimes it is slowly (or quickly!) changing along the way. Sometimes this means an error has been introduced, or replicated.

A Game of Telephone in Research Citations

Imagine a research study from 2016 that makes a statement based on the best available data at the time. Over the next few years, other papers cite that original study, repeating the statement. Some authors might slightly rephrase it, adding their own interpretations. By 2019, newer research has emerged that contradicts the original statement. Some researchers start citing this new, corrected information, while others continue citing the outdated statement because they either haven’t updated their knowledge or are relying on older sources, especially because they see other papers pointing to these older sources and find it easiest to point to them, too. It’s not necessarily made clear that this outdated statement is now known to be incorrect. Sometimes that becomes obvious in the literature and field of study, and sometimes it’s not made explicit that the prior statement is ‘incorrect’. (And if it is incorrect, it doesn’t become known as incorrect until later – at the time it’s made, it’s considered to be correct.) 

By 2022, both the correct and incorrect statements appear in the literature. Eventually, a majority of researchers transition to citing the updated, accurate information—but the outdated statement never fully disappears. A handful of papers continue to reference the original incorrect fact, whether due to oversight, habit (of using older sources and repeating citations for simple statements), or a reluctance to accept new findings.

The gif below illustrates this concept, showing how incorrect and correct statements coexist over time. It also highlights how researchers may rely on citations from previous papers without always checking whether the original information was correct in the first place.

Animated gif illustrating how citations branch off and even if new statements are introduced to the literature, the previous statement can continue to appear over time.

This is not necessarily a criticism of researchers/authors of research publications (of which I am one!), but an acknowledgement of the situation that results from these processes. Once you’ve written a paper and cited a basic fact (let’s imagine you wrote this paper in 2017 and cite the 2016 paper and fact), it’s easy to keep using this citation over time. Imagine it’s 2023 and you’re writing a paper on the same topic area, it’s very easy to drop the same citation from 2016  in for the same basic fact, and you may not think to consider updating the citation or check if the fact is still the fact.

Why This Matters

Over time, a once-accepted “fact” may be corrected or revised, but older statements can still linger in the literature, continuing to influence new research. Understanding how this process works can help you critically evaluate medical research and recognize when a widely accepted statement might actually be outdated—or even incorrect.

If you’re looking into a medical topic, it’s important to pay attention not just to what different studies say, but also when they were published and how their key claims have evolved over time. If you notice a shift in the literature—where newer papers cite a different fact than older ones—it may indicate that scientific understanding has changed.

One useful strategy is to notice how frequently a particular statement appears in the literature over time.

Whenever I have a new diagnosis or a new topic to research on one of my chronic diseases, I find myself doing this.

I go and read a lot of abstracts and research papers about the topic; I generally observe patterns in terms of key things that everyone says, which establishes what the generally understood “facts” are, and also notice what is missing. (Usually, the question I’m asking is not addressed in the literature! But that’s another topic…)

I pay attention to the dates, observing when something is said in papers in the 1990s and whether it’s still being repeated in the 2020s era papers, or if/how it’s changed. In my head, I’m updating “this is what is generally known” and “this doesn’t seem to be answered in the literature (yet)” and “this is something that has changed over time” lists.

Re-Evaluating the Original ‘Fact’

In some cases, it turns out the original statement was never correct to begin with. This can happen when early research is based on small sample sizes, incomplete data, or incorrect assumptions. Sometimes that statement was correct, in context, but taken out of context immediately and this out of context use was never corrected. 

For example, a widely cited statement in medical literature once claimed that chronic pancreatitis is the most common cause of exocrine pancreatic insufficiency (EPI). This claim was repeated across numerous papers, reinforcing it as accepted knowledge. However, a closer examination of population data shows that while chronic pancreatitis is a known co-condition of EPI, it is far less common than diabetes—a condition that affects a much larger population and is also strongly associated with EPI. Despite this, many papers still repeat the outdated claim without checking the original data behind it.

(For a deeper dive into this example, you can read my previous post here. But TL;DR: even 80% of .03% is a smaller number than 10% of 10% of the overall population…so it is not plausible that CP is the biggest cause of EPI/PEI.)

Stay Curious

This realization can be really frustrating, because if you’re trying to do primary research to help you understand a topic or question, how do you know what the truth is? This is peer-reviewed research, but what this shows us is that the process of peer-review and publishing in a journal is not infallible. There can be errors. The process for updating errors can be messy, and it can be hard to clean up the literature over time. This makes it hard for us humans – whether in the role of patient or researcher or clinician – to sort things out.

But beyond a ‘woe is me, this is hard’ moment of frustration, I do find that this perspective of literature as a process of telephone makes me a better reader of the literature and forces me to think more critically about what I’m reading, and take papers in context of the broader landscape of literature and evolving knowledge base. It helps remove the strength I would otherwise be prone to assigning any one paper (and any one ‘fact’ or finding from a single paper), and encourages me to calibrate this against the broader knowledge base and the timeline of this knowledge base.

That can also be hard to deal with personally as a researcher/author, especially someone who tends to work in the gaps, establishing new findings and facts and introducing them to the literature. Some of my work also involves correcting errors in the literature, which I find from my outsider/patient perspective to be obvious because I’ve been able to use fresh eyes and evaluate at a systematic review level/high level view, without being as much in the weeds. That means my work, to disseminate new or corrected knowledge, is even more challenging. It’s also challenging personally as a patient, when I “just” want answers and for everything to already be studied, vetted, published, and widely known by everyone (including me and my clinician team).

But it’s usually not, and that’s just something I – and we – have to deal with. I’m curious as to whether we will eventually develop tools with AI to address this. Perhaps a mini systematic review tool that scrapes the literature and includes an analysis of how things have changed over time. This is done in systematic review or narrative reviews of the literature, when you read those types of papers, but those papers are based on researcher interests (and time and funding), and I often have so many questions that don’t have systematic reviews/narrative reviews covering them. Some I turn into papers myself (such as my paper on systematically reviewing the dosing guidelines and research on pancreatic enzyme replacement therapy for people with exocrine pancreatic insufficiency, known as EPI or PEI, or a systematic review on the prevalence of EPI in the general population or a systematic review on the prevalence of EPI in people with diabetes (Type 1 and Type 2)), but sometimes it’s just a personal question and it would be great to have a tool to help facilitate the process of seeing how information has changed over time. Maybe someone will eventually build that tool, or it’ll go on my list of things I might want to build, and I’ll build it myself like I have done with other types of research tools in the past, both without and with AI assistance. We’ll see!

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TL;DR: be cognizant of the fact that medical literature changes over time, and keep this in mind when reading a single paper. Sometimes there are competing “facts” or beliefs or statements in the literature, and sometimes you can identify how it evolves over time, so that you can better assess the accuracy of research findings and avoid relying on outdated or incorrect information.

Whether you’re a researcher, a clinician, or a patient doing research for yourself, this awareness can help you better navigate the scientific literature.

A screenshot from the animated gif showing how citation strings happen in the literature, branching off over time but often still resulting in a repetition of a fact that is later considered to be incorrect, thus both the correct and incorrect fact occur in the literature at the same time.

Assessing the Impact of Diabetes on Gastrointestinal Symptom Severity in Exocrine Pancreatic Insufficiency (EPI/PEI): A Diabetes Subgroup Analysis of EPI/PEI-SS Scores – Poster at #ADA2024

by Dana Lewis

Last year, I recognized that there was a need to improve the documentation of symptoms of exocrine pancreatic insufficiency (known as EPI or PEI). There is no standardized way to discuss symptoms with doctors, and this influences whether or not people get the right amount of enzymes (pancreatic enzyme replacement therapy; PERT) to treat EPI and eliminate symptoms completely. It can be done, but like insulin, it requires matching PERT to the amount of food you’re consuming. I also began observing that EPI is underscreened and underdiagnosed, whether that’s in the general population or in people with diabetes. I thought that if we could create a list of common EPI symptoms and a standardized scale to rate them, this might help address some of these challenges.

I developed this scale to address these needs. It is called the “Exocrine Pancreatic Insufficiency Symptom Score” or “EPI/PEI-SS” for short.

I had a handful of people with and without EPI help me test the scale last year, and then I opened up a survey to the entire world and asked people to share their experiences with GI-related symptoms. I specifically sought people with EPI diagnoses as well as people who don’t have EPI, so that we could compare the symptom burden and experiences to people without EPI. (Thank you to everyone who contributed their data to this survey!)

After the first three weeks, I started analyzing the first set of data. While doing that, I realized that (both because of my network of people with diabetes and because I also posted in at least one diabetes-specific group), I had a large sub-group of people with diabetes who had contributed to the survey, and I was able to do a full subgroup analyses to assess whether having diabetes seemed to correlate with a different symptom experience of EPI or not.

Here’s what I found, and what my poster is about (you can view my poster as a PDF here), presented at ADA Scientific Sessions 2024 (#ADA2024):

1985-LB at #ADA2024, “Assessing the Impact of Diabetes on Gastrointestinal Symptom Severity in Exocrine Pancreatic Insufficiency (EPI/PEI): A Diabetes Subgroup Analysis of EPI/PEI-SS Scores”

Exocrine pancreatic insufficiency has a high symptom burden and is present in as many as 3 of 10 people with diabetes. (See my systematic review from last year here). To help improve conversations about symptoms of EPI, which can then be used to improve screening, diagnosis, and treatment success with EPI, I created the Exocrine Pancreatic Insufficiency Symptom Score (EPI/PEI-SS), which consists of 15 individual symptoms that people separately rate the frequency (0-5) and severity (0-3) for which they experience those symptoms, if at all. The frequency and severity get multiplied for an individual symptom score (0-15 possible) and these get added up for a total EPI/PEI-SS score (0-225 possible, because 15 symptoms times 15 possible points per symptom is 225).

I conducted a real-world study of the EPI/PEI-SS in the general population to assess the gastrointestinal symptom burden in individuals with (n=155) and without (n=169) EPI. Because there was a large cohort of PWD within these groups, I separately analyzed them to evaluate whether diabetes contributes to a difference in EPI/PEI-SS score.

Methods:

I calculated EPI/PEI-SS scores for all survey participants. Previously, I had analyzed the differences of people with and without EPI overall. For this sub-analysis, I analyzed and compared between PWD (n=118 total), with EPI (T1D: n=14; T2D: n=20) or without EPI (T1D: n=78; T2D: n=6), and people without diabetes (n=206 total) with and without EPI.

I also looked at sub-groups within the non-EPI cohorts and broke them into two groups to see whether other GI conditions contributed to a higher EPI/PEI-SS score and whether we could distinguish EPI from other GI and non-GI conditions.

Results:

People with EPI have a much higher symptom burden than people without EPI. This can be assessed by looking at the statistically significant higher mean EPI/PEI-SS score as well as the average number of symptoms; the average severity score of individual symptoms; and the average frequency score of individual symptoms.

This remains true irrespective of diabetes. In other words, diabetes does not appear to influence any of these metrics.

People with diabetes with EPI had statistically significant higher mean EPI/PEI-SS scores (102.62 out of 225, SD: 52.46) than did people with diabetes without EPI (33.64, SD: 30.38), irrespective of presence of other GI conditions (all group comparisons p<0.001). As you can see below, that is the same pattern we see in people without diabetes. And the stats confirm what you can see: there is no significant difference overall or in any of the subgroups between people with and without diabetes.

Box plot showing EPI/PEI-SS scores for people with and without diabetes, and with and without EPI or other GI conditions. The scores are higher in people with EPI regardless of whether they have diabetes. The plot makes it clear that the scores are distinct between the groups with and without EPI, even when the people without EPI have other GI conditions. This suggests the EPI/PEI-SS can be useful in distinguishing between EPI and other conditions that may cause GI symptoms, and that the EPI/PEI-SS could be a useful screening tool to help identify people who need screening for EPI.

T1D and T2D subgroups were similar
(but because the T2D cohort is small, I did not break them out separately in this graph).

For example, people with diabetes with EPI had an average of 12.59 (out of 15) symptoms, with an average frequency score of 3.06 and average severity score of 1.79, and an average individual symptom score of 5.48. This is a pretty clear contrast to people with diabetes without EPI who had had an average of 7.36 symptoms, with an average frequency score of 1.4 and average severity score of 0.8, and an average individual symptom score of 1.12. All comparisons are statistically significant (p<0.001).

A table comparing the average number of symptoms, frequency, severity, and individual symptom scores between people with diabetes with and without exocrine pancreatic insufficiency (EPI). People with EPI have more symptoms and higher frequency and severity than without EPI: regardless of diabetes.

Conclusion 

  • EPI has a high symptom burden, irrespective of diabetes.
  • High scores using the EPI/PEI-SS among people with diabetes can distinguish between EPI and other GI conditions.
  • The EPI/PEI-SS should be further studied as a possible screening method for EPI and assessed as a tool to aid people with EPI in tracking changes to EPI symptoms over time based on PERT titration.

What does this mean if you are a healthcare provider? What actionable information does this give you?

If you’re a healthcare provider, you should be aware that people with diabetes may be more likely to have EPI – rather than celiac or gastroparesis (source) – if they mention having GI symptoms. This means you should incorporate fecal elastase screening into your care plans to help further evaluate GI-related symptoms.

If you want to further improve your pre-test probability of the elastase testing, you can use the EPI/PEI-SS with your patients to assess the severity and frequency of their GI-related symptoms. I will explain the cutoff and AUC numbers we calculated, but first understand the caveat that these were calculated in the initial real-world study that included people with EPI who are already treating with PERT; thus these numbers might change a little when we repeat this study and evaluate it in people with untreated EPI. (However, I actually predict the mean score to go up in an undiagnosed population, because scores should go down with treatment.) But that different population study may change these exact cutoff and sensitivity specificity numbers, which is why I’m giving this caveat. That being said: the AUC was 0.85 which means a higher EPI/PEI-SS is pretty good for differentiating between EPI and not having EPI. (In the diabetes sub-population specifically, I calculated a suggested cutoff of 59 (out of 225) with a sensitivity of 0.81 and specificity of 0.75. This means we estimate that if people are bringing up GI symptoms to you and you have them take the EPI/PEI-SS and their score is greater than or equal to 59, you would expect that out of 100 people that 81 with EPI would be identified (and 75 of 100 people without EPI would also correctly be identified via scores lower than 59). That doesn’t mean that people with EPI can’t have a lower score; or that people with a higher score do have EPI; but it does mean that the chances of having fecal elastase <=200 ug/g is a lot more likely in those with higher EPI/PEI-SS scores.

In addition to the cutoff score, there is a notable difference in people with diabetes and EPI compared to people with diabetes without EPI in their top individual symptom scores (representing symptom burden based on frequency and severity). For example, the top 3 symptoms of those with EPI and diabetes include avoiding certain food/groups; urgent bowel movements; and avoiding eating large meals. People without EPI and diabetes also score “Avoid certain food/groups” as their top score, but the score is markedly different: the mean score of 8.94 for people with EPI as compared to 3.49 for people without EPI. In fact, the mean score on the lowest individual symptom is higher for people with EPI than the highest individual symptom score for people without EPI.

QR code for EPI/PEI-SS - takes you to https://bit.ly/EPI-PEI-SS-WebHow do you have people take the EPI/PEI-SS? You can pull this link up (https://bit.ly/EPI-PEI-SS-Web), give this link to them and ask them to take it on their phone, or save this QR code and give it to them to take later. The link (and the QR code) go to a free web-based version of the EPI/PEI-SS that will calculate the total EPI/PEI-SS score, and you can use it for shared decision making processes about whether this person would benefit from a fecal elastase test or other follow up screening for EPI. Note that the EPI/PEI-SS does not collect any identifiable information and is fully anonymous.

(Bonus: people who use this tool can opt to contribute their anonymized symptom and score data for an ongoing observational study.)

If you have feedback about whether the EPI/PEI-SS was helpful – or not – in your care of people with diabetes; or if you want to discuss collaborating on some prospective studies to evaluate EPI/PEI-SS in comparison to fecal elastase screening, please reach out anytime to Dana@OpenAPS.org. 

What does this mean if you are a patient (person with diabetes)? What actionable information does this give you?

If you don’t have GI symptoms that bother you, you don’t necessarily need to take action. (Just put a note in your brain that EPI is more likely than celiac or gastroparesis in people with diabetes so if you or a friend with diabetes have GI symptoms in the future, you can make sure you are assessed for EPI.) You can also choose to take the EPI/PEI-SS regardless, and also opt in to donate your data.

If you do have GI symptoms that are annoying, you may want to take the EPI/PEI-SS to help you evaluate the frequency and severity of your GI symptoms. You can take it for free and anonymously – no identifiable information is needed to access the tool. It will generate the EPI/PEI-SS score for you.

Based on the score, you may want to ask your doctor (which could be the doctor that treats your diabetes, or a primary/general care provider, or a gastroenterologist – whoever you seek routine care from or have an appointment from next) about your symptoms; share the EPI/PEI-SS score; and explain that you think you may warrant screening for EPI.

(You can also choose to contribute your anonymous symptom data to a research dataset, to help us improve the EPI/PEI-SS and help us figure out how to help improve screening and diagnosis and treatment of EPI. Remember, this tool will not ask you for any identifying information. This is 100% optional and you can opt out of doing so if you do not prefer to contribute to research, while still using the tool.)

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You can see a pre-print version of the diabetes sub-study here or pre-print of the general population data here.

If you’re looking for more personal experiences about living with EPI, check out DIYPS.org/EPI, and also for people with EPI looking to improve their dosing with pancreatic enzyme replacement therapy – you may want to check out PERT Pilot (a free iOS app to record enzyme dosing).

Researchers & clinicians, if you’re interested in collaborating on studies in EPI (in diabetes, or more broadly on EPI), whether specifically on EPI/PEI-SS or broader EPI topics, please reach out! My email is Dana@OpenAPS.org

Being a raccoon and living with chronic disease

by Dana Lewis

Being a raccoon loading a dishwasher is a really useful analogy for figuring out: what you want to spend a lot of effort and precision on, where you can lower your effort and precision and still obtain reasonable outcomes, or where you can allow someone else to step in and help you when you don’t care how as long as the job gets done.

Huh? Raccoons?!

A few years ago Scott and I spotted a meme/joke going around that in every relationship there is a person who loads the dishwasher precisely (usually “stacks the dishwasher like a Scandinavian architect”) and one who loads the dishwasher like a “raccoon on meth” or a “rabid raccoon” or similar.

Our relationship and personality with dishwasher loading isn’t as opposite on the spectrum as that analogy suggests. However, Scott has a strong preference for how the dishwasher should be loaded, along with a high level of precision in achieving it. I have a high level of precision, but very low preference for how it gets done. Thus, we have evolved our strategy where I put things in and he re-arranges them. If I put things in with a high amount of effort and a high level of precision? He would rearrange them ANYWAY. So there is no point in me also spending high levels of effort to apply a first style of precision when that work gets undone. It is more efficient for me to put things in, and then he re-organizes as he sees fit.

Thus, I’ve embraced being the ‘raccoon’ that loads the dishwasher in this house. (Not quite as dramatic as some!)

A ChatGPT-created illustration of a cute raccoon happily loading the dishwasher, which looks fine but not precisely loaded.This came to mind because he went on a work trip, and I stuck things in the dishwasher for 2 days, and jokingly texted him to “come home and do the dishes that the raccoon left”. He came home well after dinner that night, and the next day texted when he opened the dishwasher for the first time that he “opened the raccoon cage for the first time”. (LOL).

Over the years, we’ve found other household tasks and chores where one of us has strong preferences about the way things should be done and the other person has less strong preferences. Similarly, there are some things that feel high-effort (and not worth it) for one of us but not the other. Over time, we’ve sorted tasks so things that feel high-effort can be done by the person for which it doesn’t feel high-effort, and depending on the preference level determines ‘how’ it gets done. But usually, the person who does it (because it’s low-effort) gets to apply their preferences, unless it’s a really weak preference and the preference of the non-doer doesn’t require additional effort.

Here are some examples of tasks and how our effort/preference works out. You can look at this and see that Scott ends up doing the dishwasher organization (after I load it like a raccoon) before starting the dishwasher and also has stronger preferences about laundry than I do. On the flip side, I seem to find it easier with routines for staying on top of household supply management including buying/re-ordering and acquiring and putting those away where we have them ready to go, because they’re not on a clear scheduled cadence. Ditto for managing the cats’ health via flea/tick medication schedules, scheduling and taking them to the vet, signing them up for cat camp when we travel, coordinating with the human involved in their beloved cat camp, etc. We end up doing a mix of overall work, split between the two of us.

A four-quadrant grid. Across the top it says "Effort" with low effort on the left and high effort on the right. Along the side it says "preference" with weak preference on the bottom and strong preference at the top. The implication is you can have a mix of preference and how much work certain chores are. Usually the person in the top left quadrant for a particular chore - representing easy or lower effort anad stronger preference - ends up doing that chore. For me that's household supply ordering; managing cat vet appts, etc. where due to Scott's much stronger preference his include the dishwasher, laundry, etc.
Could each of us do those tasks? Sure, and sometimes we do. But we don’t have to each do all of them, all the time, and we generally have a split list of who does which type of things as the primary doer.

Raccoons and burnout with chronic diseases

I have now lived with type 1 diabetes for almost 22 years. When I met Scott, I had been living with diabetes for 11 years. When he asked on one of our early dates what he could do to help, my answer was: “…nothing?” I’m an adult, and I’ve successfully managed my diabetes solo for decades.

Obviously, we ended up finding various ways for him to help, starting with iterating together on technological solutions for remote monitoring (DIYPS) to eventually closing the loop with an automated insulin delivery system (OpenAPS). But for the longest time, I still did all the physical tasks of ordering supplies, physically moving them around, opening them, managing them, etc. both at a 3-month-supply order level and also every 3 days with refilling reservoirs and changing pump sites and sensors.

Most of the time, these decades-long routines are literally routines and I do them without thought, the same way I put on my shoes before I leave the house. Yet when burnout is approaching – often from a combination of having five autoimmune diseases or having a lot of life going on while also juggling the ‘routine’ tasks that are voluminous – these can start to feel harder than they should.

Should, being the key word here.

Scott would offer to do something for me and I would say no, because I felt like I “should” do it because I normally can/am able to with minimal effort. However, the activation energy required (because of burnout or volume of other tasks) sometimes changes, and these minimal, low-effort tasks suddenly feel high-effort. Thus, it’s a good time to examine whether someone can – even in the short term and as a one-off – help.

It’s hard, though, to eradicate the “should”. I “should” be able to do X, I “should” be able to handle Y. But honestly? I should NOT have to deal with all the stuff and management of living with 5 autoimmune diseases and juggling them day in and day out. But I do have to deal with these and therefore do these things to stay in optimal health. “Should” is something that I catch myself thinking and now use that as a verbal flag to say “hey, just because I CAN do this usually doesn’t mean I HAVE to do it right now, and maybe it’s ok to take a break from always doing X and let Scott do X or help me with Y.”

Some of these “I should do it” tasks have actually become tasks that I’ve handed off long-term to Scott, because they’re super low effort for him but they’re mildly annoying for me because I have roughly 247 other tasks to deal with (no, I didn’t count them: that would make it 248).

For example, one time I asked him to open my shipment with 3 months worth of pump supplies, and unbox them so I could put them away. He also carried them into the room where we store supplies and put them where they belonged. Tiny, but huge! Only 246 tasks left on my list. Now, I order supplies, and he unboxes and puts them away and manages the inventory rotation: putting the oldest boxes on top (that I draw from first) and newer ones on bottom. This goes for pump supplies, CGM supplies, and anything else mail order like that.

A similar four quadrant chart with the same axes as the other graph, with effort on top (low left; high right) and execution preference (weak bottom, strong top). Similar to chores, we look at how our preferences and how much work it feels like, relative to each other, to decide if there are any tasks I can ask Scott to take on related to chronic disease management (like opening boxes and rotating stock of supplies being lower effort for him than me, due to my overall volume of tasks being higher)

This isn’t always as straightforward, but there are a lot of things I have been doing for 20+ years and thus find very low effort once the supplies are in my hand, like changing my pump site and CGM. So I do those. (If I was incapacitated, I have no doubt Scott could do those if needed.) But there’s other stuff that’s low effort and low preference like the opening of boxes and arranging of supplies that I don’t have to do and Scott is happy to take on to lower my task list of 247 things so that I only have about 240 things left to do for routine management.

Can I do them? Sure. Should I do them? Well, again, I can but that doesn’t mean I have to if there’s someone who is volunteering to help.

And sometimes that help is really useful in breaking down tasks that are USUALLY low effort – like changing a pump site – but become high effort for psychological reasons. Sometimes I’ll say out loud that I need to change my pump site, but I don’t want to. Some of that might be burnout, some of that is the mental energy it takes to figure out where to put the next pump site (and remembering the last couple of placements from previous sites, so I rotate them), combined with the physical activation energy to get up from wherever I am and go pull out the supplies to do it. In these cases, divide and conquer works! Scott often is more than happy to go and pull out a pump site and reservoir and place it where it’s convenient for me when I do get up to go do something else. For me, I often do pump site changes (putting a new one on, but I keep the old one on for a few extra hours in case the new one works) after my shower, so he’ll grab a pump site and reservoir and set it on the bathroom counter. Barrier removed. Then I don’t have to get up now and do it, but I also won’t forget to do it because it’s there in flow with my other tasks to do after my shower.

A gif showing a similar four quadrant graph (effort across top, execution preference along the side), showing a task going from the top left (low effort usually, strong preference for how it is done) moving to the right (high effort and still high preference), then showing it being split into two halves, one of which becomes a Scott task because it's lower effort sub-tasks and the remaining part is still high preference for me but has lowered the effort it takes.

There are a lot of chronic disease-related tasks like this that when I’m starting to feel burnout from the sheer number of tasks, I can look for (or sometimes Scott can spot) opportunities) to break a task into multiple steps and do them at different times, or to have someone do the task portions they can do, like getting out supplies. That then lowers the overall effort required to do that task, or lowers the activation energy depending on the task. A lot of these are simple-ish tasks, like opening something, getting something out and moving it across the house to a key action spot (like the bathroom counter for after a shower), or putting things away when they no longer need to be out. The latter is the raccoon-style approach. A lot of times I’ll have the activation energy to start and do a task, but not complete (like breaking down supply boxes for recycling). I’ll set them aside to do later, or Scott will spot this ‘raccoon’ stash of tasks and tackle it when he has time/energy, usually faster than me getting around to do it because he’s not burdened with 240 other tasks like that. (He does of course have a larger pile of tasks than without this, but the magnitude of his task list is a lot smaller, because 5 autoimmune diseases vs 0.)

Be a friend to your friend who needs to be a raccoon some of the time

I am VERY lucky to have met & fallen in love & married someone who is so incredibly able and willing to help. I recognize not everyone is in this situation. But there may be some ways our friends and family who don’t live with us can help, too. I had a really fantastic example of this lately where someone who isn’t Scott stepped up and made my raccoon-life instantly better before I even got to the stage of being a raccoon about it.

I have a bunch of things going on currently, and my doctor recommended that I have an MRI done. I haven’t had an MRI in years and the last one was pre-pandemic. Nowadays, I am still masking in any indoor spaces including healthcare appointments, and I plan to mask for my MRI. But my go-to n95 mask has metal in the nose bridge, which means I need to find a safe alternative for my upcoming MRI.

I was busy trying to schedule appointments and hadn’t gotten to the stage of figuring out what I would wear as an alternative for my MRI. But I mentioned to a friend that I was going to have an MRI and she asked what mask I was going to wear, because she knows that I mask for healthcare appointments. I told her I hadn’t figured it out yet but needed to eventually figure it out.

She instantly sprang into action. She looked up options for MRI-safe masks and asked a local friend who uses a CAN99 mask without wire whether the friend had a spare for me to try. She also ordered a sample pack of another n95 mask style that uses adhesive to stick to the face (and thus doesn’t have a metal nose bridge piece). She ordered these, collected the CAN99 from the local friend, and then told me when they’d be here, which was well over a week before I would need it for the MRI and offered to bring them by my house so I had them as soon as possible.

Meanwhile, I was gobsmacked with relief and appreciation because I would have been a hot mess of a raccoon trying to get around to sorting that out days or a week after she had sorted a variety of options for me to try. Instead, she predicted my raccoon-ness or otherwise was being a really amazing friend and stepping up to take something off my plate so I had one less thing to deal with.

Yay for helpers. In this case, she knew exactly what was needed. But a lot of times, we have friends or family who want to help but don’t know how to or aren’t equipped with the knowledge of what would be helpful. Thus, it’s useful – when you have energy – to think through how you could break apart tasks and what you could offer up or ask as a task for someone else to do that would lower the burden for you.

That might be virtual tasks or physical tasks:

  • It might be coming over and taking a bunch of supplies out of boxes (or medicine) and splitting them up and helping put them in piles or all the places those things need to go
  • It could be researching safe places for you to eat, if you have food allergies or restrictions or things like celiac
  • It could be helping divvy up food into individual portions or whatever re-sizing you need for whatever purpose
  • It could be researching and brainstorming and identifying some safe options for group activities, e.g. finding places with outdoor dining or cool places to walk and hike that suits everyone’s abilities and interests

Sometimes it’s the physical burden that it’s helpful to lift; sometimes it’s the mental energy burden that is helpful to lift; sometimes a temporary relief in all the things we feel like we have to do ourselves is more important than the task itself.

If you have a chronic disease, it’s ok to be a raccoon. There is no SHOULD.

Part of the reason I really like the raccoon analogy is because now instead of being annoyed at throwing things in the dishwasher, because whether I exert energy or not Scott is going to re-load it his way anyway, I put the dishes in without much precision and giggle about being a raccoon.

The same goes for chronic disease related-tasks. Even for tasks where Scott is not involved, but I’m starting to feel annoyed at something I need to do, I find ways to raccoon it a little bit. I change my pump site but leave the supplies on the counter because I don’t HAVE to put those away at the same moment. I usually do, but I don’t HAVE to. And so I raccoon it a bit and put the supplies away later, because it doesn’t hurt anyone or anything (including me) for those not to get put away at the same time. And that provides a little bit of comedic relief to me and lightens the task of changing my pump site.

It also helps me move away from the SHOULD weighing heavily in my brain. I should be able to get all my pump site stuff out, change it, and throw away and put away the supplies when done. It shouldn’t be hard. No one else has this challenge occasionally (or so my brain tells me).

But the burden isn’t about that task alone. It’s one task in the list of 247 things I’m doing every day to take care of myself. And sometimes, my list GROWS. January 18, my list was about 212 things I needed to do. Beginning January 19, my list jumped up to 230. Last week, it grew again. I have noticed this pattern that when my list of things to do grows, some of the existing “easy” tasks that I’ve done for 20 years suddenly feel hard. Because it is hard to split my energy across more tasks and more things to focus on; it takes time to adapt. And so being a raccoon for some of those tasks, for some of the time, provides a helpful steam-valve to output some of the challenges I’m juggling of dealing with all the tasks, because those tasks 100% don’t have to be done in the same way as I might do during “calm” static times where my task list hasn’t expanded suddenly.

And it doesn’t matter what anyone else does or what they care about. Thus, remove the should. You should be able to do this, sure – if you weren’t juggling 246 other things. But you do have 246 things and that blows apart the “should”.

Free yourself of the “should” wherever possible, and be a raccoon wherever it helps.

New Systematic Review Showing General Population Prevalence of Exocrine Pancreatic Insufficiency Is Higher Than In Co-Conditions

by Dana Lewis

For those unfamiliar with academic/medical journal publishing, it is slow. Very slow. I did a systematic review on EPI prevalence and submitted it to a journal on May 5, 2023. It underwent peer review and a round of revisions and was accepted on July 13, 2023. (That part is actually relatively quick.) However, it sat, and sat, and sat, and sat, and sat. I was impatient and wrote a blog post last year about the basic premise of the review, which is that despite commonly repeated statements about the prevalence of EPI being so high in co-conditions that those conditions therefore are the highest drivers of EPI… this unlikely to be true because it is mathematically improbable.

And then this paper still sat several more months until it was published online ahead of print…today! Wahoo! You can read “An Updated Review of Exocrine Pancreatic Insufficiency Prevalence finds EPI to be More Common in General Population than Rates of Co-Conditions” in the Journal of Gastrointestinal and Liver Diseases ahead of print (scheduled for the March 2024 issue).

It’s open access (and I didn’t have to pay for it to be!), so click here to go read it and download your own PDF copy of the article there. (As a reminder, I also save a version of every article including those that are not open access at DIYPS.org/research, in case you’re looking for this in the future or want to read some of my other research.) If you don’t want to read the full article, here’s a summary below and key takeaways for providers and patients (aka people like me with EPI!).

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I read and systematically categorized 649 articles related to exocrine pancreatic insufficiency, which is known as EPI or PEI depending on where in the world you are. EPI occurs when the pancreas no longer produces enough enzymes to successfully digest food completely; when this occurs, pancreatic enzyme replacement therapy (PERT) is needed. This means swallowing enzyme pills every time you eat or drink something with fat or protein in it.

Like many of my other EPI-related research articles, this one found that EPI is underdiagnosed; undertreated; treatment costs are high; and prevalence is widely misunderstood, possibly leading to missing screening key populations.

  • Underdiagnosis – for a clearer picture and specific disease-related example of how EPI is likely underdiagnosed in a co-condition, check out my other systematic review specifically assessing EPI in diabetes. I show in that paper how EPI is likely many times more likely than gastroparesis and celiac disease, yet it’s less likely to be screened for.
  • Undertreated – another recent systematic review that I wrote after this paper (but was published sooner) is this systematic review on PERT dosing guidelines and dosing literature, showing how the overwhelming majority of people are not prescribed enough enzymes to meet their needs. Thus, symptoms persist and the literature continues to state that symptoms can’t be managed with PERT, which is not necessarily true: it just hasn’t been studied correctly with sufficient titration protocols.
  • PERT costs are high – I highlight that although PERT costs continue to rise each year, there are studies in different co-condition populations showing PERT treatment is cost-effective and in some cases reduces the overall cost of healthcare. It’s hard to believe when we look at the individual out of pocket costs related to PERT sometimes, but the data more broadly shows that PERT treatment in many populations is cost-effective.
  • Prevalence of EPI is misunderstood. This is the bulk of the paper and goes into a lot of detail showing how the general population estimates of EPI may be as high as 11-21%. In contrast, although prevalence of EPI is much higher within co-conditions, these conditions are such a small fraction of the general population that they therefore are also likely a small fraction of the EPI population.

As I wrote in the paper:

“The overall population prevalence of cystic fibrosis, pancreatitis, cancer, and pancreatic-related surgery combined totals <0.1%, and the lower end of the estimated overall population prevalence of EPI is approximately 10%, which suggests less than 1% of the overall incidence of EPI occurs in such rare co-conditions.

We can therefore conclude that 99% of EPI occurs in those without a rare co-condition.”

I also pointed out the mismatch of research prioritization and funding to date in EPI. 56-85% of the EPI-related research is focused on those representing less than ~1% of the overall population with EPI.

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So what should you take away from this research?

If you are a healthcare provider:

Make sure you are screening people who present with gastrointestinal symptoms with a fecal elastase test to check for EPI. Weight loss and malnutrition does not always occur with EPI (which is a good thing, meaning it’s caught earlier) and similarly not everyone has diarrhea as their hallmark symptoms. Messy, smelly stools are often commonly described by people with EPI, among other symptoms such as excess gas and bloating,

Remember that conditions like diabetes have a high prevalence of EPI – it’s not just chronic pancreatitis or cystic fibrosis.

If you do have a patient that you are diagnosing or have diagnosed with EPI, make sure you are aware of the current dosing guidelines (see this systematic review) and 1) prescribe a reasonable minimal starting dose; 2) tell the patient when/how they can adjust their PERT on their own and when to call back for an updated prescription as they figure out what they need, and; 3) tell them they will likely need an updated prescription and you are ready to support them when they need to do so.

If you are a person living with EPI:

Most people with EPI are not taking enough enzymes to eliminate their symptoms. Dose timing matters (take it with/throughout meals), and the quantity of PERT matters.

If you’re still having symptoms, you may still need more enzymes.

Don’t compare what you are doing to what other people are taking: it’s not a moral failing to need a different amount of enzymes (or insulin, for that matter, or any other medication) than another person! It also likely varies by what we are eating, and we all eat differently.

If you’re still experiencing symptoms, you may need to experiment with a higher dose. If you still have symptoms or have new symptoms that start after taking PERT, you may need to try a different brand of PERT. Some people do well on one but not another, and there are different kinds you can try – ask your doctor.

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How to cite this systematic review:

Lewis D. An Updated Review of Exocrine Pancreatic Insufficiency Prevalence finds EPI to be More Common in General Population than Rates of Co-Conditions. Journal of Gastrointestinal and Liver Diseases. 2024. DOI: 10.15403/jgld-5005

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For other posts related to EPI, see DIYPS.org/EPI for more of my personal experiences with EPI and other plain-language research summaries.

For other research articles, see DIYPS.org/research

A systematic review shows EPI prevalence is more common in the general population than in co-conditions

Understanding Fecal Elastase Test Results Including Sensitivity And Specificity And What It Means For Exocrine Pancreatic Insufficiency (EPI or PEI)

by Dana Lewis

One of the challenges related to diagnosing exocrine pancreatic insufficiency (known as EPI or PEI) is that there is no perfect test.

With diabetes, we can see in several different ways what glucose is doing: via fasting glucose levels, HbA1c (an average of 3 months glucose), and/or continuous glucose monitoring. We can also test for c-peptide to see if insulin production is ongoing.

Yet for EPI, the tests for assessing whether and how much the pancreas is producing digestive enzymes are much less direct, more invasive, or both.

Some of the tests include a breath test; an invasive secretin pancreatic function test; a 72-hour fecal fat collection test, or a single sample fecal elastase test.

  • A breath test is an indirect test, which assesses the end-product of digestion rather than digestion itself, and other conditions (like SIBO) can influence the results of this test. It’s also not widely available or widely used.
  • The secretin pancreatic function test is an invasive test involving inserting a tube into the small intestine after giving secretin, which is a hormone that stimulates the pancreas. The tube collects digestive juices produced by the pancreas, which are tested. It’s invasive, costly, and therefore not ideal.
  • For reliability, the 72-hour fecal fat collection test might be ideal, because it’s checking the amount of fat in the stool. It requires stopping enzymes, if someone is taking them already, and consuming a high fat diet. But that includes collecting stool samples for 3 days – ugh. (The “ugh” is my personal opinion, clearly).
  • The fecal elastase test, in contrast, does not require stopping enzymes. It measures human elastase, whereas digestive enzymes are typically pig-based, so you don’t have to stop enzymes when doing this test. It’s also a single stool sample (so you’re not collecting poop for 3 days in a row). The sensitivity and specificity are different based on the diagnostic threshold, which I’ll talk about below, and the accuracy can be influenced by the sample. Diarrhea, meaning watery poop, can make this test even less reliable. But that’s why it’s good that you can take enzymes while doing this test. Someone with diarrhea and suspected EPI could go on enzymes, reduce their diarrhea so they could have a formed (non-watery) sample for the elastase test, and get a better answer from the fecal elastase test.

The fecal elastase test is often commonly used for initial screening or diagnosis of EPI. But over the last two years, I’ve observed a series of problems with how it is being used clinically, based on reading hundreds of research and clinical practice articles and reading thousands of posts of people with EPI describing how their doctor is ordering/reviewing/evaluating this test.

Frequent problems include:

  • Doctors refuse to test elastase, because they don’t believe the test indicates EPI due to the sensitivity/specificity results for mild/moderate EPI.
  • Doctors test elastase, but won’t diagnose EPI when test results are <200 (especially if 100-200).
  • Doctors test elastase, but won’t diagnose EPI even when test results are <100!
  • Doctors test elastase, diagnose EPI, but then do not prescribe enzymes because of the level of elastase (even when <200).
  • Doctors test elastase, diagnose EPI, but prescribe a too-low level of enzymes based on the level of elastase, even though there is no evidence indicating elastase should be used to determine dosing of enzymes.

Some of the problems seem to result from the fact that the elastase test has different sensitivity and specificity at different threshold levels of elastase.

When we talk about “levels” of elastase or “levels” or “types” of EPI (PEI), that usually means the following thresholds / ranges:

  • Elastase <= 200 ug/g indicates EPI
  • Elastase 100-200 ug/g indicates “mild” or “mild/moderate” or “moderate” EPI
  • Elastase <100 ug/g often is referred to as “severe” EPI

You should know that:

  • People with severe EPI (elastase <100) could have no symptoms
  • People with mild/moderate EPI (elastase 100-200) could have a very high level of symptoms and be malnourished
  • People with any level of elastase indicating EPI (elastase <=200) can have EPI even if they don’t have malnourishment (usually meaning blood vitamin levels like A, D, E, or K are below range).

So let’s talk about sensitivity and specificity at these different levels of elastase.

First, let’s grab some sensitivity and specificity numbers for EPI.

  1. One paper that is widely cited, albeit old, is of sensitivity and specificity of fecal elastase for EPI in people with chronic pancreatitis. You’ll see me talk in other posts about how chronic pancreatitis and cystic fibrosis-related research is over-represented in EPI research, and it may or may not reflect the overarching population of people with EPI.But since it’s widely used, I’ll use it in the below examples, especially because this may be what is driving clinician misunderstanding about this test.With a cut off of <200 ug/g, they found that the sensitivity in detecting moderate/severe EPI is 100%, and 63% sensitivity for detecting mild EPI. At that <200 ug/g threshold, the specificity is 93% (which doesn’t distinguish between severities). With a cut off of <100 ug/g, the sensitivity for detecting mild EPI drops to 50%, but the specificity increases to 98%.This means that:
    1. 63% of people with mild EPI would be correctly diagnosed using an elastase threshold of 200 ug/g (vs. only 50% at 100 ug/g).
    2. 100% of people with moderate/severe EPI would be correctly diagnosed using an elastase threshold of 200 ug/g (compared to only 93% or 96% for moderate/severe at 100 ug/g).
    3. Only 7% of people testing <200 ug/g would be incorrectly diagnosed with EPI, and only 2% of people testing <100 ug/g.
  2. For comparison, a systematic review evaluated a bunch of studies (428 people from 14 studies) and found an average sensitivity of 77% (95% CI of 58-89%) and average specificity of 88% (95% CI of 78-93%).This sensitivity is a little higher than the above number, which I’ll discuss at the end for some context.

So what does sensitivity and specificity mean and why do we care?

At an abstract level, I personally find it hard to remember what sensitivity and specificity mean.

  • Sensitivity means: how often does it correctly identify the thing we want to identify?

This means a true positive. (Think about x-ray screening at airport security: how often do they find a weapon that is there?)

  • Specificity means: how often does it avoid mistakenly identifying the thing we want to identify? In other words, how often is a positive a true positive rather than a false positive?

(Think about x-ray screening at airport security: how often does it correctly identify that there are no weapons in the bag? Or how often do they accidentally think that your jam-packed bag of granola and snacks might be a weapon?)

Here is how we apply this to fecal elastase testing for EPI.

For those with moderate/severe EPI, the test is 100% sensitive at correctly detecting those cases if you use an elastase cut off of <200 ug/g. For those with mild EPI, the test drops to only being 63% sensitive at correctly detecting all of those cases. And 93% of the time, the test correctly excludes EPI when it doesn’t exist (at a <200 ug/g cut off, vs. 98% of the time at a <100 ug/g cut off). Conversely, 7% (which we get from subtracting 93% from 100%) of people with elastase <200 ug/g might not have EPI, and 2% (98% subtracted from 100%) of people with elastase <100 ug/g might not have EPI.

Here’s another way of thinking about it, using a weather forecast analogy. Think about how easy it is to predict rain when a major storm is coming. That’s like trying to detect severe EPI, it’s a lot easier and forecasters are pretty good about spotting major storms.

But in contrast, what about correctly predicting light rain? In Seattle, that feels close to impossible – it rains a lot, very lightly. It’s hard to predict, so we often carry a light rain jacket just in case!

And for mild EPI, that’s what the sensitivity of 63% means: less than two thirds of the time can it correctly spot mild EPI by looking for <200 ug/g levels, and only half the time by looking for <100 ug/g. The signal isn’t as strong so it’s easier to miss.

The specificity of 93% means that the forecast is pretty good at identifying not-rainy-days, even with a cut off of elastase >200 ug/g. But, occasionally (around 7/100 times), it’s wrong.

Table comparing the sensitivity for severe and mild EPI alongside specificity, plus comparing to weather forecast ability for rain in major storms.

Why might clinicians be incorrectly using the value of these numbers for the fecal elastase test?

I hypothesize that in many cases, for the elastase levels now considered to indicate mild/moderate EPI (elastase 100-200 ug/g), clinicians might be accidentally swapping the sensitivity (63%) and specificity (93%) numbers in their mind.

What these numbers tell us is that 63% of the time, we’ll catch mild EPI through elastase testing. This means 37/100 people with actual mild EPI might be missed!

In contrast, the specificity of 93% tells us about accidental false positives, and that 7/100 people without EPI might accidentally get flagged as having possible EPI.

Yet, the clinical practice in the real-world seems to swap these numbers, acting as if the accuracy goes the other way, suspecting that elastase 100-200 doesn’t indicate EPI (e.g. thinking 37/100 false positives, which is incorrect, the false positive rate is 7/100).

There’s plenty of peer-reviewed and published evidence that people with elastase 100-200 have a clear symptom burden. There’s even a more recent paper suggesting that those with symptoms and elastase of 200-500 benefit from enzymes!

Personally, as a person with EPI, I am frustrated when I see/hear cases of people whose clinicians refuse testing, or don’t prescribe PERT when elastase is <=200 ug/g, because they don’t believe elastase 100-200 ug/g is an accurate indicator of EPI. This data shows that’s incorrect. Regardless of which paper you use and which numbers you cite for sensitivity and specificity, they all end up with way more common rates of false negatives (missing people with EPI) than false positives.

And, remember that many people with FE 200-500 benefit from enzymes, too. At a cutoff of 200 ug/g, the number of people we are likely to miss (sensitivity) at the mild/moderate level is much higher than the number of false positives who don’t actually have EPI. That puts the risk/benefit calculation – to me – such that it warrants using this test, putting people on enzymes, and evaluating symptom resolution over time following PERT dosing guidelines. If people’s symptom burden does not improve, titrating PERT and re-testing elastase makes sense (and that is what the clinical guidelines say to do), but the cost of missing ~37 people out of 100 with EPI is too high!

Let’s also talk about elastase re-testing and what to make of changed numbers.

I often also observe people with EPI who have their elastase re-tested multiple times. Here are some examples and what they might mean.

  • A) Someone who tests initially with a fecal elastase of 14, later retests as 16, then 42 ug/g.
  • B) Someone who tests initially at 200 and later 168.
  • C) Someone who tests initially at 72 and later 142.
  • D) Someone who tests initially as 112 and later 537.

Remember the key to interpreting elastase is that <=200 ug/g is generally accepted as indicating EPI. Also it’s key to remember that the pancreas is still producing some enzymes, thus elastase production will vary slightly. But in scenarios A, B, and C – those changes are not meaningful. In scenario A, someone still has clear indicators of severe (elastase <100) EPI. Slight fluctuations don’t change that. Same for scenario B, 200 and 168 are both still in mild/moderate EPI (elastase <=200). Even scenario C isn’t very meaningful, even though there is an “increase”, this is still clearly EPI.

In most cases, the fluctuations in test results are likely a combination of both natural fluctuations in pancreas production and/or test reliability. If someone was eating a super low fat diet, taking enzymes effectively, that may influence how the pancreas is producing its natural enzymes – we don’t actually know what causes the pancreas to fluctuate the natural enzyme levels.

The only case that is meaningful in these examples is scenario D, where someone initially had a result of 112 and later clearly above the EPI threshold (e.g. 537). There are a few cases in the literature where people with celiac seem to have temporary EPI and later their elastase production returns to normal. This hasn’t been documented in other conditions, which doesn’t mean that it’s not possible, but we don’t know how common it is. It’s possible the first sample of 112 was due to a watery sample (e.g. during diarrhea) or other testing inaccuracy, too. If a third test result was >500, I’d assume it was a temporary fluctuation or test issue, and that it’s not a case of EPI. (Yay for that person!). If it were me (and I am not a doctor), I’d have them try out a period without enzymes to ensure that symptoms continued to be managed effectively. If the third test was anywhere around 200 or below, I’d suspect something going on contributing to fluctuations in pancreatic production and not be surprised if enzymes were continued to be needed, unless the cause could be resolved.

But what about scenario C where someone “went from severe to mild/moderate EPI”?!

A lot of people ask that. There’s no evidence in the hundreds (seriously, hundreds) of papers about EPI that indicate clearly that enzymes should be dosed based on elastase level, or that there’s different needs based on these different categories. The “categories” of EPI originally came from direct measurements of enzyme secretion via invasive tests, combined with quantitative measurements of bicarbonate and fat in stools. Now that fecal elastase is well established as a non-invasive diagnostic method, severities are usually estimated based on the sensitivity of these cutoffs for detecting EPI, and that’s it. The elastase level doesn’t actually indicate the severity of the experience through symptoms, and so enzymes should be dosed and adjusted based on the individual’s symptoms and their diet.

In summary:

  • Elastase <=200 ug/g is very reliable, indicates EPI, and warrants starting PERT.
  • There is one small study suggesting even people with elastase 200-500 might benefit from PERT, if they have symptoms, but this needs to be studied more widely.
  • It’s possible clinicians are conflating the sensitivity and specificity, thus misunderstanding how accurately elastase tests can detect cases of mild/moderate EPI (when elastase is 100-200 ug/g).

—

Let me know if anyone has questions about elastase testing, sensitivity, and specificity that I haven’t answered here! Remember I’m not a doctor, and you should certainly talk with your doctor if you have questions about your specific levels. But make sure your doctor understands the research, and feel free to recommend this post to them if they aren’t already familiar with it: https://bit.ly/elastase-sensitivity-specificity

Accepted, Rejected, and Conflict of Interest in Gastroenterology (And Why This Is A Symptom Of A Bigger Problem)

by Dana Lewis

Recently, someone published a new clinical practice update on exocrine pancreatic insufficiency (known as EPI or PEI) in the journal called Gastroenterology, from the American Gastroenterology Association (AGA). Those of you who’ve read any of my blog posts in the last year know how much I’ve been working to raise awareness of EPI, which is very under-researched and under-treated clinically despite the prevalence rates in the general population and key sub-populations such as PWD. So when there was a new clinical practice update and another publication on EPI in general, I was jazzed and set out to read it immediately. Then frowned. Because, like so many articles about EPI, it’s not *quite* right about many things and it perpetuates a lot of the existing problems in the literature. So I did what I could, which was to check out the journal requirements for writing a letter to the editor (LTE) in response to this article and drafting and submitting a LTE article about it. To my delight, on October 17, 2023, I got an email indicating that my LTE was accepted.

You can find my LTE as a pre-print here.

See below why this pre-print version is important, and why you should read it, plus what it reminds us about what journal articles can or cannot tell us in healthcare.

Here’s an image of my acceptance email. I’ll call out a key part of the email:

A print of the acceptance email I received on October 17, 2023, indicating my letter would be sent to authors of the original articles for a chance to choose to respond (or not). Then my LTE would be published.

Letters to the Editor are sent to the authors of the original articles discussed in the letter so that they might have a chance to respond. Letters are not sent to the original article authors until the window of submission for letters responding to that article is closed (the last day of the issue month in which the article is published). Should the authors choose to respond to your letter, their response will appear alongside your letter in the journal.

Given the timeline described, I knew I wouldn’t hear more from the journal until the end of November. The article went online ahead of print in September, meaning likely officially published in October, so the letters wouldn’t be sent to authors until the end of October.

And then I did indeed hear back from the journal. On December 4, 2023, I got the following email:

A print of the email I received saying the LTE was now rejected
TLDR: just kidding, the committee – members of which published the article you’re responding to – and the editors have decided not to publish your article. 

I was surprised – and confused. The committee members, or at least 3 of them, wrote the article. They should have a chance to decide whether or not to write a response letter, which is standard. But telling the editors not to publish my LTE? That seems odd and in contrast to the initial acceptance email. What was going on?

I decided to write back and ask. “Hi (name redacted), this is very surprising. Could you please provide more detail on the decision making process for rescinding the already accepted LTE?”

The response?

Another email explaining that possible commercial affiliations influenced their choice to reject the article after accpeting it originally
“In terms of this decision, possible commercial affiliations, as well as other judgments of priority and relevance among other submissions, dampened enthusiasm for this particular manuscript. Ultimately, it was not judged to be competitive for acceptance in the journal. “

Huh? I don’t have any commercial affiliations. So I asked again, “Can you clarify what commercial affiliations were perceived? I have none (nor any financial conflict of interest; nor any funding related to my time spent on the article) and I wonder if there was a misunderstanding when reviewing this letter to the editor.”

The response was “There were concerns with the affiliation with OpenAPS; with the use of the term “guidelines,” which are distinct from this Clinical Practice Update; and with the overall focus being more fit for a cystic fibrosis or research audience rather than a GI audience.”

A final email saying the concern with my affiliation of OpenAPS, which is not a commercial organization nor related to the field of gastroenterology and EPI

Aha, I thought, there WAS a misunderstanding. (And the latter makes no sense in the context of my LTE – the point of it is that most research and clinical literature is a too-narrow focus, cystic fibrosis as one example – the very point is that a broad gastroenterology audience should pay attention to EPI).

I wrote back and explained how I, as a patient/independent researcher, struggle to submit articles to manuscript systems without a Ringgold-verified organization. (You can also listen to me describe the problem in a podcast, here, and I also talked about it in a peer-reviewed journal article about citizen science and health-related journal publishing here). So I use OpenAPS as an “affiliation” even though OpenAPS isn’t an organization. Let alone a commercial organization. I have no financial conflict of interest related to OpenAPS, and zero financial conflict of interest or commercial or any type of funding in gastroenterology at all, related to EPI or not. I actually go to such extremes to describe even perceived conflicts of interest, even non-financial ones, as you can see this in my disclosure statement publicly available from the New England Journal of Medicine here on our CREATE trial article (scroll to Supplemental Information and click on Disclosure Forms) where I articulate that I have no financial conflicts of interest but acknowledge openly that I created the algorithm used in the study. Yet, there’s no commercial or financial conflict of interest.

A screenshot from the publicly available disclosure form on NEJM's site, where I am so careful to indicate possible conflicts of interest that are not commercial or financial, such as the fact that I developed the algorithm that was used in that study. Again, that's a diabetes study and a diabetes example, the paper we are discussing here is on exocrine pancreatic insufficiency (EPI) and gastroenterology, which is unrelated. I have no COI in gastroenterology.

I sent this information back to the journal, explaining this, and asking if the editors would reconsider the situation, given that the authors (committee members?) have misconstrued my affiliation, and given that the LTE was originally accepted.

Sadly, there was no change. They are still declining to publish this article. And there is no change in my level of disappointment.

Interestingly, here is the article in which my LTE is in reply to, and the conflict of interest statement by the authors (committee members?) who possibly raised a flag about supposed concern about my (this is not true) commercial affiliation:

The conflict of interest statement for authors from the article "AGA Clinical Practice Update on the Epidemiology, Evaluation, and Management of Exocrine Pancreatic Insufficiency 2023"

The authors disclose the following: David C. Whitcomb: consultant for AbbVie, Nestlé, Regeneron; cofounder, consultant, board member, chief scientific officer, and equity holder for Ariel Precision Medicine. Anna M. Buchner: consultant for Olympus Corporation of America. Chris E. Forsmark: grant support from AbbVie; consultant for Nestlé; chair, National Pancreas Foundation Board of Directors.

As a side note, one of the companies with consulting and/or grant funding to two of the three authors is the biggest manufacturer of pancreatic enzyme replacement therapy (PERT), which is the treatment for EPI. I don’t think this conflict of interest makes these clinicians ineligible to write their article; nor do I think commercial interests should preclude anyone from publishing – but in my case, it is irrelevant, because I have none. But, it does seem weird given the stated COI for my (actually not a) COI then to be a reason to reject a LTE, of all things.

Here’s the point, though.

It’s not really about the fact that I had an accepted article rejected (although that is weird, to say the least…).

The point is that the presence of information in medical and research journals does not mean that they are correct. (See this post describing the incorrect facts presented about prevalence of EPI, for example.)

And similarly, the lack of presence of material in medical and research journals does not mean that something is not true or is not fact! 

There is a lot of gatekeeping in scientific and medical research. You can see it illustrated here in this accepted-rejected dance because of supposed COI (when there are zero commercial ties, let alone COI) and alluded to in terms of the priority of what gets published.

I see this often.

There is good research that goes unpublished because editors decide not to prioritize it (aka do not allow it to get published). There are many such factors in play affecting what gets published.

There are also systemic barriers.

  • Many journals require fees (called article processing charges or “APC”s) if your article is accepted for publication. If you don’t have funding, that means you can’t publish there unless you want to pay $2500 (or more) out of pocket. Some journals even have submission fees of hundreds of dollars, just to submit! (At least APCs are usually only levied if your article is accepted, but you won’t submit to these journals if you know you can’t pay the APC). That means the few journals in your field that don’t require APCs or fees are harder to get published in, because many more articles are submitted (thus, influencing the “prioritization” problem at the editor level) to the “free” journals.
  • Journals often require, as previously described, your organization to be part of a verified list (maintained by a third party org) in order for your article to be moved through the queue once submitted. Instead of n/a, I started listing “OpenAPS” as my affiliation and proactively writing to admin teams to let them know that my affiliation won’t be Ringgold-verified, explaining that it’s not an org/I’m not at any institution, and then my article can (usually) get moved through the queue ok. But as I wrote in this peer-reviewed article with a lot of other details about barriers to publishing citizen science and other patient-driven work, it’s one of many barriers involved in the publication process. It’s a little hard, every journal and submission system is a little different, and it’s a lot harder for us than it is for people who have staff/support to help them get articles published in journals.

I’ve seen grant funders say no to funding researchers who haven’t published yet; but editors also won’t prioritize them to publish on a topic in a field where they haven’t been funded yet or aren’t well known. Or they aren’t at a prestigious organization. Or they don’t have the “right” credentials. (Ahem, ahem, ahem). It can be a vicious cycle for even traditional (aka day job) researchers and clinicians. Now imagine that for people who are not inside those systems of academia or medical organizations.

Yet, think about where much of knowledge is captured, created, translated, studied – it’s not solely in these organizations.

Thus, the mismatch. What’s in journals isn’t always right, and the process of peer review can’t catch everything. It’s not a perfect system. But what I want you to take away, if you didn’t already have this context, is an understanding that what’s NOT in a journal is not because the information is not fact or does not exist. It may have not been studied yet; or it may have been blocked from publication by the systemic forces in play.

As I said at the end of my LTE:

“It is also critical to update the knowledge base of EPI beyond the sub-populations of cystic fibrosis and chronic pancreatitis that are currently over-represented in the EPI-related literature. Building upon this updated research base will enable future guidelines, including those like the AGA Clinical Practice Update on EPI, to be clearer, more evidence-based, and truly patient-centric ensuring that every individual living with exocrine pancreatic insufficiency receives optimal care. “

PS – want to read my LTE that was accepted then rejected, meaning it won’t be present in the journal? Here it is on a preprint server with a DOI, which means it’s still easily citable! Here’s an example citation:

Lewis, D. Navigating Ambiguities in Exocrine Pancreatic Insufficiency. OSF Preprints. 2023. DOI: 10.31219/osf.io/xcnf6

New Survey For Everyone (Including You – Yes, You!) To Help Us Learn More About Exocrine Pancreatic Insufficiency

by Dana Lewis

If you’ve ever wanted to help with some of my research, this is for you. Yes, you! I am asking people in the general public to take a survey (https://bit.ly/GI-Symptom-Survey-All) and share their experiences.

Why?

Many people have stomach or digestion problems occasionally. For some people, these symptoms happen more often. In some cases, the symptoms are related to exocrine pancreatic insufficiency (known as EPI or PEI). But to date, there have been few studies looking at the frequency of symptoms – or the level of their self-rated severity – in people with EPI or what symptoms may distinguish EPI from other GI-related conditions.

That’s where this survey comes in! We want to compare the experiences of people with EPI to people without EPI (like you!).

Will you help by taking this survey?

Your anonymous participation in this survey will help us understand the unique experiences individuals have with GI symptoms, including those with conditions like exocrine pancreatic insufficiency (EPI). In particular, data contributed by people without EPI will help us understand how the EPI experience is different (or not).

A note on privacy:

  • The survey is completely anonymous; no identifying information will be collected.
  • You can stop the survey at any point.

Who designed this survey:

Dana Lewis, an independent researcher, developed the survey and will manage the survey data. This survey design and the choice to run this survey is not influenced by funding from or affiliations with any organizations.

What happens to the data collected in this survey:

The aggregated data will be analyzed for patterns and shared through blog posts and academic publications. No individual data will be shared. This will help fill some of the documented gaps in the EPI-related medical knowledge and may influence the design of targeted research studies in the future.

Have Questions?
Feel free to reach out to Dana+GISymptomSurvey@OpenAPS.org.

How else can you help?
Remember, ANYONE can take this survey. So, feel free to share the link with your family and friends – they can take it, too!

Here’s a link to the survey that you can share (after taking it yourself, of course!): https://bit.ly/GI-Symptom-Survey-All

You (yes you!) can help us learn about exocrine pancreatic insufficiency by taking the survey linked on this page.

MacrosOnTheRun: an iOS app for tracking activity fuel consumption

by Dana Lewis

Last year, I built a spreadsheet template (and shared it here) to use while training and running ultramarathons to track my fuel consumption. It was helpful for me, as a person with exocrine pancreatic insufficiency, to see and decide based on macronutrient counts for each snack how many enzyme pills I needed to take each time I fueled, which is every 30 minutes.

This year, I got tired of messing with the spreadsheet while running. I don’t mind the data entry, but because of the iterative calculations updating with the hourly and overall totals of carbs, sodium, calories per hour etc, the Google Sheet would get bogged down over time, especially when I was running for 16 hours (like during my 100k in March). That would cause the Google Sheets app to crash and reload, or kick me out of the sheet and require me to click back in, wait for it to catch up, before entering my fuel item. It only took a couple of seconds, but it was annoying to have that delay while I was running.

I thought about not logging my fueling while running, especially because I had switched to a slightly more expensive but also larger over-the-counter (OTC) enzyme pill that basically covers every single snack I take with one single pill. That requires less mid-run decision making about how many to take, so it’s less important during the run to see each snack’s composition: I simply swallow a pill each time I do fuel.

Yet, after 1-2 runs of 2-3 hours where I didn’t log my intake, I still found myself missing the data from the run. Although the primary use case of in-run decision making wasn’t there for enzyme dosing, the secondary use case of making sure I was consuming enough sodium per hour and calories per hour relative to my goals was still there. I still wanted to offload that hourly tracking so I didn’t have to remember how much I had had in the last hour. Plus, the post-run data summary was nice, because it helped me evaluate my fueling overall in the grand scheme of my daily nutritional intake, which is particularly helpful for me in making sure I’m consuming enough protein to match my ultra-running activities.

And, I had figured out last year how to develop iOS apps (check out PERT Pilot if you have EPI, and Carb Pilot if you’re someone who’d like to simply use AI to generate estimates of how many carbs or macronutrients are in what you’re eating) with the help of an LLM. So I decided to try to build a custom, just for me app to mimic my spreadsheet in order to easily track my fueling on the run.

Tada! I made MacrosOnTheRun.Macros on the run logo showing "on the run" below the word Macros, stylized to look like 'on the run' is a drop down menu, reminiscent of the fuel list drop down in the app

It’s pretty simple: I open the app, hit ‘start run’, and then click the drop down and tap the fuel item (or electrolyte) that I’m consuming. I hit “add fuel”, and the items drops into the list on the screen and is added to the hourly and overall estimates shown above the drop down.

Screenshot of MacrosOnTheRun showing a pre-populated fuel list to select from and on the right, a screenshot at the end of a 9 hour run with fuel totals and individual fuel items entered
An example during a long run where after the run I open the app to export my in-run data. This is after the run, so you’ll see it’s been 97 minutes since the last fuel when I took that screenshot, and thus the sodium per hour and calories per hour calculation shows 0 given that it’s been >60 minutes since the last fuel. Below that is the total run stats, including enzymes and electrolytes counts. Given that I fuel like clockwork every 30 minutes, you can infer this was a 9 hour run since I took 18 enzymes!

When I’m done with the run, I tap the “stop and export” button at the bottom, which opens the iOS share sheet and enables me to email the CSV file to myself, so I can copy/paste the data back into the same spreadsheet template I was using before. It’s useful because I have all my runs stored as individual tabs in the sheet, and the template (same one I was using last year) autopopulates the pivot table with hourly summaries so I can see across each hour whether I was meeting my sodium and fueling goals. (Check out the 27 hour summary table in my 100 mile recap if you’re curious to see an example!)

Right now, I haven’t bothered to add a feature to edit in-app what the fuel list is – mine is programmed in via the code of the app itself, since I’m the only one using it – and I haven’t published it to the iOS App Store because I didn’t think anyone else would want to use it.

But, if I’m wrong, and this is something you’d like to use – let me know by commenting here or emailing me (Dana+MacrosOnTheRun@OpenAPS.org) and letting me know. If there’s interest, I can modify the app to allow in-app fuel list entry and modifications of the fuel list and then share it via TestFlight or in the App Store for other people to download and use.