Datasets:

Shamus

/

multimed_short

like 0

As already said, I'm a wife, a mother, and a full-time finance professionals with a daily three-hour round-trip commute. I'm an ME/CFS patient and I am one of the lucky ones.

I was diagnosed in 1995 after recovering from Epstein-Barr virus. A few weeks of resting and dancing the try hourly Tylenol,

advil shovel and I was okay and then one day I wasn't. So contact in 1995, I was 12 years old.

More people were familiar with the term yuppie flu and then the diagnosis or even the veracity of chronic fatigue syndrome. There was no Google and I couldn't ask you.

In 1995, during the late night hours that I was too tired to sleep, which is the most frustrating contradiction of all ME/CFS symptoms.

I learned that I wasn't dying from watching midnight reruns on the Golden Girls. Season 5 Episodes 2 was titled, Sick and Tired.

By repeatedly receiving a clean bill of health after months of physical and cognitive impairments, so debilitating, so you had to stop working,

start these warn Act was diagnosed with chronic fatigue syndrome, and I could have written the episode myself. If brain fog didn't make it too hard to find the word and it's

pain and didn't keep me from grasping a pen tightly enough to write. On the days that I couldn't even lift my arm. I have made the episode more exciting by adding a painting cell from

intermittent hypoglycemia and I complicated it with doctoral orthostatic tachycardia. I am lucky that this rheumatologists didn't dismiss my symptoms and growing pains or puberty or anxiety,

which happens more than once. I'm lucky I didn't wait months or years for a diagnosis and I'm lucky to have the opportunity to speak with you today.

I have two vials of injectable acts our gel in the fridge is the last resort. Last resort because it's $30,000 a vial. The financial assistance program is so administratively burdensome,

it causes post exertional malaise. Also in my fridge is cassette decks for the psoriatic arthritis, I was diagnosed with it H33.

Do rheumatologists that I need classic fiber okay. Until he noticed the scars from the bilateral total knee replacement had 25 for what the surgeon calls total side compartmental

degeneration is that rivaled a retired football player. I started taking a low dose of the immunosuppressants to their limits in November of 22 and the fog started listing.

There's a difference between fog and fatigue. Half the time I can put through this again with Modafinil, but then I crashed and I need a few days to recover.

I couldn't find the toilet paper, which was on a roll on the toilet paper holder, I'd have the roll where it's always been. My fourth day on Carolinas,

I realized it was working when I got home and didn't meet my husband help to pack the dinner on my plate. I bet in most any CFS patients gravitate

towards finger goods over anything that requires a fork and knife. Microwaveable pizza pocket doesn't require strength or energy or dexterity and it's less likely to cause post exertional malaise.

It's also a lot easier to navigate from inside the fog. Lucky because my recent progress is not short-lived but there are two sides to every coin.

I spent three decades to fog, to comprehend this pain. Life outside the Bosnians, I am acutely,

profoundly aware of my pain and chronic pain causes chronic fatigue. I'm lucky, 30 years of trial and error has taught me and most of my family,

because it takes most of my family, including my children who still don't have the mother they deserved how to balance my symptoms with the rest of my life.

As painful as it is, I'm lucky now, more so than ever to apply what I've learned about CNS symptom management from outside the fog.

Please make this your compass when defining the ME/CFS research roadmap. Symptom management in a vacuum is not working. I'm not discounting, it's important.

But we must treat and prevent the higher cascade of central nervous system disruptions to regain any quality of life. I am by no means healthy,

but I'm the healthiest ever been and 40 years old, a wife, a mother and since 1995, a full-time ME/CFS patient.

I'm one of the lucky ones. Thank you. Jarred Younger: Thank you, Trisha. I don't know if everyone can hear me,

I heard that my Zoom was not working very well. I hope it is working better now. If not, I will figure out what to do about that,

but it looks better so far. Thank you very much. I want to introduce the next speaker Gudrun Lange, and Gudrun is a clinical neuropsychologist.

She's at the Pain of Fatigue Study Center in New York. There is so much clinical and scientific confusion, and misconception when it comes to cognition in

fibromyalgia or go for illness or ME/CFS or long COVID. Cognition is a core part of these conditions for sure. But sometimes it seems to me that it's the least understood and so I'm

very glad that Gudrun can be the light in all the confusion. Every time I stumble upon a group starting to haphazardly incorporate cognitive measures into what they're doing.

I can just gently say, hold on a second, there's somebody you should speak to first, and that is Gudrun Lange. It's all yours.

Gudrun Lange: Thank you very much Jarred, and thank you very much, Trisha, for your report of the lived experience because it taps

right into what I'm actually going to be talking about today. John, I'm just going to say next slide, and go on to the next slide.

What I'll be talking about today is the status of current knowledge about cognitive function in s and the gaps in knowledge.

But it turned out that I'm going to be talking mostly about inclusion of cognitive assessment in clinical trial design.

Then finally, I'm going to focus on what we can do to make it better as we go forward. Next slide, please.

Not a rich history of neuropsychological research, Cordova for about 40 years, but 25 of those have been around,,

and we know at this point pretty much that it's there. We know its nature. It is mostly focused on

a complex information processing and efficient information processing as Trisha was so well describing before.

It is perceived as severe as disabling. In fact, very early on, Lenny Jason, already estimated that cognitive function to receive by about 89% of ME/CFS patients.

The deficits they perceive most commonly are described as memory and concentration problems. I'll go into that a little bit.

Next slide, please. When I reviewed the literature, it quickly occurred to me that I had bitten off a lot for this presentation.

I was surprised by the fact that cognitive assessments are not very often used in clinical trial design.

Despite the fact that we know that they are real, that they are not manifestations of depressive disorder,

even though it's present disorder can be comorbid, and make sure to also put that they're not manifestation of somatic symptoms. They are real.

They are not due to war effort, no motivation to do well on cognitive tasks. They are a real deficit and impact life.

Next slide, please. I'm going to briefly talk about patient reported measures of cognitive dysfunction and emit the best.

Most managers addressing cognitive functioning, ME/CFS studies and trials trying not to be patient reported outcome measures, also called PROs.

I have a little list here of patient reported outcome measures that are often used clinical trials.

The first three are specific to any ME/CFS and the rest is not specific to ME/CFS. With the SF-36 pretty much used in most clinical trials,

but not as the primary outcome measure. But somewhere in the secondary outcome major list. What's missing on this list are questionnaires that are specific to function.

It's not that they're not available, they are than normed and standardized. Next slide please.

If you are interested in finding out more information about the use and efficacy parameters of the tools that I just presented,

this is a really good resource. It's the management of myalgias, encephalomyelitis, chronic fatigue syndrome report,

updated review that was prepared for the CDC by Pacific Northwest Evidence-based Practice Center and published in April 22.

It gives you before and after treatment group comparisons of patient reported outcome measures that have shown to have not only statistical significance,

but also estimates of clinical meaningfulness, which is a measure that has to be taken into

account when you report data of clinical trials and that is often lacking. Assessment of cognitive function is not commonly used as a

primary or even co-primary efficacy outcome measure or function. By function what is often meant are categories of mental fatigue.

In general, the attention, concentration, memory problems, but not specifically addressing the processes that underlie cognitive dysfunction in Emmys first.

Now the next slide, please. There is no doubt that the use of patient reported outcome measures in clinical trials is appropriate.

If the research question is false, what is an individual's perception or experience of cognitive dysfunction in comparison to a previous time point?

This question reflects inquiry into a person's interpretation of what cognitive dysfunction needs to know. Cognitive dysfunction is often

perceived as catastrophic as was so well-described by Tricia this morning. As complex cognitive processes are affected,

that previously runs in the background automatically. Now, all of a sudden they have

risen to consciousness and the person has to attend to them. To make this experience a little bit more real life,

a lot of our patients describe the changes in the driving it. Since you were 18 years old,

most of us learned how to drive so we get in the car, run the car, get out of the driveway and do what we have to do to get to where we need to get.

Not so for ME/CFS patients or persons with ME/CFS. They have to now think about every little step of driving a car.

The environment becomes much more stressful and impactful on cognitive function. But also the person in the car

sometimes describes that they're talking to themselves saying, I have to now turn the blinker out. Boy, where's the lights which fully in this car,

even though they've had this car for a long time? Some people are missing the exits. that they use every day. Some people even drive by their homes or end up

in a different street in a neighborhood that they lived in for a long time. This is highly disturbing and it's really sad.

Next slide, please. Now I will turn to the objective assessment of cognitive function in ME/CFS events. Importantly, cognitive function, rather the processes underlying cognitive function.

But cognitive dysfunction is one of the few symptoms of ME/CFS that can be objectively quantified, psychometrically with valid, and reliable measures.

How come we don't see it more often? I reviewed Kim et al's recent systematic review of primary outcome measures for ME/CFS in randomized controlled trials.

They considered 500 trials, but only 52 passed eligibility criteria for review. About 60% of the RCTs in the analysis was the single primary outcome measure,

the rest used two or more co-primary outcome measures. My review of these 52 trials revealed that only 11 RCTs use an objective cognitive measure

administered in clinic face-to-face as one of the primary outcome measures and majority of the remaining 41 trials employed patient reported outcomes,

most of them nonspecific to ME/CFS. The objective neuropsychological measures used

included brief measures that are often not sensitive enough. For statistical significance never mind clinical meaningfulness. The topic that I'll address in the next few slides.

The outcome measures that were used were Digit Span, forward and backward Symbol Digit Modalities, which is actually a robust as trails A and B,

not so much a Stroop, yes and the computerized arithmetic task, which I don t know what the norms are. It's one of those lab specific things that I use to evaluate cognitive function.

Next slide please. The recent systematic review and meta-analysis by Sebaiti et al, makes some very important points.

They looked at original case control research studies using objective cognitive measures, published between January 1988, February 2019.

All studies included in the analysis evaluated ME/CFS adults that were clinically diagnosed with ME/CFS and had known

neurological or psychiatric comorbidities and could get them to healthy adults. The group applied rigorous statistical criteria

that I was happy to see that include the following. Measures under investigation had to have been used at least two studies. Important because it's hard to compare

assessment tools across studies if they are used in a non standardized way. The group differences between ME/CFS and controls needed to be of

statistical significance at the P 0.05 level and had to be accompanied, at least with a moderate waited effect size of 0.5.

Here I'm going to briefly address why it's important to include an effect size as recommended by the American Psychological Association by the way.

A P-value of 0.05, simply infers that a comparison between group means is applicable to 95% of the sample under study.

The calculated effect size between groups as defined by Cohen informs about the magnitude or size of the effect as the difference

between group means actually have practical or clinical significance. In order to determine that, Cohen defines the effect size in the following way,

0.2 is a small negligible effect size, 0.5 is a medium effect size and

often considered the minimum threshold in treatment trials. An effect size of 0.8 or greater is considered large and really robust. Since calculated effect sizes are standardized measures, for instance,

and effect size of 0.5 equals half a standard deviation independent of sample size. Comparison of effect sizes across trials is possible.