Shamus/multimed_short · Datasets at Hugging Face

audio audioduration (s) 3.17 30.4	transcription stringlengths 18 455	duration float64 3 30
	There are criticisms of Cohen's effect sizes, but in my book, at least they provide some framework of evaluating clinical meaning.	13
	Next slide, please. In the interest of time,	9
	I will focus on the gist of the information provided in the next three slides. They all address with a clinically meaningful changes were obtained with	10
	traditional neuropsychological measures listed on each of the slides in domains relevant to cognitive dysfunction and ME/CFS. The Bahitian co-workers found no differences in performance	17
	between ME/CFS and controls on tasks, tapping in the domains of overall intellectual function as measured by NAART	12
	and also WAIS R sub-tests that tap into verbal comprehension. In the executive functions with a focus on impulsivity,	16
	ability to conceptualize and strategize without time constraints and then what we call instrumental functions focusing on language skills, visual functions, and computational abilities.	14
	In my opinion, these are important negative findings as they affirm that especially intellectual functions without dynamic sub-components,	12
	but acquired over a lifetime is likely to be normal in ME/CFS. Does not signal the likelihood that it signals a neurodegenerative process is fairly low.	16
	It is important to know about cognitive strengths does it helps to highlight cognitive weakness. In my opinion, an estimate of overall intellectual function should be included	13
	in every clinical trial RCT addressing cognitive function. These tests are quick. Take maybe five minutes of research time, no breakfast,	12
	and can be administered remotely. Next slide, please. Now stepping into simpler, even complex reaction time and speed of motor movement coordination	12
	provide inconsistent results across studies due to variable effect sizes across study. Unfortunately, some of the simple tasks are used	10
	as trial outcome measures and then not very informative, so I would not recommend using any of them especially as a primary outcome measure. Next slide, please.	14
	Gudrun Lange: Thank you. The Bahitian co-workers reported robust findings that these moderate effect sizes and	11
	a low variability across studies in the following domains, sustained and divided attention with working memory and speed components, reflecting multi-tasking.	11
	Number 1 problem or patients or persons with ME/CFS. The tests used here are the Continuous Performance	13
	Test and the conditions were the numbers for them without distraction as well as the Paced Auditory Serial Attention Tests.	10
	There are several versions of that test. The one with four conditions going from very quick inter-stimulus intervals to longer inter-stimulus interval	12
	is the one that we'll give you a medium effect size. Another area of robust findings is	12
	another area that is of interests and it's affected in ME/CFS, which is processing speed, Symbol Digital Modalities Test or the WAIS Coding Test,	13
	is the most commonly used for that. Then we go to the area of that memory deficit is proceed.	15
	Memory demonstrate in ME/CFS up this is most commonly due to difficulties with encoding and learning of novel information and is	13
	not the memory problem that we generally see in patients with dementia. When patients report that they have a memory problem,	11
	they report it because they cannot remember the entire information that they were supposed to absorb but didn't. But you can only recall that information that you encode it.	15
	If you didn't encode it, you won't recall it. But they do not forget information. That's enough about this.	10
	Can you please switch to the next slide? I've already alluded to some gaps in knowledge that could be possible reasons to accomplish hesitancy between objective neuropsychological measures,	15
	in ME/CFS based RCT clinical trial design. Two methodological issues are really obvious.	10
	First one is that, traditional neuropsychological measures use that. The subjects need to come into the office last week well enough to travel.	14
	Supervision is necessary to ascertain proper test administration and completion. The problem associated with a travel issue is	16
	that potential participants may already be exhausted just from the experience of traveling to the study site. We don't know how will that impact on	12
	cognitive function that's measured after their arrival. The second big deal is that investigators often	12
	focus on the use of brief measures that may only have small negligible effect sizes, such as the WAIS IV Digit Span Forward and Backward and thus may not be	12
	robust indicators sensitive to clinically meaningful changes in group means due to an intervention or treatment. Therefore, I recommend that investigators shy	13
	away from Madras as primary or co-primary evidence, even though they are perceived as weak, easy, and not tapping in a lot of research time.	13
	Next slide, please. At this time, I would like to shine a special light on the participant recruitment issue that I alluded to in the previous slide.	14
	Due to the predominance of clinic administered neuropsychological measures, researchers are often not able to include patient groups that cannot travel to the research design.	11
	Those are homebound or even bedbound ME/CFS as patients. An estimated about 840,000-2.5 million Americans suffer from	11
	ME/CFS and about 10-25% of these are estimated to be either homebound or bedbound. Patients are rarely, if ever,	12
	participating in studies employing objective cognitive evaluation. Even though home and bedbound persons with ME/CFS might be	11
	the important beneficiaries of pharmacological or non-pharmacological treatment and thus need to be captured in first. Next slide, please.	18
	So how can we move forward to integrate cognitive assessment in clinical trial design? How much better is now exist that can be administered remotely?	13
	They more and more often include practice trials and easy to understand instructions, possibly reducing the workload on study personnel, facilitating use of in-home test administration as well.	14
	The COVID pandemic helped us to accelerate development in this area. An increasing number of studies show face-to-face and remote income test administration produces	13
	equivalent results even final neuropsychological measures that have shown to produce robust group differences between ME/CFS and healthy controls.	11
	Those traditional neuro-psychological measures I mentioned earlier. Next slide please. Some of them remotely administered batteries that have been	11
	used in ME/CFS samples are listed here. They include the NIH toolbox that has the flanker test that we evaluated.	13
	The flanker test is a little bit difficult to administer. The Cambridge Neuropsychological Tests Automated Battery, Computerized reaction time measure,	12
	the continuous performance test version, and the Cogstate Brief Battery. Next slide please.	8
	Under the leadership of Dr. Hunger, the CDC has tried to address some of the questions I pose with the multi-site clinical assessment of ME/CFS,	11
	also called MCAM cognitive substudy of 261 ME/CFS, and 165 healthy controls.	10
	We are currently preparing the findings for journal submission. The goals of this sub study were to evaluate the brief computerized neuropsychological screening battery that can be	12
	administered reliably and repeatedly in clinic and remotely at home after an exercise challenge. Needed a brief computerized cognitive battery that had been created and used in	15
	populations with similar cognitive dysfunction as seen in ME/CFS. That was a sample of patients with mild traumatic brain injury.	14
	The battery also needed to be able to be administered in clinic as well as remotely at home. It needed to be sensitive to cognitive deficits shown to exist between	13
	ME/CFS versus healthy control and had to have good test, retest reliability to assess cognitive function following an exercise challenge over time.	12
	Next slide please. Based on our review of the peer reviewed data in the early 2010s, when we conceptualize that study,	12
	we decided to use the computerized cognitive Brief battery developed by Cogstate. The battery include six standardized short tasks	11
	psychometrically appropriate for detecting cognitive change in, within subject designs. Administration in short 17 minutes plus or minus one or two.	13
	Our outcome measures were accuracy, performance accuracy, and speed of performance. Next slide, please.	9
	I will not go into the details of the study at this time, and we will report on it soon in our upcoming paper. The important point I want to make here is that there was no difference in performance,	13
	accuracy on any of the CBSB tasks, confirming previous observations by our group and others. We found significant statistical differences though on all speeded outcome measures.	15
	The take home point right here is, speeded outcome measures most likely give you a result of group differences while accuracy outcome measures do not.	15
	see a graph showing the mean latency of a simple reaction time task. The observed small but statistically significant group differences and simple reaction time,	10
	and use it as a covariate for the other tasks. On the right side of the slide, you see the growth of maze learning tasks,	11
	which showed to be very effective in finding differences across groups. Slower is lower, and the blue line is the healthy controls.	13
	They're doing significantly better to a clinically meaningfully. Next slide, please. Here's the task.	9
	I'm not going to go into it in the interest of time. Next slide, please. At this time, the Cogstate Batteries validated for unsupervised at	12
	home using cognitively normal as well as mild cognitive individuals, and it's not perceived as overly stressful or tiresome. Cogstate also has been used in other ME/CFS as studies	13
	with large sample sizes at this point. Next slide, please. I'm not going to go over all of these points because of time issues.	11
	But we know which areas are affected in ME/CFS in terms of cognitive dysfunction. We have standardized tool sensitive to differences and changes in	12
	cognitive dysfunction and meet them appropriately. Next slide, please. ME/CFS,	10
	cognitive dysfunctional can be assessed remotely. It's cost-effective, and we can reach people that we haven't been able to reach with traditional methods. At this point.	12
	I'm going to wrap this up with the last slide. Next slide, please. I would like to direct your attention to	8
	the NINDS Common Data Elements that is available on the Internet and has a compendium of neuropsychological measures in there that have	12
	shown to be sensitive to differences between groups,and ME/CFS. And with this, I'm finishing up. Thank you for your attention.	9
	I hope this was informative. Jarred Younger: Thank you. Awesome. I really appreciate it and we're going to move right along.	11
	We had a little bit time for Q&A, but I know everyone has so much to talk about, so we're just going to keep on with the talks. I want to introduce Dr. Rowe,	10
	so Peter's Professor of Pediatrics at Johns Hopkins. He's director of the clinic at The Children's Center for Chronic Fatigue. He's going to be talking about dysautonomia.	10
	There are lots of ways I can introduce Peter, but I will say that there are very few people that are willing to tackle ME/CFS and Ehlers-Danlos syndrome and mast cell activation syndrome.	15
	Then when you take that group and the, reduce it down to the people who are willing to tackle those things in children. That is a rarefied and a heartbreakingly small group,	12
	and so Peter is essential. He quite simply does the things clinically and scientifically that must be done, but no one else does them.	10
	Every time I hear of a new interesting research direction, I say, wow, someone is pursuing this. Peter's name always comes up attached to it.	9
	I'm really excited to hear from Peter. Peter Rowe: Thank you very much, Jarred. Thanks to you, and Vicky for the invitation to present today.	10
	I think I can make these slides go ahead. I wanted to start off with Jarred's direction, which was, what do we know about dysautonomia in ME/CFS,	16
	what do we need to know? Then how do we move forward with clinical trials? We've known for a long time that	9
	orthostatic stress can provoke the cardinal symptoms of this illness, including fatigue, but also including exercise intolerance, cognitive dysfunction, and PEM.	12
	characterized by an excessive acceleration of the heart when the patient has changed from the recumbent to the erect posture, orthostatic exhaustion, blurring of vision,	10
	weakness on exercise, and syncopal episodes may occur. They said this is a syndrome which seems identical with effort syndrome, irritable heart or neurocirculatory asthenia,	11
	which were the names at the time for what we now call ME/CFS. All they had available to treat patients was a high intake of sodium chloride up to 16 grams a day.	11
	Then this elevation of the head of the bed that you see in the upper right. They went on four years later to publish another paper subtitled Defects in the Return of Venous Blood to the Heart.	14
	They understood in 1944 what we now call preload failure or inadequate venous return to the heart as being a key feature in the pathophysiology of these symptoms.	11
	Unfortunately, this work was essentially buried or ignored. We didn't know about it, but when we found out about it afterwards,	8
	we started looking at patients with ME/CFS in the mid or early 1990s. In one of our studies, we had 23 ME/CFS patients who are a mix of adolescents and adults, 14 controls.	14
	This was a pilot study that was intended to help us estimate the sample size for a randomized trial of Florida. But what we found was striking that is,	10
	all of the patients who we put on a 70 degree head up tilt had an increase in their fatigue and lightheadedness. They had warmth and nausea,	9
	whereas the controls are simply bored. We also learned very quickly that patients were unwell for several days after the tilt test.	10
	But we introduced an intervention which was to give them two liters of normal saline intravenously. That prevented the posterior tilt exacerbation of	11
	symptoms and made them leave the clinic feeling better than when they came in. This work has been extended	9
	and done more elegantly by a number of other groups since then. This is a slide from Julian and Newton's group in the United Kingdom, showing that if you measure a variety of	11

There are criticisms of Cohen's effect sizes, but in my book, at least they provide some framework of evaluating clinical meaning.

13

Next slide, please. In the interest of time,

9

I will focus on the gist of the information provided in the next three slides. They all address with a clinically meaningful changes were obtained with

10

traditional neuropsychological measures listed on each of the slides in domains relevant to cognitive dysfunction and ME/CFS. The Bahitian co-workers found no differences in performance

17

between ME/CFS and controls on tasks, tapping in the domains of overall intellectual function as measured by NAART

12

and also WAIS R sub-tests that tap into verbal comprehension. In the executive functions with a focus on impulsivity,

16

ability to conceptualize and strategize without time constraints and then what we call instrumental functions focusing on language skills, visual functions, and computational abilities.

14

In my opinion, these are important negative findings as they affirm that especially intellectual functions without dynamic sub-components,

12

but acquired over a lifetime is likely to be normal in ME/CFS. Does not signal the likelihood that it signals a neurodegenerative process is fairly low.

16

It is important to know about cognitive strengths does it helps to highlight cognitive weakness. In my opinion, an estimate of overall intellectual function should be included

13

in every clinical trial RCT addressing cognitive function. These tests are quick. Take maybe five minutes of research time, no breakfast,

12

and can be administered remotely. Next slide, please. Now stepping into simpler, even complex reaction time and speed of motor movement coordination

12

provide inconsistent results across studies due to variable effect sizes across study. Unfortunately, some of the simple tasks are used

10

as trial outcome measures and then not very informative, so I would not recommend using any of them especially as a primary outcome measure. Next slide, please.

14

Gudrun Lange: Thank you. The Bahitian co-workers reported robust findings that these moderate effect sizes and

11

a low variability across studies in the following domains, sustained and divided attention with working memory and speed components, reflecting multi-tasking.

11

Number 1 problem or patients or persons with ME/CFS. The tests used here are the Continuous Performance

13

Test and the conditions were the numbers for them without distraction as well as the Paced Auditory Serial Attention Tests.

10

There are several versions of that test. The one with four conditions going from very quick inter-stimulus intervals to longer inter-stimulus interval

12

is the one that we'll give you a medium effect size. Another area of robust findings is

12

another area that is of interests and it's affected in ME/CFS, which is processing speed, Symbol Digital Modalities Test or the WAIS Coding Test,

13

is the most commonly used for that. Then we go to the area of that memory deficit is proceed.

15

Memory demonstrate in ME/CFS up this is most commonly due to difficulties with encoding and learning of novel information and is

13

not the memory problem that we generally see in patients with dementia. When patients report that they have a memory problem,

11

they report it because they cannot remember the entire information that they were supposed to absorb but didn't. But you can only recall that information that you encode it.

15

If you didn't encode it, you won't recall it. But they do not forget information. That's enough about this.

10

Can you please switch to the next slide? I've already alluded to some gaps in knowledge that could be possible reasons to accomplish hesitancy between objective neuropsychological measures,

15

in ME/CFS based RCT clinical trial design. Two methodological issues are really obvious.

10

First one is that, traditional neuropsychological measures use that. The subjects need to come into the office last week well enough to travel.

14

Supervision is necessary to ascertain proper test administration and completion. The problem associated with a travel issue is

16

that potential participants may already be exhausted just from the experience of traveling to the study site. We don't know how will that impact on

12

cognitive function that's measured after their arrival. The second big deal is that investigators often

12

focus on the use of brief measures that may only have small negligible effect sizes, such as the WAIS IV Digit Span Forward and Backward and thus may not be

12

robust indicators sensitive to clinically meaningful changes in group means due to an intervention or treatment. Therefore, I recommend that investigators shy

13

away from Madras as primary or co-primary evidence, even though they are perceived as weak, easy, and not tapping in a lot of research time.

13

Next slide, please. At this time, I would like to shine a special light on the participant recruitment issue that I alluded to in the previous slide.

14

Due to the predominance of clinic administered neuropsychological measures, researchers are often not able to include patient groups that cannot travel to the research design.

11

Those are homebound or even bedbound ME/CFS as patients. An estimated about 840,000-2.5 million Americans suffer from

11

ME/CFS and about 10-25% of these are estimated to be either homebound or bedbound. Patients are rarely, if ever,

12

participating in studies employing objective cognitive evaluation. Even though home and bedbound persons with ME/CFS might be

11

the important beneficiaries of pharmacological or non-pharmacological treatment and thus need to be captured in first. Next slide, please.

18

So how can we move forward to integrate cognitive assessment in clinical trial design? How much better is now exist that can be administered remotely?

13

They more and more often include practice trials and easy to understand instructions, possibly reducing the workload on study personnel, facilitating use of in-home test administration as well.

14

The COVID pandemic helped us to accelerate development in this area. An increasing number of studies show face-to-face and remote income test administration produces

13

equivalent results even final neuropsychological measures that have shown to produce robust group differences between ME/CFS and healthy controls.

11

Those traditional neuro-psychological measures I mentioned earlier. Next slide please. Some of them remotely administered batteries that have been

11

used in ME/CFS samples are listed here. They include the NIH toolbox that has the flanker test that we evaluated.

13

The flanker test is a little bit difficult to administer. The Cambridge Neuropsychological Tests Automated Battery, Computerized reaction time measure,

12

the continuous performance test version, and the Cogstate Brief Battery. Next slide please.

8

Under the leadership of Dr. Hunger, the CDC has tried to address some of the questions I pose with the multi-site clinical assessment of ME/CFS,

11

also called MCAM cognitive substudy of 261 ME/CFS, and 165 healthy controls.

10

We are currently preparing the findings for journal submission. The goals of this sub study were to evaluate the brief computerized neuropsychological screening battery that can be

12

administered reliably and repeatedly in clinic and remotely at home after an exercise challenge. Needed a brief computerized cognitive battery that had been created and used in

15

populations with similar cognitive dysfunction as seen in ME/CFS. That was a sample of patients with mild traumatic brain injury.

14

The battery also needed to be able to be administered in clinic as well as remotely at home. It needed to be sensitive to cognitive deficits shown to exist between

13

ME/CFS versus healthy control and had to have good test, retest reliability to assess cognitive function following an exercise challenge over time.

12

Next slide please. Based on our review of the peer reviewed data in the early 2010s, when we conceptualize that study,

12

we decided to use the computerized cognitive Brief battery developed by Cogstate. The battery include six standardized short tasks

11

psychometrically appropriate for detecting cognitive change in, within subject designs. Administration in short 17 minutes plus or minus one or two.

13

Our outcome measures were accuracy, performance accuracy, and speed of performance. Next slide, please.

9

I will not go into the details of the study at this time, and we will report on it soon in our upcoming paper. The important point I want to make here is that there was no difference in performance,

13

accuracy on any of the CBSB tasks, confirming previous observations by our group and others. We found significant statistical differences though on all speeded outcome measures.

15

The take home point right here is, speeded outcome measures most likely give you a result of group differences while accuracy outcome measures do not.

15

see a graph showing the mean latency of a simple reaction time task. The observed small but statistically significant group differences and simple reaction time,

10

and use it as a covariate for the other tasks. On the right side of the slide, you see the growth of maze learning tasks,

11

which showed to be very effective in finding differences across groups. Slower is lower, and the blue line is the healthy controls.

13

They're doing significantly better to a clinically meaningfully. Next slide, please. Here's the task.

9

I'm not going to go into it in the interest of time. Next slide, please. At this time, the Cogstate Batteries validated for unsupervised at

12

home using cognitively normal as well as mild cognitive individuals, and it's not perceived as overly stressful or tiresome. Cogstate also has been used in other ME/CFS as studies

13

with large sample sizes at this point. Next slide, please. I'm not going to go over all of these points because of time issues.

11

But we know which areas are affected in ME/CFS in terms of cognitive dysfunction. We have standardized tool sensitive to differences and changes in

12

cognitive dysfunction and meet them appropriately. Next slide, please. ME/CFS,

10

cognitive dysfunctional can be assessed remotely. It's cost-effective, and we can reach people that we haven't been able to reach with traditional methods. At this point.

12

I'm going to wrap this up with the last slide. Next slide, please. I would like to direct your attention to

8

the NINDS Common Data Elements that is available on the Internet and has a compendium of neuropsychological measures in there that have

12

shown to be sensitive to differences between groups,and ME/CFS. And with this, I'm finishing up. Thank you for your attention.

9

I hope this was informative. Jarred Younger: Thank you. Awesome. I really appreciate it and we're going to move right along.

11

We had a little bit time for Q&A, but I know everyone has so much to talk about, so we're just going to keep on with the talks. I want to introduce Dr. Rowe,

10

so Peter's Professor of Pediatrics at Johns Hopkins. He's director of the clinic at The Children's Center for Chronic Fatigue. He's going to be talking about dysautonomia.

10

There are lots of ways I can introduce Peter, but I will say that there are very few people that are willing to tackle ME/CFS and Ehlers-Danlos syndrome and mast cell activation syndrome.

15

Then when you take that group and the, reduce it down to the people who are willing to tackle those things in children. That is a rarefied and a heartbreakingly small group,

12

and so Peter is essential. He quite simply does the things clinically and scientifically that must be done, but no one else does them.

10

Every time I hear of a new interesting research direction, I say, wow, someone is pursuing this. Peter's name always comes up attached to it.

9

I'm really excited to hear from Peter. Peter Rowe: Thank you very much, Jarred. Thanks to you, and Vicky for the invitation to present today.

10

I think I can make these slides go ahead. I wanted to start off with Jarred's direction, which was, what do we know about dysautonomia in ME/CFS,

16

what do we need to know? Then how do we move forward with clinical trials? We've known for a long time that

9

orthostatic stress can provoke the cardinal symptoms of this illness, including fatigue, but also including exercise intolerance, cognitive dysfunction, and PEM.

12

characterized by an excessive acceleration of the heart when the patient has changed from the recumbent to the erect posture, orthostatic exhaustion, blurring of vision,

10

weakness on exercise, and syncopal episodes may occur. They said this is a syndrome which seems identical with effort syndrome, irritable heart or neurocirculatory asthenia,

11

which were the names at the time for what we now call ME/CFS. All they had available to treat patients was a high intake of sodium chloride up to 16 grams a day.

11

Then this elevation of the head of the bed that you see in the upper right. They went on four years later to publish another paper subtitled Defects in the Return of Venous Blood to the Heart.

14

They understood in 1944 what we now call preload failure or inadequate venous return to the heart as being a key feature in the pathophysiology of these symptoms.

11

Unfortunately, this work was essentially buried or ignored. We didn't know about it, but when we found out about it afterwards,

8

we started looking at patients with ME/CFS in the mid or early 1990s. In one of our studies, we had 23 ME/CFS patients who are a mix of adolescents and adults, 14 controls.

14

This was a pilot study that was intended to help us estimate the sample size for a randomized trial of Florida. But what we found was striking that is,

10

all of the patients who we put on a 70 degree head up tilt had an increase in their fatigue and lightheadedness. They had warmth and nausea,

9

whereas the controls are simply bored. We also learned very quickly that patients were unwell for several days after the tilt test.

10

But we introduced an intervention which was to give them two liters of normal saline intravenously. That prevented the posterior tilt exacerbation of

11

symptoms and made them leave the clinic feeling better than when they came in. This work has been extended

9

and done more elegantly by a number of other groups since then. This is a slide from Julian and Newton's group in the United Kingdom, showing that if you measure a variety of

11