Hypothetical Benefit

Of course, the numbers shown in this thread's August 30 post are much higher than the number of neurons with involvement in the motor system, estimated as 100,000,000 - controlling about 640 muscles; here is a name list:

List of all the muscles - Functions of the Human Body Systems

Of these, the diaphragm counts as two.

One might say there were four groups in the study, with the best candidate group _excluded_ from the study before randomization - theoretically leaving about three groups. We can hypothesize about these remainders by contemplating where the remaining candidates, the ones who opted out before randomization but qualified for the study, fit into the three groups . . . they might have been the best of the candidates . . . or the worst of the candidates. If we add to these candidates the three - one who could not be implanted due some technical difficulty, one who opted out at six months and one who opted out at one year . . . collectively these patients constituted about one-half of a group. They could have been of the best candidate group or of the worst candidate group . . . or distributed among the entire group.

They may have been the BEST of the REMAINING candidates:
As such, could they have opted out because they felt the study was not for the best candidates because the top twenty-five percent (75%-85% FVC range) where disqualified from the study?

They may have been the WORST of the REMAINING candidates:
As such, they would likely have drawn the averages down . . . but by how much?

The report says the FVC average was just above 65% and implies there were no slow regressor/long term survivors in the implanted group but those selected seemed to produce a near-normal distribution of those who qualified.

There were 759 candidates to the study but at the study's closure there may not have been sufficient candidates remaining to fill the final openings as the disqualification rate was much higher than 50%, whereas the FDA HUD/HDE gave an expectation at least 50% would qualify.

. . . more soon . . .

Could one synapse be all it takes:

Terry Wallis, Mountain View, Arkansas:

Coma man wakes after 19 years
Coma man wakes after 19 years | Daily Mail Online

Rom Houben, Belgium:

'I screamed, but there was nothing to hear': Man trapped in 23-year 'coma' reveals horror of being unable to tell doctors he was conscious
Rom Houben: Patient trapped in a 23-year 'coma' was conscious all along | Daily Mail Online

Time's Top Ten Coma Cases:
Complete List - Top 1 Comas - TIME

I thought I should mention the status of my review of the data I have found on the internet provided by patients who have shared their experiences regarding their use of the pacer. I have found about 180 such patients, only three are believed to have been in the DiPALS study. Based on data supplied by these various patients, the case for the pacer is STRONGER today than at any previous time. Plausibly, the MEDIUM for well timed administration of the pacer may bring patient survival to beyond six years - quite an improvement over the previous achievements. In Bulbar onset though, the MEDIUM might only barely exceed three years. New cases would need to be discovered and such cases would have to be weak cases in order to draw-down the MEDIUM projection appearing to be reasonable interpretations of the current date.

As near as I can tell, the DiPALS group did not report change they detected in the FVS subsequent to implant, whether improved diaphragm movement developed, whether diaphragm thickness improvement developed or whether patients reported any improvement in their sleep.

Its possible none for the DiPALS group met many of the implanted patients because the study was multi-center . . . its theoretically possible no doctor met more than a dozen ALS patients and thus it is reasonable to believe they would not go out on a limb in this case. Therefore, with such limited patient interaction, the Doctors are unlikely to form a strong opinion on the practice - they would need to much larger to occasion - they would want to see many clearly favorable cases].

In short, there is

I just realized the previous post was poorly written, I will re-write and re-post it.

In the electronic edition of the DiPALS report it should be noted they may not have reached their goal of 108 patients even with 759 candidates. After excluding the best 25% of the candidates and relying on the FDA's estimate of about 70% of cases likely to have an eligibility window, a yield of about 400 cases ought to have resulted, yet they were well short of this yield and had less than 100 cases remaining after seventy-four candidates were found.

I thought I should mention the status of my review of the data I have found on the internet provided by patients who have shared their experiences regarding their use of the pacer. I have found about 180 such patients, only three are believed to have been in the DiPALS study. Based on data supplied by the patients, the case for the pacer is STRONGER today than at any previous time. Plausibly, the _MEDIAN_ for well timed implantation of the pacer may bring patient survival to beyond six years - quite an improvement over the previous achievements. In Bulbar onset though, the _MEDIAN_ might only reach about three years.

As near as I can tell, the DiPALS group did not report change they detected in the FVC subsequent to implant, whether improved diaphragm movement developed, whether diaphragm thickness improvement developed or whether patients reported any improvement in their sleep - as the Onders group reported.

Its possible none of the DiPALS group's doctors met many of the implanted patients because the study was 'multi-center' . . . its theoretically possible no doctor met more than a dozen ALS patients who were implanted and thus it is reasonable to believe they would not go out on a limb in this case - most wouldn't based on such little evidence. Therefore, with few patient interactions, doctors are unlikely to form a strong opinion - they would need larger number of cases - they would want to see many clearly favorable ones.

Further, organizations newly implanting patients are likely to find a larger proportion of cases arriving late in the operating room because patients are more likely to make a timely arrival when the surgery was available in their locality at the time the opportunity window began to open. Such is apparently evident in the series of papers published by the Orders group reflecting steady improvement in apparent efficacy in the later cases.

I should also point out DiPALS challenged the FDA HUD/HDE designation but not the lead research team (Onders, et alia). The HUD/HDE did not contain an efficacy claim. Onders, et alia, have reported evidence of efficacy seen in reduction of FVC slope, thickening of diaphragm muscles, improved movement thereof and improved sleep. What are the credentials of the reporters who commented on the DiPALS report? Do they have an in-industry reputation?

So the statistics suggesting we should expect 300 to 600 fALS diagnoses per year. Vitamin E was discovered to be associated with a decrease incidence of ALS in a study of the American Cancer Society's Cancer Prevention Study II; the study involved nearly one million patients, but further studies found after ALS onset, vitamin E was ineffective. This 2005 report reflects the observations:

Vitamin E intake and risk of amyotrophic lateral sclerosis.
Vitamin E intake and risk of amyotrophic lateral sclerosis. - PubMed - NCBI

Eleven years have passed, we are 3,000 to 7,000 fALS diagnoses later - has a study conducted to test the observation on fALS candidates (who are about 50% likely to develop an ALS diagnosis) to determine whether such patients achieved temporal shift of their ALS symptoms by way of ensuring their pre-symptomatic use of vitamin E favorably shifted their ALS diagnosis or maintained the disease(s) dormancy?

If one were to remove the most successful candidates of the NIV group (to achieve balanced groups because five of the DPS group were not implanted and two of the DPS group left, one at six months and the other at one year) the DPS plus NIV group would clearly prevail . . . although with weaker than expected statistics . . . see figure 2, were they would be about tied at eighteen months and ahead at twenty four months.