One area where the DiPALS report may be flawed involves their discussion of whether ALS patients ought to undergo surgery, a reference being made to a paper by Pinto, et alia, published in 2004 suggested disease progression may increase in ALS patients who undergo surgery. They do not suggest constraining gastronomy tube surgeries, et alia or tracheostomy surgeries, however. Since I began observing remarks by ALS patients in 1999, the pacer was unanimously regarded as the least difficult of those who underwent same and expressed their opinion in on-line remarks I discovered. The DiPALS authors express an interest in the full set of data used by the FDA in support of the HUD/HDE determination; indeed I also wish this data, but even if such were available there are likely not enough cases to support conclusions needed to perfect medical opinion on the pacer. The symptom variance in ALS patients is very large and as a result, I estimated the number of cases needed to complete the medical review is likely more than 5,000 to 10,000 cases.

Their analysis was by intent to treat; Sandeep Gupta describes here:

Intention-to-treat concept: A review
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159210/

According to Sandeep Gupta "Intent to Treat" analysis usually produces more conservative estimates of efficacy because the ". . . estimate of treatment effect is generally conservative because of dilution due to noncompliance. Also, heterogeneity might be introduced if noncompliants, dropouts and compliant subjects are mixed together in the final analysis."

In a normal pilot sample one would expect about two patients who regress slowly, in the referenced study each group had about two pilot samples wherefore, about four patients in each group, were the pilot samples normal, would be expected to last at least five years. Such may have been the case in the NIV group as, at the close of the study, approximately thirty months, four patients remained alive but only one did in the DPS group and they decided to undergo tracheostomy. A slow regression patient would likely not need to do so for some time, hence, either the DPS group was not normal or the slow regression patients left the study early.

Quick note, at present I have so far found 38, 31 and 34 pacing ALS patients in 2012, 2013 and 2014 respectively. Only 13 for 2015 so far but not too unusual as many patients do not immediately disclose their medical strategy.

I saw a report in only one apparent news source indicated about 6,400 patients had died in 2014 several months into 2015 . . . recently ALSA apparently updated their statistics to say the expected number of diagnoses each year is now 6,400 . . . up from 5,600 . . . known since at least 1999.

I think the DiPALS report might be best thought of as a minimus . . . within the report, a statement implies an informal per-protocol analysis was made and showed 'low efficacy.' Their report covers much 'territory,' often with very limited depth. Centers ought to at least meet and should exceed their results. Each of their centers administered less than a pilot study of implants (less then about sixteen). Patients are more likely to obtain an implant at their nearest center . . . patients are more likely to be later in their 'implant opportunity window' in the early period of a center's initiation of implants.

I keep trying to remind myself to note the several cases were remarks exist regarding incomplete happiness with the pacer . . . these are:

regarding Harrell of PatientsLikeMe.com by their care provider.
regarding llbjgb of inspire.com by their care provider.
by Susan F., an M.D. regarding their spouse in response area of a notice.
(will try to rediscover the notice).

and

Knudson in http://dailylifewithals.blogspot.com/
noting '. . . sleeps better without the pacer . . .' but uses during the day. In contrast, "Tom M" of PatientsLikeMe.com could not use the pacer during the day (due to asynchronization issues) but was able to use while sleeping.

Many patients have commented on discomfort associated with feeling electrical sensations during the period the pacer is being adjusted but I know of none persisting after calibration was complete.

The DiPALS report refers to this paper:

Does surgery accelerate progression of amyotrophic lateral sclerosis?
http://www.ncbi.nlm.nih.gov/pubmed/2...?dopt=Abstract

by Pinto et alia, wherein some fifty patients experience noticeable drop in ability shortly after surgery . . . of these approximately two thirds were for surgeries appearing to be unnecessary because the condition the patient was believed to have before the surgery was not found to be the case during surgery. In my experience observing the remarks of patients suffering from ALS I recall several patients who noted a sudden change in the rate of their regression; HarryAZ of BrainTalk communities after they underwent an umbilical cord blood procedure (the dozen or so fellow patients who also underwent the procedure did not). A patient who was participating in a fundraiser by 'driving' the full length of New York's Long Island in their power wheelchair while nearing the end of the trek. Another I don't clearly recall at this moment . . . resulted in my hypothesis patients under a drop in their supposedly 'linear' regression for some unknown reason - (currently unknown). Patients often report a 'trigger' to their ALS symptoms. I further hypothesize patients didn't need the surgery but may have felt they did due to this 'drop' and thus the Pinto report may have gotten the 'cart before the horse' so to speak. MORE on this issue later.

I am hoping we will hear of Knudson soon, they were planning on moving into their new home and where having trouble with their computer's adaptive components (as way too many patients have). We have not heard from them since New Years Eve.

One quick note before the long weekend . . . be careful about the difference between Average and Median: In most cases, in ALS papers, average will be higher than median . . . because slow regressors can pull these datums up more forcefully than rapid regressors can pull them down. Median is the 50:50 point . . . a randomly chosen patient 'ordinarily' has a fifty percent chance of making the median . . . in most cases, at this time, the chances of a randomly chosen patient making the Average is significantly less than making the Median (less than fifty percent).

Happy Valentines and President's day weekend.

Quick note to advise several pacing patients are in or breaking into their ninth year of pacing.

I am inclined to believe the report of the DiPALS committee is intended primarily as an alert to a possible problem and not a referendum on the pacer because they do not criticize the lead surgical team, only the United States Food and Drug Administration (possibly because their HUD/HDE approval did not take into account the possibility the pacer might be implanted but not activated).

Upon the news of djbailey's death (of alsforums.com) In at least two ways I continue to see gender bias in my review of ALS cases . . . In cases were patients are alive nearly nine years after initiating pacing I have found about a dozen cases, only two are female . . . unclear how real those two cases are . . . ; in this list of studies, only five studies found bias against females but no study has found bias against males:

http://neurotalk.psychcentral.com/sh...29#post1203229

Although females are much less likely to incur ALS, when they have, they may be less successful in fight off the disease. djbailey apparently had a more aggressive form of the disease, as they became unable to move their eyes only three years in from symptom onset of limb onset ALS. Ocular immobolization is rare in ALS, occuring late in the disorder's process.

Further, of the eight apparently least successful cases wherein full data is available, five are female and three are male . . .

MuonOne
I appreciate your taking the time to keep ALS patients and caregivers so very well informed. I do not have ALS, but have been diagnosedwith Parkinson's for 20+ years.

There are many similarities between ALS and PD. By studying all neurological illnesses, I believe we will come closer to finding therapies that work. I want to thank Thelma for her work in this area, also.
Peggy