1118 stories
·
1 follower

Does It Work? Does it Do Harm? And More Basic Questions.

1 Share

I have inveighed several times here against the recently approved anti-amyloid antibody treatments for Alzheimer’s (and against their predecessors), but I think the thing to do at this point is just refer people to this open-access article. Written by long-practicing neurologists, it makes a clear case that the efficacy of lecanemab and donanemab is unimpressive and the the evidence for harm to patients is much more solid than the evidence of any noticeable benefit.

The improvements seen on the dementia rating scales are below what is generally accepted to be a perceptible level (by patients or their caregivers). The often-quoted improvements of between 20% and 40% are based on ratios as compared to the placebo group, and obscure the tiny magnitude of the actual differences. This paper provides useful graphs of the clinical trial data that make this much more obvious. And as the authors note, there is no guarantee that even the observed differences between the placebo group and treatment group will continue to diverge, making even the quoted improvements the best-case situation. As the authors say, all the ways that the data have been publicly described are legitimate, but incomplete.

Another thing that has been lost in the noise around these treatments is that the improvements measured are actually far less than those seen with donepezil, a cholinesterase inhibitor that has been on the market for many years and which is considered a pretty weak stopgap therapy overall. Donezepil slows the progression of the disease a little, in some people, for a little while - and these new antibodies, by all available evidence, are even less impressive than that. I know, I know, you have to be careful comparing across different trials: but if the anti-amyloid therapies were truly modifying the course of the disease, wouldn’t you be able to see that as opposed to a symptomatic agent like donezepil?

And unfortunately, the safety situation is nowhere near as fuzzy as the efficacy numbers. I’ll let the paper speak for itself:

With a disease as devastating as AD, even a small effect size should be considered by clinicians if treatments were safe. However, these mAb are not safe. In both trials, adverse events afflicted sizable numbers of participants. With lecanemab, 45% of the participants had treatment-related adverse events, with nearly one in four patients developing brain swelling and/or bleeding, which proved to be severe in some persons. Severe bleeding occurred to a greater extent compared with placebo (five vs one in the lecanemab trial; seven vs two in the donanemab trial), including three fatal cases. With donanemab, 89% of patients had treatment-related adverse events and more than one in three patients developed brain swelling and/or bleeding. Brain swelling is a major contributor to the acceleration of brain atrophy, a feature of most mAb.

This is not where we should be. The FDA should be approving therapies that make a difference in patient’s lives and which have a greater chance of helping them than hurting them. You’d think that would be the baseline. Instead, in Alzheimer’s, Duchenne muscular dystropy, and other areas we’re seeing a tendency to approve things on a “Wouldn’t it be nice” basis, which - to be a pain in the ass about it - is a route to disaster.    The first criterion is always efficacy. Then you weight safety against that. Making people happy comes last compared to those two. This isn’t medicine - it’s Hope-ium. We (the drug industry, the FDA, and the patient advocacy groups) should all be doing a lot better.

Read the whole story
tabithaclem
11 days ago
reply
Share this story
Delete

CHARLIE—HONORARY PVPC PEKE

1 Share

Remember a few weeks ago when I posted a young Peke needing a home?  Well, Charlie found his home. 😁
One of my friends, a Peke lover, adopted him.  
He’s a beautiful little boy. 
He just needed to be an only dog and now he is. It was so hard for his owner to let him go but she was concerned for Charlie and the other two bigger dogs.  I applaud her for wanting the best for him. 
Charlie is already checking out his new home- especially the kitchen. 😂. Yum!  
He has some new kid friends and it looks like he likes he’s enjoying his new home.  
Yes. I think he is home. ❤️🐾
 

Read the whole story
tabithaclem
27 days ago
reply
Share this story
Delete

Pressure From the Top

1 Share

The post here last week about faked papers prompts me to mention this recent publication (which I learned about in Nature): an anonymous survey from inside several Chinese universities. It's quite interesting from that standpoint, and it shows that the Chinese institutions and authorities are indeed becoming worried about the increasing flood of low- (or zero-) quality papers that come from all sorts of Chinese sources. As everyone would have figured, this is a consequence of pressure to Publish, Publish, Publish, and Publish Some More:

. . .this article focuses on China’s plan to build world-class universities and disciplines, titled the World First-Class University and First-Class Academic Discipline Construction (known as the Double First-Class Initiative). The initiative offers significant incentives for individual researchers in elite Chinese universities to produce a rapidly increasing number of articles in top international journals, which has resulted in a swift rise in their world university rankings. On the other hand, the initiative provides ‘organisational reasons’ for wrongdoing, such as unethical research practices. . .

Airing this sort of dirty laundry is not something that any country or any institution ever likes to do, so the bluntness of this article is quite something to see. It takes what it terms "rampant research misconduct" in Chinese science as a given, and then goes on to ask how this spread and what can be done about it. And the authors state that they are not interested in telling tales of individual bad actors who somehow lost their way, as if that was the whole explanation, but rather are trying to link national policies and institutional pressures to all these individual cases. Both authors are from Hong Kong, but remember that the Chinese government has spent years now tightening the clamps there on political expression (but note the statement in a quote below about being from outside mainland China still). That makes it quite refreshing to see things stated as they are:

Most universities in China, including all those listed in the Double First-Class Initiative, are government funded, with their presidents and party chiefs appointed directly by central and local governments. The Communist Party of China has established party units at various levels within universities, such as at the university level, the faculty level and the department level, and the administrative heads of the various levels (e.g. presidents, deans, department heads) typically serve as deputy heads of the corresponding party unit. Through this political design, the Chinese government can ensure that universities strictly implement public policies, serve political demands, and become a part of the Chinese bureaucracy.

It is also refreshing, and a bit startling, to see the authors go on to analyze the situation with reference to the literature on institutional malfeasance and organized crime. A key part of this is the decoupling of goals and means: goals are set with no particular attention paid to the means by which they're accomplished. This is a basic invitation to misconduct - you see it in corporations when managers say (for example) "Make your numbers this quarter or I'll find someone who will". In this situation the numbers to be made were publications, ideally in the highest-impact journals possible. And there was a cascading effect through the bureaucracy (cengceng jiama, as the authors render it in Chinese) as lower-level functionaries each set their own subordinates to exceed the original goals that came down to them. By the time this gets down to the people who are actually going to have to implement these goals (i.e., crank out these manuscripts), there can be no legitimate way to make things work.

The authors actually were able to interview scientists who had gone through this, although it wasn't easy:

Our focus on researchers from the discipline of natural sciences was due to the feasibility of obtaining interview data. We initially attempted to approach social science researchers at elite universities, but most of the potential interviewees we approached declined our interview invitations. This may be because their research topics were more relevant to Chinese policy and society, and they were very reluctant to accept invitations from researchers outside mainland China. We eventually noticed that researchers in the discipline of natural sciences were comparatively more willing to accept our interview invitations, perhaps because their research topics were less sensitive and unrelated to policy and politics. We began by utilising our local connections to interview several researchers in faculties of natural sciences, who then introduced us to colleagues and friends whom we could also interview.

They also note that they conducted further informal interviews with PhD students, who were said to be eager to share details about research misconduct among professors (!) That was because, being at the lowest level of the process, they were the most ill-treated of all. The professors themselves describe having their backs against the wall: there was no way to generate the amount of work (and the amount of papers from it) that they were being asked to provide, so it was fake stuff or be disciplined/fired. Meanwhile, department heads and the like were completely aware that this sort of thing was going on, but did not want to derail the plans that they were being ordered to follow. A quote from an interview:

As leaders, we are well aware of academic misconduct within the faculty. Apart from a few senior professors, most of the younger generation engage in various forms of misconduct with differing severity levels. They do so because they face difficulties meeting promotion criteria, and we do not want to complicate matters. As long as they publish their articles [in SCI journals], that is all the university and faculty need.

Who needs anything more than that, honestly? Why "complicate matters", indeed? Anyone who tries to do such a thing might find themselves being made the scapegoat to protect others on the faculty. The authors note that the usual technique is to minimize the big problems while making a big showy deal out of little ones (dashi huaxiao, xiaoshi hualiao) as a way of keeping up appearances.

It's a fascinating paper, I have to say, and part of that fascination is the recognition that all of us have seen such behaviors in various situations and in various institutions. This is not a China-specific problem - the English language has plenty of phrases that bear on this, e.g. CYA, lipstick on a pig, manage upwards, turn a blind eye, keep the boss happy. . .you can add plenty of others. What I think is particularly Chinese about this situation is the degree of central control and organization in setting such goals, coupled with an immediate, simultaneous willingness to completely ignore how they might be achieved. Because that's your problem. It's a larger and more comprehensive scale for this behavior than you can usually attain in other countries, and I would guess that generations of having to adapt to sometimes capricious demands made with all the force of a centralized state behind them has made this all too common.

Read the whole story
tabithaclem
37 days ago
reply
Share this story
Delete

CHARLIE - LOOKING FOR A HOME

1 Share

CHARLIE 
Charlie just turned a year old. Isnt he cute!! 
He loves to snuggle.  He’s about 16 pounds, housetrained and sweet.  
But… he kind of beats up on his brother.  Some dogs would prefer to be an only dog.  Charlie is one of them.  He is in Virginia and can only go to a home in our area of Virginia or Maryland.  
You can message me on Facebook if you are interested.  Message Potomac Valley Pekingese. Club, a Rescue. I am helping the owner find him a wonderful home.  🥰 


 

Read the whole story
tabithaclem
40 days ago
reply
Share this story
Delete

HENNIE GOES TO THE BEACH

1 Share

Hennie went on vacation to the beach!    She had doggles to protect her eyes from the blowing sand.   GREAT IDEA.   They stayed on pretty well.   She enjoyed the wind, and her eyes were safe.  
Her mom Claretta took her along for the week.   Hennie was so good.   Her mom's niece went, too.   It looked like they had a great time!  
Hennie sat on the porch while Judy read.   The temperature was good most of the time.  
Hennie was good about picking just the right spot to do her business.  She preferred an area in front where there wasn't much vegetation-- much better.  No tall sea grass there.  
They watched a beautiful moon rise. 
It was a wonderful way to end the day.  
Hennie has the compromised front leg, but we believe she was born this way.   She still gets around well.  
Some days it was a little windy and blew her hair around.   But she had her doggles if it got too much.  
I'm so glad she and her mom had a time away-- to read, to have fun with her niece, and to rest.   That's what vacations are for.  💜
 

Read the whole story
tabithaclem
48 days ago
reply
Share this story
Delete

TUK TUK, TOASTY AND NEW FURNITURE

1 Share

 You know how much our Pekes like to help.   

Big boxes arrived at the house.  
Toasty and Tuk Tuk are no exceptions to helping.   Their mom bought a new porch couch.  
Tuk Tuk showed it off after it was all set up.  
He was so proud of how he did much pushing and moving everything into place.  

Granger's mom put him in the large box-- you know how much he loves boxes.  
Then, the youngsters jumped in.  Granger cannot do that.  Jumping is for young Pekes, not seniors.  
Tuk Tuk and Toasty fought over one of the paper tubes.  Granger just watched from the back of the box.    Shenanigans!

The smaller boxes came out to the porch and Tuk Tuk supervised.  
As you can imagine, his guidance was instrumental in getting everything set up correctly.  

There are cushions underneath and Granger is happy to test them out the space.  
Is this going to stay here?  
Once it was all in place, he got on the new couch (he may have had some help), he checked it out.  Perfect!  A new place to nap. 
 Granger, Tuk Tuk and Toasty are happy pups!  

Read the whole story
tabithaclem
53 days ago
reply
Share this story
Delete
Next Page of Stories