0:00

You know Paul, I don't

0:02

know if you remember this but last year it wasn't

0:05

that fun for me having that broken neck Go

0:09

on, but you know Paul at least

0:11

now I can look back and laugh All

0:15

right Don't

0:17

get it I

0:21

don't know if I get it either I'm

0:23

assuming because you're so mangled that you

0:25

can look at your own back. I'm not really yeah I

0:27

was thinking maybe something like that. So Paul would you add

0:29

anything? so I shout

0:32

out again to fun stereo comm which just

0:34

has It reads like it

0:36

was translated from a foreign language into English

0:39

Unwell by AI but the

0:42

one I like the best is I used to hate smoking

0:44

But I finally decided to ask for forgiveness. That was actually

0:46

not bad When

0:49

it comes to smoking it's important to have a light sense of humor. I

0:53

Feel like you guys aren't laughing the way that you you could

0:55

be with these No, this is good. What

0:57

do cigarettes and batteries have in common? This is my favorite

0:59

one. I Don't they

1:01

both have a positive and negative terminal. Can you tell me what

1:03

that means? Cuz I don't know All

1:07

right, well, I think we've struck out on this one Paul

1:13

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1:27

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1:37

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1:39

Matthew Frank Waddow here with my

1:41

great friend and America's primary care

1:43

physician. Dr. Paul Nelson Williams Hey

1:46

Paul As

1:49

a throwback capable hi Matt, how are you

1:52

I'm doing well Paul This is a

1:54

hotcakes episode and we have a lot

1:56

of great topics To talk about tonight me

1:58

talking about. Cigarettes should we

2:01

are, shouldn't we be using them?

2:03

Talk about gab a penta noise

2:05

and C O P D exacerbation

2:07

something I'd never heard of. ah

2:09

little bit of light a cane

2:11

patches and do those things work

2:13

and couple other fun topics. some

2:15

see this, antibiotics and. Ah,

2:17

what's the last topic? Their oh yeah Glp one

2:20

agonists and should be be dosing them by clicks

2:22

A will will get into all that stuff. Paw.

2:25

On, before we do and before we introduce

2:27

our wonderful cohost, can you please tell people

2:29

what is that we do on curb siders.

2:33

Sherman tanks we are as be and dramatist

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2:37

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2:41

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2:43

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2:45

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they're actually really nice incorrectly and uncertain whether

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I typically points role our yeah. I'm.

2:52

Great! How are you all. I'm good,

2:54

it's it's kind of close as we're recording this

2:56

as this is coming out. You know a C

2:59

P is coming up in Boston and we're going

3:01

to be able to hang out in real life.

3:03

Rahul, which is something that happens maybe once

3:05

a year these days. So that's that's

3:07

exciting. Period. Sell it. And

3:10

I i think i hear past cat

3:12

in the background also various site a

3:14

sister don't and it's assist with my

3:16

that your child. So.

3:20

Yeah, this is that says I think

3:22

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3:25

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who listen to the show. So.

4:01

With that power. Would.

4:03

You like to introduce. The first article. I.

4:08

Love to as as I do in case

4:10

you couldn't hear from the pine this was

4:12

the the article on easier At So this

4:14

is from our at All Electronic Nicotine Delivery

4:16

Systems for Smoking Cessation which is from the

4:18

new Internal Medicine in February of this year.

4:21

And. This is. Substantial group

4:23

of researchers are asking does the use of

4:25

Ie cigarettes in addition to standard of care

4:27

association counseling? We tune in to increase rates

4:29

of absence from smoking. Survey

4:32

See what they're asking is can we use his

4:34

cigarettes or council patients easy cigarettes Now Quit smoking. And.

4:37

The reason this is is relevant as a matter how does

4:39

for you all but i'd and of for my patients in

4:41

those you no cigarettes many them also be many of them

4:43

have used. He cigarettes. To try to quit

4:45

smoking, a person so often come in with their He

4:48

cigarettes kind of hanging around their neck or in their

4:50

pockets. Readily available so and I the rates are. Are.

4:52

Going up say i think it does the who has to

4:54

be able to cancer patients. About. The safety

4:56

and and and frankly if it can be using

4:58

to quit smoking does any evidence to support that

5:01

and if it's as a better than smoking worse

5:03

than smoking is a recent study out at that

5:05

People perceive. Iti. Cigarettes to probably

5:07

be even less safe than they actually are, which

5:09

is interesting that people may not even think of

5:11

them as tobacco cessation needs must the times I

5:13

think this is an important state up as counsellor

5:15

patience. And. As regards. Fall.

5:18

This is like for me in primary

5:20

care if people are thinking about are

5:22

trying to quit smoking. I. Just

5:24

assume they've tried ie cigarettes because it seems

5:26

to be pretty common when I ask people

5:28

and some of them are like oh yeah,

5:31

quit smoking I'm like oh great and then

5:33

I forgot to ask another guy. they now

5:35

have to sell them. Yeah and so what

5:38

will talk about That's a what was the

5:40

what were the topline results of the study

5:42

and they will get into the details. Yet

5:45

so you're take away from this is this was

5:47

a positive study so. What? They're looking

5:49

at as a as a primary endpoint was

5:51

biochemically validated continuous absence from smoking at six

5:54

months out from there quit date and this

5:56

occurred and twenty point nine percent of individuals

5:58

the intervention group or got the. The Grass

6:00

and sixteen point three percent a control group which is

6:02

still not bad numbers. Be honest with you, But.

6:05

The patients any intervention group as her using my

6:07

tie cigarettes were more or less is more likely

6:09

to be using nicotine and by the into the

6:11

studies not smoking cigarettes mind you but using nicotine

6:13

products and there was no difference in the serious

6:15

adverse events between the two groups, but there were

6:17

more adverse events seen. Any intervention group a name

6:19

it's we Get swinging and how they measure than

6:22

what that means necessarily. But by and large the

6:24

patients he used his cigarettes were more likely be

6:26

done with a cigarette smoking by the end of

6:28

the study was had because. It.

6:30

Is Islam with against people the vouchers that

6:32

they could use for nicotine replacement therapy as

6:35

they wanted to. In. The

6:37

control group. That's right. So both groups Exactly

6:39

so. the way this this is an open

6:41

label randomized trial and a randomized patients. no

6:44

one to one of fastened to be there

6:46

to control the interventions. The control group a

6:48

study nurse given counseling and and also they

6:50

got his fifty swiss francs at the beginning

6:53

of a c to do with what they

6:55

will so I'd I'd ideally they are nicotine

6:57

replacement therapy or varenicline or some other because

6:59

they were council about that. the various and

7:02

medications used quit smoking but they didn't after

7:04

and then and the intervention group they were.

7:07

It's they were given. An.

7:09

Electronic. Cigarette. Kids. They are

7:11

also allowed to sort of sampled a

7:13

smorgasbord of nicotine products so they were

7:15

of six different flavors import from concentrations

7:17

of Stick, a sample of the twenty

7:19

four different varietals of have a Cigarette

7:21

Stuff. And. At that point the actually

7:23

used out themselves, quit smoking ideally. Com

7:26

and then they have I was This helps

7:28

at one, two, four and eight weeks after

7:30

their target quit date. Add. To see

7:32

how they were doing with the ultimate and result being

7:34

measured as at six months with biochemical have stance and

7:36

and also some or interview stuff. Yet

7:39

Paul I was very curious about. This is

7:41

when people tell me they're they're using nicotine

7:43

with and they're raping he cigarettes with nicotine

7:45

to see. I guess you don't have to,

7:48

but it seems like most people do. Those

7:51

pods come in different strengths and like I

7:53

I think from what I could read. It.

7:55

When you smoke a cigarette, you don't get all

7:57

the nicotine it's actually contained in that cigarettes, just

7:59

a small amount. And if you smoke a pack

8:02

of cigarettes, you get like twenty or thirty milligrams

8:04

of nicotine. Or and they said

8:06

that though those pods have about like forty

8:08

milligrams of nicotine, they they, I think they

8:11

com and thirty five milligrams or system milligram

8:13

pods of you smoke like the whole pot

8:15

of nicotine that goes in your veins device.

8:17

Then it's like smoking a pack of cigarettes.

8:20

As far as the nicotine content goes, Which.

8:22

I and I had never really like took the time

8:25

to look into that before, but it seems. They.

8:27

So they're getting nicotine, which I think will factor

8:29

into what we're talking about here. He

8:32

I think one of things that I struggle with.

8:35

In terms of aping, counseling is exactly like up is

8:37

also you be published, you rape and innovations for every

8:39

like I don't know how to answer that. might is

8:41

a six percent closures. That's a thing I heard of

8:43

one time like an analysis of a mess in terms

8:45

of quantifying, but I it's I think that's at a

8:47

helpful framing and. Yes,

8:50

So. With. Can we get

8:52

into the limitations to this was a positive trial So

8:54

I guess we need to look for sources of chance

8:57

or bias that might have a to that outcome. Of.

9:00

We won a phone Rahul for this since he's always

9:02

good with those are. Trying

9:04

to i want a mission. a couple points out

9:06

the trousers think work as a nifty and a

9:09

not that I guess they're all cheerfully tag unraveled.

9:11

Let me know if there's if there's buyers are

9:13

research skeptical here so they were. The biochemical confirmation

9:15

was actually done, the patience to brought their you're

9:18

into the office which is you know at the

9:20

with having. Fortunately smoking clinics is typically not how

9:22

you do you're ingesting for anything which I'm not

9:24

saying that people rotten figure and but I am

9:26

by I'm saying it's it's not perfect but the

9:29

adherents was confirmed measuring and never seen which I

9:31

had never heard of. Have you heard of map.

9:33

Know. It's a tobacco

9:35

alkaloid and so what It can do as

9:38

you can actually detect whether someone's been smoking,

9:40

even if they're using nicotine replacement therapy. So

9:42

started Nicotine metabolite is. It's. Independent

9:44

from that's you can see smoking without it

9:47

being interfered with by nicotine of understand correctly

9:49

so it it measures smoking still backhoe that

9:51

nicotine concentrations was was usually in that. The.

9:53

Center during drug tests. I thought that was kind of cool. I

9:56

did want to touch on exclusion criteria and and rumble,

9:58

I'd love to hear your thoughts. Terms of the

10:00

strength and things that maybe we should just look

10:02

for for bias but I didn't other the patients

10:04

who are excluded. If you look at

10:06

them, the upwards of like eighty five percent had

10:08

tried to quit previously, but exclusion criteria included folks

10:11

who had not used or trying cigarettes in the

10:13

past three months or nicotine replacement therapy and up

10:15

last three months I thought it was. In.

10:17

Terms of selection bias which as it

10:19

even call it is it serious group

10:21

who. Advocate who are interested

10:24

enough to call number and British Been a research

10:26

trial but have nevertheless not tried. I tried a

10:28

cigarette addiction placement during the past three months or

10:30

I'm not saying that invalidates anything, I just think

10:32

that's I think it's like for a certain type

10:34

of person I can't characterize entirely well by I

10:37

yeah I think this era was a strong study

10:39

but I I was of the durable thoughts in

10:41

terms of how they how they did entertaining as

10:43

be serious about freedom, advocating for the team for

10:45

free cigarettes or obligations yeah well I I I

10:47

thought the same thing when I lifted the participant

10:50

characteristics but then I. Sort. Of thought

10:52

about why wonder if practices around you

10:54

cigarettes are different in tone, subtle and

10:56

then hear me to marketing is you

10:59

more aggressive here? On but

11:01

you're thinking about and sources of chance

11:03

in bias that could explain a positive

11:05

trial finding Love that framing Starting off

11:07

this is a positive trial meaning in

11:09

association with sound between the intervention, the

11:11

outcome to the first thing that I

11:13

look for when and evaluating a positive

11:16

trial is be I'd primary outcome history

11:18

on clinical trials die odds an for

11:20

this trial the primary and secondary outcomes

11:22

that were registered in the protocol at

11:24

the same ones we see the paper

11:26

so that's good In in the next

11:28

see a look for is. Is there

11:31

obvious evidence of selection bias and a

11:33

great place to find? This is in

11:35

the concert diagram which in this study's

11:37

figure one that flowchart really sure you

11:40

know number patients who were assessed for

11:42

eligibility The number patients ultimately randomized a

11:44

quick and dirty dipstick method to you

11:47

can use to sort of get a

11:49

sense was this a highly selected say

11:51

population? Where was this a very you

11:53

know open arms recruiting type of study

11:56

is what was the percentage of patients

11:58

who are screens were also. Randomized

12:00

In In this study I could they be

12:02

more worried about a steady were like you

12:04

know, five percent of patients who are screen

12:06

or ultimately randomized than I would be about

12:08

a city where ninety five percent efficiency were

12:10

screened A randomized To this city, like most

12:12

steady falls somewhere in the middle it was.

12:14

You know, more than half the patients who

12:16

were screened made it and which is good.

12:19

Sues. Nights a glaring signal for pre

12:21

randomization selection bias and then post randomization

12:23

selection bias. You can also look for

12:25

the diagram and you can see here

12:28

are six hundred patients and change were

12:30

assigned to each group in the same

12:32

number of patients who are I included

12:34

in the primary? else it so that

12:36

tells you is it intention to treat

12:38

analysis? So yeah absence of red flags

12:40

for I saw his of chance bias

12:42

for this positive trial. Yeah.

12:45

So. So. Paul: Anything else

12:47

you want to talk about in this one? I

12:49

mean. I. Think there's a little bit

12:51

more discussion beyond this to just say like

12:53

how's this going to change our practice Because

12:55

there was some interesting editorials that have been

12:58

written in in the past couple months of

13:00

and one one went along with this. So.

13:03

Where. Do you think. The Idea: I

13:05

think there's a lot to dig into. Hear the

13:07

city increase great your include people who intended to

13:09

quit within three months and so a notices actual

13:11

the contrary to sort of how I actually. Cancer.

13:14

Patients to quit smoking like it. If someone's even thought

13:16

about or even mentions like maybe some point I quit

13:18

I start. Encouraging. Intervention from

13:20

of our modalities immediately. but get on a guide

13:22

or I am quit dates anymore. And

13:25

so it just even from to the framing of thing

13:27

so a bit different than actually practiced registered of the

13:29

bigger question. We. Should be talking about his

13:31

work and of the or handy assumption that I try

13:33

cigarettes are safer than than cigarettes in or a better

13:35

alternative to it like otherwise what's the point? Like if

13:37

it turns out there more harmful than cigarettes and there's

13:39

no reason actually be. Conducting. A study,

13:42

I think that's that's the part where we're kind

13:44

of fucked up in a we're talking up for

13:46

restarted is there's not a lot of super compelling

13:48

trials looking at very long term data in terms

13:50

of people use which I cigarettes and are at

13:52

their of their long term safety this are shorter

13:54

term stuff. But. The longer term it's

13:56

hard to feel super comfortable with, though probably

13:58

on balance. they're safer than smoking. Tobacco.

14:01

right? So a couple things that we

14:03

looked at for there's there's a cochrane

14:06

review. It's a living review of the

14:08

cigarettes In this it was most recently

14:10

updated and Twenty Twenty Four and and

14:12

they basically conclude that they he cigarettes

14:14

are. The. You know that the

14:17

adverse events or things like nausea and

14:19

throat irritation, you know there's nothing. nothing

14:21

serious their that Cochrane review says there's

14:23

pretty good evidence that they're that it

14:25

works Better than just nicotine replacement therapy,

14:28

your standard nicotine replacement therapy and and

14:30

better than he cigarettes without nicotine. The

14:32

you know the cigarettes with nicotine work

14:34

better. And. This editorial in

14:36

The New England Journal by. Doctor.

14:39

Regard he is She at the end sort

14:41

of concludes. We have to start thinking of

14:43

his cigarettes as a tool for smoking cessation

14:45

and especially if patients have tried other first

14:47

line agency northern Iraq river and a clean

14:50

your nicotine replacement therapy in the haven't had

14:52

success than this is something we have to

14:54

think about. So. You.

14:56

Know that's kind of where I'm at for now. I'm

14:59

I haven't heard any really bad long term adverse

15:01

events, but Rahul I know you were mentioning you

15:03

had. Read. Something recently about this.

15:06

Yeah, there is just a systematic

15:08

review and meta analysis published in

15:10

February and it met him. Evidence which

15:12

we can linked in the show

15:14

notes and this basically looked at a

15:17

lot of ah observational studies of

15:19

patients using his cigarettes to look

15:21

at the comparison of outcomes for different

15:23

and points between patients who are

15:25

still using tobacco products and patients you're

15:27

using the cigarettes to get that

15:29

assumption are you cigarettes really safer and

15:32

will they found is that for

15:34

cardiovascular disease I'd stroke and metabolic

15:36

syndrome. Ah there's really no

15:38

improvement from switching t cigarettes but

15:40

for pulmonary things like as most

15:42

you p or and also oral

15:45

diseases general category or pieces do

15:47

do better with certainty. cigarettes of

15:49

does seem like there some I

15:51

need for individual nuance and decision

15:53

making. In advice pesticides, Though

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16:55

Zoc. Paul.

17:02

You are making the point about like

17:04

you know that observational data. And

17:06

looking at cardiovascular risk in the In: a

17:08

person who's using cigarettes? Where do you think?

17:11

So a couple things that yeah I think

17:14

that the pulmonary benefits not surprising is not

17:16

ignoring smoke were getting. That's really the mashable,

17:18

the cardiovascular equivalence. I do hesitated. To

17:21

hang on to strongly. today. I think that

17:23

probably unhealthy behaviors tend to ride together and

17:25

I think that patients who ravens what we're

17:27

trying cigarettes may engage another sort of myself.

17:29

arteries are me, sort of was awful, die

17:31

or to meet you don't like indices a

17:33

broad generalization I I fully appreciate by when

17:35

I would would wonder if they're not other

17:37

factors that that's making to be towards. Argued

17:40

progressive disease or maybe not nursery schools with

17:42

you on a cigarette route. Now be

17:44

meditation or. To. This is

17:46

in association with cardiovascular risk.

17:49

However, we can't say causal and

17:51

then. Was. There mechanism proposed

17:53

for why he cigarettes Was it

17:55

the nicotine is. Increasing cardiovascular

17:57

risk? Where is it? There's something else.

18:00

Some other chemical that's in the. In.

18:02

The vapor because you have to have like

18:04

a mechanism right in order for to even

18:06

suggest there could be a causal relationship gift.

18:08

ever proposed mechanism did they put on in

18:10

their the ice. And. Enough you know

18:12

that off and roll know it's a

18:14

good question. First I'll say paul your

18:16

concern about could do associations be confounded

18:18

by other behaviors that are also associated

18:20

with smoking? Very legitimate

18:22

concern. Ah, A Mac is

18:25

your question of is there a potential

18:27

mechanistic hypothesis for why nicotine might worse

18:29

and cardiovascular outcomes that not ah pulmonary

18:31

ones is is a thing where I

18:33

t subject matter experts at night nicotine

18:36

in certain replacement their be be really

18:38

helpful it seems to me like it

18:40

might be mechanistically plausible of nicotine has

18:42

your resume active properties and you know

18:44

least visit instruction and might worse and

18:47

hypertension over time i consider being a

18:49

causal lived in are printed on the

18:51

the. Or it.

18:53

so I think we should wrap this one out.

18:55

Paul if you want to give your pancakes reading

18:57

for the original article we are talking about and

19:00

then. Let. The audience know like

19:02

what he suggests they do with this information

19:04

that we just presented. Yeah

19:06

I I I I just dove where we

19:08

have a size like a serious note at

19:10

this point out of five this he us

19:12

hello three It's not gonna change things I

19:14

think it adds to as it is important

19:16

article on a thing as to body knows

19:18

that needs to be developed even further still

19:20

am I. Think. This will fit into

19:22

the realm of does. It will build the shared decision

19:24

making amber season right would actually probably bring this up

19:27

like on balance people Marquee be done with smoking am

19:29

and good You debate when they try to use a

19:31

been to quit so I think is important Pieces know

19:33

what to expect and a dead. The safety seems to

19:35

be there so far as we know but we really

19:37

good long term data and I think that's. A.

19:40

Fair things to patients. I am not going

19:42

to actively discouraged someone from using which I

19:44

cigarettes to quit smoking is is part of

19:46

i take way source on wasn't right I

19:48

think it's certainly reasonable and probably I'm. The.

19:51

Help we I don't act and and years arrest Amos. And.

19:53

Recording the process of we safer and healthier.

19:55

Sorry for now I think I would. At

19:58

not discourage and would even consider yeah my

20:00

trousers hobbies to quit smoking. I.

20:03

Like the point that you made that. A

20:05

lot of the patients were still using his

20:08

cigarettes. you know because they're sit there he

20:10

they remain on nicotine on radar. It's not

20:12

like they just use ie cigarettes, quit smoking

20:14

and then stop the cigarettes. A lot of

20:17

like more than half the patients in this

20:19

study and other studies ah remain on them

20:21

so I think that's the issue and you

20:23

might have to use the traditional. Met.

20:26

The Mic methods for smoking cessation to get

20:28

people off the he cigarettes. but that's I

20:30

don't think anyone has actually published that Jaeger.

20:32

You know, we don't know for sure what

20:34

to do. Their. For an unclean so

20:36

far as I know and we can american remember, Splashy

20:39

has been studied for that seems to be honest. Sexes

20:41

we have. Yeah, Yeah.

20:43

I don't make one last point blaze it actually kind

20:45

of ironic as I think it maybe it was the

20:47

regard the editorial that mention that history and you states

20:49

of electronic cigarettes not being used for seasons because they

20:52

want to bypass the of the a process would enamoured

20:54

and some. So. Read so since

20:56

read it at me with as a medication,

20:58

ages when resurrected consumer. And this honestly

21:00

this would be a dream medication for pharmaceutical

21:02

company right? Like a something that. Missions

21:04

use and the Marine on in perpetuity. So this

21:07

is as it's I. It's kind of surprising this

21:09

one actually hasn't gone down that route. Actually, try

21:11

to yep, area how your matters. I am. I

21:13

think the cigarette companies are already making so much

21:15

money off of them that they don't even care.

21:17

But I guess pharmaceutical companies can jump in and

21:19

make this money to. I don't know. Or.

21:22

A Well Rahul or next article is

21:24

is your said you on introduce it.

21:27

Yeah. Sure certain to talk about a

21:29

paper dasa do with kind of the

21:31

other end of the consequences of smoking.

21:33

What happens at people who have had

21:35

a long history smoking? So this is

21:37

a paper by Rom on and Colleagues

21:39

News published in a Feb Twenty twenty

21:41

Four issue of the Annals of Internal

21:43

Medicine. This is gathered pens noise and

21:45

risk for severe exacerbations in Seattle Pd.

21:48

Suit the research question that these authors

21:50

wanted to said he was whether Gap

21:52

a Penta knew we'd use which is

21:54

basically Gab, Fenton and Pregabalin, But I'm

21:56

just gonna say Gabapentin for simplicity and

21:59

whether Gap of. The news is

22:01

associated with hospitalizations for Cbd

22:03

exacerbation. So. I'm just curious.

22:05

was a something that was on either of

22:07

your radar before talking about this paper is

22:09

a something he had been thinking about. I.

22:12

Have to say Rahal. Oh we read a

22:14

lot for the show. We.

22:16

Do? We've been doing hotcakes since at least

22:19

twenty eighteen and at has not been on

22:21

my radar at all. I've seen fully.

22:23

I did not know about it. I

22:25

wouldn't build seem into it because I think I'm

22:27

a rebel which was burning up the twitterverse her

22:29

all of like today's that uniform and I'll destroy

22:31

the idea. Sorry I don't think it's I don't

22:33

think it's on us. It was not a well

22:35

known phenomenon that it it didn't exist. Yet

22:38

to I mean you know kind of

22:40

is important to think about your wives

22:42

the say.mises Important? Who cares? So the

22:44

reason at the study was done is

22:47

that it's definitely set off label prescribing

22:49

of gab the Pentagon and we see

22:51

I'd states is becoming increasingly common people

22:53

kind of think of it is safer

22:56

alternative to opioids in patients with chronic

22:58

pain and other indications for opioids and

23:00

but it turns out that in the

23:02

early twenty ten there have been a

23:05

number of reports severe and fatal respiratory

23:07

depression. Attributed to get attention reported to

23:09

the Sdk into this prompted a security

23:11

warning in Twenty Nine Keen on but

23:13

the evidence at that point wasn't great

23:15

to discovered said he was done to

23:17

sort of figure out you know is

23:19

there ah ah evidence of harm our

23:21

from respiratory depression from Gavin Henson to

23:24

what are the author's find one terms

23:26

but the top line finding to the

23:28

said he this is a positive study

23:30

in association was found among patients with

23:32

C O P D in Canada who

23:34

had a median of one and a

23:36

half years of follow. Up. Gather

23:38

had to use when compared with nine use

23:40

of Gabbert tent and. In. This gives

23:42

get repented been used for median

23:44

of that six months was associated

23:46

with an increased risk for hospitalization

23:49

for C O P D exacerbation

23:51

regardless of whether the indication was

23:53

epilepsy, neuropathic pain or out a

23:55

chronic pain In this translated in

23:57

absolute terms to about a forty

23:59

percent relative. Crease in hazard

24:01

ratio he had.and access at

24:03

about seven hospitalizations for hundred

24:05

patients per year. So. He

24:08

a real evidence of harm at both in

24:10

the absolute sense and year old to sense.

24:13

Yeah in it's so the they think

24:16

it's maybe respiratory depression that's causing part

24:18

of it and then I guess you're

24:20

more likely to have see a pt

24:22

exacerbations as well. I was

24:24

a really clear ah others and respiratory depression

24:26

which makes a little bit a sense to

24:28

me to serve said somewhat sedating medications and

24:30

there may be Poly Pharmacy going on. But.

24:33

I'm not sure. If there's another

24:35

mechanism, Gap. Think we

24:37

are exactly where it might be

24:39

the causal mechanism. Here he evidence

24:41

askance Bread and users at least

24:43

one study showing that Gabapentin is

24:45

thought to worsen at respiratory parameters

24:47

during sleep in patients with obstructive

24:49

sleep apnea leading to more episodes

24:51

of hypothermia, more hypoxia, and there's

24:53

also evidence that Gap and and

24:55

leads to increased incidence of respiratory

24:57

depression when given Perry operatively. So

24:59

there's at least two settings in

25:01

which Scabbard Benton has been observed

25:03

to cause respiratory issues, and I

25:05

think. We are kind of, you're not

25:08

really sure. Beyond Dad and it gets

25:10

Gabbert properties in a sort of similar

25:12

to alcohol could it be to respiratory

25:14

depression and in high doses similar to

25:16

that. Can I found a proposition?

25:18

I think other people's a study because I'm not a researcher.

25:21

But. Recall the get Revenge is actually want to

25:23

medication suggested for someone who has a path a

25:25

chronic cough. Like. I wonder? If.

25:27

I cause depression and a nurturing out situations

25:30

where you for axes or is suppressing a

25:32

mechanism that actually kind of clear out some

25:34

guns is not our contribution as well that

25:36

they'll be my next visit proposition so I

25:38

like to enjoy now. Dot. Wraith.

25:41

Second, They're trying to get

25:43

her old shows try making us what

25:45

a pro. The success of. Your.

25:48

Question about that mechanism and how this might

25:50

work out makes in my mind the details

25:52

of how they did this. That's really important

25:54

because you know if if mechanism does make

25:56

sense then you that is an important piece

25:58

of how evaluate the fine. This day,

26:00

so they had the city carried

26:02

out. This is a retrospective cohort

26:04

study that was done using and

26:07

insurance database and Canada. In Basically

26:09

the authors had access to all

26:11

the administrative. I data

26:13

for a pharmacy dispensing for about

26:15

forty percent of the population in

26:17

Quebec and he had access to

26:19

a hundred percent of hospitalization data

26:21

for the population Quebec. Okay to

26:23

be denied people with soupy using

26:25

a receipt of inhaled medications for

26:27

C O P D lob as

26:29

long as and I see us

26:32

in the used a city nine

26:34

toads to get if I hospitalizations

26:36

for C O P D Okay,

26:38

so. This means that the outcome

26:40

is going to be you know assessed

26:42

with basically one hundred percent certainty because

26:44

they have I said unanimous or hospitalization

26:46

to the exposure is only gonna be

26:48

assessed with it out of forty percent

26:50

fidelity. Okay because there's a huge session

26:52

of the population that doesn't get their

26:54

ah that the who's our farmers the

26:56

Lpc did it doesn't make it into

26:58

this database to this means there is

27:01

good be miss classification of exposure in

27:03

this study in that is going to

27:05

tend to bias towards and know finding

27:07

to the fact that the study. Was

27:09

a positive one found in association. even

27:11

despite that makes me worry that you

27:13

know maybe to signal I have the

27:15

strength of association between Gabapentin in the

27:18

outcome or is even greater than what

27:20

we found these for principally score matching

27:22

in a steady to match I users

27:24

with nine users and as many characteristics

27:26

as we could and in they use

27:29

something called i'm an Active Computer new

27:31

user design and base to be necessary

27:33

to try to emulate a randomized trial

27:35

as closely as possible. I to avoid

27:37

some devices and parents. And observational research.

27:39

You can think this is kind of like

27:42

an intention to treat analysis and randomized controlled

27:44

trial. In. Damn yeah this will

27:46

increase exposure miss classification overtime but as he

27:48

said that would tend to bias towards the

27:50

know finding so that is a is in

27:52

my mind kind of a strengthen the study.

27:55

Yeah. To. Me. I guess that

27:57

the big question for America's primary care physician?

27:59

it is. How as someone who

28:02

and I'm i'm i'm joking when I say

28:04

this you you're a huge fan of Gab

28:06

A and you love it is your favorite

28:08

medication. Or you You give

28:10

it to most people who does this change

28:13

anything in your practice? It's.

28:16

Not my eat I'd I'm of. Focal

28:19

Eight are gathered under no circumstances in part and

28:21

with when we talk about the full of because

28:23

it does seem to be held mary Pass where

28:25

it is used as human survival off label for

28:27

a lot of indications of is not needed for

28:29

and then when it doesn't work it remains in

28:31

the medication or so gets applied, treated, gets parts.

28:34

And. Then patients renal function change nine cents

28:36

or toxicity and bad outcome. So I

28:38

think if anything. You. Know it's

28:40

I'm struggling with the mechanism I think any any of

28:42

these are his chart mining trials. I i just after

28:44

a at the get in trouble with cost know the

28:46

seems about clean as you can do it. But.

28:49

It it's still isis another reason to be

28:51

element more cautious when thing that ever happened

28:53

as well maybe outright for this patients whatever

28:55

pain because if it's. It's. Not indicated.

28:57

Runner up added pain The barely works for neuropathic

28:59

pain so I get just media media shouldn't is

29:01

I might ugly for them. Yeah. Yeah,

29:04

the side effects. I mean, We gain

29:06

a dema dizziness, vision changes. you

29:08

know there's a lot of the

29:11

like the Kindle cognition for some

29:13

people, so definitely has a lot

29:15

of downsides to it. and. I

29:18

think it gets thrown around way to

29:20

sort of can like People are just

29:22

very. Easy. To just be likely Alice

29:24

are some Gavin Henson at them and and and

29:26

I think not even thinking about the starting dose

29:28

either to say oh yes, start him on three

29:30

hundred three times a day in their nine year

29:33

old, you know, right? And these are multi more

29:35

vacations. Which means. They're. Going to

29:37

have variable real function. And so it

29:39

in this is a really does medications so off I

29:41

see someone who declined. But the doses these exactly the

29:43

seems like a singer. So much potential for taxes already

29:46

so to have one more thing to worry about with

29:48

it's just again. yeah. Maybe. Only cautious with

29:50

them. So. To get back to

29:52

the study Rahul like what what would

29:54

you give this as a hot Cakes

29:56

rating? What would be your recommendations? the

29:58

audience, as far as what conclusions they

30:01

can draw from. yeah I mean you

30:03

know dissipated limitations of observational of research

30:05

and that you're brought up and and

30:07

these authors used as robust methods to

30:09

sort of trying to aid in our

30:11

or inference of causality innocent it's likely

30:13

to be the best information organ get

30:15

to try to clarify you know is

30:17

there evidence of harm from Get Henson

30:19

in patients C O P D So

30:21

I you know my take away that

30:24

because off label prescribing is You know

30:26

I recently of uncertain benefit and now

30:28

we're You know it's getting more. Evidence

30:30

of harm. This is gonna make me

30:32

avoid initiation of Gavin Henson Editions with

30:35

Cbd. I'll try other alternatives first sight.

30:37

Do this for if advocates. Excellent.

30:40

Or a moving on to the

30:42

next. Now from from Gab, attend

30:45

into another chronic pain Hail Mary

30:47

Pass fight again if it sounds

30:49

so. This is by a study

30:51

by Cohen et al and it's

30:53

a multicenter randomized placebo controlled. Crossover.

30:56

Trial this was looking at

30:58

Topical lied again for mechanical

31:00

Cervical Painter mechanical neck pain

31:03

disappeared in the Journal Anesthesiology

31:05

and twenty twenty four. And

31:07

we wanna do This paper does because.

31:10

You. Know Paul ladder key I wanted to do. A. Little

31:12

bit of a deep dive on my

31:14

again patches because in my experience most

31:16

patients have tried them. Some patients love

31:18

them some peace and say they do

31:20

nothing. But. They're They're

31:22

pretty easy for patients to get their

31:25

hands on and people love to. Do.

31:27

Something active to try to treat their

31:29

pain is so the question here was

31:31

you know is why to better than

31:33

Placebo for mechanical neck pain. And.

31:35

This was actually a negative

31:37

trial. Say they actually published

31:40

a negative trial which I

31:42

think is you know, commendable

31:44

and on. This used a

31:46

topical system of one point

31:48

eight percent white, eighteen, and

31:50

so basically Paul. These were

31:52

fancy. One point eight percent white

31:54

again patches that are thinner and more

31:56

efficient at delivering lied again but the

31:58

of deliver equivalent amount of right again

32:00

to eight years your traditional. larger.

32:03

Heavier five percent by two teams hatch the

32:05

seats are ran daddy's I became bass yeah

32:08

and I read like three or four articles

32:10

it can a deep diving on my cow

32:12

there's you know these these fancy patch

32:14

the use in this study need less likely

32:16

came per gram adhesive and he the patches

32:19

need much less likely came to get

32:21

you know the same kind of the and

32:23

maybe they add here better and maybe though

32:25

I duchene penetrates a little deeper. And

32:28

anyway, so this study found they were

32:30

looking to see at least a one

32:32

point difference on a ten point neck

32:34

pain scale. And they ended up

32:36

having only about a half a point between group

32:39

difference on a ten point scale so they did

32:41

not meet their. On the and point

32:43

there were looking for. Any questions

32:45

about this or any thing that struck you

32:47

guys from this about this study. And

32:50

met. You may not know the answer to this,

32:53

but you're usually so good at Second Universal, What

32:55

on this particular skill was deemed clinically relevant. Do

32:57

remember what the. They. They

32:59

wanted at least the one more than

33:01

one point, but usually it's at least

33:03

a two point difference. You know, like

33:05

you want to see a twenty or

33:07

thirty percent difference in most medication studied

33:09

for pain and this goes way back

33:11

to like our fibromyalgia episode, which is

33:13

one of our first ten episodes the

33:15

most drugs do less than two points

33:17

on a ten point scale. It

33:20

when you're talking about chronic pain, you know it's It's

33:22

different than if you give somebody like a handful ibuprofen

33:24

for like a sprained ankle in in it, but you

33:26

know they might have more pain relief. But if you're

33:28

taken a day in day out. So. Yeah,

33:31

this was certainly you could. You could argue

33:33

even if they did meet their one point

33:35

between groups different. Would that

33:37

have been clinically significant to the pace?

33:39

I'm. So.

33:41

Good. Question Row: anything from your and.

33:44

Yeah, I mean you're a good you're framing

33:47

of this is a negative trial. Big ears

33:49

are starting to turn in my brain. you

33:51

know could do have been sources of chance

33:53

or bias that need to see false negative

33:55

finding. I'm curious if there's anything in your

33:57

overview of the paper that you could. Beat

34:00

us one way or another to think could the

34:02

city have been under powered? For example, where yeah

34:04

reports about that. You. Know was interesting

34:06

that the the study said they needed

34:09

or and roll eighty some patience to

34:11

achieve the power that they were looking

34:13

for. They were. they were looking to

34:15

get ninety percent power and the enrollment

34:18

was delayed because of the pandemic. Paul,

34:20

you'll love this as many Then the

34:22

patches and the placebo patches expired said

34:25

i guess we're done Needed for this

34:27

so they had to stop and roman

34:29

at only seventy six patients. So.

34:32

You know that sort of handicap things a

34:34

little bit. and then I think also Paul

34:36

and Rahal. The other thing that I notice

34:38

is that this was a crossover trial. So

34:41

patience either started with Placebo for four weeks

34:43

at a one week wash out, then went

34:45

to Lied again, or they started with Lied

34:47

again. And. Then the the wash

34:49

out then went to placebo and the

34:51

group that started with placebo it like

34:53

they were more likely to drop out

34:56

from that group. Then. They were

34:58

if they started with lied again. And.

35:01

The. Blinding although they said that he

35:03

did some so they said the

35:05

patches were quote identical in dimensions,

35:07

texture, and smell. Paul House for

35:09

what about Taste Assess assess. Assess

35:15

law. don't like a question whether or not

35:17

like that that the you had the more

35:19

drop out in law in the placebo group

35:22

After that first phase I just wonder if

35:24

patients could guess which group they were and

35:26

and recite as forget it on mckenna. And.

35:29

Not going to stick with this. Role.

35:31

Anything else you saw. I know that there was a couple

35:33

other things, but. Yeah. Deserve the

35:35

right things to be asking about. I

35:37

mean did Did Strengths is a study

35:40

in my mind. d Crossover designed very

35:42

strong design for randomised trials and the

35:44

fact that this was double blind is

35:46

kind of what you want to see

35:49

for cities where the outcome is and

35:51

service subjective determination like be experienced of

35:53

pain. And

35:55

you also want to see did they

35:57

have an hour adequate washoe pureed between

36:00

and city dragon placebo which they had

36:02

here. so only things you know kind

36:04

of increase my confidence that this is

36:06

likely to be just a true finding

36:08

that there it is not really benefit

36:10

of topical light. Came for mechanical neck

36:12

pain he unsteady that are under powered

36:14

you know those tend to look different

36:16

where you see a point estimates that

36:18

is and your on par with are

36:21

bigger than what you powered the city

36:23

for. but t i d confidence interval

36:25

you know just missed statistical significance that

36:27

was not case here be effect size

36:29

and was. You know I think of

36:31

point five points difference between the two

36:33

they actually found in that difference in

36:35

recent Siskel significant. So all the signs

36:37

increase my my confidence in the determination

36:39

that it's awesome. I said business and

36:42

underpowered said he. I think this is

36:44

that there's really no evidence of. This

36:50

episode is brought to you by

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38:03

In. Part of why they were looking at neck

38:06

pain I just wanted to mention to the

38:08

audience because I know this is a common

38:10

reason so people commonly try to use Why

38:12

the cane patches for low back pain and

38:14

that's been studied. There was at least five

38:16

open label trials. That. Were uncontrolled.

38:18

And then there were two randomised trials

38:20

of. Fight. Again, patches for chronic low

38:23

back pain and the open label trials seem

38:25

to see verbal what they weren't comparing it

38:27

to anything. And then in the randomized trials.

38:29

Lied. Again and Placebo I one

38:31

of the trials perform the same:

38:34

the Larrikin Patches versus Placebo. And.

38:36

In the other trial. It. Was a

38:38

wide eighteen and menthol patch versus Placebo may

38:41

be performed a little bit better, so maybe

38:43

maybe the smell they are. Paul got it

38:45

over the line against Placebo, but I think

38:47

that they were thinking okay, didn't work in

38:49

the low back. Maybe that's because the tissues

38:51

are. there's too much tissue their can't penetrate

38:53

enough, but the next is like there's less

38:55

tissue to penetrate through, so maybe the lot

38:57

of came will be more effective in the

39:00

neck. And there had been some other studies

39:02

of neck pain that were. With.

39:04

With lied again patches that seemed like how maybe there's

39:06

something here. so I think that's why they were studying

39:08

is. No. Integrating to say it's

39:10

a neck, it's short shrift because most of

39:12

the data regarding the management of neck pain

39:14

we would medications extrapolated from oh, back pain

39:17

and yeah, mechanically they. They. Suffer from

39:19

difference here for and and have different issues entirely.

39:21

So it's I've actually thrilled at some. was actually

39:23

looking silly against the same as was hour and

39:25

a this man. And just

39:27

looking at topical lied again in general

39:29

I mean the or the lied again

39:32

patches are approved for posts are Paddick

39:34

neuralgia officially and that's really where that

39:36

strength of evidence is on people. In.

39:39

The guidelines for like diabetic neuropathy and things

39:41

like that at their the it's mentioned as

39:43

something you can use but. You.

39:45

Know So I think neuropathic pain is really where

39:48

I'll be using Lied again patches in this. This.

39:50

Won't change my practice. I would give this

39:52

like three and a half hotcakes. I thought

39:54

it was. A commendable as

39:56

a said that they publish the negative study and

39:59

I like the fact that are trying to look

40:01

at something for neck pain. On.

40:03

It's good to have randomized evidence that we can

40:06

point to for something like this. and I as

40:08

Rahul said, I like the crossover design, especially for

40:10

a placebo trial. Just seems like to make sense.

40:12

You know to see how much of a placebo

40:15

effect in a given patient had when you do

40:17

that. Crossover. Like that. So.

40:20

I. Right? Or that's that's all I had

40:22

an that once. We have a couple hot

40:25

takes to get to and Rahul our first

40:27

hot take his. I don't know how to

40:29

transition this from why to keynes from the

40:31

neck to see death, so let's just. Let's

40:35

let's say you're starting to get out

40:37

of your much yeah just the had

40:39

gov of panesar dangerous here. Okay so

40:41

I am gonna I just a. Tire.

40:44

Quickly about a tapered it was published

40:46

in now open form Infectious Diseases last

40:49

year. This is

40:51

a I case control study ah

40:53

that was looking at the strength

40:55

of association between at different classes

40:58

of antibiotics in needed he acquired

41:00

see different section So previous studies

41:02

on the strength of association between.

41:05

Antibiotic sensitive has all been really

41:07

small limited by different exposure windows

41:09

into these Authors sought to do

41:12

a mast case control study using

41:14

nationally representative data from insurance claims

41:16

from United States from Two Thousand

41:19

One to Twenty Twenty One and

41:21

he lifted patients who had out

41:23

pc diagnoses of see this and

41:25

compared them to matched controls within

41:28

the dataset who did not have

41:30

a diagnosis to see death during

41:32

that time period in the looked

41:34

for exposure. To twenty seven commonly used

41:37

our piece of antibiotics in the second is

41:39

three. Do you really do what has to

41:41

do a case control study for because there's

41:43

an outcome of interest see desk and then

41:45

maybe exposures and interest to in this case

41:47

that groups are defined. Maybe I'll com in

41:49

a looked back in time to see what

41:51

antibiotics they are exposed to. School and the

41:54

reason this is limited to our patience is

41:56

because they wanted to Really trying I say

41:58

the effect of the answer by. On

42:00

risk I and remove kind of the

42:02

other you know risks of reddit of

42:04

seat if that are kind of more

42:06

related to and hospitalization and impeached stays

42:08

to basically what they found. Ah bottom

42:11

line. Was. That there is a

42:13

lot of variation that only between antibiotic classes.

42:15

That also we see an antibiotic classes in

42:17

terms of risk for suggests it. So it's

42:19

really kind of too simple to say You

42:21

know this class of antibiotics is better than

42:23

this class of the details really matter so

42:26

I have a a general take away then

42:28

I'll tell you now mortar you did did

42:30

you will have kind of or thought going

42:32

in like things you had heard were really

42:34

bad in terms as he does things you

42:36

had heard were safe. Paul.

42:39

I know your first love as an

42:41

antibiotic would you prescribed for everything is

42:43

Clinton Mice In much like Gabapentin I

42:45

think it's actually that's the com be

42:47

prescribed Gabapentin and Clinton my senses And

42:49

rice. and every babbel pill? Yeah, right.

42:51

So once you have diarrhea, you're much

42:53

more likely to fall running to the

42:55

bathroom. So serious that I so. I

42:58

I know we talked about see this

43:00

on an episode and I believe it

43:02

was with Paul Sacks cause he's the

43:04

one that told us that part of

43:06

the reason why Doxycycline. One other additional

43:08

reason why Doxycycline is every Id ducks

43:10

favorite antibiotic is because it seems to

43:12

be pretty see the a friendly and

43:14

maybe even has like a little inherent

43:16

activity against. See this. I.

43:18

Would have that going into this that that

43:20

was gonna be the one that had the

43:22

least you know least but raw hotel as

43:24

well what antibiotics came out looking bad and

43:27

which ones look good in this regard. Yeah.

43:29

To a dirty kind of knew about

43:31

that. Quinta my Sinbad Darcy good serve.

43:34

Mater up it would. They found the

43:36

antibiotics that had the highest risk your

43:38

eyes odds of the season with see

43:40

desks and we're talking odds races in

43:42

the ten to twenty range. Clinton, my

43:44

son and later generations Atlas Points of

43:47

A does seem to be worst. The

43:49

next level of risk odds ratios of

43:51

between five and ten. These are your

43:53

fluoroquinolones and actually penicillins. A On Cleveland

43:55

A gas it's all in this category

43:58

says of the I previously. Thought of as. It's

44:00

safe, you know, actually had a moderate

44:02

rest, lower risk in a biotics odds

44:04

ratios of one to three cellphone or

44:06

minds and macro lights off. Kind of

44:09

surprising to me that you know Mack

44:11

provides are not as high risk as

44:13

I was kind of. I ended antibiotics

44:15

with really no or minimal risk odds

44:17

ratios of one or in some cases

44:19

even less the tetracycline. Ah, And

44:22

poachers finding minutes cycling which I've

44:24

never used that are actually had

44:26

a significantly. Protective. Odds

44:29

ratio for seat of so maybe there's some

44:31

role for minutes. I clean a dream and

44:33

who knows but kind of cool little I'd

44:35

bump at low granularity to our i kinda

44:37

bad doxie good. In the two

44:40

things that struck me from this you

44:42

you mention the cephalosporins so you don't

44:44

really think of. At least I didn't

44:46

really think of the later generations cephalosporins

44:48

as being so see this unfriendly. And

44:50

and then the other thing Rahul was

44:53

this time from a antibiotic exposure. Can

44:55

you talk about that a little bit?

44:57

Because I think that was significant as

44:59

well. Yeah. Stare Decisis for in

45:01

Peace brings up an important limitation of this

45:04

study which is you they really don't have

45:06

data. I'm kind of the more in patients

45:08

antibiotics because this is all odds. You know

45:10

diagnoses established in the outpatient setting. so we

45:12

can really make conclusions about people getting set

45:14

tracks, own set of kin cetera. And but

45:16

the the time from exposure. piece of one

45:18

of cool things about this study. You know

45:21

causal inference is really limited from a case

45:23

control study. this is sort of thought to

45:25

be one of the week is tied to

45:27

stay designs for causal inference. but they did

45:29

do a cool. Thing which was they

45:31

very beat. Suppose your window d Primary

45:33

now says was receipt of antibiotics and

45:36

thirty days of the see this diagnosis

45:38

and indeed it is sensitivity analysis. Looking

45:40

at longer windows, sixty days Negatives: hundred

45:42

twenty other have to hundred ninety days

45:44

in you'd expect it is you get

45:47

farther away from day I or seat

45:49

of Antibiotics are in your seat if

45:51

diagnosis. That association said week it and

45:53

that's exactly what they saw. The odds

45:55

ratios for every at about it decreased

45:58

the longer out you liked. So.

46:00

Kind of a cool piece of Scotland's

46:03

their influence. If. You the causal

46:05

inference buried in this paper I'd suggest

46:07

that yeah these these relationships probably or

46:09

causal and die it. To highlight the

46:12

limitation previous studies which is that inconsistent

46:14

exposure windows you really do need to

46:16

be looking at antibiotics within a short

46:18

duration proceeded seat of diagnosis. Yeah.

46:21

So. People. She definitely like a

46:23

bookmark this one so they can. I look

46:26

at that table with the the twenty Seven

46:28

antibiotic so they can kind of see how

46:30

they rank when they're when they're setting which

46:32

settlers foreign to prescribed prescribed for people

46:34

and our just trying to figure out which

46:37

antibiotics or prescribing especially. Someone has a history

46:39

of see death now so. Odd.

46:41

The last thing we wanted to talk about here

46:43

paw you know to to set this up Paul.

46:46

Are you having trouble of prescribing Glp?

46:48

One agonising are they were will lump

46:50

in the G eyepiece last year p

46:53

One agonists to zip tied. Are you

46:55

having trouble right now prescribing them Nerve

46:57

pete with your pieces actually getting them.

47:00

Yet. Will yes yeah no. Problem solvers. Crimean

47:02

is my patients can pick it up or

47:04

com find any sources of it's or it

47:06

yet at. There's been a lot of manufacturer

47:08

shortages and in specific doses to is it's

47:10

been. A. Real challenge prescribed you

47:12

doing I'm inconsistency. Rights.

47:14

The genesis of this topic

47:16

was a listener on our

47:18

discord. Mentioned. As

47:21

pawn I a question like are you

47:23

seeing people locally that are dosing. The.

47:25

G O P one agonists the mega

47:28

tied by clicks. And. Upon

47:30

our like what? I? I've never heard

47:32

of that before. Paul actually. Put.

47:34

Out a twitter poll. That. Dot E

47:36

O Two hundred some votes and and about

47:38

half of the people will do more than

47:40

half of the people had never heard of

47:43

this practice of dosing. By. Clicks

47:45

and. Little. Less than

47:47

ten percent said they actually do this. Some

47:49

people said they heard of it but don't

47:51

do it So it was higher number than

47:53

I expected. Like the nine percent that are

47:55

actually doing it. I was kind of surprised

47:57

by yeah so I guess that was what

47:59

Sir you know thirty four percent of people

48:02

that are you know either heard of it,

48:04

are actually doing it. Thirty four Thirty five

48:06

percent Based on that Paul and and I

48:08

had never heard of this so there actually

48:10

was an article you know that this is

48:12

someone has actually published about this outside of

48:14

Reddit which was where I initially sound and

48:16

less than information for there's a Reddit thread

48:18

my main source of medical information actually or

48:20

splice it's a first they came across budget

48:22

of them pay Paul which was just people

48:25

recommending on Tic Toc that that you take

48:27

if you can't afford of them pick ah

48:29

sorry for saying the brand name or that

48:31

you should just take a bunch of laxatives

48:33

and that will that will have you heard

48:35

me. Say. Don't do

48:37

our I. Assert assists.

48:39

Then I found the Reddit thread which

48:41

actually in the Reddit thread there was

48:43

a link to this Canadian doctor. He

48:46

shared the Pts as his hand out.

48:48

He gives the patience, telling them how

48:50

the dose by clicks. And then

48:52

I found this paper by with li. Et

48:54

al. It's a bunch of pharmacists arm.

48:56

It's a special report that appeared in

48:58

Clinical Diabetes in the summer of Twenty

49:01

Twenty Three to talking about. How

49:03

do we handle this shortage of. Job.

49:05

He won in the G eyepiece last year

49:07

be one agonists said are out there and.

49:10

The. Interesting thing about some aggro tied

49:12

pens. His. Dad. They.

49:14

Are more their multi dose pens. and

49:16

so let's say Paul someone has the

49:18

one milligram pen. Will. They have to

49:21

turn this dial on it. A.

49:23

Bunch of times until it gets to

49:25

the one milligram dose. So. Someone

49:27

figured out that. Well, if you count how

49:29

many clicks it takes to get the one

49:31

milligram, then you know if you give half

49:33

that many clicks, maybe you can give half

49:35

the dose. Paul, you're putting your head in

49:37

your hands and are. Your

49:40

thoughts as America's primary care physician To suffer

49:42

through the spear to help your system is

49:44

deeply and fundamentally broken is my my thought

49:47

may square Yeah so these pharmacists were you

49:49

know the the These pharmacists were just mentioning

49:51

potential strategies of like is they know they're

49:53

not to be oh to get a refill

49:56

because as a. Shortage do they take it

49:58

every other week? Or. If

50:00

they have a pen, do they dose by

50:02

clicks? And maybe they take a smaller dose,

50:04

or they even said, if some people are

50:07

having side effects, if they have

50:09

a one milligram pen, and they're having side effects, maybe they don't

50:11

click it all the way up, they just click it part way

50:13

up, and then take a smaller dose. So it

50:15

was coming from a practical place, and they actually have a

50:17

table in there in this paper

50:19

that's just talking about how many clicks.

50:22

So it's, Paul, how many clicks

50:24

do you think it takes to get to, I

50:26

feel like this is a, something pops, come on.

50:28

How many clicks to the center of an attempt

50:30

at pen? How many total clicks to the one

50:32

milligram dose? Supposedly the number of

50:34

clicks is the same across all pens to get

50:36

to the max, to get to the top. I'm

50:38

likely. I know. But

50:41

it's a bunch, right? It's like 76 clicks or

50:43

something for the full dose, and then like three sometimes to.

50:46

Yeah, yeah, they published 74 clicks to

50:48

get to the full dose. So if you wanna, let's say

50:50

someone has a one milligram pen just to make the math

50:53

easy for us, Paul. 74

50:55

clicks, that'll get them one milligram. 37

50:57

clicks, that will get them half a milligram.

50:59

And then you can scale down or up

51:02

as you want based

51:04

on, give them 18 clicks

51:06

if you want them to get like a

51:09

quarter of a dose, basically. So it's interesting.

51:13

It's not something that I necessarily are gonna be telling

51:15

my patients to do, but it

51:17

might be something that people come in

51:19

asking you about. And what our listener,

51:21

Scott, on Discord was actually mentioning was

51:23

that this was a budget thing where

51:26

if you prescribe someone a one milligram pen and

51:28

they do 18 clicks, then

51:31

that pen can last them for many more

51:33

weeks than if they were doing the

51:35

full 74 clicks for each dose. And

51:38

to be clear, I just sort of like,

51:41

I'm casting no shade on the patients who are doing

51:43

this and the people who are actually trying to help

51:45

them. Like this is clearly just an

51:47

issue from a system standpoint. So all my agamol eye

51:50

rolling and stuff that this can actually be seen by

51:52

anyone watching the video is not directed towards the people

51:54

doing this because it just seems like a necessary evil

51:56

after we start this chronic medication that has you rebound

51:58

from if you stop taking. Like this is

52:00

just, it's more, it's a shame that our system is

52:03

so flawed that we're actually have to revert to these

52:05

kinds of tactics. So I just want to make sure

52:07

that people don't take my criticism as directed towards patients

52:09

or the people trying to help them, which is not

52:12

what I'm rolling my eyes at. Yeah. And

52:15

I mean, let's say we had a perfect

52:17

supply. I think where I'd be interested in

52:19

this is if somebody is on a pen

52:21

and they're having a lot of side effects

52:23

and they're like, how can

52:25

you help? How can you help me with this? You tell

52:27

them, okay, click it up, but don't click it up the

52:29

full way. That's potentially something you could

52:31

do. But again, you'd have to, you'd

52:33

have to confirm how many clicks it takes to

52:35

get to the full dose. Yeah.

52:38

Because I'm just not 100% that,

52:40

you know, it's really going to be 74 clicks

52:42

on all the pens. But

52:45

anyway, I thought this was kind of a

52:47

neat thing. I did look and, you know,

52:49

where this is coming out the end of

52:51

March, I've been told by local

52:53

pharmacists, they're thinking the end of April or May

52:55

that they might be able to get more of

52:57

a supply of this. And

52:59

in Forbes, I found an article talking about

53:02

how the drug companies are

53:04

trying to ramp up production. I

53:06

guess they were, they, this has been an issue since the

53:08

end of 2022 and it persisted through 2023.

53:12

So they apparently are trying to ramp

53:14

up production. It should get better because

53:16

a lot of patients do need and

53:18

benefit from these medications. So hopefully it

53:20

will. And that's

53:22

all I have to say about it, Rahul. Any

53:24

comments, concerns, questions about this one? Yeah.

53:27

I mean, I could see if it's

53:29

for side effects like titrating down. I

53:31

mean, that could be part of like

53:33

a good strategy for, you know, achieving

53:35

kind of the minimum tolerated

53:38

dose. But if it's,

53:40

you know, for budgeting and for kind of rationing,

53:42

you know, for drugs that exhibit a threshold effect,

53:44

you know, that could be bad

53:47

if you kind of, you know, drop

53:49

below the level of what's effective in

53:51

a patient. So it

53:53

kind of depends why somebody would be doing it.

53:55

But it's a great illustration of, you know, knowing

53:58

how patients are using medications, It

54:00

in ways that we might not know about or

54:02

might not be a gave out said scratch know.

54:05

In. In that reminding me I should, I

54:07

should mention that the. To. Lag the

54:09

tide enters Epa. Tied pens have is

54:11

a single dose you know you can't

54:13

dose by clicks with those pens. This

54:15

is specifically the some aggro tied. Pens.

54:18

Which I guess they're mechanism is that

54:20

they. Had those clicks to get

54:22

to the the the set. Don't see you

54:24

can't do this with every single. C.

54:26

O p won or g I p slashed your

54:29

p one agonist. right?

54:31

Well, any closing comments, I think I

54:33

think we've done it. It's a fair.

54:35

Great show as always and it's probably

54:37

time for an outer far. This

54:43

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55:54

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