Questioning Medicine

Noncontrast CT Selected Thrombectomy vs Medical Management for Late-Window Anterior Large Vessel Occlusion | Neurology

Most studies that have shown a benefit from endovascular thrombectomy (EVT) for ischemic stroke in the late time window (6 to 24 hours after time last known well) have used either perfusion imaging or advanced imaging to identify core infarct volume.

Whether plain CT alone can identify EVT candidates in the late time window is unknown.

multinational cohort study that looked at Consecutive patients presenting within 6–24 hours of time last seen well with proximal anterior LVO stroke that were either selected for EndoVascular therapy by Noncontrast CT or medically managed

The primary outcome was 90-day ordinal shift on the modified Rankin scale. Symptomatic intracranial hemorrhage (sICH) and mortality at 90 days were key safety outcomes.

results

 Functional independence (mRS 0–2) was observed in 40% of the EVT group and 18% of the MM-alone group. Symptomatic ICH was nonsignificantly more common with EVT than with MM alone (8.5% vs. 1.4%), but overall mortality was lower with EVT (24% vs. 32%).

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820369

With as many as 1 in 3 US adults using multivitamin supplements, the question as to whether these supplements reduce mortality

They used

three large observational cohort studies with nearly 400,000 participants (median age, 62) who were followed for as long as 27 years (mean, 20 years); these studies included data on diet, self-reported multivitamin use, and mortality.

In adjusted analyses, daily multivitamin use was associated with a very small, but significant (4%), higher all-cause mortality risk. (multivariable-adjusted hazard ratio, 1.04; 95% CI, 1.02-1.07)

Results from the current study — casting some doubt on a mortality benefit of multivitamin use — are unlikely to change the feelings of reassurance that many patients gain.

https://www.acpjournals.org/doi/10.7326/M23-3236

Angiotensin-converting–enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) seldom are initiated among patients with chronic kidney disease (CKD) stage 4 or 5, despite guideline recommendations for these agents--- 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines - ScienceDirect

“In adults with hypertension and CKD (stage 3 or higher or stage 1 or 2 with albuminuria [≥300 mg/d, or ≥300 mg/g albumin-to-creatinine ratio or the equivalent in the first morning void]), treatment with an ACE inhibitor is reasonable to slow kidney disease progression “

Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease: A Systematic Review and Retrospective Individual Participant–Level Meta-analysis of Clinical Trials: Annals of Internal Medicine: Vol 177, No 7 (acpjournals.org)

 In a patient-level meta-analysis of 18 randomized trials, researchers identified 1700 patients with stage 4 or 5 CKD to determine if initiating ACE inhibitors or ARBs affected progression to dialysis or death. follow-up ≈3 years.

Patients with CKD stage 4 or 5 (mean eGFR, 22 mL/minute/1.73 m2) who initiated ACE inhibitors or ARBs (vs. placebo or other antihypertensive agents) were  less likely to progress to dialysis (12% vs. 17% annually; number needed to treat, 20), mortality was similar (≈3% annually). 

Composite outcomes

You add multiple outcomes together… this is great because you can increase the event rate.. if you are just looking at death lots of people might now die but if you look at death and hospitalizations well then it is easier to get to your expected event rate because its much easier to be hospitalized. This make it so you can have smaller sample sizes and it wont be nearly as expensive.

The problem is all the events are given the same importance and we know they are not the same importance to patients

Death and hospitalizations NOT THE SAME

PE and death—not the same

3 questions to asked. 

Part of the endpoints of similar importance to patient's?

Due to the more or less significant endpoints occur with the same frequency?

Due to the endpoints share similar relative risk reductions?

ening, the offer of a blood-based screening test boosted CRC screening by 17.5 percentage points over usual care.

That is because

CRC screening proportions were 17.5 percentage points higher in the blood test group versus usual care (30.5% vs 13.0%; OR 2.94, 95% CI 2.34 to 3.70; p<0.001).

So more people are screened for colon cancer but who cares if they get screened if your screening test does a terrible job of telling me stage 1 or precancer lesions. A history and physical will tell you stage 3 and 4 and a lot of the time even stage 2. Blood, change in size, or frequency.

Take away bottom line is---

This sounds cool. This sound awesome. This sounds like it would be great for pateints that don’t want to do other forms of coloncancer screening which I do talk about on episode 237. HOWEVER for me this is a no go, the reason I want to screen is to catch cancer early. That is one of the pillars of cancer screening. To catch it early and have something you can do with the results that will change the outcome. This does a terrible job of catching it early and if anything may give your patient a false hope or false sense of security. I understand the sex appeal of this test but this should not be used or recommended for your patients

https://pubmed.ncbi.nlm.nih.gov/38945140/

The primary outcome was a composite of myocardial infarction, revascularisation, hospitalisation for heart failure, stroke, or death from cardiovascular causes

The mean systolic blood pressure throughout the follow-up (except the first 3 months of titration) was 119·1 mm Hg (SD 11·1) in the intensive treatment group and 134·8 mm Hg (10·5) in the standard treatment group. 

 During a median of 3·4 years of follow-up, the primary outcome event occurred in 547 (9·7%) participants in the intensive treatment group and 623 (11·1%) in the standard treatment group (hazard ratio [HR] 0·88, 95% CI 0·78-0·99; p=0·028).

primarily driven by a reduction in the risks of stroke, heart failure, and death from cardiovascular causes.

Serious adverse events of syncope occurred more frequently in the intensive treatment group (24 [0·4%] of 5624) than in standard treatment group (eight [0·1%] of 5631; HR 3·00, 95% CI 1·35-6·68).  

INHALE-3, a randomized trial, 123patients with type 1 dm that compared the efficacy of an inhaled insulin regimen (Afrezza) plus degludec insulin (Tresiba®) against usual care over 17 weeks

The study's primary endpoint was a change in HbA1c levels, a critical marker of long-term blood glucose control. 

More participants using the inhaled insulin regimen experienced significant improvements in HbA1c levels compared to those on usual care.

21% of those on inhaled insulin had an HbA1c improvement of greater than 0.5%, while only 5% of those with standard care. 

21 – 5 that is an absolute difference of 16% (NNT of 6.25)

And they found a bunch of things when they went back like more people with a1c >7 reached their goal—which was not their end point they just found it and like to talk about

 inhaled insulin and degludec was not for everyone: and everyone is missing this—we know how many people had an improvement in their a1c by 0.5% but how many had a worsening???

well 26% of the patients in the inhaled insulin group had a worsening of HbA1c greater than 0.5%

compared with only 3% with standard care.

26-3== 23 100/23== 4.3 NNH

So out of 100 people that still have to give themselves insulin

This doesn’t remove insulin

But we now add inhaled insulin we should expect to see 16 people out of the 100 have a 0.5% improvement in their a1c at 4 months

And we would expect to see 23 poeople have a 0.5% worsening in their A!C

That math don’t math—people are excited about this and all I can say is maybe they are getting paid by the drug company maybe they don’t understand number needed to treat and number needed to harm but this makes no sense.

What is a quick and easy way to calculate the NNT

What is the different between Absolute and Relative risk reduction

https://heart.bmj.com/content/108/12/964

https://www.ahajournals.org/doi/10.1161/JAHA.116.003815



We have a study that says leads to increase all cause death with calcium supplements

We have a study that says calcium supplement leads to increase in coronary artery calcium

Foods that are high in calcium besides dairy include things like kale, spinach, broccoli, chia sees, collard greens…

Hard for me to believe someone with a diet of excess kale and spinach will have an increase in all cause mortality anytime soon.

It is easy for me to believe that supplements in a pill don’t fix the problems like we wish—we see this all the time with some many electrolytes and nutrients—there is a difference between taking a pill and eating a nutritious diet