The problems with observation data is real—

 randomized trial, U.K. researchers identified 519 patients (mean age, 68) with mostly moderate COPD (mean forced expiratory volume in 1 second [FEV1], 50%), ≥2 exacerbations during the previous year, and no cardiovascular (CV) indications for β-blockers. 

Patients were randomized to receive the cardioselective β-blocker bisoprolol (initially 1.25 mg daily, titrated to 5 mg if tolerated) or placebo.

At 1 year, no significant differences were noted between groups in incidence of COPD exacerbations or in other important benefits or harms.

Cardioselective β-blockers remain appropriate for COPD patients who have valid cardiovascular indications for their use, but taken these two studies together suggests that COPD patients without such indications should avoid bblockers—even cardio selective beta blockers

https://jamanetwork.com/journals/jama/article-abstract/2819083

When you want to do an RCT but you realize there might be some cross contamination so instead of randomizing individuals you randomize cluters or groups

Lets say you want to do fluids--- what is better LR or NS instead of doing individuals and room you just put whole hospitals in either LR or NS

Or you want to test if mask work for some virus—you would say this city gets all the mask in the world and this city gets zero mask…you know that If you just gave some individuals in the city a mask then maybe someone who give their extra mask to their friends and you would have cross contamination meaning that that individuals in the group end up getting the intervention you are trying to test.

Cluster RCT are GREAT for logistics and trying to figure out logistically can something or does something actually work

However cluster RCT can be harder to analyze because the clusters may not always have the same exposures or the confounders might not be equal between clusters

In our mask example that we just talked about lets assume that one village or city never has a case of covid—will it doesn’t matter if they get mask or not because they are so isolated they never get a case of it. However if  you had a perfect individual RCT the number of people in that never covid village would be exactly equal.

In the IV fluid example lets assume that one hospital gives their patients on average 20L of fluid per admission while other hospital is more reasonable in their fluid management. We know the more fluid or volume overload you are the worse your outcomes. On an individual level this wouldn’t be a problem as the same number of people would be randomized to the hospital with excess fluid exposure. So for cluster RCT while you might be able to randomize the type of fluid that cluster gets you cant control for other confounders which may throw off your result, things like exposure to the amount of fluid or type of nursing care. These excess confounders balance each other out in a individual trial as ideally individuals will have everything else the same, from volume of fluid to nursing care and the only difference will be the fluid.  

1° outcome: hemostatic efficacy = which was defined as;

(A) Hematoma expansion ≤ 35% at 12h

(B) increase in NIHSS ≤ 7 at 12h

(C) No rescue therapy 3-12h

Results hemostatic efficacy: 76.7% andexanet vs 64.6% usual care    

30 day mortality: no difference

30 day Modified Rankin Score ≤3: no difference

Thrombotic events: almost x2 with andexanet 10.3% vs 5.6% - statistically significant. Most were strokes and MI - not trivial.

The question you should ask: How does effective is hemostatic efficacy as a marker for patient outcomes?? Yes, we don’t want the brain bleed to get bigger but patients don’t care if the bleed gets bigger if they still die or if they still are in a coma for the rest of their life.

We know from warfarin that increase in hematoma expansion leads to worse outcomes (https://pubmed.ncbi.nlm.nih.gov/21346218/). We don’t have clear data on this for the DOACs. HOWEVER, just because an expanding hematoma leads to a bad outcome that does not mean that giving a medication to decrease hematoma expansion leads to better survival or improvement in disability.

In fact the randomized, double-blind, placebo-controlled trial we have that gave recombinant activated factor VII for acute intracerebrall hemorrhage showed that rFVIIa significantly reduced the growth of the hematoma but failed to improve survival or functional outcome at 90 days. https://pubmed.ncbi.nlm.nih.gov/19959538/

So we have a trial that shows improvement in hematoma expansion. It shows no difference in mortality or Rankin scale and demonstrates twice the rates of thrombotic events.

Bottom line-- ANNEXA-I does not show clear evidence of clinical benefit but there is definite evidence of harm. The logical argument for hematoma expansion as an outcome is compelling but not proven for patient oriented outcomes.

In patients with atrial fibrillation (AF), how do CHA2DS2-VASc 1 subgroups compare with one another 

64 141 patients with a first AF diagnosis 

Patients were categorized as CHA2DS2-VASc 1 if they had any 1 of age 65 to 74 years, congestive heart failure (HF), hypertension, diabetes, or vascular disease 

found no large differences in ischemic stroke, transient cerebral ischemia, or systemic arterial embolism among clinical risk factor subgroups of patients with AF who did not receive anticoagulant therapy and fell into (CHA2DS2-VASc score of 1

good news if you have a chadvasc score of one it doesn’t matter which 1 made you the one you have roughly the same risk for a bad event.


https://pubmed.ncbi.nlm.nih.gov/38152890/

Bottom line

Do I think if you stop drinking alcohol in the next thirty days you are less likely to come to the hospital for a heart attack? A stroke? Pneumonia? copd exacerbations or CHF exacerbations?? The answer is no!! not in thirty days.. sure if you drag that out for months or years then yes you are at greater risk but for only 30 days of follow up realistically should be no difference in coming back to the hospital for things that are not alcohol related.

However there was still a significant improvement or decrease in alcohol related return to the hospital.

-- This is what most supporters will look at and say ‘see we should give this medication to everyone’

This get tricky because they lump together alcojol related ED visit and alcohol related readmission in their definition of alcohol related return to the hospital---- well hello!!!! You cant get readmitted if you don’t go to the ED so the real ‘return to the hospital’ is just alcohol return to the ED and by including alcohol relatated readmission with alcohol related ED visit you are just trying to artificially inflate your finding.

I know that they were just trying to artificially manipulate their finidings because as they say “””Alcohol-related ED visits did not reach statistical significance in relative terms (IRR, 0.61 [95% CI, “””

If your patient wants fda approved medications for alcohol use disorder then give it to them!! We shouldn’t without these medications but if you are giving it to them thinking it is some magical pill with a nnt of 4 to prevent death and the patient returning to the hospital then you will be sad!

https://pubmed.ncbi.nlm.nih.gov/38551564/

In a retrospective cohort study of Veterans Affairs (VA) nursing home residents during 2006 to 2019, researchers identified 13,000 residents who initiated a first or additional antihypertensive medication and 52,000 propensity score–matched controls (mean age, 78). The primary outcome was a composite of pelvic fracture, surgically treated hip fracture, and fractures of the humerus, radius, and ulna that required intervention within 30 days of starting antihypertensive medication.

Initiating medication also was associated with elevated risks for falls that required emergency room visits or hospitalizations (aHR, 1.8) and elevated risks of syncope (aHR, 1.7).

Fracture risks were elevated, compared with controls, in initiators with a  systolic blood pressure ≥140 mm Hg (aHR, 3.1), diastolic blood pressure ≥80 mm Hg (aHR, 4.4), and no recent antihypertensive medication use (aHR, 4.8).

SGLT-2 inhibitors have not been evaluated in patients with stage 5 CKD (CKD 5; eGFR, ≤15 mL/minute/1.73 m2). Investigators in Taiwan retrospectively assessed 5 years of outcome data for nearly 48,000 patients with type 2 diabetes and CKD 5 — half of patients had newly initiated SGLT-2 inhibitors, and half were not taking these drugs.

compared with no SGLT2i use, SGLT2i use was associated with lower risks for dialysis (hazard ratio [HR], 0.34 [95% CI, 0.27 to 0.43]), hospitalization for heart failure (HR, 0.80 [CI, 0.73 to 0.86]), AMI (HR, 0.61 [CI, 0.52 to 0.73]), DKA (HR, 0.78 [CI, 0.71 to 0.85]), and AKI (HR, 0.80 [CI, 0.70 to 0.90]), but there was no difference in the risk for all-cause mortality (HR, 1.11 [CI, 0.99 to 1.24]).    So almost higher rates of mortality if you are betting man with 95% confidence

https://www.acpjournals.org/doi/10.7326/M23-1874

• glucagon-like peptide-1 (GLP-1) receptor agonists can delay gastric emptying, the American Society of Anesthesiologists (ASA) say For patients on daily dosing consider holding GLP-1 agonists on the day of the procedure/surgery. For patients on weekly dosing consider holding GLP-1 agonists a week prior to the procedure/surgery.

 Now, the American Gastroenterological Association (AGA) has published a “Rapid Clinical Practice Update,”

note that evidence is insufficient to make strong recommendations about continuing or withholding GLP-1 agonists prior to endoscopy. The AGA suggests an individualized approach: GLP-1 agonists “could be withheld” in patients who take the drugs solely for obesity, but the authors worry that omitting a dose in a patient with diabetes might confer more risk than benefit. 

They say the scope should go on as long as the pt has been on an 8 hour solid fast and a 2 hour liquid fast



https://www.sciencedirect.com/science/article/pii/S1542356523008698?via%3Dihub

But now we have RCT data—

278 adults with moderate CAP who were hospitalized (but not in intensive care) to receive either a β-lactam antimicrobial plus clarithromycin or a β-lactam alone. (all patients met sepsis or severe sepsis criteria)

composite primary endpoint of improved respiratory symptoms and improved SOFA score by day 4 occurred in significantly more patients in the dual-antibiotic group (68% vs. 38%; number needed to treat, ≈3).

Individuals on dual antibiotics also were significantly less likely to develop sepsis (13% vs. 24%; NNT, 10), significantly more likely to be discharged and alive at 3 months (79% vs. 62%; NNT, 6), and less likely to be readmitted within 90 days (8% vs. 15%; NNT, 14; P=0.09)


https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S2213260023004125?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2213260023004125%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.jwatch.org%2F