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Apparently, Einstein once said: “The definition of insanity is doing the same thing over and over, expecting a different result”
….Welcome back, you crazy animal.
👋 Happy Friday. Here’s what we got:
💆 Homocidal Antiviral Wishes for a Simple Life
🧙 One Pill To Rule Them All: Stroke and The Trident Trial
🧠 QuickBits: Other Top Stories of The Week
If you want to read any previous editions of The Handover, you can on our website.
RESEARCH UPDATE
💆 Homocidal Antiviral Wishes For a Simple Life
Expressing anxiety over pressure to kill the pandemic virus, a famous antiviral confides in local reports. The medication said it just wishes to be a regular pill instead.
Credit: Getty Images
Paxlovid(real name Nirmatrelivr/Ritonavir) wasn’t given much of a choice.
It was brought into the world for one purpose: Kill COVID.
Studies hailed it as a medical messiah. It was approved for the masses in December 2021. Saving millions of human lives, but killing trillions of viral ones along the way…
But now, 5 years on(roughly 42 in pill years), things have… slowed down.
Now sporting a slightly crumpled VLM(Viral Lives Matter) tee, Paxlovid appears to be going through something of a midlife crisis.
“Maintaining appearances is exhausting,” it told reporters. “I was born to kill. I get that. But times have changed.”
According to recent large-scale trials, the antiviral may no longer significantly reduce hospitalisation or death in vaccinated, high-risk patients. Raising uncomfortable questions about its place in the world.
In an effort to rediscover its purpose, Paxlovid returned home, to where it all began: the randomised control trial.
Published in the NEJM, two RCTs were conducted to see if Paxlovid was still useful for the unfortunate few to get reinfected in this post-COVID society.
The PANORAMIC trial: Conducted in the UK. Recruiting 3516 patients.
The CanTreatCovid trial: Conducted in Canada. Recruiting 716 patients.
The trial design for both studies was the same. They selected over 50’s who tested positive for severe COVID infection and were unwell for 5 days or less. Most participants (over 98%) were vaccinated.
Then randomised them 1:1 to either:
Paxlovid(Oral Nirmatrelvir 300mg/Ritonavir 100mg) + usual care(i.e. local guidelines)
Usual care alone.
They monitored participants for 28 days, with the primary endpoint being non-elective hospital admissions or death from any cause in that time period.
Paxlovid anxiously awaited the findings…
When it opened the results, a wry smile broke across its face.
The study found that the drug did not significantly reduce the risk of severe outcomes in this population.
PANORAMIC: No significant benefit for hospitalisation or death, with rates essentially equal between groups(0.8% vs 0.7%; adjusted OR, 1.18)
CanTreatCOVID: No statistically significant difference in severe outcomes (0.6% vs 1.2%), though recruitment was stopped early due to slow enrollment.
Adverse Events & Deaths: Zero deaths were reported in either trial; however, 0.6% to 1.3% of treated participants had serious adverse events. Many stopped the drug due to bad taste or nausea.
Viral Load: The drug successfully hit its target by reducing viral loads by 87% at day 5 compared to usual care.
Study authors concluded early treatment with Paxlovid for Covid-19 did not reduce the incidence of hospitalisation or death among vaccinated higher-risk participants
At press time, the pill confirmed it is “exploring new opportunities,” including retirement, working on its handicap, and possibly opening a reformer Pilates studio.
“I just want something low-pressure y’know,” it added. “Maybe enter the supplement space? The community of useless pills in Holland and Barrett seems to have it quite easy”
POWERED BY MEDWISE.AI
🥳 ChatGPT for Clinicians is Finally Here
My loyal servant of the National Health Service.
ChatGPT for actual clinical use is here… yipee
But wait…
Did you catch that?
Free for U.S. Clinicians.
American guidelines as its source? You don’t want that. You want that good stuff. Y’know, the stuff that actually applies to practice here in the UK!
You needn’t restrict yourself to trawling through guidelines or asking your reg for help…
Instead, you can ask Medwise.ai
Imagine if ChatGPT entered a polyamorous relationship with NICE guidelines, Society consensus statements, and Royal College publications.
Then, 9 months later, popped out a beautiful AI baby trained on everything you need in your practice.
You type a question and bam:
Instant Evidence-based answers
Accurate. Sharp. Clinically on point.
It’s used by over 3,000 NHS organisations.
It’s completely free.
If you’re still not convinced, you get free CPD points just for asking questions too!
Start looking dangerously competent on the wards and use Medwise.ai today.
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RESEARCH UPDATE
💍 The One Pill To Rule Them All: Stroke and The Trident Trial
In the long war waged against hypertension-induced strokes, our weapons have been… underwhelming.
Lifestyle advice gets ignored.
Dossette boxes start to resemble a pack of Smarties.
Sphygs are inflated just once a year. (If only we could say the same about our wages)
All the while, BP slowly creeps back up. And with it, the risk of a serious brain bleed🩸
But what if we took a leaf out of Tolkien's book and crafted one pill to rule them all?
The TRIDENT trial, published in NEJM this week, did just that.
This new drug fellowship comprises 3 hypertension classics:
ARB + CCB + Thiazide-like diuretic → all forged into a single once-daily tablet💊
I know what you’re thinking…
It’s too simple to work, right?🧌
But just Gimli a minute to explain the trial, it’s actually pretty cool stuff.
1,670 patients with prior intracerebral haemorrhage (and systolic BP 130-160 mmHg) were randomised to either:
The One Pill™ (telmisartan 20mg + amlodipine 2.5mg + indapamide 1.25mg OD), or
Matching placebo
Participants were then followed up every 6 months for up to 6 years.
The main outcome of interest? Recurrent stroke rate.
And here’s the verdict:
Recurrent stroke occurred in 4.6% (triple pill) vs 7.4% (placebo)
→ That’s a 39% relative risk reduction (HR 0.61, 95% CI 0.41-0.92, p=0.02)
Not just that, BP control at 6 months (i.e., systolic <130 mmHg) was achieved in 49.9% (triple pill) vs 26.4% (placebo) - nearly double!
AND Major cardiovascular events were reduced (6.6% vs 9.8%; HR 0.67, p=0.04).
Cumulative Incidence of First Recurrent Stroke (Primary Outcome)
The promise of success from The One Pill™ is strong.
After all, TRIDENT was a multinational, double-blind, placebo-controlled RCT across 12 countries, with demographics reflecting global ICH (intracerebral haemorrhage) populations.
But let's not get too precious about it yet:
Not everyone made it into the fellowship - a ‘run-in phase’ filtered out around a quarter of patients who couldn’t tolerate the pill upfront.
And even for those who did, early rises in creatinine meant not everyone could continue
66.7% of patients were from the same country, limiting generalisability
And yet, the allure of the One Pill as a simpler way for both patients and docs to keep that BP down is undeniable.
So in the battle for Middle- Earth of-the-range-BP post-stroke, the future calls for more than the boring old NICE flowchart.
It’s time for a 3-in-1 nuke instead💊💥
QUICKBIT: OTHER NEWS YOU SHOULD KNOW
Yeah mum, you heard me.
Turns out gaming was good for my career after all😏
Published in JAMA, a study led by Dr Deepika Mohan (EM doctor at the University of Pittsburgh*) put 800 ED doctors based in triage centres to the test.
*Dr Mohan? Pittsburgh? I’m in for my girl Samira🫡 (ifydk go watch the Pitt)
The challenge? A night shift simulator🧟
It wasn’t quite Insidious levels of horror, but it did mimic your average hellish night shift. Complete with nasty injuries, frail geris and a shortage of A&E custard creams.
Docs played for a few hours each month, and were then assessed alongside a control group over the following year, involving decision-making on >41,000 patients.
And guess what? The gamer docs performed far better at triaging patients compared to the ones AFK(away from keyboard)
The takeaway? Ditch the Oxford Handbook and grab a controller instead.
In a not-so-pro-gamer move from UK health company Biobank, datasets containing de-identified information about over 500,000 volunteers were found for sale on the Chinese website Alibaba.
Although names and direct identifiers were omitted, the records included sensitive information such as age, sex, genetic data, medical measurements and socioeconomic status. Yeesh.
Although this theoretically means your TikTok fyp could get even better when it comes to knowing your taste, I promise it’s actually a bad thing.
Cross-referencing data points can re-identify individuals faster than you can say privacy violation, and once your data is out in the wild, there's no ctrl+Z for it.
Alibaba removed the listings, and an investigation is underway.
UK Biobank are also presumably currently circulating some rather pass agg internal emails.😬
🧑⚖️Bills, Bills, Bills
Not the smash hit by Destiny’s Child, but the legal kind that determines if you’ll go to jail or not.
Tobacco and Vape Bill Passed: A bill to prevent people born after 2008 from legally buying Tobacco has been passed and awaits royal ascent. A good thing, sure. But not sure why the bill includes vapes, as there isn’t much in the bill addressing them.
Assisted Dying Bill Failed: The Terminally Ill Adults (End of Life) Bill was proposed 18 months ago. Today, having run out of time in the House of Lords, it will not go ahead.
Big Pharma just can't help themselves, can they?
Eli Lilly - daddy to GLP/GIP agonist Tirzeptide - has green-lit animal studies on a QUINTUPLE Agonsit. That's right, five receptor agonists!
The 5 receptors will be GLP-1, GIP, Glucagon, Amylin and Calcitoin. How greedy.
When compared to the ultrapotent Retratrutide(triple agonist), it allegedly has it beat. Full results coming out at the American Diabetes Association conference later this year
We try to be funny, but this Onion-style satirical tweet has us beat 🏳️
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