🤔 What Happened In Medicine This Week?

Good evening to everyone who reads this newsletter to stay updated on the latest medical news!

And good evening to everyone else who thought, “Sure, why the hell not?” after checking your email to see if your Uber Eats delivery is on the way. We love you all equally 🫶

👋 Happy Friday. Here’s what we got:

If you want to read any previous editions of The Handover, you can on our website.

Dear Ozempic,

Oh, how I despise you…

You just won’t stop, will you? On TV. In the papers. Whispered reverently in brunch cafes and GP waiting rooms. Like you’re this…this injectable messiah who promises to melt fat, lower HbA1C and solve global warming if given enough time. What is it that you can’t do?!?!

GLP-1’s curbs drug and alcohol addiction(...okay)
Semaglutide is linked with reduced Alzheimer's risk(...dude?)
Wegovy this, Tirzeptide that. I’m sick of it. Sick of it all. 

But I’ve been digging. And beneath the headlines and hype, you’ve got a secret.

I know, I know. Last time I threatened to expose you, the evidence was a tiny bit shaky. But now, the research gods that be have bestowed upon me new evidence about your dirty little secret…

This meta-analysis and systematic review, published in Diabetes Care, looked into you to see if GLP-1RAs are associated with an increased risk of optic nerve or vision-threatening events using data from 20 randomised controlled trials 😏

Yes, these trials rounded up 82,288 participants with T2DM or cardiometabolic disease. Following them for over 2.97 years. That’s a cumulative exposure of 240,000 patient years.

The primary outcome being a composite of serious optic nerve and vision-threatening adverse events. That includes blindness, papilledema, blurred vision, visual impairment AND reduced visual acuity. 

And for the moment of truth. The results of the meta-analysis showed… 

GLP-1 RAs were not significantly associated with increased risk of optic nerve or vision-threatening events overall (OR 1.20, 95% CI 0.73–1.97).

What? How disappointing.

Drat… so it would seem eye damage isn’t your shortcoming after all. 

That won’t stop me from picking holes in the study design, though! It had its fair few limitations.

Well… who needs a meta-analysis when I’ve got the MHRA on my side. Although the absolute risk is tiny(73 cases), cases exist nonetheless. So they recommended doctors warn of visual side effects to patients prescribed GLP-1’s. If they experience such side effects, B-line straight to ophthalmology. 

I will continue my pursuit to discover your definitive Achilles heel. Then, perhaps, the world might finally remember I exist. 

You haven’t heard the last of me. 

Yours sincerely,
Forever praying on your downfall
Orlistat - The original weight loss drug.

So… your patient has ✨Major Depressive Disorder ✨

That PHQ-9 score doesn’t lie.
The HADS score confirms it.
And the paracetamol overdose last week removes any lingering doubt.

No problemo! A little CBT and an antidepressant should do the trick. 

We have a whole candy store to choose from. Sertraline or fluoxetine. Citalopram… or oohh, maybe mitarzapine😋. It’s all well and good having a shelf full of medications to pick from.
The problem, of course, is the picking.

You see, psychiatric management has a problem. 

It’s all kinda based on vibes. 

Why do we use lithium for bipolar disorder? 
What exactly is going on in the mind of one with schizophrenia? 
I don’t know. You don’t know. The psychiatrist is scratching their head too!

As a result, effective management is frustratingly inconsistent. 

Only 20–25% of patients achieve remission with the first antidepressant prescribed. Roughly half experience minimal to no improvement at all. It’s no wonder many patients eventually think to hell with this and stop taking their medication altogether.

The trial-and-error system wasn’t working. Psych has been practically begging for a better method to this medical madness. 

Enter PETRUSHKA: A (surprise surprise) AI-based prediction tool developed by the University of Oxford. This robot combines clinical evidence with patient preferences and a bunch of other data points. Slaps them all together and spits out a personalised antidepressant recommendation.

But this isn’t the first time a fancy tool with big promises has stepped foot in the wild west of psychiatry. 

But before any shiny new tool gets taken seriously, it has to face the local sheriff: a randomised clinical trial.

So the aim of this RCT, published in JAMA, was to test whether using the PETRUSHKA tool to select an antidepressant, compared with clinician-led usual care:

They recruited 520 eligible patients for the trial from 47 sites across Brazil, Canada and the UK. Mean starting scores? PHQ-9 = 16.6, HAM-D = 16.3 and GAD-7 = 11.5. 

The patients were then followed up at 4, 8 and 24 weeks, with the primary endpoint being all‑cause discontinuation of the initially prescribed antidepressant at 8 weeks (switching drug or stopping counted as discontinuation).

What did they find? 

Well… it worked!
Patients whose antidepressants were selected using the PETRUSHKA tool were significantly less likely to stop their medication within the first 8 weeks(Control discontinuation 27% vs intervention discontinuation 17%). A roughly 38% relative risk reduction

Not only that:

Even down to the drug selection, differences were apparent. Whilst the clinician favoured sertraline (52%), PETRUSHKA recommended a wider variety of meds. Mirtazapine (29%), escitalopram (28%), and vortioxetine (24%) were the top choices.

Impressively, this is the first time a mental health clinical prediction tool has been demonstrated to be effective, according to the researchers. 

Further research is needed to explore long-term outcomes and cost-effectiveness, but in this battle of doctor vs AI, AI takes the advantage.

The UKMG Medical Training (Prioritisation) Act Has Arrived

On the 5th March(yesterday), the UKMG prioritisation bill received Royal Assent. 

That means King Charles gave the bill a big, sloppy kiss of approval, turning it from a parliamentary suggestion into official law. Effective immediately!

The act changes how medical training posts in the UK are prioritised, giving preference to graduates from UK medical schools when allocating training places. Which, depending on who you ask, is either common-sense workforce planning… or the start of a much larger argument about fairness in the NHS pipeline.

If you’re a UKMG, IMG, UK citizen studying abroad, or a curious bugger, we’ve written a full explainer 👉 here

New Medication Alert 1: For My People with Migraines

In case you didn’t know, there are two new kids on the migraine care block. Their names are atogetpant and rimegepant. Approved in 2023-24, they’ve seen a massive uptake - being prescribed to over 22,000 patients in primary care.

These tablets are built different. They’re CGRP(calcitonin gene-related peptide) antagonist - TLDR: they block the chemical released during migraine attacks that causes inflammation. Patients seem to really like it.

If you're in primary care, worth knowing these exist.
DYOR 👉 NICE guidance on atogepant & rimegepant

New Medication Alert 2: For My People with Vitiligo

Better yet, there’s a new kid on the vitiligo block, too. 

NICE have blessed us with a new medication that (for the first time ever) treats the underlying cause of vitiligo. Which definitely beats giving topical steroids and hoping the pt doesn’t get Cushing's 💯

It’s called Ruxolitnib and it’s a JAK inhibitor. This interrupts the signalling cascade that mounts the autoimmune attack on those poor melanocytes. Thus allowing them to survive and re-melinate the skin. 

It’s a new hope for the over 80,000 people in the UK who suffer from the condition. Good stuff 👍

Is Tramadol Overrated?

Perhaps, according to this meta-analysis and systematic review published in the BMJ. 

Turns out one of England's most prescribed opioids barely clears the bar for meaningful pain relief. The review of 6,500+ patients found that tramadol reduces pain by 0.93 points on a 10-point scale. But the threshold for "clinically meaningful" result was 1.0 points.

So it works, sorta kinda. The real issue lies in its serious adverse events, which were twice as likely compared to placebo, and these were primarily cardiac events.

And this was supposed to be the “safe opioid”. Worthy of a full article tbh. Coming next week.

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