👋 Happy Friday. The sun is shining. Weather is sweet 😎. Unless of course you happen to be in a hopsital right now. In which case, I’m sorry. Nothing like melting under fluorescent lights, slowly succumbing to death by lack of aircon.

Here’s what we’ve got:

• 📩 A Letter To Ozempic: Medical Messiah or Macular Menace?

• ♋ The ZODIAC Trial: Gravity vs Stroke Protocals

• 🦠 Cervical Screening Every 5 Years: Fewer Smears, Same Safety

• #TheMoreYouKnow: Other Top Stories of The Week

RESEARCH UPDATES

A Hate Letter To Ozempic: You Ruined Me

Dear Ozempic,
You and I have a problem…

Everywhere I go, it’s you. On TV. In magazines. Whispered reverently in brunch cafes and dermatology waiting rooms. Like you’re this…this injectable messiah who promises to melt fat, lower HbA1C and solve global warming if given enough time. 

Semaglutide is linked with reduced cancer risk(...okay)
Semaglutide is linked with reduced Alzheimer's risk(...how?)
Wegovy this, Ozempic 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.
Something you’d rather not have seen. (Pun intended. Cue evil laugh)

This retrospective cohort study, published in JAMA Ophthalmology aimed to see if prolonged GLP-1 RA use(>= 6 months) increased the incidence of neovascular age-related macular degeneration(nAMD) risk in patients with older patients with diabetes compared to non-users. 

The hypothesis is that the rapid reduction in blood glucose levels by GLP-1 RAs could lead to a hypoxic state in the retina. This could lead to angiogenesis, thus visual symptoms like floaters, flashes and vision loss.

They recruited 139,002 patients from Ontario, Canada. Aged >= 66 with diabetes, and excluding those with prior nAMD. 46,334 patients were taking GLP-1 RAs and the remainder were unexposed. The primary outcome measure were:

1. The incidence of nAMD - as measured by anti-VEGF injection treatment

2. The time to event(anti-VEGF treatment) within the 3 year follow up period.

What did they find:

• Incidence of nAMD: The incidence of nAMD in the exposed cohort was 0.2%(93 patients) compared to control (0.1%, 88 patients)

• Hazard Ratio: These results meant that even after socio demographic info was taken into account, the risk of developing nAMD was over twice as high. With an Adjusted HR of 2.21(95% CI, 1.65-2.96).

• Exposure Duration: Longer exposure spelt bad news too, For exposure >30 months, the adjusted HR was 3.62(95% CI 2.56-5.13). 

Limitations you say? Sure, an absolute risk of 0.2%(93 out of 46,334) is miniscule. Sure, the study didn’t account for certain variables such as smoking status and sun exposure due to limited data availability.

But that won’t stop me taking this information straight to the BBC. Or even better - Steven Bartletts Diary of a CEO! A healthcare resource more trusty than the BNF.

You will be exposed. Then, people might finally remember I exist.

Yours Sincerely,
Wishing you the worst
Orlistat - The original weight loss drug.

RESEARCH UPDATE

The ZODIAC Trial: Gravity vs Stroke Protocals

When you think of the word “Zodiac”. What goes through your mind? Star signs? Greek Gods? RDJ and Jake Gyellenhall staring at clues for 2.5 hours?(A timeless classic by the way)

How about stroke management? You know… head positioning, thrombectomy and a clinical trial so riveting they named it ZODIAC. Just me? Alright then.

But according to this study published in JAMA neurology, the way a patient's head is tilted could be the supernatural force standing between recovery and rapid decline in stroke management. 

The study asked a simple question? In patients with large vessel occlusion(LVO) stroke, who are waiting for thrombectomy. Is it better to lie them flat at 0°, or tilt them up to 30°?

Seems like a pedantic little tweak to make, especially for someone who’ll likely die without intervention. But the theory checks out: Gravity helps blood flow to the penumbria(the part of the brain that’s salvageable by thrombectomy) when the head of the bed is at 0°. And if you buy a little more time before shipping them off the theatre, that's a huge win.

A prospective, randomised control trial was done across several hospitals in the States between 2018 and 2023. They recruited patients over 18 with CT-defined LVOs, with a viable penumbria.

It was a tiny RCT. Just 92 patients were randomised 1:1 to either the 0°(45) or 30°(47) groups. Their position was monitored every 10 minutes until being pushed into the cath lab. And the primary outcome measure was worsening of 2 or more National Institute of Health Stroke Scale(NIHSS) points prior to thrombectomy. 

What did they find out?

• Clinical Worsening: Only 1 patient in the 0° head position group experienced a worsening of >= 2 NIHSS points compared to 26 patients in the 30° head position group. This led to a Hazard Ratio of a whopping 24.40(95% CI, 4.65-254.37). 

• Severe Neurological Deterioration: Defined as worsening of NIHSS score of >= 4 points, 1 patient in the 0° group experienced this compared to the 20 in the 30° group

• All-Cause Deaths at 3 months: 2 patients(4.4%) in the 0° group died, compared to 10 patients (21.7%) in the 30° group

The results were so stark they stopped the study early due to clear efficacy(hence the small sample size). This means the generalisability of these results are far from being mandated in practice. But still an interesting minor adjustment to improve outcomes 🤝 

In other news, there is a new thrombectomy technique in the woodworks. You compact the clot like rubbish in a landfill then take it out with ease. Check out a video demonstration here

IN PARTNERSHIP WITH FIRST GEN DOCTORS

You’re The First of Your Kind: Join Your Community

Are you the first in your family to pursue Medicine?
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FirstGenDoctors (FGD) is an international network supporting First Gen applicants, medical students, and doctors at every stage of the journey. Our 1,000+ member Discord is a space for connection, shared experience, and real support. 🤝

Through our Discord, newsletter, and events, we offer:
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We’re growing fast and have big plans - so this is the perfect time to get involved

Connect. Learn. Belong. Let's lift as we climb.

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NHS NEWS

Cervical Screening Every 5 Years: Fewer Smears, Same Safety

Finally there’s a pretty big change to the national screen programme for cervical cancer, set to take effect in July this year. 

Instead of a screening test every 3 years, NHSE have extended the routine screen to 5 years. Women all over the UK rejoice 🥳. This means three less trips to gynaecology in a lifetime. Three insertions of that funny speculum device. Three less times you have to cross your fingers hoping for an all clear from the staff. 

These changes come as a result of an observational study conducted by King College which found a 5-yearly screen to be just as safe. No difference in the number of cancers detected or confirmed between the two. Additionally, with the HPV vaccine coming into effect in 2008 cervical cancer rates have dropped by 90% here in England. 

So that means the programme is simply 5-yearly check ups from the age of 25-65. Much easier to remember for Finals 😉. 

• If you do happen to be HPV +ve with no cell changes, you’ll be asked to come back in 1 year.

• If you’re HPV+ve with cell changes you’ll be referred to colposcopy. Just like before. 

The NHS will be hoping this reduced frequency will encourage more women to come for their visits. The Latest Cervical Screening Programme report showed 68.8% actually attended when invited for screening. 

The NHS App is now pretty good, which means you can book your appointments through that. But over in the States, something more interesting is brewing. Mailed self-collection HPV sampling 

In a randomised control trial conducted by JAMA Internal Medicine, women who did the self assessment were over 2 times more likely to participate in screening compared to just telephone invites alone.

OTHER NEWS YOU SHOULD KNOW

• NICE Guideline Updates to chronic heart failure

• Progresterone-only pill and links to brain tumour

• Artificial Blood: Sci-Fi Breakthrough or False Hope?

• Some NHS Positivity: Lowest Backlog in two years

• GP Partnership On The Decline: RCGP urges for action

Handover Over 🫡 

If you liked it, tell your mates (forward this email to them if you’d be so kind)
If you hated it, tell your enemies.

Also I’d like to know a bit about you. Where are you on your medical journey? Are you a doctor at all?

Let me know in the poll below 👇️