u/Moimoihobo101

CURB-65.
It's beautifully simple.
Five letters. Five criteria.

In a career full of dumb, convoluted acronyms and funny-sounding drugs, CURB-65 is a breath of fresh air. It’s the guideline, AND its letters spell out its criteria. 

Confusion
Urea >7 
Resp Rate > 30
Blood Pressure <90/65 mmHg
Age > 65

It’s oh, so simple. But it hasn’t always been…

The year is 2002. But to your respiratory consultant, it is 1 BC. Before CURB. 

Patients with pneumonia were arriving in A&E every day with the same question hanging over them. How bad is this infection anyway? 

In the years before CURB, we had two main tools to use. 

1. The Pneumonia Severity Index(PSI): A thorough scoring criterion… but it had 20 different variables to plug into to get an answer. Calculating it felt like filling in your tax return before prescribing antibiotics.
2. The modified British Thoracic Society rule (mBTS): It had just 4 criteria. Confusion, Resp rate, Diastolic BP, Urea > 7. But it was too black and white. Score >2 = severe, Score <2 = not severe. A very blunt instrument.

So, an opportunity emerged.
Hope for the Goldilocks score.
Granular enough to guide the full range of decisions (home, ward or ICU). But without an onboarding process longer than opening a new bank account.

In 2003, the landmark study was published in Thorax, A BMJ journal 

https://preview.redd.it/gejegq8lcith1.png?width=1780&format=png&auto=webp&s=bb9e1578fc28f9cb6d5d4bd59a7953608a050bc1

The primary aim was simple: Develop a better severity score. Make it practical. Make it sort patients based on mortality risk. Make it work both in hospital and, if possible, community settings. 

The hunt for the Goldiocks score begins…

The researchers combined data from three prospective CAP studies in the UK, New Zealand and the Netherlands. Rounding up to a total of 1,068 patients.

Things get a little complex here.
To come up with the Goldilocks score, they first needed to find the relevant criteria. Now comes the detective work.

The researchers threw dozens of variables into a mathematical model and did some statistical wizardry to find out: Which of them actually predicted death?

It just so happens the letters that make up CURB were the biggest needle movers in regards to mortality.

• They excluded variables like serum albumin – whilst independently associated with mortality, it’s not readily available at the time of initial assessment. So they binned it.
• They later on included age, as it was just so damn easy to get a hold of.

With that, CURB-65 was born. `
It was made in such a way that each factor was equally weighted. It didn’t matter which letter was ticked. As you went from 0 => 1 => 2 => 3 and beyond, your risk of death increased a proportional amount. 

So the acronym sounds good, n’ all, but does it accurately predict severity?

That's where the validation step comes in. Of the 1,086 patients included in the study:

• 80% were used to build CURB-65 (derivation group)
• 20% were used to test if CURB-65 actually worked (validation group)

https://preview.redd.it/919l1p8lcith1.png?width=1946&format=png&auto=webp&s=ccdc2555ab6abd8a18b6d1a54d480bb75a3244c0

The validation group supported the trend seen in the derivation group. Mortality rose as CURB-65 increased. 

• Score 0: 0 deaths out of 55 patients.
• Score 1: 5 deaths out of 86 patients, about 5.8%.
• Score 2: 8 deaths out of 46 patients, about 17.4%.
• Score 3: 6 deaths out of 23 patients, about 26%.
• Score 4: 1 death out of 4 patients, about 25%.
• Score 5: 1 death out of 3 patients, about 33.3%

Now, compared to the old tools:

• CURB vs PSI: A systematic review found no significant difference in overall mortality prediction between PSI and CURB-65.
• CURB vs mBTS: Roughly a coin flip in raw accuracy; sensitivity and specificity were near identical between the two in the analysis. But CURB wins as it splits results into more buckets and tells you what to do about it. Home, ward or ICU.

Shortly afterwards, CURB-65 spread.
Through guidelines. To hospitals around the UK. Then around the world. 

And now, more than 20 years later, it’s still one of the first scores doctors learn and one of the few scores that actually sticks.  

One jab for GLP-1, back when it all began;
A second with GIP added on, big pharma’s grander plan.
A third now with glucagon, to burn through the fat stores;
Exhaustion for readers, who can’t take one paper more.

One drug to beat them all, three receptors to target;
One drug to shrink them all, and tear up the drug market.

In the land of Indianapolis, in the labs of Eli Lilly, scientists forged in secret a master drug, to rule over all.
Into this molecule, they poured their capital, their clinical trials, and their will to dominate all of metabolic medicine.
Their new elixir binds tightly not only to GLP-1 and GIP receptors, but invokes the ancient fires of glucagon, for a threefold conquest of obesity. 

Soon it will surely claim a more catchy name, but for now, it is known only as Retatrutide

One by one, the complications of obesity fell to the power of the triple agonist 💪

So confident were they in the power of their creation that the scientists presumptuously named their key study TRIUMPH-1.

Published in the sacred scrolls of The New England Journal of Medicine, this phase 3 trial gathered a great host of 2,339 adults with obesity, but without diabetes.

Over 80 weeks, the subjects were randomly assigned to once-weekly injections of retatrutide (at doses of 4 mg, 9 mg, or 12 mg) OR a phantom placebo 👻

And the final reckoning? 

Retatrutide resulted in a mean weight reduction of 17.6% (4mg), 23.7% (9mg), and 25.0% (12mg) under intention-to-treat analysis, compared to just 3.9% with placebo (P < 0.001).

• At 104 weeks, a subset of patients achieved a 29.9% reduction at a 12mg dose.
• In fact, one-fifth of those on the maximum dose achieved over 35% weight loss!🤸

More weight loss than Gollum after finding the ring

Not content with mere weight reduction, the trial also took aim at other obesity related issues.

• 574 weary travellers with knee OA saw their pain scores improve by up to 3.6 points, vs. 1.9 with placebo (P < 0.001).
• 243 patients suffering from obstructive sleep apnoea had a reduction of 31.7 apnoeic events per hour vs. 9.9 on placebo (P < 0.001).
• For people who entered the trial with prediabetes, a massive 90% achieved complete normoglycemia vs. 54.2% on placebo.
• And across all arms, there were drops in blood pressure, triglycerides, and non-HDL cholesterol.

 

But all quests have their setbacks, with TRIUMPH-1 being no exception:

• GI upset was the most common side effect: patients reported nausea (up to 42.4%), diarrhoea (up to 34.1%), vomiting (up to 25.3%), and constipation (up to 26.1%)
• Thus, the drug discontinuation rates were high, peaking at 11.2% at the maximum dose of 12 mg.
• A high proportion of the placebo group understandably weren’t too pleased with their tic tac and ditched the trial to quest elsewhere.

Notably, the drug was pitted only against a silent placebo, avoiding a clash of arms with the great titans of semaglutide and tirzepatide.

But despite this, we may now truly have found a weight loss drug that bows to no one. 👑

One drug to beat them all, three receptors to target;
One drug to shrink them all, and tear up the drug market.

If you enjoyed reading this and want to get smarter on the latest medical research Join 16,000 Clinicians reading The Handover here 👉 Read The Handover

When it comes to matters of the heart, cardiologists are the resident experts. 
Equally…
When it comes to matters of the heart, cardiologists are the resident dummies. 

You see, CCTing as a heart doctor DOES NOT make you a love doctor, unfortunately.

Our consultant, fresh off his fourth unsuccessful marriage, was inconsolable. At ESC Congress 2026*(Comic-Con for Cardiology)*, a study was released that hit a little too close to home: 

SINGLE-AF. 

\"I should have known she was in it for the money\", said Dr Dahl, after being left by his 4th wife - who, coincidentally, is the same age as his last born daughter.

Let me ask you this. When do we anticoagulate a patient with atrial fibrillation? 
Easy - when that CHA2DS2-VASc score is > 1 for the XY and > 2 for the XX.

Next question… why? 

…

Don’t give me the smart arse “bEcaUse NICE sAid sO” answer 😑

Yes, this is another one of those things in medicine. It is the way it is, largely because no one questioned it. According to the study authors, guidelines have been formulated from a hodgepodge of conflicting observational data… which is crazyy for such a ubiquitous guideline. 

So for the first time, researchers decided to put it to the test with a randomised controlled trial. Think of it like a guideline audit of sorts. Legit checking guidance.

This RCT, published in the NEJM, recruited 1,803 patients across South Korea with AF + a  CHA2DS2-VASc score of 1(men) or 2(women). 

Patients were randomised 1:1 to receive either DOAC therapy OR no anticoagulation at all. Then they were scrupulously monitored for 24 months to see which participants had either a stroke, systemic embolism, major bleed or died from CVD events. 

Extra points:

• This was an open-label trial - so patients and prescribers knew what they were or were not given. 
• It was adjudicator-masked - so the independent committee deciding whether suspected events actually met the definitions for stroke, major bleeding, etc., didn’t know which treatment group the patient was in
• DOAC given was either apixaban (5mg BD) or rivaroxaban (20mg OD).

And after two years, the results were in: Thankfully, for the millions of people already on therapy, DOACs remain on top.

• Primary Endpoint Results: Of the 1,803 patients included, only 17 total events were recorded. DOAC group: 4/902 (0.5%) vs no anticoagulation: 13/901 (1.5%). A difference of −1.0% (95% CI −2.0 to −0.1), HR 0.31 (95% CI 0.10–0.94), P=0.03.
• Stroke Events Carried: As I said, there were only 17 total events. 13 of them were stroke events. 3 (0.3%) vs 10 (1.1%).
• No Deaths: There were no deaths from a CVD cause in either group, despite being part of the primary composite.
• No Bleeding Difference: Major bleeding: 3 (0.3%) vs 4 (0.5%), HR 0.75 (95% CI 0.17–3.35).

 

https://preview.redd.it/m5hp6q6or2rh1.png?width=2020&format=png&auto=webp&s=395f4e9fc3ab1803b06cd10bcbcf38cdfecb15af

Ultimately, this study confirmed what we already knew. DOACs + intermediate-risk AF is a match made in heaven. Now we finally have an RCT to back it. 

At the end of the day, the heart wants what the heart wants.
When in AF, getting in bed with a DOAC remains a pretty good idea.

If you enjoyed reading this and want a journal club(that’s actually entertaining) Join 16,000 Clinicians reading The Handover

In the beginning there was nothing. 
Shortly after the beginning, there were rats.
Much detested, but common household rodents.
Infiltrating homes, chewing wires and cooking Michelin-star dishes when animated by Pixar. 

Exterminators and modern science decided the best way to rid ourselves of these rodents would be to poison them. And by poison, I mean have them eat something that led to severe internal bleeding that would cause them to die. 

The compound, discovered by the Wisconsin Alumni Research Foundation, was appropriately named Warf-arin.

In 1954, just 6 years after it was approved for use as rat poison, some bright spark decided it would be fit for human consumption. Its clot-stopping powers made it the ideal candidate for stopping blood clots, pulmonary embolism and strokes. 

And thus began the Age of Warfarin. For a good 50 years, Warfarin was goated. It was top of the food chain – largely because there was literally no other option.
bIt prevented 64% of strokes in AF patients.

Whilst Warfarin revelled in its glory, a conspiracy was starting to brew…

Unfortunately, decades at the top make you complacent. Warfarin was needy. Regular INR checks, bleeding risks and a love-hate relationship with leafy greens [finish here]

Scientists believed they could outdo this boomer-made drug. Come up with something newer, sexier, safer. A class of drugs that prevent clots without the incessant monitoring. 

They were called DOAC’s. Direct Oral AntiCoagulants. 

The plan was simple. Instead of Warfarin's scattergun approach(it blocks multiple clotting factors at once, go after just one clotting factor. Directly. Precisely. Sniper instead of a shotgun. 

In 2009, the bleeding wars began…

First up was The RE-LY: Dabigatran vs Warfarin

https://preview.redd.it/32m54oxunokh1.png?width=1683&format=png&auto=webp&s=d3b27667adac941b5a73e52e1ed3dbe38ec6bdc9

This classic RCT pitted the first DOAC against warfarin, in a non-inferiority trial.

Method: 18,113 patients with atrial fibrillation were randomised either to a warfarin or dabigatran group and followed for 2 years. 

Primary Endpoint: What percentage ended up having a stroke or systemic embolism. 

Result? Dabigatran wins. 

1. Stroke/Embolism Events: 1.11%/year with dabigatran 150mg vs 1.69%/year with warfarin (RR 0.66, 95% CI 0.53–0.82, P<0.001).
2. Major Bleeding Events: 2.71%/year with dabigatran 110mg vs 3.36%/year with warfarin.

Then the floodgates opened…

2011 came with a double whammy. ROCKET AF(Rivaroxaban vs Warfarin) and ARISTOTLE (Apixaban vs Warfarin).

Both trials set up just like RE-LY

ROCKET AF Results: 

• Stroke/Embolism Events: 1.7%/year with rivaroxaban vs 2.2%/year with warfarin (HR 0.79, 95% CI 0.66–0.96, P<0.001 for noninferiority)
• Intracranial haemorrhage: 0.5% vs 0.7%/year (P=0.02), fatal bleeding 0.2% vs 0.5% (P=0.003), both lower with rivaroxaban

ARISTOTLE Results:

• Stroke/Embolism: 1.27%/year with apixaban vs 1.60%/year with warfarin (HR 0.79, P=0.01 for superiority). Apixaban won
• Major bleeding: 2.13%/year vs 3.09%/year (HR 0.69, P<0.001). Apixaban won.

 

Then, in 2013, even Edoxaban beat out Warfarin in stroke risk and bleeding risk reduction.

https://preview.redd.it/h9ew2vo4ookh1.png?width=604&format=png&auto=webp&s=f0232d5ca5c944e29f2727f33cb5dfc056fe399b

In the end, Warfarin’s time was up.

It had been outwitted, outclassed and shortly after  replaced by the DOAC’s as firstline for AF, DVT’s and PE’s.

However…
Even a deposed king has one final card to play…

DOAC reversal - Idarucizumad: fifteen grand. Warfarin reversal - Vit K: about a tenner.

And in a skin NHS, cheap has a funny way of coming back in fashion.

If you enjoyed reading this and want a journal club(that’s actually entertaining) Join 16,000 Clinicians reading The Handover

At its core, surgery is the art of inflicting well-meaning trauma in a (moderately) controlled environment.

We slice and dice, hoping the anaesthetist isn’t too distracted and the blood (mostly) stays inside the patient.

But while the most obvious injury in cardiac surgery is the giant saw wound through the sternum, the poor kidneys often take collateral damage in the process.

In fact, post-op acute kidney injury strikes up to 50% of patients undergoing elective cardiac operations.
Each of these events increases mortality and the risk of developing long-term renal failure.

Historically, the typical management plan consisted of prescribing a (very evidence-based) deluge of IV fluid, the crossing of fingers, and hoping the creatinine behaves.

But all of that is about to change…

Because some drugs just can’t help but stay out of the headlines.

Originally designed to lower blood glucose in type 2 diabetes, Dapagliflozin has evolved into the Swiss Army knife of renal and cardiac protection.

It works by blocking sodium and glucose reabsorption in the proximal tubule, lowering glomerular pressure, and keeping the nephron cosy.

Dapper-gliflozin

Which brings us to the all-important research: the MERCURI-2 trial, published in JAMA.
They randomised 784 adult patients having elective cardiac surgery across the Netherlands to receive either dapagliflozin or a sneaky placebo.

The dosing schedule was simple: one 10mg tablet a day, for four days, starting the afternoon before surgery.
Renal impairment post-surgery was then measured using both creatinine and urine output.

So how did our favourite SGLT-2 inhibitor fare against the surgeons?

• Dapagliflozin slashed the incidence of AKI within the first 7 days down to 28%, compared to 52% in the placebo group (P < 0.001).
• This was achieved across different severities of injury, with stage 1 AKIs dropping to 23% from 40%, and stage 2 dropping to 4.1% from 13% in the placebo group.
• However, secondary outcomes like major cardiac events, length of stay, or new arrhythmias showed no significant difference between groups.

Dapa-graph-lozin

Of course, like all studies, MERCURI-2 had its quirks and imperfections. 

The studied population was 97% white and 76% male, so it's unclear if we can generalise beyond this.
The improvement seen from the drug was predominantly in urine output, not in serum creatinine.
And patients already taking SGLT-2 inhibitors were excluded from the trial (which at this point is quite a large number of at-risk people).

But if four little tablets can make such a massive difference, with very little risk, it’s hard to see the downside.
Because our retroperitoneal VIPs are under constant threat, and deserve a protection detail to match.

SGLT… Security Guard for our Little Tubules 🛡️

If you enjoyed reading this and want to get smarter on the latest medical research Join 15,000 Clinicians reading The Handover

CURB-65.
It's beautifully simple.
Five letters. Five criteria.

In a career full of dumb, convoluted acronyms and funny-sounding drugs, CURB-65 is a breath of fresh air. It’s the guideline, AND its letters spell out its criteria. 

Confusion
Urea >7 
Resp Rate > 30
Blood Pressure <90/65 mmHg
Age > 65

It’s oh, so simple. But it hasn’t always been…

The year is 2002. But to your respiratory consultant, it is 1 BC. Before CURB. 

Patients with pneumonia were arriving in A&E every day with the same question hanging over them. How bad is this infection anyway? 

In the years before CURB, we had two main tools to use. 

1. The Pneumonia Severity Index(PSI): A thorough scoring criterion… but it had 20 different variables to plug into to get an answer. Calculating it felt like filling in your tax return before prescribing antibiotics.
2. The modified British Thoracic Society rule (mBTS): It had just 4 criteria. Confusion, Resp rate, Diastolic BP, Urea > 7. But it was too black and white. Score >2 = severe, Score <2 = not severe. A very blunt instrument.

So, an opportunity emerged.
Hope for the Goldilocks score.
Granular enough to guide the full range of decisions (home, ward or ICU). But without an onboarding process longer than opening a new bank account.

In 2003, the landmark study was published in Thorax, A BMJ journal 

https://preview.redd.it/fm00836ipsfh1.png?width=1780&format=png&auto=webp&s=ddda8daed61afa0411d0d0d40905ce883dc2e0f8

The primary aim was simple: Develop a better severity score. Make it practical. Make it sort patients based on mortality risk. Make it work both in hospital and, if possible, community settings. 

The hunt for the Goldiocks score begins…

The researchers combined data from three prospective CAP studies in the UK, New Zealand and the Netherlands. Rounding up to a total of 1,068 patients.

Things get a little complex here.
To come up with the Goldilocks score, they first needed to find the relevant criteria. Now comes the detective work.

The researchers threw dozens of variables into a mathematical model and did some statistical wizardry to find out: Which of them actually predicted death?

It just so happens the letters that make up CURB were the biggest needle movers in regards to mortality.

• They excluded variables like serum albumin – whilst independently associated with mortality, it’s not readily available at the time of initial assessment. So they binned it.
• They later on included age, as it was just so damn easy to get a hold of.

With that, CURB-65 was born. `
It was made in such a way that each factor was equally weighted. It didn’t matter which letter was ticked. As you went from 0 => 1 => 2 => 3 and beyond, your risk of death increased a proportional amount. 

So the acronym sounds good, n’ all, but does it accurately predict severity?

That's where the validation step comes in. Of the 1,086 patients included in the study:

• 80% were used to build CURB-65 (derivation group)
• 20% were used to test if CURB-65 actually worked (validation group)

https://preview.redd.it/jzqnd46ipsfh1.png?width=1946&format=png&auto=webp&s=42acd831fdd2584355c4fad84e5867fa3098a50f

The validation group supported the trend seen in the derivation group. Mortality rose as CURB-65 increased. 

• Score 0: 0 deaths out of 55 patients.
• Score 1: 5 deaths out of 86 patients, about 5.8%.
• Score 2: 8 deaths out of 46 patients, about 17.4%.
• Score 3: 6 deaths out of 23 patients, about 26%.
• Score 4: 1 death out of 4 patients, about 25%.
• Score 5: 1 death out of 3 patients, about 33.3%

Now, compared to the old tools:

• CURB vs PSI: A systematic review found no significant difference in overall mortality prediction between PSI and CURB-65.
• CURB vs mBTS: Roughly a coin flip in raw accuracy, sensitivity and specificity were near identical between the two in the analysis. But CURB wins as it splits results into more buckets and tells you what to do about it. Home, ward or ICU.

Shortly afterwards, CURB-65 spread.
Through BTS guidance. To hospitals around the UK. Then around the world. 

And now, more than 20 years later, it’s still one of the first scores doctors learn and one of the few scores that actually sticks. 

If you enjoyed reading this and want a journal club(that’s actually entertaining) Join 15,000 Clinicians reading The Handover

Troponin
The cardiac kind.

This tiny regulatory complex lives inside muscle all around the body.
It’s kinda like a nightclub bouncer for the body.

Year 1 physiology tells you it's there to stop muscle contraction

"No calcium? You're not on the list."

But slip it a few calcium ions…

"Oh! Why didn't you say so? Right this way."

Suddenly everyone’s inside; muscles are contracting, and actin and myosin are dancing like it’s 1966. 

But that's not all Tropinin can do.
It found a very successful side hustle in cardiology.Turns out leaking into someone's bloodstream is a surprisingly lucrative career move.

Y’know: ST-Depression + Raised Troponin = NSTEMI for sure. 

It's pretty basic at this point. But it hadn’t always been this way… 

Let’s take it back to the 80s. Before the age of troponin, clinicians used a different cardiac marker to guide diagnosis. Creatine Kinase-MB. 

Creatine Kinase was good…ish. It had some serious problems.

1. It’s present in skeletal muscle and healthy blood - this means the cutoff had to be way, way above baseline to have any clinical influence.
2. Its sensitivity is POOR! It couldn’t pick up small amounts of necrosis/minor infarcts. This means the patient could have real heart damage and still get back a “normal” CK-MB result.

Less than ideal for our patient with crushing chest pain. The quest for a better marker began…

There were glimmers of hope for AST, LDH and even myoglobin. But it wasn’t until 1996 that they found the golden child.

As previously stated, Troponin wasn’t a newcomer. It was first discovered in 1965. The difficulty was localising it to the heart. This was all solved in 1987, when the first cardiac-specific troponin I and T were discovered. Even after localising it to the heart, it required a serial measurement over 24-48 hours. Which is fantastic... if your patient's heart attack is willing to wait too.

Finally, this paper by Antman et al. was published in the NEJM was the first to show that a single troponin I measurement at presentation could identify patients at higher risk of death

https://preview.redd.it/p2x05acwojfh1.png?width=1798&format=png&auto=webp&s=389f4773c4607f938f5e2f16a12a0b6a3d2c4c6c

The aim was simple: 

1. See if troponin I could predict who was at higher risk of dying after a heart attack (it’s value as a prognostic indicator)
2. See if Tropin I could give extra information that CK-MB and clinical features could not.

 

This study was a subgroup analysis of the famous TIMI IIIB trial, which enrolled symptomatic adults with ischemic chest pain and documented coronary artery disease. 

Blood samples from 1,405 patients were used and analysed or cardiac troponin I, while CK-MB was also measured for comparison. 

The assay's reliable cutoff was 0.4 ng/mL, so that became the line in the sand.

Then the researchers unleashed the statistical wizardry that is multivariable Cox regression to answer the big question: if troponin goes up, do the chances of dying go up with it?

Here’s what they found:

LANDMARK FINDING: Patients with a troponin I ≥0.4 ng/mL had a 42-day mortality of 3.7%, compared with 1.0% in patients below 0.4 ng/mL.

https://preview.redd.it/snq689cwojfh1.png?width=1376&format=png&auto=webp&s=41930332ed6880f28387c91ed1f2142a505597fd

Additionally:

• Mortality rose stepwise as troponin I rose. Each 1ng/ml increased relative risk by 3% (95% CI 1.00–1.05; P = 0.03).
• Timing mattered. After 6 hours, elevated troponin I was associated with a 9.5× higher risk of death at 42 days (95% CI 2.2–41.4).

And last but not least, amongst the 948 patients classified under unstable angina, 238 patients (25%) had elevated troponin I but their CK-MB was normal. Showing for the first time that Troponin I could detect myocardial injury where CK-MB would miss it. 

Once word got out about the prophetic biomarker, it wasn’t long before things changed for the better:

• 2000: The ESC/ACC issued a new definition of MI, naming troponin as the preferred biomarker
• 2007: The Global Task Force (bit of a dramatic name) universally changed the definition

Then finally in 2010 NICE published guidance to officially induct troponin to the default ACS pathway.

And that’s the story of how troponin became the ACS golden child.
Except for when it’s a STEMI, then it’s kinda pointless.

If you enjoyed reading this and want a journal club(that’s actually entertaining) Join 15,000 Clinicians reading The Handover

CURB-65.
It's beautifully simple.
Five letters. Five criteria.

In a career full of dumb, convoluted acronyms and funny-sounding drugs, CURB-65 is a breath of fresh air. It’s the guideline, AND its letters spell out its criteria. 

Confusion
Urea >7 
Resp Rate > 30
Blood Pressure <90/65 mmHg
Age > 65

It’s oh, so simple. But it hasn’t always been…

The year is 2002. But to your respiratory consultant, it is 1 BC. Before CURB. 

Patients with pneumonia were arriving in A&E every day with the same question hanging over them. How bad is this infection anyway? 

In the years before CURB, we had two main tools to use. 

1. The Pneumonia Severity Index(PSI): A thorough scoring criterion… but it had 20 different variables to plug into to get an answer. Calculating it felt like filling in your tax return before prescribing antibiotics.
2. The modified British Thoracic Society rule (mBTS): It had just 4 criteria. Confusion, Resp rate, Diastolic BP, Urea > 7. But it was too black and white. Score >2 = severe, Score <2 = not severe. A very blunt instrument.

So, an opportunity emerged.
Hope for the Goldilocks score.
Granular enough to guide the full range of decisions (home, ward or ICU). But without an onboarding process longer than opening a new bank account.

In 2003, the landmark study was published in Thorax, A BMJ journal 

https://preview.redd.it/d9kku6w576eh1.png?width=1780&format=png&auto=webp&s=850f7a09fe1d6276c774228dbef47b7d93628ca6

The primary aim was simple: Develop a better severity score. Make it practical. Make it sort patients based on mortality risk. Make it work both in hospital and, if possible, community settings. 

The hunt for the Goldiocks score begins…

The researchers combined data from three prospective CAP studies in the UK, New Zealand and the Netherlands. Rounding up to a total of 1,068 patients.

Things get a little complex here.
To come up with the Goldilocks score, they first needed to find the relevant criteria. Now comes the detective work.

The researchers threw dozens of variables into a mathematical model and did some statistical wizardry to find out: Which of them actually predicted death?

It just so happens the letters that make up CURB were the biggest needle movers in regards to mortality.

• They excluded variables like serum albumin – whilst independently associated with mortality, it’s not readily available at the time of initial assessment. So they binned it.
• They later on included age, as it was just so damn easy to get a hold of.

With that, CURB-65 was born. `
It was made in such a way that each factor was equally weighted. It didn’t matter which letter was ticked. As you went from 0 => 1 => 2 => 3 and beyond, your risk of death increased a proportional amount. 

So the acronym sounds good, n’ all, but does it accurately predict severity?

That's where the validation step comes in. Of the 1,086 patients included in the study:

• 80% were used to build CURB-65 (derivation group)
• 20% were used to test if CURB-65 actually worked (validation group)

https://preview.redd.it/umpss4w576eh1.png?width=1946&format=png&auto=webp&s=bbb4bcb0ecc899ef474d64f6729edf3de3dc0893

The validation group supported the trend seen in the derivation group. Mortality rose as CURB-65 increased. 

• Score 0: 0 deaths out of 55 patients.
• Score 1: 5 deaths out of 86 patients, about 5.8%.
• Score 2: 8 deaths out of 46 patients, about 17.4%.
• Score 3: 6 deaths out of 23 patients, about 26%.
• Score 4: 1 death out of 4 patients, about 25%.
• Score 5: 1 death out of 3 patients, about 33.3%

Now, compared to the old tools:

• CURB vs PSI: A systematic review found no significant difference in overall mortality prediction between PSI and CURB-65.
• CURB vs mBTS: Roughly a coin flip in raw accuracy, sensitivity and specificity were near identical between the two in the analysis. But CURB wins as it splits results into more buckets and tells you what to do about it. Home, ward or ICU.

Shortly afterwards, CURB-65 spread.
Through BTS guidance. To hospitals around the UK. Then around the world. 

And now, more than 20 years later, it’s still one of the first scores doctors learn and one of the few scores that actually sticks. 

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The humble toothbrush.
Fighting the daily battle against tooth decay, gum disease, and halitosis.

You might brush once a day or twice a day.
You might do it before breakfast or after breakfast (FYI, before is actually better).
You might even actually floss alongside brushing. You performative freak.

Now think of Pneumonia. A classic infection known for long hospital stays, patient distress, and death.

You’ve got CAP (Community-Acquired Pneumonia).
You’ve got HAP (Hospital-Acquired Pneumonia).
In that, you got VAP(Ventilator) and NV-HAP(Non-Ventilator).
Say all of those in a freestyle, and you’ve got a Pneumo Rap.

Now, you might be wondering, ‘What’s the link between toothbrushes and Pneumonia?’ 

Well, a toothbrush may actually prevent more than just plaque; it may also prevent NV-HAP.

You’re probably starting to get suspicious. Did a dentist sneak his way into a doctor's newsletter? But, fear not, this is not just propaganda from Big Dental.

https://preview.redd.it/j60evh0qb08h1.png?width=2048&format=png&auto=webp&s=841ea22d54a79828c820c5ceb39abf0a1729d86f

This link was studied in the HAPPEN trial. Published in The Lancet Infectious Diseases, this multicentre stepped‑wedge cluster RCT ran across nine medical and stroke wards in three Australian hospitals. It included 8,870 adults who stayed in the hospital for at least 48 hours.

How did they test it?

• All the wards started on usual care, i.e. just brushing like always.
• Every 3 months, some wards switched to the HAPPEN bundle:
  • Toothbrush + fluoride/sodium bicarb toothpaste in a bag 
  • Research nurses helped with lip care + cleaning teeth/dentures/tongue
  • Regular patient & staff education + Monthly Audits of oral care
• By 12 months, everyone was on the bundle, and no one was left behind. How sweet.

What was the primary outcome?

Incidence of NV‑HAP >48 hours after ward admission, using strict ECDC criteria

The Big Question: Would 9 out of 10 Resp Consultants recommend this intervention?

Apparently so:

• NV‑HAP dropped from 1.0% in usual care to 0.7% with the HAPPEN bundle.
• That’s about a 60% relative reduction in NV‑HAP! (cumulative hazard ratio 0.40, 95% CI 0.19–0.82).
• Documented oral care completion jumped from 15.9% to 61.9% after the bundle. (The people yearn for the brush)

https://preview.redd.it/g7eqmi0qb08h1.png?width=2048&format=png&auto=webp&s=a4f51ccd26838e4fa6473f9d9c3a26ad6f377c56

But here’s some info from that pesky last consultant who doesn’t agree:

• Only nine wards across three hospitals → a strong start, but not a large, diverse sample.
• The control group had more antibiotic use, which wasn’t adjusted for.
• Oral care was measured from documentation, not direct observation.
• The whole thing was run with dedicated research nurses. Not exactly standard staffing on a stretched medical ward.

So what does this say? 

Well… it shows evidence that an overengineered oral hygiene routine might make the difference when it comes to pneumonia. Dentists can finally earn that Dr title of theirs and actually save a life. And a reminder that simple things matter in healthcare too. Tazocin is nice, but Colgate has a spot on the roster too.  

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What’s the peak performance supplement stack? Glad you asked.

We got Huel to replace mealtime.  
Multivitamins because they’re yummy. 
Ashwaganda to horny my libido. 
Iron to make my poo black. 
Creatine because Steven Bartlet said so. 
And Vitamin D plus Calcium - keep my bones nice and strong. 

Now, I can’t personally vouch for the effectiveness of every substance currently being peddled to men by podcasters with Turkish veneers. But vitamin D and calcium?

Between osteoporosis advice, Petits Filous ads, and every GP over the age of 45, I thought it was basically settled?  Calcium and vitamin D help prevent fractures.

We’re bullish on vitamin D and calcium because of their critical role in bone homeostasis. I won’t bore you with a repeat of pre-clinical medicine, but in short, low levels of calcium and vitamin D have been associated with:

• Increased falls
• Increased fracture risk
• Reduced muscle function
• Loss of bone mineral density

So, logically, keeping them high should reduce all these terrible outcomes, right? …right? 

This meta-analysis and systematic review, published in The BMJ, put this thinking to the test. 

Of course we’ll have a look

If we gave patients calcium, vitamin D, or both, would it reduce their risk of fracture and falls? Let’s find out

They looked out at 69 randomised controlled trials, including 153,902 participants. Sizable indeed…

They excluded patients already on bone protection medication and those who were already very frail. Leaving only regular community-dwelling elderly(average age 71).

After crunching data from 69 randomised controlled trials using random-effects meta-analysis, they came to a fairly awkward conclusion:

For reducing fractures and falls, Vitamin D and Calcium are overrated. 

• Calcium Monotherapy: Across 11 trials, calcium had an insignificant effect on the risk of sustaining fractures(RR 0.91, 95% CI 0.81 to 1.01; moderate certainty).
• Vitamin D Monotherapy: Across 36 trials and 92,045 patients, vitamin D also offered no benefit or risk reduction for overall fractures (RR 1.00, 95% CI 0.95 to 1.06).
• Risk of Falls: Somewhat unsurprisingly, nada. Neither Calcium nor Vitamin D could stop people from hitting the deck.

 

However, when you put the two together(Calcium + Vit D), there is a glimmer of hope. 

Combined supplementation showed a statistically significant relative reduction in the risk of any fracture (15 trials, 51,126 participants; RR 0.91, 95% CI 0.84 to 0.99).

https://preview.redd.it/bvl8ty6j423h1.png?width=2072&format=png&auto=webp&s=ec6c36d63dcb63a126892dac02a0efae7b9cd366

But that glimmer was quickly extinguished.

• The absolute risk reduction for overall fractures was just 1.0%. 
• The authors had predefined 2.0% as the threshold for clinical significance – meaning the result technically “worked,” but not enough to matter to actual humans

https://preview.redd.it/3auno0ul423h1.png?width=2068&format=png&auto=webp&s=4acd5b12ab63cd6d6204dfe7058dc691737def1e

This is pretty fascinating because as of 2021, the NHS pay £111 million per year on Vitamin D prescriptions. £111 million! I wonder what else that money could be put towards 🤔…

To be fair, the paper doesn’t say vitamin D is useless in every situation. Evidence was limited for people with severe deficiencies, people living in residential care, and patients already at very high fracture risk.  

But for regular people in the community? 
The evidence for routine supplementation suddenly looks a lot shakier than the wellness industry would probably prefer. 

Anyway, I’m still taking Huel. Nothing tastier than liquid food slop 😋

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Common things are common. And there is nothing common-er than a headache. 

Usually, you can chalk it up to dehydration, stress, or mysteriously needing a sick note on a Monday morning 🤔

But when those headaches come in that one-sided, throbbing, please-turn-off-the-sun flavour, we need a more tailored approach. 

https://preview.redd.it/g7bpsfg66e0h1.png?width=709&format=png&auto=webp&s=3d7a8a80cf5d0c9a80d7d9fb20d4733f1080ebfd

You see, migraine management has a problem…

Treating a migraine attack is super straightforward.

1. Take a triptan. 
2. Take an NSAID. 
3. Take it easy.

But stopping it from coming back? Something curious happens. It takes the pain in your patient's head and makes it a pain in your arse. 

How about propanolol? Oh… you’re asthmatic
How about toparimate? Oh… you’re trying to get pregnant
And acupuncture(NICE-recommended)? Oh… you’re traumatised by Final Destination 5

There are a load of wonderful ways to tackle migraine prophylaxis. 

Contenders included heritage drugs, like propranolol, topiramate, and Botox(Botulinum Toxins). None of which has the primary job of treating migraines. It’s like a side-hustle for them. 

And also, the new, sexy CGRP-targeted therapies. A class of drugs that finally treats migraines as a day job. TLDR: they block the chemical released during migraine attacks that causes inflammation.

But which is definitively the best? And which aren’t worth the hype? This meta-analysis and systematic review from the Annals of Internal Medicine has the answers. 

This study is the Migraine Olympics.
A head-to-head comparison of the biggest names in chronic migraine prevention.

The review looked at 43 randomised controlled trials involving 14,725 patients with chronic migraine.

Researchers wanted to answer three big questions:

1. Which treatments reduced monthly migraine days and by how many?
2. Which drugs cause people to stop due to side effects?
3. Which drugs had weak studies backing them?

And after an industrial quantity of unpaid academic labour, these were the key findings:

Headline Finding = CGRP therapies on top.
The new-gen CGRP-targeted therapies were the most effective class overall. A load of them reducing monthly migraine days by about 2 days vs placebo

• Erenumab vs placebo: MD -2.08 days per month (95% CI -2.82 to -1.33).
• Eptinezumab vs placebo: MD -2.34 days per month (95% CI -2.76 to -1.92).
• Fremanezumab vs placebo: MD -1.77 days per month (95% CI -2.45 to -1.09).
• Galcanezumab vs placebo: MD -2.00 days per month (95% CI -2.96 to -1.04).
• Atogepant vs placebo: MD -2.10 days per month (95% CI -3.06 to -1.14).

What about the old faithfuls? Well… they had an evidence quality problem

• Bad studies: The review didn’t find a solid, dependable body of trials for topiramate, propranolol and valproate. The authors concluded that the studies were not robust enough to give them confidence that these drugs are any good. 
• Botox held its own: Migraine Days -1.34 (95% CI -2.27 to -0.41). BUT did have increased adverse-event-related discontinuation. RR 3.36 (95% CI 1.75 to 6.45).

You would think these findings would lead to the Migraine Union boycotting the American Headache Society, but the study found several shortcomings. 

• High risk of bias.
• Short follow-up period(12 weeks only).
• Conflicting interests(pharma-funded) are some of the big ones.

 

Overall, after years of treating migraines with meds that don’t quite fit the bill, we might finally have a class of meds that takes these “headaches” as seriously as patients do 🤝

Common things are common. And there is nothing common-er than a headache. 

Usually, you can chalk it up to dehydration, stress, or mysteriously needing a sick note on a Monday morning 🤔

But when those headaches come in that one-sided, throbbing, please-turn-off-the-sun flavour, we need a more tailored approach. 

https://preview.redd.it/fkpnwbftea0h1.png?width=1462&format=png&auto=webp&s=62f99727647bb68e0aba84383bdc0cbc03ed8611

You see, migraine management has a problem…

Treating a migraine attack is super straightforward.

1. Take a triptan. 
2. Take an NSAID. 
3. Take it easy.

But stopping it from coming back? Something curious happens. It takes the pain in your patient's head and makes it a pain in your arse. 

How about propanolol? Oh… you’re asthmatic
How about toparimate? Oh… you’re trying to get pregnant
And acupuncture(NICE-recommended)? Oh… you’re traumatised by Final Destination 5

There are a load of wonderful ways to tackle migraine prophylaxis. 

Contenders included heritage drugs, like propranolol, topiramate, and Botox(Botulinum Toxins). None of which has the primary job of treating migraines. It’s like a side-hustle for them. 

And also, the new, sexy CGRP-targeted therapies. A class of drugs that finally treats migraines as a day job. TLDR: they block the chemical released during migraine attacks that causes inflammation.

But which is definitively the best? And which aren’t worth the hype? This meta-analysis and systematic review from the Annals of Internal Medicine has the answers. 

This study is the Migraine Olympics.
A head-to-head comparison of the biggest names in chronic migraine prevention.

The review looked at 43 randomised controlled trials involving 14,725 patients with chronic migraine.

Researchers wanted to answer three big questions:

1. Which treatments reduced monthly migraine days and by how many?
2. Which drugs cause people to stop due to side effects?
3. Which drugs had weak studies backing them?

And after an industrial quantity of unpaid academic labour, these were the key findings:

Headline Finding = CGRP therapies on top.
The new-gen CGRP-targeted therapies were the most effective class overall. A load of them reducing monthly migraine days by about 2 days vs placebo

• Erenumab vs placebo: MD -2.08 days per month (95% CI -2.82 to -1.33).
• Eptinezumab vs placebo: MD -2.34 days per month (95% CI -2.76 to -1.92).
• Fremanezumab vs placebo: MD -1.77 days per month (95% CI -2.45 to -1.09).
• Galcanezumab vs placebo: MD -2.00 days per month (95% CI -2.96 to -1.04).
• Atogepant vs placebo: MD -2.10 days per month (95% CI -3.06 to -1.14).

What about the old faithfuls? Well… they had an evidence quality problem

• Bad studies: The review didn’t find a solid, dependable body of trials for topiramate, propranolol and valproate. The authors concluded that the studies were not robust enough to give them confidence that these drugs are any good. 
• Botox held its own: Migraine Days -1.34 (95% CI -2.27 to -0.41). BUT did have increased adverse-event-related discontinuation. RR 3.36 (95% CI 1.75 to 6.45).

This is fascinating because the CGRPs, according to NICE scripture(1.3.24), should only be recommended only AFTER 3 of our old fathfuls had failed. Even though they have stronger evidence...

You would think these findings would lead to the Migraine Union boycotting NICE HQ, but the study found several shortcomings. 

• High risk of bias.
• Short follow-up period(12 weeks only).
• Conflicting interests(pharma-funded) are some of the big ones.

 

Overall, after years of treating migraines with meds that don’t quite fit the bill, we might finally have a class of meds that takes these “headaches” as seriously as patients do 🤝

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Being a junior in medicine is a lot like being a brand new sniffer dog.

You start when you’re just a puppy, do some cute basic exercises in school and before you know it, you’re chucked into a busy airport at 3 am and told to weed out the Class A drugs amidst a sea of perfume, mints and coffee.

Day 1 of med school VS day 1 of F1

Spotting the patients to actually worry about is the most important part of being a doctor. 
And when it comes to obstetric patients, the stakes couldn't be higher.

So be a good boy and pay attention, because the latest evidence suggests we may have been sniffing the wrong trail …

Published in PLOS Medicine this week, researchers from Melbourne challenged the eclampsia symptom status quo:

Q: Visual disturbances, headache and tummy pain?
A: Easy! Pregnant patient reports them, and it’s time to bark for the reg🗣️

Not so fast.
Turns out, that classic triad might actually be a pretty poor predictor of eclampsia

The researchers recruited over 2,000 pregnant women across South Africa and Pakistan to figure it out. Here’s what they did: 

• Split them into 3 groups - those who’d had eclampsia, preeclampsia, or normotensive (normal blood pressure) pregnancies.
• Asked whether they’d experienced 20 neurological symptoms within 7 days of the seizure for those who had eclampsia.
• The primary analysis was the likelihood of symptoms occurring before eclampsia, compared to being present with preeclampsia.

And turns out, there were 10 new symptoms that were greater predictors of eclampsia🤯

The strongest odds ratios (>30) included:

• Twitching or jerking limbs (OR 42)
• Affected hearing (OR 36)
• Altered mental state (OR 33.6)
• and impaired speech (OR 33)

Other significant symptoms were severe vertigo (OR 26.6), feelings of doom (OR 23.7), and confusion (OR 20.5).
And the classic triad? Far less likely than the above to be predictive of eclampsia.

Makes sense: headaches happen for a host of reasons, but a pregnant woman tells you she’s experiencing impending doom?💀
Maybe don’t just give paracetamol and call it a day  

This is important research.
Eclampsia can cause maternal death or serious complications like brain haemorrhage or lasting neurological deficits. The treatment is simple:

https://preview.redd.it/03twroi6ckzg1.png?width=1144&format=png&auto=webp&s=e8de7b12a445b634491cc891b82018168230f4f5

Of course, it wasn’t a perfect study:

• Recall bias likely influenced the results, as well as the usual issues with self-reporting
• The study was only conducted across 3 hospitals in 2 countries

But a staggering 97.6% of women had at least one prodromal symptom.
Eclampsia is rarely sudden.

So pick up on the scent when something feels wrong. Remember Mag sulphate and escalate. 

You've done the training. You've got the evidence.
Time to stop sniffing the perfume and find the narcotics.

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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.

Paxlovid Tell All. 

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:

1. Paxlovid(Oral Nirmatrelvir 300mg/Ritonavir 100mg) + usual care(i.e. local guidelines)
2. 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.

https://preview.redd.it/nf0wvj0gv5zg1.png?width=784&format=png&auto=webp&s=0a86d1e4725550d86e49018b9df20625673312da

• 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”

Dearest Gentle Reader,

As you young ladies of the ton approach that most momentous milestone of five and twenty, so too does the looming spectre of the smear grow ever nearer.

Fresh from your quarter life crisis, you ascend the examination couch, assume the lithotomy position and steel yourself for what can only be described as the least festive of birthday offerings.

​Alas, it must be done.

Or… must it?

For this author bears a most titillating Public Cervix Announcement.

Hot off the BMJ press comes a rather thrilling dispatch from China, wherein researchers dared to challenge the supremacy of the speculum.

Instead of continuing to subject women to an invasive and uncomfortable procedure, these intrepid investigators posed the question: 

What if we could simply test menstrual blood instead?

A most promising idea! But how did they put it to the test?

Over three thousand women across China participated, providing three specimens each:

1. Two traditional cervical samples collected in the clinic (for HPV and cytology testing)*
2. A sterile ‘minipad’ of menstrual blood self-collected by participants (for HPV testing)*

(*Women with positive findings on any test received subsequent colposcopy and biopsy)

​The hope was that these ‘minipads’ might prove as capable at detecting CIN (cervical intraepithelial neoplasia - ie, precancerous changes) just as well as a smear.

And what a CIN-derella story it proved to be.💎

In essence, a negative menstrual blood HPV test was just as effective at ruling out high-grade neoplasia as the traditional cervical sample.

But before you cast aside your speculum, a caution:

• The study was cross-sectional, and therefore, long-term follow-up was limited
• The prototype minipad strips are still in very early development
• Although the findings are compelling, further validation across diverse populations is needed

Nevertheless, the implications could be considerable.

Too often are women dissuaded from the smear, be it the discomfort, the stigma around women’s health or cultural reasons. 

A future in which unnecessary pain, embarrassment and discomfort is avoided for women is one this author embraces most fervently. 

So take heart, dear reader.

The season of the speculum may soon be coming to a close.

Yours in both scandal and science,

Lady Whistledown🪶

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