The edition · Top Clinical Updates
Replacing what narcolepsy lost, and replacing induction chemotherapy in AML
An oral orexin agonist restores wakefulness to near-normal in two phase 3 trials; azacitidine-venetoclax beats induction chemotherapy in patients fit for it; a bacterial lysate fails to prevent childhood wheeze; and 17 African countries show what acute heart failure looks like where care arrives late.
The edition in brief
Four findings for every clinician. Oveporexton, an oral orexin receptor 2 agonist, was tested in two phase 3 trials in 273 people with narcolepsy type 1. Mean sleep latency on the Maintenance of Wakefulness Test rose by 14.3 to 19.8 minutes from baseline against a fall of 0.4 to 0.8 minutes on placebo, Epworth scores fell by 9.7 to 11.8 points against 1.5 to 1.7, and weekly cataplexy fell by a median 79.0% to 88.8% against 27.7% to 39.1%. Adverse events affected 86% to 89% of those on the drug against 43% to 54% on placebo, mostly urinary frequency and transient insomnia. PARADIGM randomised 172 adults with untreated AML who were eligible for induction chemotherapy to azacitidine-venetoclax or induction chemotherapy. Median event-free survival was 14.5 months against 6.2 (hazard ratio 0.57, 95% CI 0.39 to 0.84), with less grade 3 or higher infection (28% vs 41%) and haemorrhage (2% vs 12%). It was a phase 2 trial, and several favourable genetic subgroups were excluded. ORBEX gave the bacterial lysate OM-85 or placebo for ten days a month for two years to 822 children aged 6 to 18 months at high risk of asthma, then followed them for three years off treatment. Time to first wheezing illness did not differ (hazard ratio 1.16, 95% CI 0.82 to 1.64). THESUS-HF II enrolled 1,578 adults with acute heart failure across 50 hospitals in 17 African countries. Median age was 56, hypertensive heart disease was the leading cause at 36.5%, in-hospital mortality was 8.7%, and mortality reached 20.6% at 180 days despite high rates of discharge prescribing.
An orexin agonist restores wakefulness in narcolepsy type 1
Oveporexton raised objective sleep latency by 14 to 20 minutes and cut cataplexy by around 80% in two 12-week phase 3 trials, at the cost of urinary frequency and transient insomnia in most patients treated.
Azacitidine-venetoclax outperforms induction chemotherapy in patients fit for induction
In induction-eligible AML outside the favourable genetic subgroups, azacitidine-venetoclax more than doubled median event-free survival against induction chemotherapy (14.5 vs 6.2 months, HR 0.57) with less severe infection and bleeding.
A bacterial lysate does not prevent preschool wheeze
OM-85 given for two years to high-risk toddlers did not delay or prevent wheezing illness over three subsequent years (hazard ratio 1.16, 95% CI 0.82-1.64), so bacterial lysates should not be used for asthma prevention.
Acute heart failure at 56, and a fifth dead within six months
In 17 African countries, acute heart failure presented at a median age of 56, was most often hypertensive in origin, and killed one in five within 180 days despite most patients leaving hospital on the right drugs at less than target doses.
Ask about the knees buckling when someone laughs
In anyone with unexplained daytime sleepiness, ask whether hard laughter makes their knees buckle or jaw sag while they stay fully aware, because cataplexy is the feature that turns a vague complaint into a diagnosis.
The alcohol admission ends with a phone number, and that is why it fails
Before discharging a patient admitted with alcohol use disorder, start the medication, book a named appointment and involve their support network, because interventions combining these were the only ones that improved follow-up and medication was included in just 14% of those tested.
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