- Ann Robinson, NHS GP and health writer and broadcaster
Donanemab for Alzheimer’s disease
Donanemab has been hailed in the global media as a “turning point in the fight against Alzheimer’s disease” on the back of donanemab’s manufacturer releasing final results of the phase 3 Trailblazer Alz-2 trial simultaneously at a conference and in JAMA. The drug that is designed to break up amyloid-beta clumps (like lecanemab, which recently gained FDA approval) seemed to slow cognitive and functional decline by an average 36% and 40% over 18 months respectively in people with early Alzheimer’s disease whose brain scans showed low to medium levels of tau (the secondary abnormal protein that accumulates) compared with placebo. The treatment effect was modest, the long term impact and efficacy compared with lecanemab unknown, and the risk of drug induced cerebral oedema not fully understood. There’s room for optimism and avenues to explore, but those hoping for a magic bullet may be sorely disappointed.
JAMA doi:10.1001/jama.2023.13239
Group B streptococcus vaccine in pregnancy
The World Health Organization says that new vaccines are urgently needed against group B streptococcus (GBS) in pregnancy, which is commoner than previously recognised and—though harmless for most pregnant women who carry it—can be linked to prematurity, stillbirths, and long term disability. GBS is usually picked up by babies as they travel down the birth canal and can cause sepsis and meningitis in newborns. Less often, an ascending infection can get into the amniotic fluid causing premature labour or stillbirth. Many high income countries (but not the UK) screen pregnant women for GBS colonisation in the third trimester and give intravenous antibiotics in labour if positive. The rationale for not screening in the UK is that many women carry GBS and most of their babies are born safely and don’t develop infection.
This ongoing phase 2 study found that an experimental vaccine (GBS6) was effective in eliciting antibodies against GBS in pregnant women and that the antibodies were transferred to their infants at levels associated with a reduced risk of invasive GBS disease and with no significant safety concerns. Further studies are needed to define the antibody levels needed for protection in different settings such as low income countries where other diseases such as HIV can impair antibody transfer.
N Engl J Med doi:10.1056/NEJMoa2116045
Cementing the pieces together in hip fractures
We all know of older patients and relatives who fall, break a hip and have it fixed, but then die in hospital. Many deaths are attributed to postoperative complications, including deep surgical site infection. The one year mortality of an infected hip hemiarthroplasty is a shocking 50%. In a bid to reduce the risk of deep surgical site infection, an antibiotic is usually mixed in with the bone cement. Previous studies have suggested that two antibiotics may be better than one.
This larger and more rigorous study compared cements loaded with high dose, dual antibiotic versus single antibiotic in just under 5000 patients aged 60 years and over across 26 UK hospitals. The study found no significant difference in deep surgical site infections (1.7% v 1.2%) or other complications at three months, or in mobility, health related quality of life, or deaths (20%) at four months between the two groups. Given concerns about antibiotic resistance, it seems that sticking to current standard practice is preferable to adding in another antibiotic.
Lancet doi:10.1016/S0140-6736(23)00962-5
Adding insult to injury
Acute kidney injury usually happens in people who are ill with sepsis or who don’t have enough blood getting to the kidneys because of hypovolaemia or hypotension. Injudicious prescribing of nephrotoxic drugs or diuretics can readily tip a frail person into acute kidney injury. Methodologically flawed studies have suggested that renal function deteriorates more rapidly than expected after acute kidney injury in people who have existing chronic kidney disease. So it’s a bit of a relief to learn from this US multicentre prospective cohort study of 3150 people with chronic kidney disease that a documented episode of mild to moderate acute kidney injury didn’t affect the existing rate of change of renal function in the following few years (median follow-up 3.9 years). Admittedly, there were hardly any cases of severe acute kidney injury, but it’s reassuring nonetheless.
Ann Intern Med doi:10.7326/M22-3617
When is a penicillin allergy not an allergy? Most of the time
Of the many patients with “allergic penicillin” in their notes, some 95% aren’t, but who’s going to risk it? Specialist testing involves prick and intradermal skin testing followed by an oral challenge, but that isn’t accessible to most citizens. So millions of people avoid this safe, available, effective, and cheap group of drugs unnecessarily.
In this small multicentre randomised trial of 382 patients with low risk penicillin allergy (PEN-FAST score 0 or 1), direct oral penicillin challenge was safe and non-inferior to standard skin testing followed by oral challenge (0.5% developed an immune mediated reaction in both groups in the first hour and 5% in the following five days). There were no serious adverse events, although the study excluded anyone with known anaphylaxis. Being able to offer direct oral challenge without the faff of skin tests is an attractive proposition, but further work is needed before it can be safely offered outside of specialist allergy clinics.
JAMA Intern Med doi:10.1001/jamainternmed.2023.2986