- Ann Robinson, NHS GP and health writer and broadcaster
Antihypertensives and risk of falls in older people
Falls are common and dangerous for older and more vulnerable people. The main modifiable risk factor for falls is prescription drugs, and the most commonly prescribed drugs in older people are antihypertensives. The problem is that they can make people fall over when they stand up as orthostatic hypotension kicks in, especially in the immediate period after treatment is started.
This cohort study of nearly 30 000 nursing home residents, 97% of whom were men with a mean age of 78 years, found that, compared with a matched control group, initiation of antihypertensives was associated with an increased risk of fractures (5.4 v 2.2 per 100 person-years) and falls, especially among residents with dementia, high baseline blood pressures, and no recent antihypertensive treatment. The key question for clinicians is whether the expected cardiovascular benefits of treating hypertension are likely to outweigh the clear hazards of starting treatment.
JAMA Intern Med doi:10.1001/jamainternmed.2024.0507
Steroids for prematurity
Corticosteroids are often given to pregnant women at high risk of late premature delivery to reduce neonatal respiratory problems and deaths. But corticosteroids can cause short term hypoglycaemia in the neonates, and there is concern that they could be linked to neurodevelopmental problems in the children once they get past 6 years old.
This randomised trial of 2831 children (mean age 7 years) found no significant differences in tests of thinking and problem solving (general conceptual abilities score) between the corticosteroid group (betamethasone 12 mg given intramuscularly twice in 24 hours) and placebo (17.1% v 18.5%). There was no differences in secondary outcomes such as motor function, social responsiveness, and behaviour. The study was smaller than planned because of the covid pandemic, but it will be reassuring for pregnant women who are urged to have the steroid jabs to help their baby.
JAMA doi:10.1001/jama.2024.4303
Leukaemia lifeline?
CAR T cells are a potential lifeline for people with aggressive blood cancers that have recurred or failed to respond to conventional treatments. The patient’s T cells are genetically manipulated to produce specialised surface receptors (chimeric antigen receptors (CARs)). Once they’re infused back into the patient, they latch onto antigens on the surface of cancer cells and kill them. The NHS has provided CAR T therapies for children with aggressive B cell acute lymphoblastic leukaemia since 2018.
Bridge therapy gives the CAR T cells after the patient’s T cells have been harvested but before haemopoietic stem cell transplant (HSCT). The problem is that the aggressive chemotherapy needed before HSCT and drugs given to prevent graft versus host disease (GVHD) weaken the patient and can kill residual CAR T cells before they’ve completed their job of mopping up rogue leukaemia cells.
A novel “all-in-one” strategy used CAR T cell therapy engineered against tumour antigen CD7 and haploidentical (half-matched donor, usually a family member) HSCT. This avoided the need for myeloablation or GVHD prophylaxis. It was tested in 10 patients with relapsed or refractory CD7-positive cancers. The strategy was safe and effective in achieving remission, though with serious but reversible side effects.
N Engl J Med doi:10.1056/NEJMoa2313812
All that glisters is not gold
Empagliflozin, an SGLT-2 drug originally developed for type 2 diabetes, is a bit of a wonder drug. It has also been shown to improve cardiovascular outcomes in patients with heart failure, type 2 diabetes at high cardiovascular risk, and chronic kidney disease. So can we assume it would reduce heart failure after acute myocardial infarction?
This randomised trial of patients at increased risk of heart failure after acute myocardial infarction found that, compared with placebo, empagliflozin was safe but ineffective in reducing the risk of hospital admission for heart failure (9.1% v 8.2%) or death from any cause (5.5% v 5.2%) over an 18 month period. Further trials with more women, older people, and a racially diverse population might still yield favourable results. But for now, it’s a no.
N Engl J Med doi:10.1056/NEJMoa2314051
Full steam ahead for paratyphoid A vaccine
Enteric fever (typhoid and paratyphoid fever) caused by various subtypes of Salmonella enterica, may be rare in high income countries, but it certainly hasn’t gone away. In 2017, there were around 14.3 million cases worldwide with about 135 000 deaths from what should be a preventable disease. There are two effective vaccines against typhoid in widespread use, but none against paratyphoid.
This first ever phase 1 human study of a bivalent paratyphoid A-typhoid conjugate vaccine (Sii-PTCV) found that it was safe and immunogenic for both typhoid and paratyphoid antigens compared with the currently used typhoid vaccine—typhoid conjugate vaccine. There were no serious adverse effects over six months and robust immune responses to both typhoid and paratyphoid A. This implies that the new vaccine could potentially offer comprehensive protection against enteric fever of both types.
Lancet doi:10.1016/S0140-6736(24)00249-6
