You might be interested in…General Update

This week I would like to report on a few different studies recently published that should be of general interest.

Risk of fracture after stopping Hormone Replacement Therapy
Women benefit from reduced fracture risk while using menopausal hormone therapy. However, information on risks after stopping menopausal hormone therapy is inconsistent, with no information on longer-term fracture risk as women age. This was a nested case–control study1 using UK primary and secondary care data from the Clinical Practice Research Datalink.

Dr Ray O’Connor

The subjects were women, aged 40 years and older, registered with a primary care practice between Jan 1, 1998, and Feb 28, 2023, and with a first record for any fracture. These were matched at the fracture index date with up to five female controls with no fracture history, who were of the same age and registered at the same general practice. Menopausal hormone therapy-related fracture risks were assessed.

Age of average fracture cases was 68⋅5 years. The results showed that compared with never-use, overall fracture risk was reduced for current use (oestrogen-only odds ratio [OR] 0⋅76, oestrogen–progestogen OR 0⋅75). Fracture risk became higher 1–10 years after discontinuation (oestrogen-only OR 0⋅99, oestrogen–progestogen OR 1⋅06) but was again lower for more than 10 years post-cessation (oestrogen-only OR 0⋅93, oestrogen–progestogen OR 0⋅95). Risk levels varied by menopausal hormone therapy type and by duration of treatment.

Estimated extra fracture cases per 10 000 women-years 1–10 years after oestrogen–progestogen treatment were equivalent to 14 cases for less than five years menopausal hormone therapy exposure and five cases for five or more years of exposure. This is a complex paper but is very helpful to refer to when counselling women on the risks and benefits of HRT.

The effectiveness of an exercise programme post-hospital-discharge
Acute hospitalisation is a recognised risk factor for adverse outcomes in older adults, including hospital associated disability. Post-discharge exercise interventions might mitigate physical and cognitive decline, although the few meta-analyses performed previously present limitations. This systematic review and meta-analysis2 aimed to evaluate the effect of post-discharge exercise interventions on health-related outcomes in older adults.

The authors conducted a systematic search of PubMed, Scopus, Web of Science, and ScienceDirect. Randomised controlled trials published from Jan 1, 2000, to May 16, 2025, were included.

These studies assessed the effectiveness of muscular strength and endurance exercises in older adults (aged 60 years and older) discharged from acute hospitalisation. The search yielded 2,868 results, of which 17 articles (1,458 participants) met inclusion criteria, with moderate to high quality.

The findings were that post-discharge exercise interventions significantly improved physical function. No significant effects were observed for health-related quality of life or readmission risk. Exercise effects on functional independence, cognitive function, frailty, and mortality were synthesised descriptively due to insufficient data for meta-analysis and results remain inconclusive.

The effectiveness of brief alcohol counselling
Globally, harmful alcohol use is a major public health concern, contributing to three million deaths and 5.1 per cent of the global burden of disease annually. Hazardous drinking, originally defined by a “quantity or pattern of alcohol use that places patients at risk for adverse consequences,” is seen in about 20 per cent of patients in primary care settings and is associated with a wide range of physical, mental, and social harms.

To address this global health issue, brief interventions consisting of screening and short counselling sessions have been widely recommended as an effective approach to reduce hazardous drinking in primary care settings. This was a large scale pragmatic cluster randomised controlled trial.3 Its objective was to evaluate the effectiveness of a doctor delivered screening and ultra-brief intervention (<1 minute) compared with simplified assessment only for reducing alcohol intake among patients with hazardous drinking in primary care.

The setting was 40 primary care clinics in Japan. The participants were 1,133 outpatients aged 20-74 years with hazardous drinking (AUDIT-C (alcohol use disorders identification test-consumption) scores ≥5 for men and ≥4 for women). The intervention group comprised screening with AUDIT-C followed by brief oral advice and an alcohol information leaflet delivered in <1 minute. The control group comprised simplified assessment with AUDIT-C only. The primary outcome was total alcohol consumption in the four weeks preceding the 24 week follow up. Unfortunately, the results showed no evidence to support the effectiveness of a doctor delivered ultra-brief intervention for hazardous drinking compared with simplified assessment only.

COVID-19 treatment update
As of November 2024, more than seven million people have died with coronavirus disease 2019 (COVID-19). The evidence on COVID-19 continues to evolve as global efforts to identify effective interventions for the prevention and treatment of covid-19 have resulted in more than 8,000 completed or ongoing trials. Summarising the rapidly growing evidence base has proved challenging.

Different treatments are most effective at certain disease stages. This systematic review and network meta analysis4 focuses on patients with mild or moderate (non-severe) COVID-19. Network meta-analysis of 187 of 259 randomised trials (72 per cent) comparing 40 different drug treatments in people with mild or moderate covid-19 concludes that Nirmatrelvir-ritonavir and remdesivir probably reduce hospital admission; molnupiravir and systemic corticosteroids may reduce hospital admission. Several drugs, including molnupiravir and systemic corticosteroids, probably reduce symptom duration, whereas nirmatrelvir-ritonavir and remdesivir may not.

References:

1. Vinogradova Y et al. Discontinuation of menopausal hormone therapy and risk of fracture: nested case–control studies using routinely collected primary care data. Lancet Healthy Longev 2025; 6: 100729 Published Online July 23, 2025 https://doi.org/10.1016/j.lanhl.2025.100729.
2. Etayo-Urtasun P et al. Effectiveness of post-discharge exercise interventions in older adults following acute hospitalisation: a systematic review and meta-analysis. Lancet Healthy Longev 2025; 6: 100730 Published Online https://doi.org/10.1016/j.lanhl.2025.100730.
3. So R et al. Effectiveness of screening and ultra-brief intervention for hazardous drinking in primary care: pragmatic cluster randomised controlled trial. BMJ 2025;390:e083985 http://dx.doi.org/10.1136/bmj-2024‑083985.
4. Ibrahim S et al. Drug treatments for mild or moderate covid-19: systematic review and network meta-analysis. BMJ 2025;389:e081165 http://dx.doi.org/10.1136/bmj-2024‑081165.