Background

The population is getting older (over 3 million people in the UK are aged 80 years or older) and the number of people living with multiple illnesses and taking lots of tablets to manage these illnesses is increasing. High blood pressure is one of the most common medical conditions in older people and many take two or more drugs to treat it. Recent scientific studies suggest that large reductions in blood pressure, and too many drug prescriptions may be associated with an increase in falls and death in older patients, particularly in those suffering from lots of medical conditions. This study aims to assess the safety of reducing the number of drugs prescribed to older people (defined as being aged 80 years or older) who have blood pressure in a normal range and are taking two or more medications.

Design

This study used a randomised, controlled, open label, non-inferiority trial design. Participants aged at least 80 years with SBP (systolic blood pressure) of less than 150 mmHg and receiving 2 or more antihypertensive medications, whose GP considered appropriate for medication reduction were recruited from 69 general practices across England. Those enrolled were randomised (1:1 ratio) to antihypertensive medication reduction (intervention) or usual care (control). The primary outcome was difference (<10%) in proportion of participants with clinically acceptable SBP (<150 mmHg) at 12-week follow-up. Secondary outcomes included difference in SBP and adverse events.

Outcome

Of 569 participants who were randomised, 35 (6%) were lost to follow-up. Overall, 229 (86.4%) patients in the intervention group and 236 (87.7%) patients in the control group had clinically acceptable systolic blood pressure at follow-up. Medication reduction was sustained in 187 (66.3%) participants in the intervention group who were taking fewer antihypertensive medications than the control group at 12 weeks. Systolic blood pressure corrected for baseline was 3.5 mmHg higher in the intervention group. Adverse events were higher in the intervention group but there was no significant difference in rates of serious adverse events.

Conclusion

Antihypertensive medication reduction can be achieved in two thirds of older multi-morbid patients with systolic blood pressure remaining within clinically acceptable limits. However, potential benefits must be balanced against the possible harms from increased systolic blood pressure (and therefore cardiovascular risk) plus increased adverse events (although most were apparently unrelated).

This NIHR CRN portfolio study was sponsored by the University of Oxford and funded by NIHR Research Professorship.

Background

Antibiotic resistance is a global public health threat. Antibiotics are very commonly prescribed for children presenting with uncomplicated lower respiratory tract infections (LRTIs), but there is little evidence from randomised controlled trials of the effectiveness of antibiotics, both overall or among key clinical subgroups.

In ARTIC PC, the research team assessed whether amoxicillin reduced the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) LRTI in primary care, overall and in key clinical subgroups. The key clinical subgroups of children were those who had one or more particular features – chest signs, fever, physician rating of unwell, sputum or chest rattle, and short of breath.

It is a real priority to show which groups of children that GPs prescribe for currently benefit and which do not, so that antibiotics can be targeted appropriately.

Design

ARTIC PC was a double-blind, randomised, placebo-controlled trial done at 56 general practices in England. Eligible children were those aged 6 months to 12 years presenting in primary care with acute uncomplicated LRTI judged to be infective in origin, where pneumonia was not suspected clinically, with symptoms for less than 21 days. Patients were randomly assigned in a 1:1 ratio to receive amoxicillin 50 mg/kg per day or placebo oral suspension, in three divided doses orally for 7 days.

Patients and investigators were masked to treatment assignment. The primary outcome was the duration of symptoms rated moderately bad or worse (measured using a validated diary) for up to 28 days or until symptoms resolved. The primary outcome and safety were assessed in the intention-to-treat population.

Outcome

Between Nov 9, 2016, and March 17, 2020, 432 children were randomly assigned to the antibiotics group (n=221) or the placebo group (n=211). Complete data for symptom duration were available for 317 (73%) patients; missing data were imputed for the primary analysis.

Median durations of moderately bad or worse symptoms were similar between the groups - 5 days in the antibiotics group vs 6 days in the placebo group.

No differences were seen for the primary outcome between the treatment groups in the five prespecified clinical subgroups (patients with chest signs, fever, physician rating of unwell, sputum or chest rattle, and short of breath). Estimates from complete-case analysis and a per-protocol analysis were similar to the imputed data analysis.

Conclusion

Amoxicillin for uncomplicated chest infections in children is unlikely to be clinically effective either overall or for key subgroups in whom antibiotics are commonly prescribed. Unless pneumonia is suspected, clinicians should provide safety-netting advice but not prescribe antibiotics for most children presenting with chest infections.

This NIHR CRN Portfolio study was sponsored by University of Southampton and funded by the NIHR Health Technology Assessment (HTA) Programme.

Background

As people get older, they often find that walking, climbing stairs and doing their normal daily activities become more difficult. The REtirement in ACTion (REACT) study tested whether or not a group exercise programme run in local communities could reduce this decline in older adults, and whether or not it provided good value for money. The programme encouraged social interaction and fun and provided support to find out about and get involved in other physical activities.

Design

A multicentre, pragmatic, two-arm, parallel-group randomised controlled trial, for physically frail or pre-frail older adults aged ≥ 65 years. Recruitment was primarily via 35 primary care practices. Participants were randomly assigned to receive three healthy ageing education sessions or a 12-month, group-based exercise programme delivered in fitness and community centres. The primary outcome was improved lower limb function at 24 months, this was measured using the – Short Physical Performance Battery score.

Outcome

Between June 2016 and October 2017, 777 participants (mean age 77.6 years, 66% female) were randomised to the intervention arm (n = 410) or the control arm (n = 367). Data collection was completed in October 2019. Primary outcome data at 24 months were provided by 628 (80.8%) participants.

At the 24-month follow-up, participants mobility was significantly greater in the intervention arm than in the control arm). The difference in lower limb function between intervention and control participants was clinically meaningful at both 12 and 24 months. Self-reported physical activity significantly increased in the intervention arm compared with the control arm.

Dropout rates were low (19% at 24 months) and adherence was high. Engagement with the REACT intervention was associated with positive changes in exercise competence, relatedness and enjoyment and perceived physical, social and mental well-being benefits. The intervention plus usual care was cost-effective compared with care alone over the 2 years of REACT. The intervention saved £103 per participant within the 2-year trial window. Lifetime horizon modelling estimated that further cost savings and quality-adjusted life-year gains were accrued up to 15 years post randomisation.

Conclusion

People that took part in the REACT intervention reported better mobility throughout the study. This most importantly included the final assessment which took place 24 months after the programme had started, 12 months after REACT sessions had finished.

The REACT intervention deliver enhanced mobility, and also proved to be a cost effective means of delivering such health benefits.

This CRN Portfolio study was sponsored by University of Bath and funded by the NIHR Public Health Research Programme.