Potentially inappropriate prescriptions (PIPs) in older adults, such as long-term use of benzodiazepines, proton pump inhibitors without indication or antipsychotics in dementia, are associated with adverse events and increased healthcare utilisation. Despite clinical guidelines discouraging their use, PIPs remain frequent in primary care. An audit and feedback (A&F) intervention of PIPs to general practitioners (GPs), led by pharmacists, may reduce the prescription of PIPs in primary care.

A two-arm, pragmatic, controlled trial will be conducted to evaluate the effectiveness of an A&F-based intervention and a pharmacist-led intervention to reduce the proportion of patients aged ≥65 years receiving inappropriate prescriptions. A total of 170 participating GPs, 85 per group, are required. GPs will be randomised into intervention or control groups (1:1). The intervention includes feedback reports, pharmacist-led academic detailing and access to online training modules. The primary outcome is the proportion of older adults receiving at least one PIP at 12 months as well as the total number of PIPs. A random effects Tobit regression model, censored at 0 and 100, will be used to estimate between-group differences adjusted for baseline prescribing. Subgroup analyses will explore heterogeneity of effect by baseline prescribing level and healthcare region. Implementation outcomes, including reach, fidelity, engagement and maintenance, will be evaluated using the Reach, Effectiveness, Adoption, Implementation and Maintenance framework, combining quantitative and qualitative data.

Ethical approval was obtained by the Balearic Island Committee Ethics (IB5219/23PI). Study findings, including primary and secondary outcomes and qualitative implementation results, will be disseminated through peer-reviewed publications and stakeholder reports.

ISRCTN14449434.

Haemodynamic management, and particularly the management of blood pressure (BP), is critical to reduce mortality and preserve the functional capacity of people with cardiovascular disease.1 However, there is insufficient evidence to justify lower BP targets (≤135/85 mm Hg) in people with hypertension and established cardiovascular disease.1 Wang et al have undertaken a multicentre clinical trial in 26 hospitals across China to explore both...

Since 2018, WHO has endorsed the use of whole-genome sequencing (WGS) of Mycobacterium tuberculosis complex isolates to detect drug-resistant tuberculosis (DR-TB). This endorsement was based on the assumption that a faster and more detailed description of the resistance profile would improve treatment prescription for DR-TB by healthcare providers, and hence the treatment outcomes of patients. Nonetheless, this assumption has not been tested in routine clinical practice and different scenarios. In Brazil, WGS is not routinely used for the diagnosis of DR-TB, having been carried out in only a few centres for research purposes. With this trial, we will evaluate whether a WGS-based drug-resistance report improves treatment adequacy in patients with pulmonary DR-TB, compared with the current standard-of-care diagnostic methods used in the state of São Paulo, Brazil.

We will conduct a non-randomised controlled clinical trial with two arms to compare the intervention group (ie, individuals receiving a WGS-based report) with a historical control group (i.e., individuals who received resistance diagnostics based on the standard of care of conventional genotyping and phenotyping techniques). The primary outcome will be the proportion of patients whose treatment scheme was adequate based on complete resistance profile determined by WGS and/or phenotypic drug-susceptibility testing (pDST). Other secondary outcomes will also be considered. The target sample size is 88 eligible patients per group. The intervention group will be prospectively recruited over 18 months and the control group will be composed of patients diagnosed with pulmonary DR-TB up to 2 years before the start of the trial. To ensure comparability, isolates from the control group will undergo WGS retrospectively, and pDST will be performed retrospectively in both groups. This clinical trial will take place in six medical centres for the treatment of DR-TB in the state of São Paulo. This study is intended to support the implementation of the WGS in the routine diagnosis of DR-TB in the state of São Paulo.

Ethical approval was obtained from the Human Research Committee of the Institute of Biomedical Sciences, University of São Paulo, Brazil (CAAE: 79497924.1.1001.5467). Study results will be published in peer-reviewed journals and disseminated to policymakers and stakeholders.

U1111-1308-4669.

To evaluate the cost-effectiveness of anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) using a value-based model that considers drug durability, dosing regimens and real-world administration strategies, including safe vial fractionation.

Model-based pharmacoeconomic analysis using data from randomised clinical trials and network meta-analyses. Analysis conducted from the payer perspective using cost data from the Spanish National Health System.

A model-based analysis compared five anti-VEGF agents—innovator and biosimilar ranibizumab, aflibercept 2 mg, brolucizumab and faricimab—across three dosing regimens: fixed, Pro Re Nata and Treat-and-Extend (TAE). Administration formats included single-use vials, prefilled syringes and vial fractionation (VF), with or without dead-space-free (DSF) syringes to minimise waste. The primary outcome was cost per optimal responder, defined as a patient gaining ≥15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, with and without adverse events. Cost-effectiveness was evaluated using Number Needed to Treat (NNT), Net Efficacy Adjusted for Risk-NNT (adjusted for safety) and incremental cost-effectiveness ratios. Secondary outcomes included the number of treated patients and optimal responders achievable within a fixed 1 000 000 budget.

The most cost-effective strategy was aflibercept 2 mg under a TAE regimen using DSF VF, with a total cost of 6214 per patient and a cost per optimal responder of 27 155. Under a fixed budget of 1 000 000, this approach allowed treatment of 160 patients, yielding 36 optimal responders. Faricimab with DSF VF ranked second, with a total cost of 5847 and a cost per optimal responder of 28 652, treating 171 patients and achieving 34 responders. In contrast, single-use vials without VF led to substantially higher total costs (eg, 11 305 for aflibercept TAE) and lower treatment capacity (eg, 88 patients treated).

This model demonstrates that combining durable agents, extended dosing intervals and optimised delivery strategies (eg, prefilled syringes and DSF VF) can substantially improve the cost-effectiveness and sustainability of anti-VEGF therapy in public health systems.

Exacerbations of chronic obstructive pulmonary disease (COPD) can lead to reduced lung function and worse clinical outcomes. Previous studies have reported associations between severe exacerbations and increased risk of hospitalisation and/or mortality. This meta-analysis examined the impact of moderate exacerbations on the risk of future exacerbations and all-cause mortality.

This meta-analysis included seven observational studies from the EXACOS (EXAcerbations of COPD and their OutcomeS)/AVOIDEX (Impact of AVOIDing EXacerbations of COPD) programme studies.

This meta-analysis used data from regional claims databases or electronic healthcare records from seven countries.

The individual studies included patients with a diagnosis of COPD and ≥12 months of data availability before (regarded as baseline) and after the index (ie, the date of the first COPD diagnosis), with postindex data considered the follow-up period.

The number of COPD exacerbations experienced during the baseline period (ie, the exposure variable) was used to categorise patients into the following groups: no exacerbations, one moderate exacerbation only or two or more moderate/severe exacerbations. Outcomes assessed included risk of COPD exacerbations and all-cause mortality during follow-up as a function of baseline exacerbations. For meta-analyses, all rate ratios (RRs) were log-transformed, and associations were pooled across studies using random-effects meta-analysis models.

Among 2 733 162 patients with COPD, one moderate exacerbation was significantly associated with a twofold increased risk of future exacerbations compared with having no exacerbations during baseline, with pooled RRs (95% CIs) of 2.47 (1.47 to 4.14) at 1 year, 2.49 (1.38 to 4.49) at 2 years and 2.38 (1.30 to 4.34) at 3 years postindex. The pooled RR (95% CI) for all-cause mortality was 1.30 (1.05 to 1.62), indicating a 30% increase in risk following one moderate exacerbation versus no exacerbations.

Preventing moderate exacerbations in patients with COPD should be a priority that may improve patient trajectories and outcomes.