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Prevention of respiratory syncytial virus (RSV) infection is now a global health priority, with a long-acting monoclonal antibody and two RSV vaccines recently licenced for clinical use. Most licenced and candidate interventions target the RSV fusion (RSV-F) protein. New interventions may be associated with the spread of mutations, reducing susceptibility to antibody neutralization in RSV-F. There is a need for ongoing longitudinal global surveillance of circulating RSV strains. To achieve this large-scale genomic surveillance, a reliable, high-throughput RSV sequencing assay is required. Here we report an improved high-throughput RSV whole-genome sequencing (WGS) assay performed directly on clinical samples without additional enrichment, using a 4-primer-pool, short-amplicon PCR-tiling approach that is suitable for short-read sequencing platforms. Using upper respiratory tract (URT) RSV-positive clinical samples obtained from a sentinel network of primary care providers and from hospital patients (29.7% and 70.2%, respectively; n = 1,037), collected over the period 2019 to 2023, this assay had a threshold of approximately 4 × 10 3 to 8 × 10 3 copies/mL (RSV-B and RSV-A sub-types, respectively) as the lowest amount of virus needed in the sample to achieve >96% of whole-genome coverage at a high-quality level. Using a Ct value of 31 as an empirical cut-off, the overall assay success rate of obtaining >90% genome coverage at a read depth minimum of 20 was 96.83% for clinical specimens successfully sequenced from a total of 1,071. The RSV WGS approach described in this study has increased sensitivity compared to previous approaches and can be applied to clinical specimens without the requirement for enrichment. The updated approach produces sequences of high quality consistently and cost-effectively, suitable for implementation to underpin national programs for the surveillance of RSV genomic variation., Importance: In this paper, we report an improved high-throughput respiratory syncytial virus (RSV) whole-genome sequencing (WGS) assay performed directly on clinical samples, using a 4-primer-pool, short-amplicon PCR-tiling approach that is suitable for short-read sequencing platforms. The RSV WGS approach described in this study has increased sensitivity compared to previous approaches and can be applied to clinical specimens without the requirement for enrichment. The updated approach produces sequences of high quality consistently and cost-effectively, suitable for implementation to underpin national and global programs for the surveillance of RSV genomic variation. The quality of sequence produced is essential for preparedness for new interventions in monitoring antigenic escape, where a single point mutation might lead to a reduction in antibody binding effectiveness and neutralizing activity, or indeed in the monitoring of retaining susceptibility to neutralization by existing and new interventions., Competing Interests: The authors declare no conflict of interest.

Strict control of systolic blood pressure is known to slow progression of chronic kidney disease (CKD). Here we compared audit-based education (ABE) to guidelines and prompts or usual practice in lowering systolic blood pressure in people with CKD. This 2-year cluster randomized trial included 93 volunteer general practices randomized into three arms with 30 ABE practices, 32 with guidelines and prompts, and 31 usual practices. An intervention effect on the primary outcome, systolic blood pressure, was calculated using a multilevel model to predict changes after the intervention. The prevalence of CKD was 7.29% (41,183 of 565,016 patients) with all cardiovascular comorbidities more common in those with CKD. Our models showed that the systolic blood pressure was significantly lowered by 2.41 mm Hg (CI 0.59-4.29 mm Hg), in the ABE practices with an odds ratio of achieving at least a 5 mm Hg reduction in systolic blood pressure of 1.24 (CI 1.05-1.45). Practices exposed to guidelines and prompts produced no significant change compared to usual practice. Male gender, ABE, ischemic heart disease, and congestive heart failure were independently associated with a greater lowering of systolic blood pressure but the converse applied to hypertension and age over 75 years. There were no reports of harm. Thus, individuals receiving ABE are more likely to achieve a lower blood pressure than those receiving only usual practice. The findings should be interpreted with caution due to the wide confidence intervals.