There is increasing recognition of an important contribution of chemokines and their receptors in the pathology of atherosclerosis and related cardiovascular disease. The chemokine receptor CCR5 was initially known for its role as a co-receptor for HIV infection of macrophages and is the target of the recently approved CCR5 antagonist maraviroc. However, evidence is now emerging supporting a role for CCR5 and its ligands CCL3 (MIP-1α), CCL4 (MIP-1β) and CCL5 (RANTES) in the initiation and progression of atherosclerosis. Specifically, the CCR5 deletion polymorphism CCR5delta32, which confers resistance to HIV infection, has been associated with a reduced risk of cardiovascular disease and both CCR5 antagonism and gene deletion reduce atherosclerosis in mouse models of the disease. Antagonism of CCL5 has also been shown to reduce atherosclerotic burden in these animal models. Crucially, CCR5 and its ligands CCL3, CCL4 and CCL5 have been identified in human and mouse vasculature and have been detected in human atherosclerotic plaque. Not unexpectedly, CC chemokines have also been linked to saphenous vein graft disease, which shares similarity to native vessel atherosclerosis. Distinct roles for chemokine-receptor systems in atherogenesis have been proposed, with CCR5 likely to be critical in recruitment of monocytes to developing plaques. With an increased burden of cardiovascular disease observed in HIV-infected individuals, the potential cardiovascular-protective effects of drugs that target the CCR5 receptor warrant greater attention. The availability of clinically validated antagonists such as maraviroc currently provides an advantage for targeting of CCR5 over other chemokine receptors.

Summary The endogenous and lipopolysaccharide stimulated interleukin (IL)‐1β production in vitro by peritoneal monocytes/macrophages from patients on continuous ambulatory peritoneal dialysis (CAPD) was examined during episodes of infection and inflammation. Measurement of immunoreactive IL‐1β and bioactive IL‐1 in both supernatants and cell lysates after culture for 18 h revealed that these cells secreted a significantly lower proportion of total IL‐1 than that measured for elutriated blood monocytes. For the inflammatory peritoneal cells, the proportion of total IL‐1β that was cell‐associated resembled that reported for more differentiated pulmonary alveolar macrophages and for adherent monocytes cultured for 18 h prior to stimulation. A similar reduced ability to secrete IL‐1β was detected for unfractionated peritoneal cells from CAPD patients without peritonitis upon direct comparison with the IL‐1β production by blood mononuclear cells from the same patients. These results suggested that at a time when a pro‐inflammatory response by extravasated host monocytes/macrophages was required by CAPD patients with peritonitis, only a minor proportion of total IL‐1β would be available extracellularly. This study highlights the rapidity with which extravasated monocytes lose their ability to secrete IL‐lβ and raises the possibility that an important site of utilization of IL‐1βin vivo may be intracellular in its location.

Introduction According to the Health Education England (HEE) Framework for Enhanced Health in Care Homes 2020, 33% of people over 65 and 50% of people over 80 have one or more fall a year, figures which significantly increase in care home residents. Prevention of falls promotes the quality of life of elderly patients and could significantly reduce the burden on primary and secondary care stemming from fall induced fractures, loss of mobility and community follow up. The Comprehensive Geriatric Assessment (CGA) for falls includes a full falls assessment questionnaire, medication review, lying/standing blood pressure and frailty index. The HEE set out a requirement that all care home patients should have a CGA assessment within 7 days of readmission to a care home following a hospital episode because of a fall. This audit examined the compliance of Four Counties primary care network (PCN) to the 7-day CGA HEE guideline for falls. Methods Retrospective analysis of 68 eligible patients from Four Counties PCN between 31st March 2021 and 1st March 2022. Analysis indicated a poor compliance to the HEE CGA guidelines (15%). After presenting to the MDT, we formulated a system-wide plan to improve reporting of care home falls to OTs, creating protected time for pharmacists to conduct care home medication reviews and promoting in-person weekly care-coordinator meetings. The PCN was audited for a second time after 3 months. Results A significant improvement (15% to 57%) in adherence to the HEE CGA framework was noted after implementation of above changes. Medication review in 7 days improved from 42% to 80% and falls assessment questionnaire in 7 days compliance improved from 23% to 70%. Conclusion Creating clear protocols for reporting falls and clarifying MDT roles in the CGA are essential to identifying and preventing falls in at-risk care home residents.