Background routine frailty identification and management is national policy in England, but there remains a lack of evidence on the impact of frailty on healthcare resource use. We evaluated the impact of frailty on the use and costs of general practice and hospital care. Methods retrospective longitudinal analysis using linked routine primary care records for 95,863 patients aged 65–95 years registered with 125 UK general practices between 2003 and 2014. Baseline frailty was measured using the electronic Frailty Index (eFI) and classified in four categories (non, mild, moderate, severe). Negative binomial regressions and ordinary least squares regressions with multilevel mixed effects were applied on the use and costs of general practice and hospital care. Results compared with non-frail status, annual general practitioner consultation incidence rate ratios (IRRs) were 1.24 (95% CI: 1.21–1.27) for mild, 1.41 (95% CI: 1.35–1.47) for moderate, and 1.52 (95% CI: 1.42–1.62) for severe frailty. For emergency hospital admissions, the respective IRRs were 1.64 (95% CI 1.60–1.68), 2.45 (95% CI 2.37–2.53) and 3.16 (95% CI: 3.00–3.33). Compared with non-frail people the IRR for inpatient days was 7.26 (95% CI 6.61–7.97) for severe frailty. Using 2013/14 reference costs, extra annual cost to the healthcare system per person was £561.05 for mild, £1,208.60 for moderate and £2,108.20 for severe frailty. This equates to a total additional cost of £5.8 billion per year across the UK. Conclusions increasing frailty is associated with substantial increases in healthcare costs, driven by increased hospital admissions, longer inpatient stay, and increased general practice consultations.

Aims: Diabetes is two to three times more prevalent in people with severe mental illness, yet little is known about the challenges of managing both conditions from the perspectives of people living with the co-morbidity, their family members or healthcare staff. Our aim was to understand these challenges and to explore the circumstances that influence access to and receipt of diabetes care for people with severe mental illness. Methods: Framework analysis of qualitative semi-structured interviews with people with severe mental illness and diabetes, family members, and staff from UK primary care, mental health and diabetes services, selected using a maximum variation sampling strategy between April and December 2018. Results: In all, 39 adults with severe mental illness and diabetes (3 with type 1 diabetes and 36 with type 2 diabetes), nine family members and 30 healthcare staff participated. Five themes were identified: (a) Severe mental illness governs everyday life including diabetes management; (b) mood influences capacity and motivation for diabetes self-management; (c) cumulative burden of managing multiple physical conditions; (d) This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The effect of chemotherapy on programmed cell death-ligand 1 (PD-L1) expression has been previously studied in lung cancer, while the results remain controversial. The aim of this study was to investigate the variation of PD-L1 expression after neoadjuvant chemotherapy and explore the association between chemotherapy response, prognosis and the variation of PD-L1 expression in lung cancer patients. A total of 63 lung cancer patients who received platinum-based neoadjuvant chemotherapy and subsequently underwent surgical resection were selected. PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC) was assessed by immunohistochemistry using 22C3 monoclonal antibody in these 63 matched lung cancer specimens before and after neoadjuvant chemotherapy. The positivity of PD-L1 on TC changed from 17.5% to 39.7% after neoadjuvant chemotherapy and the positivity of PD-L1 on IC changed from 19.0% to 71.4% after neoadjuvant chemotherapy. The elevation of PD-L1 expression on TC after neoadjuvant chemotherapy was more frequently observed in patients achieving stable disease or progressive disease than in patients achieving partial response ( P =0.026). Patients with elevated PD-L1 expression on TC after neoadjuvant chemotherapy showed a trend to have a shorter progression-free survival than patients without elevated PD-L1 expression on TC, although the difference was not statistically significant in multivariate analysis (hazard ratio=2.38, 95% confidence interval=0.99–5.73, P =0.053). PD-L1 expression can be elevated by chemotherapy in lung cancer. Furthermore, elevation of PD-L1 expression on TC after neoadjuvant chemotherapy was associated with reduced chemotherapy response and inferior progression-free survival in patients with lung cancer.

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Background: People with severe mental illnesses (SMI) have reduced life expectancy compared with the general population. Diabetes is a major contributor to this disparity with higher prevalence and poorer outcomes in people with SMI. Aim: To determine the impact of SMI on healthcare processes and outcomes for diabetes. Design and setting: Retrospective observational matched nested case-control study using patient records from the Clinical Practice Research Datalink linked to Hospital Episode Statistics. Methods: We compared a range of healthcare processes (primary care consultations, physical health checks, metabolic measurements) and outcomes (prevalence and hospitalisation for cardiovascular disease (CVD), and mortality risk) for 2,192 people with SMI and type 2 diabetes (cases) with 7,773 people with diabetes alone (controls). Socio-demographics, comorbidity and medication prescription were covariates in regression models. Results: SMI was associated with increased risk of all-cause mortality (Hazard Ratio [HR]: 1.92; 95% CI: 1.60 to 2.30) and CVD-specific mortality (HR: 2.24; 1.55 to 3.25); higher physician consultation rates (Incidence Rate Ratio [IRR]: 1.15; 1.11 to 1.19); more frequent checks of blood pressure (IRR: 1.02; 1.00 to 1.05) and cholesterol (IRR: 1.04; 1.02 to 1.06); lower prevalence of angina (Odds Ratio [OR]: 0.67; 0.45 to 1.00); higher emergency admissions for angina (IRR: 1.53; 1.07 to 2.20) and lower elective admissions for ischaemic heart disease (IRR: 0.68; 0.51 to 0.92). Conclusion: Monitoring of metabolic measurements was comparable for people with diabetes with and without SMI. Increased mortality rates observed in SMI may be attributable to under-diagnosis of CVD and delays in treatment.