Low circulatory levels of total cholesterol, HDL-C and LDL-C are associated with death of patients with sepsis and critical illness: systematic review, meta-analysis, and perspective of observational studies.

BACKGROUND: Mechanistic studies have established a biological role of sterol metabolism in infection and immunity with clinical data linking deranged cholesterol metabolism during sepsis with poorer outcomes. In this systematic review we assess the relationship between biomarkers of cholesterol homeostasis and mortality in critical illness. METHODS: We identified articles by searching a total of seven electronic databases from inception to October 2023. Prospective observational cohort studies included those subjects who had systemic cholesterol (Total Cholesterol (TC), HDL-C or LDL-C) levels assessed on the first day of ICU admission and short-term mortality recorded. Meta-analysis and meta-regression were used to evaluate overall mean differences in serum cholesterol levels between survivors and non-survivors. Study quality was assessed using the Newcastle-Ottawa Scale. FINDINGS: From 6469 studies identified by searches, 24 studies with 2542 participants were included in meta-analysis. Non-survivors had distinctly lower HDL-C at ICU admission -7.06 mg/dL (95% CI -9.21 to -4.91, p < 0.0001) in comparison with survivors. Corresponding differences were also seen less robustly for TC -21.86 mg/dL (95% CI -31.23 to -12.49, p < 0.0001) and LDL-C -8.79 mg/dL (95% CI, -13.74 to -3.83, p = 0.0005). INTERPRETATION: Systemic cholesterol levels (TC, HDL-C and LDL-C) on admission to critical care are inversely related to mortality. This finding is consistent with the notion that inflammatory and metabolic setpoints are coupled, such that the maladaptive-setpoint changes of cholesterol in critical illness are related to underlying inflammatory processes. We highlight the potential of HDL-biomarkers as early predictors of severity of illness and emphasise that future research should consider the metabolic and functional heterogeneity of HDLs. FUNDING: EU-ERDF-Welsh Government Ser Cymru programme, BBSRC, and EU-FP7 ClouDx-i project (PG).

Appraisal of Novel Oncological Therapies by the Scottish Medicines Consortium and the National Institute for Health and Care Excellence: A Comparative Study of Six Years of Data.

Background and aims Pharmacoeconomic assessment of novel oncological therapies is an increasingly important factor in determining patient access to therapies. Organisations such as the National Institute for Health and Care Excellence (NICE) in England and the Scottish Medicines Consortium (SMC) in Scotland assess medications for their cost-effectiveness through health technology assessments (HTA) and provide guidance on whether the public health service should fund a therapy. We assessed six years of data to determine if there were any differences in timescales and decisions between NICE and SMC for new oncological therapies. Methods and results Time (days) from marketing authorisation (MA) to publication of final HTA guidance was calculated for single technology appraisals published by NICE and SMC between January 1, 2017, and December 31, 2022, for oncological therapies. We assessed 161 HTAs by NICE and 148 HTAs by SMC published in the study period. The median time from MA to publication of HTA guidance was 291 days (IQR 222-406) for SMC and 257 days (IQR 167-448) for NICE (p=0.054). For solid organ cancer therapies, NICE was significantly faster in publishing guidance, with a median of 231.5 days (IQR 148-392.25), compared to SMC, which took 273 days (IQR 202-378) (p=0.039). Overall recommendation of technologies was similar between the SMC and NICE (90.5% and 89.4%, respectively), with discordance in a minority of cases (12.6%). Conclusions Recommendation rates for single HTAs are similar between NICE and SMC for oncological therapies with discordance in a minority of cases. The time from MA to publication of HTA guidance was similar overall, but NICE was faster in publishing HTA guidance for solid organ cancer indications. Differences in methodology and process between the two organisations, in particular the presence of the Cancer Drugs Fund in England, may explain this difference in publication times.

Interesting biological activities from plants traditionally used by Native Australians.

Four plants routinely used for medicinal purposes by Native Australians were screened for various biological activities. Methanol extracts of Eremophila maculata, Acacia auriculoformis and Acacia bivenosa exhibited antibiotic effects, while Eremophila alternifolia yielded an extract that induced significant changes to the heart activity of spontaneously hypertensive rats. We report on these biological activities.