The Royal Sussex County Hospital is an acute teaching hospital in Brighton, England. Together with the Princess Royal Hospital, it is administered by the University Hospitals Sussex NHS Foundation Trust. The services provided at the hospital include an emergency department, cancer services at the Sussex Cancer Centre, cardiac surgery, maternity services, and both adult and neonatal intensive care units.
Rapid diagnosis of giant cell arteritis (GCA) is essential to prevent ischemic complications. Color Doppler ultrasound (CDUS) and high-resolution magnetic resonance imaging (MRI) are increasingly used as alternatives or adjuncts to temporal artery biopsy, but their comparative diagnostic performance remains uncertain. We performed a systematic review and bivariate random-effects meta-analysis of diagnostic accuracy studies in adults with suspected GCA. Studies reporting extractable 2×2 data against temporal artery biopsy, or accepted clinical reference standards when biopsy was unavailable, were included. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Pooled sensitivity, specificity, diagnostic odds ratios (DOR), and summary receiver operating characteristic (ROC) curves were calculated, with evaluation of heterogeneity and publication bias. Thirty-nine studies, including 3,619 patients, met the inclusion criteria. Thirty-one studies assessed CDUS (2,766 patients) and 12 evaluated MRI (853 patients). For CDUS, the median sensitivity was 0.83 (range 0.17-1.00) and the median specificity was 0.88 (range 0.59-1.00), with a median DOR of 24.9 and substantial between-study variability. MRI demonstrated a median sensitivity of 0.88 (range 0.61-1.00), a median specificity of 0.92 (range 0.71-1.00), and a higher median DOR of 72.0, with more consistent estimates. Evidence of small-study or publication bias was observed for MRI (p≈0.0004) and was borderline for CDUS (p≈0.055). QUADAS-2 assessments were generally favorable, though common limitations included variable blinding, heterogeneous imaging protocols, and differences in corticosteroid timing. MRI demonstrates higher and more consistent diagnostic performance than CDUS. CDUS can achieve high accuracy in experienced centers but shows notable operator dependence. Both modalities support imaging-based diagnostic pathways for GCA, with the choice influenced by local expertise, resource availability, and corticosteroid exposure.
BACKGROUND:Current society guidelines recommend physiological assessment of intermediate coronary lesions to guide revascularization. Data regarding revascularization guided by vessel fractional flow reserve (vFFR), derived from three-dimensional quantitative coronary angiography without the need for a pressure wire or hyperemic agent, as compared with pressure-wire-based fractional flow reserve (FFR), are lacking. METHODS:We conducted an international, open-label, randomized, noninferiority trial at 37 sites in Europe. Patients with intermediate coronary-artery lesions (diameter stenosis of 30 to 80%) who presented with chronic or acute coronary syndromes were randomly assigned in a 1:1 ratio to undergo either vFFR-guided or FFR-guided revascularization of the intermediate coronary-artery lesions. The primary end point was a composite of death from any cause, any myocardial infarction, or any revascularization at 1 year. The noninferiority margin was 3.0 percentage points. RESULTS:The primary end point was assessed in 1116 patients in the vFFR group and 1095 in the FFR group. The mean age of the patients was 67 years, 24.3% were women, 18.7% presented with an acute coronary syndrome, and 26.6% had diabetes mellitus. At 1 year, a primary end-point event had occurred in 80 patients (Kaplan-Meier estimate, 7.5%) in the vFFR group and in 79 patients (Kaplan-Meier estimate, 7.5%) in the FFR group (risk difference, -0.02 percentage points; 95% confidence interval, -2.25 to 2.21; P = 0.004 for noninferiority). The incidence of serious adverse events appeared to be similar in the two groups. CONCLUSIONS:Among patients with intermediate coronary lesions, vFFR-guided revascularization was noninferior to FFR-guided revascularization with respect to a composite of death, myocardial infarction, or revascularization at 1 year. (Funded by Pie Medical Imaging and Siemens Healthineers; FAST III ClinicalTrials.gov number, NCT04931771.).
BACKGROUND:Percutaneous coronary intervention (PCI) is increasingly used for revascularization of unprotected left main coronary artery disease. Whether intravascular ultrasonographic (IVUS) guidance during PCI results in better clinical outcomes than conventional angiographic guidance alone is uncertain. METHODS:In an international, multicenter, open-label trial, we randomly assigned patients with unprotected left main coronary artery disease in a 1:1 ratio to undergo either IVUS-guided PCI or angiography-guided PCI. The primary end point was a patient-oriented composite of any stroke, any myocardial infarction, any revascularization, or death from any cause at the longest follow-up. RESULTS:A total of 806 patients underwent randomization; 401 were assigned to undergo IVUS-guided PCI and 405 to undergo angiography-guided PCI. The mean (±SD) age of the patients was 71.4±10.7 years, 78.4% of the patients were men, and 34.7% had diabetes. At a median follow-up of 2.9 years, a primary end-point event had occurred in 135 patients (33.7%) in the IVUS-guided PCI group and in 125 patients (30.9%) in the angiography-guided PCI group (hazard ratio, 1.11; 95% confidence interval, 0.87 to 1.42; P = 0.40). The incidence of death, myocardial infarction, or revascularization appeared to be similar in the two groups. The percentages of patients with procedure-related and overall safety events also appeared to be similar in the two groups. CONCLUSIONS:Among patients with unprotected left main coronary artery disease, IVUS-guided PCI showed no additional benefit over angiography-guided PCI with respect to the incidence of stroke, myocardial infarction, any revascularization, or death from any cause at a median follow-up of 2.9 years. (Funded by Philips Image Guided Therapy Devices and Boston Scientific; OPTIMAL ClinicalTrials.gov number, NCT04111770.).
INTRODUCTION:Nitazenes are potent synthetic opioids. Following reports questioning their post-mortem stability, nitazene-related deaths may have been underestimated in the United Kingdom. We investigated this using a rat model and regional coronial data, and also present national pharmacoepidemiologic trends in nitazene-related deaths. METHOD:In vivo/ex vivo study: Anaesthetised Wistar rats (n = 12) received intravenous nitazene (metonitazene, N-desethyl isotonitazene, or N-pyrrolidino etonitazene). Rats were euthanised 15 min post-administration if cardiorespiratory arrest had not already occurred (n = 8). Blood and urine were collected, with repeat blood samples taken following cadaver refrigeration (4 °C) for one week. All samples were immediately frozen (-80 °C). Upon defrosting, half were analysed immediately by liquid chromatography tandem mass spectroscopy with half stored at 4 °C for 1 month before analysis. PHARMACOEPIDEMIOLOGY:Nitazene deaths were extracted from the National Programme on Substance Use Mortality in March 2025 along with all deaths from the Birmingham & Solihull coronial area (2019-2023). Descriptive analyses were conducted along with exponential smoothing models to compare observed and forecasted deaths in Birmingham & Solihull in 2023. RESULTS:In vivo/ex vivo study: A small fraction of the nitazene detected in the immediate post-mortem blood sample remained in the post-mortem day 7 blood sample that had been refrigerated for 1 month. PHARMACOEPIDEMIOLOGY:In Birmingham and Solihull, non-nitazene drug deaths rose 33% in 2023 compared to 2019-2022 (predicted n = 107, actual n = 142). By March 2025, 285 deaths with nitazene detections were reported to the National Programme on Substance Use Mortality, with small clusters in 2021 (n = 23) and 2022 (n = 15) before markedly increasing in 2023 (n = 131). Twelve nitazenes were detected with the predominant nitazene shifting over time (2021: isotonitazene; 2022: N-pyrrolidino etonitazene; 2023: N-desethyl isotonitazene). Coroners deemed nitazenes causative in 90% of cases (n = 256/285). CONCLUSIONS:Nitazene-related deaths have increased in England, Wales, and Northern Ireland, and may have been underestimated due to post-mortem instability. Urgent public health action is required to reduce nitazene-related harms.
