Social determinants of health inequalities in early phase clinical trials in Northern England.

BACKGROUND: Early phase clinical trials in Oncology represent a subspecialised area where UK patient selection is influenced by access to Experimental Cancer Medicine Centres (ECMCs). Equity of access with respect to social determinants of health (SDoH) were explored for two major ECMCs. METHODS: A retrospective cohort study including all referrals to Newcastle and Manchester ECMCs in 2021 was completed. Consent to screening or pre-screening was stratified against SDoH characteristics, including: Index of Multiple Deprivation (IMD) decile, ethnicity and distance to centre. RESULTS: 1243 patients were referred for trials. IMD quintile 1 (most deprived) patients had reduced likelihood of referral compared to expected population models (OR, 0.67; 95% CI: 0.55 to 0.80, p = <0.0001). IMD quintile 5 (least deprived) had increased likelihood of referral (OR, 1.46; 95% CI: 1.17 to 1.82, p = 0.0007). Living beyond median distance from Manchester reduced the likelihood of consenting to trials (OR, 0.72; 95% CI: 0.55 to 0.94, p = 0.015). Ethnicity data represented a White British propensity. CONCLUSIONS: Inequalities in socioeconomic and geographic factors influence referral and enrolment to early phase clinical trials in Northern England. This has implications for equity of access and generalisability of trial results internationally and warrants further study.

Life after abciximab; what's next for intracoronary thrombus?

A case is described in which the short-acting glycoprotein IIb/IIIa receptor antagonist tirofiban was used in combination with heparin, aspirin and prasugrel to successfully treat extensive intracoronary thrombus in a delayed presentation STEMI, illustrating the utility of this approach.

Significant inhibitory impact of dibenzyl trisulfide and extracts of Petiveria alliacea on the activities of major drug-metabolizing enzymes in vitro: An assessment of the potential for medicinal plant-drug interactions.

Dibenzyl trisulfide (DTS) is the major active ingredient expressed in Petiveria alliacea L., a shrub widely used for a range of conditions, such as, arthritis, asthma and cancer. Given its use alone and concomitantly with prescription medicines, we undertook to investigate its impact on the activities of important drug metabolizing enzymes, the cytochromes P450 (CYP), a key family of enzymes involved in many adverse drug reactions. DTS and seven standardized extracts from the plant were assessed for their impact on the activities of CYPs 1A2, 2C19, 2C9, 2D6 and 3A4 on a fluorometric assay. DTS revealed significant impact against the activities of CYPs 1A2, 2C19 and 3A4 with IC50 values of 1.9, 4.0 and 3.2µM, respectively, which are equivalent to known standard inhibitors of these enzymes (furafylline, and tranylcypromine), and the most potent interaction with CYP1A2 displayed irreversible enzyme kinetics. The root extract, drawn with 96% ethanol (containing 2.4% DTS), displayed IC50 values of 5.6, 3.9 and 4.2µg/mL respectively, against the same isoforms, CYPs 1A2, 2C19 and 3A4. These investigations identify DTS as a valuable CYP inhibitor and P. alliacea as a candidate plant worthy of clinical trials to confirm the conclusions that extracts yielding high DTS may lead to clinically relevant drug interactions, whilst extracts yielding low levels of DTS, such as aqueous extracts, are unlikely to cause adverse herb-drug interactions.

An in-vacuo optical levitation trap for high-intensity laser interaction experiments with isolated microtargets.

We report on the design, construction, and characterisation of a new class of in-vacuo optical levitation trap optimised for use in high-intensity, high-energy laser interaction experiments. The system uses a focused, vertically propagating continuous wave laser beam to capture and manipulate micro-targets by photon momentum transfer at much longer working distances than commonly used by optical tweezer systems. A high speed (10 kHz) optical imaging and signal acquisition system was implemented for tracking the levitated droplets position and dynamic behaviour under atmospheric and vacuum conditions, with ±5 µm spatial resolution. Optical trapping of 10 ± 4 µm oil droplets in vacuum was demonstrated, over timescales of >1 h at extended distances of ∼40 mm from the final focusing optic. The stability of the levitated droplet was such that it would stay in alignment with a ∼7 µm irradiating beam focal spot for up to 5 min without the need for re-adjustment. The performance of the trap was assessed in a series of high-intensity (10(17) W cm(-2)) laser experiments that measured the X-ray source size and inferred free-electron temperature of a single isolated droplet target, along with a measurement of the emitted radio-frequency pulse. These initial tests demonstrated the use of optically levitated microdroplets as a robust target platform for further high-intensity laser interaction and point source studies.

Multiwavelength interferometry system for the Orion laser facility.

We report on the design and testing of a multiwavelength interferometry system for the Orion laser facility based upon the use of self-path matching Wollaston prisms. The use of UV corrected achromatic optics allows for both easy alignment with an eye-safe light source and small (∼ millimeter) offsets to the focal lengths between different operational wavelengths. Interferograms are demonstrated at wavelengths corresponding to first, second, and fourth harmonics of a 1054 nm Nd:glass probe beam. Example data confirms the broadband achromatic capability of the imaging system with operation from the UV (263 nm) to visible (527 nm) and demonstrates that features as small as 5 µm can be resolved for object sizes of 15 by 10 mm. Results are also shown for an off-harmonic wavelength that will underpin a future capability. The primary optics package is accommodated inside the footprint of a ten-inch manipulator to allow the system to be deployed from a multitude of viewing angles inside the 4 m diameter Orion target chamber.

The Anti-cancer Activity of Vernonia divaricata Sw against Leukaemia, Breast and Prostate Cancers In Vitro.

BACKGROUND: Vernonia divaricata is one of five endemic Vernonia species of Jamaica. The ethno-medicinal uses of other species have been established, however, scientific validation of this species has not yet been done and as such this paper is aimed at identifying the anti-cancer activity of V divaricata against leukaemia, breast and prostate cancer cell lines. METHODS: Leaves and stems of V divaricata were dried and milled into powder. The crude hexane and methanol extracts of the leaves and stems were obtained and bio-assayed using WST-1 cell proliferation assay against leukaemia, breast and prostate cancer cell lines. RESULTS: The crude hexane and methanol extracts of V divaricata were able to significantly retard the growth of the MCF-7 (breast), HL-60 (leukaemia) and the PC-3 (prostate) cancer cell lines. The crude methanol extract of the stem was the strongest, exhibiting anti-proliferation activity with IC50 values of 10.14, 12.63 and 9.894 µg/ml for the HL-60, MCF-7 and PC-3 cancer cell lines, respectively, with the most potent toward prostate cancer. CONCLUSION: The medicinal use of V divaricata as an anti-cancer agent was corroborated as the crude hexane and methanol extracts demonstrated potent anti-proliferation activity and as such hold potential for further research and development into a drug to prevent or treat various cancers.

Acute coronary syndrome and stable coronary artery disease: are they so different? Long-term outcomes in a contemporary PCI cohort.

BACKGROUND: Patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) are known to have poorer short-term prognosis compared to stable coronary artery (CAD) patients undergoing elective PCI. Few studies have made direct comparison of long-term mortality between ACS and stable CAD patients undergoing PCI. The aim of our study was to compare the long-term mortality following PCI between patients with ACS and those with stable CAD. METHODS: We examined consecutive patients undergoing PCI with stenting at a tertiary referral hospital. Clinical, angiographic and biochemical data were collected and analysed. The primary outcome was all-cause mortality retrieved from the Statewide Death Registry database. RESULTS: Included were 1923 consecutive PCI patients (970 stable CAD and 953 ACS). The mean follow-up time was 4.1 years ± 1.8 years. In-hospital mortality was 1.4% overall, seen exclusively in patients with ACS (n=28, 2.9%). Post-discharge mortality was 6.7% among patients with stable CAD and 10.5% for ACS (P<0.01). Multivariate predictors of post-discharge deaths for both groups included age (HR 1.08 per year, P<0.001) and impaired renal function (HR 2.49, P<0.001). Following adjustment for these factors, an ACS indication for PCI was not associated with greater post-discharge mortality (adjusted HR 1.18: 0.85-1.64, P=0.32). CONCLUSIONS: Patients undergoing PCI following an ACS have higher long-term mortality to those with stable CAD, which is potentially explained by a greater prevalence of comorbidities. This suggests that for the ACS population, contemporary interventional and medical management strategies may effectively and specifically counter the adverse prognostic impact of coronary instability and myocardial damage.

In vitro and in vivo anti-cancer effects of tillandsia recurvata (ball moss) from Jamaica.

OBJECTIVE: Tillandsia recurvata, also commonly known as Ball Moss, is endemic to Jamaica and some parts of the Caribbean and South America. The plant, despite being reported to be used in folk medicine, had not previously been evaluated for its anti-cancer potential. The aim of this study was to evaluate the anti-cancer activity ofBall Moss. METHODS: The anti-proliferation activity of the crude methanolic extract of the T recurvata was evaluated in vitro in five different histogenic cancer cell lines (prostate cancer - PC-3, breast cancer Kaposi sarcoma, B-16 melanoma and a B-cell lymphoma from a transgenic mouse strain) using the trypan blue assay. The crude extract was also evaluated in vivo in tumour-bearing mice. Immunohistochemistry staining with Apoptag was used for histology and determination of apoptosis. RESULTS: The crude methanolic extract of T recurvata demonstrated anti-proliferation activity against all the cell lines, killing > 50% of the cells at a concentration of 2.5 microg/ml. Kaposi sarcoma xenograft tumours were inhibited by up to 75% compared to control in the in vivo study (p < 0.05). There was evidence of DNA fragmentation and a decrease in cell viability on histological studies. The methanolic extract showed no toxic effect in the mice at a dose of 200 mg/kg. CONCLUSIONS: Our data suggest that T recurvata has great potential as an anti-cancer agent and that one of its mechanisms of cell kill and tumour inhibition is by the induction of apoptosis.

Intravascular optical coherence tomography (OCT) during contrast injection: a leap forward in intracoronary imaging.

Imaging the coronary vasculature using Optical Coherence Tomography (OCT) is now possible using motorised pullback during contrast injection.