Real-world analysis of clinical and economic impact of 21-gene recurrence score (RS) testing in early-stage breast cancer (ESBC) in Ireland.

PURPOSE: Results from TAILOR-X suggest that up to 70% of hormone receptor-positive (HR+) node-negative (N0) ESBC patients (pts) may avoid chemotherapy (CT) with RS ≤ 25. We assess clinical and economic impacts of RS testing on treatment using real-world data. METHODS: From October 2011 to February 2019, a retrospective, cross-sectional observational study was conducted of HR+ N0 ESBC pts who had RS testing in Ireland. Pts were classified low risk (RS ≤ 25) and high risk (RS > 25). Clinical risk was calculated. Data were collected via electronic patient records. Cost data were supplied by the National Healthcare Pricing Regulatory Authority. RESULTS: 963 pts. Mean age is 56 years. Mean tumour size is 1.7 cm. 114 (11.8%), 635 (66%), 211 (22%), 3 (0.2%) pts had G1, G2, G3 and unknown G, respectively. 796 pts (82.8%) low RS, 159 (16.5%) high RS and 8 pts (0.7%) unknown RS. 263 pts (26%) were aged ≤ 50 at diagnosis; 117 (45%) had RS 0-15, 63 (24.5%) 16-20, 39 (15.3%) 21-25 and 40 (15.2%) RS 26-100. 4 pts (1.5%) had unknown RS. Post-RS testing, 602 pts (62.5%) had a change in CT decision; 593 changed to hormone therapy (HT) alone. In total, 262 pts received CT. Of pts receiving CT; 138 (53%) had RS > 25, 124 (47%) had RS ≤ 25. Of pts aged ≤ 50, 153 (58%) had high clinical risk, of whom 28 had RS 16-20. Assay use achieved a 62.5% change in treatment with 73% of pts avoiding CT. This resulted in savings of €4 million in treatment costs. Deducting assay costs, savings of €1.9 million were achieved. CONCLUSION: Over the 8 years of the study, a 62.5% reduction in CT use was achieved with savings of over €1,900,000.

Trauma Training and Workload: A National Survey.

Trauma is a major source of mortality and morbidity throughout Ireland. Training in trauma is dependant on experience gained by trainees within specific posts. Trauma services are a topical issue at present with much discussion about delivery and restructuring. With this in mind we conducted an online survey of trainees in emergency medicine, orthopaedic and general surgery to assess current experience and opinions with regard to trauma. The survey was vetted and distributed by the relevant training bodies. 59(98.33%) respondents believed smaller units should be bypassed for major trauma and 55 (91.67%) believed that larger hospitals receiving major trauma should have a trauma theatre available 24-hours a day. 55 (91.67%) also foresaw themselves covering major trauma as consultants, consequently these trainees will be the consultants developing, moulding and working in this restructured trauma service.

Cognitive performance effects of subcutaneous nicotine in smokers and never-smokers.

In a double-blind placebo-controlled crossover study the effects of two doses of subcutaneous nicotine and saline were compared on a range of performance measures in 18 abstaining smokers and 18 never-smokers. Each subject received two injections (40 min apart) of saline, 0.3 mg nicotine, or 0.6 mg nicotine in a balanced order over three sessions. Performance was assessed before and after the injections on nine tests [news recall, Sternberg memory task, finger tapping, logical reasoning, rapid visual information processing (RVIP), long-term word recognition, digit recall, Stroop test, and critical flicker fusion threshold]. In the abstinent smokers, nicotine produced significantly faster correct responses on the logical reasoning test, more target hits, faster reaction times and improved sensitivity on the RVIP task, and more correct responses on word recognition. In never-smokers, nicotine produced faster reaction times on the RVIP and digit-recall tasks, although in the latter case this was at the expense of fewer correct responses. There were no significant differences between the two groups' responses to nicotine but smokers performed worse than never-smokers prior to injections, even controlling for background characteristics. These results are consistent with other recent research suggesting a primary effect of nicotine in enhancing cognitive performance.

Effect of subcutaneous nicotine injections of EEG alpha frequency in non-smokers: a placebo-controlled pilot study.

The effect of two subcutaneous injections of 0.6 mg nicotine, administered 40 min apart, was compared with placebo in four non-smoking subjects in a counter-balanced double-blind crossover design. The nicotine injections produced mean peak plasma nicotine concentrations of 5.3 ng/ml 10 min after the first injection and 8.5 ng/ml 10 min after the second injection. The nicotine injections produced an increase in mean dominant alpha frequency on the electroencephalogram (EEG) which was 2 Hz greater than the effect of placebo (P = 0.049) and also produced a heart-rate boost which was 8 beats per minute greater than that produced by placebo (P = 0.022). These effects on dominant alpha frequency and heart rate were most apparent in the 10 min following each nicotine injection. The increase in dominant alpha frequency found in non-smokers in this study was similar to that following nicotine inhalation in abstinent smokers in previous studies, and suggests that this is a primary effect of nicotine, rather than simply a reversal of withdrawal-induced EEG slowing.

Stress fiber reformation after ATP depletion.

Fluorescently labeled heavy meromyosin, alpha-actinin, and vinculin were used to localize actin, alpha-actinin, and vinculin, respectively, in permeabilized and living cells during the process of stress fiber reassembly, which occurred when cells were removed from ATP-depleting medium (20 mM sodium azide and 10 mM 2-deoxyglucose). In 80% of the cells recovering from ATP depletion, small, scattered plaques containing actin, alpha-actinin, and vinculin were replaced by long, thin, periodic fibers within 5 minutes of removal of the inhibitors. These nascent stress fibers grew broader as recovery progressed, until they attained the thickness of stress fibers in control cells. In the other 20% of the cells, the scattered plaques aggregated within 5 minutes of reversal, and almost all the actin, alpha-actinin, and vinculin in the cells became localized in one perinuclear aggregate, with a diameter of approximately 15-25 micron. As recovery progressed, all aggregates resembled rings, with diameters that increased at about 0.5 micron/minute and grew to as large as 70 micron in some giant cells. As the size of the rings increased, fibers radiated outward from them and sometimes spanned the diameter of the rings. The shape of the cells did not change during this time. By 1 hour after reversal, the rings were no longer present and all cells had networks of stress fibers. Indirect immunofluorescence techniques used to localize tubulin and vimentin indicated that microtubules and intermediate filaments were not constituents of the rings, and the rings were not closely apposed to the substrate, judging from reflection contrast optics. The rapid rearrangement of attachment plaques into a perinuclear aggregate that spreads radially in the cytoplasm occurs at the same speed as fibroblast and chromosomal movement, but is unlike other types of intracytoplasmic motility.