Background Capivasertib (AZD5363) is a potent selective oral inhibitor of all three isoforms of the serine/threonine kinase AKT. The FAKTION trial investigated whether the addition of capivasertib to fulvestrant improved progressionfree survival in patients with aromatase inhibitor-resistant advanced breast cancer.Methods In this randomised, double-blind, placebo-controlled, phase 2 trial, postmenopausal women aged at least 18 years with an Eastern Cooperative Oncology Group performance status of 0-2 and oestrogen receptor-positive, HER2-negative, metastatic or locally advanced inoperable breast cancer who had relapsed or progressed on an aromatase inhibitor were recruited from 19 hospitals in the UK. Enrolled participants were randomly assigned (1:1) to receive intramuscular fulvestrant 500 mg (day 1) every 28 days (plus a loading dose on day 15 of cycle 1) with either capivasertib 400 mg or matching placebo, orally twice daily on an intermittent weekly schedule of 4 days on and 3 days off (starting on cycle 1 day 15) until disease progression, unacceptable toxicity, loss to follow-up, or withdrawal of consent. Treatment allocation was done using an interactive web-response system using a minimisation method (with a 20% random element) and the following minimisation factors: measurable or non-measurable disease, primary or secondary aromatase inhibitor resistance, PIK3CA status, and PTEN status. The primary endpoint was progression-free survival with a one-sided alpha of 0•20. Analyses were done by intention to treat. Recruitment is complete, and the trial is in follow-up. This trial is registered with ClinicalTrials.gov, number NCT01992952.

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SummaryAlthough haematology analysers provide reliable full blood counts, they are known to be inaccurate at enumerating platelets in severe thrombocytopenia. If the thresholds for platelet transfusion, currently set at 10 · 10 9 /l, are to be further reduced, it is vital that the limitations of current analysers are fully understood. The aim of this large multicentre study was to determine the accuracy of haematology analysers in current routine practice for platelet counts below 20 · 10 9 /l. Platelet counts estimated by analysers using optical, impedance and immunological methods were compared with the International Reference Method for platelet counting. The results demonstrated variation in platelet counting between different analysers and even the same type of analyser at different sites. Optical methods for platelet counting on the XE 2100, Advia 120, Cell-Dyn 4000 and H3* were not superior to impedance methods on the XE 2100, LH750 and Pentra analysers. All analysers except one overestimated the platelet count, which would result in under transfusion of platelets. This study highlights the inaccuracies of haematology analysers in platelet counting in severe thrombocytopenia. It re-emphasizes the need for external quality control to improve analyser calibration for samples with low platelet counts, and suggests that the optimal thresholds for prophylactic platelet transfusions should be re-evaluated.

A barcode patient identification system was found to simplify the clinical transfusion process and improve practice. These results provide support for further work on the development of such systems for transfusion and for other hospital procedures requiring patient identification.

These findings suggest that universal LD has further reduced the already low risk of TA-GVHD in immunocompetent recipients and has altered the profile of PTP cases.

In patients without preoperative evidence of myocardial ischaemia undergoing elective hip and knee replacement surgery, a restrictive transfusion strategy seems unlikely to be associated with an increased incidence of SMI. A proportion of these patients experience moderate SMI, regardless of the transfusion trigger. Use of a restrictive transfusion strategy did not increase length of hospital stay, and use of this strategy would lead to a significant reduction in red cell transfusion in orthopaedic surgery. Our data did not indicate any potential for harm in employing such a strategy in patients with no prior evidence of cardiac ischaemia who were undergoing elective orthopaedic surgery.

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Objectives To model the determinants of serious operative and post-operative complications of hysterectomy and their potential risk factors. Design A prospective cohort of women undergoing hysterectomies for benign indications in 1994/1995, with a six-week postsurgery follow up. Population and setting A total of 37,512 women from 276 NHS and 145 private hospitals in England, Wales and Northern Ireland, originally recruited to compare the outcomes of endometrial destruction with those of hysterectomy. Methods Gynaecologists reported hysterectomies for non-malignant indications carried out during a 12-month period beginning in October 1994 and follow up data were obtained at outpatient follow up six weeks postsurgery. Odds ratios of severe complications by indication and method, adjusting for measured intrinsic risk factors, were calculated. Main outcome measures Severe operative and post-operative complications.Results Severe operative complications occurred in 3%. The risk decreased with age and increased with greater parity and history of serious illness. Women with symptomatic fibroids (4.4%, 95% CI 3.9 -4.9) experienced more complications than women with dysfunctional uterine bleeding (3.6%, 3.2 -3.8), adjusted odds ratio (OR) ¼ 1.3 (95% CI 1.1 -1.6). Laparoscopic procedures (6.1%) doubled the risk of operative complications of abdominal hysterectomy (3.6%) (adjusted OR ¼ 1.9, 1.5-2.5). Post-operative complications occurred in around 1% of women, with a slight decrease with increasing age, and the strongest risk factor was a history of operative complications. Relative to dysfunctional uterine bleeding (1.0%), a higher risk for fibroids (1.2%) persisted after adjustments (RR ¼ 1.5, 1.1-2.0). Both vaginal (1.2%) and laparoscopic (1.7%) techniques had significantly higher adjusted risks than abdominal operations (0.9%), RR ¼ 1.4 (1.0 -1.9) and RR ¼ 1.6 (1.0 -2.7). There were no operative deaths; 14 women died within the six-week postsurgery (a crude mortality rate of 3.8/1000, 2.5 -6.4). Conclusions Hysterectomy is a common, routine surgery with comparatively rare serious complications.However, younger women, women with more vascular pelvises, who undergo hysterectomy, especially laparoscopically assisted vaginal surgery for symptomatic fibroids, are at most risk of experiencing severe complications both operatively and post-operatively. Therefore, a less invasive alternative treatment for symptomatic fibroids could particularly benefit this group of women, while less invasive treatments for dysfunctional uterine bleeding, such as various methods of endometrial ablations or resections, would need to meet the current low levels of clinical complications in order to replace hysterectomy.