A proof of concept for a deep learning system that can aid embryologists in predicting blastocyst survival after thaw.

The ability to understand whether embryos survive the thaw process is crucial to transferring competent embryos that can lead to pregnancy. The objective of this study was to develop a proof of concept deep learning model capable of assisting embryologist assessment of survival of thawed blastocysts prior to embryo transfer. A deep learning model was developed using 652 labeled time-lapse videos of freeze-thaw blastocysts. The model was evaluated against and along embryologists on a test set of 99 freeze-thaw blastocysts, using images obtained at 0.5 h increments from 0 to 3 h post-thaw. The model achieved AUCs of 0.869 (95% CI 0.789, 0.934) and 0.807 (95% CI 0.717, 0.886) and the embryologists achieved average AUCs of 0.829 (95% CI 0.747, 0.896) and 0.850 (95% CI 0.773, 0.908) at 2 h and 3 h, respectively. Combining embryologist predictions with model predictions resulted in a significant increase in AUC of 0.051 (95% CI 0.021, 0.083) at 2 h, and an equivalent increase in AUC of 0.010 (95% CI -0.018, 0.037) at 3 h. This study suggests that a deep learning model can predict in vitro blastocyst survival after thaw in aneuploid embryos. After correlation with clinical outcomes of transferred embryos, this model may help embryologists ascertain which embryos may have failed to survive the thaw process and increase the likelihood of pregnancy by preventing the transfer of non-viable embryos.

The impact of coronavirus disease 2019 on suspected head and neck cancer two-week-wait referrals.

BACKGROUND: The impact of coronavirus disease 2019 extends far beyond the immediate burden on healthcare systems caused by hospitalisation of patients with the disease itself. OBJECTIVE: To investigate the impact of the coronavirus disease 2019 pandemic on the referral rate of patients to the suspected head and neck cancer two-week-wait clinic. METHODS: A multicentre retrospective study was performed investigating data collected for all patients attending the suspected head and neck cancer two-week-wait clinic in ENT departments in the West Midlands. RESULTS: A total of 509 fast-track referrals were received from February to April in 2019, compared to 399 referrals in 2020. April 2020 saw a 62.4 per cent reduction in referral rate compared to April 2019. CONCLUSION: The coronavirus disease 2019 pandemic has resulted in changes to health-seeking behaviours, and healthcare provision and delivery. Urgent policy interventions may be required to compensate for the hidden impact that the coronavirus disease 2019 pandemic has had on those with cancer.

Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two-staged, adaptive placebo-controlled trial (APRICOT).

BACKGROUND: Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease that affects the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)-1. OBJECTIVES: To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit in PPP. METHODS: This was a randomized (1 : 1), double-blind, two-staged, adaptive, UK multicentre, placebo-controlled trial [ISCRTN13127147 (registered 1 August 2016); EudraCT number: 2015-003600-23 (registered 1 April 2016)]. Participants had a diagnosis of PPP (> 6 months) requiring systemic therapy. Treatment was 8 weeks of anakinra or placebo via daily, self-administered subcutaneous injections. Primary outcome was the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. RESULTS: A total of 374 patients were screened; 64 were enrolled (31 in the anakinra arm and 33 in the placebo arm) with a mean (SD) baseline PPPASI of 17·8 (10·5) and a PPP investigator's global assessment of severe (50%) or moderate (50%). The baseline adjusted mean difference in PPPASI favoured anakinra but did not demonstrate superiority in the intention-to-treat analysis [-1·65, 95% confidence interval (CI) -4·77 to 1·47; P = 0·30]. Similarly, secondary objective measures, including fresh pustule count (2·94, 95% CI -26·44 to 32·33; favouring anakinra), total pustule count (-30·08, 95% CI -83·20 to 23·05; favouring placebo) and patient-reported outcomes, did not show superiority of anakinra. When modelling the impact of adherence, the PPPASI complier average causal effect for an individual who received ≥ 90% of the total treatment (48% in the anakinra group) was -3·80 (95% CI -10·76 to 3·16; P = 0·285). No serious adverse events occurred. CONCLUSIONS: No evidence for the superiority of anakinra was found. IL-1 blockade is not a useful intervention for the treatment of PPP.

Implementing core NICE guidelines for osteoarthritis in primary care with a model consultation (MOSAICS): a cluster randomised controlled trial.

OBJECTIVE: To determine the effectiveness of a model osteoarthritis consultation, compared with usual care, on physical function and uptake of National Institute for Health and Care Excellence (NICE) osteoarthritis recommendations, in adults ≥45 years consulting with peripheral joint pain in UK general practice. METHOD: Two-arm cluster-randomised controlled trial with baseline health survey. Eight general practices in England. PARTICIPANTS: 525 adults ≥45 years consulting for peripheral joint pain, amongst 28,443 population survey recipients. Four intervention practices delivered the model osteoarthritis consultation to patients consulting with peripheral joint pain; four control practices continued usual care. The primary clinical outcome of the trial was the SF-12 physical component score (PCS) at 6 months; the main secondary outcome was uptake of NICE core recommendations by 6 months, measured by osteoarthritis quality indicators. A Linear Mixed Model was used to analyse clinical outcome data (SF-12 PCS). Differences in quality indicator outcomes were assessed using logistic regression. RESULTS: 525 eligible participants were enrolled (mean age 67.3 years, SD 10.5; 59.6% female): 288 from intervention and 237 from control practices. There were no statistically significant differences in SF-12 PCS: mean difference at the 6-month primary endpoint was -0.37 (95% CI -2.32, 1.57). Uptake of core NICE recommendations by 6 months was statistically significantly higher in the intervention arm compared with control: e.g., increased written exercise information, 20.5% (7.9, 28.3). CONCLUSION: Whilst uptake of core NICE recommendations was increased, there was no evidence of benefit of this intervention, as delivered in this pragmatic randomised trial, on the primary outcome of physical functioning at 6 months. TRIAL REGISTRATION: ISRCTN06984617.

Eltanolone for induction of anaesthesia and to supplement nitrous oxide for minor gynaecological surgery.

We have used eltanolone to induce anaesthesia and by intermittent injection to supplement nitrous oxide during maintenance in 50 patients undergoing minor gynaecological surgery; opioids were not used. Induction of anaesthesia was remarkably trouble free and achieved with a single dose of 0.5 mg.kg-1 in 90% of patients. Pain on injection was not a feature. Satisfactory anaesthesia was achieved in 84% of patients; eight required addition of isoflurane. There were minimal cardiovascular changes and apnoea on induction occurred in only one patient. Recovery times were acceptable.

The use of high-dose intravenous immunoglobulins in Guillain-Barré syndrome.

A patient with severe Guillain-Barré syndrome responded to treatment with high-dose intravenous immunoglobulins. It is suggested, on the basis of recent case reports, that immunoglobulins may have an important rôle in the future treatment of this immune-mediated disease.

The use of diazepam in chloroquine poisoning.

A 39-year-old patient was found to be unconscious after having taken 2.5 g of chloroquine. Treatment consisted mainly of gastric lavage and diazepam. Experimental and clinical evidence is presented to show that diazepam in varying doses significantly decreases the mortality rate.