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The decision in the Montgomery Supreme Court Ruling (UK 2015) has important implications for those involved in counselling pregnant women and it is suggested it is relevant not only in relation to potential risks to the baby but also potential risks to the mother. This article aims to consider the impact of the decision of the Supreme Court in Montgomery on information disclosure to patients in the UK but the decision may also have ethical implications which will be relevant in other countries.

Background Metformin is a hypoglycaemic medication that has been proposed to treat or prevent preeclampsia. Combining national birth data from Scotland and Sweden, we investigated whether metformin used during pregnancy was associated with an altered risk of developing a hypertensive disorder of pregnancy. Methods We utilised data from two population-based cohorts: Scotland (2012–2018) and Sweden (2007–2019). Nulliparous women with gestational diabetes or type 2 diabetes who had birth outcome data linked with medications prescribed during pregnancy were included. The association between metformin prescription and hypertensive disorders of pregnancy was characterised using inverse probability weighted regression analysis, adjusting for variables that predict metformin use and potential confounders. Adverse neonatal outcomes were included as secondary outcomes. Results from both countries were then combined in a meta-analysis using a random effects model. Results The Scottish cohort included 3859 women with gestational diabetes or type 2 diabetes. Of these women, 30.8% ( n  = 1187) received at least one metformin prescription during pregnancy. For Sweden, 7771 women with gestational diabetes were included where 19.3% (1498) used metformin during pregnancy. Metformin prescription was not associated with an altered risk of any hypertensive disorder of pregnancy (Scotland adjusted relative risk (aRR) 0.88 [95% confidence interval (CI) 0.66–1.19]; Sweden aRR 1.08 [95% CI 0.86–1.37]) or preeclampsia (Scotland aRR 1.02 [95% CI 0.66–1.60]; Sweden aRR 1.00 [95% CI 0.72–1.39]). Combining adjusted results in a meta-analysis produced similar findings, with a pooled RR of 0.98 (95% CI 0.79–1.18) for any hypertensive disorder and RR 1.01 ([95% CI 0.73–1.28]) for preeclampsia. For neonatal outcomes, metformin was associated with a reduced risk of birthweight > 4500 g in Scotland (aRR 0.39 [95% CI 0.21–0.71]) but not in Sweden. There was no association between metformin and preterm birth or birthweight < 3rd or < 10th percentiles. Pooling results from both countries, metformin was not associated with adverse neonatal outcomes, including preterm birth (RR 1.00 [95% CI 0.89–1.13]), and birthweight < 10th percentile (RR 0.82 [95% CI 0.60–1.13]) or < 3rd percentile (RR 0.78 [95% CI 0.41–1.48]). Conclusions In this two-country analysis, metformin use in pregnancy among women with diabetes was not associated with an altered risk of developing any hypertensive disorder of pregnancy. In the combined meta-analysis, metformin was not associated with an altered risk of adverse neonatal outcomes.

Background Endometriosis affects 190 million women and those assigned female at birth worldwide. For some, it is associated with debilitating chronic pelvic pain. Diagnosis of endometriosis is often achieved through diagnostic laparoscopy. However, when isolated superficial peritoneal endometriosis (SPE), the most common endometriosis subtype, is identified during laparoscopy, limited evidence exists to support the common decision to surgically remove it via excision or ablation. Improved understanding of the impact of surgical removal of isolated SPE for the management of chronic pelvic pain in women is required. Here, we describe our protocol for a multi-centre trial to determine the effectiveness of surgical removal of isolated SPE for the management of endometriosis-associated pain. Methods We plan to undertake a multi-centre participant-blind parallel-group randomised controlled clinical and cost-effectiveness trial with internal pilot. We plan to randomise 400 participants from up to 70 National Health Service Hospitals in the UK. Participants with chronic pelvic pain awaiting diagnostic laparoscopy for suspected endometriosis will be consented by the clinical research team. If isolated SPE is identified at laparoscopy, and deep or ovarian endometriosis is not seen, participants will be randomised intraoperatively (1:1) to surgical removal (by excision or ablation or both, according to surgeons’ preference) versus diagnostic laparoscopy alone. Randomisation with block-stratification will be used. Participants will be given a diagnosis but will not be informed of the procedure they received until 12 months post-randomisation, unless required. Post-operative medical treatment will be according to participants’ preference. Participants will be asked to complete validated pain and quality of life questionnaires at 3, 6 and 12 months after randomisation. Our primary outcome is the pain domain of the Endometriosis Health Profile-30 (EHP-30), via a between randomised group comparison of adjusted means at 12 months. Assuming a standard deviation of 22 points around the pain score, 90% power, 5% significance and 20% missing data, 400 participants are required to be randomised to detect an 8-point pain score difference. Discussion This trial aims to provide high quality evidence of the clinical and cost-effectiveness of surgical removal of isolated SPE. Trial registration ISRCTN registry ISRCTN27244948. Registered 6 April 2021.

The law relating to consent and the process dentists need to go through to gain valid and informed consent to treat patients changed significantly following the landmark ruling of Montgomery v Lanarkshire Health Board. In this paper, we revisit the history of patient consent, give an update on the current legal situation in the UK, and produce a unique 'consent workflow' to aid in the process of gaining valid and informed consent to treat. The aim is to clarify the legal standing and provide a framework that dentists and other healthcare professionals can adapt to their current clinical practice while increasing the confidence of those involved in the consent process; both professionals and patients.Key pointsProvides an overview of the current legal position regarding consent to treat. Describes the consent process in detail.Introduces a unique workflow to aid in gaining valid and informed consent in practice.

Tubal ectopic pregnancies can cause substantial morbidity or even death. Current treatment is with methotrexate or surgery. Methotrexate treatment fails in approximately 30% of women who subsequently require rescue surgery. Gefitinib, an epidermal growth factor receptor inhibitor, might improve the effects of methotrexate. We assessed the efficacy of oral gefitinib with methotrexate, versus methotrexate alone, to treat tubal ectopic pregnancy. We performed a multicentre, randomised, double-blind, placebo-controlled trial across 50 UK hospitals. Participants diagnosed with tubal ectopic pregnancy were administered a single dose of intramuscular methotrexate (50 mg/m2) and randomised (1:1 ratio) to 7 days of additional oral gefitinib (250 mg daily) or placebo. The primary outcome, analysed by intention to treat, was surgical intervention to resolve the ectopic pregnancy. Secondary outcomes included time to resolution of ectopic pregnancy and serious adverse events. This trial is registered at the ISRCTN registry, ISCRTN 67795930. Between Nov 2, 2016, and Oct 6, 2021, 328 participants were allocated to methotrexate and gefitinib (n=165) or methotrexate and placebo (n=163). Three participants in the placebo group withdrew. Surgical intervention occurred in 50 (30%) of 165 participants in the gefitinib group and in 47 (29%) of 160 participants in the placebo group (adjusted risk ratio 1·15, 95% CI 0·85 to 1·58; adjusted risk difference –0·01, 95% CI –0·10 to 0·09; p=0·37). Without surgical intervention, median time to resolution was 28·0 days in the gefitinib group and 28·0 days in the placebo group (subdistribution hazard ratio 1·03, 95% CI 0·75 to 1·40). Serious adverse events occurred in five (3%) of 165 participants in the gefitinib group and in six (4%) of 162 participants in the placebo group. Diarrhoea and rash were more common in the gefitinib group. In women with a tubal ectopic pregnancy, adding oral gefitinib to parenteral methotrexate does not offer clinical benefit over methotrexate and increases minor adverse reactions. National Institute of Health Research.

Purpose Red-blood-cell (RBC) transfusion is one of the most frequent interventions in critical care patients. While patients with acute cardiac conditions are more likely to receive transfusions at higher haemoglobin thresholds than other critically ill patients, data on RBC transfusion practice for critically ill patients with pre-existing cardiac conditions are scarce. Methods Using the International Point-Prevalence Study of Intensive-Care Unit Transfusion Practices cohort, weighted logistic regression investigated the association between the RBC units transfused and the primary composite outcome of 28-day mortality, new-onset acute kidney injury or ventilatory weaning failure. Interactions with cardiac history (acute coronary syndrome and/or heart failure) were tested. Results Cardiac history was present in 746 of 3643 patients (20%) and 894 of 3643 (25%) received at least one RBC unit. Transfusion rates were similar in patients with and without cardiac history (25% vs. 24%; p = 0.51). Among transfused patients, median nadir haemoglobin during ICU stay was slightly higher in those with cardiac history (7.6 g/dL vs. 7.4 g/dL respectively; p = 0.007), whereas stated haemoglobin transfusion threshold did not statistically differ (8.5 g/dL vs. 8.0 g/dL; p = 0.11). Each additional RBC unit increased the odds of the composite outcome in the whole cohort (2.18, 95% CI 1.85–2.56, p < 0.0001), without interaction with cardiac history (p = 0.44). Conclusions RBC transfusion was commonly and similarly prescribed in critically ill patients with or without cardiac history. Each additional unit was associated with a worse outcome with no evidence of differential effect due to cardiac history. Trial registration NL9049 (Dutch Trial Register), registered on 16 November 2020. Graphical Abstract

The purpose of this study was to determine how a teacher accountability partner can affect student attendance, perception of school, and the long-term impact on attendance of a high school senior. Goal setting, self-advocacy, and progress monitoring were also examined. Thirty at -risk seniors completed surveys on attendance and perception of schools. These students created attendance goals and monitored themselves to determine if they were achieving their individual goals. There was an increase in attendance over the intervention period. Some changes in the reasons why students were missing school were also shown. The results indicated a very weak impact on school perceptions.

We report a fatal case of COVID-19 in a 51-year-old African American woman with multiple sclerosis on natalizumab. She had multiple risk factors for severe COVID-19 disease including race, obesity, hypertension, and elevated inflammatory markers, but the contribution of natalizumab to her poor outcome remains unknown. We consider whether altered dynamics of peripheral immune cells in the context of natalizumab treatment could worsen the cytokine storm syndrome associated with severe COVID-19. We discuss extended interval dosing as a risk-reduction strategy for multiple sclerosis patients on natalizumab, and the use of interleukin-6 inhibitors in such patients who contract COVID-19.

The tumour suppressor gene p53 is one of the most frequently mutated genes in lung cancer and these defects are associated with poor prognosis, albeit some debate exists in the lung cancer field. Despite extensive research, the exact mechanisms by which mutant p53 proteins promote the development and sustained expansion of cancer remain unclear. This review will discuss the cellular responses controlled by p53 that contribute to tumour suppression, p53 mutant lung cancer mouse models and characterisation of p53 mutant lung cancer. Furthermore, we discuss potential approaches of targeting mutant p53 for the treatment of lung cancer.