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Summary: Background: The 7th National Audit Project of the Royal College of Anaesthetists studied peri‐operative cardiac arrest because of existing knowledge gaps in this important topic. This applies in particular to cardiology patients receiving anaesthetic care, because numbers, types and complexity of minimally invasive interventional procedures requiring planned and unplanned anaesthesia in the cardiac intervention suite is increasing. Methods: We analysed collected data to determine the epidemiology, clinical features, management and outcomes of peri‐operative cardiac arrest in adult patients receiving anaesthetic care for cardiology procedures. Results: There were 54 reports of peri‐operative cardiac arrest in adult patients receiving anaesthetic care for cardiology procedures, accounting for 54/881 (6.1%) of all reports to NAP7. The estimated incidence (95%CI) of cardiac arrests in this group was 1/450 or 0.22 (0.17–0.29)%. These patients were older than other adult patients in the NAP7 population, with a notably high proportion of patients of Asian ethnicity when compared with the remaining NAP7 cohort (9/54, 17% vs. 35/709, 5%). Rates of extracorporeal membrane oxygenation cardiopulmonary resuscitation were low (3/53, 6%). A common theme was that of logistical issues and teamworking, with reporters commenting on the difficulties of remote and/or unfamiliar locations and communication issues between specialties, on occasion resulting in poor teamworking and a lack of focus. The NAP7 panel review identified several other common themes which included: cardiogenic shock; late involvement of anaesthesia in the case; and transcatheter aortic valve implantation. Conclusion: Cardiology procedures requiring anaesthesia care account for < 1% of anaesthesia activity but generate 6% of all peri‐operative cardiac arrests. The incidence of cardiac arrest was disproportionately high in cardiological procedures requiring anaesthetic care. The nature of the cardiac arrest reports to NAP7 indicate that logistical and human factors in multidisciplinary teams in the cardiac intervention suite merit addressing to improve care. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion Pilonidal sinus disease (PSD) is a common condition. Despite a relatively large proportion of patients presenting as post‐pubertal adolescents, only small cohorts focusing on this PSD subcategory have been published, and surgical treatment remains challenging.The study is based on a prospective database established at Randers Regional Hospital in 2016. All patients undergoing Bascom's cleft lift (BCL) surgery from June 2016 until June 2020 were included in this study, focusing on patients ≤18 years of age comparing them to adult patients. Indications for BCL surgery were primary extensive manifestation, non‐healing disease after previous elective surgery or disease recurrence.In total, n = 380 PSD patients were operated, of which n = 79 were post‐pubertal adolescents with a median age at time of surgery of 17.2 years (interquartile range 16.3, 18.0). Sixty‐six (84%) were boys. Twenty‐seven (34%) presented with primary extensive manifestation, 34 (43%) due to non‐healing wounds and 18 (23%) due to recurrence. Fifty‐four patients (69%) healed uneventfully. There was no difference between the indications of surgery groups in terms of overall healing or time to healing if prolonged (P = 0.6). The median follow‐up was 62 months (interquartile range 48, 73), with a 5‐year recurrence rate of 19%, compared to 17% (P = 0.6) in the adult population.Our study is the first to investigate long‐term clinical outcomes of BCL surgery for PSD in post‐pubertal adolescent patients. Recurrences seem to occur more frequently compared to adults. However, we demonstrate that post‐pubertal adolescent patients with advanced PSD can be treated with BCL surgery with acceptable outcomes. [ABSTRACT FROM AUTHOR]

Summary: Frailty increases peri‐operative risk, but details of its burden, clinical features and the risk of, and outcomes following, peri‐operative cardiac arrest are lacking. As a preplanned analysis of the 7th National Audit Project of the Royal College of Anaesthetists, we described the characteristics of older patients living with frailty undergoing anaesthesia and surgery, and those reported to the peri‐operative cardiac arrest case registry. In the activity survey, 1676 (26%) of 6466 patients aged > 65 y were reported as frail (Clinical Frailty Scale score ≥ 5). Increasing age and frailty were both associated with increasing comorbidities and the proportion of surgery undertaken as an emergency. Except in patients who were terminally ill (Clinical Frailty Scale score 9), increasing frailty was associated with an increased proportion of complex or major surgery. The rate of use of invasive arterial blood pressure monitoring was associated with frailty only until Clinical Frailty Scale score 5, and then plateaued or fell. Of 881 cardiac arrests reported to the 7th National Audit Project, 156 (18%) were in patients aged > 65 y and living with frailty, with an estimated incidence of 1 in 1204 (95%CI 1 in 1027–1412) and a mortality rate of 1 in 2020 (95%CI 1 in 1642–2488), approximately 2.6‐fold higher than in adults who were not frail. Hip fracture, emergency laparotomy, emergency vascular surgery and urological surgery were the most common surgical procedures in older patients living with frailty who had a cardiac arrest. We report a high burden of frailty within the surgical population, requiring complex, urgent surgery, and the extent of poorer outcomes of peri‐operative cardiac arrest compared with patients of the same age not living with frailty. [ABSTRACT FROM AUTHOR]

As climate change thrives, and the frequency of intense droughts is affecting many forested regions, a mechanistic understanding of the factors conferring drought tolerance in trees is increasingly important. However, studies linking the observed growth reduction to mechanistic traits are still rare. We compared the median growth anomalies of 16 native tree species, gathered across a network of study plots in Bavaria, with the mean species‐specific turgor loss point (πtlp) measured at five locations in Central Europe πtlp explained 37% of the growth anomalies observed in response to the intense droughts between 2018 and 2020 compared to the pre‐drought period between 2006 and 2017 across sites. πtlp constitutes an important leaf drought tolerance trait and influences the growth response of native tree species during extraordinary dry periods. As climate change‐induced droughts intensify, tree species with drought‐tolerant leaves will be less vulnerable to growth reductions. πtlp provides a useful indicator for selecting tree species to adapt forest management systems to climate change. [ABSTRACT FROM AUTHOR]

Objective: Subclinical leaflet thrombosis (SLT) develops in 15% of patients undergoing trans‐catheter aortic valve replacement (TAVR). TAVR is a procedure in which a faulty aortic valve is replaced with a mechanical one. An aortic valve replacement can be done with open‐heart surgery; this is called surgical aortic valve replacement (SAVR). A significant problem is defining the best course of treatment for asymptomatic individuals with SLT post‐TAVR, including the use of oral anticoagulation (OAC) in it. Study design: Systematic review. Method: The most pertinent published research (original papers and reviews) in the scientific literature were searched for and critically assessed using the online, internationally indexed databases PubMed, Medline, and Cochrane Reviews. Keywords like "Transcatheter valve replacement" and "Subclinical leaflet thrombosis" were used to search the papers. Selected studies were critically assessed for inclusion based on predefined criteria. Results: The review examined the prevalence and characteristics of SLT after TAVR. To note, the incidence of SLT is seen to be higher in TAVR compared SAVR. Dual antiplatelet therapy, which is utilized in antithrombotic regimens post‐TAVR, can possibly hasten SLT progression which could result in the impaired mobility of leaflets and the worsening of pressure gradients. Conclusion: The use of dual antiplatelet drugs in routine antithrombotic therapy tends to accelerate initial subclinical leaflet thrombosis after TAVI, which results in a developing restriction of leaflet mobility and an increase in pressure differences. [ABSTRACT FROM AUTHOR]

Blast disease causes significant damage to millets (pearl millet, finger millet and foxtail millet) and rice in India. This study investigates strains of Pyricularia, the causal agent of blast disease, in rice and millets in India in terms of their diversity, host preferences and phylogeny. One hundred and thirty‐six Pyricularia isolates causing rice and millet blast were collected from 46 locations in India. They displayed morphological diversity irrespective of host or location. All Pyricularia isolates were separated into two major clusters by a multilocus sequence‐based phylogenetic tree, which also demonstrated that most isolates are grouped according to their host associations. In contrast, a few finger millet isolates were found to be grouped with foxtail millet isolates. We explored how Pyricularia isolates behaved when exposed to rice and millets. Finger millet isolates were shown to be pathogenic on a wide variety of millets, whereas rice isolates were only found to infect rice and wheat. The majority of the blast isolates of millets were shown to be pathogenic on common weed species of the millet ecosystem, such as Echinochloa crusgalli, Eleusina indica and Erogrotis gagantica. Our findings emphasize the importance of pathogen surveillance in both cultivated crops and weed hosts, as well as the possible risk of blast fungus infection in Indian millets due to host expansion. Blast disease control programmes in India will be greatly enhanced by the knowledge gained in this study on the diversity and host association of Pyricularia strains. [ABSTRACT FROM AUTHOR]

Summary: Current guidance recommends that, in most circumstances, cardiopulmonary resuscitation should be attempted when cardiac arrest occurs during anaesthesia, and when a patient has a pre‐existing 'do not attempt cardiopulmonary resuscitation' recommendation, this should be suspended. How this guidance is translated into everyday clinical practice in the UK is currently unknown. Here, as part of the 7th National Audit Project of the Royal College of Anaesthetists, we have: assessed the rates of pre‐operative 'do not attempt cardiopulmonary resuscitation' recommendations via an activity survey of all cases undertaken by anaesthetists over four days in each participating site; and analysed our one‐year case registry of peri‐operative cardiac arrests to understand the rates of cardiac arrest in patients who had 'do not attempt cardiopulmonary resuscitation' decisions pre‐operatively. In the activity survey, among 20,717 adults (aged > 18 y) undergoing surgery, 595 (3%) had a 'do not attempt cardiopulmonary resuscitation' recommendation pre‐operatively, of which less than a third (175, 29%) were suspended. Of the 881 peri‐operative cardiac arrest reports, 54 (6%) patients had a 'do not attempt cardiopulmonary resuscitation' recommendation made pre‐operatively and of these 38 (70%) had a clinical frailty scale score ≥ 5. Just under half (25, 46%) of these 'do not attempt cardiopulmonary resuscitation' recommendations were formally suspended at the time of anaesthesia and surgery. One in five of these patients with a 'do not attempt cardiopulmonary resuscitation' recommendation who had a cardiac arrest survived to leave hospital and of the seven patients with documented modified Rankin Scale scores before and after cardiac arrest, four remained the same and three had worse scores. Very few patients who had a pre‐existing 'do not attempt cardiopulmonary resuscitation' recommendation had a peri‐operative cardiac arrest, and when cardiac arrest did occur, return of spontaneous circulation was achieved in 57%, although > 50% of these patients subsequently died before discharge from hospital. [ABSTRACT FROM AUTHOR]

Summary: The 7th National Audit Project of the Royal College of Anaesthetists studied peri‐operative cardiac arrest in the UK, a topic of importance to patients, anaesthetists and surgeons. We report the results of the 12‐month registry phase, from 16 June 2021 to 15 June 2022, focusing on management and outcomes. Among 881 cases of peri‐operative cardiac arrest, the initial rhythm was non‐shockable in 723 (82%) cases, most commonly pulseless electrical activity. There were 665 (75%) patients who survived the initial event and 384 (52%) who survived to hospital discharge. A favourable functional outcome (based on modified Rankin Scale score) was reported for 249 (88%) survivors. Outcomes varied according to arrest rhythm. The highest rates of survival were seen for bradycardic cardiac arrests with 111 (86%) patients surviving the initial event and 77 (60%) patients surviving the hospital episode. The lowest survival rates were seen for patients with pulseless electrical activity, with 312 (68%) surviving the initial episode and 156 (34%) surviving to hospital discharge. Survival to hospital discharge was worse in patients at the extremes of age with 76 (40%) patients aged > 75 y and 9 (45%) neonates surviving. Hospital survival was also associated with surgical priority, with 175 (88%) elective patients and 176 (37%) non‐elective patients surviving to discharge. Outcomes varied with the cause of cardiac arrest, with lower initial survival rates for pulmonary embolism (5, 31%) and bone cement implantation syndrome (9, 45%), and hospital survival of < 25% for pulmonary embolism (0), septic shock (13, 24%) and significant hyperkalaemia (1, 20%). Overall care was rated good in 464 (53%) cases, and 18 (2%) cases had overall care rated as poor. Poor care elements were present in a further 245 (28%) cases. Care before cardiac arrest was the phase most frequently rated as poor (92, 11%) with elements of poor care identified in another 186 (21%) cases. These results describe the management and outcomes of peri‐operative cardiac arrest in UK practice for the first time. [ABSTRACT FROM AUTHOR]

Summary: Complications and critical incidents arising during anaesthesia due to patient, surgical or anaesthetic factors, may cause harm themselves or progress to more severe events, including cardiac arrest or death. As part of the 7th National Audit Project of the Royal College of Anaesthetists, we studied a prospective national cohort of unselected patients. Anaesthetists recorded anonymous details of all cases undertaken over 4 days at their site through an online survey. Of 416 hospital sites invited to participate, 352 (85%) completed the survey. Among 24,172 cases, 1922 discrete potentially serious complications were reported during 1337 (6%) cases. Obstetric cases had a high reported major haemorrhage rate and were excluded from further analysis. Of 20,996 non‐obstetric cases, 1705 complications were reported during 1150 (5%) cases. Circulatory events accounted for most complications (616, 36%), followed by airway (418, 25%), metabolic (264, 15%), breathing (259, 15%), and neurological (41, 2%) events. A single complication was reported in 851 (4%) cases, two complications in 166 (1%) cases and three or more complications in 133 (1%) cases. In non‐obstetric elective surgery, all complications were 'uncommon' (10–100 per 10,000 cases). Emergency (urgent and immediate priority) surgery accounted for 3454 (16%) of non‐obstetric cases but 714 (42%) of complications with severe hypotension, major haemorrhage, severe arrhythmias, septic shock, significant acidosis and electrolyte disturbances all being 'common' (100–1000 per 10,000 cases). Based on univariate analysis, complications were associated with: younger age; higher ASA physical status; male sex; increased frailty; urgency and extent of surgery; day of the week; and time of day. These data represent the rates of potentially serious complications during routine anaesthesia care and may be valuable for risk assessment and patient consent. [ABSTRACT FROM AUTHOR]

Summary: The 7th National Audit Project of the Royal College of Anaesthetists studied peri‐operative cardiac arrest in the UK, a topic of importance to patients, anaesthetists and surgeons. Here we report the results of the 12‐month registry, from 16 June 2021 to 15 June 2022, focusing on epidemiology and clinical features. We reviewed 881 cases of peri‐operative cardiac arrest, giving an incidence of 3 in 10,000 anaesthetics (95%CI 3.0–3.5 per 10,000). Incidence varied with patient and surgical factors. Compared with denominator survey activity, patients with cardiac arrest: included more males (56% vs. 42%); were older (median (IQR) age 60.5 (40.5–80.5) vs. 50.5 (30.5–70.5) y), although the age distribution was bimodal, with infants and patients aged > 66 y overrepresented; and were notably more comorbid (73% ASA physical status 3–5 vs. 27% ASA physical status 1–2). The surgical case‐mix included more weekend (14% vs. 11%), out‐of‐hours (19% vs. 10%), non‐elective (65% vs. 30%) and major/complex cases (60% vs. 28%). Cardiac arrest was most prevalent in orthopaedic trauma (12%), lower gastrointestinal surgery (10%), cardiac surgery (9%), vascular surgery (8%) and interventional cardiology (6%). Specialities with the highest proportion of cases relative to denominator activity were: cardiac surgery (9% vs. 1%); cardiology (8% vs. 1%); and vascular surgery (8% vs. 2%). The most common causes of cardiac arrest were: major haemorrhage (17%); bradyarrhythmia (9%); and cardiac ischaemia (7%). Patient factors were judged a key cause of cardiac arrest in 82% of cases, anaesthesia in 40% and surgery in 35%. [ABSTRACT FROM AUTHOR]

Summary: The Royal College of Anaesthetists' 7th National Audit Project baseline survey assessed knowledge, attitudes, practices and experiences of peri‐operative cardiac arrests among UK anaesthetists and Anaesthesia Associates. We received 10,746 responses, representing a 71% response rate. In‐date training in adult and paediatric advanced life support was reported by 9646 (90%) and 7125 (66%) anaesthetists, respectively. There were 8994 (84%) respondents who were confident in leading a peri‐operative cardiac arrest, with males more confident than females, but only 5985 (56%) were confident in leading a debrief and 7340 (68%) communicating with next of kin. In the previous two years, 4806 (46%) respondents had managed at least one peri‐operative cardiac arrest, of which 321 (7%) and 189 (4%) of these events involved a child or an obstetric patient, respectively. Respondents estimated the most common causes of peri‐operative cardiac arrest to be hypovolaemia, hypoxaemia and cardiac ischaemia, with haemorrhage coming fifth. However, the most common reported causes for the most recently attended peri‐operative cardiac arrest were haemorrhage; (927, 20%); anaphylaxis (474, 10%); and cardiac ischaemia (397, 9%). Operating lists or shifts were paused or stopped after 1330 (39%) cardiac arrests and 1693 (38%) respondents attended a debrief, with 'hot' debriefs most common. Informal wellbeing support was relatively common (2458, 56%) and formal support was uncommon (472, 11%). An impact on future care delivery was reported by 196 (4%) anaesthetists, most commonly a negative psychological impact. Management of a peri‐operative cardiac arrest during their career was reported by 8654 (85%) respondents. The overall impact on professional life was more often judged positive (2630, 30%) than negative (1961, 23%), but impact on personal life was more often negative. [ABSTRACT FROM AUTHOR]

Summary: We report the results of the Royal College of Anaesthetists' 7th National Audit Project organisational baseline survey sent to every NHS anaesthetic department in the UK to assess preparedness for treating peri‐operative cardiac arrest. We received 199 responses from 277 UK anaesthetic departments, representing a 72% response rate. Adult and paediatric anaesthetic care was provided by 188 (95%) and 165 (84%) hospitals, respectively. There was no paediatric intensive care unit on‐site in 144 (87%) hospitals caring for children, meaning transfer of critically ill children is required. Remote site anaesthesia is provided in 182 (92%) departments. There was a departmental resuscitation lead in 113 (58%) departments, wellbeing lead in 106 (54%) and departmental staff wellbeing policy in 81 (42%). A defibrillator was present in every operating theatre suite and in all paediatric anaesthesia locations in 193 (99%) and 149 (97%) departments, respectively. Advanced airway equipment was not available in: every theatre suite in 13 (7%) departments; all remote locations in 103 (57%) departments; and all paediatric anaesthesia locations in 23 (15%) departments. Anaesthetic rooms were the default location for induction of anaesthesia in adults and children in 148 (79%) and 121 (79%) departments, respectively. Annual updates in chest compressions and in defibrillation were available in 149 (76%) and 130 (67%) departments, respectively. Following a peri‐operative cardiac arrest, debriefing and peer support programmes were available in 154 (79%) and 57 (29%) departments, respectively. While it is likely many UK hospitals are very well prepared to treat anaesthetic emergencies including cardiac arrest, the survey suggests this is not universal. [ABSTRACT FROM AUTHOR]

Summary: The probability of death after emergency laparotomy varies greatly between patients. Accurate pre‐operative risk prediction is fundamental to planning care and improving outcomes. We aimed to develop a model limited to a few pre‐operative factors that performed well irrespective of surgical indication: obstruction; sepsis; ischaemia; bleeding; and other. We derived a model with data from the National Emergency Laparotomy Audit for patients who had emergency laparotomy between December 2016 and November 2018. We tested the model on patients who underwent emergency laparotomy between December 2018 and November 2019. There were 4077/40,816 (10%) deaths 30 days after surgery in the derivation cohort. The final model had 13 pre‐operative variables: surgical indication; age; blood pressure; heart rate; respiratory history; urgency; biochemical markers; anticipated malignancy; anticipated peritoneal soiling; and ASA physical status. The predicted mortality probability deciles ranged from 0.1% to 47%. There were 1888/11,187 deaths in the test cohort. The scaled Brier score, integrated calibration index and concordance for the model were 20%, 0.006 and 0.86, respectively. Model metrics were similar for the five surgical indications. In conclusion, we think that this prognostic model is suitable to support decision‐making before emergency laparotomy as well as for risk adjustment for comparing organisations. [ABSTRACT FROM AUTHOR]

Ibrutinib is a Bruton tyrosine kinase (Btk) inhibitor for treating chronic lymphocytic leukemia (CLL). It has also been associated with hypertension. The optimal dosing schedule for mitigating this adverse effect is currently under discussion. A quantification of relationships between systemic ibrutinib exposure and efficacy (i.e., leukocyte count and sum of the product of perpendicular diameters [SPD] of lymph nodes) and hypertension toxicity (i.e., blood pressure), and their association with overall survival is needed. Here, we present a semi‐mechanistic pharmacokinetic‐pharmacodynamic modeling framework to characterize such relationships and facilitate dose optimization. Data from a phase Ib/II study were used, including ibrutinib plasma concentrations to derive daily 0–24‐h area under the concentration‐time curve, leukocyte count, SPD, survival, and blood pressure measurements. A nonlinear mixed effects modeling approach was applied, considering ibrutinib's pharmacological action and CLL cell dynamics. The final framework included (i) an integrated model for SPD and leukocytes consisting of four CLL cell subpopulations with ibrutinib inhibiting phosphorylated Btk production, (ii) a turnover model in which ibrutinib stimulates an increase in blood pressure, and (iii) a competing risk model for dropout and death. Simulations predicted that the approved dosing schedule had a slightly higher efficacy (24‐month, progression‐free survival [PFS] 98%) than de‐escalation schedules (24‐month, average PFS ≈ 97%); the latter had, on average, ≈20% lower proportions of patients with hypertension. The developed modeling framework offers an improved understanding of the relationships among ibrutinib exposure, efficacy and toxicity biomarkers. This framework can serve as a platform to assess dosing schedules in a biologically plausible manner. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to explore the perspectives of adults born prematurely on guidelines for management at extreme premature birth and personalisation at the limit of viability. Methods: We conducted four 2‐h online focus group interviews in the Netherlands. Results: Twenty‐three participants born prematurely were included in this study, ranging in age from 19 to 56 years and representing a variety of health outcomes. Participants shared their perspectives on different types of guidelines for managing extremely premature birth. They agreed that a guideline was necessary to prevent arbitrary treatment decisions and to avoid physician bias. All participants favoured a guideline that is based upon multiple prognostic factors beyond gestational age. They emphasised the importance of discretion, regardless of the type of guideline used. Discussions centred mainly on the heterogeneity of value judgements about outcomes after extreme premature birth. Participants defined personalisation as 'not just looking at numbers and statistics'. They associated personalisation mainly with information provision and decision‐making. Participants stressed the importance of involving families in decision‐making and taking their care needs seriously. Conclusion: Adults born prematurely prefer a periviability guideline that considers multiple prognostic factors and allows for discretion. [ABSTRACT FROM AUTHOR]

Background and aim: Malnutrition in older patients is linked to poor appetite. Cannabis‐based medicine may have orexigenic properties in older patients, but this has to our knowledge never been investigated. In older patients, uncertainty applies to the accuracy of estimated glomerular filtration rate (eGFR) based on creatinine, which is crucial for medication prescribing. In older patients with poor appetite, the study aims (1) to assess the efficacy of Sativex® (8.1‐mg delta‐9‐tetrahydrocannabinol [THC] and 7.5‐mg cannabidiol [CBD]) to stimulate appetite and (2) to compare the performance of various GFR‐estimates and measured‐GFR (mGFR) for determining gentamicin clearance utilizing population pharmacokinetic (popPK) modelling methods. Methods and objectives: This study is composed of two substudies. Substudy 1 is an investigator‐initiated single‐center, double‐blinded, randomized, placebo‐controlled, superiority, cross‐over study. Substudy 1 will recruit 17 older patients with poor appetite, who will also be invited to substudy 2. Substudy 2 is a single‐dose pharmacokinetics study and will recruit 55 patients. Participants will receive Sativex® and placebo in substudy 1 and gentamicin with simultaneous measurements of GFR in substudy 2. The primary endpoints are as follows: Substudy 1—the difference in energy intake between Sativex® and placebo conditions; substudy 2— the accuracy of different eGFR equations compared to mGFR. The secondary endpoints include safety parameters, changes in the appetite hormones, total ghrelin and GLP‐1 and subjective appetite sensations, and the creation of popPK models of THC, CBD, and gentamicin. [ABSTRACT FROM AUTHOR]

Summary: It is essential that academic publishing complies with the highest standards in terms of ethics, research conduct and manuscript preparation. This protects the rights and welfare of research participants, ensures the integrity of study results and aids the communication and dissemination of novel findings into clinical practice. This position statement outlines the current policies and practices of the Editors of Anaesthesia and Anaesthesia Reports in relation to academic medical publishing. [ABSTRACT FROM AUTHOR]

Objective: To develop a core set of prenatal and neonatal outcomes for clinical studies evaluating perinatal interventions for congenital diaphragmatic hernia, using a validated consensus‐building method. Methods: An international steering group comprising 13 leading maternal–fetal medicine specialists, neonatologists, pediatric surgeons, patient representatives, researchers and methodologists guided the development of this core outcome set. Potential outcomes were collected through a systematic review of the literature and entered into a two‐round online Delphi survey. A call was made for stakeholders with experience of congenital diaphragmatic hernia to review the list and score outcomes based on their perceived relevance. Outcomes that fulfilled the consensus criteria defined a priori were discussed subsequently in online breakout meetings. Results were reviewed in a consensus meeting, during which the core outcome set was defined. Finally, the definitions, measurement methods and aspirational outcomes were defined in online and in‐person definition meetings by a selection of 45 stakeholders. Results: Overall, 221 stakeholders participated in the Delphi survey and 198 completed both rounds. Fifty outcomes met the consensus criteria and were discussed and rescored by 78 stakeholders in the breakout meetings. During the consensus meeting, 93 stakeholders agreed eventually on eight outcomes, which constituted the core outcome set. Maternal and obstetric outcomes included maternal morbidity related to the intervention and gestational age at delivery. Fetal outcomes included intrauterine demise, interval between intervention and delivery and change in lung size in utero around the time of the intervention. Neonatal outcomes included neonatal mortality, pulmonary hypertension and use of extracorporeal membrane oxygenation. Definitions and measurement methods were formulated by 45 stakeholders, who also added three aspirational outcomes: duration of invasive ventilation, duration of oxygen supplementation and use of pulmonary vasodilators at discharge. Conclusions: We developed with relevant stakeholders a core outcome set for studies evaluating perinatal interventions in congenital diaphragmatic hernia. Its implementation should facilitate the comparison and combination of trial results, enabling future research to better guide clinical practice. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Aim: We explored professionals' views on sharing decision‐making with parents before and after an extremely preterm birth and what healthcare professionals considered severe outcomes. Methods: A nationwide, multi‐centre online survey was carried out among a wide range of perinatal healthcare professionals in the Netherlands from 4 November 2020 to 10 January 2021. The medical chairs of all nine Dutch Level III and IV perinatal centres helped to disseminate the survey link. Results: We received 769 survey responses. Most respondents (53%) preferred to place equal emphasis on two treatment options during shared prenatal decision‐making: early intensive care or palliative comfort care. The majority (61%) wanted to include a conditional intensive care trial as a third treatment option, but 25% disagreed. Most (78%) felt that healthcare professionals were responsible for initiating postnatal conversations to justify continuing or withdrawing neonatal intensive care if complications were associated with poor outcomes. Finally, 43% were satisfied with the current definitions of severe long‐term outcomes, 41% were unsure and there were numerous for a broader definition. Conclusion: Although Dutch professionals expressed diverse preferences on how to reach decisions about extremely premature infants, we observed a trend towards shared decision‐making with parents. These results could inform future guidelines. [ABSTRACT FROM AUTHOR]

Summary: Vagus nerve stimulation is a well‐established treatment option for patients with drug‐resistant epilepsy and has an expanding range of other clinical indications. Side effects of vagus nerve stimulation therapy include: cough; voice changes; vocal cord adduction; rarely, obstructive sleep apnoea; and arrhythmia. Patients with implanted vagus nerve stimulation devices may present for unrelated surgery and critical care to clinicians who are unfamiliar with their function and safe management. These guidelines have been formulated by multidisciplinary consensus based on case reports, case series and expert opinion to support clinicians in the management of patients with these devices. The aim is to provide specific guidance on the management of vagus nerve stimulation devices in the following scenarios: the peri‐operative period; peripartum period; during critical illness; and in the MRI suite. Patients should be aware of the importance of carrying their personal vagus nerve stimulation device magnet with them at all times to facilitate urgent device deactivation if necessary. We advise that it is generally safer to formally deactivate vagus nerve stimulation devices before general and spinal anaesthesia. During periods of critical illness associated with haemodynamic instability, we also advise cessation of vagus nerve stimulation and early consultation with neurology services. [ABSTRACT FROM AUTHOR]

Summary: Detailed contemporary knowledge of the characteristics of the surgical population, national anaesthetic workload, anaesthetic techniques and behaviours are essential to monitor productivity, inform policy and direct research themes. Every 3–4 years, the Royal College of Anaesthetists, as part of its National Audit Projects (NAP), performs a snapshot activity survey in all UK hospitals delivering anaesthesia, collecting patient‐level encounter data from all cases under the care of an anaesthetist. During November 2021, as part of NAP7, anaesthetists recorded details of all cases undertaken over 4 days at their site through an online survey capturing anonymous patient characteristics and anaesthetic details. Of 416 hospital sites invited to participate, 352 (85%) completed the activity survey. From these, 24,177 reports were returned, of which 24,172 (99%) were included in the final dataset. The work patterns by day of the week, time of day and surgical specialty were similar to previous NAP activity surveys. However, in non‐obstetric patients, between NAP5 (2013) and NAP7 (2021) activity surveys, the estimated median age of patients increased by 2.3 years from median (IQR) of 50.5 (28.4–69.1) to 52.8 (32.1–69.2) years. The median (IQR) BMI increased from 24.9 (21.5–29.5) to 26.7 (22.3–31.7) kg.m–2. The proportion of patients who scored as ASA physical status 1 decreased from 37% in NAP5 to 24% in NAP7. The use of total intravenous anaesthesia increased from 8% of general anaesthesia cases to 26% between NAP5 and NAP7. Some changes may reflect the impact of the COVID‐19 pandemic on the anaesthetic population, though patients with confirmed COVID‐19 accounted for only 149 (1%) cases. These data show a rising burden of age, obesity and comorbidity in patients requiring anaesthesia care, likely to impact UK peri‐operative services significantly. [ABSTRACT FROM AUTHOR]

Summary: Cardiac arrest in the peri‐operative period is rare but associated with significant morbidity and mortality. Current reporting systems do not capture many such events, so there is an incomplete understanding of incidence and outcomes. As peri‐operative cardiac arrest is rare, many hospitals may only see a small number of cases over long periods, and anaesthetists may not be involved in such cases for years. Therefore, a large‐scale prospective cohort is needed to gain a deep understanding of events leading up to cardiac arrest, management of the arrest itself and patient outcomes. Consequently, the Royal College of Anaesthetists chose peri‐operative cardiac arrest as the 7th National Audit Project topic. The study was open to all UK hospitals offering anaesthetic services and had a three‐part design. First, baseline surveys of all anaesthetic departments and anaesthetists in the UK, examining respondents' prior peri‐operative cardiac arrest experience, resuscitation training and local departmental preparedness. Second, an activity survey to record anonymised details of all anaesthetic activity in each site over 4 days, enabling national estimates of annual anaesthetic activity, complexity and complication rates. Third, a case registry of all instances of peri‐operative cardiac arrest in the UK, reported confidentially and anonymously, over 1 year starting 16 June 2021, followed by expert review using a structured process to minimise bias. The definition of peri‐operative cardiac arrest was the delivery of five or more chest compressions and/or defibrillation in a patient having a procedure under the care of an anaesthetist. The peri‐operative period began with the World Health Organization 'sign‐in' checklist or first hands‐on contact with the patient and ended either 24 h after the patient handover (e.g. to the recovery room or intensive care unit) or at discharge if this occured earlier than 24 h. These components described the epidemiology of peri‐operative cardiac arrest in the UK and provide a basis for developing guidelines and interventional studies. [ABSTRACT FROM AUTHOR]

There is a need to prioritise equity, diversity and inclusion within anaesthesia and medicine as a whole. This position statement outlines the Anaesthesia Editors' current policies and practices aiming to achieve equity, represent the diversity of our specialty and actively include people engaged with this journal and beyond. We will define, promote and embed principles of equity, diversity and inclusion across all our work. We will monitor and report author and editor characteristics and ensure recruitment practices are transparent and adhere to our principles on equity, diversity and inclusion. We will attempt to remove systemic barriers restricting those from under-represented groups from progressing into leadership roles within anaesthesia. We will respond to threats and barriers to the principles and practices we set. With these principles and specific actions we undertake, we aim to be pro-active rather than reactive. We commit to embracing and embedding equity, diversity and inclusion in all our practices and regularly reviewing, improving and updating our policies and practices. [ABSTRACT FROM AUTHOR]

Organisations spend much money on Information Technology (IT) development and maintenance activities with the intention that these activities will create results that enable benefits for the organisations. This paper seeks to understand potential associations between IT development and maintenance activities and the adoption of benefits management practices to realise value for the organization. The aim is also to uncover potential differences between public and private organisations. We surveyed 86 Norwegian public and private organisations, including data collected in similar surveys every five years since 1993. For the period between 1998 and 2018, we observe a stable pattern of IT work distribution. We found that organisations that managed benefits put more effort into advancing functionality for the end‐users than other organisations, and they realised more benefits. This advantage was particularly true for organisations that managed benefits beyond the early stages of the development lifecycle. Private organisations both managed and realised benefits to a larger extent than public organisations. Our findings can enable organisations to be evidence‐based when choosing management practices to achieve a higher return on investments in IT development and maintenance activities. [ABSTRACT FROM AUTHOR]

Summary: Pulse oximetry is used widely to titrate oxygen therapy and for triage in patients who are critically ill. However, there are concerns regarding the accuracy of pulse oximetry in patients with COVID‐19 pneumonitis and in patients who have a greater degree of skin pigmentation. We aimed to determine the impact of patient ethnicity on the accuracy of peripheral pulse oximetry in patients who were critically ill with COVID‐19 pneumonitis by conducting a retrospective observational study comparing paired measurements of arterial oxygen saturation measured by co‐oximetry on arterial blood gas analysis (SaO2) and the corresponding peripheral oxygenation saturation measured by pulse oximetry (SpO2). Bias was calculated as the mean difference between SaO2 and SpO2 measurements and limits of agreement were calculated as bias ±1.96 SD. Data from 194 patients (135 White ethnic origin, 34 Asian ethnic origin, 19 Black ethnic origin and 6 other ethnic origin) were analysed consisting of 6216 paired SaO2 and SpO2 measurements. Bias (limits of agreement) between SaO2 and SpO2 measurements was 0.05% (−2.21–2.30). Patient ethnicity did not alter this to a clinically significant degree: 0.28% (1.79–2.35), −0.33% (−2.47–2.35) and −0.75% (−3.47–1.97) for patients of White, Asian and Black ethnic origin, respectively. In patients with COVID‐19 pneumonitis, SpO2 measurements showed a level of agreement with SaO2 values that was in line with previous work, and this was not affected by patient ethnicity. [ABSTRACT FROM AUTHOR]

Objective: This article provides an updated overview of restorative procedures of endodontically treated teeth. Clinical considerations: The different techniques and procedures to restore an endodontic treated tooth were considered in the last decades. While they are generally performed using bonding procedures in combination with or without the placement of a post into the root to build up the abutment, there has been a lack of interest in restorative difficulties that can be faced. Failures are represented such as debonding of the post, fracture of the root, decementation, and/or fracture of the restoration, microleakage of the margins. Essentially, the presence of a sufficient failure is considered a key point of a long prognosis. Different clinical factors can directly influence the type of restoration and the longevity of the treatment. The restorative difficulty evaluation system (RDES) is proposed in this article. This new system is composed of eight different clinical factors that are divided into six levels of difficulties. The RDES is composed of 1. Endodontic complexity and outcome, 2. Vertical amount of coronal residual structure and dimension of the pulp chamber, 3. Horizontal amount of coronal residual structure, 4. Restoration marginal seal, 5. Local interdisciplinary conditions, 6. the complexity of the treatment planning, 7. Functional need, 8. Dental wear and esthetic need. Conclusion: This article reviews the RDES and outlines critical steps and tips for clinical success. Clinical significance: The RDES allows to any clinician to evaluate restorative difficulties when an endodontic treated tooth must be restored, combines clinical aspects that can involve from the single tooth to a full mouth rehabilitation. [ABSTRACT FROM AUTHOR]

Summary: The use of cuffed tracheal tubes in paediatric anaesthesia is now common. The use of nitrous oxide in anaesthesia risks excessive tracheal tube cuff pressures, as nitrous oxide can diffuse into the cuff during the course of surgery. The aim of this single‐centre, prospective, randomised controlled trial was to compare the effect of saline versus air for the inflation of tracheal tube cuffs on the incidence of excessive intra‐operative cuff pressure in children undergoing balanced anaesthesia with nitrous oxide. Children (age ≤ 16 y) were randomly allocated to receive either saline (saline group) or air (air group) to inflate the cuff of their tracheal tube. The pressure in the tracheal tube cuff was measured during surgery and brought down to the initial inflation level if it breached a safe limit (25 cmH2O). Post‐extubation adverse respiratory events were noted. Data from 48 patients (24 in each group), aged 4 months to 16 y, were analysed. The requirement for reduction in intra‐cuff pressure occurred in 1/24 patients in the saline group, compared with 16/24 patients in the air group (p < 0.001). The incidence of extubation‐related adverse events was similar in the saline and air groups (15/24 vs. 13/24, respectively; p = 0.770). The use of saline to inflate the cuff of paediatric cuffed tubes reduces the incidence of high intra‐cuff pressures during anaesthesia. This may provide a pragmatic extra safety barrier to help reduce the incidence of excessive tracheal cuff pressure when nitrous oxide is used during paediatric anaesthesia. [ABSTRACT FROM AUTHOR]

Personality traits, such as the propensity to cooperate, are often inherited from parents to offspring, but the pathway of inheritance is unclear. Traits could be inherited via genetic or parental effects, or culturally via social learning from role models. However, these pathways are difficult to disentangle in natural systems as parents are usually the source of all of these effects. Here, we exploit natural 'cross fostering' in wild banded mongooses to investigate the inheritance of cooperative behaviour. Our analysis of 800 adult helpers over 21 years showed low but significant genetic heritability of cooperative personalities in males but not females. Cross fostering revealed little evidence of cultural heritability: offspring reared by particularly cooperative helpers did not become more cooperative themselves. Our results demonstrate that cooperative personalities are not always highly heritable in wild, and that the basis of behavioural traits can vary within a species (here, by sex). [ABSTRACT FROM AUTHOR]

The nature of the variability of the Total Electron Content (TEC) over Europe is investigated during 2009 and 2019 Northern Hemisphere (NH) SSW events in this study by using a combination of Global Navigation Satellite System (GNSS) based TEC observations and Thermosphere‐Ionosphere Electrodynamics General Circulation Model (TIE‐GCM) simulations. To simulate the SSW effects in TIE‐GCM, the dynamical fields from the Whole Atmosphere Community Climate Model with thermosphere and ionosphere extension (WACCM‐X) simulations of 2009 and 2019 SSWs are specified at the TIE‐GCM lower boundary. The observed and simulated TEC are in overall good agreement and therefore the simulations are used to understand the sources of mid‐latitude TEC variability during both SSWs. Through comparison of TIE‐GCM simulations with and without geomagnetic forcing, we find that the TEC variability during the 2019 SSW event, was predominantly geomagnetically forced, while for the 2009 SSW, the major variability in TEC was accounted for by the changes in vertically propagating migrating semidiurnal solar (SW2) and lunar (M2) tides. By comparing the TIE‐GCM simulations with and without the SW2 and M2 tides, we find that these semidiurnal tides contribute to ∼20%–25% increase in the quiet background TEC. Plain Language Summary: The region of Earth's upper atmosphere between the altitude range 80–1,000 km known as the ionosphere is made up of a mixture of charged and neutral gases. As the ionosphere is sandwiched between the Earth's lower atmosphere and the magnetosphere, it is prone to being influenced by the Earth's lower atmospheric weather and to the solar driven space weather. The impact of the Earth's meteorological processes on the ionosphere becomes particularly important during periods of low solar activity and one large‐scale meteorological phenomenon known as Sudden Stratospheric Warming (SSW) is known to cause major changes in the ionosphere. Much of our knowledge about these ionospheric changes have come from studying the 2009 SSW event, which occurred under extremely rare quiet solar and geomagnetic conditions. Another SSW event occurred toward in 2019 under similarly rare and favorable conditions, which serves a motivation to further investigate the ionospheric impacts of SSWs. Using numerical models, we quantify the ionospheric variability that is caused by both geomagnetic and lower atmospheric forcings during both SSWs. For the 2019 SSW, the mid‐latitude ionospheric variability is found to be predominantly geomagnetically forced while during the 2009 SSW it is found to be lower atmospherically forced. Key Points: The mid‐latitude Total Electron Content (TEC) variability over Europe is observed and simulated during 2009 and 2019 Sudden Stratospheric Warmings (SSWs)Observations and simulation results show that the TEC variability was caused predominantly by geomagnetic forcing for the 2019 SSWThe TEC variability at European mid‐latitudes due to semidiurnal solar (SW2) and lunar (M2) tidal changes during both SSWs remain within ∼20%–25% of the background TEC [ABSTRACT FROM AUTHOR]

Differing environmental conditions can have profound effects on many behaviours in animals, especially where species have large geographic ranges. Seasonal changes or progression through life history stages impose differential constraints, leading to changes in behaviours. Furthermore, species which show flexibility in behaviours, may have a higher capacity to adapt to anthropogenic-induced changes to their environment. The red-throated diver (RTD) is an aquatic bird, that is able to forage in both freshwater and marine environments, though little else is known about its behaviours and its capacity to adapt to different environmental conditions. Here, we use timedepth recorders and saltwater immersion loggers to examine the foraging behaviour of RTDs from three regions across northwest Europe. We found that in the breeding season, birds from two regions (Iceland and Scotland) foraged in the marine environment, while birds from Finland, foraged predominantly in freshwater. Most of the differences in diving characteristics were at least partly explained by differences in foraging habitat. Additionally, while time spent foraging did not change through the breeding season, dives generally became more pelagic and less benthic over the season, suggesting RTDs either switched prey or followed vertical prey movements, rather than increasing foraging effort. There was a preference for foraging in daylight over crepuscular hours, with a stronger effect at two of the three sites. Overall, we provide the first investigation of RTD foraging and diving behaviour from multiple geographic regions and demonstrate variation in foraging strategies in this generalist aquatic predator, most likely due to differences in their local environment. [ABSTRACT FROM AUTHOR]

Objective: To investigate if cancer in pregnancy causes a higher risk of venous thromboembolism (VTE) during pregnancy and postpartum compared with pregnant women without cancer.Design: A historical prospective cohort study using data from nationwide registries.Setting and Population: We assessed all pregnancies in Denmark between 1 January 1977 and 31 December 2017.Methods: We linked information concerning cancer diagnosis, pregnancy and VTE diagnosis and potential confounders. Event rates of VTE for women with pre-pregnancy cancer, cancer in pregnancy and without cancer were calculated per 10 000 pregnancies and compared using logistic regression analysis.Main Outcome Measures: Occurrence of VTE during pregnancy or the postpartum period.Results: A total of 3 581 214 pregnancies were included in the study and we found 1330 women with cancer in pregnancy. In pregnant women with cancer, the event rate of VTE was 75.2 per 10 000 pregnancies compared with 10.7 per 10 000 pregnancies in the no cancer group. The findings correspond to an increased adjusted odds ratio of 6.50 (95% CI3.5-12.1) in the cancer in pregnancy group in comparison with the no cancer group.Conclusions: Women with cancer in pregnancy have a markedly higher risk of pregnancy-associated VTE compared with women without cancer. In pregnancy-related VTE risk assessment, the presence of cancer alone may be sufficient to indicate thromboprophylaxis.Tweetable Abstract: Cancer in pregnancy increases the risk of VTE during pregnancy and the postpartum period. [ABSTRACT FROM AUTHOR]

In this paper, existing classical Korteweg‐de Vries (KdV) equations are converted into the corresponding time‐fractional KdV equations by using Caputo‐Fabrizio fractional derivative and then solved with appropriate initial conditions by implementing semi‐numerical technique, that is, Laplace transform together with an iterative scheme. The obtained solutions are novel, and previous literature lacks such derivations. The stability of implemented technique is analyzed by applying Banach contraction principle and S‐stable mapping. Efficiency of Caputo‐Fabrizio fractional derivative is exhibited through graphical illustrations, and fractional results are drafted in tabular form for specific values of fractional parameter to validate the numerical investigation. [ABSTRACT FROM AUTHOR]

Reelin is a protein that is best known for its role in controlling neuronal layer formation in the developing cortex. Here, we studied its role for post‐natal cortical network function, which is poorly explored. To preclude early cortical migration defects caused by Reelin deficiency, we used a conditional Reelin knock‐out (RelncKO) mouse, and induced Reelin deficiency post‐natally. Induced Reelin deficiency caused hyperexcitability of the neocortical network in vitro and ex vivo. Blocking Reelin binding to its receptors ApoER2 and VLDLR resulted in a similar effect. Hyperexcitability in RelncKO organotypic slice cultures could be rescued by co‐culture with wild‐type organotypic slice cultures. Moreover, the GABAB receptor (GABABR) agonist baclofen failed to activate and the antagonist CGP35348 failed to block GABABRs in RelncKO mice. Immunolabeling of RelncKO cortical slices revealed a reduction in GABABR1 and GABABR2 surface expression at the plasma membrane and western blot of RelncKO cortical tissue revealed decreased phosphorylation of the GABABR2 subunit at serine 892 and increased phosphorylation at serine 783, reflecting receptor deactivation and proteolysis. These data show a role of Reelin in controlling early network activity, by modulating GABABR function. Cover Image for this issue: https://doi.org/10.1111/jnc.15054. [ABSTRACT FROM AUTHOR]

Considerable resources are wasted on software projects delivering less than the planned benefits. Herein, the objective is to synthesize empirical evidence of the adoption and impact of benefits management (BM) in software development, and to suggest directions for future research. A systematic review of the literature is performed and identified 4836 scientific papers of which the authors found 47 to include relevant research. While most organizations identify and structure benefits at the outset of a project, fewer organizations report implementing BM as a continuous process throughout the project lifecycle. Empirical evidence gives support for positive impact on project outcome from the following BM practices: identifying and structuring benefits, planning benefits realization, BM during project execution, benefits evaluation and the practice of having people responsible for benefits realization. The authors suggest four research directions to understand (1) why BM practices sometimes not are adopted, (2) BM in relation to other management practices, (3) BM in agile software development and (4) BM in the context of organizations' value creation logics. [ABSTRACT FROM AUTHOR]

Fast, simple, accurate, and inexpensive methods for obtaining analyte concentration data are desirable in the industrial sector. In the present study, the use of Fourier transform mid‐infrared (FT‐MIR) spectroscopy, combined with partial least squares (PLS) regression, was investigated as a tool for real‐time monitoring of processes of ethanol absorption in glycols. Calibration was performed using simple synthetic samples containing ethanol, water, and monoethylene glycol (MEG) or diethylene glycol (DEG). The PLS models presented excellent performance, with correlation coefficients (R2) close to unity and root‐mean‐square errors of cross‐validation (RMSECV) and prediction (RMSEP) lower than 2% of the calibration data ranges for both analytes (ethanol and water) in both absorbents (MEG and DEG). The monitoring technique developed has potential to be applied in absorption processes and could also be used in other large‐scale unit operations, providing information in real time and enhancing process control. [ABSTRACT FROM AUTHOR]

Keywords: acute kidney injury; hypotension; myocardial injury; peri-operative care; stroke EN acute kidney injury hypotension myocardial injury peri-operative care stroke 132 134 3 01/11/22 20220201 NES 220201 I What people say, what people do and what they say they do are entirely different things i Margaret Mead, US anthropologist The precise blood pressure thresholds that should prompt intervention under anaesthesia are a matter of ongoing debate, not least because there are uncertainties surrounding what constitutes hypotension and its potential consequences for each individual patient. From this survey, three complementary sets of data were reported: the prevalence of intra-operative hypotension; the apparent threshold for when hypotension was treated; and the threshold at which anaesthetists said they would treat. Outcomes As intra-operative hypotension is associated with adverse patient outcomes, anaesthetists may see its occurrence as being reflective of substandard care on their part even though hypotension can arise despite their best efforts and even though it may have been appropriately managed. [Extracted from the article]

Keywords: Parkinson's disease; delirium; cognitive dysfunction; frailty; comprehensive geriatric assessment EN Parkinson's disease delirium cognitive dysfunction frailty comprehensive geriatric assessment 8 10 3 01/12/22 20220102 NES 220102 The ageing of the surgical population is well described in high-income countries [1]. For example, with delirium being the most common postoperative neurocognitive complication (associated with high morbidity and mortality), the need for identification of patients at risk of delirium is clear. Despite the association between delirium and long-term morbidity, and its impact on the trajectories of underlying cognitive impairment and mortality, consent processes do not routinely document the risk of peri-operative delirium [14]. [Extracted from the article]

Introduction: Dogs treated for hypoadrenocorticism are monitored through analysis of their blood electrolytes. This is routinely performed with point‐of‐care analysers and doses of medications are adjusted based on the results. Objectives: To investigate the performance of two point‐of‐care analysers (IDEXX Catalyst Dx and IDEXX VetStat) against a reference laboratory method for the measurement of blood sodium, potassium and chloride concentrations, as well as sodium: potassium ratios, in dogs diagnosed with and treated for hypoadrenocorticism. Methods: Forty‐eight dogs were enrolled into a prospective cross‐sectional study. Paired blood samples were taken and tested on two point‐of‐care analysers and at a reference laboratory. Statistical analysis was then performed with Bland‐Altman analysis and Passing‐Bablok regression. The clinical effects of inaccurate electrolyte analysis were investigated. Results: In total, 329 samples were tested on the Catalyst analyser, while another 72 samples were tested on the VetStat. Passing‐Bablok regression identified both proportional and constant bias for some analytes. There was poor agreement between sodium and chloride concentrations on both analysers. Both analysers tended to give higher results than the reference method for all analytes, except for potassium when measured on the VetStat. Clinical Significance: There are inherent differences between the electrolyte concentrations measured by these two point‐of‐care analysers and reference laboratory methods in dogs with hypoadrenocorticism. [ABSTRACT FROM AUTHOR]

Glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) is a key enzyme in the glycolytic pathway that catalyzes the conversion of d‐glyceraldehyde 3‐phosphate to 1,3‐diphosphoglycerate. Here, the full‐length GAPDH type 1 from Escherichia coli (EcGAPDH1) was cloned and overexpressed, and the protein was purified. Biochemical analyses found that the optimum reaction temperature and pH of EcGAPDH1 were 55°C and 10.0, respectively. The protein has a certain amount of thermostability. Crystals of EcGAPDH1 were obtained using the sitting‐drop vapor‐diffusion technique and X‐ray diffraction data were collected to 1.88 Å resolution. Characterization of the crystals showed that they belonged to space group P41212, with unit‐cell parameters a = b = 89.651, c = 341.007 Å, α = β = γ = 90°. The structure of EcGAPDH1 contains four subunits, each of which includes an N‐terminal NAD+‐binding domain and a C‐terminal catalytic domain. Analysis of the NAD+‐bound form showed some differences between the structures of EcGAPDH1 and human GAPDH. As EcGAPDH1 shares 100% identity with GAPDH from Shigella sonnei, its structure may help in finding a drug for the treatment of shigellosis. [ABSTRACT FROM AUTHOR]

Around 76,000 people fracture their hip annually in the UK at a considerable personal, social and financial cost. Despite longstanding debate, the optimal mode of anaesthesia (general or spinal) remains unclear. Our aim was to assess whether there is a significant difference in mortality and morbidity between patients undergoing spinal anaesthesia compared with general anaesthesia during hip fracture surgery. A secondary analysis examined whether a difference exists in mortality for patients with pre-existing cardiovascular disease or chronic obstructive pulmonary disease. This was a clinical database analysis of patients treated for hip fracture in Nottingham, UK between 2004 and 2015. Propensity score-matching was used to generate matched pairs of patients, one of whom underwent each mode of anaesthesia. Data were analysed using conditional logistic regression, with 7164 patients successfully matched. There was no difference in 30- or 90-day mortality in patients who had spinal rather than general anaesthesia (OR [95%CI] 0.97 [0.8-1.15]; p = 0.764 and 0.93 [0.82-1.05]; p = 0.247 respectively). Patients who had a spinal anaesthetic had a lower-risk of blood transfusion (OR [95%CI] 0.84 [0.75-0.94]; p = 0.003) and urinary tract infection (OR [95%CI] 0.72 [0.61-0.84]; p < 0.001), but were more likely to develop a chest infection (OR [95%CI] 1.23 [1.07-1.42]; p = 0.004), deep vein thrombosis (OR [95%CI] 2.18 [1.07-4.45]; p = 0.032) or pulmonary embolism (OR [95%CI] 2.23 [1.16-4.29]; p = 0.016). The mode of anaesthesia for hip fracture surgery resulted in no significant difference in mortality, but there was a significant difference in several measures of postoperative morbidity. [ABSTRACT FROM AUTHOR]

Background: As common risk factors of dementia, nine factors (low education, hearing loss, obesity, hypertension, smoking, depression, physical inactivity, diabetes and social isolation) were proposed. However, the joint impact of these factors on incident dementia is still uncertain; hence, we aimed to examine this impact.Methods: We conducted a cohort study of 9017 cognitively intact individuals aged ≥ 65 years in the Swedish Twin Registry. The main exposure was the total number of reported risk factors (ranging from 0 to 9). Data on dementia diagnoses were based on clinical workup and national health registers. After estimating the adjusted hazard ratios of incident dementia, the population attributable fraction (PAF) was calculated. We then conducted additional analyses, including APOE ε4 status in a genotyped subsample (n = 2810) to check the relative impact of the main exposure and discordant twin pair (n = 1158) analysis to consider confounding by familial effects (shared genetic or familial environmental factors).Results: The number of dementia cases was 1950 (21.6%). A dose-response relationship between the number of risk factors and incident dementia was observed; hazard ratio (95% confidence interval) per one-unit increment in number of risk factors was 1.07 (1.03 to 1.11). The PAF for the combination of the nine risk factors was 10.4%. The PAF of all nine risk factors was smaller than that of APOE ε4 genotype (20.8%) in the subsample. Discordant pair analysis suggested that the observed association was not likely explained by familial effects.Conclusion: The nine risk factors may have considerable impact as modifiable factors on incident dementia. [ABSTRACT FROM AUTHOR]

The applicability of the results of any clinical trial will depend to a large extent on whether the study population is representative of the population seen in clinical practice. The growing older surgical population presents challenges for peri-operative researchers to ensure there is adequate representation of patients in terms of their age, sex, race and ethnicity in clinical trials. A review of purposively sampled published randomised controlled trials was performed to establish the age, sex, race and ethnicity of study participants. These data were compared with national registry data for the relevant surgical populations. We included 224 peri-operative trials that were cited in 469 retrieved meta-analyses. Of these, 50 (22.3%) had an upper age limit to recruitment. The median (range [IQR]) difference in study population age from the registry population age was: -2.4 (-6.2 to 1.0 [-34.7 to 14.5]) years for all randomised controlled trials; -6.2 (-9.4 to -2.8 [-18.6 to 4.6]) years for randomised controlled trials of patients undergoing hip arthroplasty; and -3.4 (-9.6 to -1.1 [-34.7 to 2.9]) years for randomised controlled trials of patients undergoing hip fracture surgery. In 92 (41.1%) randomised controlled trials, the proportion of each sex in the study population was more than 25% different from the proportion in the registry population. Only 5 (2.2%) trials published data on the race or ethnicity of participants. We conclude that peri-operative randomised controlled trials are unlikely to be representative of the age and sex of clinically treated surgical populations. Researchers must endeavour to ensure representative study populations are recruited to future clinical trials. [ABSTRACT FROM AUTHOR]

Background and purpose: Studies on using antiplatelet agents for secondary prevention in ischaemic stroke patients with renal dysfunction are limited. The Taiwan Stroke Registry database was used to compare the efficacy of antiplatelet agents. Methods: From the Taiwan Stroke Registry data, 39 174 acute ischaemic stroke patients were identified and were classified into three groups by antiplatelet agent: aspirin, clopidogrel and dual antiplatelet therapy (DAPT) with a combination of aspirin and clopidogrel. The re‐stroke incidence and 1‐year mortality were stratified by estimated glomerular filtration rate (eGFR) levels at admission: ≥90, 60–89 and <60 ml/min/1.73 m2 or on dialysis. Results: Compared to the aspirin group, the re‐stroke differences were not statistically significant for the clopidogrel group [adjusted subhazard ratio 0.95, 95% confidence interval (CI) 0.84–1.08] and the DAPT group (adjusted subhazard ratio 1.03, 95% CI 0.77–1.39) after controlling for the competing risk of death. The mortality rate increased as the eGFR level declined. In addition, compared to patients taking aspirin, there was no statistically significant difference in overall 1‐year mortality for the clopidogrel group (adjusted hazard ratio 1.11, 95% CI 0.95–1.29) and for the DAPT group (adjusted hazard ratio 1.01, 95% CI 0.67–1.54). The results were consistent in different subgroups stratified by eGFR levels. Conclusions: There was no difference in the risks of recurrent stroke and 1‐year mortality amongst ischaemic stroke patients with or without renal dysfunction receiving antiplatelet agents with aspirin, clopidogrel or dual agents with a combination of aspirin and clopidogrel, regardless of their renal dysfunction status. [ABSTRACT FROM AUTHOR]