The effectiveness and safety of antifibrinolytics in patients with acute intracranial haemorrhage: statistical analysis plan for an individual patient data meta-analysis

Introduction: The Antifibrinolytic Trialists Collaboration aims to increase knowledge about the effectiveness and safety of antifibrinolytic treatment by conducting individual patient data (IPD) meta-analyses of randomised trials. This article presents the statistical analysis plan for an IPD meta-analysis of the effects of antifibrinolytics for acute intracranial haemorrhage. Methods: The protocol for the IPD meta-analysis has been registered with PROSPERO (CRD42016052155). We will conduct an individual patient data meta-analysis of randomised controlled trials with 1000 patients or more assessing the effects of antifibrinolytics in acute intracranial haemorrhage. We will assess the effect on two co-primary outcomes: 1) death in hospital at end of trial follow-up, and 2) death in hospital or dependency at end of trial follow-up. The co-primary outcomes will be limited to patients treated within three hours of injury or stroke onset. We will report treatment effects using odds ratios and 95% confidence intervals. We use logistic regression models to examine how the effect of antifibrinolytics vary by time to treatment, severity of intracranial bleeding, and age. We will also examine the effect of antifibrinolytics on secondary outcomes including death, dependency, vascular occlusive events, seizures, and neurological outcomes. Secondary outcomes will be assessed in all patients irrespective of time of treatment. All analyses will be conducted on an intention-to-treat basis. Conclusions: This IPD meta-analysis will examine important clinical questions about the effects of antifibrinolytic treatment in patients with intracranial haemorrhage that cannot be answered using aggregate data. With IPD we can examine how effects vary by time to treatment, bleeding severity, and age, to gain better understanding of the balance of benefit and harms on which to base recommendations for practice

Mechanical design, materials selection, fabrication and assembly of ultraclean, high-gain, Nd: glass disk laser amplifiers

Particulate contamination in disk amplifiers with high flashlamp fluxes (which can generate particles) causes three types of laser beam obscuration, which cause small-scale self-focusing. Methods for obtaining disk amplifiers that stay clean are described. (auth

Successful recruitment to trials: findings from the SCIMITAR plus Trial

BACKGROUND: Randomised controlled trials (RCT) can struggle to recruit to target on time. This is especially the case with hard to reach populations such as those with severe mental ill health. The SCIMITAR+ trial, a trial of a bespoke smoking cessation intervention for people with severe mental ill health achieved their recruitment ahead of time and target. This article reports strategies that helped us to achieve this with the aim of aiding others recruiting from similar populations. METHODS: SCIMITAR+ is a multi-centre pragmatic two-arm parallel-group RCT, which aimed to recruit 400 participants with severe mental ill health who smoke and would like to cut down or quit. The study recruited primarily in secondary care through community mental health teams and psychiatrists with a smaller number of participants recruited through primary care. Recruitment opened in October 2015 and closed in December 2016, by which point 526 participants had been recruited. We gathered information from recruiting sites on strategies which led to the successful recruitment in SCIMITAR+ and in this article present our approach to trial management along with the strategies employed by the recruiting sites. RESULTS: Alongside having a dedicated trial manager and trial management team, we identified three main themes that led to successful recruitment. These were: clinicians with a positive attitude to research; researchers and clinicians working together; and the use of NHS targets. The overriding theme was the importance of relationships between both the researchers and the recruiting clinicians and the recruiting clinicians and the participants. CONCLUSIONS: This study makes a significant contribution to the limited evidence base of real-world cases of successful recruitment to RCTs and offers practical guidance to those planning and conducting trials. Building positive relationships between clinicians, researchers and participants is crucial to successful recruitment

Food insecurity in adults with severe mental illness living in Northern England: A co-produced cross-sectional study

\ua9 2024 The Authors. Nutrition & Dietetics published by John Wiley & Sons Australia, Ltd on behalf of Dietitians Australia.Aim: This study aimed to explore food insecurity prevalence and experiences of adults with severe mental illness living in Northern England. Methods: This mixed-methods cross-sectional study took place between March and October 2022. Participants were adults with self-reported severe mental illness living in Northern England. The survey included demographic, health, and financial questions. Food insecurity was measured using the US Department of Agriculture Adult Food Security measure. Quantitative data were analysed using descriptive statistics and binary logistic regression; and qualitative data using content analysis. Results: In total, 135 participants completed the survey, with a mean age of 44.7 years (SD: 14.1, range: 18–75 years). Participants were predominantly male (53.3%), white (88%) and from Yorkshire (50.4%). The food insecurity prevalence was 50.4% (n = 68). There was statistical significance in food insecurity status by region (p = 0.001); impacts of severe mental illness on activities of daily living (p = 0.02); and the Covid pandemic on food access (p < 0.001). The North West had the highest prevalence of food insecurity (73.3%); followed by the Humber and North East regions (66.7%); and Yorkshire (33.8%). In multivariable binary logistic regression, severe mental illness\u27 impact on daily living was the only predictive variable for food insecurity (odds ratio = 4.618, 95% confidence interval: 1.071–19.924, p = 0.04). Conclusion: The prevalence of food insecurity in this study is higher than is reported in similar studies (41%). Mental health practitioners should routinely assess and monitor food insecurity in people living with severe mental illness. Further research should focus on food insecurity interventions in this population

A model and experimental approach to the middle ear transfer function related to hearing in the humpback whale (Megaptera novaeangliae)

At present, there are no direct measures of hearing for any baleen whale (Mysticeti). The most viable alternative to in vivo approaches to simulate the audiogram is through modeling outer, middle, and inner ear functions based on the anatomy and material properties of each component. This paper describes a finite element model of the middle ear for the humpback whale (Megaptera novaeangliae) to calculate the middle ear transfer function (METF) to determine acoustic energy transmission to the cochlea. The model was developed based on high resolution computed tomography imaging and direct anatomical measurements of the middle ear components for this mysticete species. Mechanical properties for the middle ear tissues were determined from experimental measurements and published values. The METF for the humpback whale predicted a better frequency range between approximately 15 Hz and 3 kHz or between 200 Hz and 9 kHz based on two potential stimulation locations. Experimental measures of the ossicular chain, tympanic membrane, and tympanic bone velocities showed frequency response characteristics consistent with the model. The predicted best sensitivity hearing ranges match well with known vocalizations of this species

Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions

The harm benefit analysis (HBA) is the cornerstone of animal research regulation and is considered to be a key ethical safeguard for animals. The HBA involves weighing the anticipated benefits of animal research against its predicted harms to animals but there are doubts about how objective and accountable this process is.i. To explore the harms to animals involved in pre-clinical animal studies and to assess these against the benefits for humans accruing from these studies; ii. To test the feasibility of conducting this type of retrospective HBA.Data on harms were systematically extracted from a sample of pre-clinical animal studies whose clinical relevance had already been investigated by comparing systematic reviews of the animal studies with systematic reviews of human studies for the same interventions (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis, corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids for neonatal respiratory distress and thrombolytics for stroke). Clinical relevance was also explored in terms of current clinical practice. Harms were categorised for severity using an expert panel. The quality of the research and its impact were considered. Bateson's Cube was used to conduct the HBA.The most common assessment of animal harms by the expert panel was 'severe'. Reported use of analgesia was rare and some animals (including most neonates) endured significant procedures with no, or only light, anaesthesia reported. Some animals suffered iatrogenic harms. Many were kept alive for long periods post-experimentally but only 1% of studies reported post-operative care. A third of studies reported that some animals died prior to endpoints. All the studies were of poor quality. Having weighed the actual harms to animals against the actual clinical benefits accruing from these studies, and taking into account the quality of the research and its impact, less than 7% of the studies were permissible according to Bateson's Cube: only the moderate bisphosphonate studies appeared to minimise harms to animals whilst being associated with benefit for humans.This is the first time the accountability of the HBA has been systematically explored across a range of pre-clinical animal studies. The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted. Our findings indicate a pressing need to: i. review regulations, particularly those that permit animals to suffer severe harms; ii. reform the processes of prospectively assessing pre-clinical animal studies to make them fit for purpose; and iii. systematically evaluate the benefits of pre-clinical animal research to permit a more realistic assessment of its likely future benefits

Standard smoking cessation services in sites participating in the SCIMITAR+ trial for people with severe mental ill health

Aims and methodThe SCIMITAR+ trial was commissioned to evaluate the effectiveness of a bespoke smoking cessation intervention for people with severe mental ill health compared with usual services. It is difficult to define what constitutes usual care in smoking cessation services. We aimed to define what this was during the trial. Twenty-two National Health Service healthcare providers participated in a bespoke survey asking about usual care in their area. RESULTS: All sites offered smoking cessation support; however, service provider and service type varied substantially. In some cases services were not streamlined, meaning that people received smoking cessation counselling from one organisation and smoking cessation medication from another.Clinical implicationsTo better implement the National Institute for Health and Care Excellence guideline PH48, clearer referral pathways need to be implemented and communicated to patients, staff and carers. People with severe mental ill health need to be able to access services that combine nicotine replacement therapy and behavioural support in a streamlined manner.Declaration of interestNone

The effects of an enhanced simulation programme on medical students' confidence responding to clinical deterioration

BACKGROUND: Clinical deterioration in adult hospital patients is an identified issue in healthcare practice globally. Teaching medical students to recognise and respond to the deteriorating patient is crucial if we are to address the issue in an effective way. The aim of this study was to evaluate the effects of an enhanced simulation exercise known as RADAR (Recognising Acute Deterioration: Active Response), on medical students’ confidence. METHODS: A questionnaire survey was conducted; the instrument contained three sections. Section 1 focused on students’ perceptions of the learning experience; section 2 investigated confidence. Both sections employed Likert-type scales. A third section invited open responses. Questionnaires were distributed to a cohort of third-year medical students (n = 158) in the North East of Scotland 130 (82 %) were returned for analysis, employing IBM SPSS v18 and ANOVA techniques. RESULTS: Students’ responses pointed to many benefits of the sessions. In the first section, students responded positively to the educational underpinning of the sessions, with all scores above 4.00 on a 5-point scale. There were clear learning outcomes; the sessions were active and engaging for students with an appropriate level of challenge and stress; they helped to integrate theory and practice; and effective feedback on their performance allowed students to reflect and learn from the experience. In section 2, the key finding was that scores for students’ confidence to recognise deterioration increased significantly (p. < .001) as a result of the sessions. Effect sizes (Eta(2)) were high, (0.68–0.75). In the open-ended questions, students pointed to many benefits of the RADAR course, including the opportunity to employ learned procedures in realistic scenarios. CONCLUSIONS: The use of this enhanced form of simulation with simulated patients and the judicious use of moulage is an effective method of increasing realism for medical students. Importantly, it gives them greater confidence in recognising and responding to clinical deterioration in adult patients. We recommend the use of RADAR as a safe and cost-effective approach in the area of clinical deterioration and suggest that there is a need to investigate its use with different patient groups

Mineralogia, morfologia e análise microscópica de solos do bioma cerrado.

As características macro e micromorfológicas dos horizontes diagnósticos superficiais e subsuperficiais de Latossolos e Neossolos Quartzarênicos das superfícies Sul-Americana e Velhas foram estudadas em perfis sob cobertura de vegetação nativa, visando estabelecer um referencial para futuras comparações com áreas similares sob constante intervenção antrópica em termos de sustentabilidade. Com os solos referenciados por sub-região e pela superfície geomórfica que representam, três agrupamentos foram constituídos: Grupo 1: solos de textura argilosa a muito argilosa e hipo a mesoférricos; Grupo 2: solos de textura média a arenosa e hipoférricos, e Grupo 3: solos de textura argilosa a muito argilosa e férricos. O horizonte Bw dos Latossolos argilosos e muito argilosos estudados (Grupos 1 e 3), com relações cauliníticas/(caulinita + gibbsita) variando de 0,27 a 0,77, apresentaram grande coincidência de estrutura e microestrutura, respectivamente, forte muito pequena granular e de microagregados. Os solos do Grupo 2, Latossolos de textura média e um Neossolo Quartzarênico, apresentaram o plasma preferencialmente como películas aderidas aos grãos que dominam o fundo matricial. A presença marcante de agregados na fração areia, resistentes ao tratamento para dispersão da terra fina, se deu apenas nos Latossolos argilosos e muito argilosos do Grupo 3 (com caráter férrico) e em parte do Grupo 1 (naqueles mais gibbsíticos). No leste de Goiás, o horizonte Bw dos perfis de G2, Latossolos Amarelos de mineralogia gibbsítica e isenta de hematita, apresentaram feições observadas em lâmina delgada de cor vermelha e agregados residuais da fração areia com hematita detectada pela difração de raios-X, aspectos que corroboram a hipótese de um pedoambiente mais úmido dessa posição na paisagem relativamente à posição G1, com perfis de Latossolos Vermelhos