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Our objective was to assess the predictive value of physiologic dead space fraction for mortality in patients undergoing the comprehensive stage 2 operation.
Methods:
This was a single-centre retrospective observational study conducted at a quaternary free-standing children’s hospital specialising in hybrid palliation of single ventricle cardiac disease. 180 patients underwent the comprehensive stage 2 operation. 76 patients (42%) underwent early extubation, 59 (33%) standard extubation, and 45 (25%) delayed extubation. We measured time to extubation, post-operative outcomes, length of stay and utilised Fine gray models, Youden’s J statistic, cumulative incidence function, and logistic regression to analyse outcomes.
Results:
Delayed extubation group suffered significantly higher rates of mortality (31.1% vs. 6.8%), cardiac arrest (40.0% vs. 10.2%), stroke (37.8% vs. 11.9%), and need for catheter (28.9% vs. 5.1%) and surgical intervention (24.4% vs. 8.5%) (P < 0.001). Physiologic dead space fraction was significantly higher in the delayed extubation group and in non-survivors with a value of 0.3, which was found to be the discriminatory point by Youden’s J statistic. For a 0.1 unit increase in physiologic dead space fraction on post-operative day 1, the odds of a patient expiring increase by a factor of 2.26 (95% CI 1.41–3.97, p < 0.001) and by a factor of 3.79 (95% CI 1.65–11.7, p 0.01) on post-operative day 3.
Conclusions:
Delayed extubation impacts morbidity and mortality in patients undergoing the comprehensive stage 2 operation. Increased physiologic dead space fraction in the first 60 hours after arrival to the ICU is associated with higher mortality.
Trauma is prevalent amongst early psychosis patients and associated with adverse outcomes. Past trials of trauma-focused therapy have focused on chronic patients with psychosis/schizophrenia and comorbid Post-Traumatic Stress Disorder (PTSD). We aimed to determine the feasibility of a large-scale randomized controlled trial (RCT) of an Eye Movement Desensitization and Reprocessing for psychosis (EMDRp) intervention for early psychosis service users.
Methods
A single-blind RCT comparing 16 sessions of EMDRp + TAU v. TAU only was conducted. Participants completed baseline, 6-month and 12-month post-randomization assessments. EMDRp and trial assessments were delivered both in-person and remotely due to COVID-19 restrictions. Feasibility outcomes were recruitment and retention, therapy attendance/engagement, adherence to EMDRp treatment protocol, and the ‘promise of efficacy’ of EMDRp on relevant clinical outcomes.
Results
Sixty participants (100% of the recruitment target) received TAU or EMDR + TAU. 83% completed at least one follow-up assessment, with 74% at 6-month and 70% at 12-month. 74% of EMDRp + TAU participants received at least eight therapy sessions and 97% rated therapy sessions demonstrated good treatment fidelity. At 6-month, there were signals of promise of efficacy of EMDRp + TAU v. TAU for total psychotic symptoms (PANSS), subjective recovery from psychosis, PTSD symptoms, depression, anxiety, and general health status. Signals of efficacy at 12-month were less pronounced but remained robust for PTSD symptoms and general health status.
Conclusions
The trial feasibility criteria were fully met, and EMDRp was associated with promising signals of efficacy on a range of valuable clinical outcomes. A larger-scale, multi-center trial of EMDRp is feasible and warranted.
OBJECTIVES/GOALS: Studies have shown that SARS-CoV-2 specific memory B cells can be maintained at least a year after exposure. However, reports show an altered B cell response during infection in severe COVID-19 cases. This study aims to describe the B cell response during COVID-19 convalescence with a focus on signatures that contribute to durable and robust immunity. METHODS/STUDY POPULATION: Our study cohort consisted of individuals who had recovered from non-severe (hospitalized) or severe (hospitalized and requiring invasive mechanical ventilation) COVID-19. In our comparative analysis, samples from both groups were carefully matched to fall within 4-5 weeks post-symptom onset. We also performed a longitudinal analysis of non-severe patients with sampling ending 5 months post-symptom onset. Using high parameter flow cytometry, we characterized the phenotype of memory B cells using 19 distinct cell markers and fluorescently labeled probes to identify B cells reactive with SARS-CoV-2 spike and receptor-binding domain protein. Additionally, serum collected from individuals was used to quantify antibody titers. RESULTS/ANTICIPATED RESULTS: The frequency of spike-specific B cells and serum antibody titers were similar between severe and non-severe groups. However, we observed that individuals recovered from severe COVID-19 have a significantly reduced frequency of spike specific IgG+ memory B cells expressing Tbet and FcRL5 (markers associated with long lived immunity). In the non-severe patients, we observed IgG+Tbet+ B cells targeting the spike protein peak at 2-3 weeks post-symptom onset, decrease by almost fifty percent 4-5 weeks post-symptom onset, and return to baseline 5 months post-symptom onset. Our study also validated previous findings of a short-lived primary response of IgM+ B cells targeting the spike protein. DISCUSSION/SIGNIFICANCE: Our findings highlight potential implications for long-term immunity against re-infection or severity of the resulting disease in patients with severe COVID-19. Further investigation will be necessary to determine whether the maintenance of immunological protection is hindered in patients who overcame severe COVID-19.
Young people with social disability and severe and complex mental health problems have poor outcomes, frequently struggling with treatment access and engagement. Outcomes may be improved by enhancing care and providing targeted psychological or psychosocial intervention.
Aims
We aimed to test the hypothesis that adding social recovery therapy (SRT) to enhanced standard care (ESC) would improve social recovery compared with ESC alone.
Method
A pragmatic, assessor-masked, randomised controlled trial (PRODIGY: ISRCTN47998710) was conducted in three UK centres. Participants (n = 270) were aged 16–25 years, with persistent social disability, defined as under 30 hours of structured activity per week, social impairment for at least 6 months and severe and complex mental health problems. Participants were randomised to ESC alone or SRT plus ESC. SRT was an individual psychosocial therapy delivered over 9 months. The primary outcome was time spent in structured activity 15 months post-randomisation.
Results
We randomised 132 participants to SRT plus ESC and 138 to ESC alone. Mean weekly hours in structured activity at 15 months increased by 11.1 h for SRT plus ESC (mean 22.4, s.d. = 21.4) and 16.6 h for ESC alone (mean 27.7, s.d. = 26.5). There was no significant difference between arms; treatment effect was −4.44 (95% CI −10.19 to 1.31, P = 0.13). Missingness was consistently greater in the ESC alone arm.
Conclusions
We found no evidence for the superiority of SRT as an adjunct to ESC. Participants in both arms made large, clinically significant improvements on all outcomes. When providing comprehensive evidence-based standard care, there are no additional gains by providing specialised SRT. Optimising standard care to ensure targeted delivery of existing interventions may further improve outcomes.
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
Method
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
Results
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
Conclusion
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
Current policy emphasises the importance of ‘living well’ with dementia, but there has been no comprehensive synthesis of the factors related to quality of life (QoL), subjective well-being or life satisfaction in people with dementia. We examined the available evidence in a systematic review and meta-analysis. We searched electronic databases until 7 January 2016 for observational studies investigating factors associated with QoL, well-being and life satisfaction in people with dementia. Articles had to provide quantitative data and include ⩾75% people with dementia of any type or severity. We included 198 QoL studies taken from 272 articles in the meta-analysis. The analysis focused on 43 factors with sufficient data, relating to 37639 people with dementia. Generally, these factors were significantly associated with QoL, but effect sizes were often small (0.1–0.29) or negligible (<0.09). Factors reflecting relationships, social engagement and functional ability were associated with better QoL. Factors indicative of poorer physical and mental health (including depression and other neuropsychiatric symptoms) and poorer carer well-being were associated with poorer QoL. Longitudinal evidence about predictors of QoL was limited. There was a considerable between-study heterogeneity. The pattern of numerous predominantly small associations with QoL suggests a need to reconsider approaches to understanding and assessing living well with dementia.
We present evidence for melting at the base of the ice that overlies Lake Concordia, an 800 km2 subglacial lake near Dome Concordia, East Antarctica, via a combination of glaciohydraulic melting (associated with the tilted ice ceiling and its influence on lake circulation/melting temperature) and melting by extreme strain heating (where the ice sheet is grounded). An influx of water is necessary to provide nutrients, material and biota to support subglacial lake ecosystems but has not been detected previously. Freezing is the dominant observed basal process at over 60% of the surface area above the lake. The total volume of accreted ice above the lake surface is estimated as 50-60 km3, roughly 25-30% of the 200 ± 40 km3 estimated lake volume. Estimated rates of melting and freezing are very similar, ±2-6 mm a-1. The apparent net freezing may reflect the present-day response of Lake Concordia to cooling associated with the Last Glacial Maximum, or a large influx of water either via a subglacial hydrological system or from additional melting of the ice sheet. Lake Concordia is an excellent candidate for subglacial exploration given active basal processes, proximity to the Dome Concordia ice core and traverse resupply route.
Three central Arctic Ocean sediment cores were sampled for percentage carbonate, number of foraminifera, and texture. These three parameters were used in spectral analyses to test the idea that the ice-covered Arctic Ocean may respond to orbital forcing in a different manner than has been indicated for lower latitude ice-free oceans. The record for two of the cores represents approximately 1 my, and the record for the third, approximately 400,000 yr. The 100,000-yr frequency is well represented in all of the cores. A 40,000-yr frequency may be present, as well. An unexpected 70,000-yr frequency occurs in most of the spectra and may reflect nonlinear sedimentation rates or the combined effect of obliquity and eccentricity. The strong 100,000-yr signal confirms that, in spite of ice feedback, the Arctic Ocean has responded to orbital forcing in much the same manner as have ice-free oceans.
Many researchers, either directly or indirectly, rely on statistical ideas when carrying out animal experiments. While some statistical tools are well known and are applied routinely, other tools are less well understood and so are less well used. The overall aim of this book is to discuss statistical methodologies that can be applied throughout the many stages of the experimental process. Researchers should be able to carry out most of the techniques described, although the advice of a professional statistician is advisable for some of the more advanced topics. Making use of these techniques will ensure that experiments are conducted in a logical and efficient way, which should result in reliable and reproducible decisions.
The particular types of study addressed in this book, as the title suggests, are studies involving animals. We attempt to cover all of the statistical tools that the animal researcher should use to run successful studies. Of course many of the problems faced by the animal researcher are common to other disciplines, and hence the ideas contained within this book can be applied to other areas. It should be noted that certain topics described in the text have been simplified to allow non-statisticians to apply the ideas without professional statistical support. Such pragmatic descriptions, while simplifying the technical details, are not universal and will not be applicable in all scientific disciplines.
InVivoStat is a free-to-use statistical software package developed specifically for animal researchers. It consists of a series of modules, which produce graphical plots, summary statistics and statistical analyses. In this chapter we shall discuss how to use InVivoStat, describe the individual modules and consider some of the technical details of the analyses.
Getting started
InVivoStat can be downloaded from the website: www.invivostat.co.uk. Once installed it can be accessed via the Windows start menu.
Data import
Data can be imported into InVivoStat from Excel (using the xls or xlsx file formats) or from a text editor using the csv (comma delimited) format. It is recommended that the final dataset is first created in Excel, including all data manipulations, before importing into InVivoStat. If the Excel file contains multiple worksheets, then the user is prompted to select one of the worksheets to import into InVivoStat. Multiple datasets can be opened within InVivoStat but they must be imported individually.
Datasets cannot contain commas in either the variable names or within the body of the data. Variable names cannot also contain the symbols: ~ (tilde), + (plus) or * (asterisk), as these characters are used internally within InVivoStat. Users will not be able to import datasets that include these characters.
This book is aimed at practitioners who do not have a statistics degree and yet wish to apply statistics to help them arrive at valid and reliable conclusions while minimising the animal numbers required. Descriptions of the mathematical methods underpinning the topics covered in the book are purposefully kept to a minimum. If readers wish to gain a better understanding of the mathematics behind experimental design and statistical analysis then reading a more advanced textbook would help further their understanding.
The solutions to practical problems encountered when conducting animal experiments are explained using non-technical approaches. We believe that in many situations advanced statistical ideas can be employed successfully by researchers with no statistical qualification, using a combination of common sense and modern statistical analysis software packages. In our experience statistical ideas are often introduced to scientists using mathematical terminology. This can be off-putting to non-mathematicians and can leave researchers with, at best, only rudimentary statistical tools and at worst a fear of statistics.
To keep the descriptions of the statistical tools covered in this book as simple as possible, we shall occasionally give pragmatic explanations. While such explanations may not apply in all cases and in all scientific disciplines, this approach does allow us to introduce methods in a clear and concise way. By allowing ourselves the freedom to simplify the problems pragmatically, we aim to make statistical tools more accessible. The reader is invited, once they have familiarised themselves with (and hopefully found the benefit of using) the tools described in this book, to read more advanced texts on the subject.
It has long been recognised that the use of experimental design is crucial in animal research. By using more efficient experimental designs we can maximise the amount of information gained, while reducing the number of animals required. Even seemingly straightforward experiments employ designs that have features that may, in certain cases, help reduce the number of animals. It is also true that if the scientist spends time considering the experimental design, then practical problems can be solved systematically. Experimental design provides a logical framework that will allow the scientist to develop and understand the animal model in a more refined way.
Experimental design is also a useful tool for researchers who do not feel confident running statistical analyses. As observed by Montgomery (1997, p. 18), if you plan the design carefully and correctly, using a little common sense, then the analysis will almost certainly be relatively straightforward. The validity of the results of many statistical tests relies on the underlying experimental design and randomisation.
We shall begin by considering in more detail some of the real benefits to be gained when using experimental designs, from both practical and statistical perspectives. We will then define the fundamental concepts that define an experimental design and finally describe some commonly applied families of designs.