Quality of evidence in studies evaluating neuroimaging for neurologic prognostication in adult patients resuscitated from cardiac arrest

Aim

Neuroimaging has been proposed as a predictor of neurologic outcome in comatose survivors of cardiac arrest. We reviewed the quality and level of evidence of the current neuroimaging literature for predicting neurologic outcome in cardiac arrest patients treated with or without therapeutic hypothermia (TH).

Data Sources

Medline, EMBASE, and Cochrane Databases were searched using the terms “cardiac arrest,” “cardiopulmonary resuscitation,” “brain hypoxia,” “brain anoxia,” “brain hypoxia-ischaemia,” “neuroimaging,” and “prognosis.” Eligible studies were reviewed and classified by level of evidence and methodological quality as defined by the International Liaison Committee on Resuscitation (ILCOR).

Results

928 studies were identified, 84 of which met inclusion criteria: 74 were supportive of neuroimaging to predict outcome, eight unsupportive, and two equivocal. Several studies investigated more than one imaging modality: 27 investigated computed tomography (CT), 46 magnetic resonance imaging (MRI), and 18 alternate imaging modalities, including positron emission tomography and single photon emission computed tomography. No randomized controlled trials were identified. Seven cohort and case control studies were identified, only one of which was graded “good” quality, two were “fair” and four were “poor.”

Conclusion

Neuroimaging is an evolving modality as a prognostic parameter in cardiac arrest survivors. However, the quality of the available literature is not robust, highlighting the need for higher quality studies before neuroimaging can be supported as a standard tool for prognostication in the patient population.     

Traitement de 22 cas de tendinites du coude, rebelles aux traitements classiques, par injection de plasma riche en plaquettes (PRP)

This 22 months study focussed on the treatment of epicondylitis and chronic tricipital tedinitis using platelets rich plasma injections. These 22 elbows had worsened for 7 months and had failed to improve after at least two standard treatments. Over half were treated with corticoid infiltrations or presented contraindication (tricipital tendinitis) and for some, surgery was suggested. In this study, the average measurement of pain, as visually observed in “every day life”, was above 5.50. Approximately half of the patients received a “good” or “very good” result after the first treatment. For nine of the patients, a second treatment was needed and for three, a third one. The overall outcome showed 86% “good” and “very good” results. Follow-up examination after 9 months for the latest treatments and 22 months for the earliest ones showed no evidence of relapse, but instead continued improvement.     

Frontal and transverse plane hip kinematics and gluteus maximus recruitment correlate with frontal plane knee kinematics during single-leg squat tests in women

Background

Hip muscle dysfunction may be associated with knee valgus that contributes to problems like patellofemoral pain syndrome. The purpose of this study was to (1) compare knee and hip kinematics and hip muscle strength and recruitment between “good” and “poor” performers on a single-leg squat test developed to assess hip muscle dysfunction and (2) examine relationships between hip muscle strength, recruitment and frontal plane knee kinematics to see which variables correlated with knee valgus during the test.

Methods

Forty-one active women classified via visual rating as “good” or “poor” performers on the test participated. Participants completed 5-repetition single-leg squat tests. Isometric hip extension and abduction strength, gluteus maximus and gluteus medius recruitment, and 3-dimensional hip and knee kinematics during the test were compared between groups and examined for their association with frontal plane knee motion.

Findings

“Poor” performers completed the test with more hip adduction (mean difference = 7.6°) and flexion (mean difference = 6.3°) than “good” performers. No differences in knee kinematics, hip strength or hip muscle recruitment occurred. However, the secondary findings indicated that increased medial hip rotation (partial r = 0.94) and adduction (partial r = 0.42) and decreased gluteus maximus recruitment (partial r = 0.35) correlated with increased knee valgus.

Interpretation

Whereas hip muscle function and knee kinematics did not differ between groups as we'd hypothesized, frontal plane knee motion correlated with transverse and frontal plane hip motions and with gluteus maximus recruitment. Gluteus maximus recruitment may modulate frontal plane knee kinematics during single-leg squats.     

Brain mediators of the effects of noxious heat on pain

Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. Although useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this study, we used multi-level mediation analysis to identify brain mediators of pain—regions in which trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across 4 levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including the following: somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and 2 networks co-localized with “default mode” regions in which stimulus intensity-related decreases mediated increased pain. We also identified “thermosensory” regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain.     

Outcome measures utilized in clinical trials of interventions for post-cardiac arrest syndrome: A systematic review

Background

The post-cardiac arrest syndrome (period of critical illness following return of spontaneous circulation [ROSC]) is a promising window of opportunity for clinical trials of therapeutic interventions to improve outcome from cardiac arrest. However, the methodological rigor of post-ROSC trials and the ability to compare or pool data on treatment effects across studies requires consistent and appropriate outcome measures. We aimed to determine the current degree of uniformity of outcome measures in clinical trials of post-ROSC interventions.

Methods

We conducted a systematic review of Cochrane Library, MEDLINE, EMBASE, CINAHL, conference proceedings, and clinical trial registrations using a comprehensive strategy. We identified experimental or quasi-experimental trials testing post-ROSC interventions in adults. Four authors independently extracted data and assessed study quality using standardized instruments.

Results

The search yielded 33 potential studies, of which 13 randomized controlled trials (n = 1937) were included in the final analysis. Seven trials tested pharmacologic therapies and six tested non-pharmacologic therapies. Our main finding is that heterogeneity in the selection and reporting of outcomes limited comparability of results across studies. No two trials used exactly the same primary outcome, and timing of measurement varied widely. We found only two commonalities: (1) indices of functional survival were used rather than survival alone, and (2) ordinal scales of neurological function were collapsed into clinically meaningful groups (“good” versus “bad” outcome).

Conclusion

Currently there is a lack of uniformity in selection and reporting of outcome measures among trials of post-ROSC interventions. Achieving consensus would be an important advance for resuscitation science.     

Test-Retest Reliability of Pain-Related Brain Activity in Healthy Controls Undergoing Experimental Thermal Pain

Although functional magnetic resonance imaging (fMRI) has been proposed as a method to elucidate pain-related biomarkers, little information exists related to psychometric properties of fMRI findings. This knowledge is essential for potential translation of this technology to clinical settings. The purpose of this study was to assess the test-retest reliability of pain-related brain activity and how it compares to the reliability of self-report. Twenty-two healthy controls (mean age = 22.6 years, standard deviation = 2.9) underwent 3 runs of an fMRI paradigm that used thermal stimuli to elicit experimental pain. Functional MRI summary statistics related to brain activity during thermal stimulation periods were extracted from bilateral anterior cingulate cortices and anterior insula. Intraclass correlations (ICCs) were conducted on these summary statistics and generally showed “good” test-retest reliability in all regions of interest (ICC range = .32–.88; mean = .71); however, these results did not surpass ICC values from pain ratings, which fell within the “excellent” range (ICC range = .93–.96; mean = .94). Findings suggest that fMRI is a valuable tool for measuring pain mechanisms but did not show an adequate level of test-retest reliability for fMRI to potentially act as a surrogate for individuals' self-report of pain.     

The importance of context: When relative relief renders pain pleasant

Context can influence the experience of any event. For instance, the thought that “it could be worse” can improve feelings towards a present misfortune. In this study we measured hedonic feelings, skin conductance, and brain activation patterns in 16 healthy volunteers who experienced moderate pain in two different contexts. In the “relative relief context,” moderate pain represented the best outcome, since the alternative outcome was intense pain. However, in the control context, moderate pain represented the worst outcome and elicited negative hedonic feelings. The context manipulation resulted in a “hedonic flip,” such that moderate pain elicited positive hedonics in the relative relief context. Somewhat surprisingly, moderate pain was even rated as pleasant in this context, despite being reported as painful in the control context. This “hedonic flip” was corroborated by physiological and functional neuroimaging data. When moderate pain was perceived as pleasant, skin conductance and activity in insula and dorsal anterior cingulate were significantly attenuated relative to the control moderate stimulus. “Pleasant pain” also increased activity in reward and valuation circuitry, including the medial orbitofrontal and ventromedial prefrontal cortices. Furthermore, the change in outcome hedonics correlated with activity in the periacqueductal grey (PAG) of the descending pain modulatory system (DPMS). The context manipulation also significantly increased functional connectivity between reward circuitry and the PAG, consistent with a functional change of the DPMS due to the altered motivational state. The findings of this study point to a role for brainstem and reward circuitry in a context-induced “hedonic flip” of pain.     

Cultural influences on neural basis of intergroup empathy

Cultures vary in the extent to which people prefer social hierarchical or egalitarian relations between individuals and groups. Here we examined the effect of cultural variation in preference for social hierarchy on the neural basis of intergroup empathy. Using cross-cultural neuroimaging, we measured neural responses while Korean and American participants observed scenes of racial ingroup and outgroup members in emotional pain. Compared to Caucasian-American participants, Korean participants reported experiencing greater empathy and elicited stronger activity in the left temporo-parietal junction (L-TPJ), a region previously associated with mental state inference, for ingroup compared to outgroup members. Furthermore, preferential reactivity within this region to the pain of ingroup relative to outgroup members was associated with greater preference for social hierarchy and ingroup biases in empathy. Together, these results suggest that cultural variation in preference for social hierarchy leads to cultural variation in ingroup-preferences in empathy, due to increased engagement of brain regions associated with representing and inferring the mental states of others.     

Accurate brain age prediction with lightweight deep neural networks

Deep learning has huge potential for accurate disease prediction with neuroimaging data, but the prediction performance is often limited by training-dataset size and computing memory requirements. To address this, we propose a deep convolutional neural network model, Simple Fully Convolutional Network (SFCN), for accurate prediction of brain age using T1-weighted structural MRI data. Compared with other popular deep network architectures, SFCN has fewer parameters, so is more compatible with small dataset size and 3D volume data. The network architecture was combined with several techniques for boosting performance, including data augmentation, pre-training, model regularization, model ensemble and prediction bias correction. We compared our overall SFCN approach with several widely-used machine learning models. It achieved state-of-the-art performance in UK Biobank data (N = 14,503), with mean absolute error (MAE) = 2.14y in brain age prediction and 99.5% in sex classification. SFCN also won (both parts of) the 2019 Predictive Analysis Challenge for brain age prediction, involving 79 competing teams (N = 2,638, MAE = 2.90y). We describe here the details of our approach, and its optimisation and validation. Our approach can easily be generalised to other tasks using different image modalities, and is released on GitHub.     

Altered gray matter volume in the frontal pain modulation network in patients with cluster headache

Previous functional imaging studies in episodic cluster headache (CH) patients revealed altered brain metabolism concentrated on the central descending pain control system. However, it remains unclear whether changes in brain metabolism during the “in bout” period are due to structural changes and whether these structural changes vary between the “in bout” and “out of bout” periods. To quantify brain structural changes in CH patients, the regional gray matter volume (GMV) was compared among 49 episodic CH patients during the “in bout” period and 49 age- and sex-matched controls. Twelve patients were rescanned during the “out of bout” period to evaluate the changes, if any, between these 2 periods. Compared with healthy controls, CH patients showed significant “in bout” GMV reductions in the bilateral middle frontal, left superior, and medial frontal gyri. Compared to “out of bout” scans, the “in bout” scans revealed significant GMV increases in the left anterior cingulate, insula, and fusiform gyrus. Additionally, compared to healthy controls, the “out of bout” scans revealed a trend of GMV reduction in the left middle frontal gyrus. These affected regions primarily belong to frontal pain modulation areas, and thus these GMV changes may reflect insufficient pain-modulating capacity in the frontal areas of CH patients.     

A Spike-Timing Pattern Based Neural Network Model for the Study of Memory Dynamics

It is well accepted that the brain's computation relies on spatiotemporal activity of neural networks. In particular, there is growing evidence of the importance of continuously and precisely timed spiking activity. Therefore, it is important to characterize memory states in terms of spike-timing patterns that give both reliable memory of firing activities and precise memory of firing timings. The relationship between memory states and spike-timing patterns has been studied empirically with large-scale recording of neuron population in recent years. Here, by using a recurrent neural network model with dynamics at two time scales, we construct a dynamical memory network model which embeds both fast neural and synaptic variation and slow learning dynamics. A state vector is proposed to describe memory states in terms of spike-timing patterns of neural population, and a distance measure of state vector is defined to study several important phenomena of memory dynamics: partial memory recall, learning efficiency, learning with correlated stimuli. We show that the distance measure can capture the timing difference of memory states. In addition, we examine the influence of network topology on learning ability, and show that local connections can increase the network's ability to embed more memory states. Together theses results suggest that the proposed system based on spike-timing patterns gives a productive model for the study of detailed learning and memory dynamics.     

Improving verbal communication in critical care medicine

Human errors are the most common reason for planes to crash, and of all human errors, suboptimal communication is the number 1 issue. Mounting evidence suggests the same for errors during short-term medical care. Strong verbal communication skills are key whether for establishing a shared mental model, coordinating tasks, centralizing the flow of information, or stabilizing emotions. However, in contrast to aerospace, most medical curricula rarely address communication norms during impending crises. Therefore, this article offers practical strategies borrowed from aviation and applied to critical care medicine. These crisis communication strategies include “flying by voice,” the need to combat “mitigating language,” the uses of “graded assertiveness” and “5-step advocacy,” and the potential role of Situation, Background, Assessment, and Recommendation communication. We also outline the “step-back method,” the concept of communication “below ten thousand feet,” the impetus behind “closed-loop communication,” and the closely related “repeat-back method.” The goal is for critical care practitioners to develop a “verbal dexterity” to match their procedural dexterity and factual expertise.     

From SOLER to SURETY for effective non-verbal communication

Background

This paper critiques the model for non-verbal communication referred to as SOLER (which stands for: “Sit squarely”; “Open posture”; “Lean towards the other”; “Eye contact; “Relax”). It has been approximately thirty years since Egan (1975) introduced his acronym SOLER as an aid for teaching and learning about non-verbal communication.

Aim

There is evidence that the SOLER framework has been widely used in nurse education with little published critical appraisal. A new acronym that might be appropriate for non-verbal communication skills training and education is proposed and this is SURETY (which stands for “Sit at an angle”; “Uncross legs and arms”; “Relax”; “Eye contact”; “Touch”; “Your intuition”).

The new model

The proposed model advances the SOLER model by including the use of touch and the importance of individual intuition is emphasised. The model encourages student nurse educators to also think about therapeutic space when they teach skills of non-verbal communication.     

A possible neural basis for stress-induced hyperalgesia

Intense stress and fear have long been known to give rise to a suppression of pain termed “stress-induced analgesia”, mediated by brainstem pain-modulating circuitry, including pain-inhibiting neurons of the rostral ventromedial medulla. However, stress does not invariably suppress pain, and indeed, may exacerbate it. Although there is a growing support for the idea of “stress-induced hyperalgesia”, the neurobiological basis for this effect remains almost entirely unknown. Using simultaneous single-cell recording and functional analysis, we show here that stimulation of the dorsomedial nucleus of the hypothalamus, known to be a critical component of central mechanisms mediating neuroendocrine, cardiovascular and thermogenic responses to mild or “emotional” stressors such as air puff, also triggers thermal hyperalgesia by recruiting pain-facilitating neurons, “ON-cells”, in the rostral ventromedial medulla. Activity of identified RVM ON-cells, OFF-cells and NEUTRAL cells, nociceptive withdrawal thresholds, rectal temperature, and heart rate were recorded in lightly anesthetized rats. In addition to the expected increases in body temperature and heart rate, disinhibition of the DMH induced a robust activation of ON-cells, suppression of OFF-cell firing and behavioral hyperalgesia. Blocking ON-cell activation prevented hyperalgesia, but did not interfere with DMH-induced thermogenesis or tachycardia, pointing to differentiation of neural substrates for autonomic and nociceptive modulation within the RVM. These data demonstrate a top-down activation of brainstem pain-facilitating neurons, and suggest a possible neural circuit for stress-induced hyperalgesia.     

One brain, two selves

Having a sense of self is an explicit and high-level functional specialization of the human brain. The anatomical localization of self-awareness and the brain mechanisms involved in consciousness were investigated by functional neuroimaging different emotional mental states of core consciousness in patients with Multiple Personality Disorder (i.e., Dissociative Identity Disorder (DID)). We demonstrate specific changes in localized brain activity consistent with their ability to generate at least two distinct mental states of self-awareness, each with its own access to autobiographical trauma-related memory. Our findings reveal the existence of different regional cerebral blood flow patterns for different senses of self. We present evidence for the medial prefrontal cortex (MPFC) and the posterior associative cortices to have an integral role in conscious experience.     

Video-rate full-ring ultrasound and photoacoustic computed tomography with real-time sound speed optimization

Full-ring dual-modal ultrasound and photoacoustic imaging provide complementary contrasts, high spatial resolution, full view angle and are more desirable in pre-clinical and clinical applications. However, two long-standing challenges exist in achieving high-quality video-rate dual-modal imaging. One is the increased data processing burden from the dense acquisition. Another one is the object-dependent speed of sound variation, which may cause blurry, splitting artifacts, and low imaging contrast. Here, we develop a video-rate full-ring ultrasound and photoacoustic computed tomography (VF-USPACT) with real-time optimization of the speed of sound. We improve the imaging speed by selective and parallel image reconstruction. We determine the optimal sound speed via co-registered ultrasound imaging. Equipped with a 256-channel ultrasound array, the dual-modal system can optimize the sound speed and reconstruct dual-modal images at 10 Hz in real-time. The optimized sound speed can effectively enhance the imaging quality under various sample sizes, types, or physiological states. In animal and human imaging, the system shows co-registered dual contrasts, high spatial resolution (140 µm), single-pulse photoacoustic imaging (< 50 µs), deep penetration (> 20 mm), full view, and adaptive sound speed correction. We believe VF-USPACT can advance many real-time biomedical imaging applications, such as vascular disease diagnosing, cancer screening, or neuroimaging.     

Experiences of sudden cardiac arrest survivors regarding prognostication and advance care planning

Objective

We sought to better understand SCA survivors’ beliefs about complex issues that arise in the immediate post-arrest period and explore advance care planning. Specifically, we wished to explore four themes: (1) patient and family perception of medical providers’ prognostication in the immediate post-arrest phase; (2) patient definitions of death; (3) use of advance directives (ADs); and (4) perceptions of health and organ donation.

Methods

We conducted a qualitative study of adult arrest survivors using semi-structured telephone interviews. Participants were recruited from a nonprofit national organization for SCA.

Results

Nine of 11 subjects contacted completed the survey. In the immediate post-arrest phase, subjects believed that medical professionals made errors in giving poor prognosis early in the course of resuscitation. While some subjects felt they had experienced “death,” some subjects felt the term “death” was an inappropriate term to describe their experience. The majority of the subjects did not have an AD prior to their SCA and no subjects reported having a conversation about ADs with their medical team. While the majority of subjects classified their health as “very good” or “excellent,” few subjects were registered organ donors, citing comorbidities and skepticism about future resuscitative efforts as rationale.

Conclusions

Our study elucidated the attitudes and experiences of SCA survivors. Variability in prognostication timing and inconsistency in describing SCA can complicate discussions between the medical team and families. AD and organ donation discussions may help to provide sensitive care concordant with a patient's wishes.     

Maintaining dignity for residents of care homes: A qualitative study of the views of care home staff,community nurses,residents and their families

This study uses the Framework approach to qualitative analysis to explore and compare the views of residents in care homes for older people, their families and care providers on maintaining dignity. We interviewed 33 care home managers, 29 care assistants, 18 care home nurses, 10 community nurses, 16 residents and 15 members of residents' families. The most prevalent themes were: “independence,” and “privacy”; followed by “comfort and care,” “individuality,” “respect,” “communication,” “physical appearance” and “being seen as human.” Residents and their families sometimes described incidents where a resident's dignity had been compromised. How to help residents maintain dignity and focusing on fostering dignity, can be a starting point for improving the quality of care and quality of life of residents. It is, however, important to remove the gap between the rhetoric of dignity conserving care and the reality experienced by residents in these and other care settings.