Clinical Research in Prehospital Care: Current and Future Challenges.

Prehospital care plays a critical role in improving patient outcomes, particularly in cases of time-sensitive emergencies such as trauma, cardiac failure, stroke, bleeding, breathing difficulties, systemic infections, etc. In recent years, there has been a growing interest in clinical research in prehospital care, and several challenges and opportunities have emerged. There is an urgent need to adapt clinical research methodology to a context of prehospital care. At the same time, there are many barriers in prehospital research due to the complex context, posing unique challenges for research, development, and evaluation. Among these, this review allows the highlighting of limited resources and infrastructure, ethical and regulatory considerations, time constraints, privacy, safety concerns, data collection and analysis, selection of a homogeneous study group, etc. The analysis of the literature also highlights solutions such as strong collaboration between emergency medical services (EMS) and hospital care, use of (mobile) health technologies and artificial intelligence, use of standardized protocols and guidelines, etc. Overall, the purpose of this narrative review is to examine the current state of clinical research in prehospital care and identify gaps in knowledge, including the challenges and opportunities for future research.

Design a Clinical Research Protocol: Influence of Real-World Setting.

The design of a clinical research protocol to evaluate new therapies, devices, patient quality of life, and medical practices from scratch is probably one of the greatest challenges for the majority of novice researchers. This is especially true since a high-quality methodology is required to achieve success and effectiveness in academic and hospital research centers. This review discusses the concrete steps and necessary guidelines needed to create and structure a research protocol. Along with the methodology, some administrative challenges (ethics, regulatory and people-management barriers) and possible time-saving recommendations (standardized procedures, collaborative training, and centralization) are discussed.

Opposed attentional hemi-bias on a visuoconstructive task in children with severe hyperactivity versus severe inattention.

Twenty six empirical investigations have now established that children and adults with DSM-defined Attention deficit/Hyperactivity disorder (ADHD) of the Hyperactive type (ADHD-H) or, more commonly, Combined Hyperactive/Inattentive types (ADHD-C) manifest a small but significant visual attentional bias to the right side (left subclinical neglect), consistently suggesting the existence of a subtle right hemisphere dysfunction or hemispheric imbalance in hyperactive people. Only one research team has investigated and compared the DSM-defined Inattentive subtype (ADHD-I) to the Hyperactive subtype (ADHD-H), confirming that line bisection is biased to the right in ADHD-H and discovering that it is biased to the left in ADHD-I. We aimed to test whether a similar crossed double dissociation would extend to Rey's Complex Figure Copy Task (RCF-CT), a simple visuospatial-constructive task. Clinical files of 205 juvenile clients from 6 to 16 years of age from a neuropsychological private clinic specialized in ADHD were analysed. Extreme scores on the Connors-3 Hyperactivity vs Inattention Parent Rating scales associated, respectively, with significant rightward and significant leftward emplacement of the drawing on the page on the RCF-CT. These results replicate previous findings and extend the "energetics" model of hemispheric specialization.

Building a competitive infrastructure to support clinical research in healthcare institution.

BACKGROUND: Clinical research is becoming increasingly popular in Europe at a growth rate much higher than expected, especially in Benelux. Although traditionally thought to be the purview of academic health centres, clinical research to evaluate new drugs, devices and medical practices is being done more and more in healthcare organizations with little or no academic affiliation. METHODS: By managing a new infrastructure and centralizing resources and demands, clinical research unit (CRU) has become an effective mechanism for hospital research. The 'infrastructure' or CRU refers to the necessary resources and how the CRU is organized and communicates operationally to conduct clinical research within the institution. The creation of a new CRU within the Robert Schuman Hospital in Luxembourg is described in this article. RESULTS: This article discusses the concrete steps and basic elements such as patient-centric and hospital approaches needed to create and structure a CRU to provide academic or industry-sponsored research support in clinical research. CONCLUSIONS: Some infrastructure challenges (insufficient engagement, regulatory and administrative barriers) and possible courses of action (standardized procedures, training and centralization) will be discussed.

Reaction Time of Erroneous Responses in the Go/No-Go Paradigm.

Reaction time (RT) of erroneous responses in go/no-go tasks tends to be shorter than RT of correct responses. An opposite difference has been reported ( Halperin, Wolf, Greenblatt, & Young, 1991 ) which could be attributed to differences in go trial probability, or to high memory demand. Two experiments aimed here to test these two explanations, a simultaneous matching task with low memory load (Experiment 1), and a sequential matching task with high memory load (Experiment 2). Go trial probability was also manipulated. Short false positive RT was obtained only in the sequential matching task with high go trial probability, while long false positive RT was obtained in the other three conditions. Low go trial probability and high memory load were both found to be sufficient, by themselves, to create long false positives attributable to confusion. Short false positives in the high go trial probability/low memory load condition were attributed to failure of response inhibition.

Intellectual outcome after a cortical lesion with versus without epilepsy: A life span neurodevelopmental view.

In patients with cortical lesions, the structure of intelligence has never been studied as a function of age at lesion onset and presence vs absence of lesional epilepsy over the life span. METHOD: Two thousand one hundred eighty-six cases were assembled bearing unilateral cortical lesions occurring at all ages (1301 with seizures) with postlesion verbal intelligence quotient (IQ) (VIQ) and performance IQ (PIQ). RESULTS: Global IQ significantly and constantly decreased as a function of age at lesion onset in the cases without epilepsy, and increased in the cases with epilepsy. Beyond the lesion onset age of 12 years, VIQ was significantly higher than PIQ in the cases without epilepsy, and lower in the cases with epilepsy. The VIQ/PIQ × lesion-side interaction indicative of hemispheric specialization increased significantly linearly with age at lesion onset in the patients without epilepsy but ceased to progress at the lesion-onset age of 30 years and beyond in the cases with epilepsy. CONCLUSION: Postlesion global IQ, the difference between VIQ and PIQ, and the laterality index all vary significantly as a function of age at lesion onset. In addition, these changes over the life span are all quite different between cases with and without epilepsy.

Effects of stimulus pair orientation and hand switching on reaction time estimates of interhemispheric transfer.

Two behavioral estimates of interhemispheric transfer time, the crossed-uncrossed difference (CUD) and the unilateral field advantage (UFA), are thought to, respectively, index transfer of premotor and visual information across the corpus callosum in neurotypical participants. However, no attempt to manipulate visual and motor contingencies in a set of tasks while measuring the CUD and the UFA has yet been reported. In two go/no-go comparison experiments, stimulus pair orientations were manipulated. The hand of response changed after each correct response in the second, but not the first experiment. No correlation was found between the CUD and the UFA, supporting the hypothesis that these two measures index different types of information transfer across hemispheres. An effect of manipulation of stimulus pair orientation on UFAs was attributed to the homotopy of callosal fibers transferring visual information, while an effect of hand switching on CUDs was attributed mostly to spatial compatibility.

Development of "material-specific" hemispheric specialization from beginning to end.

Disparity of verbal and performance intelligence (VIQ, PIQ) on the Wechsler scales of intelligence is a conceptually cluttered and empirically weak measure of hemispheric specialization (HS). However, in the context of life span research, it is the only measure that can be exploited meta-analytically with the lesion method from prenatal life to late senescence. We assembled 1917 cases with a unilateral cortical focal brain lesion occurring at all ages and a post-lesion VIQ and PIQ. Lesion locus, volume and side were documented for each case, as well as age at lesion onset, age at first symptoms and age at the IQ test, presence/absence of epilepsy, lesion aetiology, gender, date of publication or of transfer of medical file. With and without covariate adjustment, HS was significant across the life span though its pattern changed. HS increased linearly and highly significantly until late senescence. Only in early adulthood did VIQ appear to vacate the right temporal lobe and occupy the left and PIQ vacate the left parietal lobe and occupy the right until late senescence. Biomaturational factors are more important in the ontogeny of material-specific HS over the whole life span than previously established.

Callosal Sensitivity to Short-Range Stimulus Orientation and Long-Range Stimulus Context Orientation: Tachistoscopic Evidence.

To study local-global relationships in interhemispheric interactions, tachistoscopically presented pairs of lines (1.15 degrees) were compared for their relative orientation by 48 neurotypical adults. Orientations of line stimuli (local aspect of the task) were vertical, horizontal, forward slash or backslash, as were those of the interstimulus axes. The latter created a global context that could influence line discrimination. Stimulus pairs were presented within a field (not requiring callosal participation for line orientation comparison) or one on each side of the visual field meridian (requiring callosal participation). The primary purpose of the design was to determine whether local or global violations of stimulus "homotopy" across the meridian would impose costs of interhemispheric integration. The rationale for this expectation is that the fiber projection of the corpus callosum is highly symmetric across the midsagittal plane (i.e., homotopic). The expected "callosal homotopy" effect was significantly upheld as a whole but broke down or became extravagant in certain specific conditions, with specific costs of interhemispheric integration varying from null to a highly significant 20-ms as a function of interactions of interstimulus and stimulus orientations. The corpus callosum seems to be particularly sensitive to local stimulus orientation in interaction with long-range stimulus context orientation.

Inter-hemispheric dynamics revealed by reaction time in the Dimond paradigm.

The Dimond paradigm (DP) consists of tachistoscopically presenting two stimuli to be discriminated--either both stimuli in a single visual hemifield or one in each. The DP has recently been implemented using predecessors to index homotopy of the callosal fibre projection with reaction time (RT) as the dependent measure. Using simple perceptual discrimination tasks, it has recently been reported that the advantage of the unilateral stimulation condition significantly decreases with practice. This effect has been interpreted as being due to the plasticity of the callosal network. Two experiments were designed to replicate these two little-known effects, namely callosal homotopy and callosal network plasticity. In addition, new evidence of another type of callosal network plasticity, termed "callosal network dispatching", was sought by introducing double manipulation of orientations of both stimulus-contours and inter-stimulus arrays to the DP. Strong support for the callosal homotopy and callosal network plasticity effects was obtained. In addition, evidence for a "callosal network dispatcher" effect accrued.

Gender-related protection from or vulnerability to severe CNS diseases: gonado-structural and/or gonado-activational? A meta-analysis of relevant epidemiological studies.

BACKGROUND: A vast scientific literature has dealt with gender-specific risk for brain disorder. That field is evolving toward a consensus to the effect that the estrogen hormone family is outstandingly and uniquely neuroprotective. However, the epidemiology relevant to this general outlook remains piecemeal. METHOD: The present investigation strategically formats the relevant epidemiological findings around the world in order to quantitatively meta-analyze gender ratio of risk for a variety of relevant severe central nervous system (CNS) diseases at all three gonadal stages of the life cycle, pre pubertal, post adolescent/pre menopausal, and post menopausal. RESULTS: The data quantitatively establish that (1) no single epidemiological study should be cited as evidence of gender-specific neuroprotection against the most common severe CNS diseases because the gender-specific risk ratios are contradictory from one study to the other; (2) risk for severe CNS disease is indeed significantly gender-specific, but either gender can be protected: it depends on the disease, not at all on the age bracket. CONCLUSION: Our assay of gender-specific risk for severe brain disease around the world has not been able to support the idea according to which any one gender-prevalent gonadal steroid hormone dominates as a neuroprotective agent at natural concentrations.

Intra and inter hemispheric dynamics revealed by reaction time in the Dimond paradigm: a quantitative review of the literature.

In stimulus matching tasks requiring discrimination of two unilaterally or bilaterally presented stimuli (Dimond paradigm), a well established intrahemispheric processing bottleneck model predicts that an increase in task difficulty as measured by reaction time should provide an advantage to bilateral stimulations. The purpose of the current investigation was to review the entire relevant literature on the Dimond paradigm and identify the experimental variables which reliably yield such effects. Forty nine experimental effects compatible with the "intrahemispheric processing bottleneck" model and 26 contrary effects were found. Manipulation of the complexity of the stimulus matching criterion significantly produced intrahemispheric bottleneck effects. This effect was also significantly greater when non-target stimuli required heavier processing. These two findings support the intrahemispheric bottleneck model: computationally complex tasks seem to overload a hemisphere׳s processing capacity, an effect seen in the unilateral presentation conditions. However, manipulating the similarity of target stimuli produced contrary effects. Contrary effects were also obtained more readily when two physical matching tasks were compared. These two latter effects may best be explained as low level visual-perceptual limitations of interhemispheric transfer or integration.

Evidence from unilateral lesions of early uncompensable implementation of opposed response-biases in each hemisphere of the brain.

PURPOSE: The intact right hemisphere presents an omissive response-bias and the left hemisphere a commissive response-bias in adults. This research sought to determine whether these hemispherically lateralized response-biases manifest early developmental and uncompensable brain implementation. METHODS: Sixteen teenager and adult participants with focal left hemisphere lesions and fourteen with focal right hemisphere lesions (all with childhood onset: M=13 year recovery period) and 14 normal control participants were recruited. A computerized multitask high order working memory procedure was designed to generate many errors of omission and of commission. RESULTS: The expected double dissociation of response-bias distortion as a function of lesion side was significantly demonstrated on this task and was significantly frontal-lobe dependent. CONCLUSION: The hemispheres of the brain have an opposed response bias that is robustly implemented in infancy through adulthood.

Comparison of two models of hemispheric specialization with unilaterally lesioned patients: material-specific impairment vs response-bias distortion.

Validity of two models of hemispheric specialization was compared. The "material-specific impairment" model was radicalized as postulating that left hemisphere (LH) lesions impair processing of verbal material and that right hemisphere (RH) lesions impair processing of visuospatial material, independently of response-bias distortions. The "response-bias distortion" model was radicalized as postulating that LH lesions distort response style toward omissiveness and that RH lesions distort response style toward commissiveness, regardless of material-specific impairments. Participants had comparable left (N=27) or right (N=24) hemisphere cortical lesions having occurred between birth and early adolescence. Four cognitive neuropsychological tests were adjusted to optimize applicability and comparability of the two theoretical models: Rey Complex Figure, Kimura's Recurring Figures, the Story Recall subtest of the Children's Memory Scale, and the California Verbal Learning Test. Both models significantly, independently, and equally distinguished the LH from the RH patients. Both these forms of hemispheric specialization seemed to be implemented very early in life and very rigidly. Intrahemispheric lesion sites, e.g., frontal vs nonfrontal, held no significant relation to the effects described above.

EEG amplitude spectra before near threshold visual presentations differentially predict detection/omission and short-long reaction time outcomes.

Performance in simple stimulus detection manifests as both probability of detection and speed of signaling detected stimuli. These two dimensions of performance across trials were examined with respect to brain states just prior to stimulus delivery, using near threshold stimuli targeting the magnocellular or the parvocellular visual streams in an attempt to isolate differential perceptual preparation. The EEG amplitude of 12 university students was analyzed in spectral bands from 2 to 50 Hz at 9 bilateral channel pairs in a window covering -450 ms to +50 ms relative to stimulus onset. A hierarchical statistical procedure was applied to control false positive results. EEG power in the 2, 4, 8 and 10 Hz bands was found significantly lower at the F7-F8 channel pair both before detected compared to omitted stimuli and before the fastest compared to slowest reaction time quartiles, with no stimulus type effect. In addition, the 22 and 24 Hz band activity was lower prior to better performance frontally (F3-F4, F7-F8) in reaction time but not in detection, while it was larger centro-parietally (CP1-CP2, P3-P4) in detection but not in reaction times. Spectral analysis thus shows stimulus detection and response speed to depend partly on common and partly on distinct pre-stimulus brain states.

Specific early vulnerability of high-order executive function to focal brain lesions and long-term impact on educational persistence: Sparing of incidental episodic memory.

OBJECTIVE: We investigated mental functions expected to remain impaired or not ain adulthood following childhood-onset brain lesions. METHODS: Thirty unilaterally lesioned young adults were tested a decade after lesion onset with an effort-demanding complex executive function (EF) task as well as a task of incidental declarative retrospective episodic recognition memory (IRM). Thirty neurotypical participants were also tested. RESULTS: The EF task was significantly impaired in the lesion group and significantly more so than the IRM task. Regarding the lesioned cases, performance on EF, but not IRM, was significantly positively correlated with long-term educational persistence (EP). Both EF and EP but not IRM were significantly positively correlated with the age of onset of the lesion. Severity of neurological impairment was unrelated to any variable. CONCLUSION: Mental abilities acquired through early schooling remain impaired into adulthood when early schooling is disturbed, not everyday memory which does not depend on schooling.

Atypical left-right balance of visuomotor awareness in adult ADHD (combined type) on a test of executive function.

Significant left subclinical hemi-neglect or "hemi-unawareness" in juvenile and adult ADHD has been reported many times. However, this literature has never been thoroughly reviewed, and is generally ignored in neuropsychological accounts of ADHD. The purposes of the present report were (1) to introduce a systematic review of this literature and (2) to prospectively test whether adults with ADHD (combined type) would present left hemi-unawareness measurable on a test of executive function commonly used with children and adults with ADHD, the Colour-Word Interference Test of the Delis-Kaplan Executive Functions System. This test requires participants to discriminate unusual stimulus characteristics by stating words aloud while visually scanning plates comprising either 50 colour patches or 50 words. A total of 28 ADHD adults (combined type) and 30 IQ-, age-, and gender-matched controls completed the task. The ADHD group manifested a significantly higher proportion of errors on the left than right sides of the plates. This atypical left-right balance was related to severity of the ADHD according to the Conners' Adult ADHD Rating Scale (CAARS) as well as to several other indicators from the Continuous Performance Test-II.

New variations of intrahemispheric and interhemispheric processing indexed by the dimond paradigm.

We report 2 experiments designed to demonstrate that unilateral tachistoscopic stimulation would yield a response time (RT) advantage over bilateral stimulation in a simple experiment, whereas the opposite pattern would occur in a complex version of the same task, as predicted by the intrahemispheric resource limitation model of Banich and colleagues. Experiment 1 was a go/no-go task in which participants had to press a key when two shapes (circles or squares) were identical on the computer screen. A unilateral field advantage was obtained that was accentuated in several task conditions that yielded overall longer RTs, mostly in the bilateral condition. Experiment 2 was similar but required a more complex judgment: The go trials were to 2 stimuli identical on 1 dimension (shape or color) but not both or neither. The RTs were significantly and substantially longer than in Experiment 1 and exhibited a nonsignificant bilateral field advantage, which differed significantly from the unilateral field advantage obtained in Experiment 1. These results support the intrahemispheric resource limitation model of Banich and colleagues. However, several within-experiment effects are in direct opposition to this model and are best explained as limitations of commissural relay of perceptual information.

A context for normalizing impulsiveness at work for adults with attention deficit/hyperactivity disorder (combined type).

Impaired executive function and impulsiveness or intolerance to boredom in adult attention deficit/hyperactivity disorder (ADHD) are thought to compromise performance at work. Several task parameters help people with ADHD to perform better on computerized cognitive tasks, namely reduced response-to-stimulus interval, discriminative feedback, or a format resembling a videogame. However, still very little is known about how these contexts might be helpful in a real work environment. We developed a computerized task resembling a fast-paced videogame with no response-to-stimulus interval and constant and diverse discriminative error feedback. The task included several measurements of high-order executive function (planning, working memory, and prospective memory) formatted as a single multitask simulating occupational activities (SOA). We also administered the Continuous Performance Test-II (CPT-II), a very simple vigilance task without discriminative feedback and with long response-to-stimulus intervals. We tested 30 adults answering to DSM-IV criteria of ADHD (combined type) and 30 IQ-matched adults without ADHD. As has been reported many times, the ADHD participants made significantly more errors of commission than the control participants on the CPT-II, whereas the two groups made the same number of errors of commission on the SOA. The ADHD group also sought discriminative feedback significantly more actively on the SOA than the control group and performed at par with the control group in all respects. There was no speed/accuracy trade-off, nor was there any evidence of other costs of normalization on the SOA. Impulsiveness in adult ADHD is compensable on a task simulating the work environment.

Opposed hemispheric specializations for human hypersexuality and orgasm?

With a multiple case report analysis we demonstrate that hypersexuality more often results from right hemisphere (RH) (n=26) than left hemisphere (LH) (n=7) lesions, possibly because of LH release after the RH lesion, and that ictal orgasm more often occurs in patients with right-sided (n=23) than left-sided (n=8) seizure foci, with the symptom probably resulting from RH activation. The LH may be specialized for increasing sexual tension, whereas the RH may be specialized for release of this tension (orgasm), the former being catabolic and the latter anabolic. Several other interpretations of the findings are also discussed.