Parental perceptions of the impact of neonatal unit visitation policies during COVID-19 pandemic.

OBJECTIVES: To ascertain parental perceptions of the impact of restricted visiting policies to neonatal intensive care units during the current COVID-19 pandemic. DESIGN: Cross-sectional survey of parents impacted by visitation policies. SETTING: Six tertiary level neonatal units, four from the UK and two from the USA, participated in the study. PARTICIPANTS: Parents and families of infants hospitalised in the participating centres between 1 May 2020 and 21 August 2020. METHODS: Online-based and/or paper-based survey, querying the visitation policies and their impact on parents' ability to visit, care for and bond with their infants. RESULTS: A total of 231 responses were received. Visitation limited to a single visitor with no restrictions on duration was the most frequently reported policy; 140/217 (63%). Visitation policies were perceived as being restrictive by 62% (138/219) of the respondents with 37% (80/216) reporting being able to visit less often than desired, 41% (78/191) reporting being unable to bond enough and 27% (51/191) reporting not being able to participate in their baby's daily care. Mild to severe impact on breast feeding was reported by 36% (75/209) of respondents. Stricter policies had a higher impact on families and were significantly associated with a lack of bonding time, inability to participate in care and an adverse impact on breast feeding. CONCLUSIONS: Visitation policies during the COVID-19 pandemic varied between centres and over time with stricter restrictions implemented earlier on in the pandemic. Parents reported significant impacts on their ability to visit, care for and bond with their infants with perceived severity of impact worse with stricter restrictions.

Locomotor training: as a treatment of spinal cord injury and in the progression of neurologic rehabilitation.

Scientists, clinicians, administrators, individuals with spinal cord injury (SCI), and caregivers seek a common goal: to improve the outlook and general expectations of the adults and children living with neurologic injury. Important strides have already been accomplished; in fact, some have labeled the changes in neurologic rehabilitation a "paradigm shift." Not only do we recognize the potential of the damaged nervous system, but we also see that "recovery" can and should be valued and defined broadly. Quality-of-life measures and the individual's sense of accomplishment and well-being are now considered important factors. The ongoing challenge from research to clinical translation is the fine line between scientific uncertainty (ie, the tenet that nothing is ever proven) and the necessary burden of proof required by the clinical community. We review the current state of a specific SCI rehabilitation intervention (locomotor training), which has been shown to be efficacious although thoroughly debated, and summarize the findings from a multicenter collaboration, the Christopher and Dana Reeve Foundation's NeuroRecovery Network.

A systematic review of non-invasive pharmacologic neuroprotective treatments for acute spinal cord injury.

An increasing number of therapies for spinal cord injury (SCI) are emerging from the laboratory and seeking translation into human clinical trials. Many of these are administered as soon as possible after injury with the hope of attenuating secondary damage and maximizing the extent of spared neurologic tissue. In this article, we systematically review the available pre-clinical research on such neuroprotective therapies that are administered in a non-invasive manner for acute SCI. Specifically, we review treatments that have a relatively high potential for translation due to the fact that they are already used in human clinical applications, or are available in a form that could be administered to humans. These include: erythropoietin, NSAIDs, anti-CD11d antibodies, minocycline, progesterone, estrogen, magnesium, riluzole, polyethylene glycol, atorvastatin, inosine, and pioglitazone. The literature was systematically reviewed to examine studies in which an in-vivo animal model was utilized to assess the efficacy of the therapy in a traumatic SCI paradigm. Using these criteria, 122 studies were identified and reviewed in detail. Wide variations exist in the animal species, injury models, and experimental designs reported in the pre-clinical literature on the therapies reviewed. The review highlights the extent of investigation that has occurred in these specific therapies, and points out gaps in our knowledge that would be potentially valuable prior to human translation.

A systematic review of directly applied biologic therapies for acute spinal cord injury.

An increasing number of therapies for spinal cord injury (SCI) are emerging from the laboratory and seeking translation into human clinical trials. Many of these are administered as soon as possible after injury with the hope of attenuating secondary damage and maximizing the extent of spared neurologic tissue. In this article, we systematically reviewed the available preclinical research on such neuroprotective therapies that are administered in a non-invasive manner for acute SCI. Specifically, we reviewed treatments that have a relatively high potential for translation due to the fact that they are already used in human clinical applications or are available in a form that could be administered to humans. These included: erythropoietin, NSAIDs, anti-CD11d antibodies, minocycline, progesterone, estrogen, magnesium, riluzole, polyethylene glycol, atorvastatin, inosine, and pioglitazone. The literature was systematically reviewed to examine studies in which an in vivo animal model was utilized to assess the efficacy of the therapy in a traumatic spinal cord injury paradigm. Using these criteria, 122 studies were identified and reviewed in detail. Wide variations exist in the animal species, injury models, and experimental designs reported in the preclinical literature on the therapies reviewed. The review highlights the extent of investigation that has occurred in these specific therapies, and points out gaps in our knowledge that would be potentially valuable prior to human translation.

Lack of robust neurologic benefits with simvastatin or atorvastatin treatment after acute thoracic spinal cord contusion injury.

Although much progress has been made in the clinical care of patients with acute spinal cord injuries, there are no reliably effective treatments, which minimize secondary damage and improve neurologic outcome. The time and expense needed to establish de novo pharmacologic or biologic therapies for acute SCI has encouraged the development of neuroprotective treatments based on drugs that are already in clinical use and, therefore, have the advantage of a well-characterized safety and pharmacokinetic profile in humans. Statins are the most commonly prescribed class of lipid-lowering drugs, and recently, it has been recognized that statins also have powerful immunomodulatory and anti-inflammatory effects. This paper describes a series of experiments that were performed to evaluate the comparative neuroprotective effects of simvastatin and atorvastatin. We observed a promising signal of neurologic benefit with simvastatin in our first experiment, but in repeated attempts to replicate that effect in three subsequent experiments, we failed to reveal any behavioral or histologic improvements. We would conclude that simvastatin given orally or subcutaneously at doses previously reported by other investigators to be effective in different neurologic conditions does not confer a significant neurologic benefit in a thoracic contusion injury model (OSU Impactor) when administered with a 1-h delay in intervention. We contend that further preclinical investigation of atorvastatin and simvastatin is warranted before considering their translation into human SCI.

Translational research in spinal cord injury: a survey of opinion from the SCI community.

Much like our colleagues studying neuroprotection for acute stroke, we in the spinal cord injury (SCI) community have witnessed the preclinical emergence of numerous promising neuroprotective and neuro-regenerative treatments that have then disappointingly failed to demonstrate convincing efficacy in clinical trials. In contrast to the stroke field, the SCI community lacks guidelines to steer the preclinical development of therapies and maximize their chance of success prior to translation into expensive and laborious clinical trials. We conducted a survey of the SCI research community to garner perspectives on the question of what preclinical evidence was required before translating an experimental treatment into clinical trials. The opinions of the 324 respondents about what constitutes necessary preclinical evidence before moving to human SCI trials revealed strong support for the demonstration of efficacy in large-animal models, cervical injury models, and for independent replication of promising results. Marked differences exist between the sentiments of the respondents and the translational experience of our field. A framework for guiding the preclinical development of novel therapies prior to human translation would be helpful for ensuring clinical success. Greater dialogue on this issue is necessary to improve our chances of successfully bringing effective treatments to patients with this devastating injury.

A new measure of hindlimb stepping ability in neonatally spinalized rats.

One of the most widely used animal models for assessing recovery of locomotor functioning is the spinal rat. Although true differences in locomotor abilities of these animals are exhibited during treadmill testing, current measurement techniques often fail to detect them. The HiJK (Hillyer-Joynes Kinematics) scale was developed in an effort to distinguish more effectively between groups of spinal rats. Scale items were compiled after extensive review of the literature concerning development and analysis of rat locomotion and a thorough examination of the current tools. Treadmill tests for 137 Sprague-Dawley rats were taped and scored. The structure of the scale was tested with principle components and factor analysis, in which six of the eight items accounted for 59% of the variance, while all eight accounted for 78%. Validity tests demonstrate that HiJK is measuring locomotor performance accurately and powerfully. First, the HiJK scale correlates highly (>.8) with the widely used BBB scale and second, as shown with ANOVA, can distinguish between different groups of spinal rats. Reliability of the scale was also analyzed. Cronbach's alpha was shown to be .91, indicating considerable internal consistency. Additionally, inter-rater and intra-rater reliabilities were substantial, with correlations for most items reaching above .80. We believe that the HiJK scale will help researchers verify existing experimental differences, advance the field of spinal cord research, and, hopefully, lead to discovery of methods to enhance recovery of function.

The neonatal injury-induced spinal learning deficit in adult rats: central mechanisms.

Previous research has shown that small injuries early in development can alter adult pain reactivity and processing of stimuli presented to the side of injury. However, the mechanisms involved and extent of altered adult spinal function following neonatal injury remain unclear. The present experiments were designed to 1) determine whether the effects of neonatal injury affect processing contralateral to the injury and 2) evaluate the role of cells expressing the NK1 receptor, shown to be involved in central sensitization in adults, in the negative effects of neonatal injury. The present findings indicate that the effects of neonatal injury are primarily isolated to the injured hind limb and do not result in a bilateral alteration in adult spinal function. In addition, the effects of neonatal injury appear to be partially dependent on cells expressing the NK1 receptor as ablating these cells at the time of injury or in adulthood results in attenuation of the neonatal injury-induced spinal learning deficit.

Local anesthetic treatment significantly attenuates acute pain responding but does not prevent the neonatal injury-induced reduction in adult spinal behavioral plasticity.

Recent findings indicate that neonatal injury results in decreased spinal plasticity in adult subjects (E. E. Young, K. M. Baumbauer, A. E. Elliot, & R. L. Joynes, 2007). Previous research has shown that acute manipulations of pain processing (i.e., administration of formalin, carrageenan, capsaicin) result in a loss of spinal behavioral plasticity (A. R. Ferguson, E. D. Crown, & J. W. Grau, 2006). Moreover, neonatal injury results in a lasting reduction in adult spinally mediated plasticity resembling the deficit seen following acute manipulations in adults (E. E. Young et al., 2007). The present study was designed to determine whether the effects of neonatal injury could be prevented by lidocaine administration during the initial healing period. Subjects (injured or uninjured) received lidocaine or saline on 1 of 4 administration schedules (preinjury only, postinjury only, for 24 hr postsurgery, or for 72 hr postsurgery). Results demonstrated that lidocaine administration did not prevent the hypersensitivity and reduced spinal plasticity associated with neonatal injury. This suggests that (a) the mechanisms underlying neonatal injury are independent of peripheral input in the initial healing period and (b) lidocaine is ineffective at preventing long-term spinal plasticity changes following neonatal injury.