Publications

OBJECTIVE: The objectives were to examine changes in kinesiophobia, pain self-efficacy, and knowledge of the neurophysiology of pain. We hypothesized that implementing an adapted-pain neuroscience education (a-PNE) curriculum, as a single intervention, for patients who experience chronic musculoskeletal pain and concurrent opioid dependence, would demonstrate positive change in kinesiophobia and self-efficacy regarding pain management, which may translate to improvements in functional ability.

DESIGN: This study used a pretest-post-test, quasi-experimental design.

SETTING: A formal opioid management program (OMP) within a clinic associated with the University of Kentucky.

PARTICIPANTS: Patients actively participating in the OMP.

INTERVENTIONS: Pain neuroscience education.

MAIN OUTCOME MEASURES: The Tampa Scale for Kinesiophobia-11, the Pain Self-Efficacy Questionnaire (PSEQ), and the Neurophysiology of Pain Questionnaire (NPQ) were utilized during this study. Subjects completed each questionnaire at three time points: preintervention, post-intervention, and 90 days post-intervention.

RESULTS: No significant interactions between groups and the three time points were found. The a-PNE group significantly improved their knowledge between pre- and post-intervention on the NPQ and PSEQ according to paired-samples t-tests. The a-PNE group scored significantly higher at post-intervention and 90-day post-intervention than the general health education control group on the NPQ according to independent-samples t-tests.

CONCLUSION: An a-PNE curriculum may be beneficial in assisting patients to understand the neurophysiology behind their pain experience. Furthermore, positive changes were noted in pain self-efficacy. The results also indicate that an a-PNE curriculum intervention was acceptable in terms of approach and understandability for the participating patients.

BACKGROUND: There is a paucity of data depicting post-operative opioid consumption in pediatric solid organ transplant (SOT) recipients, limiting ability to perform power analyses in designing prospective trials focusing on analgesia or adjuvant therapies in these populations. There is additionally unclear effect magnitude of various confounders of analgesic and sedative medications encountered in the pediatric intensive care unit (PICU).

METHODS: Retrospective review of pediatric patients aged 2 months-18 years at a single institution was performed on 137 SOT recipients (cardiac, liver, renal, total pancreatectomy with islet cell autotransplantation [TPIAT]) to evaluate post-operative opioid consumption in the PICU, analgesic confounders, pain scores, and opioid-related adverse effects (constipation, ileus, pruritus, nausea, urinary retention, delirium, respiratory depression, withdrawal). Values for correlative and multiplicative effect magnitude were analyzed for planned variables.

RESULTS: Average daily opioid requirement in oral morphine equivalents per kilogram was (cardiac) 12.5 (median 6.98, interquartile range [IQR] 14.3), (liver) 12.6 (median 10.1, IQR 15.3), (renal) 1.47 (median 0.614, IQR 0.95), and (TPIAT) 4.1 (median 3.44, IQR 2.6). Mechanical ventilation dependence, extracorporeal membrane oxygenation use, and open abdomen or chest demonstrated the highest correlation and effect magnitudes with opioid consumption of variables evaluated. No trends were identified for opioid-related adverse effects.

CONCLUSION: Children receiving SOT have high opioid consumption relative to many populations in the PICU. Control for and evaluation of pain confounders such as mechanical ventilation and extracorporeal membrane oxygenation should be utilized in prospective studies analyzing opioid use, adjuvant analgesics, or outcomes in critically ill transplant recipients.

OBJECTIVE: In the context of increased use of buprenorphine for pain management, comparison of real-world data (RWD) on prescription opioid nonmedical use (NMU) based on their controlled substance schedule may assist providers in providing effective pain management therapy while mitigating the risk of opioid NMU.

DESIGN: A systematic literature review of articles reporting RWD on prescription opioid NMU involving Schedule II (CII), Schedule III (CIII), and Schedule IV (CIV) opioid medications was conducted using PubMed®.

PATIENTS/PARTICIPANTS: Human RWD collected in the United States from January 2010 to December 2023.

MAIN OUTCOME MEASURE(S): Articles reporting RWD of prescription opioid NMU. Exclusions included buprenorphine/methadone medications for opioid use disorder, chronic use, or overdose without clearly established NMU (could not rule out legitimate medical use).

RESULTS: There were 2,585 articles screened for inclusion, 102 articles were assessed with a validated data extraction form, and 16 articles were reviewed that compared NMU and/or secondary NMU-related outcomes. Of these, only five articles contained RWD on NMU; all showed more NMU associated with CII than CIII or CIV opioids. Two articles evaluated buprenorphine (CIII) for analgesia and found lower rates of CIII NMU than comparator CII opioids.

CONCLUSIONS: Results of this systematic review support the differentiation in scheduling between CII and CIII/CIV opioid medications with RWD. This study also reveals a research gap in comparing CIII opioid medications for analgesia to CII and CIV opioids, an area of current and future interest, considering the growing use of buprenorphine for pain management, along with initiatives to curb opioid NMU.

BACKGROUND: Spinal opioids are frequently coadministered with local anesthetics for analgesia, allowing the use of a lower dose of each agent, thus minimizing side effects. Most opioid-induced side effects, such as nausea, vomiting, and respiratory depression, are usually encountered with systemic use, while pruritus is more common with intrathecal or epidural administration.

OBJECTIVES: To compare the action of gabapentin versus metoclopramide in prevention of intrathecal opioid-induced pruritus.

STUDY DESIGN: After ethical committee approval and informed patient' consent, this prospective randomized comparative clinical trial was conducted at Ain Shams University Hospitals on 62 adult patients undergoing elective operations under spinal anesthesia. The subjects were randomly divided into two groups: Group G (received 300 mg of oral gabapentin) and group M (received 10 mg of oral metoclopramide) 2 hours before spinal anesthesia.

RESULTS: The overall incidence of pruritus in both groups was 31.5 percent (48.8 percent in group G and 45.2 percent in group M). There was no statistically significant difference between the two groups. As for the severity, both drugs showed low visual analog scale scores from the first hour after intrathecal fentanyl administration. Gabapentin showed more potency in decreasing the severity of pruritus as only two patients in group G needed rescue treatment compared to five patients in group M (but the difference was of no statistical significance).The overall incidence of nausea was 17.7 percent (22.58 percent in group G and 12.9 percent in group M), while the incidence of vomiting was 11.29 percent (16.13 percent in group G and 6.45 percent in group M). There was no statistically significant difference between the two groups.

CONCLUSION: Gabapentin is as effective as metoclopramide in prevention of intrathecal opioid-induced pruritus. Moreover, gabapentin proved to be slightly more effective in reducing the severity of pruritus than metoclopramide.

In the flash-grab effect, an object flashed on a moving background appears to be shifted in the direction of the motion. The same background motion also distorts the flashed object's perceived shape. An even greater shift in the perceived location is produced by the frame effect, raising the question of whether it also produces a shape distortion. This phenomenon is important because the frame effect has been linked to perceptual stabilization during eye movements where the whole visual field acts as the frame. We found that, unlike the flash-grab case, shape was preserved for the frame effect to a much greater extent than for the flash-grab. Next, we tested the extent to which shape distortions could be predicted from the size of the shifts in position of individual shape elements. We found that observed distortions were weaker than predicted distortions for the frame effect, but stronger for the flash-grab stimulus. Finally, we examined whether the greater shape distortion for the flash-grab was due to the nature of the background motion (rotation vs. translation) or the aperture within which the background motion was presented (circular vs. rectangular). We found that both factors contributed to greater shape distortion. Our findings show that motion-induced shape distortions are not solely based on the individual position shifts of the shape elements when tested in isolation. The shape preservation for the frame effect may be achieved through engaging shape-based mechanisms tuned to the dynamics of saccadic eye movements.

PURPOSE: The purpose of this study is to address the challenge of limited donor retinal ganglion cell (RGC) migration into the retina after transplantation, which is largely due to donor neuron accumulation at the inner limiting membrane (ILM). We present a minimally invasive technique, ILM photodisruption, to locally ablate the ILM and thereby promote RGC engraftment.

METHODS: ILM photodisruption uses indocyanine green as a photosensitizer, which is delivered to the ILM and activated with ultra-short laser pulses. This process generates vapor nanobubbles (VNBs) that, upon collapse, create localized disruptions in the ILM. In this study, we finetuned this technology in bovine and postmortem human organotypic retinal explants to generate patterned ILM pores. To assess the impact of these photodisruption patterns on RGC transplantation, we applied induced pluripotent stem cell (iPSC)-derived RGCs to the ILM surface and co-cultured them for 7 days. Using advanced microscopy and spatial metric tools, we assessed donor RGC survival, spreading, and neurite localization. We compared ILM photodisruption to a current standard method of enzymatically digesting the ILM.

RESULTS: ILM photodisruption was highly effective in creating pores in both the bovine ILM and the thicker, more complex human ILM. In contrast, collagenase treatment had no effect on the human ILM. Both collagenase and ILM photodisruption significantly promoted donor RGC survival, enhanced cell spreading, and resulted in more neurites that extended deeper into the retina.

CONCLUSIONS: Our findings demonstrate that ILM photodisruption can overcome a key barrier in RGC replacement therapy and, as such, may help advance vision restoration strategies for glaucoma.

Despite more than five decades of research into eye movements in reading, questions remain about the relationship between lower-level lexical and higher-level semantic factors. We explored the simultaneous effects of word frequency (lower, higher), contextual predictability (lower, higher), and parafoveal preview (valid, invalid) on the processing of target words embedded in short passages of text. Using a repeated-measures design, 80 participants read 240 two-line passages, each containing a four- or five-letter target word. Corpus-based word frequencies and Cloze predictabilities were used as continuous variables in Bayesian mixed-effect analyses of fixation time and skipping measures. Key findings included robust main effects of frequency, predictability, and preview validity, as well as two-way interactions between Frequency × Preview in gaze duration, and Predictability × Preview in gaze duration and skipping. Frequency effects on gaze duration were greater under invalid preview conditions, suggesting that higher-frequency words facilitate corrective processing when preview is misleading. Predictability effects on gaze duration and skipping were enhanced under valid preview, indicating that contextual facilitation depends on coherent parafoveal input. No interaction was observed between frequency and predictability nor a three-way interaction, supporting the view that lexical access and contextual integration operate via distinct mechanisms. These findings highlight the critical role of parafoveal information in shaping the expression of lexical and contextual influences during reading.

Reported perception can exhibit a repulsive bias away from a task-irrelevant prior stimulus. Previous research has suggested that this repulsive serial bias is driven by low-level adaptation, such that the prior stimulus repels the representation of the new stimulus during encoding. To test this account, the present study compared the repulsive serial bias with another perceptual bias that is known to be driven by an adaptation mechanism (e.g., the tilt aftereffect). We measured the repulsive serial bias using a common location delayed estimation task and the adaptation-driven bias using a location estimation task with an inducer stimulus. We found that, although both repulsive serial bias and adaptation-driven bias were evident, the two biases were not correlated. In addition, only the repulsive serial bias was associated with a response time effect, where responses were slower when the bias was stronger. Moreover, mouse-tracking data for the repulsive serial bias exhibited a pattern that started with a stronger repulsion and ended with smaller repulsion, which cannot be explained by an adaptation mechanism alone. Taken together, our findings suggest that repulsive serial bias in continuous estimation tasks involves post-perceptual decisional processes that are not present in the adaptation-driven bias.

As research on human behavior, such as spatial navigation, increasingly adopts naturalistic settings, establishing best practices for such experiments becomes essential. Although virtual reality offers a bridge between laboratory control and real-world complexity, it does not fully capture the experiential richness of real-world environments. Here, we present a demonstration of a mobile eye-tracking study conducted in a large-scale, outdoor urban environment, featuring unconstrained, long-duration free exploration and outside-pointing tasks. Using the city of Limassol, Cyprus, as our testbed, we showcase the feasibility of collecting high-quality mobile eye-tracking, head orientation, and GPS data "in the wild," capturing a wide range of natural behavior with minimal experimental constraints. Based on this experience, we provide a set of best practices tailored to the logistical and methodological challenges posed by complex, real-world urban settings, challenges unlikely to arise in traditional indoor or highly controlled environments. Although these recommendations have general relevance, we exemplify them in the context of spatial navigation research. By establishing methodological standards for studies at this scale, we aimed to encourage and inform future research into naturalistic human behavior outside the laboratory.