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The Nurse Professional Development Model (NPD) has been utilized to improve quality of care for several conditions. Patients with Parkinson's Disease (PD) are susceptible to higher risks while in the hospital. Educational efforts for this patient population are challenged by the small, disbursed number of patients as well as increased turn-over and reliance on temporary nursing staff. To properly care for this patient group, any education has to be hospital wide and ongoing for maintenance of competency. We have used the NPD Model to initiate education for new incoming nurses as well as for continued education for a program that requires hospital-wide reach. Our utilization of the NPD Model for this high risk, low volume patient population has helped us improve the safety of this patient population in the hospital. With this manuscript we detail the need and the educational platform with the hope of it serving as a reference for other institutions facing similar challenges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bobek, Pascarelli, Cocoziello and Azmi.)

Electronic Health Record (EHR) systems are often configured to address challenges and improve patient safety for persons with Parkinson's disease (PWP). For example, EHR systems can help identify Parkinson's disease (PD) patients across the hospital by flagging a patient's diagnosis in their chart, preventing errors in medication and dosing through the use of clinical decision support, and supplementing staff education through care plans that provide step-by-step road maps for disease-based care of a specific patient population. However, most EHR-based solutions are locally developed and, thus, difficult to scale widely or apply uniformly across hospital systems. In 2020, the Parkinson's Foundation, a national and international leader in PD research, education, and advocacy, and Epic, a leading EHR vendor with more than 35% market share in the United States, launched a partnership to reduce risks to hospitalized PWP using standardized EHR-based solutions. This article discusses that project which included leadership from physician informaticists, movement disorders specialists, hospital quality officers, the Parkinson's Foundation and members of the Parkinson's community. We describe the best practice solutions developed through this project. We highlight those that are currently available as standard defaults or options within the Epic EHR, discuss the successes and limitations of these solutions, and consider opportunities for scalability in environments beyond a single EHR vendor. The Parkinson's Foundation and Epic launched a partnership to develop best practice solutions in the Epic EHR system to improve safety for PWP in the hospital. The goal of the partnership was to create the EHR tools that will have the greatest impact on outcomes for hospitalized PWP., Competing Interests: AW is a volunteer member of the Epic Neuroscience Specialty Steering Board. BW serves as Section Head of Movement Disorders at the Cleveland Clinic. Over the years, he has received research grants from the NIH and Parkinson’s Foundation. He has served as site investigator and/or co-investigator for clinical research studies sponsored by grants from Industry to Cleveland Clinic. Currently, he is the site PI for Neuroderm (Mitsubishi Tanabe Pharma), Discern (Great Lakes Neurotech/NIH R44), Tempo 2, and Tempo 3 studies (Cerevel Therapeutics) and a grant from the Parkinson’s Foundation to improve the inpatient care of People with PD. He has served as a consultant or speaker for Medtronic, Boston Scientific, and Abbott. AB Director of Strategic Initiatives, Parkinson’s Foundation EB Associate Director of Strategic Initiatives, Parkinson’s Foundation. KA was supported by the Michael J Fox Edmund J. Safra Fellowship in Movement Disorders from July 2017–July 2019. She previously served as Investigator and/or medical monitor for clinical trials supported by Aptinyx Inc. Genentech Roche Ltd., EIP Pharma Inc., Michael J Fox foundation for PD research, NINDS, and Acadia Pharmaceuticals Inc., and Biogene. She previously served as Co-I of a Lewy Body Dementia Association Research Center of Excellence site. The work presented here was supported by a Parkinson Foundation Community Grant (awarded to IR). IR serves as Director of the University of Rochester Parkinson’s Foundation Center of Excellence and her contributions to this article were supported by a Parkinson’s Foundation Community Grant, Parkinson’s Disease Hospital Optimization Project (PD-HOP) for which she served as PI. IR has received research and/or training grants from NIH, Parkinson’s Foundation and the Michael J. Fox Foundation. IR has served as a site investigator and/or co-investigator for clinical research studies sponsored by grants from Industry to the University of Rochester, currently including F. Hoffmann-La Roche Ltd., Acadia Pharm, and Jazz Pharmaceuticals. KM is an employee of Epic, a health IT software company which licenses electronic health record software and provides related services to health care organizations that pay Epic for such software and services. She and Epic have no financial disclosures or conflicts of interest related to this article. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Wu, Walter, Brooks, Buetow, Amodeo, Richard, Mundth and Azmi.)

Background: Patients with Parkinson's disease (PD) are at increased risk for hospital acquired complications. Deviations from home medication schedules and delays in administration are major contributing factors. We had previously developed a protocol to ensure adherence to home medication schedules using "custom" ordering. In this study we are assessing the impact this order type may have on reducing delays in PD medication administration in the hospital., Material and Methods: We reviewed 31,404 orders placed for PD medications from January 2, 2016 to April 30 2021. We evaluated the orders to determine if they were placed in a Custom format or using a default non-custom order entry. We further evaluated all orders to determine if there was a relationship with the order type and timely administration of medications. We compared medications that were administered within 1 min, 15 min, 30 min and 60 min of due times across custom orders vs. non-custom default orders. We also evaluated the relationship between ordering providers and type of orders placed as well as hospital unit and type of orders placed., Results: 14,204 (45.23%) orders were placed using a custom schedule and 17,200 (54.77%) orders were placed using non-custom defaults. The custom group showed a significantly lower median delay of 3.06 minutes compared to the non-custom group ( p <.001). Custom orders had a significantly more recent median date than non-custom default orders (2019-10-07 vs. 2018-01-06, p <0.001). In additional analyses, medication administration delays were significantly improved for custom orders compared to non-custom orders, with likelihoods 1.64 times higher within 1 minute, 1.40 times higher within 15 minutes, and 1.33 times higher within 30 minutes of the due time ( p <0.001 for all comparisons)., Conclusion: This is the largest study to date examining the effects of order entry type on timely administration of PD medications in the hospital. Orders placed using a custom schedule may help reduce delays in administration of PD medications., Competing Interests: JMP is employed and hold equity in Superior Medical Experts, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Azmi, Cocoziello, Ruzicka, Clar, Pederson, Jacob, Thomas, Rocco, Bobek, Pereira-Argenziano, Roth and Thomas.)

This paper introduces a novel robust adaptive fault detection and diagnosis (FDD) observer design approach for a class of nonlinear systems with parametric uncertainty, unknown system fault and time-varying internal delays. The conditions for the existence of the proposed FDD are obtained based on the well-known Linear Matrix Inequalities (LMI) technique. Using Lyapunov stability theory, the adaptation laws for updating the observer weights and unknown faults estimation are derived based on which the convergence of the state estimation error to zero and asymptotic stability of the error dynamics are proven. Toward this, a new structural algorithm for FDD observer design is also derived based on LMIs. The performance of the proposed method is also investigated while applying to some industrial systems. Simulation results illustrate superior performance of the proposed method for the systems subject to time-varying unknown delays on states, uncertainty in nonlinear system modeling and unknown system faults., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 ISA. Published by Elsevier Ltd. All rights reserved.)

Introduction There has been a recent increase in the number of spinal procedures that can be performed in ambulatory surgical centers (ASCs). Studies have found that patients who undergo procedures at ASCs tend to have lower complication rates following procedures, including lower infection rates. Furthermore, ASCs offer significantly lower costs of procedures to patients and health insurance companies as compared to the costs of procedures performed in a hospital. Despite precautions and screening in place by ASCs, patients may be hesitant to undergo procedures outside of the hospital. Conversely, the ongoing COVID-19 pandemic has created hesitancy for many to go to the hospital for care due to the presence of COVID patients.  Objective To assess patient preferences in the location of elective spine procedures between ASCs and hospitals, the authors conducted a survey of spine surgery candidates in a single practice. Methods A survey measuring patient age, vaccination status, fear of contracting COVID-19, and preference of surgery location was given to spinal surgery candidates at a single practice between fall 2021 and winter 2022. Statistical differences between the means of response groups were measured by a two-sample Z-score test. Results A total of 58 surveys were completed by patients. No difference in preference was observed by age. A difference was observed between genders, with 66% of females preferring ASCs to 40% of males (α=0.03). Patients with a fear of contracting COVID-19 preferred to have their procedure performed in an ASC. No difference was observed in location due to vaccination status, but unvaccinated patients had a significantly lower fear of contracting COVID-19 (α=0.02). Conclusion The differences in patient preferences have no clear cause, highlighting the need for better patient education in regard to the risks and benefits of each location of surgery. The fear of contracting COVID-19 on the day of surgery appears to be more ideological than rational for unvaccinated patients, who had less fear of contracting COVID-19 than vaccinated patients, despite being more likely to contract COVID-19 than vaccinated patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Cassimatis et al.)

Alzheimer's disease (AD) and other forms of dementia can have a large impact on patients, their families, and for the society as a whole. Current medical treatments have not shown enough potential in treating or altering the course of the disease. Deep brain stimulation (DBS) has shown great neuromodulatory potential in Parkinson's disease, and there is a growing body of evidence for justifying its use in cognitive disorders. At the same time there is mounting interest at less invasive and alternative modes of neuromodulation for the treatment of AD. This manuscript is a brief review of the infrastructure of memory, the current understanding of the pathophysiology of AD, and the body of preclinical and clinical evidence for noninvasive and invasive neuromodulation modalities for the treatment of cognitive disorders and AD in particular., Competing Interests: None

Background: Patients with Parkinson's Disease (PD) are at higher risk of complications when admitted to the hospital. Delays in PD medications and use of contraindicated medications contribute to the increased risk and prolong their lengths of stay (LOS). Using a hospital-wide PD protocol, we aimed to ensure PD medications were placed with "custom" timing to resemble the home schedules, and also to avoid ordering or administering contraindicated medications., Material and Methods: 569 patients admitted in 2017 and 2018, were reviewed retrospectively. Mean age was 76.5 (SD 10.6), 332 were males and 237 were females. Charts were reviewed to assess if A) PD medications were ordered with custom timing, B) if not, were the orders changed to custom timed C) if contraindicated medications were ordered, and D) if they were administered. We also assessed the actual/expected length of stay during this time period. Chi Square and post hoc analyses were done to compare time points. Poisson regression analysis was done to assess relative improvement of variables., Results: There was a 2.7 fold increase in orders placed with custom timing in 2018 compared to 2017 (RR = 2.651, 95%CI: 1.860-3.780, p < 0.0001), and a 3.2 fold increase in correction of non-custom orders in the same time period (RR = 3.246, 95%CI: 1.875-1.619, p < 0.0001). We also observed a decrease in the actual/expected LOS ratio from 1.54  to 1.32  (p < 0.05)., Conclusion: By utilizing an established platform for quality improvement, we were able to improve adherence to the home medication regimen timing in admitted PD patients. Our findings also suggests that adherence to a strict medication regimen protocol may decrease LOS for this patient population., Competing Interests: None., (© 2020 The Author(s).)

Background: Intraoperative magnetic resonance imaging (ioMRI) has led to significant advancements in neurosurgery with improved accuracy, assessment of the extent of resection, less invasive surgical alternatives, and real-time confirmation of targeting as well delivery of therapies. The costs associated with developing ioMRI units in the surgical suite have been obstacles to the expansion of their use. More recently, the development of hybrid interventional MRI (iMRI) units has become a viable alternative. The process of designing, developing, and implementing operations for these units requires the careful integration of environmental, technical, and safety elements of both surgical and MR practices. There is a paucity of published literature providing guidance for institutions looking to develop a hybrid iMRI unit, especially with a limited footprint in the radiology department., Methods: The experience of designing, developing, and implementing an iMRI in a preexisting space for neurosurgical procedures at a single institution in light of available options and the literature is described., Results: The development of the unit was accomplished through the engagement of a multidisciplinary team of stakeholders who utilized existing guidelines and recommendations and their own professional experience to address issues including physical layout, equipment selection, operations planning, infection control, and oversight/review, among others., Conclusion: Successful creation of an iMRI program requires multidisciplinary collaboration in integrating surgical and MR practice. The authors' aim is that the experience described in this article will serve as an example for facilities or neurosurgical departments looking to navigate the same process., Competing Interests: The corresponding author has a consulting agreement with Medtronic Inc and Abbott Scientific. All of the other authors certify that they have no conflicts of interest.

Background: Interventional magnetic resonance imaging (iMRI) guided deep brain stimulation (DBS) for Parkinson's disease (PD) has been shown to be effective. The costs of a dedicated intraoperative MRI may be prohibitive. The procedure can also be performed in a diagnostic scanner, however this presents challenges for utilization of time when the scanner is used both as a diagnostic and an interventional unit. This report outlines our novel methodology for patient selection for implantation in a diagnostic MR scanner, as an attempt to streamline the use of resources. A retrospective review of our outcomes is also presented., Methods: DBS candidacy evaluation included a PD questionnaire-39. Anxiety, age, difficulties in communication and body habitus were factors that were assessed in selecting patients for this technique. Eleven patients underwent iMRI-guided DBS implantation in the subthalamic nucleus. All patients were implanted bilaterally. Unified PD rating scale (UPDRS) part III and L-dopa dose were compared pre- and post-stimulation. A cohort of 11 DBS patients not selected for iMRI-guided DBS were also reported for comparison., Results: For the iMRI-guided patients, mean "Off" UPDRS III score was 47.6 (standard deviation [SD] 8.26). Postoperative "On" medication, "On" stimulation UPDRS III was 13.6 (SD 5.23). Mean preoperative L-dopa dose was 1060 mg (SD 474.3) and mean postoperative L-dopa dose was 320 (SD 298.3)., Conclusion: iMRI-guided DBS is a newly emerging technique for surgical treatment of patients with PD. We present a novel scoring system for patient selection assessing anxiety, age, ability to communicate, and body habitus to identify patients who will be benefited most from this technique.

CD40L on CD4(+) T cells plays a vital role in the activation of antigen-presenting cells, thus catalyzing a positive feedback loop for T-cell activation. Despite the pivotal juxtaposition of CD40L between antigen-presenting cells and T-cell activation, only a T-cell receptor stimulus is thought to be required for early CD40L surface expression. We show, for the first time, that CD40L expression on peripheral blood CD4(+) T cells is highly dependent on a cell-cell interaction with CD14(hi)CD16(-) monocytes. Interactions with ICAM-1, LFA-3, and to a lesser extent CD80/CD86 contribute to this enhancement of CD40L expression but are not themselves sufficient. The contact-mediated increase in CD40L expression is dependent on new mRNA and protein synthesis. Circulating myeloid dendritic cells also possess this costimulatory activity. By contrast, CD14(lo)CD16(+) monocytes, plasmacytoid dendritic cells, B-cell lymphoma lines, and resting, activated, and Epstein-Barr virus-immortalized primary B cells all lack the capacity to up-regulate early CD40L. The latter indicates that a human B cell cannot activate its cognate T cell to deliver CD40L-mediated help. This finding has functional implications for the role of biphasic CD40L expression, suggesting that the early phase is associated with antigen-presenting cell activation, whereas the late phase is related to B-cell activation.

Humanized anti-CD25 antibodies (eg, daclizumab) have been successfully used to treat several autoimmune diseases. Paradoxically, IL-2 blockade in mice can induce autoimmunity. An interspecies difference in the relative contribution of IL-2 to CD25(+) T regulatory cell (CD25(+)Treg) versus CD25(+) effector cell function might explain this conundrum. Consistent with this are reports that daclizumab inhibits human CD25(+) effector cell cytokine production by blocking the expression of CD40L. However, in mice, IL-4 and IL-12 regulate CD40L expression. As human Th1/Th2 cytokine production is also dependent on IL-2, daclizumab's inhibition of CD40L expression could be due to an indirect, rather than a direct, effect of IL-2. Here, we clarify the mechanisms underlying CD40L expression. In contrast to the mouse, human CD40L is regulated by CD28 signaling and IL-2, not the principal Th1/Th2-polarizing cytokines. We find that CD40L is expressed on naive and memory cells and inhibited by daclizumab independently of cell division. Collectively, our results indicate that daclizumab could inhibit CD25(+) effector T-cell function in vivo by directly blocking CD40L expression. This difference between mice and human may help explain the paradoxical effects of IL-2R blockade in the 2 species.

Hypersynchronous neuronal firing is a hallmark of epilepsy, but the mechanisms underlying simultaneous activation of multiple neurons remains unknown. Epileptic discharges are in part initiated by a local depolarization shift that drives groups of neurons into synchronous bursting. In an attempt to define the cellular basis for hypersynchronous bursting activity, we studied the occurrence of paroxysmal depolarization shifts after suppressing synaptic activity using tetrodotoxin (TTX) and voltage-gated Ca(2+) channel blockers. Here we report that paroxysmal depolarization shifts can be initiated by release of glutamate from extrasynaptic sources or by photolysis of caged Ca(2+) in astrocytes. Two-photon imaging of live exposed cortex showed that several antiepileptic agents, including valproate, gabapentin and phenytoin, reduced the ability of astrocytes to transmit Ca(2+) signaling. Our results show an unanticipated key role for astrocytes in seizure activity. As such, these findings identify astrocytes as a proximal target for the treatment of epileptic disorders.

The interleukin-2 mRNA is a labile transcript containing AU-rich elements that is transiently stabilized by CD28 receptor signaling. For a number of proto-oncogenes and cytokines, the HuR protein has been shown to avidly bind the AU-rich elements that confer instability upon their mRNAs. HuR was originally thought to participate in mRNA degradation but subsequent studies indicated that it actually functions to stabilize mRNA. Binding of HuR to the mouse interleukin-2 mRNA has not been studied. We tested if HuR binds the interleukin-2 mRNA and whether such binding is related to CD28-mediated stabilization of the mRNA. First, we confirm that T cell receptor signaling, which is sufficient to induce interleukin-2 transcription, also triggers translocation of HuR from the nucleus to the cytoplasm. Interestingly, T cell receptor-triggered translocation is selective as heterogeneous nuclear ribonucleoprotein A1 does not shuttle under the same conditions. Engagement of both the T cell and CD28 receptors, which enhance interleukin-2 transcription and induce stabilization of the mRNA, did not further increase the level of cytoplasmic HuR. Using an in vitro binding assay, we demonstrate that HuR binds the interleukin-2 mRNA and localize binding to a sequence downstream of the single nonameric AU-rich element that is present in its 3'-untranslated region. However, we conclude that HuR binding to the interleukin-2 mRNA, both in vitro and in vivo, is not associated with alterations in mRNA stability.

Anterior cervical decompression and fusion has gained popularity because of its applicability to a variety of cervical spine disorders. The authors of long-term follow-up studies have demonstrated the development of degenerative changes in segments adjacent to fusion. So-called adjacent-segment disease causes symptomatic deterioration in up to 25% of the patients who have undergone anterior cervical decompression and fusion for cervical spondylotic myelopathy. The causes of this condition are debated in the literature. The authors provide a review of the available literature on the pathogenesis, prevention, and treatment of postarthrodesis adjacent-segment degenerative disease.