Search

Introduction : The use of remote patient monitoring (RPM) services for neurological disorders remains understudied, particularly in the context of newer billing codes introduced before the COVID-19 pandemic. Methods : This retrospective cohort study utilized data from commercial and Medicare employer-sponsored administrative claims between January 1, 2019, to December 31, 2021. The study population included all patients with at least one qualifying RPM-related Current Procedural Terminology (CPT) code for a neurological disorder, separated into first-generation (CPT 99091) codes and second-generation (CPT 99453, 99454, 99457, 99458) code cohorts. We compared patient and encounter characteristics between both cohorts. Results : We identified 27,756 encounters attributable to 11,326 patients who received RPM services for neurological disorders, of whom 5,785 (51.1%) received RPM via second-generation billing codes, 3,941 (34.8%) were female, 6,712 (59.3%) were between 45 and 64 years old, and 10,488 (92.6%) had a primary diagnosis of sleep-wake disorder. The second-generation cohort was significantly more likely to be female (41.5% vs. 27.8%, p < 0.001), be of age 65 or older (15.7% vs. 7.1%, p < 0.001), and reside in urban areas (93.4% vs. 87.6%, p < 0.001) than the first-generation cohort. Patients in the second-generation cohort were more likely to receive RPM in office settings (86.3% vs. 62.5%, p < 0.001), by physicians (77.0% vs. 40.3%, p < 0.001), and less likely for sleep-wake disorders (87.9% vs. 97.5%, p < 0.001) than the first-generation cohort. Patients who received RPM from physicians were most often evaluated by pulmonologists (31.4%). Discussion : In this commercially insured patient population receiving RPM for neurological disorders, we found that sleep-wake disorders and non-neurologists were over-represented.

Background and Aims: In the Northwest of England, a national allocation of funding to minimise the effects of differential attainment has been used to support experienced GP educators to act as Differential Attainment Champions (DAC) since October 2021. An evaluation of the role's impact was undertaken., Methods: The evaluation was designed to gather the views and experiences of DACs and their trainees via online semi-structured interviews during the first 12 months following establishment of the intervention programme., Results: Thematic framework analysis identified three main themes: DACs' adaptive approach to support trainees; barriers to fulfilling the DAC role; and the positive impact of the DAC role on training. The following aspects of the DAC role worked well: the freedom to tailor support to the individual needs of the trainees; the targeted and proactive support early on in GP core training; the support of trainees in a wide range of areas including e-portfolio advice, examination preparation, and personal help. Trainees valued one-to-one support when needed. Reported improvements included: improved examination outcomes; portfolio engagement recognised in some cases by Annual Review of Competence Progression (ARCP) panels., Conclusions: The individualised and adaptive approach works well but it does mean it is difficult to quantify how many trainees can be supported by one DAC and their workload needs to be monitored.

Background: Flexion-extension magnetic resonance imaging (MRI) has potential to identify cervical pathology not detectable on conventional static MRI. Our study evaluated standard quantitative and novel subjective grading scales for assessing the severity of cervical spondylotic myelopathy in dynamic sagittal MRI as well as in static axial and sagittal images., Methods: Forty-five patients underwent both conventional and flexion-extension MRI prior to anterior cervical discectomy and fusion from C4 through C7. In addition to measuring Cobb angles and cervical canal diameter, grading scales were developed for assessment of vertebral body translation, loss of disc height, change in disc contour, deformation of cord contour, and cord edema. Data were collected at all levels from C2-C3 through C7-T1. Variations in measurements between cervical levels and from flexion through neutral to extension were assessed using Mann-Whitney, Kruskal-Wallis, and two-way ANOVA tests., Results: Cervical canal diameter, vertebral translation, and posterior disc opening changed significantly from flexion to neutral to extension positions (P < 0.01). When comparing operative versus nonoperative cervical levels, significant differences were found when measuring sagittal cervical canal dimensions, vertebral translation, and posterior disc opening (P < 0.01). Degenerative loss of disc height, disc dehydration, deformation of ventral cord contour, and cord edema were all significantly increased at operative levels versus nonoperative levels (P < 0.01)., Conclusions: Flexion-extension MRI demonstrated significant changes not available from conventional MRI. Subjective scales for assessing degenerative changes were significantly more severe at levels with operative cervical spondylotic myelopathy. The utility of these scales for planning surgical intervention at specific and adjacent levels is currently under investigation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Intracerebral hemorrhage remains the deadliest form of stroke worldwide, inducing neuronal death through a wide variety of pathways. Therapeutic hypothermia is a robust and well-studied neuroprotectant widely used across a variety of specialties., Aims: This review summarizes results from preclinical and clinical studies to highlight the overall effectiveness of therapeutic hypothermia to improve long-term intracerebral hemorrhage outcomes while also elucidating optimal protocol regimens to maximize therapeutic effect., Summary of Review: A systematic review was conducted across three databases to identify trials investigating the use of therapeutic hypothermia to treat intracerebral hemorrhage. A random-effects meta-analysis was conducted on preclinical studies, looking at neurobehavioral outcomes, blood brain barrier breakdown, cerebral edema, hematoma volume, and tissue loss. Several mixed-methods meta-regression models were also performed to adjust for variance and variations in hypothermia induction procedures. Twwenty-one preclinical studies and five human studies were identified. The meta-analysis of preclinical studies demonstrated a significant benefit in behavioral scores (ES = -0.43, p = 0.02), cerebral edema (ES = 1.32, p = 0.0001), and blood brain barrier (ES = 2.73, p ≤ 0.00001). Therapeutic hypothermia was not found to significantly affect hematoma expansion (ES = -0.24, p = 0.12) or tissue loss (ES = 0.06, p = 0.68). Clinical study outcome reporting was heterogeneous; however, there was recurring evidence of therapeutic hypothermia-induced edema reduction., Conclusions: The combined preclinical evidence demonstrates that therapeutic hypothermia reduced multiple cell death mechanisms initiated by intracerebral hemorrhage; yet, there is no definitive evidence in clinical studies. The cooling strategies employed in both preclinical and clinical studies were highly diverse, and focused refinement of cooling protocols should be developed in future preclinical studies. The current data for therapeutic hypothermia in intracerebral hemorrhage remains questionable despite the highly promising indications in preclinical studies. Definitive randomized controlled studies are still required to answer this therapeutic question.

Study Question: What are outcome and procedural differences when using the semi-automated closed Gavi® device versus the manual open Cryotop® method for vitrification of pronuclear (2PN) stage oocytes within an IVF program?, Summary Answer: A semi-automated closed vitrification method gives similar clinical results as compared to an exclusively manual, open system but higher procedure duration and less staff convenience., What Is Known Already: A semi-automated closed vitrification device has been introduced to the market, however, little evaluation of its performance in a clinical setting has been conducted so far., Study Design, Size, Duration: This prospective, randomised, open non-inferiority trial was conducted at three German IVF centers (10/2017-12/2018). Randomization was performed on day of fertilization check, stratified by center and by indication for vitrification (surplus 2PN oocytes in the context of a fresh embryo transfer (ET) cycle or 'freeze-all' of 2PN oocytes)., Participant/material, Setting, Methods: The study population included subfertile women, aged 18-40 years, undergoing IVF or ICSI treatment after ovarian stimulation, with 2PN oocytes available for vitrification. The primary outcome was survival rate of 2PN oocytes at first warming procedure in a subsequent cycle and non-inferiority of 2PN survival was to be declared if the lower bound 95% CI of the mean difference in survival rate excluded a difference larger than 9.5%; secondary, descriptive outcomes included embryo development, pregnancy and live birth rate, procedure time and staff convenience., Main Results and the Role of Chance: The randomised patient population consisted of 149 patients, and the per-protocol population (patients with warming of 2PN oocytes for culture and planned ET) was 118 patients. The survival rate was 94.0% (±13.5) and 96.7% (±9.7) in the Gavi® and the Cryotop® group (weighted mean difference -1.6%, 95% CI -4.7 to 1.4, P = 0.28), respectively, indicating non-inferiority of the Gavi® vitrification/warming method for the primary outcome. Embryo development and the proportion of top-quality embryos was similar in the two groups, as were the pregnancy and live birth rate. Mean total procedure duration (vitrification and warming) was higher in the Gavi® group (81 ± 39 min vs 47 ± 15 min, mean difference 34 min, 95% CI 19 to 48). Staff convenience assessed by eight operators in a questionnaire was lower for the Gavi® system. The majority of respondents preferred the Cryotop® method because of practicality issues., Limitations, Reason for Caution: The study was performed in centers with long experience of manual vitrification, and the relative performance of the Gavi® system as well as the staff convenience may be higher in settings with less experience in the manual procedure. Financial costs of the two procedures were not measured along the trial., Wider Implications of the Findings: With increasing requirements for standardization of procedures and tissue safety, a semi-automated closed vitrification method may constitute a suitable alternative technology to the established manual open vitrification method given the equivalent clinical outcomes demonstrated herein., Study Funding/competing Interests: The trial received no direct financial funding. The Gavi® instrument, Gavi® consumables and staff training were provided for free by the distributor (Merck, Darmstadt, Germany) during the study period. The manufacturer of the Gavi® instrument had no influence on study protocol, study conduct, data analysis, data interpretation or manuscript writing. J.H. has received honoraria and/or non-financial support from Ferring, Merck and Origio. G.G. has received honoraria and/or non-financial support from Abbott, Ferring, Finox, Gedeon Richter, Guerbet, Merck, MSD, ObsEva, PregLem, ReprodWissen GmbH and Theramex. The remaining authors have no competing interests., Trial Registration Number: ClinicalTrials.gov NCT03287479., Trial Registration Date: 19 September 2017., Date of First Patient’s Enrolment: 10 October 2017., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Fluorescence-guided surgery (FGS) allows surgeons to have improved visualization of tumor tissue in the operating room, enabling maximal safe resection of malignant brain tumors. Over the past two decades, multiple fluorescent agents have been studied for FGS, including 5-aminolevulinic acid (5-ALA), fluorescein sodium, and indocyanine green (ICG). Both non-targeted and targeted fluorescent agents are currently being used in clinical practice, as well as under investigation, for glioma visualization and resection. While the efficacy of intraoperative fluorescence in studied fluorophores has been well established in the literature, the effect of timing on fluorophore administration in glioma surgery has not been as well depicted. In the past year, recent studies of 5-ALA use have shown that intraoperative fluorescence may persist beyond the previously studied window used in prior multicenter trials. Additionally, the use of fluorophores for different brain tumor types is discussed in detail, including a discussion of choosing the right fluorophore based on tumor etiology. In the following review, the authors will describe the temporal nature of the various fluorophores used in glioma surgery, what remains uncertain in FGS, and provide a guide for using fluorescence as a surgical adjunct in brain tumor surgery., Competing Interests: CH is a consultant for NX Development Corporation (NXDC) and Synaptive Medical. NXDC, a privately held company, markets Gleolan (5-ALA, aminolevulinic acid hydrochloride). Gleolan is an optical imaging agent approved for the visualization of malignant tissue during glioma surgery. CH is a consultant for NXDC and receives royalty payments for the sale of Gleolan, has also received speaker fees by Carl Zeiss and Leica. FA has received speaker's fees from Carl Zeiss Meditec, Oberkochen, Germany. 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 © 2021 Schupper, Rao, Mohammadi, Baron, Lee, Acerbi and Hadjipanayis.)

Background: Fluorescence-guided surgery (FGS) using 5-aminolevulic acid (5-ALA) is a widely used strategy for delineating tumor tissue from surrounding brain intraoperatively during high-grade glioma (HGG) resection. 5-ALA reaches peak plasma levels ~4 h after oral administration and is currently approved by the FDA for use 2-4 h prior to induction to anesthesia. Objective: To demonstrate that there is adequate intraoperative fluorescence in cases undergoing surgery more than 4 h after 5-ALA administration and compare survival and radiological recurrence to previous data. Methods: Retrospective analysis of HGG patients undergoing FGS more than 4 h after 5-ALA administration was performed at two institutions. Clinical, operative, and radiographic pre- and post-operative characteristics are presented. Results: Sixteen patients were identified, 6 of them female (37.5%), with mean (SD) age of 59.3 ± 11.5 years. Preoperative mean modified Rankin score (mRS) was 2 ± 1. All patients were dosed with 20 mg/kg 5-ALA the morning of surgery. Mean time to anesthesia induction was 425 ± 334 min. All cases had adequate intraoperative fluorescence. Eloquent cortex was involved in 12 cases (75%), and 13 cases (81.3%) had residual contrast enhancement on postoperative MRI. Mean progression-free survival was 5 ± 3 months. In the study period, 6 patients died (37.5%), mean mRS was 2.3 ± 1.3, Karnofsky score 71.9 ± 22.1, and NIHSS 3.9 ± 2.4. Conclusion: Here we demonstrate that 5-ALA-guided HGG resection can be performed safely more than 4 h after administration, with clinical results largely similar to previous reports. Relaxation of timing restrictions could improve procedure workflow in busy neurosurgical centers, without additional risk to patients., Competing Interests: CH is a consultant for NX Development Corporation (NXDC) and Synaptive Medical. NXDC, a privately held company, markets Gleolan (5-ALA, aminolevulinic acid hydrochloride). Gleolan is an optical imaging agent approved for the visualization of malignant tissue during glioma surgery. CH is a consultant for NXDC and receives royalty payments for the sale of Gleolan. CH receives financial compensation as a consultant and lecturer for Synaptive (manufacturer of the 3D Synaptive MODUS V device). He has also received speaker fees by Carl Zeiss and Leica. 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 © 2021 Maragkos, Schüpper, Lakomkin, Sideras, Price, Baron, Hamilton, Haider, Lee, Hadjipanayis and Robin.)

Importance: Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed., Objective: To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19., Design, Setting, and Participants: This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients., Interventions: Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237)., Main Outcomes and Measures: The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality., Results: Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, -0.2% [95% CI, -5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09])., Conclusions and Relevance: Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults., Trial Registration: ClinicalTrials.gov: NCT04332991.

Background: Tuberculous spondylitis (Pott's disease), a common extrapulmonary manifestation of tuberculosis (TB), typically presents with back pain, tenderness, paraparesis/paraplegia, and various constitutional symptoms. Due to radiological similarities between Pott's disease and lung cancer, some lung cancer patients may initially be erroneously diagnosed and treated for TB, allowing for extensive progression of their cancer., Case Description: A 28-year-old male presented with a chronic dry cough, weight loss, and 2 months of increased back pain accompanied by bilateral lower extremity weakness. Magnetic resonance imaging revealed an epidural collection causing compression of the spinal cord at the T5-T6 level. The initial diagnosis was Mycobacterium tuberculosis /Pott's disease. A thoracic T4-T8 decompression fusion was performed; however, pathologic examination of the tissue revealed adenocarcinoma. Postoperatively, after the patient experienced several episodes of acute respiratory distress and a tension pneumothorax, lung imaging confirmed multiple tumor infiltrates along with lung cancer extending into the thoracic vertebrae. Pelvic studies also confirmed the presence of pelvic metastases. The patient passed away 3 weeks following surgery., Conclusion: In this case report, a 28-year-old male was treated for thoracic Pott's disease that proved to be metastatic lung adenocarcinoma. To avoid such misdiagnoses in the future, physicians should better differentiate spinal TB from other malignancies that may affect the spine. This study underscores the importance of obtaining at least a chest X-ray in any patient with suspected Pott's disease, irrespective of age, to help rule out lung cancer or other pathologies., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Surgical Neurology International.)

Anti-CD83 Ab capable of Ab-dependent cellular cytotoxicity can deplete activated CD83 + human dendritic cells, thereby inhibiting CD4 T cell-mediated acute graft-versus-host disease. As CD83 is also expressed on the surface of activated B lymphocytes, we hypothesized that anti-CD83 would also inhibit B cell responses to stimulation. We found that anti-CD83 inhibited total IgM and IgG production in vitro by allostimulated human PBMC. Also, Ag-specific Ab responses to immunization of SCID mice xenografted with human PBMC were inhibited by anti-CD83 treatment. This inhibition occurred without depletion of all human B cells because anti-CD83 lysed activated CD83 + B cells by Ab-dependent cellular cytotoxicity and spared resting (CD83 - ) B cells. In cultured human PBMC, anti-CD83 inhibited tetanus toxoid-stimulated B cell proliferation and concomitant dendritic cell-mediated CD4 T cell proliferation and expression of IFN-γ and IL-17A, with minimal losses of B cells (<20%). In contrast, the anti-CD20 mAb rituximab depleted >80% of B cells but had no effect on CD4 T cell proliferation and cytokine expression. By virtue of the ability of anti-CD83 to selectively deplete activated, but not resting, B cells and dendritic cells, with the latter reducing CD4 T cell responses, anti-CD83 may be clinically useful in autoimmunity and transplantation. Advantages might include inhibited expansion of autoantigen- or alloantigen-specific B cells and CD4 T cells, thus preventing further production of pathogenic Abs and inflammatory cytokines while preserving protective memory and regulatory cells., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Purpose: The rationale for 'professional education and development' (PED) courses is to support general practitioners, enabling them to access a range of theoretical and practical skills within a supportive schema. It aims to identify whether and how a regional PED course has had a beneficial impact upon participants., Methods: The study comprised a qualitative investigation of participants' assessed coursework portfolios. The content of each portfolio gives individual accounts of the impact of the course on personal and practice development. Permission to access extant portfolios was obtained from 16 recent alumni of the course. The anonymous written material was analysed by the research team for recurring discourses and themes using a thematic framework analysis., Results: Seven major thematic categories were extrapolated from the data: leadership, resilience, quality improvement, change management, development of new services, educational expertise, and patient safety. In each category, we found evidence that the course enabled development of practitioners by enhancing knowledge and skills which had a positive impact upon their self-perceived effectiveness and motivation., Conclusion: Extended specialty training is on the horizon but such courses may still serve a valuable purpose for current trainees and the existing general practitioners workforce which will be responsible for leading the shift towards community-based service delivery.

Purpose: The purpose of this paper is to determine the impact of an integrated Medical Leadership Programme (MLP) on a cohort of participating specialty doctors and the NHS services with which they were engaged., Design/methodology/approach: This was a qualitative study designed to obtain rich textual data on a novel training intervention. Semi-structured interviews were conducted with participating MLP trainees at fixed points throughout the programme in order to capture their experiences. Resulting data were triangulated with data from extant documentation, including trainees' progress reports and summaries of achievements. Recurring discourses and themes were identified using a framework thematic analysis., Findings: Evidence of the positive impact upon trainees and NHS services was identified, along with challenges. Evidence of impact across all the domains within the national Medical Leadership Competency Framework was also identified, including demonstrating personal qualities, working with others, managing services, improving services and setting direction., Research Limitations/implications: Data were drawn from interviews with a small population of trainees undertaking a pilot MLP in a single deanery, so there are inevitable limitations for generalisability in the quantitative sense. Whilst the pilot trainees were a self-selected group, it was a group of mixed origin and ability., Practical Implications: The study has provided valuable lessons for the design of future leadership programmes aimed at doctors in training., Originality/value: Identifying the effectiveness of an innovative model of delivery with regard to the Medical Leadership Curriculum may assist with medical staff engagement and support health service improvements to benefit patient care.

Although laughter forms an important part of human non-verbal communication, it has received rather less attention than it deserves in both the experimental and the observational literatures. Relaxed social (Duchenne) laughter is associated with feelings of wellbeing and heightened affect, a proximate explanation for which might be the release of endorphins. We tested this hypothesis in a series of six experimental studies in both the laboratory (watching videos) and naturalistic contexts (watching stage performances), using change in pain threshold as an assay for endorphin release. The results show that pain thresholds are significantly higher after laughter than in the control condition. This pain-tolerance effect is due to laughter itself and not simply due to a change in positive affect. We suggest that laughter, through an endorphin-mediated opiate effect, may play a crucial role in social bonding.

WHAT IS ALREADY KNOWN IN THIS AREA • A high rate of GP retirement is likely in the next few years. • GPs with The necessary skills are needed to provide care. • Provision of MSc courses designed for GPs is limited. WHAT THIS WORK ADDS • After attending MSc accredited development courses, GPs clearly expressed their intention to retire later. • Many participants have extended their role to become educators, appraisers, GPwSI and also become involved in PCO work. • Participants demonstrated a high rate of progression to further academic modules. SUGGESTIONS FOR FUTURE RESEARCH • Follow-up of participants' intention of working longer, to measure if that translates into reduced early retirement. • Measurement of the impact of such courses directly against provision of patient care.