Comparing reactogenicity of COVID-19 vaccine boosters: a systematic review and meta-analysis.

INTRODUCTION: Different COVID-19 vaccines are being utilized as boosters. This systematic review and meta-analysis aims to evaluate the reactogenicity of COVID-19 vaccines given as booster doses, according to vaccine type, dose, timing, participant characteristics and primary immunization regimen received. METHODS: Four databases (MEDLINE, Embase, Web of Science and CENTRAL) were searched for randomized controlled trials between 1 January 2020 and 1 January 2023 according to predetermined criteria. RESULTS: Twenty-eight studies describing 19 vaccines of four different types (viral vector, inactivated, mRNA and protein sub-unit) were identified. BNT162b2 vaccine (Pfizer-BioNTech) was selected as the control as it was most often compared with other vaccines. Fever, fatigue, headache, injection-site pain, redness, and swelling were the most frequently reported solicited events. mRNA vaccines were the most reactogenic, followed by viral vector vaccines and protein sub-unit vaccines, while inactivated vaccines were the least reactogenic. Full-dose vaccines were more reactogenic than half-dose vaccines. Heterologous BNT162b2 boosters were more reactogenic than boosters with the same vaccine used for primary immunization. CONCLUSIONS: COVID-19 vaccine booster schedules have distinct reactogenicity profiles, dependent on dose and vaccine type, which may allow targeted recommendations and provide choice for specific populations. Greater standardization of adverse event reporting will aid future studies.

Development of a core outcome set for quality of life for adults with drug-resistant epilepsy: A multistakeholder Delphi consensus study.

OBJECTIVE: In 2017, the American Academy of Neurology (AAN) convened the AAN Quality Measurement Set working group to define the improvement and maintenance of quality of life (QOL) as a key outcome measure in epilepsy clinical practice. A core outcome set (COS), defined as an accepted, standardized set of outcomes that should be minimally measured and reported in an area of health care research and practice, has not previously been defined for QOL in adult epilepsy. METHODS: A cross-sectional Delphi consensus study was employed to attain consensus from patients and caregivers on the QOL outcomes that should be minimally measured and reported in epilepsy clinical practice. Candidate items were compiled from QOL scales recommended by the AAN 2017 Quality Measurement Set. Inclusion criteria to participate in the Delphi study were adults with drug-resistant epilepsy diagnosed by a physician, no prior diagnosis of psychogenic nonepileptic seizures or a cognitive and/or developmental disability, or caregivers of patients meeting these criteria. RESULTS: A total of 109 people satisfied inclusion/exclusion criteria and took part in Delphi Round 1 (patients, n = 95, 87.2%; caregivers, n = 14, 12.8%), and 55 people from Round 1 completed Round 2 (patients, n = 43, 78.2%; caregivers, n = 12, 21.8%). One hundred three people took part in the final consensus round. Consensus was attained by patients/caregivers on a set of 36 outcomes that should minimally be included in the QOL COS. Of these, 32 of the 36 outcomes (88.8%) pertained to areas outside of seizure frequency and severity. SIGNIFICANCE: Using patient-centered Delphi methodology, this study defines the first COS for QOL measurement in clinical practice for adults with drug-resistant epilepsy. This set highlights the diversity of factors beyond seizure frequency and severity that impact QOL in epilepsy.

Electronic Health Record Technology Designed for the Clinical Encounter: MS NeuroShare.

OBJECTIVE: Advances in medical discoveries have bolstered expectations of precise and complete care, but delivering on such a promise for complex, chronic neurologic care delivery requires solving last-mile challenges. We describe the iterative human-centered design and pilot process for multiple sclerosis (MS) NeuroShare, a digital health solution that brings practical information to the point of care so that clinicians and patients with MS can view, discuss, and make informed decisions together. METHODS: We initiated a comprehensive human-centered process to iteratively design, develop, and implement a digital health solution for managing MS in the routine outpatient setting of the nonprofit Sutter Health system in Northern California. The human-centered codesign process included 3 phases: discovery and design, development, and implementation and pilot. Stakeholders included Sutter Health's Research Development and Dissemination team, academic domain experts, neurologists, patients with MS, and an advisory group. RESULTS: MS NeuroShare went live in November 2018. It included a patient- and clinician-facing web application that launches from the electronic health record, visually displays a patient's data relevant to MS, and prompts the clinician to comprehensively evaluate and treat the patient. Both patients and clinicians valued the ability to jointly view patient-generated and other data. Preliminary results suggest that MS NeuroShare promotes patient-clinician communication and more active patient participation in decision-making. CONCLUSIONS: Lessons learned in the design and implementation of MS NeuroShare are broadly applicable to the design and implementation of digital tools aiming to improve the experience of delivering and receiving high-quality care for complex, neurologic conditions across large health systems.

A Case of Ewing Sarcoma of the Bladder Presenting in Early Infancy.

A 6-week-old female presented with gross hematuria and was diagnosed with Ewing sarcoma of the bladder through ultrasound and cystoscopic biopsies, along with a negative metastatic workup. She was treated with transurethral resection, chemotherapy consisting of with vincristine, cycolphosphamide, doxorubicin, ifosfamide and etoposide, and partial cystectomy. After completing chemotherapy, the patient has been doing well with no evidence of disease. There have been 14 other cases, 4 pediatric, of Ewing sarcoma of the bladder reported. To our knowledge, our case is the youngest patient reported with this disease.

An electronic, unsupervised patient-reported Expanded Disability Status Scale for multiple sclerosis.

BACKGROUND: In persons with multiple sclerosis (MS), the Expanded Disability Status Scale (EDSS) is the criterion standard for assessing disability, but its in-person nature constrains patient participation in research and clinical assessments. OBJECTIVE: The aim of this study was to develop and validate a scalable, electronic, unsupervised patient-reported EDSS (ePR-EDSS) that would capture MS-related disability across the spectrum of severity. METHODS: We enrolled 136 adult MS patients, split into a preliminary testing Cohort 1 (n = 50), and a validation Cohort 2 (n = 86), which was evenly distributed across EDSS groups. Each patient completed an ePR-EDSS either immediately before or after a MS clinician's Neurostatus EDSS evaluation. RESULTS: In Cohort 2, mean age was 50.6 years (range = 26-80) and median EDSS was 3.5 (interquartile range (IQR) = [1.5, 5.5]). The ePR-EDSS and EDSS agreed within 1-point for 86% of examinations; kappa for agreement within 1-point was 0.85 (p < 0.001). The correlation coefficient between the two measures was 0.91 (<0.001). DISCUSSION: The ePR-EDSS was highly correlated with EDSS, with good agreement even at lower EDSS levels. For clinical care, the ePR-EDSS could enable the longitudinal monitoring of a patient's disability. For research, it provides a valid and rapid measure across the entire spectrum of disability and permits broader participation with fewer in-person assessments.

A Precision Medicine Tool for Patients With Multiple Sclerosis (the Open MS BioScreen): Human-Centered Design and Development.

BACKGROUND: Patients with multiple sclerosis (MS) face several challenges in accessing clinical tools to help them monitor, understand, and make meaningful decisions about their disease course. The University of California San Francisco MS BioScreen is a web-based precision medicine tool initially designed to be clinician facing. We aimed to design a second, openly available tool, Open MS BioScreen, that would be accessible, understandable, and actionable by people with MS. OBJECTIVE: This study aimed to describe the human-centered design and development approach (inspiration, ideation, and implementation) for creating the Open MS BioScreen platform. METHODS: We planned an iterative and cyclical development process that included stakeholder engagement and iterative feedback from users. Stakeholders included patients with MS along with their caregivers and family members, MS experts, generalist clinicians, industry representatives, and advocacy experts. Users consisted of anyone who wants to track MS measurements over time and access openly available tools for people with MS. Phase I (inspiration) consisted of empathizing with users and defining the problem. We sought to understand the main challenges faced by patients and clinicians and what they would want to see in a web-based app. In phase II (ideation), our multidisciplinary team discussed approaches to capture, display, and make sense of user data. Then, we prototyped a series of mock-ups to solicit feedback from clinicians and people with MS. In phase III (implementation), we incorporated all concepts to test and iterate a minimally viable product. We then gathered feedback through an agile development process. The design and development were cyclical-many times throughout the process, we went back to the drawing board. RESULTS: This human-centered approach generated an openly available, web-based app through which patients with MS, their clinicians, and their caregivers can access the site and create an account. Users can enter information about their MS (basic level as well as more advanced concepts), visualize their data longitudinally, access a series of algorithms designed to empower them to make decisions about their treatments, and enter data from wearable devices to encourage realistic goal setting about their ambulatory activity. Agile development will allow us to continue to incorporate precision medicine tools, as these are validated in the clinical research arena. CONCLUSIONS: After engaging intended users into the iterative human-centered design of the Open MS BioScreen, we will now monitor the adaptation and dissemination of the tool as we expand its functionality and reach. The insights generated from this approach can be applied to the development of a number of self-tracking, self-management, and user engagement tools for patients with chronic conditions.

Separation of DNA by length in rotational flow: Lattice-Boltzmann-based simulations.

We use a lattice-Boltzmann based Brownian dynamics simulation to investigate the separation of different lengths of DNA through the combination of a trapping force and the microflow created by counter-rotating vortices. We can separate most long DNA molecules from shorter chains that have lengths differing by as little as 30%. The sensitivity of this technique is determined by the flow rate, size of the trapping region, and the trapping strength. We expect that this technique can be used in microfluidic devices to separate long DNA fragments that result from techniques such as restriction enzyme digests of genomic DNA.

Pharmacotherapy for post-traumatic stress disorder: systematic review and meta-analysis.

BACKGROUND: Pharmacological treatment is widely used for post-traumatic stress disorder (PTSD) despite questions over its efficacy. AIMS: To determine the efficacy of all types of pharmacotherapy, as monotherapy, in reducing symptoms of PTSD, and to assess acceptability. METHOD: A systematic review and meta-analysis of randomised controlled trials was undertaken; 51 studies were included. RESULTS: Selective serotonin reuptake inhibitors were found to be statistically superior to placebo in reduction of PTSD symptoms but the effect size was small (standardised mean difference -0.23, 95% CI -0.33 to -0.12). For individual pharmacological agents compared with placebo in two or more trials, we found small statistically significant evidence of efficacy for fluoxetine, paroxetine and venlafaxine. CONCLUSIONS: Some drugs have a small positive impact on PTSD symptoms and are acceptable. Fluoxetine, paroxetine and venlafaxine may be considered as potential treatments for the disorder. For most drugs there is inadequate evidence regarding efficacy for PTSD, pointing to the need for more research in this area.

The most effective way of delivering a train-the-trainers program: a systematic review.

INTRODUCTION: Previous literature has shown that multifaceted, interactive interventions may be the most effective way to train health and social care professionals. A Train-the-Trainer (TTT) model could incorporate all these components. We conducted a systematic review to determine the overall effectiveness and optimal delivery of TTT programs. METHODS: We searched 15 databases. Reference lists and online resources were also screened. Studies with an objective follow-up measure collected over 1 week after the intervention were included. The intervention had to be based on a TTT model for health and social care professionals. RESULTS: Eighteen studies met the inclusion criteria. TTT interventions varied greatly, ranging from didactic presentations to group discussions and role-plays. The heterogeneity of the studies and limited data prevented meta-analysis. A narrative review found that the TTT programs in 13 studies helped to increase knowledge, improve clinical behavior, or produce better patient outcomes. One study showed no effect. Three studies showed possible effect and one study showed that a CD-ROM training method was more effective than a TTT training method in improving participants' knowledge. Ratings of the studies' methodologies suggested moderate risk of bias, which limits interpretation of the results. DISCUSSION: There is evidence that using a blended learning approach to deliver TTT programs--combining different techniques such as interactive, multifaceted methods and accompanying learning materials--can help to effectively disseminate and implement guidelines and curricula to health and social care professionals. However, further research is needed to determine the optimum "blend" of techniques.

The use of intravenous palivizumab for treatment of persistent RSV infection in children with leukemia.

Palivizumab is a humanized monoclonal antibody used to decrease the threat of respiratory syncytial virus (RSV) infection among children at high risk. There are no standard guidelines due to conflicting data on palivizumab's use in the treatment of RSV lower respiratory tract infections. Intravenous (IV) palivizumab was shown to be well tolerated and associated with decreased mortality in high-risk children who have RSV disease. However, it did not prevent lower respiratory tract infections and did not affect the survival rate of allogeneic stem cell transplant recipients who had RSV infection. We present 2 children with acute lymphocytic leukemia (ALL) and persistent RSV infection while receiving chemotherapy. Patient A is a 4-year-old male with Down syndrome, ALL, and persistent RSV infection for at least 3 months. Patient B is a 3-year-old female with pre-B cell ALL whose chemotherapy intensification phase was delayed due to a month-long RSV infection. RSV infections were determined by using real-time polymerase chain reaction assays from nasopharyngeal swabs before IV palivizumab therapy; patient A was positive for RSV at 36 cycles and patient B was positive for RSV at 29 cycles. RSV infection was cleared in both patients within 72 hours after receiving IV palivizumab (patient A: 16 mg/kg; patient B: 15 mg/kg). IV palivizumab may be a treatment option for persistent RSV infection among immunocompromised patients.

Time dependence and density inversion in simulations of vertically oscillated granular layers.

We study a layer of grains atop a plate which oscillates sinusoidally in the direction of gravity, using three-dimensional, time-dependent numerical solutions of continuum equations to Navier-Stokes order as well as hard-sphere molecular dynamics simulations. For high accelerational amplitudes of the plate, the layer exhibits a steady-state "density inversion" in which a high-density portion of the layer is supported by a lower-density portion. At low accelerational amplitudes, the layer exhibits oscillatory time dependence that is strongly correlated to the motion of the plate. We show that continuum simulations yield results consistent with molecular dynamics results in both regimes.

Using a Delphi process to develop an effective train-the-trainers program to train health and social care professionals throughout Europe.

Research has shown that developing a Train-the-Trainers (TTT) program is important if agencies are to implement guidelines, but the most effective way to deliver a TTT program remains unanswered. This article presents data from a 3-round Internet-based Delphi process, which was used to help develop consensus-based guidelines for a TTT programme to deliver to health and social care professionals throughout Europe a curriculum on traumatic stress. In Round 1, 74 experts rated the importance of statements relating to the TTT field and then reassessed their scores in the light of others' responses in subsequent rounds. Forty-one (67%) of 61 statements achieved consensus (defined as having a mean score >7 or < 3 on the 0-9 rating scales used and 70% of participants scoring 7 and above or 3 and below) for inclusion. Key TTT components included interactive and practical presentations, delivery to groups of 7-12 people over 2 days, external and local expert facilitation, course manuals, refresher courses, and supervision. The Delphi process allowed a consensus to be achieved in an area in which there are limitations in the current evidence.

Efficacy, cost-effectiveness and acceptability of self-help interventions for anxiety disorders: systematic review.

BACKGROUND: Self-help interventions for psychiatric disorders represent an increasingly popular alternative to therapist-administered psychological therapies, offering the potential of increased access to cost-effective treatment. AIMS: To determine the efficacy, cost-effectiveness and acceptability of self-help interventions for anxiety disorders. METHOD: Randomised controlled trials (RCTs) of self-help interventions for anxiety disorders were identified by searching nine online databases. Studies were grouped according to disorder and meta-analyses were conducted where sufficient data were available. Overall meta-analyses of self-help v. waiting list and therapist-administered treatment were also undertaken. Methodological quality was assessed independently by two researchers according to criteria set out by the Cochrane Collaboration. RESULTS: Thirty-one RCTs met inclusion criteria for the review. Results of the overall meta-analysis comparing self-help with waiting list gave a significant effect size of 0.84 in favour of self-help. Comparison of self-help with therapist-administered treatments revealed a significant difference in favour of the latter with an effect size of 0.34. The addition of guidance and the presentation of multimedia or web-based self-help materials improved treatment outcome. CONCLUSIONS: Self-help interventions appear to be an effective way of treating individuals diagnosed with social phobia and panic disorder. Further research is required to evaluate the cost-effectiveness and acceptability of these interventions.

Role of dissolved salts in thermophoresis of DNA: lattice-Boltzmann-based simulations.

We use a lattice Boltzmann based Brownian dynamics simulation to investigate the dependence of DNA thermophoresis on its interaction with dissolved salts. We find the thermal diffusion coefficient D{T} depends on the molecule size, in contrast with previous simulations without electrostatics. The measured S{T} also depends on the Debye length. This suggests thermophoresis of DNA is influenced by the electrostatic interactions between the polymer beads and the salt ions. However, when electrostatic forces are weak, DNA thermophoresis is not found, suggesting that other repulsive forces such as the excluded volume force prevent thermal migration.

Optic canal diameter in infantile osteopetrosis.

Infants with osteopetrosis may present early for ophthalmologic examination because of threatened visual impairment, primarily related to optic nerve compression. The authors describe two children with osteopetrosis who had narrow optic canals on orbital computed tomography. These canals were statistically narrower than those of newly developed, age-matched controls. Optic canal diameters, in addition to visual evoked potential data, may be helpful in determining prognosis.

Advanced small cell carcinoma of the ovary in a seventeen-year-old female, successfully treated with surgery and multi-agent chemotherapy.

Advanced small cell carcinoma of the ovary (FIGO stage III or IV) is a rare and usually lethal tumor seen in adolescents and young women. In pediatric patients with advanced disease, there have been only two case reports of successful therapy, we report a third patient, diagnosed at 17 years of age, with an abdominal mass and metastatic disease to regional and distant lymph nodes, who was successfully treated with surgery and intensive multi-agent chemotherapy. Imatinib, thalidomide, and celecoxib were also administered for up to 24 months following initial chemotherapy. She remains in remission 3 years from diagnosis.

Platelet-derived growth factor receptor-beta in Gorham's disease.

BACKGROUND: A 17-year-old male presented with pain in his lower-left chest. He had no significant medical history and was previously in good health. He had a fractured ninth left anterior rib and the tenth, eleventh and twelfth ribs were absent, which was thought to be a congenital anomaly. Several months later, he presented again with back pain, an enlarging mass in the lower-left chest wall, erosion of the lateral pedicles of the lower thoracic vertebrae and pleural effusion. INVESTIGATIONS: Physical examination, chest X-ray, MRI of the spine, incisional biopsy, serial CT imaging of the hemithorax, immunohistochemistry, flow cytometry, and enzyme-linked immunosorbent assays. DIAGNOSIS: Gorham's lymphangiomatosis with expression of platelet-derived growth factor receptor-beta and elevated circulating platelet-derived growth factor-BB. MANAGEMENT: Spine stabilization, thalidomide, celecoxib, interferon-alpha2b, pamidronate, zoledronate, thoracotomy, pleurectomy, talc pleurodesis, and imatinib mesylate.