Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Infants, Children, and Adolescents with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy, and their representatives to develop minimum sets of standardized outcomes and outcome measurement methods for clinical practice. Using modified Delphi consensus methods with consecutive rounds of online voting over 12 months, a core set of outcomes and corresponding measurement tool packages to capture the outcomes were identified for infants, children, and adolescents with epilepsy. Consensus methods identified 20 core outcomes. In addition to the outcomes identified for the ICHOM Epilepsy adult standard set, behavioral, motor, and cognitive/language development outcomes were voted as essential for all infants and children with epilepsy. The proposed set of outcomes and measurement methods will facilitate the implementation of the use of patient-centered outcomes in daily practice.

Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Adults with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. Therefore, the International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy and their representatives to develop minimum sets of standardized outcomes and outcomes measurement methods for clinical practice that support patient-clinician decision-making and quality improvement. Consensus methods identified 20 core outcomes. Measurement tools were recommended based on their evidence of strong clinical measurement properties, feasibility, and cross-cultural applicability. The essential outcomes included many non-seizure outcomes: anxiety, depression, suicidality, memory and attention, sleep quality, functional status, and the social impact of epilepsy. The proposed set will facilitate the implementation of the use of patient-centered outcomes in daily practice, ensuring holistic care. They also encourage harmonization of outcome measurement, and if widely implemented should reduce the heterogeneity of outcome measurement, accelerate comparative research, and facilitate quality improvement efforts.

Identification and Assessment of Outcome Measurement Instruments in Cauda Equina Syndrome: A Systematic Review.

STUDY DESIGN: This was a systematic review of surgically managed Cauda Equina Syndrome (CES) Outcome Measurement Instruments (OMI). OBJECTIVE: A core outcome set (COS) defines agreed outcomes which should be reported as a minimum in any research study for a specific condition. This study identified OMIs used in the wider CES literature and compare these to the established CESCOS. METHODS: To identify measurement methods and instruments in the CES surgical outcome evidence base, a systematic review was performed. Medline, Embase and CINAHL plus databases were queried. In addition, a secondary search for validation studies of measurement instruments in CES was undertaken. Identified studies from this search were subject to the COSMIN risk of bias assessment. RESULTS: In total, 112 studies were identified investigating surgical outcomes for CES. The majority (80%, n = 90) of these OMI studies were retrospective in nature and only 55% (n = 62) utilised a measurement method or instrument. The remaining 50 studies used study specific definitions for surgical outcomes defined within their methods. Of the 59 measurement instruments identified, 60% (n = 38 instruments) were patient reported outcome measures. Only one validated instrument was identified, which was a patient reported outcome measure. The validated instrument was not used in any study identified in the initial search (to identify measurement instruments). CONCLUSIONS: This review highlights the wide heterogeneity of measurement instruments used in surgically managed CES research. Subsequently, there is need for consensus agreement on which instrument or instruments should be used to measure each core outcome for CES surgical outcomes.

Usage and impact of patient-reported outcomes in epilepsy.

BACKGROUND: The use of patient-reported outcomes (PRO) in clinical practice is gaining increasing attention. This study aimed to provide a critical assessment of the current state-of-the-art and beliefs about the use of PRO in the management of people with epilepsy across some European countries. METHODS: Structured interviews were conducted with European experts to collect insights about (I) the personal experience with PRO; (II) the value and impact of PRO in the decision-making process at the national level; and (III) the interest for and use of PRO by national health authorities. RESULTS: Nine neurologists (Austria, Belgium, Czechia, Denmark, France, Greece, Italy, Poland, and United Kingdom), three health economists (Portugal, Romania, and Sweden), and one epidemiologist (Slovakia) participated. They all stated that PRO are collected at their own countries in the context of clinical trials and/or specific projects. During everyday clinical practice, PRO are collected routinely/almost routinely in Austria and Sweden and only at the discretion of the treating physicians in Czechia, Denmark, France, Greece, and Portugal. There was complete consensus about the favorable impact that the PRO can have in terms of clinical outcomes, healthcare resources utilization, and general patient satisfaction. Only participants from Portugal and Sweden answered that the PRO are perceived as very important by the National Health Authorities of their respective countries. CONCLUSIONS: Differences exist in attitudes and perspectives about PRO in epilepsy across Europe. An active plan is warranted to harmonize the measurement of PRO and ensure they can be relevant to people with epilepsy and health services.

A systematic review of studies reporting the development of core outcome sets for use in routine care.

OBJECTIVES: Core outcome sets (COS) represent the minimum health outcomes to be measured for a given health condition. Interest is growing in using COS within routine care to support delivery of patient-focused care. This review aims to systematically map COS developed for routine care to understand their scope, stakeholder involvement, and development methods. METHODS: Medline (Ovid), Scopus, and Web of Science Core collection were searched for studies reporting development of COS for routine care. Data on scope, methods, and stakeholder groups were analyzed in subgroups defined by setting. RESULTS: Screening 25,301 records identified 262 COS: 164 for routine care only and 98 for routine care and research. Nearly half of the COS (112/254, 44%) were developed with patients, alongside input from experts in registries, insurance, legal, outcomes measurement, and performance management. Research publications were often searched to generate an initial list of outcomes (115/198, 58%) with few searching routine health records (47/198, 24%). CONCLUSION: An increasing number of COS is being developed for routine care. Although involvement of patient stakeholders has increased in recent years, further improvements are needed. Methodology and scope are broadly similar to COS for research but implementation of the final set is a greater consideration during development.

Protocol for the development of an international Core Outcome Set for treatment trials in adults with epilepsy: the EPilepsy outcome Set for Effectiveness Trials Project (EPSET).

BACKGROUND: A Core Outcome Set (COS) is a standardised list of outcomes that should be reported as a minimum in all clinical trials. In epilepsy, the choice of outcomes varies widely among existing studies, particularly in clinical trials. This diminishes opportunities for informed decision-making, contributes to research waste and is a barrier to integrating findings in systematic reviews and meta-analyses. Furthermore, the outcomes currently being measured may not reflect what is important to people with epilepsy. Therefore, we aim to develop a COS specific to clinical effectiveness research for adults with epilepsy using Delphi consensus methodology. METHODS: The EPSET Study will comprise of three phases and follow the core methodological principles as outlined by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. Phase 1 will include two focused literature reviews to identify candidate outcomes from the qualitative literature and current outcome measurement practice in phase III and phase IV clinical trials. Phase 2 aims to achieve international consensus to define which outcomes should be measured as a minimum in future trials, using a Delphi process including an online consensus meeting involving key stakeholders. Phase 3 will involve dissemination of the ratified COS to facilitate uptake in future trials and the planning of further research to identify the most appropriate measurement instruments to use to capture the COS in research practice. DISCUSSION: Harmonising outcome measurement across future clinical trials should ensure that the outcomes measured are relevant to patients and health services, and allow for more meaningful results to be obtained. CORE OUTCOME SET REGISTRATION: COMET Initiative as study 118 .

Perspectives of Three African American Chemists: Reflections on Careers, Experiences, and the Future.

Three African American analytical chemists, whose primary research careers have focused in the respective sectors of academia, government, and industry, have come together to provide personal perspectives on parameters that have impacted their careers as well as to provide their perceptions of the current and future status of African Americans in the overall science, technology, engineering, and mathematics (STEM) enterprise, and the more specific field of analytical chemistry. The authors, having ∼150 years of combined experiences, reflect on the past status and contemplate future advances for African Americans in STEM. The most important factors during their formative years that underpinned their success over the long-term are enumerated. Particularly cited are the distinct features within the Historically Black Colleges and Universities (HBCU) environment that placed them solidly on a path toward successful careers. The Grand Challenge now and for the foreseeable future, reversal of the dysfunctional metropolitan public-school systems, is cited and the only perceived light in the tunnel for addressing this issue is mentioned. Finally, recommendations are made for the future where diversity within the STEM enterprise will be a prerequisite for U.S. competitiveness in our global society.

Case Report: Myelin Oligodendrocyte Glycoprotein Antibody-Associated Relapse With COVID-19.

A 39-year-old lady with relapsing myelin oligodendrocyte glycoprotein antibody (MOG-IgG) associated disease developed coryzal symptoms, malaise, sweating, and postural dizziness. Six days later she presented with painful progressive right visual loss consistent with optic neuritis. COVID-19 was confirmed by nasopharyngeal swab and MOG-IgG serological reversion was noted. Visual function improved following steroids and plasma exchange. This case highlights a possible causal association between inflammation due to COVID-19 and a relapse of MOG-IgG associated disease. It also highlights the clinical relevance of reporting MOG-IgG titers in MOG-IgG associated disease.

Epilepsy care in the COVID-19 era.

The COVID-19 pandemic will impact on how care for chronic conditions is delivered. We use epilepsy to exemplify how care for patients will be affected, and suggest ways in which healthcare systems can respond to deliver the most effective care. Where face-to-face outpatient appointments have been cancelled, telemedicine can facilitate remote clinical consultations for new and follow-up epilepsy clinic patients while reducing the risk of infection to both patients and healthcare staff. First-seizure patients will need investigation pathways rationalised, while those with chronic epilepsy will need to have reliable alternative avenues to access clinical advice. At the same time, neurologists should support emergency departments and acute medical units, advising on appropriate management of seizures and other acute neurological presentations. Ultimately, the revolution in our clinical practice is unlikely to cease after this pandemic, with reconfiguration of services likely to bring improvements in efficiency and convenience, and a reduced environmental impact.

Autoimmune encephalitis as an increasingly recognised cause of non-convulsive status epilepticus: A retrospective, multicentre evaluation of patient characteristics and electroencephalography (EEG) results.

PURPOSE: Status epilepticus (SE) is a severe condition of unrelenting seizures requiring urgent identification and treatment. SE may be unprovoked, occurring in someone with epilepsy, or may be provoked by acute intracranial disease or metabolic derangement. Increasingly encephalitis, particularly autoimmune types, is reported to cause refractory seizures. Whilst convulsive SE is readily identified, non-convulsive SE (NCSE) can be difficult to identify clinically, and electroencephalography (EEG) is required. Therefore, it is critical to identify the key clinical features associated with NCSE on EEG to inform future use of EEG. METHODS: We conducted a multicentre, retrospective analysis of EEG requests from four general and one specialist neurology hospital in the Northwest of England (2015-2018). Cases were identified from EEG requests for patients with suspected NCSE or other indications such as encephalopathy. We compared demographic and clinical characteristics between EEG-confirmed cases of NCSE and a randomly selected sample of negative controls. RESULTS: 358 EEGs were reviewed, and 8 positive cases of NCSE were identified. Epilepsy was identified as the aetiology in 2 of these cases, and autoimmune encephalitis another 2 cases (one patient with N-methyl-d-aspartate receptor antibodies and another with voltage gated potassium channel antibodies). Previous alcohol excess (p = 0.005) and subtle motor signs (p = 0.047) on examination were observed more frequently in patients with NCSE compared to controls. CONCLUSION: Physicians should have a low threshold for urgent EEG in patients with suspected or previous encephalitis, especially if autoimmunity is suspected or subtle motor signs are present.

Computed tomography in patients with epileptic seizures admitted acutely to hospital: A population level analysis of routinely collected healthcare data.

Approximately 1.4% of emergency medical admissions are due to epileptic seizures. For the majority of such cases, computed tomography (CT) will not inform acute management and is unnecessary.Pseudonymised, routinely collected data from seven hospitals within the Cheshire and Merseyside area of the UK were analysed. All patients with emergency admissions to hospital due to seizures between 2014 and 2017 were included. Use of CT of the head was identified from routine coding.We identified 4,183 individuals with an acute seizure admission, of which over 30% received a CT of the head. There was significant variation in CT among hospital trusts.The rate of CT for patients admitted with seizures is high and CT is not being directed to those where they may be indicated. Integrated care pathways and guidelines are required to improve the management of patients presenting acutely with seizures.

Memory, attention and fluency deficits in COPD may be a specific form of cognitive impairment.

There is increasing evidence demonstrating an association between chronic obstructive pulmonary disease (COPD) and cognitive impairment. We present a narrative review of published studies on the subject and a cross-sectional study investigating domain-specific cognitive impairment in people with COPD compared to people with known Alzheimer's dementia, and controls without known COPD or cognitive impairment. The aim of the study was to compare prevalence and pattern of cognitive impairment between the three groups using the Addenbrooke's Cognitive Examination (ACE)-III tool. A total of 89 participants were recruited (44 with COPD, 17 with Alzheimer's and 28 controls). Patients with COPD had significantly lower total ACE-III scores than controls (p<0.001). When comparing the COPD group to the known Alzheimer's dementia group, overall ACE-III scores were significantly lower in the Alzheimer's dementia group than the COPD group (p=0.019). The domain-specific scores for attention (p<0.004), memory (p<0.004) and fluency (p<0.001) were significantly lower in the Alzheimer's dementia group than the COPD group. Our result suggest that the COPD group were significantly more likely to have cognitive impairment than the healthy control group. This was supported by the results of a narrative review of the published literature. Our results show that the pattern of impairment in the COPD group is different to the pattern of impairment shown in the known Alzheimer's dementia group, with significant differences in the cognitive domains affected. These results are in keeping with the findings of other previously published studies included in the narrative review.

A New Bioactive Polylactide-based Composite with High Mechanical Strength.

A new bioresorbable polylactide/calcium phosphate composite with improved mechanical strengths and a more basic filler, tetracalcium phosphate (TTCP), was prepared by melt compounding. N-(2-aminoethyl)-3-aminoproplytrimethoxysilane (AEAPS) and pyromellitic dianhydride (PMDA) were used to improve the interfacial adhesion between TTCP and polylactide (PLA). While AEAPS improved the dispersion of TTCP in the matrix, PMDA might react with the terminal hydroxyl group of PLA and the amino group on the surface of AEAPS modified TTCP, which could further enhance the interfacial strength. The tensile strength was improved to 68.4 MPa for the PLA/TTCP-AEAPS composite from 51.5 MPa for the PLA/TTCP composite (20 wt% of TTCP). Dynamic mechanical analysis suggested that there was a 51 % improvement in storage modulus compared to that of PLA alone, when PMDA (0.2 wt% of PMDA) was incorporated into the PLA/TTCP-AEAPS composite (5 wt% of TTCP). Using this new bioresorbable PLA composite incorporated with a more basic filler for biomedical application, the inflammation and allergic effect resulted from the degraded acidic product are expected to be reduced.

Bioinspired amphiphilic phosphate block copolymers as non-fluoride materials to prevent dental erosion.

Inspired by the fact that certain natural proteins, e.g. casein phosphopeptide or amelogenin, are able to prevent tooth erosion (mineral loss) and to enhance tooth remineralization, a synthetic amphiphilic diblock copolymer, containing a hydrophilic methacryloyloxyethyl phosphate block (MOEP) and a hydrophobic methyl methacrylate block (MMA), was designed as a novel non-fluoride agent to prevent tooth erosion under acidic conditions. The structure of the polymer, synthesized by reversible addition-fragment transfer (RAFT) polymerization, was confirmed by gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FTIR), and nuclear magnetic resonance spectroscopy (NMR). While the hydrophilic PMOEP block within the amphiphilic block copolymer strongly binds to the enamel surface, the PMMA block forms a hydrophobic shell to prevent acid attack on tooth enamel, thus preventing/reducing acid erosion. The polymer treatment not only effectively decreased the mineral loss of hydroxyapatite (HAP) by 36-46% compared to the untreated control, but also protected the surface morphology of the enamel specimen following exposure to acid. Additionally, experimental results confirmed that low pH values and high polymer concentrations facilitate polymer binding. Thus, the preliminary data suggests that this new amphiphilic diblock copolymer has the potential to be used as a non-fluoride ingredient for mouth-rinse or toothpaste to prevent/reduce tooth erosion.

Effects of Inorganic Fillers on the Thermal and Mechanical Properties of Poly(lactic acid).

Addition of filler to polylactic acid (PLA) may affect its crystallization behavior and mechanical properties. The effects of talc and hydroxyapatite (HA) on the thermal and mechanical properties of two types of PLA (one amorphous and one semicrystalline) have been investigated. The composites were prepared by melt blending followed by injection molding. The molecular weight, morphology, mechanical properties, and thermal properties have been characterized by gel permeation chromatography (GPC), scanning electron microscope (SEM), instron tensile tester, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic mechanical analysis (DMA). It was found that the melting blending led to homogeneous distribution of the inorganic filler within the PLA matrix but decreased the molecular weight of PLA. Regarding the filler, addition of talc increased the crystallinity of PLA, but HA decreased the crystallinity of PLA. The tensile strength of the composites depended on the crystallinity of PLA and the interfacial properties between PLA and the filler, but both talc and HA filler increased the toughness of PLA.

Immobilization of Xanthate Agent on Titanium Dioxide and Surface Initiated RAFT Polymerization.

Surface modification of titanium dioxide (TiO2) nanoparticle is essential to control its surface properties, thereby to enhance its cell penetration capability, reduce its cytotoxicity, or improve its biocompatibility. In order to graft polyvinyl acetate onto TiO2 nanoparticles, xanthate was chemically immobilized on the surface of TiO2 by acylation followed by nucleophilic substitution with a carbodithioate salt. Reversible addition fragmentation chain transfer polymerization was conducted to graft vinyl acetate onto the surface of TiO2. Both the TiO2-xanthate and TiO2-polyvinyl acetate hybrids were characterized by UV-Vis spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The chemical immobilization of xanthate on the surface of TiO2 and the subsequent controlled polymerization provide useful insight for decoration and modification of TiO2 and other nanoparticles.