bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of automated microscopy sediment analysis in urinary tract infection screening: a practical insight in adjusting fixed cut-off values for urine culture
Authors: Bovelander Elke , Raijmakers Maarten , van Dam Dick , Kraat Yvette , Berendsen Chris
Published: June 2023

Purpose

The aim of our study was to evaluate a procedure in which urine culture was only being performed based on fixed cut-off values of urine sediment analysis with intention to prevent unnecessary negative urine cultures.

Methods

From January 2018 to August 2018, all urine samples from patients visiting the urology outpatient department were analyzed. Urine culture was only performed if urine sediment contained more than 130 bacteria per microliter and/or more than 50 leukocytes per microliter.

Results

In total, 2821 urine cultures with accompanying urine sediments were analyzed. 2098 cultures (74.4%) were defined negative and 723 (25.6%) positive. By adjusting cut-off values of sediment analysis > 20 per microliter or bacteria more than 330 per microliter, 1051 cultures would have been saved with an estimated cost reduction of € 31.470. Eleven clinically relevant urine cultures would have been missed (1%).

Conclusion

Using cut-offs values leads to a notable decrease of the total number of urine cultures. According to our analysis, adjusting cut-off values could result in 37% less urine cultures and almost 50% less negative cultures. Hereby, unnecessary cost can be prevented [in our department estimated €31.470 in eight months (€ 47.205/year)].
Parental Migration in Childhood and Individual Wellbeing in Adulthood
Authors: Guo Lijia
Published: June 2023

Parental absence due to parental migration has been a prevalent phenomenon in developing countries, occurring on an exceptionally large scale in China. While previous literature focused on the concurrent effects of parental migration on children, this study aims to investigate whether the impact of parental absence during childhood is long-term and lasts into adulthood. This study examines how individuals with childhood experience of parental absence differ from their counterparts in their early adulthood, in terms of their mental wellbeing, physical health, and cognitive ability. This study uses a sample of 6031 individuals aged from 18 to 30 years old from a nationally representative dataset China Family Panel Studies. The results show that the childhood experience of both-parental absence is negatively associated with individual’s mental and physical health while positively associated with cognitive ability in their early adulthood.
Die Theorie algorithmischer Sozialität (TaS)
Authors: Seyfert Robert
Published: June 2023

Der Artikel geht davon aus, dass die digitale Transformation mit gesellschaftlichen Veränderungen einhergeht, die eine grundlegende Überarbeitung soziologischer Theoriebestände erfordern. Dazu macht der Text mit der Theorie algorithmischer Sozialität (TaS) ein Angebot. Diese Theorie soll (1.) neue (post-)soziale Beziehungen konzeptuell in den Blick nehmen, die im Prozess der digitalen Transformation entstanden sind; und diese mit anderen in der Soziologie etablierten Arten sozialer Beziehungen (intersubjektive, interobjektive Beziehungen etc.) in einen theorie-systematischen Zusammenhang bringen. Dabei soll die Digitalisierung nicht als eine vereinheitlichende (oder sogar vereinfachende) Bewegung verstanden werden, sondern (2.) als ein Prozess, in dem sowohl die Beziehungsformen als auch die Elemente in diesen Beziehungen vielfältiger und heterogener werden. (3.) werden die Individuen bzw. Elemente (menschliche Subjekte, algorithmische Objekte etc.), die in diesen Beziehungen und Prozessen eine Rolle spielen, typologisch kartographiert. Zur Konzeptualisierung der Verhältnisse und Prozesse zwischen den Individuen und Elementen verwende ich Gilbert Simondons Konzept der Disparation; zur Beschreibung der neuen (post)-sozialen Beziehungen schlage ich den Begriff der algorithmischen Sozialität vor.
Improving Oxidation Resistance of Low Fe-Si Alloys by Preheating Treatment
Authors: Li C. L. , Ma W. , Liu Z. H. , Freiberg K. E. , Liu G. J. , Lang X. Y. , Lippmann S. , Zhu Y. F. , Jiang Q.
Published: June 2023

In this work, attempts have been made to improve the oxidation resistance of Fe-Si alloys with 0.5, 1.0 and 2.0 mass pct Si by a preheating treatment, which was carried out at 1073 K for 24 hours in high purity hydrogen atmosphere. Compared with pure Fe and untreated Fe-Si alloys, the oxidation resistance of the preheated Fe-Si alloys at 673 K in O2 is drastically increased, in the case of 2 mass pct Si by two orders of magnitude. The improvement is attributed to a uniform, dense and continuous 25 nm pure SiO2 layer formed on the alloy surface during the preheating treatment in hydrogen atmosphere hindering the diffusion of Fe and O.
Is investing in the renewable energy stock market both financially and ESG efficient? A COVID-19 pandemic analysis
Authors: Bilbao-Terol Amelia , Arenas-Parra Mar , Quiroga-García Raquel , Bilbao-Terol Celia
Published: June 2023

The aim of this paper is to provide a tool for finding investments in the stocks of energy firms that achieve both good financial and reasonable environmental, social, and governance (ESG) performance. Our methodology entails two steps and is based on diversification-consistent DEA models. The first step involves constructing a financially efficient frontier of investment portfolios by applying the model originally proposed by Branda (Omega 52:65–76. 10.1016/j.ejor.2007.04.014, 2015). In the second step, a new DEA model is proposed in order to find the ESG-efficient portfolios among the ones already identified in the first step and to rank them with respect to their ESG performance. This model is parameterised by a weighting system that allows us to assign different importance to the various ESG outputs. Additionally, the proposal allows an evaluation of both ESG and financial efficiency related to the financial energy market over two periods (the pre-COVID-19 and COVID-19 periods), considering renewable energy and non-renewable energy firms both jointly and separately. The results support the better financial performance of the renewable energy stock market compared with that of the non-renewable energy market.
Integrative Perspectives on Human Development: Dynamic and Semiotic
Authors: Zittoun Tania
Published: June 2023

Werner Greve argues for an abstract and integrative theory of development; to progress toward such a theory, he suggests that evolutionary psychology can provide concepts for a processual approach to adaptation. To complement this perspective, I propose to start where the author finishes: the need to further qualify change, and to account for information. Considering ruptures and sense-making as cornerstones of a developmental approach, I recall that open dynamic approaches offer a meta-theoretical frame for an integrative developmental psychology, and that cultural approaches already and always account for meaning-making to start with. Assuming these two givens, a variety of integrative propositions account for stability and change; I present an historical example, the work of Gordon Allport, and a current one, our work as sociocultural psychologists, to show how the theoretical and heuristic interest of this proposition.
Examining situational awareness, trust in automation, and workload in engine resources management: an evaluation of head-worn display technology
Authors: Nizar Adi Mas , Miwa Takashi , Uchida Makoto
Published: June 2023

Work in the engine department is currently demanding more monitoring task. However, the current alarm systems that support operators during troubleshooting are deficient. In many cases, operators reach the engine control room (ECR) only to find a false alarm. This problem is likely to aggravate in the future as operators work in smaller numbers or even alone; therefore, task prioritization should be considered in a given context. Therefore, this study examines the application of head-worn displays in engine resources management to improve situational awareness (SA), trust in automation, and workload. A human-subject experiment was conducted using an engine plant simulator. The participants simultaneously performed maintenance and monitoring tasks in two scenarios: work conditions assisted with and without information on the head-worn display used as a cognition aid. Subjective measurement involved filling in questionnaires after each trial, whereas objective measurement used the simulator-recorded data. The results show that the availability of engine parameters and alarm indicators on a head-worn display is less significant in improving situational awareness. However, it can still help develop trust in automation and lower the workload. In addition, head-worn displays improve participants’ prioritization in a multi-tasking environment. The results indicate that examining these findings in actual work environments can help realize the future application of head-worn displays in ship operations.
Effect of (5%) CO2 on the Oxidation Rate During Cooling of Industrial Aluminum White Dross
Authors: Solem Cathrine Kyung Won , Deledda Stefano , Zedel Hannes , Tranell Gabriella , Aune Ragnhild E.
Published: June 2023

Aluminum (Al) white dross is classified as hazardous waste and originates from the primary production of Al as a result of molten metal oxidation at an industrial scale. As the produced dross reduces the annual metallic Al production by up to 10%, finding a way to reduce the dross formation has always been of interest. Several laboratory studies have shown that exposing molten Al to small amounts of CO2 has an inhibiting effect on the oxidation rate of the metal. Still, few studies have described this effect at an industrial scale. The present work has therefore studied the impact of protective cooling of industrial white dross samples on the oxidation rate of the dross to shed some light on the issue. Samples were collected from the holding furnace in a casthouse during the production of two different charges of Al alloys with varying amounts of magnesium (Mg), i.e., Charge 1 (AlMg1.0Mn0.4) and Charge 2 (AlMg1.2Mn0.4). The samples were cooled in ambient air and under a lid with 5% CO2 mixed with 95% synthetic air in two parallels and later characterized by X-Ray Diffraction and Electron Probe MicroAnalysis combined with deterministic image analysis. Both methods confirm that all samples cooled under the protective atmosphere with 5% CO2 had a higher content of metallic Al (89.4 wt%) than those cooled in ambient air (86.0 wt%), indicating that small amounts of CO2 also inhibit the oxidation rate of dross at an industrial scale.

Graphical Abstract
Study on dynamic mechanical response characteristics and fracture energy dissipation mechanism of sandstones with different saturations under real-time low temperature
Authors: Li Ming , Yu Hao , Zhang Jiazhi , Lin Gang , Zhang Lianying , Chen Yanlong , Zhu Fuqiang , Mao Yiwen , Chen Hang , Ding Zhengbang , Liang Yihang
Published: June 2023

It is of great significance to study the mechanical properties of rocks with different saturations for safe and efficient development of geotechnical engineering in low-temperature environments, such as open-pit mining and tunnel excavation in winter in cold areas, and etc. In this paper, the LT-SHPB test system was used to carry out impact loading tests for sandstones with various saturations at − 20 °C environment. SEM was used to observe the cross-sectional characteristics of the specimens. The distributions of fragments were obtained by screening after impact failure. The energy dissipation model was established during the failure process. The research results indicated that the failure strength, elastic modulus, and peak strain of sandstones showed significant strain rate strengthening. Under the fixed strain rate, as the increase of the water content, the failure strength and elastic modulus and the sensitivity increased first and then decreased, while the peak strain showed the opposite change characteristics. 75% saturation was the turning point of the change. The sandstones under saturated water content exhibited remarkable ductile failure characteristics, while the brittle failure dominated in other conditions. The fundamental reason for this change was the difference between the freezing and frost heave effects of water-bearing specimens under low temperature conditions. The change characteristics of the macroscopic damage degree of sandstones with the strain rate and water content were basically the same as the characteristics of mechanical properties. The higher the internal density, the more the dissipated energy and surface specific energy for the whole failure of the specimen. The energy dissipation difference could directly change the macroscopic failure characteristics.
Identification, prevention, and treatment of Legionella in bath facility water systems in South Korea
Authors: Lee June Hae , Lee Sejin , Yeo Myoung-Souk
Published: June 2023

Legionella bacteria infect people via aerosol transmission. These pathogens can meaningfully affect people with weak immune systems and the older adult population. Legionella proliferate in water systems at temperatures between 25 and 45 °C, the optimum range for bath facilities. Here, we discuss how and where water systems can be contaminated by Legionella in bath facility water systems in South Korea. An epidemiological investigation of Legionella detection data from the Korea Disease Control and Prevention Agency was conducted to understand the tendencies of general outbreaks of water system types in building groups. Onsite investigations were then conducted to identify the causes of contamination in water systems in actual Legionella detection cases. According to annual Legionella detection data, the highest rate of Legionella was detected in hot bathtub water. Onsite investigations revealed that sand filter circulation systems for bathtubs are susceptible to Legionella growth. Overall, this study examined the mechanisms of buidling water systems from a building engineering perspective in order to provide valuable information for future studies and strategies to control Legionella growth in bath facility water systems.
A study on multi-ranged medicinal plants and soil temperature in various sites of Garhwal Himalaya, Uttarakhand
Authors: Balkrishna Acharya , Sharma Ishwar Prakash , Kushwaha Arun Kumar , Kumar Shashi , Arya Vedpriya
Published: June 2023

Mountain ecosystems are particularly fragile while offering important environmental benefits to mankind. The Himalaya, known as the “King of the Mountains”, is the world’s youngest and tallest mountain ecosystem. The Garhwal Himalaya, where this study was conducted, is an integral part of the Himalayan mountain system, which falls under the North Indian state Uttarakhand. The study was carried out in October 2022 with respect to different altitudinal gradients in this area. Plant information was collected from the natives and multi-ranged plants were selected for their distribution. Soil samples were collected for nutrient and microbial analysis. The study was conducted at a total of ten different sites ranging from 328 m (Chilla, Haridwar) to 3510 m (Ghangaria, Chamoli). A total of three multi-ranged plants were selected. The soil temperature decreased with increasing altitudes. This is a first-time study in which multi-ranged medicinal plants were explored and analyzed.
Assessment of concentration of the potentially toxic elements and associated human health risk from particulate matter exposure along road intersections in Ibadan, southwestern Nigeria
Authors: Kolawole Tesleem O. , Olatunji Akinade S.
Published: June 2023

The harmful health effect of suspended particulate matter (PM10) is mostly associated with its mass concentrations and chemical compositions. Therefore, this study focuses on the determination of the particulate matter (PM10) concentrations and their potentially toxic elements (PTEs) composition from different road networks in Ibadan southwestern, Nigeria. In addition, human health risk assessment was estimated from the PTE data. The PM10 samples were collected from different road networks such as national highway roads (NHR), inner-city major roads (ICR), and remote roads (RRD) in Ibadan, Nigeria. The sampling was carried out with a high-volume air sampler (model #15000 manufactured by Science Resource, Walboro, USA) with a PM10 cut-off on a Whatman cellulose filter during the harmattan period. The PM10 concentrations and PTEs compositions (Al, Ba, Cd, Cu, Fe, La, Mo, Mn, Ni, Pb, V, and Zn) were determined by gravimetry and inductively coupled plasma-optical emission spectrometry (ICP-OES) methods (VISTA-MPX manufactured by Varian Incorporation), respectively. The PM10 concentrations in all three road networks were more than 3 folds higher than World Health Organization (WHO), United State Environmental Protection Agency (USEPA), and United Kingdom Environmental Protection Agency (UKEPA) standards (50 µg/m3) for 24 h. The maximum average contents of Ba, Cd, Cu, La, Mn, Pb, and V, were observed at NHR, while that of Al, Fe, Mo, and Zn, were found at ICR. The principal component analysis (PCA) showed that PC1 (Ba, Cd, Cu, La, Mo, Pb, and V) and PC4 (Zn) were characterised by elemental markers of both exhaust emission and non-exhaust emissions, while PC2 (Mn) and PC3 (Al, Fe) were characterised by crustal elements. The Enrichment factor (EF) analysis classified all the PTEs as moderately to very highly enriched, especially in NHR and ICR, except Al, Fe, and to some extent Mn. Both the maximum and average hazard quotient (HQ) levels of Cd, Cu, Mn, Pb, and Zn were < 1, which was within the permissible level. Also, the carcinogenic risk (CR) was also within the permissible limit.
Homogenization of non-symmetric jump processes
Authors: Huang Qiao , Duan Jinqiao , Song Renming
Published: June 2023

We study homogenization for a class of non-symmetric pure jump Feller processes. The jump intensity involves periodic and aperiodic constituents, as well as oscillating and non-oscillating constituents. This means that the noise can come both from the underlying periodic medium and from external environments, and is allowed to have different scales. It turns out that the Feller process converges in distribution, as the scaling parameter goes to zero, to a Lévy process. As special cases of our result, some homogenization problems studied in previous works can be recovered. We also generalize the approach to the homogenization of symmetric stable-like processes with variable order. Moreover, we present some numerical experiments to demonstrate the usage of our homogenization results in the numerical approximation of first exit times.
F.2 Multiplatform molecular analysis of vestibular schwannoma reveals two robust subgroups with distinct microenvironment
Authors: Landry A , Wang J , Suppiah S , Zadeh G
Published: June 2023

Background: Vestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle and poses a significant morbidity for patients. While many exhibit benign behaviour, others have a more aggressive nature. There is a need for a better understanding of the molecular landscape, and important subgroups therein, of this disease. Methods: We select all VS from our tumour bank with both methylation and RNA profiling. Unsupervised clustering methods were used to define two distinct molecular subgroups of VS which were explored using computational techniques including bulk deconvolution analysis, gene pathway enrichment analysis, and drug repurposing analysis. Methylation data from two other cohorts were used to validate our findings. Results: A total of 75 tumours were analyzed. Consensus clustering and similarity network fusion defined two subgroups (“immunogenic” and “proliferative”) with significant differences in immune, stroma, and tumour cell abundance. Gene network analysis and computational drug repurposing found critical differences in targets of immune checkpoint inhibition PD-1 and CTLA-4, the MEK pathway, and the epithelial-to-mesenchymal transition program with associated candidate drug targets, suggesting a need for subgroup-specific treatment/trial design in the future. Conclusions: We leverage computational tools with multi-omic molecular data to define two robust subgroups of vestibular schwannoma with differences in microenvironment and therapeutic vulnerabilities.
F.4 Relationship between poor postoperative pain control and surgical outcomes after elective spine surgery
Authors: Far R , Sajobi TT , Riva-Cambrin J , Casha S , Yang MM
Published: June 2023

Background: Inadequate pain control after spine surgery is common, but its impact on long-term surgical outcomes has not been studied. Accordingly, this study aimed to investigate the relationship between poor postoperative pain control and surgical outcomes. Methods: Consecutive adult patients undergoing elective spine surgery were enrolled. Poor surgical outcome was defined as failure to achieve a minimal clinically important difference (MCID) of 30% improvement on the Oswestry Disability Index or Neck Disability Index at follow-up (3-months, 1-year, 2-years). Poor pain control was defined as a mean numeric rating scale score of >4 within 24-hours postoperatively. Univariable analyses followed by multivariable random-effects models were used, after adjusting for known risk factors that impact surgical outcomes. Results: 42.8% of 1305 patients failed to achieve MCID at follow-up. 56.9% had poor postoperative pain control. Poor pain control was independently associated with failure to achieve MCID (OR 2.15 [95%CI=1.42-3.25], p<0.001), after adjusting for age (p=0.15), sex (p=0.59), PHQ-9 score (p=0.030), ASA physical status >2 (p<0.001), ≥3 motion segment surgery (p=0.003), revision surgery (p=0.032), and follow-up time (p<0.001). Conclusions: Poor pain control 24-hours after elective spine surgery was an independent risk factor for poor surgical outcome. Perioperative strategies to improve pain control may lead to improved outcomes.
P.016 Impact of eptinezumab on patient-reported outcomes in patients with prior preventive treatment failures
Authors: Goadsby PJ , Barbanti P , Ettrup A , Laurberg Christoffersen C , Krog Josiassen M , Phul R , Sperling B , Duong A
Published: June 2023

Background: In DELIVER, eptinezumab reduced migraine frequency and was well tolerated in patients with migraine and prior preventive treatment failures. This analysis evaluated changes in patient-reported outcomes (PROs). Methods: DELIVER (NCT04418765; phase 3b double-blind study) randomized adults with migraine and 2-4 prior preventive treatment failures to eptinezumab or placebo every 12 weeks. The assessed PROs included EuroQol 5-Dimensions 5-Levels visual analogue scale (EQ-5D-5L VAS); 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), most bothersome symptom (MBS), and Migraine-Specific Quality of Life Questionnaire (MSQ, v2.1). Results: Patients received eptinezumab 100mg (n=299), 300mg (n=294), or placebo (n=298). Mean changes from baseline to Wk12 in EQ-5D-5L VAS scores were 2.0 (100mg, P=0.0007) and 4.4 (300mg, P<0.0001) versus -3.1 (placebo), and were maintained or further improved to Wk24 (2.0, 5.2, -2.8, respectively). Mean baseline HIT-6 total scores were ~66.4, with mean changes of -6.9 (100mg, P<0.0001) and -8.5 (300mg, P<0.0001) versus -3.1 (placebo) at Wk12 that were further improved through Wk24 (-8.9 and -9.9 vs -3.9). PGIC, MBS, and MSQ domain scores showed greater improvement for eptinezumab than placebo. Conclusions: In adults with migraine and prior preventive treatment failures, eptinezumab robustly improved health-related quality of life and migraine-related burden over 24 weeks versus placebo.
P.026 Frontal cognitive-behavioural deficits in patients with anti-leucine-rich glioma-inactivated protein 1 antibody encephalitis
Authors: Lee S , Climans SA , Day GS , Hébert J , Lapointe S , Ramos RC , Steriade C , Wennberg RA , Muccilli A , Tang-Wai DF
Published: June 2023

Background: Cognitive impairment is a common manifestation of anti-LGI1 encephalitis and is typically defined as prominent memory deficits. We frequently encounter frontal cognitive-behavioural deficits when evaluating these patients, but this has yet to be well described in the literature. Methods: Patients with anti-LGI1 encephalitis were retrospectively identified from three tertiary centres in Toronto, Ontario between 2013 and 2022. Their medical records were evaluated and frontal features were categorized based on diagnostic criteria for behavioural variant frontotemporal dementia (bvFTD). Results: Nineteen patients were identified (median age 60 years [range 18–84]; 10 [52.6%] male). Eighteen (94.7%) had frontal cognitive-behavioural symptoms. Two developed these symptoms during treatment with steroids and were excluded from further analysis. The remaining 16 presented with behavioural disinhibition (n=13), apathy or inertia (n=6), perseverative, stereotyped or compulsive/ritualistic behaviours (n=6), hyperorality and dietary changes (n=4), a neuropsychological profile with predominant deficits in executive tasks (n=4), and loss of sympathy or empathy (n=4). Nine (47.3%) met diagnostic criteria for possible bvFTD. Anterograde memory impairment was common (n=14). Of the 16 patients with frontal features, 6 had faciobrachial dystonic seizures. Conclusions: Patients with anti-LGI1 encephalitis exhibit frontal cognitive-behavioural symptoms in addition to memory impairment. Clinicians should consider anti-LGI1 encephalitis in the differential diagnosis of bvFTD.
P.027 Autoimmune encephalitis: modifiable and non-modifiable predictors of relapse
Authors: Hansen M , Hahn C
Published: June 2023

Background: Approximately 25% of encephalitis cases in North America are autoimmune (AIE). For most forms of AIE, it is unclear which patients have the highest relapse risk and whether standard treatments reduce this risk. Our objective was to determine the overall risk of relapse and whether chronic immunosuppressive therapy modifies that risk. Methods: We performed a chart review consisting of all patients with AIE presenting to the Calgary Neuro-Immunology Clinic and Tom Baker Cancer Centre between 2015 and 2020. Predictors of relapse were determined with use of t-test. Results: Outcome data was assessable in 39 patients, 17/39 (44%) patients relapsed, and most relapses (76%) occurred within 3 years. Patients not on any immunosuppression at the time of relapse had a greater increase in CASE score, a proxy for presentation severity, at relapse compared to those on immunosuppression (p=0.0035). Conclusions: The risk of relapse in AIE is high (44%). Immunosuppression at the time of relapse, which may occur up to 3 years after initial presentation, lessens the relapse severity, although it remains unclear if it can reliably prevent relapses. Our data enforces the importance of long-term follow up and that ongoing immunosuppression may be helpful, particularly in the first 3 years after initial presentation.
P.029 Relevance and home completion rate of patient reported outcome measures set in chronic inflammatory neuropathies
Authors: Ogalo E , Smith C , Ashe M , Beadon K , Chapman K
Published: June 2023

Background: Patient-centred care is important in the management of chronic inflammatory neuropathies (CIN) given the heterogeneity in disease course and treatment response. Patient Reported Outcome Measures (PROMs) support value-based healthcare by aligning treatment goals with what matters most to patients. This study evaluated the relevance of PROMs to patients and the feasibility of use in clinical management. Methods: PROMs assessing quality of life, pain, fatigue, and overall disability were collected prospectively from 32 patients with CIN every three months over a 12-month period. Patients provided feedback on relevance of the measures. PROMs were sent electronically prior to the visit. Results: Completion rate was 92%. Home vs. in-clinic completion increased from 56% to 85% over the course of the study. There was an association between completion of the panel and perceived relevance. The PROMs were consistently rated as highly relevant, with disability and fatigue measures rated highest. Conclusions: PROMs are appraised as highly relevant among patients with CIDP and MMN. Patients require support initially but adapt to electronically delivered home completion of questionnaires. We recommend inclusion of PROMs into routine clinical practice as a means of capturing aspects of health that are not easily assessed in a clinic visit.
P.034 Minimal symptom expression following treatment with efgartigimod in patients with Generalized Myasthenia Gravis
Authors: Siddiqi Z , Howard JF , Bril V , Vu T , Karam C , Pasnoor M , Muppidi S , Peric S , Murai H , Ulrichts P , T’joen C , Utsugisawa K , Verschuuren J , Mantegazza R
Published: June 2023

Background: Efgartigimod is a human IgG1 antibody Fc-fragment that reduces IgG levels through FcRn blockade. A key efficacy indicator in the treatment of IgG autoantibody-mediated generalized myasthenia gravis (gMG) is improvement in MG-ADL score. Methods: The ADAPT phase 3 trial evaluated safety and efficacy of efgartigimod in patients with gMG, including reaching and maintaining of minimal symptom expression (MSE; defined as an MG-ADL total score of 0 or 1). Results: 167 patients (AChR-Ab+, n=129; AChR-Ab-, n=38) were randomized to receive treatment cycles of 4 weekly infusions of efgartigimod or placebo. Significantly more AChR-Ab+ efgartigimod-treated patients achieved MSE during cycle 1 compared to placebo-treated patients (40.0% [n=26/65] vs 11.1% [n=7/63; P<0.0001]). In cycle 2, 31.4% (n=16/51) of AChR-Ab+ patients in the efgartigimod cohort achieved MSE compared to none in the placebo cohort. MG-ADL score improved by ≥6 points in 56.9% of AChR-Ab+ efgartigimod-treated patients compared to 20.6% of placebo-treated patients in cycle 1. Most patients achieved MSE by week 4 of a cycle, paralleling early reduction in IgG levels, and MSE duration ranged from 1 to ≥10 weeks. Adverse events were predominantly mild to moderate. Conclusions: Efgartigimod treatment resulted in more patients with AChR-Ab+ gMG achieving both MSE and clinically meaningful MG-ADL improvements.
P.042 Could Live Cell-Based Assay increase the acetylcholine receptor autoantibodies seropositivity in patients with clinical suspicion of myasthenia gravis?
Authors: Kumar P , Kaur N , Mousavi A , Kihara E , Aziz T , Cruz A , Oger J , Frykman H
Published: June 2023

Background: AChR antibodies (Abs) in Myasthnia Gravis (MG) are detected in approximately 50% of ocular and 85% of generalized MG by the current gold standard radioimmunoprecipitation assay (RIPA). Recently, fixed and lived Cell-Based assays (L-CBA) are developed. We clinically validated our in-house L-CBA in detecting AChR Ab in clinically suspected MG patients. Methods: Between January 2020 and April 2022, we assayed 10167 sera for AChR Ab by RIPA. We also assayed 4349 of AChR Ab seronegative sera of the above suspected MG samples for anti-MuSK Ab by RIPA. Then 1228 sera of double seronegative and/or borderline AChR Ab was assessed by L-CBA for AChR Ab. For clinical validation, we obtained clinical information on 36 seropositive cases for AChR Ab by L-CBA. Results: We found additional eighty-four cases seropositive for AChR Ab by L-CBA. The clinical information was obtained for 36 cases and based on their final diagnosis, twenty had generalized MG, thirteen had ocular MG, 2 not yet diagnosed and 1 case was of not-MG. Conclusions: The L- CBA has demonstrated improved sensitivity and higher diagnostics performance than RIPA. The L-CBA allowed improved clinical diagnosis and increased seropositivity (by 7%) in clinically suspected MG patients who were earlier seronegative/borderline for AChR Ab by RIPA.
P.050 Effect of lemborexant on sleep architecture in adult and elderly subjects with mild to severe obstructive sleep apnea
Authors: Zammit GK , Cheng JY , Hall N , Shah D , Moline M
Published: June 2023

Background: Obstructive sleep apnea (OSA) may be associated with sleep difficulties and decreased rapid eye movement (REM) sleep. Lemborexant (LEM), a dual-orexin-receptor-antagonist approved to treat adults with insomnia, increases total sleep time (TST) and REM sleep, and demonstrated respiratory safety in subjects with mild through severe OSA. Sleep architecture was thus analyzed after LEM treatment in those subjects. Methods: Studies E2006-A001-102 and E2006-A001-113 enrolled adults with mild (apnea-hypopnea index [AHI] ≥5 – <15) or moderate (AHI ≥15 – <30)/severe (AHI ≥30) OSA without insomnia. Subjects received LEM 10mg (LEM10) or placebo (PBO) in 2 treatment periods, Days 1 (D1) and 8 (D8), separated by ≥14 days. Least-squares-mean (minutes) for each sleep stage was compared. Treatment-emergent adverse events (TEAEs) were recorded. Results: Thirty-nine subjects with mild and 33 with moderate/severe OSA were randomized. On both days, TST was significantly higher in the LEM period for these subjects. Total non-REM on D1 in subjects with mild OSA and on both days in subjects with moderate/severe OSA were higher with LEM than PBO; REM also significantly increased in subjects with mild and moderate/severe OSA. Most TEAEs were mild. Conclusions: In OSA subjects without insomnia, LEM was associated with higher TST, non-REM, and REM versus PBO.
P.052 Trazodone for treating insomnia: abuse and safety risks
Authors: Moline M , Juday T , Cheng JY , Henningfield J , Buchhalter A , Sembower MA , Pype S , Wickwire EM , Procyshyn RM
Published: June 2023

Background: Although unapproved by the FDA for treating insomnia, trazodone is commonly prescribed in the US partly due to lack of scheduling, hence it’s perceived as safer than z-drugs and benzodiazepines. This study investigated trazodone abuse/dependence potential and safety risks. Methods: Cases involving trazodone or benzodiazepines (temazepam, triazolam, estazolam) frequently prescribed for insomnia were identified from the FDA Adverse Events Reporting System (FAERS), National Forensic Laboratory Information System (NFLIS) for confiscation data, and the American Association of Poison Control Centers’-National Poison Data System (AAPCC-NPDS). Drug-related falls risk was assessed from claims databases. Results: FAERS included 11,228 trazodone and 5120 benzodiazepine reports. Of these, drug-abuse and drug-dependence cases with trazodone were lower than benzodiazepines (drug-abuse: 6.4%/12.6%; drug-dependence: 1.1%/3.6%). Serious cases (81.8%/83.9%) and deaths (35.4%/36.0%), were similar between trazodone and benzodiazepines. NFLIS reported 612/1,575,874 (0.04%) drug-seizure cases that included trazodone. AAPCC-NPDS reported 22,225/1,446,011 (1.54%) total case mentions of trazodone/all pharmaceuticals and 8445 trazodone-related single-exposure cases. Falls risk (1year-period) in Medicare beneficiaries ≥65y and commercially-insured enrollees ≥18y was reported for trazodone and benzodiazepines: Medicare, 9.5%/11.3%; Commercially-insured: 4.6%/3.7%. Conclusions: Trazodone has abuse/dependence potential and important safety risks. Given limited data from well-controlled studies and off-label use, re-evaluation of trazodone prescribing rates in patients with insomnia is warranted.
P.053 Efficacy of lemborexant in adults with insomnia is supported by improvements in both objective and subjective measures
Authors: Moline M , Morin CM , Kumar D , Lundwall C , Pinner K , Ramos B , Desautels A
Published: June 2023

Background: Improvements in sleep-onset, maintenance, and daytime functioning, are all important outcomes for the treatment of insomnia. These improvements are usually assessed by objective or patient-reported (subjective) measures or both. Some sleep-promoting drugs do not report consistently aligned subjective and objective outcomes. Therefore, we examined concordance in change from baseline (CFB) in sleep parameters (objective/subjective measures) and daytime functioning (subjective measures) in the clinical program of lemborexant (LEM), a dual-orexin receptor antagonist. Methods: Study E2006-G000-304 (NCT02783729), a 1-month, placebo (PBO)- and active-controlled (zolpidem; not discussed here) study, and Study E2006-G000-303 (NCT02952820), a 12-month, randomized, PBO-controlled study (first 6-months), evaluated the efficacy/safety of LEM 5mg (LEM5) and LEM 10mg (LEM10) in subjects with insomnia disorder. The primary/secondary endpoints in both studies included multiple objective/subjective sleep parameters and patient-reported measures, which were assessed for concordance. Results: In both studies, statistically significant improvements with LEM5/LEM10 were reported in multiple objective and patient-reported measures versus PBO, showing a concordance of results, with observed improvements continuing through 12 months. LEM was well tolerated; most treatment-emergent adverse events were mild/moderate. Conclusions: When deciding which sleep agent to prescribe, it is important that improvement can be demonstrated in both objective and patient-reported measures. LEM treatment showed concordance among observed measures.
P.054 Older subjects with insomnia disorder and comorbid pain at baseline: response to Lemborexant
Authors: Kaplan A , Cheng JY , Suzuki M , Kumar D , Moline M , Pappadopulos E
Published: June 2023

Background: There is a well-established reciprocal relationship between pain and poor sleep. Therefore, we evaluated whether an approved sleep-promoting drug, lemborexant (LEM), could improve sleep in older adults who reported both insomnia and pain. Methods: Study E2006-G000-304 (NCT02783729) was a 1-month, placebo (PBO)- and active-controlled study in subjects (age ≥55y) with insomnia disorder. Those reporting some/severe pain on the pain/discomfort dimension of the EQ-5D-3L at baseline were included. Subjects were randomized to placebo (PBO), LEM 5mg (LEM5), 10mg (LEM10) or zolpidem (not reported here). Changes from baseline (CFB) in objective sleep parameters latency-to-persistent sleep (LPS) and total-sleep-time (TST) were analyzed in paired polysomnograms. Results: 183/743 (24.6%) subjects in the PBO (n=55/208[26.4%]), LEM5 (n=78/266[29.3%]) and LEM10 (n=50/269[18.6%]) treatment groups reported some/extreme pain at baseline, with median LPS (minutes): 31.0, 29.4, 42.1, respectively. Respective median CFB for LPS at the beginning (Nights[NT]1/2: +2.5, –8.4, –15.8; P<0.005) was significantly larger/decreased for LEM5/LEM10 versus PBO and LEM5 at treatment end (NT29/30: –7.1, –9.9, –9.0; P=0.031). Mean baseline TST (minutes) was 335.3 (PBO), 336.3 (LEM5), 324.3 (LEM10), and mean CFB was significantly larger/increased (P<0.001) for LEM5/LEM10 versus PBO at NT1/2 and NT29/30. Conclusions: Results suggest LEM may effectively treat insomnia in older adults with comorbid pain.

Support: Eisai Inc.
P.055 Does age matter in the CaRMS neurology match?
Authors: Young A , Ng M
Published: June 2023

Background: The Canadian Resident Matching Services (CaRMS) collects comprehensive data on residency applicants. However, match outcomes by age were not reported. It was unclear whether older applicants found it more difficult to match to the specialties of their choice, i.e. does age influence match? We ask in particular, does age affect the neurology match? Methods: In response to written request, CaRMS provided pre-pandemic age data for 2015-2019 inclusive, divided into group 1 (30 or younger) and group 2 (31-40 inclusive). Results: In 2019, 39 of the 69 group 1 and 6 of the 23 group 2 neurology applicants were matched into neurology (odds ratio (OR)=2.2|p=0.01). In contrast, urology (OR=6|p=0.001) had the worst odds and family medicine (OR=1.2|p=0.002) had the best odds for older applicants in 2019. Average OR (2015-2019) was 1.6 for neurology, 3.1 for urology, 1.3 for family medicine, and between 1.3 and 3.1 for nearly all other specialties. Conclusions: Older neurology applicants were less likely to match than younger peers while match probability was statistically significantly lower in nearly all specialties for older applicants.
P.059 Cerebral small vessel disease burden as a predictor of longitudinal cognition in patients with transient ischemic attack
Authors: Denroche B , Chacinski D , Wang M , Ganesh A , Barber P
Published: June 2023

Background: Cerebral small vessel disease (CSVD) is associated with stroke, cognitive decline, and dementia. In this study, we examined how SVD is longitudinally related to cognitive performance in transient ischemic attack (TIA) patients compared to controls. Methods: We rated CSVD at baseline on MRI in TIA patients (n=197) and controls (n=113) for microbleeds (CMB), lacunes, white matter hyperintensities (WMH), and perivascular spaces (EPVS). Neuropsychological testing was administered across 5 years using the following assessments: BVMT, RAVLT, TMTA, TMTB, WAIS-R. Results: Periventricular WMH≥2 yielded slower performance on TMTB across all timepoints (adjusted difference 20.3 seconds, 95%CI [8.4,32.2]), as did deep WMH≥2 (20.1 sec, 95%CI [7.6,32.6]). Basal ganglia EPVS>20 performed slower on TMTA (10.1 sec, 95%CI [4.7,15.5]) and TMTB (21.2 sec, 95%CI [3.4,39.1]). Centrum semiovale EPVS>20 performed slower on TMTB (27.2 sec, 95%CI [10.6,43.8]) and worse on WAIS-R at 5-years (-18.6, 95%CI [-35.0,-2.2]). Lacunes≥3 performed slower on TMTA across all timepoints (4.0 sec, 95%CI [0.1,7.9]). Total CSVD≥2 performed slower on TMTA (3.7 sec, 95%CI [0.4,7.0]) and TMTB (13.9 sec, 95%CI [2.9,24.9]) across 5 years. When stratifying results, associations were generally found in TIA, not controls. Conclusions: Findings demonstrate that CSVD is associated with poorer cognitive performance longitudinally, and is more pronounced in TIA compared to control.
P.060 Teamwork makes dreamwork: a stroke of genius
Authors: Casserly CS , Dilkes D
Published: June 2023

Background: Interprofessional collaboration is at the center of much of our work as Neurologists, yet often Medical Education inadequately prepares students for the complexities of interdisciplinary practice. Authentic, meaningful Interprofessional Education (IPE) requires consideration in involement of all individuals involved in interprofessional health care (IPHC) (Holbrook, 2013). Methods: We have collected authentic stories of acute stroke care through interviews with patients and other health care professionals on the acute stroke care team. Drawing on these narratives, we have crafted a multimedia story combining film, photography, and art. Results: This case will be integrated into Western University’s Undergraduate Medical Education curriculum but is intended to be a valuable tool for teaching IPE competencies in all IPE contexts. All media will be available thorugh Western Libaries open access Health Education Media Library. Main learning outcomes include improved recognition of HCP roles and the vital and diverse contributions of each team member. Conclusions: Drawing on the experiences of real stroke patients, families, and all other HCPs, we have crafted a rich educational case portraying the complexity of IPHC that will allow learners to reflect on the complex roles of health professoinals in a successful interprofessional team.
P.068 Quality improvement in Infantile Spasms through standardization: a tertiary-care centre retrospective chart review implementation study
Authors: Sjonnesen KM , Appendino J , Buchhalter J , Ho A , Jacobs-Levan J , Scantlebury M
Published: June 2023

Background: Infantile Spasms (IS) is a rare epilepsy syndrome with characteristic features, and a strong consensus regarding treatment strategies. Clinical care pathways provide standardized and evidence-based patient care, support care quality and improve patient outcomes. Standardized electronic notes may support data collection and quality. After the concurrent implementation of an IS pathway and standardized electronic note at the Alberta Children’s Hospital in 2015, improvements in patient outcomes and quality of care were anticipated. Methods: A single-centre, retrospective chart review of patients diagnosed with Infantile spasms in Alberta, Canada from 2011-2019 was completed. Patient characteristics and outcomes were analyzed by pre-pathway and post-pathway implementation status. Results: Rates of 3-month spasm remission, and of remission without relapse did not significantly differ between pre- and post-pathway cohorts. Rates of 2-week spasm remission were not obtainable from a significant proportion of pre-pathway patient records when compared to the post-pathway group, indicating patient record quality improved following the electronic note implementation. A significant proportion of patients received Prednisolone as their first treatment for IS post-pathway implementation compared to pre-pathway (p<0.001). Conclusions: A single-centre experience with concurrent implementation of an IS pathway and standardized electronic note demonstrated no significant changes in patient outcomes. Potential improvements for patient care are identified.
P.076 Tone management: an environmental scan of current management practices across Canada
Authors: Tran T , Thipse M , Tsampalieros A , Webster R , McCormick A , Alazem H , Venkateswaran S , Cheung K , Smit K , Tu A
Published: June 2023

Background: Currently, there are no standardized approaches to care or evaluation for tone dysfunction in Canada. The study authors hypothesize that there is significant practice variation across the country. This environmental scan is aimed to describe the current practice for management of patients with hypertonia across Canada. Methods: A web-based survey was developed by the authors with a multi-disciplinary approach and sent to representative rehabilitation sites in each province. All statistical analyses were performed using the R statistical software version 4.0. Results: CP was found to be the most common diagnosis for tone dysfunction, with 58% (7/12) of sites diagnosing greater than 20 new patients per year. All 12 sites offered oral baclofen and gabapentin, and 92% of sites offered trihexyphenidyl. Botulinum toxin injections were offered at 50% of sites. Upper and lower extremity procedures were offered in 83% of the sites. In 8 of 12 sites (67%), patients were seen within a formal multidisciplinary clinic to manage hypertonia. Conclusions: The information gained from this study provides some insight into the current practice across Canada for children with hypertonia. This study may assist in the development of a national, standardized strategy to tone management, potentially facilitating more equitable access to care for patients.
P.099 A novel electrophysiologic reflex in neurovascular compression syndromes serving as a marker of pain resolution
Authors: Persad A , Norton JA , Vitali AM
Published: June 2023

Background: Radiofrequency rhizotomy is a commonly used percutaneous technique for treatment of trigeminal neuralgia especially in cases not eligible for microvascular decompression. This technique is usually performed with the patient under conscious sedation. We devised a method for performance of this technique under general anesthetic with neurophysiology monitoring. Methods: The patient is put under general anaesthetic and EMG monitoring is set up. Needles are placed in temporalis muscle, masseter and mylohyoid or anterior belly of digastric. Resting activityis monitored. Rhizotomy is then performed under fluoroscopic guidance, with monitoring of EMG potentials pre- and post-lesioning, with specific attention paid to presence of an abnormal electrophysiologic reflex. Results: A total of 38 procedures were performed in 23 patients. Of these, 15 were revision procedures. Patients had improvement from BNI pain scale 3.8 ±0.8 to 1.3 ±1.5, and had a reduction in number of medications from 1.9 ±1.0 to 0.8 ±0.9. Survey results indicate greater practitioner satisfaction with this technique. Conclusions: Radiofrequency rhizotomy can be performed under GA with IONM guidance with good results. We present a novel method for EMG-based monitoring. Further study is required to validate this technique.