Background: Antibodies directed against acetylcholine receptor (AChR) are absent in approximately 15% of patients with gMG. Approved treatment options represent an unmet need in the AChR-antibody (Ab)- gMG population. Efgartigimod is an immunoglobulin G1 (IgG1) antibody Fc fragment that selectively reduces IgG levels by blocking neonatal Fc receptor (FcRn)-mediated IgG recycling. Here, we describe efgartigimod efficacy in AChR-Ab- participants with gMG receiving either efgartigimod IV or subcutaneous (SC) efgartigimod PH20 (coformulated with recombinant human hyaluronidase PH20) across clinical studies. Methods: Post hoc analyses were conducted to examine efficacy and safety of efgartigimod IV and/or efgartigimod PH20 SC in AChR-Ab- participants in ADAPT/ADAPT+ and ADAPT-SC/ADAPT-SC+ trials. Results: Among pooled AChR-Ab- participants (n=56), mean (SE) MG-ADL total score improvement from baseline to Week 3 was -3.7 (Cycle 1: 0.44 [n=55]). Consistent MG-ADL improvements occurred with repeated cycles. Clinically meaningful improvements (CMI; ≥2-point MG-ADL decrease) occurred in 76.4% (n=42/55) of participants (Cycle 1, Week 3). In Cycle 1, 23.2% (n=13/56) of participants achieved minimal symptom expression (MG-ADL 0-1). Similar efficacy results occurred across all cycles. Overall safety profile was similar between AChR-Ab+ and AChR-Ab- participants. Conclusions: Both efgartigimod IV and efgartigimod PH20 SC were well tolerated and led to CMI in participants with AChR-Ab- gMG.

Background: In the Phase 3 MycarinG study (MG0003/NCT03971422), one 6-week cycle of rozanolixizumab significantly improved myasthenia gravis (MG)-specific outcomes versus placebo. After MycarinG, patients could enrol in open-label extension studies (MG0004 then MG0007, or MG0007 directly). Methods: In MG0004 (NCT04124965), patients received once-weekly rozanolixizumab 7mg/kg or 10mg/kg for ≤52 weeks. In MG0007 (NCT04650854), after a cycle of rozanolixizumab 7mg/kg or 10mg/kg, subsequent cycles were based on symptom worsening at the investigator’s discretion. Pooled data are reported across MycarinG, MG0004 (first 6 weeks) and MG0007 (final data) for patients receiving ≥2 symptom-driven cycles (efficacy; ≤13 cycles) or ≥1 cycle (safety). Results: 196 patients received ≥1 rozanolixizumab dose of whom 129 received ≥2 symptom-driven cycles (7mg/kg: n=70; 10mg/kg: n=59). Treatment response was maintained from Cycles 1–13: mean change from baseline to Day 43 in MG-Activities of Daily Living score ranged from -3.2 to -4.9 (7mg/kg) and -3.2 to -6.7 (10mg/kg). Quantitative MG and MG Composite scores also improved. Treatment-emergent adverse events (TEAEs) did not increase with repeated cyclic treatment, and most were mild/moderate; the most common event was headache. Conclusions: Rozanolixizumab showed consistent improvements across MG-specific outcomes up to 13 cycles and repeated cyclic treatment was generally well tolerated. Funding: UCB.

Mylonchulus laocaiensis sp. n. recorded from Vietnam, is described and illustrated, and its phylogenetic relationship within the Mylonchulidae family and Mononchida order are analysed. The new species is characterized by medium body size (L = 1.0–1.5 mm); buccal cavity goblet shaped, 26–29 × 14–16.5 μm or 1.8 (1.7–1.9) times as long as wide; posterior position of dorsal tooth apex (79%–88% from the base of buccal cavity); a small subventral tooth present on subventral wall; pars refringens vaginae with faint and small (2.5 × 1.7 μm) teardrop-shaped pieces, short pars distalis vaginae; male with short spicules (54–57 μm) with rounded head. The molecular data (18S and 28S rDNA) are provided for the new species.

Background: Treatment of generalized myasthenia gravis (gMG) with reduced steroid dosages may minimize steroid-associated AEs. Corticosteroid dosage changes were not permitted during the 26-week, CHAMPION MG study of ravulizumab in adults with anti-acetylcholine receptor antibody-positive (AChRAb+) gMG. Participants who completed the study could receive ravulizumab in the open-label extension (OLE; NCT03920293); corticosteroid adjustments were permitted. Methods: Patients could receive intravenous ravulizumab (blind induction or bridging dose at Week 26 [OLE start] for those previously receiving placebo or ravulizumab, respectively, then 3000–3600 mg at Week 28 and every 8 weeks thereafter) for ≤4 years. Results: Among 161 patients (78 ravulizumab, 83 placebo) who entered the OLE and received ravulizumab for ≤164 weeks, 113 received oral or enteral corticosteroids during the OLE; the proportion treated with >10 mg/day corticosteroids decreased from 58% (n=66) at first OLE dose to 37% (n=42) (35 [31%] received ≤5 mg/day and 71 [63%] received ≤10 mg/day) at last reported dose. Fourteen patients (12%) discontinued corticosteroids. The mean (SD) corticosteroid dosage/patient decreased from 17.5 (11.9) mg/day at first OLE dose to 11.7 (10.9) mg/day at last assessment. Conclusions: Ravulizumab decreased corticosteroid use in patients with AChRAb+ gMG, suggesting a steroid-sparing role for ravulizumab.

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.

Background: Efgartigimod, a human IgG1 antibody Fc-fragment, reduces IgG levels through neonatal Fc receptor blockade. Patients with anti-acetylcholine receptor antibody–negative (AChR-Ab–) generalized myasthenia gravis (gMG) comprise 15%-20% of the gMG population and have limited approved treatment options. We evaluated long-term safety and efficacy of efgartigimod in AChR-Ab– patients from ADAPT/ADAPT+ (open-label extension). Methods: ADAPT evaluated safety and efficacy of efgartigimod versus placebo in AChR-Ab+ (n=129) and Ab– (n=38) patients with gMG. This integrated analysis includes 37 AChR-Ab– patients who received ≥1 dose of efgartigimod in ADAPT/ADAPT+ through October 2020 (median[range] follow-up: 453[85-721] days). Responder status was defined as ≥2-point (MG-ADL) and ≥3-point (QMG) improvement for ≥4 consecutive weeks (with first improvement 1 week after last infusion). Results: Among AChR-Ab– patients in ADAPT (cycle 1), 68.4% (13/19) efgartigimod-treated were MG-ADL responders (placebo, 63.2% [12/19]), and 52.6% (10/19) were QMG responders (placebo, 36.8% [7/19]). In the integrated ADAPT/ADAPT+ analysis (cycle 1), AChR-Ab– patients improved from baseline in MG-ADL/QMG scores, with consistent improvements across multiple subsequent cycles. No clinically meaningful differences in safety or efficacy outcomes between AChR-Ab+ and Ab– patients occurred. Conclusions: Long-term treatment (median >1 year) with efgartigimod was well tolerated and associated with clinically meaningful improvements in MG-ADL/QMG scores in AChR-Ab– patients.

Background: Efgartigimod is a human IgG1 antibody Fc-fragment that reduces total and pathogenic IgG autoantibody levels through FcRn blockade. ADAPT was a phase 3 trial evaluating efgartigimod in patients with generalized myasthenia gravis (gMG). Patients who completed ADAPT could enroll in ADAPT+ (open-label extension). Methods: Efgartigimod (10 mg/kg intravenous) was administered in cycles of 4 weekly infusions, with subsequent cycles initiated based on clinical evaluation. ADAPT+ evaluated long-term safety and tolerability of efgartigimod in patients with gMG. Efficacy was assessed utilizing MG-ADL and QMG scores. Results: Of 167 patients from ADAPT, 151 (90%) entered ADAPT+, and 145 received ≥1 cycle as of January 2022. Over 217.55 patient-years of follow-up (mean duration per patient, 548 days), incidence of adverse events did not increase with subsequent cycles. AChR-Ab+ patients with ≥1 year of follow-up across ADAPT/ADAPT+ (n=95) received a median (range) 5.0 (0.4–7.6) cycles per year. All AChR-Ab+ patients (n=111) demonstrated consistent improvements (mean change [SE], week 3 of cycle 1) in MG-ADL (-5.0 [0.33]; up to 14 cycles) and QMG (-4.7 [0.41]; up to 7 cycles) scores during each cycle. Conclusions: These ADAPT+ analyses suggest long-term efgartigimod treatment is well tolerated and efficacious. Additional final data cut analyses will be presented at CNSF 2023.

Introduction: Prevalence and incidence of delirium in older patients admitted to acute and long-term care facilities ranges between 9.6% and 89% but little is known in the context of emergency department (ED) incident delirium. Literature regarding the incidence of delirium in the ED and its potential impacts on hospital length of stay (LOS), functional status and unplanned ED readmissions is scant, its consequences have yet to be clearly identified in order to orient modern acute medical care. Methods: This study is part of the multicenter prospective cohort INDEED study. Three Canadian EDs completed the two years prospective study (March-July 2015 and Feb-May 2016). Patients aged 65 years old, initially free of delirium with an ED stay 8hours were followed up to 24h after ward admission. Patients were assessed 2x/day during their entire ED stay and up to 24 hours on hospital ward by research assistants (RA). The primary outcome of this study was incident delirium in the ED or within 24 h of ward admission. Functional and cognitive status were assessed using validated Older Americans’ Resources and Services and the Telephone Interview for Cognitive Status- modified tools. The Confusion Assessment Method (CAM) was used to detect incident delirium. ED and hospital administrative data were collected. Inter-observer agreement was realized among RA. Results: Incident delirium was not different between sites, nor between phases, nor between times from one site to another. All phases confounded, there is between 7 to 11% of ED related incident delirious episodes. Differences were seen in ED LOS between sites in non-delirious patients, but also between some sites for delirious participants (p<0.05). Only one site had a difference in ED LOS between their delirious and non-delirious patients, respectively of 52.1 and 40.1 hours (p<0.05). There is also a difference between sites in the time between arrival to the ED and the incidence of delirium (p=0.003). Kappa statistics were computed to measure inter-rater reliability of the CAM. Based on an alpha of 5%, 138 patients would allow 80% power for an estimated overall incidence proportion of 15 % with 5% precision.. Other predictive delirium variables, such as cognitive status, environmental factors, functional status, comorbidities, physiological status, and ED and hospital length of stay were similar between sites and phases. Conclusion: The fact that incidence of delirium was the same for all sites, despite the differences of ED LOS and different time periods suggest that many other modifiable and non-modifiable factors along LOS influenced the incidence of ED induced delirium. Emergency physician should concentrate on improving senior-friendly environment for the ED.

Introduction: It is documented that physicians and nurses fail to detect delirium in more than half of cases from various clinical settings, which could have serious consequences for seniors and for our health care system. The present study aimed to describe the rate of documented incident delirium in 5 Canadian Emergency departments (ED) by health professionals (HP). Methods: This study is part of the multicenter prospective cohort INDEED study. Patients aged 65 years old, initially free of delirium with an ED stay 8hours were followed up to 24h after ward admission. Delirium status was assessed twice daily using the Confusion Assessment Method (CAM) by trained research assistants (RA). HP reviewed patient charts to assess detection of delirium. HP had no specific routine detection of delirious ED patients. Inter-observer agreement was realized among RA. Comparison of detection between RA and HP was realized with univariate analyses. Results: Among the 652 included patients, 66 developed a delirium as evaluated with the CAM by the RA. Among those 66 patients, only 10 deliriums (15.2%) were documented in the patients medical file by the HP. 54 (81.8%) patients with a CAM positive for delirium by the RA were not recorded by the HP, 2 had incomplete charts. The delirium index was significantly higher in the HP reported group compared to the HP not reported, respectively 7.1 and 4.5 (p<0.05). Other predictive delirium variables, such as cognitive status, functional status, comorbidities, physiological status, and ED and hospital length of stay were similar between groups. Conclusion: It seems that health professionals missed 81.8% of the potential delirious ED patients in comparison to routine structured screening of delirium. HP could identify patients with a greater severity of symptoms. Our study points out the need to better identify elders at risk to develop delirium and the need for fast and reliable tools to improve the screening of this disorder.

Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.

Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, is characterized by prolonged maternal stress, undernutrition and dehydration. Maternal stress and malnutrition of pregnancy are linked to poor neonatal outcome and associated with poor adult health, and we recently showed that in utero exposure to HG may lead to increased risks of psychological and behavioral disorders in the offspring. In addition, we have shown familial aggregation of HG, which is strong evidence for a genetic component to the disease. In this study, we compare the rates of psychological and behavioral disorders in 172 adults with and 101 adults without a sibling with HG. The rate of emotional/behavioral disorders is identical (15%) in both groups. The results suggest that the etiology of HG is not likely to include genetic factors associated with emotional and behavioral disorders. In addition, this study provides evidence that the increased incidence of psychological/behavioral disorders among offspring of women with HG is attributable to the HG pregnancy itself, rather than to confounding genetic factors linked to HG.

A high proportion of plant nutrients present in animal feed are excreted and therefore animal manure can be an important source of nitrogen (N) for crop production if losses of plant nutrients to the environment during storage and processing are minimized. The present study examines gaseous N losses from stored pig slurry and during composting of solid manure as affected by protein and fibre content in the feed and manure management. Two slurry storage treatments (with and without cover) and three additives to solid manure composting (straw only, straw+lime and straw+superphosphate) were examined for three common types of pig feed in Vietnam (low-protein high-fibre, medium-protein medium-fibre and high-protein low-fibre).

Feed type was found to affect the N content in pig slurry or manure and thus potential N losses. The fraction of N loss caused by N emission from covered slurry storage was 0·25–0·30 of initial N content, while that from uncovered slurry was 0·60–0·70. After 90 days of storage, 1·15–1·20 times the initial ammonium-N (NH4-N) was found in the covered slurry and 0·40–0·50 in the uncovered. The fraction of N lost during composting with superphosphate was 0·25–0·35 of initial total N, while with lime or straw the total N loss was 0·45–0·55. With added superphosphate, 1·25–1·60 times the initial NH4-N in manure was found in the compost after 80 days compared with only 0·11–0·22 for lime and 0·22–0·36 for straw only. Covering stored slurry and addition of superphosphate when composting solid pig manure are thus important methods for Vietnamese farmers to minimize N losses and produce compost with a high content of plant-available N.

Invasive pneumococcal disease (IPD) notifications are used to monitor IPD vaccination programmes. We conducted sequential deterministic data-linkage between IPD notifications and hospitalization data in Victoria, Australia, in order to determine whether all diagnosed cases were being reported. The proportion of each relevant hospital admission ICD-10-AM code that could be linked to notified cases was calculated. Total and age-specific annual rates were calculated and compared for notified and non-notified cases. Total incidence was estimated using data-linkage results and application of a two-source capture–recapture method. The first 2 years of IPD surveillance in Victoria missed at least one-sixth of laboratory-confirmed IPD cases. Estimated annual IPD rate increased from 9·0 to 10·7/100 000 and rose even higher, to 11·5/100 000, with age-specific rates possibly reaching 90·0/100 000 children aged <2 years, when using capture–recapture. Strategies to improve notification and coding of hospitalized cases of IPD are required.

In this paper we obtain optimal bounds for the length of the longest arithmetic progression in various kinds of sum-sets. As an application, we derive a sharp estimate for the number of sets $A$ of residues modulo a prime $n$ such that no subsum of $A$ equals $x$ modulo $n$, where $x$ is a fixed residue modulo $n$.

Void evolution during electromigration was studied by recording void nucleation, growth, and displacements at various intervals during thermal (240 °C) and electrical stress tests (2 × 106 amps/cm2) of Cu interconnects. Structural data was collected for various serially arranged line segment lengths and correlated with resistance and increases in resistance due to electromigration-induced thinning and voiding. These results allowed determination of void growth rates in Cu interconnects. Void nucleation and growth show a clear dependence on segment length. Void formation did not occur at the via/interconnect interface, which improved interconnect reliability by allowing extensive voiding before catastrophic failure.

Explosive crystallisation induced by an electron beam and by a CW Ar+ laser operating in fast scanning mode is observed for the first time on amorphized silicon layers created by implantation on either polycrystalline films deposited on Si02 or single crystal silicon substrates. The grain structure in the explosive crescents is studied by preferential chemical etching in conjunction with Nomarski optical microscopy, SEM and TEM. The results are similar to the so-called solid-phase explosive crystallization previously observed in a-Si films deposited on glass substrates.