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Students from Asian countries form the largest group of mobile international students in Western anglophone countries. Despite research on the mobility experiences of international students to anglophone and non-anglophone countries, there are limited cross-comparative, mixed-method studies exploring the experiences of host language acquisition and usage and how these impact on academic performance and shapes social connectedness. This study contributes further understanding by exploring language acquisition experiences of international university students in Taiwan and Australia, where the language of instruction is not their native language. In the two universities studied, usage levels (general usage, speaking, reading, listening and writing) differed and depended on situational and contextual needs. Those studying in Australia consistently reported higher mean scores of host language usage across three of the five components: listening, reading and writing. Written communication was perceived to be a challenge for both groups during interviews. Overall, students preferred face-to-face classroom learning and highly valued peer support. Information communication and technology use was common in supporting vocabulary and pronunciation. We discuss how the findings of our study inform the types of academic learning support needed, and how these differed, depending on the host language, and student background.

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Background and aims Real-world evidence characterising the burden of eosinophilic granulomatosis with polyangiitis (EGPA) in Europe is limited. The aim of this study was to characterise patients in a large European EGPA cohort. Methods This retrospective, non-interventional, longitudinal study (GSK ID: 214661) recruited cross-specialty physicians from France, Germany, Italy, Spain and the UK to conduct medical chart reviews for patients with a physician-confirmed diagnosis of EGPA. Patients were ≥12 years of age at diagnosis with ≥1 year of follow-up data from the first clinical visit with the physician (index date). Outcome measures collected from index date to end of follow-up included clinical manifestations and healthcare resource utilisation (HCRU). Results In total, 407 patient medical charts were reviewed by 204 physicians; median (interquartile range) duration of follow-up from index date was 2.2 (1.7−3.5) years. Most patients (73.5%) had asthma. Patients underwent multiple diagnostic assessments, and 74.9% received ≥3 different therapies between diagnosis and end of follow-up (98.8% oral corticosteroids, 63.9% immunosuppressive therapies, 45.5% biologics). During follow-up, 84.5% of patients experienced EGPA clinical manifestations; most were considered moderate or severe and commonly affected the lungs (55.8%; including lung infiltrates 25.8% and severe asthma 24.8%), ear, nose and throat (53.3%), and skin (41.8%). HCRU was substantial: 26.0% of patients made emergency department visits, 36.6% were hospitalised and 84.8% had outpatient visits. Conclusions These real-world data show that EGPA presents a substantial burden to patients and the healthcare system. Earlier and better differential diagnosis and appropriate treatment may help reduce incidence of clinical manifestations and HCRU.

Abstract Digital measures of health status captured during daily life could greatly augment current in-clinic assessments for rheumatoid arthritis (RA), to enable better assessment of disease progression and impact. This work presents results from weaRAble-PRO, a 14-day observational study, which aimed to investigate how digital health technologies (DHT), such as smartphones and wearables, could augment patient reported outcomes (PRO) to determine RA status and severity in a study of 30 moderate-to-severe RA patients, compared to 30 matched healthy controls (HC). Sensor-based measures of health status, mobility, dexterity, fatigue, and other RA specific symptoms were extracted from daily iPhone guided tests (GT), as well as actigraphy and heart rate sensor data, which was passively recorded from patients’ Apple smartwatch continuously over the study duration. We subsequently developed a machine learning (ML) framework to distinguish RA status and to estimate RA severity. It was found that daily wearable sensor-outcomes robustly distinguished RA from HC participants (F1, 0.807). Furthermore, by day 7 of the study (half-way), a sufficient volume of data had been collected to reliably capture the characteristics of RA participants. In addition, we observed that the detection of RA severity levels could be improved by augmenting standard patient reported outcomes with sensor-based features (F1, 0.833) in comparison to using PRO assessments alone (F1, 0.759), and that the combination of modalities could reliability measure continuous RA severity, as determined by the clinician-assessed RAPID-3 score at baseline (r 2, 0.692; RMSE, 1.33). The ability to measure the impact of the disease during daily life—through objective and remote digital outcomes—paves the way forward to enable the development of more patient-centric and personalised measurements for use in RA clinical trials.

Background Herpes zoster (HZ) is a painful condition caused by reactivation of the varicella-zoster virus. The objectives of this study were to compare HZ incidence in adults with asthma versus adults without asthma and to compare healthcare resource use as well as direct costs in adults with HZ and asthma versus adults with asthma alone in the USA.Methods This retrospective longitudinal cohort study included adults aged ≥18 years across the USA. Patients were identified from Optum’s deidentified Clinformatics Data Mart Database, an administrative claims database, between 1 October 2015 and 28 February 2020, including commercially insured and Medicare Advantage with part D beneficiaries. Cohorts of patients with and without asthma, and separate cohorts of patients with asthma and HZ and with asthma but not HZ, were identified using International Classification of Diseases 10th Revision, Clinical Modification codes. HZ incidence, healthcare resource use and costs were compared, adjusting for baseline characteristics, between the relevant cohorts using generalised linear models.Results HZ incidence was higher in patients with asthma (11.59 per 1000 person-years) than patients without asthma (7.16 per 1000 person-years). The adjusted incidence rate ratio (aIRR) for HZ in patients with asthma, compared with patients without asthma, was 1.34 (95% CI 1.32 to 1.37). Over 12 months of follow-up, patients with asthma and HZ had more inpatient stays (aIRR 1.11; 95% CI 1.02 to 1.21), emergency department visits (aIRR 1.26; 95% CI 1.18 to 1.34) and outpatient visits (aIRR 1.19; 95% CI 1.16 to 1.22), and direct healthcare costs that were US dollars ($) 3058 (95% CI $1671 to $4492) higher than patients with asthma without HZ.Conclusion Patients with asthma had a higher incidence of HZ than those without asthma, and among patients with asthma HZ added to their healthcare resource use and costs.

Objective To investigate the real-world impact of intravenous belimumab treatment among patients with SLE using rheumatoid arthritis-derived disease activity measures and SLE-related laboratory values.Methods This retrospective cohort study used US electronic medical record data from the United Rheumatology Normalised Integrated Community Evidence (UR-NICE) database. Adult patients with SLE who initiated intravenous belimumab between 1 January 2012 and 3 December 2019 (index), had 12 months of pre-index and 24 months of post-index clinical activity, and had ≥6 infusions of belimumab during the 24 months post-index were included. The primary outcome measure was time to first improvement of minimally important difference (MID) for Routine Assessment of Patient Index Data 3 (RAPID3), Patient Pain Index (PPI), swollen joint count, tender joint count (TJC), complement C3 and C4 and anti-double-stranded DNA antibodies during the on-treatment follow-up period of up to 24 months. The secondary outcome measure evaluated the trajectories of these outcome measures for up to 24 months of belimumab treatment.Results Of 495 patients included, between 21.0% and 52.1% had ≥1 record for each of the disease activity measures or laboratory values in the pre-index and post-index periods and were included in analyses for that measure. The proportion of patients achieving MID for each measure increased rapidly within 3 months, with continued gradual improvement throughout the remaining on-treatment period, up to 24 months. After 6 months, 52.3% and 55.3% of patients had achieved MID in RAPID3 and PPI, respectively. Outcome measure trajectories indicated improved disease activity with belimumab treatment, particularly in RAPID3, TJC and laboratory values.Conclusions In this real-world effectiveness study, belimumab therapy for SLE resulted in clinically meaningful improvements in rheumatoid arthritis-derived disease activity measures within 3 months of treatment, with patients who remained on belimumab therapy experiencing improvement even up to 24 months of observation.

Abstract Rheumatoid arthritis (RA) is a fluctuating progressive disease requiring frequent symptom assessment for appropriate management. Continuous tracking using digital technologies may provide greater insights of a patient’s experience. This prospective study assessed the feasibility, reliability, and clinical utility of using novel digital technologies to remotely monitor participants with RA. Participants with moderate to severe RA and non-RA controls were monitored continuously for 14 days using an iPhone with an integrated bespoke application and an Apple Watch. Participants completed patient-reported outcome measures and objective guided tests designed to assess disease-related impact on physical function. The study was completed by 28 participants with RA, 28 matched controls, and 2 unmatched controls. Completion rates for all assessments were > 97% and were reproducible over time. Several guided tests distinguished between RA and control cohorts (e.g., mean lie-to-stand time [seconds]: RA: 4.77, control: 3.25; P

Abstract Regulation of global transcription output is important for normal development and disease, but little is known about the mechanisms involved. DNA topoisomerase I (TOP1) is an enzyme well-known for its role in relieving DNA supercoils for enabling transcription. Here, we report a non-enzymatic function of TOP1 that downregulates RNA synthesis. This function is dependent on specific DNA-interacting residues located on a conserved protein surface. A loss-of-function knock-in mutation on this surface, R548Q, is sufficient to cause hypertranscription and alter differentiation outcomes in mouse embryonic stem cells (mESCs). Hypertranscription in mESCs is accompanied by reduced TOP1 chromatin binding and change in genomic supercoiling. Notably, the mutation does not impact TOP1 enzymatic activity; rather, it diminishes TOP1-DNA binding and formation of compact protein-DNA structures. Thus, TOP1 exhibits opposing influences on transcription through distinct activities which are likely to be coordinated. This highlights TOP1 as a safeguard of appropriate total transcription levels in cells.

Abstract Introduction Patients with psoriasis (PsO) are at increased risk of herpes zoster (HZ), but recent data on the incidence of HZ among patients with PsO and the impact of HZ on healthcare resource use (HRU) and costs for patients with PsO have not been described. Methods This retrospective, longitudinal, cohort study estimated HZ incidence in cohorts of adults with vs without PsO (PsO + vs PsO–) and HRU and costs among those with PsO, with vs without HZ (PsO + /HZ + vs PsO + /HZ–) using Optum’s de-identified Clinformatics Data Mart Database during 2015–2020. Patients with psoriatic arthritis were excluded from all four cohorts. Comparisons between cohorts used generalized linear models to adjust outcomes based on various baseline characteristics. Results The incidence rate of HZ was significantly higher in the PsO + (n = 144,115) vs PsO– (n = 23,837,237) cohorts at 11.35 vs 7.67 per 1000 patient-years; adjusted incidence rate ratio (aIRR): 1.21, 95% confidence interval (CI): 1.16–1.25. HRU (outpatient, emergency department, and inpatient) was significantly higher in the PsO + /HZ + (n = 1859) vs PsO + /HZ– (n = 78,664) cohorts during 1 month and 3 months after HZ diagnosis (e.g., outpatient visits during month: 2.83 vs 1.30 per patient; aIRR: 1.96; 95% CI 1.86–2.06). Mean all-cause costs were also significantly higher in the PsO + /HZ + vs PsO + /HZ– cohort during both month ($5020 vs $2715 per patient; adjusted cost difference: $1390; 95% CI $842–$1964) and 3 months ($12,305 vs $8256; adjusted cost difference: $1422; 95% CI $280–$2889) after HZ diagnosis. Conclusion These findings show the increased incidence of HZ among patients with PsO and the clinical and economic burdens of HZ in this population. Considering the high prevalence of PsO, insights into the impact of HZ in these patients provide valuable evidence to inform clinical decision-making. Graphical abstract

Abstract Introduction Dolutegravir/lamivudine (DTG/3TC) is a 2-drug regimen for HIV-1 treatment with long-term efficacy and good tolerability comparable to 3- or 4-drug regimens. This study evaluated DTG/3TC cost versus other standard single-tablet regimens during its first year of approval. Methods This retrospective study analyzed US claims data from adults with HIV-1. Eligibility criteria included ≥ 1 dispensing of DTG/3TC, DTG/abacavir (ABC)/3TC, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF, and darunavir (DRV)/COBI/FTC/TAF (index date was first dispensing) and ≥ 6 months of continuous eligibility before index date (baseline period). All-cause and HIV-related healthcare costs were evaluated during the observation period (index date until earliest of end of continuous eligibility or data availability). Adjusted cost differences and adjusted cost ratios were estimated using multivariable regression models controlling for differences in baseline characteristics between cohorts. Results Overall, 22,061 individuals with HIV-1 and dispensed treatment with DTG/3TC (n = 590), DTG/ABC/3TC (n = 4355), BIC/FTC/TAF (n = 9068), EVG/COBI/FTC/TAF (n = 7081), or DRV/COBI/FTC/TAF (n = 967) were included. Most claims data were from men (mean age ~ 46 years). Mean unadjusted all-cause total healthcare costs per patient per month were significantly lower for DTG/3TC versus BIC/FTC/TAF and DRV/COBI/FTC/TAF, and mean unadjusted HIV-related healthcare costs per patient per month were significantly lower for DTG/3TC versus DRV/COBI/FTC/TAF. Cost differences were primarily driven by significantly lower pharmacy costs for DTG/3TC versus other regimens (P

Abstract Real-world data were collected to examine antimicrobial resistance (AMR) prevalence, treatment patterns, and clinical outcomes among female patients with uncomplicated urinary tract infection (uUTI) in Germany. Data were from a retrospective physician-based chart review completed by physicians treating patients with uUTI. Non-pregnant women aged ≥ 12 years, with a uUTI diagnosis, an E. coli-positive urine culture between January 2017–December 2019, and susceptibility test results for ≥ 4 drug classes were eligible. Patients were stratified into three cohorts by drug class susceptibility: susceptible to all (SUS), resistant to one or two drug classes (DR1/2), and resistant to ≥ 3 (MDR) drug classes tested. Among 386 eligible patients [SUS (67.1%); DR1/2 (29.0%); MDR (3.9%)], AMR prevalence was highest for FMIs (18.3%) and lowest for fluoroquinolones (5.2%). The most prescribed drugs were fosfomycin in SUS (44.0%), DR1/2 (41.4%), and fluoroquinolones in MDR (40.0%). Treatment for uUTI failed for 8.8% of patients; failure was more likely in MDR versus SUS [adjusted odds ratio [95% CI] = 4.21 [1.14–1.50]; P = 0.031); incidence of recurrent infection in the 6-months post-index period was higher in DR1/2 versus SUS. These findings may have implications for empiric prescribing, suggesting an unmet need for new treatments.

ABSTRACT The 1918 influenza pandemic was the most devastating respiratory pandemic in modern human history, with 50–100 million deaths worldwide. Here, we characterized the complete genomes of influenza A virus (IAV) from two fatal cases during the fall wave of 1918 influenza A (H1N1) pandemic in the United States, one from Walter Reed Army Hospital in Washington, DC, and the other from Camp Jackson, SC. The two complete IAV genomes were obtained by combining Illumina deep sequencing data from both total RNA and influenza viral genome-enriched libraries along with Sanger sequencing data from PCR across the sequencing gaps. This study confirms the previously reported 1918 IAV genomes and increases the total number of available complete or near-complete influenza viral genomes of the 1918 pandemic from four to six. Sequence comparisons among them confirm that the genomes of the 1918 pandemic virus were highly conserved during the main wave of the pandemic with geographic separation in North America and Europe. Metagenomic analyses revealed bacterial co-infections in both cases. Interestingly, in the Washington, DC, case, evidence is presented of the first reported Rhodococcus-influenza virus co-infection.IMPORTANCEThis study applied modern molecular biotechnology and high-throughput sequencing to formalin-fixed, paraffin-embedded autopsy lung samples from two fatal cases during the fall wave of the 1918 influenza A (H1N1) pandemic in the United States. Complete influenza genomes were obtained from both cases, which increases the total number of available complete or near-complete influenza genomes of the 1918 pandemic virus from four to six. Sequence analysis confirms that the 1918 pandemic virus was highly conserved during the main wave of the pandemic with geographic separation in North America and Europe. Metagenomic analyses revealed bacterial co-infections in both cases, including the first reported evidence of Rhodococcus-influenza co-infection. Overall, this study offers a detailed view at the molecular level of the very limited samples from the most devastating influenza pandemic in modern human history.

Objective To characterize health care resource utilization (HCRU), health care costs, and adverse events (AEs) among patients with systemic lupus erythematosus (SLE) initiating oral corticosteroids (OCS) versus patients without OCS use. Methods In this retrospective cohort study (GSK Study 213061), eligible patients (aged ≥5 years at first OCS claim) with SLE from the IQVIA Real‐World Data Adjudicated Claims‐US database (January 2006 to July 2019) had continuous enrollment during the 6‐month preindex (baseline) and 12‐month postindex (observation) periods and one or more inpatient or emergency department SLE diagnosis codes or two or more outpatient SLE diagnosis codes during baseline. The “OCS‐initiator cohort” comprised patients with one or more OCS pharmacy claims during the study period and no evidence of preindex OCS use and was classified into three exposure categories based on the number of 6‐month periods of more than 5 mg/day of OCS use (0, 1, 2). The “no‐OCS‐use cohort” comprised patients without OCS claims, although patients may have received OCS prior to the study period. Clinical and economic outcomes were reported over the observation period. Results Adjusted health care costs differed significantly ($6542 [95% confidence interval (CI): $5761‐$7368], $19,149 [95% CI: $16,954‐$21,471], $28,985 [95% CI: $25,546‐$32,885]). HCRU incidence rates were significantly greater for all OCS‐initiator exposure categories (n = 16,216) versus the no‐OCS‐use cohort (n = 11,137; adjusted incidence rate ratios [95% CI]: 1.22 [1.19‐1.24], 1.39 [1.34‐1.43], 1.66 [1.60‐1.73]). OCS‐related AEs were experienced by 67.1% to 74.1% of patients with OCS initiation, most commonly affecting the immune system. Conclusion Within 12 months of OCS initiation, patients with SLE experienced substantial clinical and economic burden, which may imply a need to minimize OCS use.

Abstract Objective To estimate the incremental healthcare resource utilization (HRU) and cost burden posed by herpes zoster (HZ) in adult patients with rheumatoid arthritis (RA) in the United States. Methods A retrospective cohort study was conducted using an administrative claims database containing commercial and Medicare Advantage with Part D data, between October 2015 and February 2020. Patients with RA and HZ (RA+/HZ+) or RA without HZ (RA+/HZ−) were identified based on diagnosis codes and relevant medications. Outcomes measured included HRU and medical, pharmacy, and total costs at month 1, quarter 1, and year 1 after the index date (HZ diagnosis for RA+/HZ+ cohort, randomly assigned for RA+/HZ− cohort). Generalized linear models incorporating propensity scores and other covariates were used to estimate differences in outcomes between cohorts. Results A total of 1866 patients from the RA+/HZ+ cohort and 38,846 patients from the RA+/HZ− cohort were included. Hospitalizations and emergency department visits occurred more frequently in the RA+/HZ+ than the RA+/HZ− cohort, especially in the month after HZ diagnosis (adjusted incidence rate ratio [95% confidence interval (CI)] for hospitalizations: 3.4 [2.8; 4.2]; emergency department visits: 3.7 [3.0; 4.4]). Total costs were also higher in the month after HZ diagnosis (mean adjusted cost difference [95% CI]: $3404 [$2089; $4779]), with cost differences driven by increased medical costs ($2677 [$1692; $3670]). Conclusions These findings highlight the high economic burden of HZ among individuals with RA in the United States. Strategies to reduce the risk of HZ in patients with RA (such as vaccination) may serve to reduce this burden. Video abstract

Abstract Background Yersinia enterocolitica has been sporadically recovered from animals, foods, and human clinical samples in various regions of Ningxia, China. However, the ecological and molecular characteristics of Y. enterocolitica, as well as public health concerns about infection in the Ningxia Hui Autonomous Region, remain unclear. This study aims to analyze the ecological and molecular epidemiological characteristics of Y. enterocolitis in order to inform the public health intervention strategies for the contains of related diseases. Methods A total of 270 samples were collected for isolation [animals (n = 208), food (n = 49), and patients (n = 13)], then suspect colonies were isolated and identified by the API20E biochemical identification system, serological tests, biotyping tests, and 16S rRNA-PCR. Then, we used an ecological epidemiological approach combined with machine learning algorithms (general linear model, random forest model, and eXtreme Gradient Boosting) to explore the associations between ecological factors and the pathogenicity of Y. enterocolitis. Furthermore, average nucleotide identity (ANI) estimation, single nucleotide polymorphism (SNP), and core gene multilocus sequence typing (cgMLST) were applied to characterize the molecular profile of isolates based on whole genome sequencing. The statistical test used single-factor analysis, Chi-square tests, t-tests/ANOVA-tests, Wilcoxon rank-sum tests, and Kruskal–Wallis tests. Results A total of 270 isolates of Yersinia were identified from poultry and livestock (n = 191), food (n = 49), diarrhoea patients (n = 13), rats (n = 15), and hamsters (n = 2). The detection rates of samples from different hosts were statistically different (χ 2 = 22.636, P

High myopia is a state of refractive error with myopia over -6.00D. High myopia is typically accompanied by multiple fundus lesions, thus making patients with high myopia suffer from varying degrees of impairment in visual function. As an emerging auxiliary way in ophthalmology, optical coherence tomography angiography(OCTA)can efficiently and non-invasively obtain microvascular stratified images of the retina and choroid and quantitatively analyze blood flow signals. Since the advent of OCTA, there have been numerous studies observing fundus changes in those with high myopia through OCTA. In this paper, some studies in which OCTA is applied to obtain retinal and choroidal thickness from patients with high myopia are reviewed, with a view to revealing the correlation between high myopia and the parameters such as retinal thickness, choroidal thickness, vessel density and the area of the foveal avascular zone and providing novel ideas to deeply investigate the mechanism of high myopia and delay the occurrence and development of high myopia.

BackgroundThe NAPOLI-1 trial demonstrated that liposomal irinotecan in combination with fluorouracil (5-FU) and leucovorin (LV) prolonged survival with a manageable safety profile in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. Real-world data on clinical outcomes associated with liposomal irinotecan in NAPOLI-1-based regimens is needed to further substantiate this.MethodsThis real-world, retrospective chart review study included patients with mPDAC who received NAPOLI-1-based regimens from six academic centers in the United States. Liposomal irinotecan initiation defined the index date. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier methodology.ResultsThere were 374 patients evaluated; median age was 68 years, and 51% were female. Among 326 patients with baseline ECOG information, approximately 74% had ECOG score

ABSTRACTObjectives In the absence of head-to-head comparisons across relapsed/refractory multiple myeloma (RRMM) treatments following the approval of the oral proteasome inhibitor ixazomib, in combination with lenalidomide and dexamethasone (IRd), we conducted an indirect comparison of the efficacy of IRd relative to several RRMM therapies using Bayesian fixed-effects network meta-analysis (NMA) models.Methods Data for the NMA were obtained through a systematic literature review (conducted in June 2020), which identified randomized controlled trials (base case) and observational studies (extended network analysis) reporting overall survival (OS), progression-free survival (PFS), and overall response rate (ORR).Results In the base case, IRd was associated with a significantly longer PFS than lenalidomide and dexamethasone (Rd), bortezomib monotherapy (V), dexamethasone (Dex), and pomalidomide and dexamethasone (Pom-dex), a significantly shorter PFS than daratumumab, lenalidomide, and dexamethasone (DRd), and a PFS comparable to elotuzumab, lenalidomide, and dexamethasone (ERd) and carfilzomib, lenalidomide, and dexamethasone (KRd). IRd was associated with a significantly longer OS than V, Dex, and Pom-dex, and an OS comparable to Rd, ERd, KRd, and DRd. The ORR of IRd was significantly higher than Rd, V, and Dex, significantly lower than KRd and DRd, and comparable to Pom-dex and ERd. The extended network analyses and sensitivity analyses were consistent with the base case.Discussion This NMA shows that IRd is relatively efficacious among RRMM treatments. Being an oral regimen, IRd is also convenient to manage.Conclusion IRd could be a preferable treatment option for many patients with RRMM, particularly those seeking an efficacious and convenient therapeutic option.

With the increasing prominence of data security in cloud storage, we propose a practical and robust cloud storage scheme, which uses quantum random numbers as encryption keys, disperses the keys using Shamir’s secret sharing scheme, applies erasure coding to the ciphertext, and securely transmits the data through quantum key distribution protected networks to the distributed clouds. This system offers several key advantages, including quantum-level security, fault tolerance, and storage space saving. To validate its feasibility, we conduct comprehensive experimental tests covering essential functionalities such as encryption/decryption, key preservation, and data storage. By successfully demonstrating the effectiveness of our proposal, we aim to accelerate the application of quantum technology in cloud storage.