Safety Warnings Research Articles

Zinc tungstate integrated onto zinc oxide h-MDs-based flexible piezoelectric power device: A new energy technology for real-time indoor laboratory safety warning system

With the rapid development of research world, the number of researchers and research laboratories is increasing rapidly. Simultaneously, accidents in laboratories are on the rise, drawing significant attention from everyone. To address this issue, the current study demonstrates a real-time safety early warning alarm system aimed at preventing accidents and enhancing safety management in laboratories. We developed a zinc tungstate nanoparticles (NPs) integrated on zinc oxide hexagonal microdiscks (h-MDs) (ZnO–ZnWO4@PDMS) composite based on a novel flexible piezoelectric nanogenerator (FPENG). The observed piezoelectric response was 1.32 V, which is ∼4 times better than that of pure ZnWO4, owing to the synergistic effect of ZnO–ZnWO4@PDMS. When subjected to finger-tapping motion, the FPENG can charge a 1 μF capacitor, and it reached 81 mV within 56 s. Subsequently, the light-emitting diodes (LEDs) are powered with amplification. The FPENG system was demonstrated and validated through real-time application in the laboratory setting, marked as a “caution/restricted” line. The application of the system demonstrated its capability to simultaneously illuminate LEDs and sound alarms when people touch or cross the caution line. Furthermore, the proposed FPENG exhibited ∼660 mV even ∼90 % humidity, with no noticeable electrical changes under different solvents, confirming that the proposed FPENG is not affected by varying humidity and various indoor conditions. These outstanding results and real-time demonstrations unequivocally establish the feasibility of this system in contexts such as bank lockers, metro systems, hilly areas, and more.

OA39 The influence of safety warnings on the prescribing of JAK inhibitors in England: an interrupted time-series analysis

Abstract Background/Aims JAK inhibitors (JAKi) were launched in the UK for rheumatoid arthritis in 2017. Licenced indications have subsequently expanded to include other inflammatory arthritides, inflammatory bowel disease, psoriasis and atopic dermatitis. Since then, there have been numerous safety warnings from regulatory bodies, with signals for cancer, venous thromboembolism and cardiovascular events. We set out to compare how these safety warnings have influenced prescribing behaviour for individual JAKi medications in England. Methods We analysed aggregate prescribing data from all NHS hospitals in England between January 2019 and July 2023. We compared monthly prescriptions issued for individual JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib) across all licenced indications. Standardisation was performed using WHO Daily Defined Doses. We conducted interrupted time-series analyses to evaluate whether changes in prescribing behaviour occurred after: i) the initial press release for the ORAL Surveillance trial data (January 2021); and ii) the European Medicines Agency (EMA) safety committee warning for the JAKi class as a whole (October 2022). Results Overall, JAKi prescribing has increased year-on-year since 2019; however, striking differences exist for individual JAKi medications. Pre-2021, an estimated additional 93 patients per month were newly initiated on tofacitinib. After the ORAL Surveillance press release (January 2021), tofacitinib initiations decreased to 26 new patients/month (p < 0.001). Following the EMA safety warning (October 2022), tofacitinib prescribing fell sharply (71 fewer patients/month; p < 0.001). A similar pattern was observed for baricitinib - pre-2021: 145 new patients/month; post-Jan 2021: 15 new patients/month; post-Oct 2022: 60 fewer patients/month (all, p < 0.001). In contrast, prescriptions for the JAK1-selective inhibitors (upadacitinib and filgotinib) have increased markedly since 2021, with no apparent impact of the pan-JAKi safety warnings. In July 2023, baricitinib remained the most prescribed JAKi in England across all indications (175,245 defined daily doses [DDD]) followed by upadacitinib (154,510 DDD), tofacitinib (105,215 DDD), and filgotinib (72,445 DDD). Conclusion Prescribing of JAKi has changed markedly in association with emerging safety warnings, with significant reductions in prescriptions for tofacitinib and baricitinib. It is notable that warnings have emerged for the JAKi class as a whole, yet prescriptions for the JAK1-selective inhibitors, upadacitinib and filgotinib, have continued to increase. Explanations could include clinicians' interpretation of risk differences within the JAKi class, as well as external pressures such as price and licenced indications. Disclosure M.D. Russell: Honoraria; AbbVie, Biogen, Eli Lilly, Galapagos, Menarini. Grants/research support; Eli Lilly, Janssen, Pfizer, UCB. Z. Yang: None. B. Walter: None. E. Alveyn: None. K. Bechman: Grants/research support; Versus Arthritis/Pfizer. A. Miracle: None. D. Nagra: None. M.A. Adas: None. J.B. Galloway: Honoraria; Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, UCB.

P044 Janus Kinase Inhibitors-a retrospective study on side effects and discontinuation reasons

Abstract Background/Aims In light of drug safety warnings for Janus kinase inhibitors (JAKi), we aimed to evaluate the occurrence of adverse events and identify reasons for discontinuation of JAKi in clinical practice. Methods Medical records of all patients prescribed JAKi in NHS Grampian from January 2021 to January 2023 for rheumatic diseases were retrospectively reviewed. Patient demographics, co-morbidities, reasons for treatment discontinuation and occurrence of adverse events (including cardiovascular events) were recorded. Results 160 patients were prescribed JAKi. 131 (81.8%) patients had rheumatoid arthritis, 16 (10%) psoriatic arthritis, five (3%) axial spondyloarthritis, three (2%) juvenile idiopathic arthritis (in adulthood), 3 (2%) undifferentiated inflammatory arthritis, one (0.6%) granulomatous polyangiitis (GPA), one (0.6%) enteropathic arthritis. Mean duration of treatment was 9.9±12 months with 34.4% on treatment for >12 months. 47.5% discontinued JAKi after an average of 7.0 ± 5.1 months. Patients discontinuing treatment were significantly older than patients who continued treatment 60.1yrs ± 11.0 vs 55.9yrs ± 12.5 respectively, p = 0.03. There were no differences between discontinuing and continuing treatment groups with respect to BMI, smoking, diabetes, cardiovascular disease, hypertension or statin use. Discontinuation rates were 66.7 % tofacitinib, 44.4 % filgotinib and 34.4 % upadacitinib. Discontinuation reasons were inefficacy (37.9 %), headache (9.2 %), infections (9.2 %) and gastrointestinal adverse effects (8.0 %). One patient discontinued JAKi due to an arterial embolism (DVT in the context of undiagnosed patent foramen ovale), three developed new onset hypertension. Common infections leading to discontinuation were urinary tract (37.5 %) and chest (25.0 %), with one case of tuberculosis. No herpes zoster infections led to JAKi discontinuation. In patients who continued treatment infections occurred in 27.1% (30% chest, 21.7%, Covid-19, 13% UTIs, 8.7% herpes zoster 8.7% otitis media). Other adverse events such as fatigue and nausea were reported in < 4 % of all patients. No malignancies were recorded. Conclusion Older patients are more likely to discontinue JAKi due to infections. Upadacitinib patients were least likely to discontinue. Treatment inefficacy, urine and chest infections were the commonest reasons for discontinuation. Disclosure J. Klein: None. J. Alexander: None. L. Robertson: Other; LR has received funding for conference attendance from UCB. R. Hollick: None.

Women's sensitivity to threat in online dating and the (in)effectiveness of standard safety warnings

Acts of sexual aggression are sometimes initiated through an online dating arrangement or encounter (e.g., through Tinder, Bumble). Certain personality and physical traits may be predictive of such sexual aggression propensity, and thus evident in online dating profiles (e.g., biographies and photographs). However, it is unclear whether (1) people are sensitive to such “red flags” and (2) whether safety recommendations employed by online dating platforms effectively enhance such sensitivity. For the first time, using an online dating simulation, we experimentally investigated the extent to which women's (n = 167) expressions of interest in men were sensitive to (i.e., influenced by) cues of threat in the men's online dating biographies and photographs, and whether the presence (vs absence) of safety recommendations enhanced this sensitivity. We find fewer expressions of interest for high (vs low) threat dating profiles, although the magnitude of this threat sensitivity/aversion effect varied across women and was not enhanced by safety recommendations. We identify some individual difference factors associated with this threat sensitivity/aversion, but our work underscores the importance of developing other interventions, technologies, or safeguards that screen for, or assist with, identifying such threats, making online dating interactions safer for all users.

Construction of a Climate Early Warning System: Predicting Future Temperatures and Climate Security Using BiLSTM

In light of the worsening global climate, providing predictive models for surface temperature and energy consumption is crucial for formulating effective climate action strategies. Initially, a Bi-directional Long Short-Term Memory (BiLSTM) network model is established to predict the maximum surface temperatures over the next century, with the Seasonal AutoRegressive Integrated Moving Average (SARIMA) model serving as a benchmark. To assess the risk levels of climate security, the k-means clustering algorithm is utilized to classify the growth rates of carbon dioxide emissions, enabling the construction of a three-tier climate security early warning index. Subsequently, a hybrid classification model based on Support Vector Machine (SVM) and Random Forest (RF) takes the energy consumption growth rates as inputs and the warning indices as outputs to construct a climate security early warning system. The BiLSTM model is employed to predict the energy consumption growth rates for the upcoming decade, and these rates are input into the SVM-RF model to forecast future warning levels. The study demonstrates that the model can effectively predict the maximum surface temperatures and provide a three-tier safety warning system for future climate risk management. The intent of this research is to offer a novel tool for global climate prevention and to deliver practical application value to policymakers in finance, energy, and environmental sectors.

Prescription Trends of Thiazide Diuretics in a Canadian Primary Care Population From 2015 to 2021

BackgroundHypertension Canada 2017 guidelines favoured the use of thiazide (TZ)-like diuretics, such as CLTD (chlorthalidone) and indapamide (IND) over hydrochlorothiazide (HCTZ). Health Canada warned in 2019 that HCTZ may be associated with increased risk of skin cancer. Our study looked at the changes in TZ prescriptions from 2015 to 2021 in Ontario, Canada. MethodsA retrospective cohort study was conducted of adults with hypertension, using electronic medical record data from the University of Toronto Practice-Based Research Network database covering mostly the Greater Toronto area. Outcomes included the proportion of patients who received a prescription of HCTZ, CLTD, or IND each month. Interrupted time-series analysis was used to evaluate the change in outcomes after publication of the 2017 guidelines and 2019 safety warning. Prescription trends were stratified by prescribing physicians’ sex and year of medical school graduation. ResultsA total of 100,428 patients with hypertension were included in the cohort, with 31,700 patients who received at least one TZ prescription from 343 family physicians. We found a declining trend in HCTZ prescriptions over time, accompanied by an increase in IND and CLTD prescriptions, with statistically significant but transient changes in prescription rates after publication of the 2017 guidelines and the 2019 safety warning for all 3 medications. Female physician and early-career physician prescription rates changed faster than that of their counterparts immediately after the Health Canada safety warning was issued. ConclusionsTZ diuretic prescription patterns have changed in recent years, but Hypertension Canada’s 2017 guidelines and the 2019 Health Canada safety warning did not have a sustained significant impact on the change in prescription rates of HCTZ, IND, and CLTD.

Deep-Learning-Assisted Sensor with Multiple Perception Capabilities for an Intelligent Driver Assistance Monitoring System.

Driver assistance systems can help drivers achieve better control of their vehicles while driving and reduce driver fatigue and errors. However, the current driver assistance devices have a complex structure and severely violate the privacy of drivers, hindering the development of driver assistance technology. To address these limitations, this article proposes an intelligent driver assistance monitoring system (IDAMS), which combines a Kresling origami structure-based triboelectric sensor (KOS-TS) and a convolutional neural network (CNN)-based data analysis. For different driving behaviors, the output signals of the KOS-TSs contain various features, such as a driver's pressing force, pressing time, and sensor triggering sequence. This study develops a multiscale CNN that employs different pooling methods to process KOS-TS data and analyze temporal information. The proposed IDAMS is verified by driver identification experiments, and the results show that the accuracy of the IDAMS in discriminating eight different users is improved from 96.25% to 99.38%. In addition, the results indicate that IDAMS can successfully monitor driving behaviors and can accurately distinguish between different driving behaviors. Finally, the proposed IDAMS has excellent hands-off detection (HOD), identification, and driving behavior monitoring capabilities and shows broad potential for application in the fields of safety warning, personalization, and human-computer interaction.

Focus on Filgotinib in Rheumatoid Arthritis: A Trial-Based Review.

Janus kinases (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is involved in pathophysiologic cascade of a notable number of rheumatic diseases. The development of JAK inhibitors has expanded treatment choices in rheumatoid arthritis (RA) with a sustained class-effect efficacy. Filgotinib is a novel selective inhibitor of JAK1 isoform licensed for use in RA and ulcerative colitis. In this review we aim to present an analysis of filgotinib's efficacy and drug-specific safety warnings. Patients with RA with or without concomitant conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) (naïve or experienced) and those who have failed biologic Disease-Modifying Antirheumatic Drugs (bDMARDs) were examined in randomised clinical trials. Filgotinib was also tested against placebo, methotrexate, or adalimumab. Long-term extension trials provide insights for up to four years of continuous filgotinib administration. Beneficial effects are depicted in both disease activity parameters and quality of life indexes in moderate or severe RA with a longitudinal efficacy. In head-to-head comparison with adalimumab, filgotinib 200 mg was non-inferior. Adverse effects alerts are marked by the elevated risk of infectious adverse effects with the exception of herpes zoster infection, which has a low incidence.

A273 A PILOT PROSPECITVE, MULTI-CENTRE, RANDOMIZED CONTROLLED TRIAL COMPARING FECAL MICROBIOTA TRANSPLANTATION (FMT) TO PLACEBO AT INDUCING REMISSION IN MILD TO MODERATE CROHN'S DISEASE

Abstract Background FMT has shown promise at inducing remission in ulcerative colitis. The effect of FMT on inducing remission in Crohn’s disease however remains unknown. Aims To evaluate the efficacy of FMT at inducing remission in mild-to-moderate Crohn’s disease Methods This double-blind, randomized, trial conducted at 3 Canadian academic centers (Edmonton, Hamilton and Calgary) randomized. Adult patients with mild-to-moderate Crohn’s disease with modified Harvey Bradshaw Index (mHBI) score of ampersand:003E5 and at least one objective measure of inflammation (CRP ≥ 8mg/L or fecal calprotectin (FCP) ≥ 250 ug/g) on stable dosing of concomitant therapy were assigned to FMT or placebo. First assigned treatment was by colonoscopy followed by 20 [DK1] capsules weekly for 7 weeks. Endoscopic severity (SES-CD) was assessed at baseline during colonoscopic delivery of assigned treatment and at week 8 by a blinded central reader using video recording. The primary endpoint was the proportion of patients in both clinical (mHBI ampersand:003C 5) and endoscopic remission (SES-CD ≤ 5) at week 8. Responders (reduction of HBI ≥ 3 or HBI ≤ 5 and reduction of CRP or FCP by ≥ 10%) in FMT group were eligible to continue with open-label FMT capsule every 2 weeks. Non-responders in the placebo group were permitted to restart the trial at week 0 with open-label FMT. Secondary outcomes included patient reported outcomes and safety outcomes. Results Between July 2017 to Jun 2021, 28 were randomized (16 to FMT and 12 to placebo). The study team voluntarily suspended the trial twice due to Health Canada safety warnings regarding potential transmission of multi-drug resistant organisms and SARS-CoV-2 through FMT. At week 8, 0% (0/16) of patients in the FMT group versus 8.3% (1/12) in the placebo group reached the primary endpoint of combined clinical and endoscopic remission. Of the 50% (8/16) in the FMT group who achieved a clinical response and continued on open-label FMT every 2 weeks, 12.5% (1/8) achieved the primary endpoint. Of the 7 non-responders in the placebo group who restarted the trial at week 0 and received open-label FMT, 28.6% (2/7) achieved primary endpoint at week 8 on open-label FMT. No death or hospitalization were observed. The study was terminated early at the recommendation of the Data Safety Monitoring Board. Conclusions FMT was not effective at inducing remission in Crohn’s disease using the FMT regimen in this study. However, this study was limited by a small sample size and recruitment barrier during the COVID pandemic. Future studies may consider other strategies to potentially enhance treatment response, including antibiotic pre-treatment, optimized donor-recipient pairing, and concomitant anti-inflammatory diet. Funding Agencies CIHR

P562 Safety and persistence oh the first JAK inhibitor Tofacitinib in patients with ulcerative colitis

Abstract Background A drug safety warning was published in 2021 about the risks associated with tofacitinib, which were found in the Oral-Surveillance study. The European Medicines Agency (EMA) and the Spanish Agency for Medicines and Medical Products (AEMPS) have recommended, due to this warning, some precautions in the prescriptions: It should not be used in patients older than 65 years of age, people who are current or past smokers, or individuals with cardiovascular or malignancy risk factors unless there are no suitable treatment alternatives. The aim fo this study was to assess the safety and treatment persistence of tofacitinib in clinical practice in three Spanish third-level hospitals. Methods Retrospective observational multicenter study of patients with Ulcerative Colitis (UC) treated with tofacitinib from January 2019 to October 2023. Sex, age, line of treatment, persistence, adverse events, discontinuations and risk factors associated with the warning were evaluated. Information was collected from the hospital’s information systems. Results A total of 56 patients, 53% women, mean age 55 (18-72) years old. Tofacitinib was the first line treatment in 2% of the patients after loss of response to the conventional treatment, second line for 57%, third line for 30% and fourth line for 11% after biological drugs (infliximab, adalimumab, vedolizumab and ustekinumab). 52% of patients needed maintenance with the higher doses (10mg dose) after induction due to the lack of response with the 5 mg dose, with an average of 52 weeks. The mean persistence was 18 months (1-56), with 19,6% discontinuations due to primary failure and secondary failure. It must be noted that one patient, who received tofacitinib for three years, underwent appendicular neoplasia and finally died due to liver metastases. There was not discontinuation due to other adverse events, which were: 3,6% herpes zoster, 46,4% increased total cholesterol level >200 mg/dl (compared with the initial measurement), of which 19% received statins.There were 27 (48%) patients with risk factors associated with the safety warning: 37% cardiovascular risk, 3,7% older than 65 years, 11,1% previous malignancy, 18,5% current or past smokers and 29,6% had several of these risks. Conclusion In this multicenter real-world treatment-refractory UC population cohort, tofacitinib was well tolerated in the long term, even in the patients with risk factors related to the warning.

P616 Prescribing practices of tofacitinib and preferences amongst high-risk patients in the UK

Abstract Background Tofacitinib was licensed for use in patients with ulcerative colitis in August 2018. Because it is administered orally, has a rapid onset of action and is relatively inexpensive, it was quickly adopted in real-world practice. Safety warnings linking high-dose tofacitinib use to venous thromboembolic events (VTE) and death followed. Further warnings were issued linking its use to an increased risk of malignancy and adverse cardiovascular events in patients: over 65 years, with a history of diabetes, current or past smokers, and those with a history of coronary vascular disease. The most recent Medicines and Healthcare products Regulatory Agency (MHRA) statement advised against the use of all commercially available JAKi in this high-risk cohort unless a suitable alternative is unavailable (MHRA 2023). We sought to define the number of patients who had, or were, being treated with tofacitinib who were in this high-risk group and the proportion who opted to switch therapy once we had outlined their risk-status and the MHRA advice to them. Methods We conducted a retrospective observational cohort study of 131 patients with UC and IBD-U (61% male [80/131]; median age 43 years [range 16-85]; 46% [60/131] patients had previously had at least one biologic agent) treated with tofacitinib from October 2018 to December 2022 in our centre with at least 3 months follow-up. Patients were categorised as high-risk according to the MHRA statement if they had at least one of the criteria above. Results Overall, about one-third, 31.3% [41/131] patients that we had treated with tofacitinib were classified in the MHRA high-risk group. Rates of treatment discontinuation were similar in the high-risk versus no risk group. In the high-risk group ten patients (24.4% [10/41]) had discontinued treatment due to lack of response (4) or an adverse event (6). The most common adverse events were herpes zoster infections (14.6%), malignancy (3.3%) and infections requiring hospitalisation (3.3%). Two patients died while on treatment (one due to complications following cervical spinal surgery and the other due to ischaemic heart disease). There were no incidences of VTE. We clinically reviewed 29 high risk patients who were being treated with tofacitinib after a median of 2.4 years (range 0.6-4.56) of treatment. 25/29 high-risk patients decided on continuing their treatment in spite of the health care warnings and alternative therapies being available. Conclusion About one-third of our tofacitinib-treated patients were classified as at high-risk. The majority of high-risk patients opted to continue therapy even though alternative therapies were available.

Incremental Risk of Adverse Events with Oral Janus Kinase Inhibitor Use in Atopic Dermatitis and Other Indications: A Systematic Review and Meta-Analysis

Introduction: The number of treatment opportunities for patients with moderate-severe atopic dermatitis (AD) is increasing, however with varying treatment safety profiles. The safety profile of oral JAKis remains a concern because of their ubiquitous mechanism of action inhibiting many cytokines. Safety warnings for these products have combined data across indications, making it difficult to assess risk for specific populations.
 Objective: We aimed to estimate the incremental risk of pre-specified adverse events (AEs) per patient-year (PY) of oral JAKi compared with standard of care (SoC), incl. topical corticosteroids, biologic agents, and other treatments, among those with AD or with other diagnoses.
 Methods: A systematic literature review was conducted on 17 preselected AEs based on randomized controlled trials of oral JAKis.
 Meta-analyses (MA) estimated the incidence rate difference (IRD) for each AE between oral JAKis and SoC, both in AD and non-AD populations. Number needed to harm (NNH) was calculated as the inverse of the IRD for each AE. 
 Results: We identified 82 studies, including 19 in AD population, for use in the MA.
 In the AD population, the estimated NNH in PY for acne was 5, indicating 1 additional acne event for every 5 patients treated with oral JAKis vs SoC per year. Moreover, the NNH was 33 for herpes zoster, 62 for anemia, 94 for serious adverse events (SAEs), and 452 for malignancies. In the non-AD population, the NNH was 52 for HZ, 56 for hyperlipidemia, 58 for SAEs, 113 for anemia, 153 for acne, and 254 for malignancies.
 Conclusions: The MA identified an increased risk with oral JAKis compared with SoC for multiple AEs, spanning from less to more severe AE, including malignancies in both AD and non-AD populations. As safety risks are observed in both the AD and non-AD populations, the use of oral JAKis should be carefully considered.

Effect of preload forces on multidimensional signal dynamic behaviours for battery early safety warning

Providing early safety warning for batteries in real-world applications is challenging. In this study, comprehensive thermal abuse experiments are conducted to clarify the multidimensional signal evolution of battery failure under various preload forces. The time-sequence relationship among expansion force, voltage, and temperature during thermal abuse under five categorised stages is revealed. Three characteristic peaks are identified for the expansion force, which correspond to venting, internal short-circuiting, and thermal runaway. In particular, an abnormal expansion force signal can be detected at temperatures as low as 42.4 °C, followed by battery thermal runaway in approximately 6.5 min. Moreover, reducing the preload force can improve the effectiveness of the early-warning method via the expansion force. Specifically, reducing the preload force from 6000 to 1000 N prolongs the warning time (i.e., 227 to 398 s) before thermal runaway is triggered. Based on the results, a notable expansion force early-warning method is proposed that can successfully enable early safety warning approximately 375 s ahead of battery thermal runaway and effectively prevent failure propagation with module validation. This study provides a practical reference for the development of timely and accurate early-warning strategies as well as guidance for the design of safer battery systems.

Access to biologics and Janus kinase inhibitors for treatment of rheumatic diseases in the biosimilars era in Poland: a nation-level study.

By reducing treatment costs, biosimilars provide an opportunity to improve accessibility to highly effective drugs. This study aimed to evaluate access to biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKis) among patients with rheumatic musculoskeletal diseases within a 10 year timeframe in Poland. We performed a retrospective analysis using a nationwide public payer database. By 2022, 11 102, 6602, and 4400 patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) were treated with bDMARDs or JAKis. Peak drug utilization was observed for adalimumab, followed by etanercept and tocilizumab. Within the study timeframe, the estimated access to innovative drugs increased from 0.8%, 1.4%, and 0.8% to 3.2%, 8.7%, and 3.5% for RA, PsA, and axSpA patients, respectively. Affordable tumor necrosis factor inhibitors (TNFis) still predominate among innovative therapeutics, but their market share declined from 87% to 46%. The number of patients treated with other bDMARDs/JAKis almost doubled within the prespecified timeframe. Overall, the average annual treatment cost per patient decreased by 60%, from 7315 EUR to 2886 EUR. Despite recent safety warnings, JAKis appear to be increasingly utilized. Additional analyses regarding the COVID‑19 pandemic showed impaired access to intravenous therapies, but not subcutaneous or oral formulations. In Poland, biosimilars‑related savings improved availability of higher‑priced innovative drugs rather than less costly TNFis. Data‑driven resource allocation and dedicated policy solutions facilitating access to affordable biologics are recommended.

Research on safety accident risk of construction engineering based on natural language processing technology and neural network technology

Abstract In recent years, China’s construction industry has achieved rapid development, while the problem of safety accident risks brought by construction projects has also arisen. In this paper, based on natural language processing technology, using a graph neural network algorithm, we constructed a graph data model of safety accident reports in construction engineering and generated a database of association rules of safety risk factors in construction engineering to identify and classify the risk of safety accidents in actual construction engineering. The pictures of safety risk behaviors at the construction site are processed with feature mapping and inputted into a convolutional neural network to build a construction engineering safety warning model. Through simulation experiments, the identification results of risk factors for the model constructed in this paper and the effective degree of safety warning are tested. The top five factors in the centrality ranking of risk factors of construction engineering safety accidents are S17, S6, S1, S9, and S8, with centrality levels of 1.9779, 1.8626, 1.8204, 1.6332 and 1.4534, and the factor attribute of S6 is the outcome factor. The warning model constructed in this paper is measured against the level of safety risk of the construction project under the non-adoption of the warning model. The safety risk is reduced by 35.8% after the adoption of the safety accident warning model, which shows that the model in this paper has a certain inhibition effect on the risk of safety accidents.

A real-time early warning method for electric vehicle fast charging safety based on multiple time scales

Abstract This paper puts forward the support technology of fast charging supply and demand matching in charging stations and analyzes the common large-capacity electrochemical energy storage technical parameters in charging stations. For the safety of electric vehicle charging, the thermal reaction and thermal runaway processes of power batteries are introduced. Design the electric vehicle charging state monitoring and safety warning methods, and select the multi-timescale ARIMA algorithm to build the electric vehicle charging safety warning model. The sliding window method is used to process the residual mean and residual standard deviation of electric vehicle charging data to improve prediction data and decrease the chance of misjudging pre- and alarms. Combined with the evaluation standard of the safety early warning model, set reasonable pre- and alarm thresholds using the residual analysis method. The safety warning model designed in this paper is verified by different charging fault warnings. Different charging fault warning examples show that the ARIMA-based charging safety early warning model proposed in this paper can be good for the charging facility’s output voltage, output current, and charging module temperature faults for early warning to ensure that the warning is carried out before the alarm of the actual fault information, to protect the charging safety of electric vehicles.

Turn-on mode probe based on the sustainable xanthohumol extract for the efficient viscosity response in a liquid system.

Viscosity is a typical physical parameter and plays an important role in nutrient transferring, diffusion process regulating and safety warning. Aberrant mitochondrial viscosity is closely associated with an imbalance in a liquid system. Nevertheless, there is currently a lack of convenient and efficient tools for the mutation of viscosity detection at the molecular level. Herein, a natural product xanthohumol (XTH) was extracted from Humulus lupulus and used to measure the microenvironmental viscosity. Due to the existence of carbonyl and phenolic hydroxyl groups, a typical twisted intramolecular charge transfer (TICT) was formed. The conjugated single and double bonds can be employed as the rotatable site. Consequently, a turn-on method based on viscosity response is developed. High sensitivity (x = 0.56) with a remarkable enhancement (55-fold) toward viscosity and a visualized fluorescent signal can be found. In addition, it displays a single selectivity with excellent photostability and pH stability in the complex liquid system. Using the extracted XTH, a typical application toward the liquid spoilage process was performed and a positive correlation was noted. Given the comprehensive properties of XTH, liquid safety inspection at a molecular level with natural source-extracted products can be obtained.

Sensitive Properties of Power Spectral Density Transmissibility (PSDT) to Moving Vehicles and Structural States in Bridge Health Monitoring

Bridge health monitoring confronts a critical challenge in extracting meaningful features that are sensitive to structural damage while remaining nonsensitive to operational environments and loads. Most of structural response features such as power spectral density (PSD) in the long‐term monitored bridge are influenced by operational vehicle loads. The power spectral density transmissibility (PSDT), defined as the power spectral density ratio of two measured output responses at two different structural locations with the same reference output response, converges independently at the system poles of the applied excitations and transferring outputs. Capitalizing on such a unique property of PSDT around the system poles, the PSDT‐based spectral moment is proposed in the paper to establish a robust structural feature in bridge health monitoring taking into account the time‐varying characteristics under operational vehicle loads. Numerical simulations and comparisons with PSD‐based spectral moment analysis reveal that the PSDT‐based spectral moment exhibits an enhanced robustness to traffic flow excitations and heightened sensitivity to changes in structural parameters. Further laboratory experimental results on the beam under moving vehicle confirm that the PSDT‐based spectral moment is less affected by moving vehicle loads, but it demonstrates higher sensitivity to structural parameter changes. Given its robust properties of low sensitivity to operational vehicle loads and sensitivity to changes in structural parameters, the proposed PSDT‐based spectral moment emerges as an ideal structural feature suitable for the effective applications in the long‐term bridge health monitoring, such as structural damage identification, model updating, condition assessment, and safety warning.

Constructing an innovative system of management and education in colleges and universities based on artificial intelligence technology

Abstract At this stage, the information literacy of teachers and students is constantly improving, and the “digital campus” represented by artificial intelligence is landing in various regions and schools. This paper accurately constructs a college management and education innovation system based on artificial intelligence technology, including institutional mechanisms, a one-stop service platform, and an early warning mechanism. The early warning mechanism has an early warning model constructed. The construction of an academic early warning model for students is based on multivariate linear regression. A model for early warning of student activity safety was constructed using multiclassification logistic regression. The impact of fusing the two models was evaluated, as well as the impact of practical application. The ROC value of the first-level warning is 0.9533, and the ROC value of the second-level warning is 0.9428, and both values are close to 1, which verifies that the model can be practically applied. By analyzing the F1-score value through practical application, the average value of the F1-score throughout the semester was as high as 84.68%, and the number of warnings of the early warning model was higher than the number of feedback from teachers. It has been verified that the early warning model in this study can effectively and efficiently manage student activities and academic anomalies in colleges and universities.

Update on the effect of dental general anaesthesia on neurocognition in children.

Dental general anaesthesia provides a comfortable treatment modality for children with early childhood caries and children's dental anxiety, but US Food and Drug Administration safety warnings have raised concerns about the neurotoxicity of general anaesthetic drugs. Currently, anaesthetic drugs have been found to impair neurocognitive function in animals, with possible mechanisms including cell damage, cell loss and impaired neuronal network function. The outcomes of clinical studies on the neurocognitive effects of surgical general anaesthesia in children have been inconsistent. However, studies focusing on dental general anaesthesia in children suggest that it does not affect neurocognitive function. In general, a growing number of studies suggest that dental general anaesthesia does not affect neurocognitive development in children. Moreover, dental general anesthesia should be used as normal when other behavioural management is unavailable.