Rates of Antipsychotic Drug Prescribing Among People Living With Dementia During the COVID-19 Pandemic.

Importance: Concerns have been raised that the use of antipsychotic medication for people living with dementia might have increased during the COVID-19 pandemic. Objective: To examine multinational trends in antipsychotic drug prescribing for people living with dementia before and during the COVID-19 pandemic. Design, Setting, and Participants: This multinational network cohort study used electronic health records and claims data from 8 databases in 6 countries (France, Germany, Italy, South Korea, the UK, and the US) for individuals aged 65 years or older between January 1, 2016, and November 30, 2021. Two databases each were included for South Korea and the US. Exposures: The introduction of population-wide COVID-19 restrictions from April 2020 to the latest available date of each database. Main Outcomes and Measures: The main outcomes were yearly and monthly incidence of dementia diagnosis and prevalence of people living with dementia who were prescribed antipsychotic drugs in each database. Interrupted time series analyses were used to quantify changes in prescribing rates before and after the introduction of population-wide COVID-19 restrictions. Results: A total of 857 238 people with dementia aged 65 years or older (58.0% female) were identified in 2016. Reductions in the incidence of dementia were observed in 7 databases in the early phase of the pandemic (April, May, and June 2020), with the most pronounced reduction observed in 1 of the 2 US databases (rate ratio [RR], 0.30; 95% CI, 0.27-0.32); reductions were also observed in the total number of people with dementia prescribed antipsychotic drugs in France, Italy, South Korea, the UK, and the US. Rates of antipsychotic drug prescribing for people with dementia increased in 6 databases representing all countries. Compared with the corresponding month in 2019, the most pronounced increase in 2020 was observed in May in South Korea (Kangwon National University database) (RR, 2.11; 95% CI, 1.47-3.02) and June in the UK (RR, 1.96; 95% CI, 1.24-3.09). The rates of antipsychotic drug prescribing in these 6 databases remained high in 2021. Interrupted time series analyses revealed immediate increases in the prescribing rate in Italy (RR, 1.31; 95% CI, 1.08-1.58) and in the US Medicare database (RR, 1.43; 95% CI, 1.20-1.71) after the introduction of COVID-19 restrictions. Conclusions and Relevance: This cohort study found converging evidence that the rate of antipsychotic drug prescribing to people with dementia increased in the initial months of the COVID-19 pandemic in the 6 countries studied and did not decrease to prepandemic levels after the acute phase of the pandemic had ended. These findings suggest that the pandemic disrupted the care of people living with dementia and that the development of intervention strategies is needed to ensure the quality of care.

TEMPO: A transformer-based mutation prediction framework for SARS-CoV-2 evolution.

The widespread of SARS-CoV-2 presents a significant threat to human society, as well as public health and economic development. Extensive efforts have been undertaken to battle against the pandemic, whereas effective approaches such as vaccination would be weakened by the continuous mutations, leading to considerable attention being attracted to the mutation prediction. However, most previous studies lack attention to phylogenetics. In this paper, we propose a novel and effective model TEMPO for predicting the mutation of SARS-CoV-2 evolution. Specifically, we design a phylogenetic tree-based sampling method to generate sequence evolution data. Then, a transformer-based model is presented for the site mutation prediction after learning the high-level representation of these sequence data. We conduct experiments to verify the effectiveness of TEMPO, leveraging a large-scale SARS-CoV- 2 dataset. Experimental results show that TEMPO is effective for mutation prediction of SARS- CoV-2 evolution and outperforms several state-of-the-art baseline methods. We further perform mutation prediction experiments of other infectious viruses, to explore the feasibility and robustness of TEMPO, and experimental results verify its superiority. The codes and datasets are freely available at https://github.com/ZJUDataIntelligence/TEMPO.

Prevalence and risk factors for repetition of non-fatal self-harm in Hong Kong, 2002-2016: A population-based cohort study.

BACKGROUND: A history of self-harm is strongly associated with future self-harm attempts. Large-scale Asian cohort studies examining risk factors for repeated self-harm are lacking. This paper reports on annual prevalence, cumulative risk, annual risk of non-fatal self-harm repetition, and risk factors among Hong Kong patients with a history of self-harm. METHODS: The Hong Kong Clinical Data Analysis and Reporting System (CDARS) provided all accident & emergency department and inpatient self-harm records between Jan 1, 2002 and Dec 31, 2016. Demographic and clinical characteristics were extracted. Annual prevalence, over-time cumulative and annual risks of non-fatal self-harm repetition were estimated, and the adjusted hazard ratios (HR; plus 95% CIs) of putative risk factors associated with repetition were estimated using Wei-Lin-Weissfeld (WLW) generalization of the Cox model for recurrent event analysis. FINDINGS: There were 127,801 self-harm episodes by 99,116 individuals. Annual prevalence of repeated self-harm, of all self-harms, ranged from 7•36% to 28•71% during the study period. Risk of self-harm repetition within one year of the index event was 14•25% (95% CI, 14•04%-14•46%). People with four or more previous self-harm episodes carried the highest risk of self-harm repetition (adjusted HR 4•81 [95% CI 4•46-5•18]). Significant risk factors for non-fatal self-harm repetition included male gender (1•08 [1•05-1•11]), older age (65+ years) (1•07 [1•01-1•13]), social welfare for payment (1•30 [1•27-1•34]), psychiatric admission (1•60 [1•50-1•72]), self-injury only (1•19 [1•15-1•23]), self-injury combined with self-poisoning (1•38 [1•24-1•53]), depression and bipolar disorders (1•09 [1•04-1•14]), personality disorders (1•18 [1•06-1•32]), substance misuse (1•31 [1•27-1•36]), and asthma (1•18 [1•02-1•36]). INTERPRETATION: Hong Kong self-harm patients with non-fatal self-harm events should be supported by effective, timely and ongoing aftercare plans based on their risk profiles, to reduce risk of self-harm reoccurrence. FUNDING: Research Grants Council, General Research Funding: 17611619.

Assessment of Opicinumab in Acute Optic Neuritis Using Multifocal Visual Evoked Potential.

BACKGROUND: Multifocal visual evoked potential (MF-VEP) assesses a wider visual field than full-field VEP (FF-VEP) and potentially offers a more precise analysis of optic nerve injury and repair following optic neuritis. MF-VEP may offer advantages over FF-VEP as an endpoint in clinical trials of remyelinating therapies. OBJECTIVE: MF-VEP testing was used to study changes in visual pathways in 48% of RENEW [phase II, opicinumab (anti-LINGO-1; BIIB033) vs. placebo after first acute unilateral optic neuritis] participants. METHODS: This exploratory MF-VEP RENEW substudy compared mean outcomes at weeks 24 and 32 among participants in the intent-to-treat (ITT; n = 39; 72% female; mean age: 32.3 years) and per-protocol (PP; n = 31; 71% female; mean age: 32.2 years) populations in affected and fellow eye latency from fellow eye baseline latency and affected and fellow eye amplitude from their own baselines. Treatment differences were evaluated using analysis of covariance (week 24) and a mixed-effect model of repeated measures (week 32). Last observation carried forward was used to impute missing data at week 24. RESULTS: A trend for improvement in affected eye MF-VEP latency with opicinumab versus placebo was seen in the ITT and PP populations at weeks 24 and 32. Both treatment groups in the ITT population experienced partial recovery of amplitude in the affected eye at week 32. Notably, the mean change in fellow eye amplitude at weeks 24 and 32 was - 17.57 and - 31.41 nanovolts (nV) in placebo but only - 0.59 and 1.93 nV in the opicinumab group [differences at weeks 24 and 32: 16.98 nV (p = 0.050) and 33.33 nV (p < 0.01), respectively]. CONCLUSION: Results from this substudy showed advantages of MF-VEP over FF-VEP in multicenter studies of central nervous system reparative therapies and provide novel evidence that fellow eye visual pathway amplitude loss occurs after optic neuritis but can potentially be prevented by opicinumab treatment. REGISTRATION: ClinicalTrials.gov identifier NCT01721161.

Racial disparities and sex-based outcomes differences after severe injury.

BACKGROUND: Controversy exists about the mechanisms responsible for sex-based outcomes differences post-injury. X-chromosome-linked immune response pathway polymorphisms represent a potential mechanism resulting in sex-based outcomes differences post-injury. The prevalence of these variants is known to differ across race. We sought to characterize racial differences and the strength of any sex-based dimorphism post-injury. STUDY DESIGN: A retrospective analysis was performed using data derived from the National Trauma Data Bank 7.1 (2002-2006). Blunt-injured adult (older than 15 years) patients, surviving >24 hours and with an Injury Severity Score >16 were analyzed (n = 244,371). Patients were stratified by race (Caucasian, black, Hispanic, Asian) and multivariable regression analysis was used to characterize the risk of mortality and the strength of protection associated with sex (female vs male). RESULTS: When stratified by race, multivariable models demonstrated Caucasian females had an 8.5% lower adjusted risk of mortality (odds ratio [OR] = 0.91; 95% CI, 0.88-0.95; p < 0.001) relative to Caucasian males, with no significant association found for Hispanics or blacks. An exaggerated survival benefit was afforded to Asian females relative to Asian males, having a >40% lower adjusted risk of mortality (OR = 0.59; 95% CI, 0.44-78; p < 0.001). Asian males had a >75% higher adjusted risk of mortality relative to non-Asian males (OR = 1.77; 95% CI, 1.5-2.0; p < 0.001), and no significant difference in the mortality risk was found for Asian females relative to non-Asian females. CONCLUSIONS: These results suggest that Asian race is associated with sex-based outcomes differences that are exaggerated, resulting from worse outcomes for Asian males. These racial disparities suggest a negative male X-chromosome-linked effect as the mechanism responsible for these sex-based outcomes differences.

Linear matrix inequality criteria for robust synchronization of uncertain fractional-order chaotic systems.

This paper is devoted to synchronization of uncertain fractional-order chaotic systems with fractional-order α: 0 < α < 1 and 1 ≤ α < 2, respectively. On the basis of the stability theory of fractional-order differential system and the observer-based robust control, two sufficient and necessary conditions for synchronizing uncertain fractional-order chaotic systems with parameter perturbations are presented in terms of linear matrix inequality, which is an efficient method and could be easily solved by the toolbox of MATLAB. Finally, fractional-order uncertain chaotic Lü system with fractional-order α = 0.95 and fractional-order uncertain chaotic Lorenz system with fractional-order α = 1.05 are taken as numerical examples to show the validity and feasibility of the proposed method.