ADHD medication discontinuation and persistence across the lifespan: a retrospective observational study using population-based databases.

BACKGROUND: Although often intended for long-term treatment, discontinuation of medication for ADHD is common. However, cross-national estimates of discontinuation are missing due to the absence of standardised measures. The aim of this study was to determine the rate of ADHD treatment discontinuation across the lifespan and to describe similarities and differences across countries to guide clinical practice. METHODS: We did a retrospective, observational study using population-based databases from eight countries and one Special Administrative Region (Australia, Denmark, Hong Kong, Iceland, the Netherlands, Norway, Sweden, the UK, and the USA). We used a common analytical protocol approach and extracted prescription data to identify new users of ADHD medication. Eligible individuals were aged 3 years or older who had initiated ADHD medication between 2010 and 2020. We estimated treatment discontinuation and persistence in the 5 years after treatment initiation, stratified by age at initiation (children [age 4-11 years], adolescents [age 12-17 years], young adults [age 18-24 years], and adults [age ≥25 years]) and sex. Ethnicity data were not available. FINDINGS: 1 229 972 individuals (735 503 [60%] males, 494 469 females [40%]; median age 8-21 years) were included in the study. Across countries, treatment discontinuation 1-5 years after initiation was lowest in children, and highest in young adults and adolescents. Within 1 year of initiation, 65% (95% CI 60-70) of children, 47% (43-51) of adolescents, 39% (36-42) of young adults, and 48% (44-52) of adults remained on treatment. The proportion of patients discontinuing was highest between age 18 and 19 years. Treatment persistence for up to 5 years was higher across countries when accounting for reinitiation of medication; at 5 years of follow-up, 50-60% of children and 30-40% of adolescents and adults were covered by treatment in most countries. Patterns were similar across sex. INTERPRETATION: Early medication discontinuation is prevalent in ADHD treatment, particularly among young adults. Although reinitiation of medication is common, treatment persistence in adolescents and young adults is lower than expected based on previous estimates of ADHD symptom persistence in these age groups. This study highlights the scope of medication treatment discontinuation and persistence in ADHD across the lifespan and provides new knowledge about long-term ADHD medication use. FUNDING: European Union Horizon 2020 Research and Innovation Programme.

Association between cognitive function and dusty weather: a propensity score matching study.

BACKGROUND: With a rapidly aging global population, the health of older adults is a national priority for countries across the world. Dusty weather has been demonstrated to be a potential risk factor of cognitive function among the elderly population. However, there is a paucity of studies exploring the associations between dusty weather and cognitive function among the older in China. METHODS: Data on individual characteristics were obtained from the China Health and Retirement Longitudinal Survey (CHARLS) 2018, whereas data on air pollution were sourced from environmental monitoring stations in China. Cognitive function, including general cognitive function, episodic memory, and linguistic competence, was assessed by self- or informant-questionnaires. We used propensity score matching and linear regression to investigate the relationship between dusty weather and cognitive function. Sensitivity analyses were conducted to test the robustness of the results. RESULTS: This study included 8,604 participants older than 60 years old. After controlling air pollutant weather, dusty weather was demonstrated to be positively associated with a decline in cognitive function (Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), 4.0, 95% confidence interval (CI): 3.11, 4.89; Mini-Mental State Exam (MMSE), 0.63, 95% CI: 0.34, 0.92). Results of sensitivity analysis showed that our research findings are robust. CONCLUSION: Older adults living in dusty weather regions suffered a higher level of cognitive impairment, and such adverse effects were more substantial among females compared with their male counterparts. Targeted health interventions to help older adults living in regions where dusty weather occurs frequently are suggested to be proposed.

Attention-deficit/hyperactivity disorder is associated with increased risk of cardiovascular diseases: A systematic review and meta-analysis.

Attention-deficit/hyperactivity disorder (ADHD) often co-occurs with other psychiatric and physical diseases. However, available evidence on associations between ADHD and cardiovascular diseases (CVDs) is mixed. To systematically review, quantitatively synthesize, and appraise available evidence on the link between ADHD with CVDs, we searched relevant articles in PubMed, Embase, PsycINFO, and Web of Science from inception to May 1, 2022. Study quality was assessed by using the Newcastle-Ottawa Scale, and random-effects model meta-analyses were performed. A total of 18,391,169 (ADHD: n = 421,224) individuals from 11 studies were included in our systematic review and 8,196,648 (ADHD = 332,619) individuals from five studies were included in the main meta-analysis of adjusted estimates. Pooled estimates showed that ADHD was significantly associated with an increased risk of CVDs in analyses based on adjusted effect size (odds ratio (OR) = 1.96; 95% confidence interval (CI) = 1.19-2.23, Q = 140.74, P Q < 0.001, I 2 = 97.2%). When restricted among adults, the heterogeneity declined to null (OR = 1.73; 95% CI = 1.14-2.62, Q = 6.28, P Q = 0.10, I 2 = 6.28%), suggesting age might be the main source of heterogeneity. In subgroup analyses, we found increased risk of CVDs associated with ADHD across age groups, type of CVDs, and data sources. This systematic review and meta-analyses indicate that ADHD is associated with increased risk for CVDs, but further studies with various study designs are warranted to advance the understanding of the underlying mechanisms for the observed association between ADHD and CVDs. Additional research is also needed to resolve the role of ADHD medications which remains unclear due to the limited number of primary studies exploring this issue.

Mid-high-frequency error suppression of small optical aspheric molds.

To suppress the mid-high-frequency error of small optical tungsten carbide aspheric molds, it is proposed to quickly select the critical process parameters by simulating the residual error after convolution of the tool influence function (TIF). After polishing for 10.47 min by the TIF, two simulation optimizations, RMS and Ra, converge to 9.3 and 5.347 nm, respectively. Their convergence rates are improved by 40% and 7.9%, respectively, compared to ordinary TIF. Then, a faster and more high-quality multi-tool combination smoothing suppression method is proposed, and the corresponding polishing tools are designed. Finally, the global Ra of the aspheric surface converges from 5.9 to 4.5 nm after smoothing for 5.5 min with a disc-shaped polishing tool with a fine microstructure and maintains an excellent low-frequency error (PV 0.0781 µm).

The relationship of income on stroke incidence in Finland and China.

BACKGROUND: Stroke incidence has continued to increase recently in most countries. The roles of individual-level income on the incidence of overall stroke and its subtypes are still unknown, especially in low- and middle-income countries and the cross-national evidence is also limited. We explored the association between individual-level income and stroke incidence in Finland and China. METHODS: Changde Social Health Insurance Database (N=571 843) and Finnish population register (N=4 046 205) data were used to calculate standard stroke incidence rates, which were employed to assess the absolute incidence difference between income quintiles. Cox regression was used to compare income differences in first-ever stroke incidence. RESULTS: The highest income quintile had lower overall and subtype stroke incidence when compared to lower-income quintiles. The relative difference was more evident in hemorrhagic stroke incidence. After adjusting for age and employment status, the disparity of stroke incidence between the lowest and highest income quintiles was high among both men and women and in Finland and China. The disparity was particularly notable among men: in Finland, the hazard ratio (HR) for hemorrhagic stroke was 0.633 [95% confidence interval (95% CI) 0.576-0.696] and HR 0.572 (95% CI 0.540-0.606) for ischemic stroke. The respective figures were HR 0.452 (95% CI 0.276-0.739) and HR 0.633 (95% CI 0.406-0.708) for China. CONCLUSIONS: Individual-level income is related to overall and subtype stroke incidence. Future studies should explore the causal relationship between individual-level income and stroke incidence.

The association between type 2 diabetes and attention- deficit/hyperactivity disorder: A systematic review, meta-analysis, and population-based sibling study.

We conducted a systematic review and a meta-analysis to quantitatively summarize evidence on the association between attention-deficit/hyperactivity disorder (ADHD) and type 2 diabetes (T2D). Moreover, a register-based sibling study was conducted to simultaneously control for confounding factors. A systematic search identified four eligible observational studies (N = 5738,287). The meta-analysis showed that individuals with ADHD have a more than doubled risk of T2D when considering adjusted estimates (OR=2.29 [1.48-3.55], d=0.46). Results from the register-based Swedish data showed a significant association between ADHD and T2D (HR=2.35 [2.14-2.58]), with substance use disorder, depression, and anxiety being the main drivers of the association, and cardiovascular and familiar risk playing a smaller role. While results from the meta-analysis provide evidence for an increased risk of T2D in individuals with ADHD, the register-based analyses show that the association between ADHD and T2D is largely explained by psychiatric comorbidities. Pending further evidence of causal association, our findings suggest that early identification and treatment of ADHD comorbidities might greatly reduce the risk of developing T2D in individuals with ADHD.

Risk of Cardiovascular Diseases Associated With Medications Used in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-analysis.

Importance: Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades, but there are concerns regarding their cardiovascular safety. Objective: To provide an updated synthesis of evidence on whether ADHD medications are associated with the risk of a broad range of cardiovascular diseases (CVDs). Data Sources: PubMed, Embase, PsycINFO, and Web of Science up to May 1, 2022. Study Selection: Observational studies investigating the association between ADHD medications (including stimulants and nonstimulants) and risk of CVD. Data Extraction and Synthesis: Independent reviewers extracted data and assessed study quality using the Good Research for Comparative Effectiveness (GRACE) checklist. Data were pooled using random-effects models. This study is reported according to the Meta-analyses of Observational Studies in Epidemiology guideline. Main Outcomes and Measures: The outcome was any type of cardiovascular event, including hypertension, ischemic heart disease, cerebrovascular disease, heart failure, venous thromboembolism, tachyarrhythmias, and cardiac arrest. Results: Nineteen studies (with 3 931 532 participants including children, adolescents, and adults; 60.9% male), of which 14 were cohort studies, from 6 countries or regions were included in the meta-analysis. Median follow-up time ranged from 0.25 to 9.5 years (median, 1.5 years). Pooled adjusted relative risk (RR) did not show a statistically significant association between ADHD medication use and any CVD among children and adolescents (RR, 1.18; 95% CI, 0.91-1.53), young or middle-aged adults (RR, 1.04; 95% CI, 0.43-2.48), or older adults (RR, 1.59; 95% CI, 0.62-4.05). No significant associations for stimulants (RR, 1.24; 95% CI, 0.84-1.83) or nonstimulants (RR, 1.22; 95% CI, 0.25-5.97) were observed. For specific cardiovascular outcomes, no statistically significant association was found in relation to cardiac arrest or arrhythmias (RR, 1.60; 95% CI, 0.94-2.72), cerebrovascular diseases (RR, 0.91; 95% CI, 0.72-1.15), or myocardial infarction (RR, 1.06; 95% CI, 0.68-1.65). There was no associations with any CVD in female patients (RR, 1.88; 95% CI, 0.43-8.24) and in those with preexisting CVD (RR, 1.31; 95% CI, 0.80-2.16). Heterogeneity between studies was high and significant except for the analysis on cerebrovascular diseases. Conclusions and Relevance: This meta-analysis suggests no statistically significant association between ADHD medications and the risk of CVD across age groups, although a modest risk increase could not be ruled out, especially for the risk of cardiac arrest or tachyarrhythmias. Further investigation is warranted for the cardiovascular risk in female patients and patients with preexisting CVD as well as long-term risks associated with ADHD medication use.

Surface Quality Control Strategy of Aspherical Mold Based on Screw Feed Polishing of Small Polishing Tool.

For small aspherical molds, it is difficult for the existing polishing method to take into account the correction of the surface error and the control of the uniformity of the surface roughness (SR) distribution, because the polishing tool is always larger than the small mold. Therefore, we used viscoelastic polyester fiber cloth to wrap the small steel ball as a polishing tool to adapt to the surface shape change of the aspherical mold, and designed a semi-flexible small polishing disc tool with microstructure, which can better adapt to the curvature change of aspherical surface and obtain better SR Ra. At the same time, a combined polishing method of constant speed and variable speed for screw feed was proposed to improve the uniformity of SR distribution in the paper. Then, a series of theoretical analysis and experimental verification were carried out in this paper to predict the tool influence function (TIF) of the two polishing tools and the effectiveness of the combined polishing method. In the experiment, a TIF bandwidth of about 0.46 mm was obtained with a small spherical polishing tool, which favors the surface shape correction of the small aspherical mold. The experiment of uniform removal with a small polishing disc tool was carried out to quickly reduce the Ra. Finally, the surface quality of the aspherical mold was effectively improved, combined with the constant speed and variable speed polishing modes of screw feed of the small spherical polishing tool and the smoothing effect of the small polishing disc tool. The peak valley (PV) of two small aspherical molds with an optical effective diameter less than 13 mm converged from 0.3572 µm and 0.2075 µm to 0.1282 µm and 0.071 µm, respectively. At the same time, the SR dispersion coefficient was reduced from 27.9% and 41.6% to 14.2% and 12.7%, respectively. The study provides a good solution for the surface quality control of small aspherical molds.

Did the universal zero-markup drug policy lower healthcare expenditures? Evidence from Changde, China.

BACKGROUND: The zero-markup drug policy (also known as the universal zero-markup drug policy (UZMDP)) was implemented in stages beginning with primary healthcare facilities in 2009 and eventually encompassing city public hospitals in 2016. This policy has been a central pillar of Chinese health reforms. While the literature has examined the impacts of this policy on healthcare utilization and expenditures, a more comprehensive and detailed assessment is warranted. The purpose of this paper is to explore the impacts of the UZMDP on inpatient and outpatient visits as well as on both aggregate healthcare expenditures and its various components (including drug, diagnosis, laboratory, and medical consumables expenditures). METHODS: A pre-post design was applied to a dataset extracted from the Changde Municipal Human Resource and Social Security Bureau comprising discharge data on 27,246 inpatients and encounter data on 48,282 outpatients in Changde city, Hunan province, China. The pre-UZMDP period for the city public hospitals was defined as the period from October 2015 to September 2016, while the post-UZMDP period was defined as the period from October 2016 to September 2017. Difference-in-Difference negative binomial and Tobit regression models were employed to evaluate the impacts of the UZMDP on healthcare utilization and expenditures, respectively. RESULTS: Four key findings flow from our assessment of the impacts of the UZMDP: first, outpatient and inpatient visits increased by 8.89 % and 9.39 %, respectively; second, average annual inpatient and outpatient drug expenditures fell by 4,349.00 CNY and 1,262.00 CNY, respectively; third, average annual expenditures on other categories of healthcare expenditures increased by 2,500.83 CNY, 417.10 CNY, 122.98 CNY, and 143.50 CNY for aggregate inpatient, inpatient diagnosis, inpatient laboratory, and outpatient medical consumables expenditures, respectively; and fourth, men and older individuals tended to have more inpatient and outpatient visits than their counterparts. CONCLUSIONS: Although the UZMDP was effective in reducing both inpatient and outpatient drug expenditures, it led to a sharp rise in other expenditure categories. Policy decision makers are advised to undertake efforts to contain the growth in total healthcare expenditures, in general, as well as to evaluate the offsetting effects of the policy on non-drug components of care.

Turning up the heat on non-immunoreactive tumors: pyroptosis influences the tumor immune microenvironment in bladder cancer.

The latest research confirms that cytotoxic lymphocytes rely on pyroptosis to kill tumor cells, suggesting that pyroptosis plays a vital role in immune response. However, the influence of pyroptosis on tumor microenvironment (TME) remodeling and immunotherapy is still unclear. We analyzed the variations in the expression of 28 pyroptosis-related molecules in pan-cancer tissues and normal tissues and the influence of genome changes. We investigated 2,214 bladder cancer samples and determined that there are three pyroptosis phenotypes in bladder cancer, and there are significant differences in cell infiltration characteristics in different pyroptosis phenotypes. Phenotypes with high expression of pyroptosis-related molecules are "hot tumors" with better immune function. We used a principal component analysis to measure the level of pyroptosis in patients with PyroScore, and confirmed that the PyroScore can predict the prognosis of bladder cancer patients, the sensitivity of the immune phenotype to chemotherapy, and the response to immunotherapy. Patients with a high PyroScore are more sensitive to chemotherapeutics such as cisplatin and gemcitabine, and have a better prognosis (HR = 0.7; 95%CI = 0.51-0.97, P = 0.041). Our study suggests a significant correlation between the expression imbalance of pyroptosis-related molecules and genome variation in various cancers and suggests pyroptosis plays an important role in modeling the TME. Evaluating pyroptosis modification patterns contributes to enhancing our understanding of TME infiltration and can guide more effective immunotherapy strategies.

Current situation and distribution equality of public health resource in China.

BACKGROUND: The public health system has been developed in China for several years while no research explores its distribution. This research aims to describe the variation and equality of public health allocation from 2013 to 2018 and explore the source of inequality. METHODS: Data in this research was obtained from the China Health Statistics Yearbook 2014 to 2019 and the China Statistical Yearbook 2019. Four indicators were chosen in describing the development and current situation of the public health system. Three of them were used to evaluate allocation equality. 31 provinces were categorized into western, middle, and eastern groups based on geographical and economic conditions. Total allocation equality, inter- and intra-difference were all measured by the Theil index. RESULTS: All indicators showed a stably upwards trend except for the number of public health institutions. The allocation gap of the public health institution per km2 was larger than that per 10,000 capita. Theil index of three indicators continually rose from 2013 to 2018 and the inequality of public health institutions allocation was the highest one. The western region had the highest Theil index in technical personnel and beds allocation. Among the three regions, the western region contributed most to inequality. CONCLUSIONS: The public health workforces and institutions are still under the requirement of the National Medical and Health Service System Plan. From 2013 to 2018, the equality of public health resources stably decreases, which is mainly contributed by the internal difference within the western region. Further research should be done to explore the possible cause of the results. Problems founded in this research should be solved by multisectoral cooperation.

Associations of cigarette smoking with psychiatric disorders: evidence from a two-sample Mendelian randomization study.

We conducted a two-sample Mendelian randomization study to determine the association of smoking initiation with seven psychiatric disorders. We used 353 independent single-nucleotide polymorphisms associated with cigarette smoking initiation as instrumental variables at genome-wide significance threshold (p < 5 × 10-8) from a recent genome-wide association study in 1,232,091 European-origin participants. Summary-level data for seven psychiatric disorders, including anxiety, bipolar disorder, insomnia, major depressive disorder, posttraumatic stress disorder, suicide attempts, and schizophrenia, was obtained from large genetic consortia and genome-wide association studies. The odds ratios of genetically predicted smoking initiation were 1.96 for suicide attempts (95% CI 1.70, 2.27; p = 4.5 × 10-20), 1.69 for post-traumatic stress disorder (95% CI 1.32, 2.16; p = 2.5 × 10-5), 1.54 for schizophrenia (95% CI 1.35, 1.75; p = 1.6 × 10-10), 1.41 for bipolar disorder (95% CI 1.25, 1.59; p = 1.8 × 10-8), 1.38 for major depressive disorder (95% CI 1.31, 1.45; p = 2.3 × 10-38), 1.20 for insomnia (95% CI 1.14, 1.25; p = 6.0 × 10-14) and 1.17 for anxiety (95% CI 0.98, 1.40; p = 0.086). Results of sensitivity analyses were consistent and no horizontal pleiotropy was detected in MR-Egger analysis. However, the associations with suicide attempts, schizophrenia, bipolar disorder, and anxiety might be related to possible reverse causality or weak instrument bias. This study found that cigarette smoking was causally associated with increased risks of a number of psychiatric disorders. The causal effects of smoking on suicide attempts, schizophrenia, bipolar disorder and anxiety needs further research.

Author Correction: Directed self-assembly of herbal small molecules into sustained release hydrogels for treating neural inflammation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Effect of Elastic Modulus on the Accuracy of the Finite Element Method in Simulating Precision Glass Molding.

Precision glass molding is a revolutionary technology for achieving high precision and efficient manufacturing of glass aspheric lenses. The material properties of glass, including elastic modulus and viscosity, are highly dependent on temperature fluctuations. This paper aims to investigate the effect of elastic modulus on the high-temperature viscoelasticity of glass and the accuracy of the finite element simulation of the molding process for glass aspheric lenses. The high-temperature elastic modulus of D-ZK3L glass is experimentally measured and combined with the glass cylinder compression creep curve to calculate the high temperature viscoelasticity of D-ZK3L. Three groups of viscoelastic parameters are obtained. Based on this, the molding process of the molded aspheric lens is simulated by the nonlinear finite element method (FEM). The surface curves of lenses obtained by simulation and theoretical analyses are consistent. The simulation results obtained at different initial elastic modulus values indicate that the elastic modulus has a great influence on the precision of the FEM-based molding process of glass aspheric lenses.

Directed self-assembly of herbal small molecules into sustained release hydrogels for treating neural inflammation.

Self-assembling natural drug hydrogels formed without structural modification and able to act as carriers are of interest for biomedical applications. A lack of knowledge about natural drug gels limits there current application. Here, we report on rhein, a herbal natural product, which is directly self-assembled into hydrogels through noncovalent interactions. This hydrogel shows excellent stability, sustained release and reversible stimuli-responses. The hydrogel consists of a three-dimensional nanofiber network that prevents premature degradation. Moreover, it easily enters cells and binds to toll-like receptor 4. This enables rhein hydrogels to significantly dephosphorylate IκBα, inhibiting the nuclear translocation of p65 at the NFκB signalling pathway in lipopolysaccharide-induced BV2 microglia. Subsequently, rhein hydrogels alleviate neuroinflammation with a long-lasting effect and little cytotoxicity compared to the equivalent free-drug in vitro. This study highlights a direct self-assembly hydrogel from natural small molecule as a promising neuroinflammatory therapy.