Trends in Treatment for Patients with Late-onset Rheumatoid Arthritis in Japan: Data from the NinJa Study.

OBJECTIVES: To investigate trends in the treatment of patients with late-onset rheumatoid arthritis (LORA) using data from the National Database of Rheumatic Diseases in Japan (NinJa). METHODS: Patients registered in the NinJa were classified according to disease onset: at <65 years (young-onset rheumatoid arthritis [YORA]); at 65-74 years (early LORA); and at ≥75 years (late LORA). Chronological changes in the treatment and disease activity were compared. RESULTS: A total of 7,178, 13,171, 15,295, and 15,943 patients were evaluated in 2010, 2013, 2016, and 2019, respectively. In all groups, the use of methotrexate gradually decreased, whereas that of biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) increased; the use of tumor necrosis factor inhibitors (TNFi) decreased, whereas that of non-TNFi increased. LORA was characterized by more single DMARD use, and less methotrexate and biological/targeted synthetic DMARD use. TNFi and interleukin-6 inhibitors were used less frequently, whereas abatacept was utilized more frequently in late versus early LORA. Conventional synthetic DMARD (excluding methotrexate) and glucocorticoid use was higher in late versus early LORA. CONCLUSIONS: This analysis revealed chronological changes in the treatment of LORA in Japan. Differences between early and late LORA suggest that patients are not a homogeneous population.

The long-term reproducibility of the white-coat effect on blood pressure as a continuous variable from the Ohasama Study.

There is little information about the reproducibility of the white coat effect, which was treated as a continuous variable. To investigate a long-term interval reproducibility of the white-coat effect as a continuous variable. We selected 153 participants without antihypertensive treatment (men, 22.9%; age, 64.4 years) from the general population of Ohasama, Japan, to assess the repeatedly measured white-coat effect (the difference between blood pressures at the office and home) in a 4-year interval. The reproducibility was assessed by testing the intraclass correlation coefficient (two-way random effect model-single measures). The white-coat effect for systolic/diastolic blood pressure slightly decreased by 0.17/1.56 mmHg at the 4-year visit on average. The Bland-Altman plots showed no significant systemic error for the white-coat effects (P ≥ 0.24). The intraclass correlation coefficient (95% confidence interval) of the white-coat effect for systolic blood pressure, office systolic blood pressure, and home systolic blood pressure were 0.41 (0.27-0.53), 0.64 (0.52-0.74), and 0.74 (0.47-0.86), respectively. Change in the white-coat effect was mainly affected by a change in office blood pressure. Long-term reproducibility of the white-coat effect is limited in the general population without antihypertensive treatment. The change in the white-coat effect is mainly caused by office blood pressure variation.

Investigating the phenotypic and genetic associations between personality traits and suicidal behavior across major mental health diagnoses.

Personality traits influence risk for suicidal behavior. We examined phenotype- and genotype-level associations between the Big Five personality traits and suicidal ideation and attempt in major depressive, bipolar and schizoaffective disorder, and schizophrenia patients (N = 3012) using fixed- and random-effects inverse variance-weighted meta-analyses. Suicidal ideations were more likely to be reported by patients with higher neuroticism and lower extraversion phenotypic scores, but showed no significant association with polygenic load for these personality traits. Our findings provide new insights into the association between personality and suicidal behavior across mental illnesses and suggest that the genetic component of personality traits is unlikely to have strong causal effects on suicidal behavior.

Developing and validating regression models for predicting household consumption to introduce an equitable and sustainable health insurance system in Cambodia.

BACKGROUND: Financial protection is a challenge for low- and middle-income countries, where the fiscal space is limited, and majority of the population is engaged in the informal economy. This study developed and validated household consumption predictive models for Cambodia to collect contributions according to one's ability to pay. METHODS: This study used nationally representative survey data collected annually between 2010 and 2017, involving 38,472 households. We developed four alternative models: the manually selected linear model, the linear model with stepwise technique, the mixed effects linear model, and the model with regularisation technique. Subsequently, we performed out-of-sample cross-validation for each model, and evaluated the model prediction performance. RESULTS: Overall, observed and predicted household consumptions were linearly related in all four models. While the prediction performance of the models did not substantially differ, the stepwise linear model showed the best performance. The regularisation and the mixed effects were not particularly effective in these regressions. The household consumption was better predicted for those with lower consumption, and the predictivity declined as the consumption level increased. CONCLUSIONS: This study suggests the possibility of predicting household consumption at a reasonable level. This would maximise the contribution revenue, optimise the government subsidy, and ensure equity in healthcare access.

Switching dynamics of silicon waveguide optical modulator driven by photothermally induced metal-insulator transition of vanadium dioxide cladding layer.

We investigated the switching dynamics of optical modulators consisting of a Si waveguide with a VO2 cladding layer by utilizing the photothermal effect, which induces a metal-insulator transition in VO2. The devices exhibited stable optical switching with a high extinction ratio exceeding 16 dB. The switching time of the insulator-to-metal transition (heating process) ranged from tens of nanoseconds to microseconds depending on the incident light power, and that of the metal-to-insulator transition (cooling process) was several microseconds regardless of the incident light power. The heat transfer in the devices was numerically simulated to reproduce the switching characteristics and revealed that the temperature change in the first few micrometers of the VO2/Si waveguide governed the switching time. The thermal structural design of the device is thus of key importance to improve the switching speed of the device.

Implementing a sustainable health insurance system in Cambodia: a study protocol for developing and validating an efficient household income-level assessment model for equitable premium collection.

BACKGROUND: As elsewhere in low- and middle-income countries, due to limited fiscal resources, universal health coverage (UHC) remains a challenge in Cambodia. Since 2016, the National Social Security Fund (NSSF) has implemented a social health insurance scheme with a contributory approach for formal sector workers. However, informal sector workers and dependents of formal sector workers are still not covered by this insurance because it is difficult to set an optimal amount of contribution for such individuals as their income levels are inestimable. The present study aims to develop and validate an efficient household income-level assessment model for Cambodia. We aim to help the country implement a financially sustainable social health insurance system in which the insured can pay contributions according to their ability. METHODS: This study will use nationally representative data collected by the Cambodia Socio-Economic Survey (CSES), covering the period from 2009 to 2019, and involving a total of 50,016 households. We will employ elastic net regression analysis, with per capita disposable income based on purchasing power parity as the dependent variable, and individual and community-level socioeconomic and demographic characteristics as independent variables. These analyses aim to create efficient income-level assessment models for health insurance contribution estimation. To fully capture socioeconomic heterogeneity, sub-group analyses will be conducted to develop separate income-level assessment models for urban and rural areas, as well as for each province. DISCUSSION: This research will help Cambodia implement a sustainable social health insurance system by collecting optimal amount of contributions from each socioeconomic group of the society. Incorporation of this approach into existing NSSF schemes will enhance the country's current efforts to prevent impoverishing health expenditure and to achieve UHC.

An Investigation of Psychosis Subgroups With Prognostic Validation and Exploration of Genetic Underpinnings: The PsyCourse Study.

Importance: Identifying psychosis subgroups could improve clinical and research precision. Research has focused on symptom subgroups, but there is a need to consider a broader clinical spectrum, disentangle illness trajectories, and investigate genetic associations. Objective: To detect psychosis subgroups using data-driven methods and examine their illness courses over 1.5 years and polygenic scores for schizophrenia, bipolar disorder, major depression disorder, and educational achievement. Design, Setting, and Participants: This ongoing multisite, naturalistic, longitudinal (6-month intervals) cohort study began in January 2012 across 18 sites. Data from a referred sample of 1223 individuals (765 in the discovery sample and 458 in the validation sample) with DSM-IV diagnoses of schizophrenia, bipolar affective disorder (I/II), schizoaffective disorder, schizophreniform disorder, and brief psychotic disorder were collected from secondary and tertiary care sites. Discovery data were extracted in September 2016 and analyzed from November 2016 to January 2018, and prospective validation data were extracted in October 2018 and analyzed from January to May 2019. Main Outcomes and Measures: A clinical battery of 188 variables measuring demographic characteristics, clinical history, symptoms, functioning, and cognition was decomposed using nonnegative matrix factorization clustering. Subtype-specific illness courses were compared with mixed models and polygenic scores with analysis of covariance. Supervised learning was used to replicate results in validation data with the most reliably discriminative 45 variables. Results: Of the 765 individuals in the discovery sample, 341 (44.6%) were women, and the mean (SD) age was 42.7 (12.9) years. Five subgroups were found and labeled as affective psychosis (n = 252), suicidal psychosis (n = 44), depressive psychosis (n = 131), high-functioning psychosis (n = 252), and severe psychosis (n = 86). Illness courses with significant quadratic interaction terms were found for psychosis symptoms (R2 = 0.41; 95% CI, 0.38-0.44), depression symptoms (R2 = 0.28; 95% CI, 0.25-0.32), global functioning (R2 = 0.16; 95% CI, 0.14-0.20), and quality of life (R2 = 0.20; 95% CI, 0.17-0.23). The depressive and severe psychosis subgroups exhibited the lowest functioning and quadratic illness courses with partial recovery followed by reoccurrence of severe illness. Differences were found for educational attainment polygenic scores (mean [SD] partial η2 = 0.014 [0.003]) but not for diagnostic polygenic risk. Results were largely replicated in the validation cohort. Conclusions and Relevance: Psychosis subgroups were detected with distinctive clinical signatures and illness courses and specificity for a nondiagnostic genetic marker. New data-driven clinical approaches are important for future psychosis taxonomies. The findings suggest a need to consider short-term to medium-term service provision to restore functioning in patients stratified into the depressive and severe psychosis subgroups.

Silicon waveguide optical modulator driven by metal-insulator transition of vanadium dioxide cladding layer.

We have fabricated compact optical modulators consisting of a Si waveguide with a VO2 cladding layer. These devices showed a sharp decrease in transmittance at around 60 °C, which is attributable to the metal-insulator transition of the VO2 cladding layer. By systematically varying the length of the device, we evaluated the transmission losses per unit length of the device to be 1.27 dB/µm, when the VO2 cladding layer was in the insulating (ON) state and 4.55 dB/µm when it was in the metallic (OFF) state. Furthermore, we found that the device showed an additional loss in the OFF state, which is attributable to a structural effect. As a result, an 8-µm-long device showed a large extinction ratio of more than 33 dB.

Broad-band surface optical coupler based on a SiO2-capped vertically curved silicon waveguide.

A chip-surface optical coupler based on a vertically curved Si waveguide was demonstrated for coupling with high-numerical-aperture single-mode optical fibers with a mode-field diameter of 5 µm. This device features a dome-like SiO2 coupler cap, which acts as collimation lens. We succeeded in fabricating this structure using an isotropic SiO2 deposition technique employing plasma-enhanced chemical vapor deposition and obtained a light output that approximates that of a 5-µm-waist Gaussian beam. The fabricated coupler showed a coupling loss of less than 4.2 dB and a 0.5-dB-loss bandwidth above 150 nm for TE-polarized light.

Production of HIV-1 vif mRNA Is Modulated by Natural Nucleotide Variations and SLSA1 RNA Structure in SA1D2prox Genomic Region.

Genomic RNA of HIV-1 contains localized structures critical for viral replication. Its structural analysis has demonstrated a stem-loop structure, SLSA1, in a nearby region of HIV-1 genomic splicing acceptor 1 (SA1). We have previously shown that the expression level of vif mRNA is considerably altered by some natural single-nucleotide variations (nSNVs) clustering in SLSA1 structure. In this study, besides eleven nSNVs previously identified by us, we totally found nine new nSNVs in the SLSA1-containing sequence from SA1, splicing donor 2, and through to the start codon of Vif that significantly affect the vif mRNA level, and designated the sequence SA1D2prox (142 nucleotides for HIV-1 NL4-3). We then examined by extensive variant and mutagenesis analyses how SA1D2prox sequence and SLSA1 secondary structure are related to vif mRNA level. While the secondary structure and stability of SLSA1 was largely changed by nSNVs and artificial mutations introduced to restore the original NL4-3 form from altered ones by nSNVs, no clear association of the two SLSA1 properties with vif mRNA level was observed. In contrast, when naturally occurring SA1D2prox sequences that contain multiple nSNVs were examined, we attained significant inverse correlation between the vif level and SLSA1 stability. These results may suggest that SA1D2prox sequence adapts over time, and also that the altered SA1D2prox sequence, SLSA1 stability, and vif level are mutually related. In total, we show here that the entire SA1D2prox sequence and SLSA1 stability critically contribute to the modulation of vif mRNA level.

Vertical silicon waveguide coupler bent by ion implantation.

We propose and demonstrate that vertically curved waveguides (VCWs) enable vertical coupling between silicon wire waveguides and optical fibers with low wavelength dependence and polarization dependence for wide telecommunication wavelength band light. To bend these VCWs, we implanted silicon ions into silicon wire cantilevers from the vertical direction. The internal stress distribution that was induced by ion implantation drove the bending force, and we achieved vertical bending of the waveguides, with curvature radii ranging from 3 to 25 µm. At a radius of curvature of 6 µm, we obtained a coupling loss of 3 dB using a lens fiber.

Influence of premature rupture of membrane on the cerebral blood flow in low-birth-weight infant after the delivery.

Cerebral white matter injury, usually called periventricular leukomalacia (PVL), is the most common form of injury to preterm infants that is associated with adverse motor and cognitive outcomes. Intrauterine infection may be an important etiological factor in PVL, and premature rupture of the membranes (PROM) can be identified antepartum. In order to investigate the pathophysiology of cerebral white matter injury induced by PROM, the cerebral blood flow (CBF) of the internal carotid artery and the vertebral artery was measured by neck ultrasonography. The CBF was determined in 84 low-birth-weight infants with gestational ages ranging from 24 to 35 weeks, including 71 infants without PROM and 13 infants with PROM. The mean blood flow velocity and diameter of each vessel were measured on postnatal days 0-70. The intravascular flow volume was determined by calculating the mean blood flow velocity and the cross-sectional area. The mean blood pressures were recorded, and the ejection fraction was determined. The total cerebral blood flow (CBF) was significantly lower in infants with PROM than in infants without PROM from day 10 to day 70. The ejection fraction was significantly higher in infants with PROM than in infants without PROM on days 0, 5, 10, 21, and 42. There was no difference in the mean blood pressure between infants with PROM and infants without PROM. The results of the present study suggest that PROM may decrease cerebral blood flow after the birth.

[Differences between primary health care and health promotion from the aspects of population, diseases, and social-political structures].

Primary Health Care (PHC) and Health Promotion (HP) have been adopted as core health strategies for socio-political interventions. Although the two have a lot of similarities in terms of concepts, they, nevertheless, have their differences. The first difference lies in the population and diseases perspectives that PHC and HP are literally defined as just "health care" and "promotion of health", respectively. The second difference, from a social and political point of view, is that PHC can be expressed as social and political efforts to make health knowledge, health care skills and the entire health service delivery system respond to the people's needs and situations, while HP is a process in which individuals and their environment are geared toward the pursuit of healthy lifestyles. These differences strengthen the unique values of each strategy. HP, which is a form of social mobilization for health, is about catering to the needs of developing countries. On the other hand, the principle of PHC, which is beneficiary-oriented, is universally applicable for both developed and developing countries.