The impact of glucocorticoid use on the outcomes of rheumatoid arthritis in a multicenter ultrasound cohort study.

OBJECTIVE: Glucocorticoids are effective in treating rheumatoid arthritis (RA) when used appropriately considering the balance of the risks and benefits, especially at low doses. We aimed to evaluate the response of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in patients having already been treated with glucocorticoids. METHODS: We reviewed RA patients treated with b/tsDMARDs in a prospective multicenter ultrasound cohort study. We compared the differences in the clinical characteristics at baseline and outcomes at 12 months between the two groups having been treated with and without glucocorticoids at baseline. The differences in the clinical characteristics and the treatments were balanced by the inverse probability weighting (IPW) with the propensity score. RESULTS: Of 307 patients with RA, 160 patients were treated with glucocorticoids at baseline. The median dose of glucocorticoids was equivalent to 5.0 mg/day of prednisolone. Significant differences were in age and concomitant methotrexate use, composite measures for the disease activity, and the ultrasound grayscale score at baseline. Patients treated with glucocorticoids had less frequent remissions defined by composite measures and ultrasound findings than those treated without glucocorticoids. These significant differences in the achievement of remissions remained robust even after adjusting differences in the clinical characteristics and the treatments between the two groups by IPW. CONCLUSION: RA patients treated with glucocorticoids had a higher disease activity at baseline and a poorer response to treatments with b/tsDMARDs than those without glucocorticoids. The states of patients requiring glucocorticoids might be associated with the poor response to the b/tsDMARDs.

Analytical and clinical validity of wearable, multi-sensor technology for assessment of motor function in patients with Parkinson's disease in Japan.

Continuous, objective monitoring of motor signs and symptoms may help improve tracking of disease progression and treatment response in Parkinson's disease (PD). This study assessed the analytical and clinical validity of multi-sensor smartwatch measurements in hospitalized and home-based settings (96 patients with PD; mean wear time 19 h/day) using a twice-daily virtual motor examination (VME) at times representing medication OFF/ON states. Digital measurement performance was better during inpatient clinical assessments for composite V-scores than single-sensor-derived features for bradykinesia (Spearman |r|= 0.63, reliability = 0.72), tremor (|r|= 0.41, reliability = 0.65), and overall motor features (|r|= 0.70, reliability = 0.67). Composite levodopa effect sizes during hospitalization were 0.51-1.44 for clinical assessments and 0.56-1.37 for VMEs. Reliability of digital measurements during home-based VMEs was 0.62-0.80 for scores derived from weekly averages and 0.24-0.66 for daily measurements. These results show that unsupervised digital measurements of motor features with wrist-worn sensors are sensitive to medication state and are reliable in naturalistic settings.Trial Registration: Japan Pharmaceutical Information Center Clinical Trials Information (JAPIC-CTI): JapicCTI-194825; Registered June 25, 2019.

Effect of omega-3 fatty acids on cardiovascular events in high-risk patients with hypertriglyceridemia in Japan: a 3-year post-marketing surveillance study (OCEAN3 survey).

BACKGROUND: Studies on the efficacy of prescription omega-3 polyunsaturated fatty acids to reduce cardiovascular events have produced conflicting results. RESEARCH DESIGN AND METHODS: This 3-year prospective post-marketing surveillance study evaluated the effect of omega-3-acid ethyl esters (O3AEE; usual dosage 2 g/day) on cardiovascular events in high-risk statin-treated Japanese patients with hypertriglyceridemia. Statin-treated patients not receiving O3AEE were included as a reference cohort. The composite primary endpoint was cardiovascular death, myocardial infarction, stroke, angina requiring coronary revascularization, or peripheral arterial disease requiring surgery or peripheral arterial intervention. RESULTS: At 3 years, Kaplan-Meier estimated cumulative incidence of the primary endpoint was 2.5% (95% confidence interval, 2.1%-2.9%) in O3AEE-treated patients (N = 6,580) and 2.7% (2.4%-3.1%) in non-O3AEE-treated patients (N = 7,784; hazard ratio, 0.99; 95% confidence interval, 0.79-1.23). Incidence of heart failure requiring hospitalization was 0.4% with O3AEE versus 0.8% in non-O3AEE-treated patients (hazard ratio, 0.47; 95% confidence interval, 0.28-0.78; P < 0.05). CONCLUSIONS: Among patients receiving statins, cardiovascular event incidence did not differ significantly between O3AEE-treated patients and non-O3AEE-treated patients. Further studies are required before definitive conclusions can be drawn on the effect of O3AEE on cardiovascular event incidence in high-risk patients with hypertriglyceridemia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02285166.

Validation and Functional Relevance of the Short Form of the Perceived Deficits Questionnaire for Depression for Japanese Patients with Major Depressive Disorder.

Purpose: To validate the five-item version of the Perceived Deficits Questionnaire for Depression (PDQ-D-5) for assessing subjective cognitive function in Japanese patients with major depressive disorder (MDD) using data from the PERFORM-J study. Patients and Methods: A total of 518 Japanese outpatients diagnosed with MDD were assessed on severity of depressive symptoms, cognitive function, social and work function, and quality of life (QoL) over 6 months following initiation of antidepressant therapy. This post hoc analysis evaluated the internal consistency and convergent validity of the PDQ-D-5 in relation to the original PDQ-D-20. Correlations of scores on these measures were examined at each time point and over time. The same set of analyses was explored between PDQ-D-5 and the Patient Health Questionnaire-nine-item (PHQ-9), Montgomery-Asberg Depression Rating Scale (MADRS), Digit Symbol Substitution Test (DSST), five-level version of EQ-5D (EQ-5D-5L), Sheehan Disability Scale (SDS), and Work Productivity and Activity Impairment (WPAI) questionnaire. Results: PDQ-D-5 scores showed good internal consistency. Strong positive correlations were observed between PDQ-D-5 and PDQ-D-20 at each time point (correlation coefficient: baseline, 0.94; month 1, 0.94; month 2, 0.96; month 6, 0.96) and over time (0.92) (all p < 0.0001). Longitudinally, there were positive correlations between PDQ-D-5 scores versus those on the PHQ-9, MADRS, and SDS. Similarly, negative correlations were noted between PDQ-D-5 scores and EQ-5D-5L and DSST scores to a variable degree. There were moderate positive correlations over time between PDQ-D-5 and all WPAI subscale scores except those on absenteeism. Conclusion: PDQ-D-5 scores rated in Japanese patients with MDD were found to adequately represent scores on the PDQ-D-20. The short version also showed associations with several measures of functional outcome, depression severity and QoL. This validates the PDQ-D-5 as a feasible and clinically reliable tool to assess subjective experience on cognition, which is applicable to time-limited consultations. UMIN Clinical Trials Registry for Primary Study: UMIN000024320.

Association between baseline cognitive symptoms and the subsequent presenteeism and global function in patients with major depressive disorder.

Cognitive symptoms in major depressive disorder (MDD) contribute to impaired functional abilities and work productivity, particularly presenteeism. We investigated the association between baseline cognitive symptoms and subsequent presenteeism, and global functional impairment in Japanese patients with MDD from PERFORM-J (Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder in Japan) - a 6-month, multicenter, epidemiological study data. A total of 518 patients initiating antidepressant monotherapy (first-line or switched from another drug) were enrolled. Assessments include Perceived Deficits Questionnaire - Depression (PDQ-D) for cognitive complaints, Sheehan Disability Scale (SDS) for global function (analysed n = 318), and Work Productivity and Activity Impairment Questionnaire for presenteeism (analysed n = 122). A strong association between changes in presenteeism and changes in SDS scores (r: total = 0.636; work/school = 0.686) was observed. After adjusting for sociodemographic and MDD-related factors, patients without cognitive complaints at baseline showed lower odds of impaired presenteeism at 6 months versus patients with cognitive complaints (0.243, 95% CI: 0.079 to 0.747, p = 0.014) and also in patients with first episode of MDD against with recurrent MDD (0.327 (95% CI: 0.136 to 0.787). Similarly, patients without cognitive complaints had healthier global functioning (lower mean SDS total score) than patients with cognitive complaints (8.3 vs 11.2; 95% CI, -5.189 to -0.578; p = 0.014). First depressive episode (lower risk of presenteeism), being male, and low baseline SDS total score (better global functioning) were also associated with improved outcomes. These results highlight the potential value of baseline PDQ-D scores in predicting subsequent workplace and global functioning in patients undergoing treatment for MDD.

Health-Related Quality of Life Over 6 Months in Patients With Major Depressive Disorder Who Started Antidepressant Monotherapy.

OBJECTIVES: Major depressive disorder (MDD) is increasing worldwide and is associated with impaired quality of life (QOL). This study aimed to assess the QOL and its association with cognitive symptoms in patients with MDD who started antidepressant monotherapy. METHODS: Data from the PERFORM (Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder) study were analyzed. A descriptive epidemiological analysis on EQ-5D-5L utility score, the level of each dimension, and the EuroQoL visual analog scale value was conducted at 4 visits during 6 months' follow-up. The association between cognitive complaints and changes in QOL measures was analyzed using multivariate linear regression analysis. RESULTS: The median EQ-5D-5L utility score improved from 0.67 at baseline to 0.82 at month 6. Although the proportion of patients reporting level 1 (no problem) in every dimension of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression increased over time, less than half of the patients achieved level 1 in pain/discomfort and depression/anxiety, which were closely related to depression and usual activities at month 6. Patients with no cognitive complaints or no history of MDD at baseline showed greater improvement in EQ-5D-5L utility scores and EuroQoL visual analog scale value for measuring QOL than those with these characteristics. CONCLUSIONS: Treatment over 6 months improved QOL in patients with MDD although there remained room for improvement in dimensions of usual activities, pain/discomfort, and depression/anxiety. Cognitive complaints or history of MDD at baseline predicted less improvement in QOL at 6 months. Any history of MDD might delay improvement in QOL after treatment.

Therapeutic Potential of Vortioxetine for Anhedonia-Like Symptoms in Depression: A Post Hoc Analysis of Data from a Clinical Trial Conducted in Japan.

AIM: Anhedonia in major depressive disorder may be resistant to first-line antidepressants. We examined the effect of vortioxetine, a multimodal antidepressant, on anhedonia-like symptoms in Japanese patients with major depressive disorder. METHODS: This was a post hoc analysis of an 8-week, randomized, double-blind, placebo-controlled, phase 3 study of vortioxetine (10 mg or 20 mg) in Japanese patients aged 20-75 years with recurrent major depressive disorder and a Montgomery-Åsberg Depression Rating Scale (MADRS) total score of at least 26. The primary outcome was the mean change from baseline to week 8 in anhedonia-like symptoms as measured by MADRS anhedonia factor score, composed of: Q1, apparent sadness; Q2, reported sadness; Q6, concentration; Q7, lassitude; and Q8, inability to feel. Mean change in MADRS total score and anhedonia factor score were compared among treatment groups, with data categorized by median baseline anhedonia factor score (0-17 or ≥18). RESULTS: Data were available for 489 patients. The least-squares mean difference in MADRS anhedonia factor score change from baseline to week 8 versus placebo was -1.34 for vortioxetine 10 mg (P = 0.0300) and -1.77 for vortioxetine 20 mg (P = 0.0044). The least-squares mean difference between vortioxetine and placebo in MADRS total score change from baseline to week 8 was -3.11 (10 mg dose) and -3.37 (20 mg dose) for patients with a higher baseline anhedonia factor score (≥18), and -2.08 (10 mg) and -2.61 (20 mg) for patients with a lower baseline score (0-17). CONCLUSION: This post hoc analysis suggests that vortioxetine may have therapeutic potential in patients with anhedonia-like symptoms of major depressive disorder. ClinicalTrials.gov identifier for primary study: NCT02389816.

Diseases prevalent before major depressive disorder diagnosis: an exploratory nested case-control study using health insurance-based claims data.

OBJECTIVES: Major depressive disorder (MDD) is often comorbid with other chronic and/or serious diseases. However, little is known about the prevalence of various diseases that are present before MDD onset. We examined the prevalence of all pre-existing diseases in the 12 months before an MDD diagnosis. DESIGN: Exploratory nested case-control study. SETTING: Data, including diagnoses based on International Statistical Classification of Diseases and Related Health Problems, 10th revision codes, were from a Japanese health insurance database (JMDC). PARTICIPANTS: Adults newly diagnosed with MDD during 2015, 2016 or 2017 (but not the preceding year) (cases) were matched (exact) 1:10 to controls by age, sex, index date and working status. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of patients in each group with each pre-existing disease during the 12 months before the index date (ie, before MDD diagnosis in cases). Odds ratios (ORs) for onset of MDD were calculated for each pre-existing disease. A post hoc multivariate analysis examined interactions of metabolic risk factors (diabetes, hypertension, dyslipidaemia), psychiatric disorders (sleep disorders, psychiatric disorders other than depression) and MDD-related symptoms (headache, pain, autonomic nerve imbalance) on MDD diagnosis. RESULTS: There were 13 420 cases and 134 200 controls (mean age 41.9 years; 66.5% male). The prevalence of almost all pre-existing diseases was higher in cases than in controls. The highest ORs (5.8-21.0) were for psychiatric diseases and sleep disorders. Insomnia (21.1% of patients; OR 8.7) and neurosis (9.7%; OR 10.6) were particularly prevalent in the case group. The odds of MDD increased in the presence of metabolic risk factors, psychiatric disorders and/or MDD-related symptoms. CONCLUSIONS: There is a high prevalence of pre-existing diseases in Japanese patients who develop MDD compared with matched controls without MDD. These results suggest that patients with chronic and/or serious diseases should be actively monitored for depression.

Prediction of residual cognitive disturbances by early response of depressive symptoms to antidepressant treatments in patients with major depressive disorder.

BACKGROUND: Patients with major depressive disorder (MDD) frequently retain cognitive disturbances after recovery from mood symptoms. We investigated the relationship between early response of mood symptoms and/or remission, and residual cognitive disturbances after 6 months of antidepressant treatment. METHODS: 518 patients with MDD were followed up for 6 months after antidepressant treatment initiation (first-line or switch from a previous drug). Subjective and objective cognitive disturbances were assessed by the Perceived Deficits Questionnaire - Depression (PDQ-D) and digit symbol substitution test (DSST), respectively. Depressive symptoms, as well as remission and early response to treatment, were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS). Multivariable linear and logistic regression models were used to adjust for confounders. RESULTS: Early response of depressive mood (≥50% reduction in MADRS score at month 1) was related with fewer residual subjective cognitive symptoms, as evaluated by the PDQ-D at month 6 (p<0.001). Likewise, early remission status at month 2 was inversely associated with PDQ-D scores at month 6 (p<0.001). Among patients with baseline DSST scores of ≥1 standard deviation below the norm, early response/remission was associated with better performance on the DSST at month 6 (p<0.05). LIMITATIONS: The cohort may not be representative of the general MDD patient population, and the possible influence of concomitant medications was not evaluated. CONCLUSIONS: These findings suggest that early improvements in depressive symptoms predict better cognitive outcomes in patients with MDD. Grouping of patients by mood and cognition status in early stages of antidepressant treatments may facilitate efforts to improve long-term functional outcomes.

Early Improvement with Vortioxetine Predicts Response and Remission: A Post Hoc Analysis of Data from a Clinical Trial Conducted in Japan.

AIM: Several weeks of treatment with an antidepressive agent may be required before efficacy is demonstrated in patients with major depressive disorder. This study investigated the predictive value of early partial improvement with vortioxetine for treatment response and remission. METHODS: This was a post hoc analysis of an 8-week, randomized, double-blind, placebo-controlled, Phase 3 study of vortioxetine (10 mg or 20 mg) in Japanese patients aged 20-75 years with recurrent major depressive disorder and a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 26. The key outcomes were the predictive value of early partial improvement (reduction in MADRS total score of ≥20% from baseline to week 2) with vortioxetine for MADRS response (≥50% decrease in score from baseline) and remission (decrease in score to ≤10) at week 8. RESULTS: Relevant data were available for 478 patients; 62/158 patients receiving placebo, 71/162 receiving vortioxetine 10 mg, and 66/158 receiving vortioxetine 20 mg were early improvers. Early improvers receiving vortioxetine (10 mg or 20 mg) were more likely than non-early improvers to achieve a week 8 response (71.2-73.2% vs 29.7-38.0%) or remission (50.7-51.5% vs 17.4-18.7%). Positive predictive values for response and remission with vortioxetine were ~70% and ~50%, respectively; negative predictive values were ~70% and ~80%, respectively. CONCLUSION: Improvement with vortioxetine may be predicted by early partial improvement in MADRS score. Some patients may benefit from longer-term treatment even without early improvement, another finding that may aid clinical decision-making. ClinicalTrials.gov registration for primary study: NCT02389816.

Patient and Physician Perspectives of Depressive Symptoms and Expectations for Treatment Outcome: Results from a Web-Based Survey.

PURPOSE: A previous international study suggested that perceptions of depression symptoms, social function, and treatment expectations are different between patients/physicians. We aimed to examine whether such differences exist in Japan. METHODS: A web-based survey was conducted with patients who reported that they had been diagnosed with depression, and physicians who reported that they had treated patients with depression, in Japan. Questionnaires were designed to quantify patients' perceptions of symptoms, social function, and treatment expectations. Patients were categorized into three stages of disorder based on their reported current symptoms: severe symptomatic, mild symptomatic, and remission. Physicians were assigned up to three patients, were provided with patient information from the questionnaire completed by those patients, and finally the completed questionnaire forms for each patient. Agreement between the perceptions of the patients and physicians was examined for each stage. RESULTS: Of the 2618 eligible patients, 828 were assigned to 326 eligible physicians. Overall, we found small differences in the perceptions of depression treatment between patients/physicians. Slightly fewer physicians than patients reported physical symptoms (85% vs 91%; p=0.018) in the mild symptomatic stage. Fewer physicians than patients reported cognitive symptoms in the severe (82% vs 87%; p=0.029) and mild (54% vs 66%; p=0.003) symptomatic stages. Social function was deemed to be lower by physicians than by patients, across all stages of disorder (p<0.001). Regarding treatment expectations, more physicians than patients reported "return to a normal life" in the mild symptomatic (51% vs 35%, p<0.001) and remission stages (57% vs 36%, p<0.001), and more patients than physicians reported "reduction of side effects" in the severe (10% vs 4%, p=0.004) and mild (12% vs 5%, p<0.001) symptomatic disorder stages. CONCLUSION: These results suggest small differences in patient/physician perceptions of depression treatment in Japan. Discrepancies between patients'/physicians' perceptions may vary depending on the medical environment.

Real-world comparative effectiveness and safety of tofacitinib and baricitinib in patients with rheumatoid arthritis.

OBJECTIVE: To compare the efficacy and safety of tofacitinib and baricitinib in patients with RA in a real-world setting. METHODS: A total of 242 patients with RA who were treated with tofacitinib (n = 161) or baricitinib (n = 81) were enrolled. We evaluated efficacy and safety between tofacitinib and baricitinib using multivariable analyses to avoid confounding. Their clinical disease activity and AEs were evaluated for 24 weeks. RESULTS: The mean (SD) DAS28-ESR change from baseline to 24 weeks was 1.57 (1.55) (tofacitinib) and 1.46 (1.36) (baricitinib). There was no significant difference in the clinical response between the two groups (adjusted mean difference, 0.04; 95% CI, -0.35 to 0.28). The efficacy was not significantly changed in the patients without concomitant MTX use in both groups, but the concomitant MTX use showed better clinical efficacy in the cases of baricitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response as revealed by a multivariable logistic analysis differed. The concomitant oral steroid use was independently associated with the achievement of DAS-low disease activity in the tofacitinib group, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used was associated. CONCLUSIONS: Our findings indicate that tofacitinib and baricitinib had comparable continuing efficacies and safety profiles. However, there is a possibility that the influence of clinical characteristics on the treatment response differs. The comparison provides useful information to the optimal use of JAK inhibitors in real-world settings.

Effect of abatacept treatment on serum osteoclast-related biomarkers in patients with rheumatoid arthritis (RA): A multicenter RA ultrasound prospective cohort in Japan.

ABSTRACT: We evaluated the effect of abatacept treatment on osteoclast-related biomarkers and explored whether the biomarkers are associated with the therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept.We enrolled 44 RA patients treated with abatacept from a multicenter prospective ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug therapy. We evaluated the disease activity score (DAS) 28-CRP (C-reactive protein), musculoskeletal ultrasound scores including the total grayscale score (GS)/power Doppler (PD) score and the serum concentrations of isoform 5b of tartrate-resistant acid phosphate (TRACP-5b) and soluble receptor activator of nuclear factor-κB ligand (sRANKL) at baseline and at 3 and 6 months of treatment. "PD responder" was defined as a patient whose Δtotal PD score over 6 months was greater than the median change of that.Abatacept significantly improved DAS28-CRP as well as the total GS/PD score over 6 months. Serum TRACP-5b was significantly elevated and serum sRANKL was significantly decreased at 6 months (P < .0001 and P < .01, respectively). At 6 months, serum sRANKL was significantly decreased in the patients who achieved DAS28-CRP remission and the PD responders but not in those who did not. However, serum TRACP-5b rose regardless of the therapeutic response.Among RA patients treated with abatacept, serum sRANKL decreased in the patients with a good therapeutic response, but serum TRACP-5b elevated paradoxically regardless of the therapeutic response.

[Usefulness of Combining Post-processing Scatter Correction and an Anti-scatter Grid in Chest Standing Radiography].

PURPOSE: The aim of this study was to evaluate the usefulness of combining post-processing scatter correction (IG) and an anti-scatter grid (RG) in chest radiography. METHOD: To determine the combination protocol (Hyb) that was closed to RG 12:1 (RG12), we measured the content rate of scattered radiation for each combination (RG12, IG12, RG3-12+IG3-12). Task-based modulation transfer function (MTF_Task) and SDNR were evaluated using RG12, IG12, and Hyb. Additionally, seven radiologists performed visual evaluation by using chest phantom. RESULT: The protocol of Hyb was RG8+IG3. In SDNR, Hyb (RG8+IG3) was equal to or higher than RG12, and MTF_Task was equal in all grid systems. Hyb (RG8+IG3) was significantly superior to RG12 in visual evaluation. CONCLUSION: The combining post-processing scatter correction should be useful for improving inspection throughput and reducing the risk of grid's damage.

Association between serum bone biomarker levels and therapeutic response to abatacept in patients with rheumatoid arthritis (RA): a multicenter, prospective, and observational RA ultrasound cohort study in Japan.

BACKGROUND: To evaluate the effect of treatment on serum bone biomarkers and explore whether serum bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept. METHODS: We enrolled 59 RA patients treated with abatacept from a multicenter, exploratory, short-term, prospective and observational ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) therapy. We evaluated the patients' clinical disease activity and musculoskeletal ultrasound (MSUS) scores. The serum concentrations of five bone biomarkers were evaluated (dickkopf-1 [Dkk-1], sclerostin [SOST], osteocalcin [OC], osteopontin [OPN], and osteoprotegerin [OPG]) by multiplex bead assays at baseline, 3, and 6 months: the change over 6 months was defined as the Δ value. 'Power Doppler (PD) responder' was defined as a patient whose Δtotal PD score over 6 months was greater than the median change. RESULTS: Abatacept significantly improved the clinical disease activity and MSUS score over 6 months. Serum OPG was significantly elevated at 6 months after the abatacept introduction (p = 0.016). The ΔSOST and ΔOPG were significantly greater in the PD responders versus the non-PD responders (p = 0.0041 and 0.0073, respectively). The serum Dkk-1 at baseline was significantly lower in the PD responders (n = 30) vs. the non-PD responders (n = 29) (p = 0.026). A multivariate logistic regression analysis showed that the serum Dkk-1 at baseline (odds ratio 0.50, 95% confidence interval [CI] 0.23-0.91, p = 0.043) was an independent predictor of PD responder status. CONCLUSION: Serum levels of bone biomarkers may be useful for predicting RA patients' therapeutic responses to abatacept. TRIAL REGISTRATION: Name of the registry: Assessment of therapeutic responsiveness by imaging of the joints in patients with rheumatoid arthritis; A observational cohort study Trial registration number: UMIN000012524 Date of registration: 12/9/2013 URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000014657.

A Claims-Based Cohort Study on the Treatment Patterns of Japanese Patients with Type 2 Diabetes Mellitus and the Association of Early First Physician Visit with Time to Prescription of Oral Hypoglycemic Agents.

INTRODUCTION: This study aimed to investigate the relationships between timing of the first physician visit after detection of an abnormal glycated hemoglobin (HbA1c) value at routine annual check and the time to antidiabetic treatment prescription; and understand treatment patterns in patients newly diagnosed with type 2 diabetes mellitus (T2DM). METHODS: This retrospective, longitudinal, observational cohort study examined data from JMDC Inc., an administrative claims database. Patients with HbA1c value of at least 6.5% at routine annual check, aged 20 years or older, and prescribed at least one antidiabetic drug were included. This cohort was classified into early physician visit and delayed physician visit groups based on the timing of the first physician visit relative to the median. Patients were monitored from the date of first HbA1c checkup of at least 6.5% to the date of first physician visit with an HbA1c test, and from the date of the first physician visit to the date of prescription of first-line and second-line T2DM treatments. The time to first prescription of antidiabetic treatment for the two groups was then compared. RESULTS: Of 4798 eligible patients, 54.8% were prescribed first-line T2DM therapy less than 2 months from the first physician visit for T2DM diagnosis. A lower percentage of the early group compared with the delayed group required T2DM pharmacological therapy in less than 2 months (46.1% vs. 63.4%). The early group had a longer median time to prescription of first-line therapy [92 days vs. 15 days, p < 0.0001; hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.24, 1.39] and second-line therapy (1599 days vs. 1315 days, p < 0.0001; HR 1.22, 95% CI 1.11, 1.34) compared with the delayed group. CONCLUSION: In Japanese patients with T2DM, early physician visit after abnormal HbA1c detection at routine annual check is associated with a longer period before T2DM medication requirement, and may improve disease course.

[Examination of the Maximum Brightness of the Monitor Suitable for Radiological Technologists' Interpretation Assistance and Image Inspection].

The purpose of this study is to examine the maximum brightness of the monitor, which is suitable for radiological technologists' (hereinafter referred to as technicians) interpretation assistance and image inspection. The signal detection ability was evaluated by receiver operating characteristic (ROC) analysis using a chest X-ray image with a simulated nodule. In order to examine the ease of observation and the effect on the subjective evaluation by changing the maximum brightness, evaluation was performed by the normalized ranking method using chest X-ray images. ROC experiments were performed using images with and without simulated nodules in the chest phantom. There was no significant difference in detectability by changing the maximum brightness (p>0.05), but the average area under the curve (AUC) was higher at 350 cd/m2 than at 100 cd/m2 and 170 cd/m2. A normalized ranking method was performed focusing on simulated nodules on chest X-ray images. In the least significant difference (l.s.d.) method, there was a significant difference between the maximum luminance, and the higher the maximum luminance, the better the evaluation. From these results, the change in the maximum brightness did not significantly affect the signal detection ability of the technician's chest X-ray image, but the higher the maximum brightness, the easier it was to observe and the higher the subjective evaluation. It has been reported that the higher the maximum brightness, the shorter the signal recognition time, and a monitor with a high maximum brightness may lead to more efficient image inspection by a technician. From the results of this study, it is considered appropriate to use a medical liquid crystal display (LCD) monitor with a maximum brightness of 350 cd/m2 for the technician's interpretation assistance and image inspection.

Utility of a simplified ultrasonography scoring system among patients with rheumatoid arthritis: A multicenter cohort study.

ABSTRACT: We aimed to evaluate the utility of a simplified ultrasonography (US) scoring system, which is desired in daily clinical practice, among patients with rheumatoid arthritis (RA) receiving biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs).A total of 289 Japanese patients with RA who were started on tumor necrosis factor inhibitors, abatacept, tocilizumab, or Janus kinase inhibitors between June 2013 and April 2019 at one of the 15 participating rheumatology centers were reviewed. We performed US assessment of articular synovia over 22 joints among bilateral wrist and finger joints, and the 22-joint (22j)-GS and 22-joint (22j)-PD scores were evaluated as an indicator of US activity using the sum of the GS and PD scores, respectively.The top 6 most affected joints included the bilateral wrist and second/third metacarpophalangeal joints. Therefore, 6-joint (6j)-GS and -PD scores were defined as the sum of the GS and PD scores from the 6 synovial sites over the aforementioned 6 joints, respectively. Although the 22j- or 6j-US scores were significantly correlated with DAS28-ESR or -CRP scores, the correlations were weak. Conversely, 6j-US scores were significantly and strongly correlated with 22j-US scores not only at baseline but also after therapy initiation.Using a multicenter cohort data, our results indicated that a simplified US scoring system could be adequately tolerated during any disease course among patients with RA receiving biological/targeted synthetic DMARDs.

Comparison of the quantitative measurement of 18F-FDG PET/CT and histopathological findings in IgG4-related disease.

OBJECTIVES: To investigate the utility of 18F-FDG PET/CT in the diagnostic procedure of IgG4-related disease (IgG4-RD), we analysed the association between quantitative method of 18F-FDG PET/CT and histological findings. METHODS: Twenty-one patients with IgG4-RD in whom 18F-FDG PET/CT was performed at the time of diagnosis were enrolled. Tissue biopsy was performed at 24 sites in 21 patients. To perform quantitative analysis of 18F-FDG PET/CT imaging, the highest standardised uptake value (SUV) of the pixels (SUVmax) and the average SUV (SUVmean) within the biopsied lesion were measured. The SUVmean of the liver was also measured as a reference. RESULTS: The mean age at diagnosis was 64.6±11.9 years, and the median serum IgG4 level was 650 mg/dl. Histological findings were consistent with IgG4-RD (histopathology-positive) at 19 out of 24 sites. Although there was no significant difference in the values of SUVmax between histopathology-positive and histopathology-negative tissues, the values of SUVmean were significantly higher in the histopathology-positive tissue (4.98 and 3.54, respectively p<0.05). The values of SUVmean/liver were also higher in the histopathology-positive tissue (2.17 and 1.52, respectively p<0.05). To establish a cut-off value of SUVmean to determine which of multiple lesions should be biopsied, a ROC curve was constructed. ROC curve analysis indicated SUVmean=4.07 or SUVmean/liver=1.66 as a cut-off value. CONCLUSIONS: Our present study suggested that quantitative analysis of 18F-FDG-PET/CT imaging might be useful for selecting the biopsy site in IgG4-RD. The calculation of SUVmean, not of SUVmax, is important for evaluating IgG4-RD-related lesions in 18F-FDG PET/CT imaging.

Therapeutic Potential of Vortioxetine for Anxious Depression: A Post Hoc Analysis of Data from a Clinical Trial Conducted in Japan.

AIM: Antidepressants, including selective serotonin reuptake inhibitors, often elicit a poor response in patients with major depressive disorder (MDD) with significant anxiety symptoms. This study investigated the effects of the multimodal antidepressant vortioxetine in patients with MDD and associated anxiety. METHODS: This was a post hoc analysis of data from an 8-week, randomized, double-blind, placebo-controlled, Phase 3 study of vortioxetine (10 mg or 20 mg) in Japanese patients aged 20-75 years with recurrent MDD and a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 26. Changes from baseline to week 8 in MADRS total score and Hamilton Depression Rating Scale (HAM-D) anxiety/somatization factor score were assessed in patients with anxious depression (HAM-D anxiety/somatization factor score ≥7) and without anxious depression. RESULTS: Data were available for 489 patients. In patients with anxious depression, the least-squares (LS) mean difference (95% confidence interval [CI]) versus placebo in change in MADRS total score was -3.44 (-6.10, -0.77) for vortioxetine 10 mg and -4.51 (-7.15, -1.87) for vortioxetine 20 mg. In patients with non-anxious depression, the LS mean difference (95% CI) versus placebo was -1.81 (-4.71, 1.09) and -1.05 (-4.00, 1.90) for vortioxetine 10 mg and 20 mg, respectively. Changes from baseline in HAM-D anxiety/somatization factor score were greater in patients treated with vortioxetine 10 mg or 20 mg than in those treated with placebo. CONCLUSION: Vortioxetine may be effective for patients with anxiety symptoms in MDD. Further research is warranted to investigate these effects in a real-world clinical setting. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier for primary study: NCT02389816.