Glycated hemoglobin (HbA1c) is independently associated with the bioelectrical impedance phase angle in junior sumo wrestlers: A pilot study.

The study explores the relationship between phase angle (PhA), an indicator of cellular health, and metabolic health parameters among junior sumo wrestlers in Japan. Given the demanding lifestyle and high-energy diets of sumo wrestlers that predispose them to metabolic syndrome post-retirement, this study focuses on a younger cohort. The primary aim is to evaluate if PhA could serve as an early indicator of metabolic health issues within this unique demographic. A total of 14 sumo wrestlers aged 9-17 years were assessed to determine the relationship between PhA and various metabolic markers, including glycated hemoglobin (HbA1c), using a TANITA MC-780A-N body composition analyzer and standard blood tests. Bivariate regression analysis and Pearson's correlation revealed a negative relationship between PhA and HbA1c even after adjusting for age and weight (ß = -0.496, r2 = 0.776, r = -0.756, p = 0.004). The results indicate a significant negative relationship between PhA and HbA1c levels, suggesting that lower PhA values, which indicate poorer cellular integrity, are associated with higher HbA1c levels, signifying impaired glycemic control. These findings underscore the potential of PhA as a valuable biomarker for monitoring metabolic health in young sumo wrestlers, with implications for early intervention and management strategies.

Fatal hemophagocytic lymphohistiocytosis with intravascular large B-cell lymphoma following coronavirus disease 2019 vaccination in a patient with systemic lupus erythematosus: an intertwined case.

Hemophagocytic lymphohistiocytosis (HLH) has been recognized as a rare adverse event following the coronavirus disease 2019 (COVID-19) vaccination. We report a case of neuropsychiatric symptoms and refractory HLH in a woman with systemic lupus erythematosus (SLE) after receiving her COVID-19 vaccine treated with belimumab, later found to have intravascular large B-cell lymphoma (IVLBCL) at autopsy. A 61-year-old woman with SLE was referred to our hospital because of impaired consciousness and fever. One month prior to consulting, she received her second COVID-19 vaccine dose. Afterward, her consciousness level decreased, and she developed a high fever. She tested negative for SARS-CoV-2. Neuropsychiatric SLE was suspected; therefore, glucocorticoid pulse therapy was initiated on day 1 and 8. She had thrombocytopenia, increased serum ferritin levels and hemophagocytosis. The patient was diagnosed with HLH and treated with etoposide, dexamethasone and cyclosporine. Despite treatment, the patient died on day 75; autopsy report findings suggested IVLBCL as the underlying cause of HLH. Differentiating comorbid conditions remains difficult; however, in the case of an atypical clinical presentation, other causes should be considered. Therefore, we speculate that the COVID-19 vaccination and her autoimmune condition may have expedited IVLBCL development.

Co-occurrence of Epstein-Barr virus-positive nodal T/NK-cell lymphoma and nodal T-follicular helper cell lymphoma of different clonal origins: An autopsy case report.

Nodal T-follicular helper cell lymphoma (TFHL) is a subset of T-cell lymphoma and frequently co-occurs with Epstein-Barr virus (EBV)-positive B-cell lymphoma but not with T/NK-cell lymphoma. Recently, a new entity with a worse prognosis, called EBV-positive nodal T/NK-cell lymphoma (NTNKL) has been established. Here, we report an autopsy case of synchronous multiple lymphomas, including TFHL and NTNKL. The patient was a 78-year-old female admitted with pneumonia. Although pneumonic symptoms were improved, fever, pancytopenia, and disseminated intravascular coagulation emerged, implicating lymphoma. She died on the 21st hospital day without a definitive diagnosis. The autopsy revealed the enlargement of multiple lymph nodes throughout her body. Histological analysis revealed three distinct regions in the left inguinal lymph node. The first region consists of small-sized lymphocytes with T-follicular helper phenotype and extended follicular dendritic cell meshwork, indicating TFHL. The second region included EBV-positive large B cells. The third region comprised EBV-positive large cells with cytotoxic T/NK cell phenotype, indicating NTNKL. Clonality analysis of the first and the third regions showed different patterns. Since various hematopoietic malignancies progress from common clonal hematopoiesis according to existing literature, this case may help to understand TFHL and NTNKL.

Identification of target cells of human papillomavirus 18 using squamocolumnar junction organoids.

Human papillomavirus 18 (HPV18) is a highly malignant HPV genotype among high-risk HPVs, characterized by the difficulty of detecting it in precancerous lesions and its high prevalence in adenocarcinomas. The cellular targets and molecular mechanisms underlying its infection remain unclear. In this study, we aimed to identify the cells targeted by HPV18 and elucidate the molecular mechanisms underlying HPV18 replication. Initially, we established a lentiviral vector (HPV18LCR-GFP vector) containing the HPV18 long control region promoter located upstream of EGFP. Subsequently, HPV18LCR-GFP vectors were transduced into patient-derived squamocolumnar junction organoids, and the presence of GFP-positive cells was evaluated. Single-cell RNA sequencing of GFP-positive and GFP-negative cells was conducted. Differentially expressed gene analysis revealed that 169 and 484 genes were significantly upregulated in GFP-positive and GFP-negative cells, respectively. Pathway analysis showed that pathways associated with cell cycle and viral carcinogenesis were upregulated in GFP-positive cells, whereas keratinization and mitophagy/autophagy-related pathways were upregulated in GFP-negative cells. siRNA-mediated luciferase reporter assay and HPV18 genome replication assay validated that, among the upregulated genes, ADNP, FHL2, and NPM3 were significantly associated with the activation of the HPV18 early promoter and maintenance of the HPV18 genome. Among them, NPM3 showed substantially higher expression in HPV-related cervical adenocarcinomas than in squamous cell carcinomas, and NPM3 knockdown of HPV18-infected cells downregulated stem cell-related genes. Our new experimental model allows us to identify novel genes involved in HPV18 early promoter activities. These molecules might serve as therapeutic targets in HPV18-infected cervical lesions.

Consideration on size, velocity and path of droplets emitted during running.

BACKGROUND: People began to wear face masks during physical activities due to spread of COVID-19. There are no previous studies about the need for wearing masks while running. METHODS: Assuming a citizen runner who runs full marathon in 4 hours, we verified the path and the amount of droplet dispersal, setting a humanoid mannequin with a mask in simulated running environment (Experiment 1). We also had six adults exercise in the same environment to examine droplet behaviors when not wearing a face mask (Experiment 2). Average droplet size was determined, and repeated measures ANOVA was carried out to examine statistical significance. To evaluate observed droplet behaviors, theoretical solutions of the downfall motion of large droplets were then derived, taking air resistance into consideration. RESULTS: Experiment 1: wearing a face mask caused more droplets to adhere to the face; Experiment 2: droplets were emitted in conversation, coughing or sneezing, and they fell within social distancing. Average droplet size was not sensitive to the wind velocity. It could vary with a significant difference for time and wind velocity. Observed velocity and path of droplet can be expressed by the theoretical solutions. CONCLUSIONS: Velocity and path of large droplets can be expressed by the theoretical solution of particles in downfall motion under air resistance. We therefore conclude that wearing a mask while running gives adverse effects in preventing infection. Possibility of droplet transmission while running is considered low even when not wearing a face mask, as long as social distancing is ensured.

Differences in the prefrontal cortex responses of healthy young men performing either water-based or land-based exercise at light to moderate intensity.

Cerebral blood flow increases more during water-based exercise than land-based exercise owing to the effects of end-tidal CO2 (PETCO2) and mean arterial pressure (MAP) changes due to water immersion. However, it is unclear whether oxygenated hemoglobin (oxy-Hb) concentrations in the prefrontal cortex (PFC) are increased more by water-based or land-based exercise. We hypothesized that oxy-Hb concentrations in the PFC are higher during water-based exercise than land-based exercise when the exercise intensity is matched. To test this hypothesis, 10 healthy participants (age: 24.2 ± 1.7 years; height: 1.75 ± 0.04 m; weight: 69.5 ± 5.2 kg) performed light- to moderate-intensity cycling exercise in water (water-based cycling (WC); chest-high water at 30 °C) and on land (LC). Stroke volume, cardio output, heart rate, MAP, respiratory rate, PETCO2, and oxy-Hb in the PFC were assessed during 15 min of exercise, with exercise intensity increased every 5 min. Both WC and LC significantly increased oxy-Hb concentrations in the PFC as exercise intensity was increased (intensity effect: p < 0.001). There was no significant difference in oxy-Hb concentrations during WC and LC in most prefrontal areas, although significant differences were found in areas corresponding to the left dorsolateral PFC (exercise effect: p < 0.001). Thus, WC and LC increase oxy-Hb concentrations in the PFC in a similar manner with increasing exercise intensity, but part of the PFC exhibits enhanced oxy-Hb levels during WC. The neural response of the PFC may differ during water-based and land-based exercise owing to differences in external information associated with water immersion.

Application of organoid culture from HPV18-positive small cell carcinoma of the uterine cervix for precision medicine.

BACKGROUND: Small cell carcinoma of the uterine cervix (SCCC) is a rare and highly malignant human papillomavirus (HPV)-associated cancer in which human genes related to the integration site can serve as a target for precision medicine. The aim of our study was to establish a workflow for precision medicine of HPV-associated cancer using patient-derived organoid. METHODS: Organoid was established from the biopsy of a patient diagnosed with HPV18-positive SCCC. Therapeutic targets were identified by whole exome sequencing (WES) and RNA-seq analysis. Drug sensitivity testing was performed using organoids and organoid-derived mouse xenograft model. RESULTS: WES revealed that both the original tumor and organoid had 19 somatic variants in common, including the KRAS p.G12D pathogenic variant. Meanwhile, RNA-seq revealed that HPV18 was integrated into chromosome 8 at 8q24.21 with increased expression of the proto-oncogene MYC. Drug sensitivity testing revealed that a KRAS pathway inhibitor exerted strong anti-cancer effects on the SCCC organoid compared to a MYC inhibitor, which were also confirmed in the xenograft model. CONCLUSION: In this study, we confirmed two strategies for identifying therapeutic targets of HPV-derived SCCC, WES for identifying pathogenic variants and RNA sequencing for identifying HPV integration sites. Organoid culture is an effective tool for unveiling the oncogenic process of rare tumors and can be a breakthrough for the development of precision medicine for patients with HPV-positive SCCC.

Prognostic significance of p16, p21, and Ki67 expression at the invasive front of colorectal cancers.

Cancer cells at the invasive front are believed to be responsible for invasion/metastasis. This has led to examining various morphological features and protein expressions at the invasive front. However, accurate assessment of the pathological section requires long-time training, and inter-observer disagreement is problematic. Immunohistochemistry and digital imaging analysis may mitigate these problems; however, the choice of which proteins to stain and the best analysis method remains controversial. We used the "go-or-grow" hypothesis to select markers with the greatest prognostic relevance. Importantly, nonproliferating cells can migrate. We used Ki67 as a proliferation marker, with p16 and p21 designating nonproliferating cells. We established a semi-automated quantification workflow to study protein expression in serial pathological sections. A total of 51 patients with completely resected colorectal cancer (stages I-IV) were analyzed, and 44 patients were followed up. Patients with cancer cells with p16-high/p21-low or p21-low/Ki67-low at the deepest invasive front demonstrated a significantly worse prognosis than those who did not display these characteristics. These results suggest that the nonproliferating cancer cells at the invasion front possess invasion/metastatic property with heterogeneity of senescence.

Derivation of pancreatic acinar cell carcinoma cell line HS-1 as a patient-derived tumor organoid.

Acinar cell carcinoma (ACC) of the pancreas is a malignant tumor of the exocrine cell lineage with a poor prognosis. Due to its rare incidence and technical difficulties, few authentic human cell lines are currently available, hampering detailed investigations of ACC. Therefore, we applied the organoid culture technique to various types of specimens, such as bile, biopsy, and resected tumor, obtained from a single ACC patient. Despite the initial propagation, none of these organoids achieved long-term proliferation or tolerated cryopreservation, confirming the challenging nature of establishing ACC cell lines. Nevertheless, the biopsy-derived early passage organoid developed subcutaneous tumors in immunodeficient mice. The xenograft tumor histologically resembled the original tumor and gave rise to infinitely propagating organoids with solid features and high levels of trypsin secretion. Moreover, the organoid stained positive for carboxylic ester hydrolase, a specific ACC marker, but negative for the duct cell marker CD133 and the endocrine lineage marker synaptophysin. Hence, we concluded the derivation of a novel ACC cell line of the pure exocrine lineage, designated HS-1. Genomic analysis revealed extensive copy number alterations and mutations in EP400 in the original tumor, which were enriched in primary organoids. HS-1 displayed homozygous deletion of CDKN2A, which might underlie xenograft formation from organoids. Although resistant to standard cytotoxic agents, the cell line was highly sensitive to the proteasome inhibitor bortezomib, as revealed by an in vitro drug screen and in vivo validation. In summary, we document a novel ACC cell line, which could be useful for ACC studies in the future.

Hydration status and running performance during cool and hot training sessions in rugby union forwards and backs.

BACKGROUND: Rugby showed a high incidence of exertional heatstroke. Different physiques and running performances between the forward and back players (FW and BK) may result in different heatstroke risks. This study aimed to compare the hydration status, running performance, and perceived heatstroke symptoms (PHS) between cool and hot environment training (HT and CT) in university rugby union FW and BK. METHODS: Thirteen university rugby players (seven forwards and six backs) participated in this study. During both conditions, players were allowed to drink water and sports drink, and the amount of fluid intake was recorded. Body mass was measured pre- and post-training, and weight loss was calculated. Sweat loss was calculated based on body mass and fluid intake. During training, running performance was measured using GPS. The presence of PHS was assessed using a questionnaire administered after training. RESULTS: Fluid intake and sweat loss were higher in the HT as opposed to the CT, and FW showed higher fluid intake and dehydration than BK. However, there were no significant differences in weight loss observed during data collection. Running distance per minute and maximum speed were higher in BK than in FW, but there was no significant difference between conditions. Although a significant weight loss was not observed between conditions, the number of PHS was higher in the HT. CONCLUSIONS: Although BK had a higher running distance and maximum speed than FW during training, a higher cycle of fluid intake and sweat loss was observed in the FW than that in the BK.

Respiratory function and breathing response to water- and land-based cycling at the matched oxygen uptake.

The impact of underwater exercise on respiratory function remains unclear when its metabolic rate is matched with exercise performed on land. Therefore, we compared the breathing responses and respiratory function during and after water (WC)- and land (LC)-based cycling performed at the matched oxygen uptake (VO2 ). Twelve healthy men performed 15 min of incremental WC and LC on separate days. During WC, participants cycled continuously at 30, 45, and 60 rpm (stages 1, 2, and 3) for 5 min each. During LC, participants cycled at 60 rpm for 15 min while wattage was increased every 5 min and adjusted to match VO2 to the WC condition. Breathing patterns during cycling and spirometry data before and after cycling were collected. VO2 during WC and LC was similar. Respiratory rate (WC: 27 ± 3 vs. LC: 23 ± 4 bpm, p = 0.012) and inspiratory flow (WC: 1233 ± 173 vs. LC: 1133 ± 200 ml/s, p = 0.035) were higher and inspiratory time (WC: 1.0 ± 0.1 vs. LC: 1.2 ± 0.2 s, p = 0.025) was shorter at stage 3 during WC than LC. After WC, forced vital capacity (p = 0.010) significantly decreased while no change was observed after LC. These results suggest that at similar metabolic rates during WC and LC, breathing is slightly shallower during WC which may have chronic effects on respiratory muscle function after multiple bouts of aquatic cycling. Underwater exercise may be beneficial for respiratory muscle rehabilitation when performed on a chronic basis.

Influence of water immersion on the airway impedance measured by forced oscillation technique.

INTRODUCTION: Few studies have examined the influence of different water depths on the airway impedance measured by forced oscillation technique in healthy adults. METHODS: Eleven healthy men (23.2 ± 1.5 years old) participated in this study. We measured the respiratory impedance assessed with the resistance at frequency of 5 Hz and 20 Hz, the reactance at frequency of 5 Hz, and frequency of resonance. To compare the influence of water depths, we carried out one dryland (DL) and two water level conditions: clavicle level (CL) and xiphoid appendix level (XA). RESULTS: The respiratory resistance at frequency of 5 Hz was higher in CL and XA than DL, and at 20 Hz was significantly higher in CL than DL. The respiratory reactance at 5 Hz was lower in CL and XA than DL, and frequency of resonance was higher in CL and XA than DL. CONCLUSION: These results suggested that water immersion above xiphoid appendix level increase airway resistance.

Exercise in Water Provides Better Cardiac Energy Efficiency Than on Land.

Although water-based exercise is one of the most recommended forms of physical activity, little information is available regarding its influence on cardiac workload and myocardial oxygen supply-to-demand. To address this question, we compared subendocardial viability ratio (SEVR, the ratio of myocardial oxygen supply-to-demand), cardiac inotropy (via the maximum rate of aortic pressure rise [dP/dTmax]), and stroke volume (SV, via a Modelflow method) responses between water- and land-based exercise. Eleven healthy men aged 24 ± 1 years underwent mild- to moderate-intensity cycling exercise in water (WC) and on land (LC) consecutively on separate days. In WC, cardiorespiratory variables were monitored during leg cycling exercise (30, 45, and 60 rpm of cadence for 5 min each) using an immersible stationary bicycle. In LC, each participant performed a cycling exercise at the oxygen consumption (VO2) matched to the WC. SEVR and dP/dTmax were obtained by using the pulse wave analysis from peripheral arterial pressure waveforms. With increasing exercise intensity, SEVR exhibited similar progressive reductions in WC (from 211 ± 44 to 75 ± 11%) and LC (from 215 ± 34 to 78 ± 9%) (intensity effect: P < 0.001) without their conditional differences. WC showed higher SV at rest and a smaller increase in SV than LC (environment-intensity interaction: P = 0.009). The main effect of environment on SV was significant (P = 0.002), but that of dP/dTmax was not (P = 0.155). SV was correlated with dP/dTmax (r = 0.717, P < 0.001). When analysis of covariance (ANCOVA) was performed with dP/dTmax as a covariate, the environment effect on SV was still significant (P < 0.001), although environment-intensity interaction was abolished (P = 0.543). These results suggest that water-based exercise does not elicit unfavorable myocardial oxygen supply-to-demand balance at mild-to-moderate intensity compared with land-based exercise. Rather, water-based exercise may achieve higher SV and better myocardial energy efficiency than land-based exercise, even at the same inotropic force.

Comparative evaluation of obesity-related parameters in junior sumo wrestlers and children with obesity.

PURPOSE: Exercise is a key factor in preventing obesity and metabolic syndrome. Sumo wrestlers increase their body size from childhood for athletic advantage; however, the risk of metabolic syndrome in junior sumo wrestlers is undetermined. Preventive measures against pediatric obesity should be initiated during childhood to prevent obesity in adulthood, considering its high global incidence. We comparatively evaluated the risk factors for metabolic syndrome in junior sumo wrestlers and children with obesity. METHODS: We enrolled 70 male children (age 9-17 years [sumo group, n = 14] and 9-14 years [other sports and non-exercise groups, n = 28 each]) and evaluated their anthropometric parameters (height, weight, body mass index z-score, obesity rate, waist circumference, waist to height ratio) and hematological parameters (total, low-density, high-density, and non-high-density lipoprotein-cholesterol; triglycerides; plasma glucose, and glycated hemoglobin levels). RESULTS: The BMI z-score, obesity rate, waist circumference (p < 0.05, along with the non-exercise group), and systolic blood pressure were significantly higher and the high-density cholesterol level was lower in the sumo group than in the other sports group (p < 0.05). The waist to height ratio was significantly higher in the non-exercise group than in the other sports group (p < 0.05). No significant difference was found in other blood lipid, plasma glucose (significantly lower level than the reference range in the sumo group, p < 0.05), and glycated hemoglobin (within the reference range in all groups) levels among the three groups. CONCLUSION: Junior sumo wrestlers had a larger body size and higher blood pressure than children with obesity who exercised regularly. This provides direction for future research into targeted preventive interventions against metabolic syndrome for junior sumo wrestlers with large body size.

Effect of Aquatic Exercise Training on Aortic Hemodynamics in Middle-Aged and Elderly Adults.

Aquatic exercise is an attractive form of exercise that utilizes the various properties of water to improve physical health, including arterial stiffness. However, it is unclear whether regular head-out aquatic exercise affects aortic hemodynamics, the emerging risk factors for future cardiovascular disease. The purpose of this study was to investigate whether head-out aquatic exercise training improves aortic hemodynamics in middle-aged and elderly people. In addition, to shed light on the underlying mechanisms, we determined the contribution of change in arterial stiffness to the hypothesized changes in aortic hemodynamics. Twenty-three middle-aged and elderly subjects (62 ± 9 years) underwent a weekly aquatic exercise course for 15 weeks. Aortic hemodynamics were evaluated by pulse wave analysis via the general transfer function method. Using a polar coordinate description, companion metrics of aortic pulse pressure (PPC = √{(systolic blood pressure)2 + (diastolic blood pressure)2}) and augmentation index (AIxC = √{(augmentation pressure)2 + (pulse pressure)2}) were calculated as measures of arterial load. Brachial-ankle (baPWV, reflecting stiffness of the abdominal aorta and leg artery) and heart-ankle (haPWV, reflecting stiffness of the whole aortic and leg artery) pulse wave velocities were also measured. The rate of participation in the aquatic training program was 83.5 ± 13.0%. Aortic systolic blood pressure, pulse pressure, PPC, AIxC, baPWV, and haPWV decreased after the training (P < 0.05 for all), whereas augmentation index remained unchanged. Changes in aortic SBP were correlated with changes in haPWV (r = 0.613, P = 0.002) but not baPWV (r = 0.296, P = 0.170). These findings suggest that head-out aquatic exercise training may improve aortic hemodynamics in middle-aged and elderly people, with the particular benefits for reducing aortic SBP which is associated with proximal aortic stiffness.

Organoid-based ex vivo reconstitution of Kras-driven pancreatic ductal carcinogenesis.

The organoid culture technique has been recently applied to modeling carcinogenesis in several organs. To further explore its potential and gain novel insights into tumorigenesis, we here investigated whether pancreatic ductal adenocarcinoma (PDA) could be generated as subcutaneous tumors in immunocompromised nude mice, by genetic engineering of normal organoids. As expected, acute induction of KrasG12Din vitro occasionally led to development of tiny nodules compatible with early lesions known as pancreatic intraepithelial neoplasia (PanIN). KrasG12D-expressing cells were enriched after inoculation in the subcutis, yet proved rather declined during culture, suggesting that its advantage might depend on surrounding environments. Depletion of growth factors or concurrent Trp53 deletion resulted in its robust enrichment, invariably leading to development of PanIN or large high-grade adenocarcinoma, respectively, consistent with in vivo mouse studies for the same genotype. Progression from PanIN was also recapitulated by subsequent knockdown of common tumor suppressors, whereas the impact of Tgfbr2 deletion was only partially recapitulated, illustrating genotype-dependent requirement of the pancreatic niche for tumorigenesis. Intriguingly, analysis of tumor-derived organoids revealed that KrasG12D-expressing cells with spontaneous deletion of wild-type Kras were positively selected and exhibited an aging-related mutation signature in nude mice, mirroring the pathogenesis of human PDA, and that the sphere-forming potential and orthotopic tumorigenicity in syngenic mice were significantly augmented. These observations highlighted the relevance of the subcutis of nude mice in promoting PDA development despite its ectopic nature. Taken together, pancreatic carcinogenesis could be considerably recapitulated with organoids, which would probably serve as a novel disease model.

Successful delivery in a patient with clinically amyopathic dermatomyositis during pregnancy despite first-trimester acute exacerbation of interstitial lung disease.

A 37-year-old woman with rheumatoid arthritis and interstitial lung disease (ILD) developed clinically amyopathic dermatomyositis (CADM) after achieving pregnancy through in vitro fertilization. She was given oral prednisolone, which improved her respiratory status, and delivered a healthy baby at 35 weeks' gestation. There are few reports of successful outcomes for CADM during pregnancy; to the best of our knowledge, this is the first report of successful delivery in a patient with both CADM and ILD.

Continual Maintenance of Remission Defined by the ACR/EULAR Criteria in Daily Practice Leads to Better Functional Outcomes in Patients with Rheumatoid Arthritis.

OBJECTIVE: To evaluate longterm functional outcomes in rheumatoid arthritis (RA) based on the number of times that the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) or the 28-joint Disease Activity Score (DAS28) remission criteria were fulfilled. METHODS: Patients with RA who participated in all 6 data collections in an observational cohort from 2008 to 2010 and who fulfilled the DAS28 remission criteria at baseline were studied. Patients were classified by the number of times they fulfilled the ACR/EULAR [Boolean trial, Boolean practice, Simplified Disease Activity Index (SDAI), or Clinical Disease Activity Index (CDAI)] or DAS28 remission criteria at each collection. The OR for the Japanese version of the Health Assessment Questionnaire (J-HAQ) progression, based on the number of times each set of remission criteria was fulfilled, were calculated by logistic regression. RESULTS: A total of 915 patients were studied. The OR (95% CI) for J-HAQ progression were 0.54 (0.33-0.87), 0.55 (0.33-0.92), 0.48 (0.28-0.82), 0.29 (0.16-0.51), 0.24 (0.13-0.47), and 0.07 (0.03-0.15) for those fulfilling the Boolean trial remission from 1 to 6 times. This tendency was also observed for the other 4 criteria. The OR (95% CI) for J-HAQ progression in patients who achieved remission at all 6 data collections were 0.07 (0.03-0.14) for the Boolean practice, 0.10 (0.05-0.20) for the SDAI, and 0.07 (0.04-0.15) for the CDAI, whereas 0.15 (0.08-0.29) for the DAS28. CONCLUSION: Continual fulfillment of any remission criteria was strongly effective in preventing patients from progression of functional disability; however, the ACR/EULAR criteria appear to be preferable.

The minimally important difference for the Japanese version of the health assessment questionnaire in patients with rheumatoid arthritis in daily practice.

OBJECTIVE: To validate the minimally important difference (MID) of physical function using the Japanese version of the Health Assessment Questionnaire (J-HAQ) in a cohort of rheumatoid arthritis (RA). METHODS: Patients who participated in a cohort study in both October 2008 and April 2009 were analyzed. Patients self-rated their change in overall status over 6 months using a 5-point Likert scale ("much better", "somewhat better", "same", "somewhat worse", or "much worse"). The MID for J-HAQ score was defined as the mean J-HAQ score change in patients who rated themselves "somewhat better". An effect size (ES) of 0.2-0.5 was considered to be suitable for MID. RESULTS: A total of 4560 patients were analyzed. The mean (standard deviation [SD]) MID for J-HAQ score was -0.06 (0.29), corresponding to an ES of 0.08. As exploratory analysis, 1999 patients with a J-HAQ score ≥0.5 and 28-joint disease activity score (DAS28) ≥ 2.6 at baseline were assessed. The mean (SD) MID for J-HAQ score of these patients was 0.13 (0.01), corresponding to an ES of 0.21. CONCLUSIONS: The MID for J-HAQ score was 0.13 in patients with baseline J-HAQ score ≥0.5 and DAS28 ≥ 2.6. The MID for J-HAQ score was influenced by disease status and functional disability.

Pharmacoeconomic analysis of biological disease modifying antirheumatic drugs in patients with rheumatoid arthritis based on real-world data from the IORRA observational cohort study in Japan.

OBJECTIVES: To evaluate the cost-effectiveness of biological disease modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) in a real-world setting in Japan. METHODS: We used a state-transition model and parameters were determined from RA patients registered in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort study on 421 patients who had failed at least one DMARD and started either 1 of 4 bDMARDs (bDMARD group; adalimumab, etanercept, infliximab, and tocilizumab) or methotrexate (control group). bDMARD group was evaluated as two groups: sequence of any 1 of 4 bDMARDs with and without tocilizumab. The incremental cost-effectiveness ratios (ICERs) for bDMARD group were estimated using base-case analysis, probabilistic sensitivity analysis (PSA) and scenario sensitivity analyses. RESULTS: ICERs of bDMARD group with or without tocilizumab were $38,179 and $48,855, respectively. By PSA, these sequences had respective probabilities of 86.8% and 75.1% of falling below the assumed cost-effectiveness threshold of $50,000 in Japan. Scenario sensitivity analyses showed that the best population for initiating bDMARD was RA patients less than 50 years old with Japanese version of HAQ between 1.1 and 1.6 and using tocilizumab as the bDMARD. CONCLUSION: bDMARDs were cost-effective for RA patients based on a real-world setting in Japan.