St. Cloud State University

Systemic baricitinib and corticosteroids play important roles in treating severely and critically ill patients with coronavirus disease 2019 (COVID-19). However, the efficacy of the combination of baricitinib and corticosteroids compared to that of corticosteroid monotherapy in severely and critically ill hospitalized patients with COVID-19 remains unclear.

Abstract Background Febuxostat and topiroxostat are non-purine selective xanthine oxidoreductase inhibitors commonly used for hyperuricaemia treatment in Japan. However, comparative data on the effects of febuxostat and topiroxostat on renal function and proteinuria are limited. This study compared proteinuria incidence and changes in the estimated glomerular filtration rate (eGFR) among prevalent febuxostat and topiroxostat users. Methods We conducted a retrospective cohort study using databases provided by DeSC Healthcare, Inc. (Tokyo, Japan). We identified 17,446 individuals (11.8% women; mean age 67.4 years) with eGFR ≥ 30 mL/min/1.73 m2 and no history of cardiovascular disease or proteinuria at baseline. Separate analyses were performed for individuals with eGFR < 60 mL/min/1.73 m2 and those with eGFR ≥ 60 mL/min/1.73 m2. The adjusted hazard ratio (HR) for proteinuria incidence in topiroxostat users compared with febuxostat users was assessed using the Cox model. Changes in eGFR were compared between the two groups using multiple regression analysis. Results During the mean follow-up period of 1.79 years, 1,433 participants developed proteinuria. In non-diabetic individuals with eGFR ≥ 60 mL/min/1.73 m2, the adjusted HR for proteinuria incidence in topiroxostat users compared with febuxostat users was 0.60 (95% confidence interval, 0.40–0.91; p = 0.016). No significant differences were observed in eGFR changes between the two groups with eGFR < 60 and ≥ 60 mL/min/1.73 m2. Conclusion Topiroxostat prevalent users had a lower risk of proteinuria than febuxostat prevalent users in non-diabetic individuals with eGFR ≥ 60 mL/min/1.73 m2. Our findings suggest that topiroxostat might be more effective than febuxostat in preventing proteinuria in non-diabetic individuals with eGFR ≥ 60 mL/min/1.73 m2.

AbstractBackgroundNeuropsychological abnormalities are common in patients with multiple sclerosis (MS); however, unlike motor and sensory deficits, their measurement in a clinical setting can be difficult.MethodsWe evaluated 80 patients with MS using the newly created Japanese version of a patient‐report form of the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) and compared the results with those of processing speed tests (PST), namely, CogEval, and health‐related quality of life (QOL). QOL was evaluated using the Medical Outcomes Study Short Form‐36 Health Survey (SF‐36).ResultsThe partial correlation coefficient, after excluding the effect of disease duration, showed that the total MSNQ score was significantly correlated with PST (r = −0.2798, P = .0125), mental component summary (MCS) (r = −0.2913, P = .0092), and social role component summary (RCS) (r = −0.2591, P = .0211) in SF‐36. Multiple linear regression analyses showed that physical component summary was significantly associated with age (P = .0158), EDSS (P = .0005), and CogEval raw score (P = .0029), whereas MCS was significantly associated with MSNQ (P = .0007). When patients with MS were divided into two groups using a median total MSNQ score threshold of 17, those with high MSNQ scores showed significantly higher EDSS scores (P = .0101), lower PST scores (P = .0426), and lower MCS scores in SF‐36 (P = .0083).ConclusionThe Japanese version of the patient‐reported MSNQ can be useful in identifying patients with decreased mental QOL, which might be more difficult than to capture physical QOL.

ABSTRACTIn this study, we aimed to reveal the trends of self‐measured blood pressure (SMBP) and SMBP‐derived indices during pregnancy and the postpartum period. The Babies and Their Parents Longitudinal Observation in Suzuki Memorial Hospital in the Intrauterine Period (BOSHI) Study is a prospective cohort study in Japan. Participants were instructed to measure SMBP daily during pregnancy and for 1 month after delivery. Among 237 participants with normotensive blood pressure (BP) during pregnancy and the postpartum period who were analyzed using mixed‐effects models for repeated measures, the SMBP was measured, on average, 14.3 times from the day before delivery to 28 days postpartum. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) on the day before delivery were 110.6 ± 1.0 and 68.1 ± 0.8 mmHg (estimate ± standard error). Postpartum BP increased from postpartum Days 3–8 in SBP and from Days 3–22 in DBP, compared to that on the day before delivery. The SBP and DBP were 4.9 and 4.7 mmHg higher on postpartum Days 8 and 7 than the day before pregnancy, respectively. During pregnancy, the pulse rate (PR) showed an inverted U‐shaped trend and then sharply increased rapidly until the first postpartum day after delivery. The Shock Index showed a similar trend to that of the PR, decreased from labor until postpartum Day 8, and plateaued thereafter. The double product peaked during labor, remained higher than the prelabor levels for approximately 10 days, and then decreased in the postpartum period.

Abstract Previous studies have shown an increase in blood pressure during the coronavirus disease 2019 (COVID-19) pandemic even among patients receiving antihypertensive treatment. This study aims to evaluate the association between equivalized annual household income and refraining from regular medical visits for hypertensive patients since the COVID-19 outbreak. We analyzed data from the Japan COVID-19 and Society Internet Survey (JACSIS), including 2832 hypertensive patients aged 20–79 years from the 2020 survey and at least one survey between 2021 and 2023. They were categorized into lower-income (<median of ¥3,182,000) and higher-income (≥median) groups. Refraining from regular medical visits was defined as not attending scheduled medical visits for hypertension in the past two months. Poisson regression or generalized linear mixed models were used, inverse probability weighted for Internet survey selection. After weighting, the mean age was 64.8 ± 10.3 years and 63.7% were men. In 2020, the proportion of hypertensive patients refraining from regular medical visits after weighting was 19.6% in the lower-income group and 8.8% in the higher-income group, with an adjusted proportion ratio (95% confidence interval) of 1.86 (1.13–3.06) for the lower-income group compared with the higher-income group. After 2020, the proportion of those refraining from regular medical visits declined in all income groups, and the income-related differences disappeared. During the social restrictions due to the COVID-19 pandemic, hypertensive patients with lower equivalized annual household incomes were more likely to refrain from regular medical visits. Strategies to reduce income-related inequities in medical care utilization may be necessary for future public health crises.

Anti-herpesvirus drug-induced encephalopathy can complicate herpes zoster treatment; however, the association between the recently developed anti-herpesvirus drug amenamevir and encephalopathy development remains unknown. Determining the characteristics of amenamevir-induced encephalopathy is essential for potentially improving patient outcomes in the treatment of herpes zoster. The aim of this study is to identify the association between amenamevir treatment and encephalopathy and to determine the risk factors for amenamevir-induced encephalopathy via disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database.

Disseminated herpes zoster (DHZ) is a severe infection associated with high incidences and mortality rates in immunocompromised patients. Although studies have shown its occurrence in immunocompetent patients, its epidemiology, clinical presentation, and treatment outcomes in this cohort remain unknown. Thus, this study aimed to examine the clinical presentation, treatment, complications, and outcomes of DHZ in immunocompetent patients and compare these findings with previous studies.

Differentiation therapy with all-trans retinoic acid (ATRA) is well established for acute promyelocytic leukemia (APL). However, the narrow application and tolerance development of ATRA remain to be improved. A number of kinase inhibitors have been reported to induce cell differentiation. In this study, we investigated several combinations of these kinase inhibitors. Recently, we revealed that the Akt inhibitor triciribine (TCN) efficiently induces differentiation of NB4 APL cells and acute myeloid leukemia (AML) M2-derived HL-60 cells through activation of the ERK/MAPK pathway. In the present study, we found that the p38 MAPK inhibitor PD169316 had profoundly enhanced the TCN effect for differentiation of NB4 and HL-60 cells. Morphologically, the combination of these two agents efficiently reduced the nuclear-to-cytoplasmic ratio and induced the expression of myelomonocytic markers (CD11b, CD11c) and some ectopic markers (erythroid glycophorin A, lymphoid CD7 and CD20), as determined by PCR and flow cytometry analyses. Western blotting analysis revealed that these agents efficiently induced phosphorylation of ERK. To clarify the molecular mechanisms involved in the TCN and PD169316-induced differentiation, we performed microarray analyses using NB4 cells. Pathway analysis using DAVID software indicated that “viral protein interaction with cytokine and cytokine receptor” and “cytokine-cytokine receptor interaction” were enriched with high significance. Real-time PCR analysis demonstrated that genes for components of these pathways, including chemokines like CCL1, CCL2, CCL3, CCL5, and CXCL8 as well as cytokines and receptors like CSF1, IL-10, IL-10RA, IL-10RB, IL-1β, and TNFSF10, were upregulated in NB4 and HL-60 cells during TCN and PD169316-induced differentiation.

Home blood pressure (BP) measurement is widely used, and home BP plays a central role in hypertension management in clinical practice in Japan. We updated the systematic review to determine whether home BP-based antihypertensive treatment is superior to office BP-based treatment in improving clinical outcomes, including BP levels, in adult patients with essential hypertension. A literature search identified 14 randomized controlled trials (RCTs). The results of meta-analysis revealed that home BP-based antihypertensive treatment was significantly associated with greater reductions in ambulatory systolic BP by 2.73 mmHg (95% confidence interval [CI], –5.23 to –2.22 mmHg; p = 0.03) and ambulatory diastolic BP by 1.61 mmHg (95% CI, –3.21 to –0.01 mmHg; p = 0.05) compared to office BP-based treatment. No RCTs evaluating cardiovascular outcomes other than ambulatory BP reduction were identified. Consistent with the previous review, this updated meta-analysis revealed home BP-based antihypertensive treatment is strongly recommended over office BP-based treatment for BP control in patients with essential hypertension.

Abstract Objectives The efficacy of avacopan as remission induction therapy for Anti-Neutrophil Cytoplasmic Autoantibody (ANCA)-associated vasculitis (AAV) is well-established. However, concerns regarding liver injury post-avacopan treatment remain, especially in Japan. Therefore, this study aimed to investigate drug-induced liver injury (DILI) associated with avacopan treatment. Methods This study included 22 patients with AAV who were treated with avacopan at multiple centers in Japan between September 2021 and March 2024. DILI was assessed by the Japanese version of a revised electronic causality assessment method (RECAM-J 2023). Results Among the 22 patients treated with avacopan, DILI was observed in nine cases (40.9%): six with microscopic polyangiitis and three with granulomatosis with polyangiitis. Severe DILI with elevated total bilirubin (T-Bil) was observed in four of the nine patients (44.4%), a few weeks after the initiation of avacopan therapy. Eight of the nine patients (88.9%) with DILI improved after discontinuation of avacopan and other medications, and one patient developed vanishing bile duct syndrome (VBDS) leading to death. Avacopan-induced DILI was classified into three patterns: 1, short-term injury without T-Bil elevation; 2, transient cholestatic liver injury with T-Bil elevation; 3, decompensated liver injury with marked T-Bil elevation (VBDS). The risk factors for severe DILI with T-Bil elevation in Japanese patients included older age, lower body mass index, and early onset DILI following the initiation of avacopan treatment. Conclusion Avacopan-induced DILI is relatively common in Japan and could be lethal. Frequent laboratory follow-ups should be considered, especially for elderly and low-body-weight patients.