Osaka Nishi Clinic

Post-COVID-19 Vaccination Syndrome (PCVS) refers to persistent, multisystemic symptoms developing after SARS-CoV-2 immunization. We established a nationwide registry across 14 Japanese outpatient clinics and analyzed 179 “clinically definitive” cases from 279 enrollees (December 2020–August 2023). All adverse events (AEs) were coded using MedDRA/J Preferred Terms and System Organ Classes; severity followed NCI-CTCAE V5.0. The cohort (66.5% female; mean age 59 years) experienced 493 AEs (median 2 per patient, range 1–29). Three System Organ Classes—General Disorders (29.2%), Nervous System Disorders (22.3%), and Musculoskeletal Disorders (10.1%)—accounted for 61.7% of events; fatigue, brain fog, dizziness, and extremity pain predominated. While 69.4% of AEs arose within 90 days post-vaccination, 12.4% appeared ≥ 360 days later. Severe AEs (≥ Grade 3) occurred in 14.6% of patients; overall improvement was 65.1%, leaving 29.4% unresolved. A provisional phenotype classification combining symptom patterns, onset timing, and severity identified high-risk subgroups with > 60% non-recovery rates. These findings underscore the need for enhanced post-vaccination surveillance systems and comprehensive care frameworks specifically tailored to address the protean manifestations and persistent nature of PCVS.

Electromyograms (EMGs) of the orbicularis oculi muscle are commonly used to assess the blink reflex, which provides clinically important information. However, mechanomyograms (MMGs) may serve as a promising alternative. This study aimed to evaluate the utility of MMGs in assessing orbicularis oculi responses to stimulation. Electrical stimulation was applied to the facial nerve axons of 25 healthy adult participants, and MMGs were recorded using an accelerometer. The reliability of amplitude-based parameters (Amax and Ap−p) and time-based parameters (Trise, Tzero, Tfall, and Trec) characterizing MMG waveforms was assessed using the intraclass correlation coefficient (ICC), standard error of measurement (SEM), and coefficient of variation (CV). Additionally, the amplitude and temporal characteristics of MMGs evoked by varying stimulus intensities were compared with simultaneously recorded EMGs. All parameters, except Trec, showed high relative reliability (95% confidence interval of ICC of > 0.75) and high absolute reliability (%SEM and CV < 10%). MMG amplitudes (Amax and Ap−p) and EMG amplitudes (Vmax and Vp−p) increased linearly with stimulus intensity. A strong correlation was found between the amplitudes of both signals (Vmax vs. Amax: r = 0.932, p < 0.0001; Vp−p vs. Ap−p: r = 0.937, p < 0.0001). The first positive MMG peak consistently appeared at a fixed interval (5.52 ± 2.10 ms) after the EMG peak, irrespective of stimulus level. These findings suggest that MMG amplitude and latency (stimulus-to-peak time) are reliable indicators of orbicularis oculi muscle activity and can be effectively used alongside EMG in clinical and research settings. Communicated by Bill Yates.

Introduction: Chronic constipation is common, but its characteristics and impact on various aspects of daily life remain unclear. This study examined patient characteristics and assessed how background factors, constipation symptoms, and defecation status impact daily life dissatisfaction, quality of life (QOL), and psychological states. Methods: A multicenter, prospective, observational study on outpatients with moderate to severe chronic constipation was conducted. The Chronic Constipation-Therapeutic Efficacy and Satisfaction Test (CC-TEST) and validated questionnaires such as the Hospital Anxiety and Depression Scale (HADS) and Short Form Health Survey-8 (SF-8) were administered to assess symptoms, defecation status, and daily life. Correlation and multiple regression analyses explored factor relationships. Results: The analysis included 201 participants. Despite treatment, with over half using magnesium oxide, many patients remained dissatisfied. Younger patients and females reported more severe abdominal symptoms, while older patients experienced greater defecation difficulty. All constipation symptoms correlated with daily life dissatisfaction, with abdominal discomfort showing the strongest association. Abdominal symptoms were significantly associated with the Mental Component Summary (MCS) of the SF-8, HADS anxiety, and HADS depression scores. Most defecation status components showed no correlation with SF-8 MCS, HADS anxiety, or HADS depression scores. Multivariate analysis revealed that abdominal symptoms, especially discomfort, significantly impacted daily life dissatisfaction, and reduced SF-8 MCS scores. Conclusions: Many patients with moderate to severe chronic constipation experience long-term symptoms and remain dissatisfied with treatment. Abdominal symptoms such as discomfort and pain significantly affect their daily life, QOL, and psychological well-being. Reducing abdominal symptoms may be crucial for improving treatment outcomes.

ABSTRACTWe previously performed data‐driven classification based on large‐scale neuroimaging datasets to identify a potential novel subtype of psychiatric disorders characterized by the pronounced enlarged ventricles and cognitive impairment (EVCI) in one cohort. However, these findings have yet to be validated across independent cohorts. Herein, we investigated the availability of cognitive data in other cohorts in the Cognitive Genetics Collaborative Research Organization (COCORO) project to assess the presence of cognitive impairment (CI). Subsequently, we compared the prevalence of CI, lateral ventricular volume, and demographic and clinical characteristics between individuals with EVCI and those with EV but without CI (EV‐nonCI). Cognitive data were available for 27 individuals with EVCI from the other 8 cohorts. Among the 27 individuals in the EV group, 5 (18.5%) exhibited EVCI, all of whom were diagnosed with schizophrenia. Three individuals (60%) in the EVCI group were male. Compared with the EV‐non‐CI group, the EVCI group presented significantly lower current intellectual quotient (IQ) scores (p = 5.8 × 10−4), but there was no significant difference in premorbid IQ (p = 0.56). Furthermore, there was no significant difference in the Z scores for lateral ventricular volume between the groups (p = 0.26). This study validated the existence of the EVCI subgroup in independent cohorts, thus supporting our previous findings.

BackgroundChronic constipation, common in clinical practice, requires treatment to enhance quality of life and possibly extend life expectancy. However, predictors of treatment efficacy remain largely unexplored. This study aimed to identify factors predicting treatment success in patients with chronic constipation.MethodsA multicenter, prospective observational study evaluated patients with moderate to severe chronic constipation using the Chronic Constipation-Therapeutic Efficacy and Satisfaction Test (CC-TEST) questionnaire. Symptoms were assessed before treatment and at 2 and 4 weeks post-treatment. Multivariate analyses identified predictive factors based on three treatment efficacy assessment criteria: patient’s impression, numeric rating scale (NRS) for symptom intensity, and spontaneous bowel movement (SBM) frequency status.ResultsConstipation medications were administered to 97 patients, with significant symptom improvements observed at 2 and 4 weeks (CC-TEST). The greatest effects were seen in hard stools, difficulty in defecation, and infrequent bowel movements. In the multiple regression analysis, baseline clinical characteristics and symptom profiles were not significant predictors of treatment response. Incorporating 2-week treatment responsiveness revealed that non-responsiveness at 2 weeks (β = 0.487), and a lower stool symptom subscale score (β = -0.344), were associated with poorer patient’s impression. For the NRS, non-responsiveness at 2 weeks (β = 0.279) was a significant predictor. For SBM, non-responsiveness at 2 weeks (β = -0.274) predicted outcomes. Including 2-week non-responsiveness improved the predictive accuracy for 4-week efficacy.ConclusionsThe therapeutic response at 2 weeks is the most significant predictor of subsequent treatment response at 4 weeks in patients with chronic constipation.

Antipsychotics are widely used for neuropsychiatric symptoms (NPSs) in dementia including Alzheimer's disease (AD), yet balancing efficacy and safety remains a major clinical challenge. Relevant randomized controlled trials were identified through a comprehensive literature search of CENTRAL, PubMed, CINAHL, and ClinicalTrials.gov. We conducted a dose-response model-based network meta-analysis to evaluate the efficacy as the change in overall NPS severity and the tolerability as treatment discontinuation due to adverse events of aripiprazole, brexpiprazole, risperidone, quetiapine and olanzapine at varying doses in patients with dementia including AD. Twenty trials involving 5844 participants were included. Most of the included antipsychotics exhibited a generally positive dose-response relationship with respect to both efficacy and tolerability, except for olanzapine, which showed a bell-shaped curve in terms of efficacy. Only aripiprazole 10 mg, brexpiprazole 1-2.5 mg, risperidone 1-2 mg, and olanzapine 2.5-5 mg were significantly more effective than placebo. Tolerability did not significantly decrease compared to placebo for aripiprazole up to 10 mg, brexpiprazole up to 3 mg, risperidone up to 1 mg, olanzapine up to 2.5 mg and at 15 mg, and quetiapine up to 200 mg. Furthermore, significant differences in efficacy and tolerability were observed between certain doses of several antipsychotics. Aripiprazole 10 mg, brexpiprazole 1-2.5 mg, risperidone 1 mg, and olanzapine 2.5 mg were both effective and well tolerated, indicating their potential as favorable treatment options. As the present model incorporates several sources of uncertainty, its findings should be interpreted with caution and regarded as a provisional framework to support clinical decision-making.

Digital therapeutics (DTx) for hypertension are among the most promising treatment options, demonstrating proven antihypertensive effects. This study investigates the determinants of the home blood pressure (BP) lowering effect of DTx, using prospectively collected daily data. The B-INDEX study (Behavioral Modification Index) is a multicenter intervention study in patients with hypertension, involving a 6-month DTx period, followed by an additional 6 months without it. Home BP, body weight and composition, physical activity, and sleep patterns were monitored daily using digital devices. This first report on B-INDEX analyzed data collected during a 6-month DTx treatment period. A total of 198 patients with hypertension (mean age, 54.9±10.6 years; 57.1% male; mean body mass index, 26.7±5.3 kg/m2; 57.6% taking antihypertensives) were included in the analysis. A marked reduction in BP was observed in the first 4 weeks (morning home BP, -6.2/-2.6 mm Hg). Mixed model analysis demonstrated that baseline home BP, older age, self-efficacy score, reduction in self-reported salt intake, and mild initial weight loss (-0.5 kg at week 4) were significant determinants of home BP reduction at 6 months. Older age, salt reduction, and initial weight loss were predictive factors for effective BP reduction through DTx, independent of baseline BP values. We propose that the first 4 weeks are the key period for hypertension treatment with DTx. URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000050479.

Obesity is a major complication in individuals with 21-hydroxylase deficiency (21-OHD) and excessive hydrocortisone (HC) dosing is a likely contributing factor. However, the association between the HC dosage and body mass index (BMI) during childhood remains unclear. We previously reported a positive correlation between HC dosage during late infancy and a subsequent increase in BMI. In this study, we expanded our research to assess the impact of HC dosage during childhood. We retrospectively collected data on HC dosages and BMI in 28 patients with 21-OHD (9 boys and 19 girls) at both 3 and 10 yr of age and conducted correlation analyses between HC dosage and BMI. No significant cross-sectional associations were observed between the body-surface-area adjusted HC dosage (HC/BSA) and BMI standard deviation score (BMI-SDS) at either 3 or 10 yr of age. However, the HC/BSA at 3 yr positively correlated with the BMI-SDS at 10 yr, indicating a longitudinal relationship. Furthermore, children whose HC/BSA at 3 yr fell almost within the guideline-recommended range exhibited significantly lower BMI-SDS at 10 yr compared to those receiving higher doses. The longitudinal association between HC dosage and BMI suggests the importance of careful HC dose monitoring, although causality could not be established.