School-based online survey on chronic headache, migraine, and medication-overuse headache prevalence among children and adolescents in Japanese one city - Itoigawa Benizuwaigani study.

BACKGROUND: We investigated the prevalence of headache, migraine, and medication-overuse headache (MOH) among children and adolescents through a school-based online questionnaire. We also investigated the triggers for migraine among them and the effect of the COVID-19 pandemic on headache frequency. METHODS: Children and adolescents aged 6-17 y.o. completed an online questionnaire. Migraine, MOH was defined as The International Classification of Headache Disorders Third edition. Factor and clustering analyses were performed for migraine triggers. The effect of the coronavirus disease 2019 (COVID-19) pandemic on headache frequency was also asked. RESULTS: Of the 2489 respondents, the prevalence of headache, migraine, and MOH were 36.44%, 9.48%, and 0.44%, respectively. Up to 70% of the respondents with headaches complained of the disturbance to daily life, but about 30% consulted doctors. The migraine triggers were grouped into 5 factors by factor analysis. The sensitivities of the migraineurs against the factors were divided into 3 clusters. Cluster 1 had stronger sensitivity for several triggers. Cluster 2 was sensitive to weather, smartphones, and video games. Cluster 3 had less sensitivity for triggers. Cluster 2 less consulted doctors even though the burden of migraine was enormous. During the COVID-19 pandemic, 10.25% of respondents increased headache attacks, while 3.97% decreased. CONCLUSIONS: This is the first detailed study on headache prevalence in Japanese students from elementary school to high school in one region. The burden of headaches is large among children and adolescents, and the unmet needs of its clinical practice should be corrected.

Headache education by leaflet distribution during COVID-19 vaccination and school-based on-demand e-learning: Itoigawa Geopark Headache Awareness Campaign.

OBJECTIVE: We prospectively performed the Itoigawa Headache Awareness Campaign from August 2021 to June 2022, with two main interventions, and evaluated its effectiveness. BACKGROUND: Headache is a common public health problem, but its burden could be reduced by raising awareness about headache and the appropriate use of acute and prophylactic medication. However, few studies on raising headache awareness in the general public have been reported. METHODS: The target group was the general public aged 15-64. We performed two main interventions synergistically supported by other small interventions. Intervention 1 included leaflet distribution and a paper-based questionnaire about headache during COVID-19 vaccination, and intervention 2 included on-demand e-learning and online survey through schools. In these interventions, we emphasize the six important topics for the general public that were described in the Clinical Practice Guideline for Headache Disorders 2021. Each response among the two interventions' cohorts was collected on pre and post occasions. The awareness of the six topics before and after the campaign was evaluated. RESULTS: We obtained 4016 valid responses from 6382 individuals who underwent vaccination in intervention 1 and 2577 from 594 students and 1983 parents in intervention 2; thus, 6593 of 20,458 (32.2%) of the overall working-age population in Itoigawa city experienced these interventions. The percentage of individuals' aware of the six topics significantly increased after the two main interventions ranging from 6.6% (39/594)-40.0% (1606/4016) to 64.1% (381/594)-92.6% (1836/1983) (p < 0.001, all). CONCLUSIONS: We conducted this campaign through two main interventions with an improved percentage of individuals who know about headache. The two methods of community-based interventions could raise headache awareness effectively. Furthermore, we can achieve outstanding results by doing something to raise disease awareness during mass vaccination, when almost all residents gather in a certain place, and school-based e-learning without face-to-face instruction due to the COVID-19 pandemic.

Clinical Significance of Fecal Calprotectin for Evaluating Mucosal Inflammation with IgA Vasculitis.

IgA vasculitis is the most common systemic small vasculitis in children. Its major clinical manifestations are palpable purpura, arthritis and arthralgias, gastrointestinal involvement, and renal manifestations. Regarding gastrointestinal manifestations, steroids are effective in reducing abdominal pain. However, exacerbation of gastrointestinal manifestation is frequently experienced when the steroid dose is being tapered. Thus, reliable biomarkers for gastrointestinal mucosal inflammation are needed. We report the case of a 4-year-old girl with abdominal-type IgA vasculitis. During the clinical course, we used several markers, such as fecal immunochemical test, fecal α1-antitrypsin and calprotectin. When fecal immunochemical test showed negative results and fecal α1-antitrypsin value returned to the normal range, corresponding to her abdominal pain improvement, fecal calprotectin levels remained high. This suggests that fecal calprotectin is more sensitive for evaluating mucosal inflammation than other markers. It could be a useful marker for mucosal inflammation in IgA vasculitis.

Clinical Status and Outcome of Isolated Right Ventricular Hypoplasia: A Systematic Review and Pooled Analysis of Case Reports.

Background: Isolated right ventricular hypoplasia (IRVH), not associated with severe pulmonary or tricuspid valve malformation, is a rare congenital myocardial disease. This study aims to evaluate the clinical status and outcome of IRVH. Methods: A systematic search of keywords on IRVH was conducted. Studies were searched from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi (Ichushi) published between January 1950 and August 2021. Results: Thirty studies met the inclusion criteria. All of these studies were case reports and included 54 patients (25 males and 29 females). The median age of the patients was 2.5 years old (0-15.3 years). Of the 54 patients, 13 (24.1%) reported a family history of cardiomyopathy. Moreover, 50 (92.6%), 19 (35.2%), and 17 (31.5%) patients were diagnosed with cyanosis, finger clubbing, and dyspnea, respectively. Furthermore, 53 (98.2%) patients had a patent foramen ovale or an atrial septal defect (ASD). Z-score of the tricuspid valve diameter on echocardiogram was -2.16 ± 1.53, concomitant with small right ventricular end-diastolic volume. In addition, 29 (53.7%), 21 (38.9%), 7 (13.0%), and 2 (3.7%) patients underwent surgery, ASD closure, Glenn operation, and one and a half ventricular repair, respectively. Among them, nine (20.4%) patients expired, and the multivariable logistic regression analysis showed that infancy, heart failure, and higher right ventricular end-diastolic pressure were risk factors for death. Conclusions: IRVH was diagnosed early in children with cyanosis and was associated with high mortality. This systematic review and pooled analysis provided evidence to assess the of IRVH degree in order to evaluate the clinical status and outcome of IRVH.

The radial augmentation index in children with Kawasaki disease without acute coronary artery lesions during the convalescent period.

PURPOSE: We recently reported that children and adolescents with a history of Kawasaki disease (KD) had slight but significant elastic arterial stiffness even when no coronary artery lesions (CALs) were present. Moreover, we hypothesized that KD-related arteriopathy may also cause peripheral artery dysfunction. The objective of this study was to assess the involvement of radial artery pulse waves, especially reflection waves from the peripheral arteries using the radial artery augmentation index (rAI) in patients without CALs after KD. MATERIALS AND METHODS: We first collected the rAI data from 312 subjects (149 consecutive patients of KD and 163 control subjects). Next, 225 cases between 6 and 15 years old were selected. Finally, 41 pairs were included for analysis. The rAI values of these two groups were compared and analyzed. Acute-phase data were also collected to reveal the possible correlation with rAI in the convalescent period. RESULTS: Multivariable analysis revealed the history of KD was positively correlated with rAI@75 value in children from 6 to 15 years old. After pairing the height and gender, the KD group also had significantly higher rAI and rAI@75 than the control group (rAI 60.63±13.77 vs 54.56±13.17, p=0.028; rAI@75 63.61±15.21 vs 55.68±14.86, p=0.003). With regard to acute-phase condition, nonresponse to initial treatment was also linked to elevated rAI during the convalescent period. CONCLUSIONS: During the convalescent period, the rAI increased in KD patients without acute CALs. Furthermore, nonresponse to initial treatment in acute phase conferred higher rAI to KD subjects than respondent cases. Elevated rAI means the reflection wave from the peripheral vascular is stronger or earlier. This small but significant change may indicate the existence of peripheral artery stiffness during the convalescent period.

Subclinical arterial stiffness in young children after Kawasaki disease.

BACKGROUND: Recent studies have revealed that atherosclerosis progresses faster than expected in young adults with a history of Kawasaki disease. However, it is unclear as to when these arterial changes become measurable. In this study, we evaluated subclinical arterial stiffness in young children with a history of Kawasaki disease using two-dimensional ultrasound speckle tracking. METHODS: A total of 75 children with a history of Kawasaki disease (mean age, 8.2 ± 2.8 years) and 50 healthy controls (mean age 8.3 ± 3.5 years) were included. The two regions of interest for speckle tracking were manually positioned at the anterior and posterior carotid arterial wall using a Philips iE33 (Philips Medical Systems, Bothell, WA, USA). The peak systolic strain, time to peak systolic strain, early systolic strain rate, and late systolic strain rate were continuously monitored between the two regions of interest. Furthermore, the intimal-medial thickness, stiffness ß, and pressure-elastic modulus, as conventional measures of arterial stiffness, were concurrently obtained. RESULTS: The peak systolic strain and late systolic strain rate differed significantly between the patients with Kawasaki disease and controls (6.69% versus 8.60%, p < 0.01, and -0.28/second versus -0.51/second, p < 0.0001, respectively). There was no difference in the time to peak systolic strain, early systolic strain rate, and conventional measures. CONCLUSIONS: The arteries of patients with Kawasaki disease appear to develop mild sclerotic changes shortly after the onset of the disease.

Effect of a single bout of moderate exercise on glucose uptake in type 2 diabetes mellitus.

BACKGROUND AND PURPOSE: Hypoglycemia during exercise is a serious problem in diabetic patients during cardiac rehabilitation, whereas normal subjects rarely experience hypoglycemia. Inappropriate glucose uptake by working muscles may be responsible. However, the precise characteristics of glucose uptake during exercise have not been fully studied. We have investigated the effect of acute exercise on glucose uptake in diabetic patients. METHODS: Nine type 2 diabetic patients (age, 57 ± 6 years; HbA1c, 7.7 ± 1.3%) performed exercise at an intensity of anaerobic threshold for 15 min. Glucose utility was determined using euglycemic hyperinsulinemic clamp technique. Glucose infusion rate (GIR) was calculated throughout the exercise and recovery session. RESULTS: Average GIR at rest was 3.4 ± 1.6 mg/(kg(BW)min). Fifteen minutes after starting exercise, it increased significantly (6.6 ± 2.4, p < 0.001). Thirty minutes after cessation of exercise, GIR decreased significantly (4.8 ± 1.9, p < 0.05) compared with peak value. Increase in GIR was greater as BMI or body fat ratio became greater (r=0.608 and 0.475). There was a weak correlation (r=0.344) between HbA1c and GIR improving ratio (GIR during exercise x 100/GIR at rest). CONCLUSIONS: Glucose uptake was revealed to augment significantly within 15 min after the commencement of exercise. This improvement was more obvious in patients with greater body weight, fat accumulation, and poorer diabetic control.

Effect of insulin sensitivity on severity of heart failure.

Insulin resistance is associated with various cardiac dysfunctions both molecularly and clinically, including cardiac muscle relaxation and blood flow. Although, these dysfunctions result in heart failure, relationship between insulin resistance and severity of heart failure is not well studied yet. Since severity of chronic heart failure can be determined by exercise tolerance, we attempted to assess the insulin resistance in patients with chronic heart failure and evaluated the relationship between insulin sensitivity and exercise tolerance. We examined nine chronic heart failure patients. Insulin sensitivity was determined with euglycemic hyperinsulinemic clamp technique. Exercise tolerance was assessed using cardiopulmonary exercise testing. There was no correlation between body mass index and insulin sensitivity, while between body fat ratio, significant negative correlation was investigated (r=-0.463). Insulin sensitivity was negatively correlated with exercise tolerance (with anaerobic threshold, r=0.548; with peak oxygen uptake, r=0.581). Insulin sensitivity also showed significant positive correlation with cardiac function during exercise (GIR versus peak oxygen pulse: r=0.535). Insulin sensitivity is revealed to have some effects on exercise tolerance and cardiac function in patients with chronic heart failure. Insulin resistance seems to be one of the important targets in managing the chronic heart failure.

HSF1 and constitutively active HSF1 improve vascular endothelial function (heat shock proteins improve vascular endothelial function).

We have been examining the role of heat shock factor 1 (HSF1) in the pleiotropic effects of statins. In parallel studies, we found that statin induces the nuclear translocation of HSF1 and that a decoy oligonucleotide encoding the heat shock element inhibits the statin-induced expression of heat shock protein 70, endothelial nitric oxide synthase (eNOS) and thrombomodulin. Also, in vascular endothelial cells, increases in the expression of human HSF1 corresponded with elevated steady-state levels of eNOS and thrombomodulin and reduced levels of endothelin-1 and plasminogen activator inhibitor-1. We also found that heat shock proteins induced eNOS and thrombomodulin expression and reduced PAI-1 and ET-1 expression. In particular, a combination of HSP70 and HSP90 strongly induced eNOS expression and reduced PAI-1 expression. In the current studies, we generated a constitutively active form of HSF1 and found that it is more effective than the wild-type HSF at inducing thrombomodulin and eNOS expression and decreasing endothelin-1 and plasminogen activator inhibitor-1 expression. These results show that the wild-type and constitutively active forms of HSF1 induce anticoagulation and relaxation factors in vascular endothelial cells and could therefore be used to treat cardiovascular disease.

Neuromuscular electrical stimulation and an ottoman-type seat effectively improve popliteal venous flow in a sitting position.

The aim of this study was to examine the effects of the sitting posture on the lower limb venous flow and to explore the beneficial effects of neuromuscular electrical stimulation (NMES) and an ottoman-type seat on the venous flow. Healthy adult volunteers without a history of lower limb surgery or thromboembolism were recruited, and the flow velocity, cross-sectional area, and flow volume of the popliteal vein were measured using Doppler ultrasound. A posture change from the prone position to the sitting position on the ottoman-type seat decreased the flow velocity and increased the cross-sectional area of the popliteal vein, and the flow volume was not altered over 120 min. The flow velocity was further decreased, and the cross-sectional area was further increased by subjects sitting on a regular driving seat when compared with the values obtained with an ottoman-type seat. The popliteal flow velocity in the NMES leg was significantly higher than in the non-NMES leg throughout the 120-min testing in the sitting position, but no difference in the cross-sectional area was found between the NMES and the non-NMES legs. Thus lower limb venous stasis elicited by the sitting posture was improved by the ottoman-type seat and NMES.