Improvement of the Ocular Prognosis of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: A National Survey in Japan.

PURPOSE: To investigate the incidence and prognostic factors of ocular sequelae in Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) cases arising between 2016 and 2018 in Japan, and compare the findings with those presented in the previous 2005-2007 survey. DESIGN: Retrospective, national trend survey . METHODS: Dermatological case report forms (CRFs) (d-CRFs) were sent to 257 institutions that treated at least 1 SJS/TEN case, and 508 CRFs were collected from 160 institutions. Ophthalmological CRFs (o-CRFs) regarding patient demographic data, onset date, ocular findings (first appearance, day of worst severity, and final follow-up), topical treatment (betamethasone), outcome (survival or death), and ocular sequelae (visual disturbance, eye dryness) were sent to the ophthalmologists in those 160 institutions. The results of this survey were then compared with that of the previous 2005-2007 survey. RESULTS: A total of 240 cases (SJS/TEN: 132/108) were included. The incidence of ocular sequelae incidence was 14.0%, a significant decrease from the 39.2% in the previous survey (SJS/TEN: 87/48). In 197 (82.1%) of the cases, systemic treatment was initiated within 3 days after admission, an increase compared to the previous survey (ie, treatment initiated in 82 [60.7%] of 135 cases). Of the 85 cases with an Acute Ocular Severity Score of 2 and 3, 62 (72.9%) received corticosteroid pulse therapy and 73 (85.9%) received 0.1% betamethasone therapy; an increase compared to the 60.0% and 70.8%, respectively, in the previous survey. Ocular-sequelae-associated risk factors included Acute Ocular Severity Score (P < 0.001) and specific year in the survey (P < 0.001). CONCLUSIONS: The ophthalmologic prognosis of SJS/TEN has dramatically improved via early diagnosis, rapid assessment of acute ocular severity, and early treatment.

Impact of Sleep Apnea on Nocturnal Parasympathetic Activity in Atrial Fibrillation Patients After Catheter Ablation　- Implications for Heart Rate Variability Analysis.

BACKGROUND: The impact of sleep apnea (SA) on heart rate variability (HRV) in atrial fibrillation (AF) patients has not been investigated.Methods and Results: Of 94 patients who underwent AF ablation between January 2021 and September 2022, 76 patients who had a nocturnal Holter electrocardiography and polysomnography conducted simultaneously were included in the analysis. A 15-min duration of HRV, as determined by an electrocardiogram during apnea and non-apnea time, were compared between patients with and without AF recurrence at 12 months' postoperatively. Patients had a mean age of 63.4±11.6 years, 14 were female, and 20 had AF recurrence at 12 months' follow-up. The root mean square of the difference between consecutive normal-to-normal intervals (RMSSD, ms) an indicator of a parasympathetic nervous system, was more highly increased in patients with AF recurrence than those without, during both apnea and non-apnea time (apnea time: 16.7±4.5 vs. 13.5±3.3, P=0.03; non-apnea time: 20.9±9.5 vs. 15.5±5.9, P<0.01). However, RMSSD during an apneic state was decreased more than that in a non-apneic state in both groups of patients with and without AF recurrence (AF recurrence group: 16.7±4.5 vs. 20.9±9.5, P<0.01; non-AF recurrence group; 13.5±3.3 vs. 15.5±5.9, P=0.03). Consequently, the effect of AF recurrence on parasympathetic activity was offset by SA. Similar trends were observed for other parasympathetic activity indices; high frequency (HF), logarithm of HF (lnHF) and the percentage of normal-to-normal intervals >50 ms (pNN50). CONCLUSIONS: Without considering the influence of SA, the results of nocturnal HRV analysis might be misinterpreted. Caution should be taken when using nocturnal HRV as a predictor of AF recurrence.

Developing a behaviour rubric for the practical model of ethical behaviour for clinical nursing.

AIM: The present study aimed to develop an ethical behaviour rubric for nurses and evaluate its reliability and validity. METHOD: This study was to designed to construct a rubric and evaluate the reliability and validity. The ethical behaviour rubric was distributed to 241 nurses and 154 were completed and returned. The intra-rater and inter-rater reliability were evaluated by intraclass correlation coefficient (ICC) for all 10 items on the ethical behaviour rubric, and the internal consistency reliability was evaluated using Cronbach's α. Construct validity was tested with explanatory factor analysis, and criterion validity was tested using the known-groups method. RESULTS: Intra-rater reliability had a high interrater agreement (ICC = 0.9), and inter-rater reliability had a high interrater agreement (ICC = 0.84). The Cronbach's α coefficient was 0.96. There was a linear correlation between the number of years of nursing experience and rubric scores p < 0.001. Exploratory factor analysis revealed 10 items loading on four factors. The result of factor analysis is that Cronbach's α was 0.93 for the first factor, 0.83 for the second factor, 0.91 for the third factor, and 0.77 for the fourth factor. CONCLUSIONS: Our rubric was found to be a valid and reliable tool for the assessment of ethical behaviour among nurses in Japan.

Severe ocular complications of SJS/TEN and associations among pre-onset, acute, and chronic factors: a report from the international ophthalmology collaborative group.

We formed an international research collaboration that included Japan, South Korea, Brazil, Thailand, Taiwan, the UK, and the US (682 patients from 13 hospitals between 2005 and 2020), to better evaluate the role of race, ethnicity, and other risk factors in the pathophysiology of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Ophthalmologists often see SJS/TEN patients with severe ocular complications (SOC; frequency 50% SJS/TEN patients) when the patients are referred to them in the chronic stage after the acute stage has passed. Global data were collected using a Clinical Report Form, capturing pre-onset factors, as well as acute and chronic ocular findings. Key conclusions of this retrospective observational cohort study were as follows: (1) Ingestion of cold medications [acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs)] was significantly and positively correlated with trichiasis, symblepharon, and/or conjunctivalization of the cornea in the chronic stage; (2) common cold symptoms prior to onset of SJS/TEN were significantly and positively correlated with acute conjunctivitis and ocular surface erosions in the acute stage and with trichiasis and symblepharon and/or conjunctivalization of the cornea in the chronic stage; (3) patients with SJS/TEN who presented with SOC tended to be female; (4) patients less than 30 years of age are more likely to develop SOC in the acute and chronic stages of SJS/TEN; (5) patients with acute severe conjunctivitis with ocular surface erosion and pseudomembrane formation in the acute stage are more likely to develop ocular sequelae in the chronic stage; and (6) onychopathy in the acute stage was positively correlated with ocular sequelae in the chronic stage. Our findings show that the ingestion of cold medications, common cold symptoms prior to the onset of SJS/TEN, and a young age might strongly contribute to developing the SOC of SJS/TEN.

The impact of home electrocardiograph measurement rate on the detection of atrial fibrillation recurrence after ablation: A prospective multicenter observational study.

Background: This multicenter prospective observational study examined the impact of additionally using a home electrocardiograph (ECG) to detect atrial fibrillation (AF) recurrence after ablation. Methods: Between May 2019 and December 2020, 128 patients undergoing ablation were enrolled in the study. After performing ablation, they were instructed to measure their ECGs at home using Complete (ECG paired with a blood pressure monitor; Omron Healthcare, Japan) every day and to visit the hospital every 3 months until after 12 months for 24-hour Holter ECG and 12-lead ECG as usual care (UC). Results: After ablation, 94 patients were followed up, and AF recurrence at 12 months was detected more commonly in adjudicators-interpreted Complete (31 [33 %]) than in UC (18 [9 %]) (hazard ratio 1.95, 95 % confidence interval [95 %CI] 1.35-2.81, P < 0.001). In patients with recurrent AF found via both modalities (n = 16), the time to first AF detection by Complete was 40.9 ± 73.9 days faster than that in UC (P = 0.04). Notably, when the adherence to Complete measurement was divided by 80 %, the add-on effect of Complete on the detection of recurrent AF in UC indicated the hazard ratio (HR) of 1.71 (95 %CI 0.92-3.18, P = 0.09) for the low adherence (<80 %) group, but it was significant for the high adherence (≥80 %) group, with HR of 2.19 (95 %CI 1.43-3.36, P < 0.001). Conclusions: Despite a shorter measurement time, Complete detected recurrent AF more frequently and faster compared with UC after AF ablation. A significant adherence-dependent difference of Complete was found in detecting AF recurrence.

Effects of Longitudinal Changes in Lifestyle-Related Risk Factors on the Incidence of Major Adverse Cardiac and Cerebrovascular Disease in Young Adults.

Metabolic syndrome (MetS) is one focus of healthcare system reform in Japan. We examined the effects of changes in individual risk factors over time on the incidence of major adverse cardio-cerebrovascular events (MACCE) in adults under the age of 50 years. Study participants under the age of 50 with neither hypertension nor hyperglycemia at baseline were analyzed. We used a parametric proportional hazard model to determine the effect of changes in abdominal circumference, blood pressure, serum lipids, and blood glucose on the incidence of MACCE.A total of 6,125 women and 6,403 men were subject to the analyses. The incidence rate of MACCE per 1,000 person-years was 1.17 for women and 2.42 for men. In men under the age of 50, an increase in abdominal circumference was associated with an increase in MACCE incidence (hazard ratio per 1 cm increase: 1.10; 95% confidence interval [CI], 1.04-1.17), whereas no statistically significant association was observed in women. Compared with Visit 1, if the abdominal circumference increased by 4 cm at Visit 3, the hazard ratio for developing MACCE was approximately 1.5 (hazard ratio 1.48; 95% CI, 1.18-1.86). In men under the age of 50, increases in abdominal circumference and systolic blood pressure were associated with an increased risk of developing MACCE, regardless of the degree of obesity at baseline. Therefore, encouraging young adults to improve their health before developing MetS may reduce the risk of MACCE.

Screening for untreated atrial fibrillation in the elderly population: A community-based study.

BACKGROUND: Strokes are common in people with atrial fibrillation (AF), and can have devastating consequences, especially in the elderly and if AF is untreated. However, community-based studies on screening for untreated AF have not been conducted in Japan, and there has been no evaluation of the effectiveness of early screening for AF in the elderly (≥65 years). METHODS: The Kyoto Prefectural University of Medicine (KPUM) Education Initiative has conducted an AF awareness campaign consisted of screening tests using a blood pressure (BP) monitor with electrocardiogram (ECG) (the Complete, Omron Healthcare Co., Ltd., Kyoto, Japan) and educational lectures for the elderly (≥65 years) from 2019 to 2020. A modeled effectiveness analysis was performed comparing the life-years and QALYs (quality-adjusted life-years) between direct-acting oral anticoagulation (DOAC)-treated AF and untreated AF in a Japanese setting. The basic description of the Markov model was used for the analysis. RESULTS: A total of 1648 participants were screened, and after excluding those with missing information or data (n = 41), 1607 were finally enrolled. The mean (± standard deviation) age of participants was 72.4±5.8 years, 827 (51.5%) were female, 628 (39.1%) had hypertension, and 1368 (85.1%) had CHA2DS2-VASc score ≥2. After cardiologists' evaluation of all ECG recordings of the Complete, 15 (0.93%) AF were newly detected. For each AF treated with DOAC, 0.859 QALYs gained over the lifetime for 65 years-old men, and 0.856 QALYs for 65 years-old women compared to non-treatment. CONCLUSION: A moderate number of untreated AF were identified in the community-based study. Identification of an increased number of patients with AF, if properly treated with DOAC, ultimately leads to a reduction in the number of strokes occurred over subjects' lifetime.

Relationship Between Body Mass Index and Incidence of Atrial Fibrillation in Young Japanese Men　- The Nishimura Health Survey.

BACKGROUND: The associations between body mass index (BMI) and incidence of atrial fibrillation (AF) in young men are scarce, especially in Asian countries, given the differences in BMI between Asians and Western populations.Methods and Results:This study analyzed 17,865 middle-aged Japanese men without AF from a cohort of employees undergoing annual health examinations. AF incidence was evaluated during a follow-up period (median 4.0 years, interquartile range 2.0-7.1 years). Among young men aged 30-49 years, AF incidence was 0.64/1,000 person-years, whereas it was 2.54/1,000 and 7.60/1,000 person-years among men aged 50-59 and ≥60 years, respectively. Multivariable Cox regression analysis among young men revealed age (hazard ratio [HR] 3.28 by 10-years' increase, 95% confidence interval [CI] 1.72-6.25, P<0.001), BMI (BMI-quadratic, HR 1.01, 95% CI 1.00-1.01, P<0.001, BMI-linear, HR 0.95, 95% CI 0.86-1.05, P=0.33), and electrocardiogram (ECG) abnormalities, such as PQ prolongation, supraventricular beat, and p wave abnormality (HR 8.79, 95% CI 3.05-25.32, P<0.001), were significantly associated with AF incidence. There was a reverse J-shaped association between BMI and AF incidence in young men, whereby the presence of ECG abnormality inversely influenced the BMI-incident AF relationship. A linear association between BMI and AF incidence in men aged 50-59 and ≥60 years was present. CONCLUSIONS: AF incidence displays a reverse J-shaped relationship with BMI in young men, but a linear association in men aged ≥50 years. The paradoxical relationship seen in young men only may reflect atrial electrical or structural abnormalities.

Age-Specific Association Between Body Mass Index and the Incidence of Atrial Fibrillation in Japanese Men.

Background: Obesity is reportedly associated with the incidence of atrial fibrillation (AF), but the patterns of age-specific associations between body mass index (BMI) and the risk of AF are unknown. Methods and Results: We analyzed 10,921 Japanese men without AF from a cohort of employees undergoing annual health examinations. During a follow-up period of 5.0±3.8 years, the incidence of AF was 118 (2.18/1,000 person-years). Using a multivariable Cox regression analysis, high BMI was associated with a risk of AF (hazard ratio; 1.07 by 1 unit change of BMI, 95% confidence interval [CI] 1.00-1.13, P=0.05) overall, and the effect of BMI on AF incidence changed with age (P for interaction=0.08); with subjects aged <65 years with BMI <25 as the reference, HR 0.74 (95% CI 0.47-1.17) in subjects aged <65 years with BMI ≥25, HR 2.98 (95% CI 1.36-6.54) in subjects aged ≥65 years with BMI <25, and HR 6.50 (95% CI 2.58-16.38) in subjects aged ≥65 years with BMI ≥25. The 5-year probability of AF incidence in subjects aged <65 years was 0.87% with BMI <25 and 0.64% in those with BMI ≥25, and in subjects aged ≥65 years it was 2.58% with BMI <25 and 5.53% with BMI ≥25. Conclusions: Our results indicated that the effect of BMI on AF incidence changes with age among Japanese men. Both physicians and cardiologists need to integrate advice on lifestyle measures, particularly for elderly obese men, into their daily medical routine.

Estimating the extent of subclinical arteriosclerosis of persons with prediabetes and diabetes mellitus among Japanese urban workers and their families: a cross-sectional study.

BACKGROUND: Diabetes mellitus (hereafter called diabetes) is considered to accelerate arteriosclerosis leading to coronary heart disease and stroke. Thus, it is important to quantitatively estimate the extent of subclinical arteriosclerosis. A new method called cardio-ankle vascular index (CAVI) is developed to reflect arterial stiffness independently from blood pressure at the time of measurement. Then, we examined if CAVI scores could discriminate the extent of arteriosclerosis between persons with prediabetes (or borderline diabetes) and with diabetes among Japanese urban workers and their families. METHODS: Subjects were 9881 men and 12033 women of company employees and their families who participated in cardiovascular disease screening in Japan. Persons having diabetes and prediabetes were defined based on the criteria set by American Diabetes Association. CAVI scores were measured by VaSera VS-1000. We applied the established age-sex specific cutoff points of CAVI scores above which were determined to be abnormally high or advanced level of arteriosclerosis. To examine the association of prediabetes and diabetes with CAVI scores, CAVI scores of screening participants were converted to a binary variable: 1 for less than cutoff points and 2 for equal or greater than cutoff points or abnormally high CAVI scores. Logistic regression method was used to examine the association of prediabetes and diabetes with CAVI scores after adjusting for major cardiovascular disease (CVD) risk factors. RESULTS: Prevalence of abnormally high CAVI scores was significantly higher after 40 years of age among persons with diabetes than either among persons with prediabetes or among normal persons in both genders. Significantly elevated odds ratios (ORs) of abnormally high CAVI scores appeared among persons with prediabetes: 1.29 (95 % confidence interval (CI), 1.11-1.48) for men and 1.14 (CI, 1.01-1.28) for women, and among persons with diabetes: 2.41 (CI, 1.97-2.95) for men and 2.52 (CI, 1.94-3.28) for women. CONCLUSIONS: The extent of subclinical arteriosclerosis (including arterial stiffness and atherosclerosis) was moderately enhanced among persons with prediabetes and was further advanced among persons with diabetes. Thus, it is important to introduce earlier interventions for changing lifestyle and diet of persons with prediabetes in order to prevent them from developing diabetes and further advancing arteriosclerosis.