Maternal diabetes and risk of offspring congenital heart diseases: the Japan Environment and Children's Study.

BACKGROUND: Few prospective cohort studies have examined the association between maternal diabetes, including pre-pregnancy and gestational diabetes, and the risk of congenital heart disease (CHD) in Asian offspring. METHODS: We examined the association between maternal diabetes and offspring CHD among 97,094 mother-singleton infant pairs in the Japan Environment and Children's Study (JECS) between January 2011 and March 2014. Odds ratios (OR) and 95% confidence intervals (CI) of offspring CHD based on maternal diabetes (pre-pregnancy diabetes and gestational diabetes) were estimated using logistic regression after adjusting for maternal age at delivery, pre-pregnancy body mass index (BMI), maternal smoking habits, alcohol consumption, annual household income, and maternal education. The diagnosis of CHD in the offspring was ascertained from the transcript of medical records. RESULTS: The incidence of CHD in the offspring was 1,132. Maternal diabetes, including both pre-pregnancy diabetes and gestational diabetes, was associated with a higher risk of offspring CHD: multivariable OR (95%CI) = 1.81 (1.40-2.33) for maternal diabetes, 2.39 (1.05-5.42) for pre-pregnancy diabetes and 1.77 (1.36-2.30) for gestational diabetes. A higher risk of offspring CHD was observed in pre-pregnancy BMI ≥25.0 kg/m2 (OR = 2.55, 95% CI: 1.74-3.75) than in pre-pregnancy BMI <25.0 kg/m2 (OR = 1.49, 95% CI: 1.05-2.10, p for interaction = 0.04). CONCLUSIONS: Maternal diabetes, including both pre-pregnancy and gestational, was associated with an increased risk of CHD in offspring.

Real-world status of treatment for lymphoid neoplasms developed during the course of myeloproliferative neoplasms in Japan.

OBJECTIVES: Patients with myeloproliferative neoplasms (MPNs) are at higher risk of developing secondary malignancies. In this study, we focused on patients with MPNs that complicated lymphoid neoplasms. To analyze the real-world status of lymphoid neoplasm treatment in patients with pre-existing MPNs in Japan, we conducted a multicenter retrospective study. METHODS: Questionnaires were sent to collect the data on patients who were first diagnosed with either polycythemia vera, essential thrombocythemia or myelofibrosis and who later were complicated with lymphoid neoplasms defined as malignant lymphoma, multiple myeloma, or chronic lymphocytic leukemia/small cell lymphoma. RESULTS: Twenty-four patients with MPNs complicated by lymphoid neoplasms were enrolled (polycythemia vera, n = 8; essential thrombocythemia, n = 14; and primary myelofibrosis, n = 2). Among these, diffuse large B-cell lymphoma (DLBCL) was the most frequently observed (n = 13, 54.1%). Twelve (92.3%) of the patients with DLBCL received conventional chemotherapy. Among these 12 patients, regarding cytoreductive therapy for MPNs, 8 patients stopped treatment, one continued treatment, and two received a reduced dose. Consequently, most patients were able to receive conventional chemotherapy for DLBCL with a slightly higher dose of granulocyte colony-stimulating factor support than usual without worse outcomes. All 3 patients with multiple myeloma received a standard dose of chemotherapy. CONCLUSION: Our data indicate that if aggressive lymphoid neoplasms develop during the course of treatment in patients with MPNs, it is acceptable to prioritize chemotherapy for lymphoma.

Remarkable increase in the detection and molecular characterization of adenovirus F41 in children with acute gastroenteritis in Japan, 2017-2023.

Human adenovirus (HAdV) is one of the causative viruses of acute gastroenteritis (AGE) in children worldwide. Species F is known to be enteric adenovirus (genotypes 40 and 41) detected in stool samples. In Japan, we conducted an epidemiological study and molecular characterization of HAdV before and after the COVID-19 pandemic from 2017 to 2023. Among 821 patients, HAdV was detected in 118 AGE cases (14.4%). During a period of 6 years, the HAdV detection rates for each year were relatively low at 3.7% and 0%, in 2017-2018, and 2020-2021, respectively. However, the detection rate increased to remarkably high rates, ranging from 13.3% to 27.3% in the other 4-year periods. Of these HAdV-positive strains, 83.1% were F41 genotypes and 16.9% were other genotypes (A31, B3, C1, C2/C6, and C5). Phylogenetic analyses of the nucleotide and deduced amino acid sequences of the full-length hexon gene demonstrated that HAdV-F41 strains were comprised of three clades, and each clade was distributed across the study period from 2017 to 2023. Analysis of deduced amino acid sequences of the hexon gene of the representative HAdV-F41 strains from each clade revealed numerous amino acid substitutions across hypervariable regions (HVRs) from HVR-1 to HVR-7, two insertions in HVR-1 and HVR-7, and two deletions in HVR-1 and HVR-2 of the hexon gene compared to those of the prototype strain, particularly, those of clade 3 HAdV-F41 strains. The findings suggested that the HAdV-F41 of each clade was stable, conserved, and co-circulated for over two decades in Japan.

Epidemiology, aetiology and diagnosis of congenital hearing loss via hearing screening of 153 913 newborns.

BACKGROUND: Congenital hearing loss (HL), one of the most common paediatric chronic conditions, significantly affects speech and language development. Its early diagnosis and medical intervention can be achieved via newborn hearing screening. However, data on the prevalence and aetiology of congenital HL in infants who fail newborn hearing screening are limited. METHODS: The sample population included 153 913 infants who underwent newborn hearing screening, and the prevalence of congenital HL, defined as moderate to profound bilateral HL (BHL) or unilateral HL (UHL) (≥40 dB HL), in one prefecture of Japan was measured to minimize the loss-to-follow-up rate, a common factor affecting the screening procedure. Comprehensive aetiological investigation, including physiology, imaging, genetic tests, and congenital cytomegalovirus screening, was performed on children diagnosed with congenital HL. RESULTS: The calculated prevalence of congenital HL was 1.62 per 1000 newborns (bilateral, 0.84; unilateral, 0.77). More than half of the cases with congenital bilateral or severe to profound UHL showed genetic aetiology or cochlear nerve deficiency (CND), respectively. Approximately 4% and 6% of the cases of congenital BHL and UHL were associated with congenital cytomegalovirus infection and auditory neuropathy spectrum disorder, respectively. CONCLUSIONS: This is an epidemiological and comprehensive aetiological study of congenital HL, as determined via newborn hearing screening according to its severity and laterality, in a large-scale general population of a developed country. Our findings can serve as a reference for optimizing care and intervention options for children with HL and their families.

Incident allergic diseases in post-COVID-19 condition: multinational cohort studies from South Korea, Japan and the UK.

As mounting evidence suggests a higher incidence of adverse consequences, such as disruption of the immune system, among patients with a history of COVID-19, we aimed to investigate post-COVID-19 conditions on a comprehensive set of allergic diseases including asthma, allergic rhinitis, atopic dermatitis, and food allergy. We used nationwide claims-based cohorts in South Korea (K-CoV-N; n = 836,164; main cohort) and Japan (JMDC; n = 2,541,021; replication cohort A) and the UK Biobank cohort (UKB; n = 325,843; replication cohort B) after 1:5 propensity score matching. Among the 836,164 individuals in the main cohort (mean age, 50.25 years [SD, 13.86]; 372,914 [44.6%] women), 147,824 were infected with SARS-CoV-2 during the follow-up period (2020-2021). The risk of developing allergic diseases, beyond the first 30 days of diagnosis of COVID-19, significantly increased (HR, 1.20; 95% CI, 1.13-1.27), notably in asthma (HR, 2.25; 95% CI, 1.80-2.83) and allergic rhinitis (HR, 1.23; 95% CI, 1.15-1.32). This risk gradually decreased over time, but it persisted throughout the follow-up period (≥6 months). In addition, the risk increased with increasing severity of COVID-19. Notably, COVID-19 vaccination of at least two doses had a protective effect against subsequent allergic diseases (HR, 0.81; 95% CI, 0.68-0.96). Similar findings were reported in the replication cohorts A and B. Although the potential for misclassification of pre-existing allergic conditions as incident diseases remains a limitation, ethnic diversity for evidence of incident allergic diseases in post-COVID-19 condition has been validated by utilizing multinational and independent population-based cohorts.

Impact of drainage retinotomy on surgical outcomes of retinal detachment: insights from the Japan-Retinal Detachment Registry.

We investigated the impact of drainage retinotomy on the outcome of pars plana vitrectomy for repair of rhegmatogenous retinal detachment (RRD). This study was a retrospective observational multicenter study. All patients were registered with the Japan-Retinal Detachment Registry. We analyzed 1887 eyes with RRD that had undergone vitrectomy and were observed for 6 months between February 2016 and March 2017. We compared the baseline characteristics and postoperative outcomes between eyes with and without drainage retinectomy. We then performed propensity score matching using preoperative findings as covariates to adjust for relevant confounders. Of 3446 eyes, 1887 met the inclusion criteria. Among them, 559 eyes underwent vitrectomy with drainage retinotomy, and 1328 eyes underwent vitrectomy without drainage retinotomy. After propensity score matching, each group comprised 544 eyes. There was no significant difference between the two groups in BCVA at 6 months after vitrectomy (0.181 vs. 0.166, P = 0.23), the primary anatomical success rate (6.3% vs. 4.4%, P = 0.22), or the rate of secondary surgery for ERM within 6 months (1.5% vs. 1.3%, P = 1.0). Drainage retinectomy does not increase the risk of decreased postoperative BCVA, surgical failure, or secondary surgery for ERM within six months outcomes.

Low plasma 25-hydroxyvitamin D levels are not associated with a high risk of recurrent falls in community-dwelling Japanese adults: the Murakami cohort study.

Reports on the association between vitamin D levels and fall risk have been mixed, and long-term follow-up studies are lacking. This 5-year cohort study of 5,343 community-dwelling Japanese people aged 40-74 years found that low vitamin D levels are not associated with a high risk of recurrent falls. PURPOSE: Findings of cohort studies on the association between plasma 25-hydoxyvitamin D (25[OH]D) levels and fall risk have been mixed, and long-term follow-up studies are lacking. The present study investigated whether low plasma 25(OH)D levels are longitudinally associated with a high risk of recurrent falls in adults. METHODS: This 5-year cohort study included 5,343 community-dwelling Japanese people aged 40-74 years. Baseline blood collection and a questionnaire survey were conducted in 2011-2013. Plasma 25(OH)D levels were determined and divided into quintiles after stratification by season, sex, and age group. Information on recurrent falls occurring in the year before the survey 5 years later was obtained, and participants with two or more falls were considered to have experienced recurrent falls. Covariates were sex, age, marital status, education, occupation, BMI, total physical activity levels, calcium intake, vitamin K intake, smoking, drinking, and disease history. RESULTS: Mean age and 25(OH)D levels were 60.9 years and 50.9 nmol/L, respectively. In the follow-up survey, 209 recurrent falls were reported. Plasma 25(OH)D levels were not significantly associated with the occurrence of recurrent falls in men, women, or men/women-combined (adjusted P for trend = 0.1198, 0.8383, and 0.2355, respectively). In men and men/women-combined, adjusted ORs for recurrent falls in the lowest quintile were significantly lower (adjusted OR = 0.42 and 0.59, respectively) than the middle quintile (reference). CONCLUSION: Low plasma 25(OH)D levels are not associated with a high risk of recurrent falls in middle-aged and older people. Further longitudinal studies will be needed to confirm our findings in other populations.

Exploring the Impact of the COVID-19 Pandemic on Twitter in Japan: Qualitative Analysis of Disrupted Plans and Consequences.

BACKGROUND: Despite being a pandemic, the impact of the spread of COVID-19 extends beyond public health, influencing areas such as the economy, education, work style, and social relationships. Research studies that document public opinions and estimate the long-term potential impact after the pandemic can be of value to the field. OBJECTIVE: This study aims to uncover and track concerns in Japan throughout the COVID-19 pandemic by analyzing Japanese individuals' self-disclosure of disruptions to their life plans on social media. This approach offers alternative evidence for identifying concerns that may require further attention for individuals living in Japan. METHODS: We extracted 300,778 tweets using the query phrase Corona-no-sei ("due to COVID-19," "because of COVID-19," or "considering COVID-19"), enabling us to identify the activities and life plans disrupted by the pandemic. The correlation between the number of tweets and COVID-19 cases was analyzed, along with an examination of frequently co-occurring words. RESULTS: The top 20 nouns, verbs, and noun plus verb pairs co-occurring with Corona no-sei were extracted. The top 5 keywords were graduation ceremony, cancel, school, work, and event. The top 5 verbs were disappear, go, rest, can go, and end. Our findings indicate that education emerged as the top concern when the Japanese government announced the first state of emergency. We also observed a sudden surge in anxiety about material shortages such as toilet paper. As the pandemic persisted and more states of emergency were declared, we noticed a shift toward long-term concerns, including careers, social relationships, and education. CONCLUSIONS: Our study incorporated machine learning techniques for disease monitoring through the use of tweet data, allowing the identification of underlying concerns (eg, disrupted education and work conditions) throughout the 3 stages of Japanese government emergency announcements. The comparison with COVID-19 case numbers provides valuable insights into the short- and long-term societal impacts, emphasizing the importance of considering citizens' perspectives in policy-making and supporting those affected by the pandemic, particularly in the context of Japanese government decision-making.

Exercise effect on pain is associated with negative and positive affective components: A large-scale internet-based cross-sectional study in Japan.

Pain is a global health problem that leads to sedentary behavior and tends to cause negative emotion. In contrast, exercise is widely recommended for a health promotion, while pain often worsens with physical activity. Although exercise therapy is often prescribed to people with pain, the mechanisms of exercise effect on pain remains unclear. In this study, we tried to identify a universal association factor between regular exercise and pain intensity utilizing a cross-sectional web-based survey involving 52,353 adult participants from a large national study conducted in Japan. Using principal component analysis, we uncovered a mediation model of exercise effect on pain through psychological components. Analyses were performed in half of the population with pain (n = 20,330) and validated in the other half (n = 20,330), and showed that high-frequency exercise had a significant association with reduction in pain intensity. We also found Negative Affect and Vigor, two psychological components, are fully associating the exercise effect on pain (indirect effect = - 0.032, p < 0.001; association proportion = 0.99) with a dose-dependent response corresponding to the frequency of exercise. These findings were successfully validated (indirect effect of high-frequency exercise = - 0.028, p < 0.001; association proportion = 0.85). Moreover, these findings were also identified in subpopulation analyses of people with low back, neck, knee pain, and the tendency of the exercise effect on pain was increased with older people. In conclusion, the effect of exercise on pain is associated with psychological components and these association effects increased in parallel with the frequency of exercise habit regardless pain location.

Heterogeneity of the effect of the COVID-19 pandemic on the incidence of Metabolic Syndrome onset at a Japanese campus.

Background: The coronavirus disease 2019 (COVID-19) outbreak began in China in December 2019, with the World Health Organization declaring a state of emergency in January 2020. Worldwide implementation of lockdown measures to slow the spread of the virus led to reduced physical activity, disrupted eating habits, mental health issues, and sleep disturbances, which increased the risk of lifestyle-related diseases such as metabolic syndrome (MetS). During the COVID-19 pandemic, healthcare workers, especially intensive care workers, experienced longer working hours and burnout, which further increased the risk of lifestyle-related diseases. Accordingly, it is important to identify individuals at a risk of new-onset MetS during a pandemic, which could direct preventive interventions. This study aimed to assess the heterogeneous impact of the COVID-19 pandemic on the incidence of new-onset MetS based on the conditional average treatment effect (CATE) and to identify at-risk populations. Methods: This study analyzed health checkup data obtained from Okayama University Shikata Campus workers using paired baseline and follow-up years. Baseline data encompassed 2017 to 2019, with respective follow-up data from 2018 to 2020. Furthermore, as the COVID-19 pandemic in Japan began in January 2020, workers who underwent follow-up health checkups in 2018 to 2019 and 2020 were considered as "unexposed" and "exposed," respectively. As the Shikata campus has several departments, comparisons among departments were made. The primary outcome was new-onset MetS at follow-up. Predictor variables included baseline health checkup results, sex, age, and department (administrative, research, medical, or intensive care department). X-learner was used to calculate the CATE. Results: This study included 3,572 eligible individuals (unexposed, n = 2,181; exposed, n = 1,391). Among them, 1,544 (70.8%) and 866 (62.3%) participants in the unexposed and exposed groups, respectively, were females. The mean age (±standard deviation) of the unexposed and exposed groups was 48.2 ± 8.2 and 47.8 ± 8.3 years, respectively. The COVID-19 pandemic increased the average probability of new-onset MetS by 4.4% in the overall population. According to the department, the intensive care department showed the highest CATE, with a 15.4% increase. Moreover, there was large heterogeneity according to the department. The high-CATE group was characterized by older age, urinary protein, elevated liver enzymes, higher triglyceride levels, and a history of hyperlipidemia treatment. Conclusions: This study demonstrated that the COVID-19 pandemic increased the incidence of new-onset MetS, with this effect showing heterogeneity at a single Japanese campus. Regarding specific populations, workers in the intensive care department showed an increased risk of new-onset MetS. At-risk populations require specific preventive interventions in case the current COVID-19 pandemic persists or a new pandemic occurs.

Comparison of the efficacy of enfortumab vedotin between patients with metastatic urothelial carcinoma who were treated with avelumab or pembrolizumab: real-world data from a multi-institutional study in Japan.

OBJECTIVES: Enfortumab vedotin (EV) is a novel antibody-drug conjugate approved for metastatic urothelial carcinoma (UC) refractory to prior treatment with immune checkpoint inhibitors (ICIs). However, the difference in efficacy of EV after each ICIs and prognostic factors are not well known. We aimed to compare the efficacy of EV in patients with metastatic UC who were treated with avelumab or pembrolizumab and to identify the prognostic factors. METHODS: The records of 100 patients with advanced metastatic UC who received EV after the administration of either avelumab or pembrolizumab were retrospectively collected from five academic hospitals in Japan. RESULTS: The median follow-up period was 6.7 months. The median overall survival (OS) and progression-free survival (PFS) in the EV after avelumab/pembrolizumab group were not reached/14.7 months (p = 0.17) and 10.4/5.2 months (p = 0.039), respectively. The objective response rates (ORR) were 66.6% and 46.8% in EV after avelumab and EV after pembrolizumab groups, respectively (p = 0.14). Multivariate analysis identified histological variants, liver metastasis, low serum albumin levels, and high serum CRP level as significant poor prognostic factors. The median OS and PFS of cachexia patients with both low serum albumin levels and high serum CRP levels were 6.0 months and 0.93 months, respectively. CONCLUSION: PFS was superior in patients treated with EV after avelumab to EV after pembrolizumab. However, OS showed no significant difference between the two groups. Because the prognosis of patients with cachexia is extremely poor, the initiation of EV should be discussed in these patients.

Impact of Polypharmacy and Risk Factors for Exacerbation of Lower Urinary Tract Symptoms in Patients with Urological Conditions: A Retrospective Study in a Japanese Municipal Hospital.

Polypharmacy exacerbates lower urinary tract symptoms (LUTS). Japan exhibits a higher prevalence of concomitant medication use in drug therapy than other countries. Previous age- and sex-specific reports exist; however, none include patients of all ages. Therefore, this retrospective study determined the impact of polypharmacy and its associated risk factors on LUTS exacerbation in outpatients with urological conditions. We included patients receiving medication who visited the Department of Urology at the Gifu Municipal Hospital (Gifu, Japan) between January, 2018 and December, 2018. The association between LUTS and polypharmacy and the risk factors for LUTS exacerbation were investigated. Patients were categorized into two groups according to their polypharmacy status. We performed propensity score matching and compared the International Prostate Symptom Score (IPSS) between the groups using the unpaired t-test. Multiple logistic regression analysis was performed to examine the risk factors, including "polypharmacy" and "taking multiple anticholinergic medications" for LUTS exacerbation. When comparing the IPSS between the groups, the polypharmacy group was found to have significantly higher scores than the non-polypharmacy group in six items, including "total score" and "storage score." Multiple logistic regression analysis results showed high significance in three items, including "polypharmacy" (odds ratio (OR) = 1.67, 95% confidence interval (CI): 1.03-2.71) and "taking multiple anticholinergic medications" (OR = 8.68, 95% CI: 1.05-71.7). In conclusion, this study revealed that "polypharmacy" and "taking multiple anticholinergic medications" were risk factors for LUTS. Particularly, "polypharmacy" is associated with storage symptom exacerbation. Therefore, eliminating "polypharmacy" and "taking multiple anticholinergic medications" is expected to improve LUTS.

Impact of pandemic-related movement restriction on public access defibrillation in Japan: a retrospective cohort study.

OBJECTIVES: To analyse monthly changes in public access defibrillation (PAD) incidence and outcomes of out-of-hospital cardiac arrest (OHCA) during the 2020-2021 COVID-19 pandemic compared with those during the 2016-2019 prepandemic period with consideration of pandemic-related movement restriction. DESIGN: Retrospective cohort study. SETTING: An extended database was created by combining and reconciling the nationwide Utstein-style OHCA and the emergency medical service (EMS) transportation databases in Japan. PARTICIPANTS: We analysed 226 182 EMS-witnessed, non-newborn and out-of-home OHCA cases in Japan. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were the PAD incidence and neurologically favourable 1-month survival rate. The secondary outcomes were bystander cardiopulmonary resuscitation (CPR) provision and dispatcher-assisted CPR attempts. RESULTS: The proportion of out-of-home OHCA cases slightly decreased during the pandemic (from 33.7% to 31.9%). Although the pandemic was associated with a decreased PAD incidence, 2-year trend analyses by an interaction test showed that the PAD incidence was lower during the first nationwide declaration of a state of emergency (p<0.001) and in the pandemic's second year (p<0.01). Regardless of location, delays in basic life support (BLS) actions and EMS contact with patients were more common and the rate of PAD-induced return of spontaneous circulation was lower during the pandemic. PAD incidence reduction was significant only in locations with a recommendation of automated external defibrillator placement (p<0.001). In other locations, a pronounced delay in BLS was found during the pandemic. The neurologically favourable survival rate was reduced in parallel with the reduced PAD incidence during the pandemic (r=0.612, p=0.002). CONCLUSIONS: Prolonged and repeated movement restrictions during the COVID-19 pandemic worsened the OHCA outcomes concurrently with disturbed BLS actions, including the reduced PAD incidence in out-of-home settings. Maintaining BLS training, re-arranging automated external defibrillator placement and establishing a local alert system for recruiting well-trained citizens to the scene are essential.

Prevalence and perceptions of flavour capsule cigarettes among adults who smoke in Brazil, Japan, Republic of Korea, Malaysia and Mexico: findings from the ITC surveys.

INTRODUCTION: The global market of flavour capsule cigarettes (FCCs) has grown significantly over the past decade; however, prevalence data exist for only a few countries. This study examined prevalence and perceptions of FCCs among adults who smoke across five countries. METHODS: Cross-sectional data among adults who smoked cigarettes came from the International Tobacco Control Policy Evaluation Project Surveys-Brazil (2016/2017), Japan (2021), Republic of Korea (2021), Malaysia (2020) and Mexico (2021). FCCs use was measured based on reporting one's usual/current brand or favourite variety has flavour capsule(s). Perceptions of the harmfulness of one's usual brand versus other brands were compared between those who used capsules versus no capsules. Adjusted logistic regression models examined correlates of FCC use. RESULTS: There were substantial differences in the prevalence of FCC use among adults who smoke across the five countries: Mexico (50.3% in 2021), Republic of Korea (31.8% in 2021), Malaysia (26.5% in 2020), Japan (21.6% in 2021) and Brazil (6.7% in 2016/2017). Correlates of FCC use varied across countries. Capsule use was positively associated with being female in Japan and Mexico, younger age in Japan, Republic of Korea and Malaysia, high education in Brazil, Japan and Mexico, non-daily smoking in Republic of Korea, and having plans to quit in Japan and Republic of Korea. There was no consistent pattern of consumer perceptions of brand harmfulness. CONCLUSION: Our study documented the high prevalence of FCCs in some countries, pointing to the need to develop and implement regulatory strategies to control these attractive products.

Incidence and characteristics of aspiration pneumonia in the Nagasaki Prefecture from 2005 to 2019.

BACKGROUND: Aspiration pneumoniae remains a major health concern, particularly in the older population and has poor prognosis; however, the concept itself remains vague worldwide. This study aimed to determine the actual situation and characteristics of aspiration pneumonia from 2005 to 2019 in Nagasaki Prefecture, Japan. METHODS: Cases of aspiration pneumonia that occurred in the Nagasaki Prefecture between 2005 and 2019 were analyzed using emergency transportation records. The number of occurrences and incidence were analyzed according to age, sex, month, day of the week, and recognition time to clarify the actual situation of aspiration pneumonia. RESULTS: The total number of new aspiration pneumonia cases was 8,321, and the mean age of the patients was 83.0 years. Annual incidence per 100,000 population increased from 12.4 in 2005 to 65.1 in 2019, with the most prominent increase in the ≥ 80-year-old stratum. Males (55.1%) were more commonly affected than females (44.9%), and 82.2% of the cases involved patients aged ≥ 70 years. No significant correlations were observed between the incidence of aspiration pneumonia and season, month, or day of the week. Aspiration pneumonia occurred frequently in houses (39.8%) and facilities for elderly individuals (40.8%). At 7 days after admission, 80.9% of patients were still hospitalized and 6.5% had died. CONCLUSIONS: The incidence of aspiration pneumonia with risks of severity and mortality is increasing among elderly individuals. Valid preventive measures are urgently needed based on the findings that the disease occurs in both household and elderly care facility settings, regardless of the season.

Epidemiology of patients with lymphangioleiomyomatosis: A descriptive study using the national database of health insurance claims and specific health checkups of Japan.

BACKGROUND: Using patient registries or limited regional hospitalization data may result in underestimation of the incidence and prevalence of rare diseases. Therefore, we used the national administrative database to estimate the incidence and prevalence of lymphangioleiomyomatosis over six years (2014-2019) and describe changes in clinical practice and mortality. METHODS: We extracted data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between January 2013 and December 2020. This database covers ≥99% of the population. We used the diagnostic code for lymphangioleiomyomatosis to estimate the incidence and prevalence from 2014 to 2019. Additionally, we examined the demographic characteristics, treatments, comorbidities, and mortality of the patients. RESULTS: In women, the incidence and prevalence of lymphangioleiomyomatosis in 2019 were approximately 3 per 1,000,000 person-years and 28.7 per 1,000,000 persons, respectively. While, in men, the incidence and prevalence of lymphangioleiomyomatosis were <0.2 per 1,000,000 person-years and 0.8 per 1,000,000 persons, respectively. From 2014 to 2019, the proportion of prescriptions of sirolimus and everolimus increased, while the use of home oxygen therapy, chest drainage, comorbid pneumothorax, and bloody phlegm decreased. The mortality rate remained stable at approximately 1%. CONCLUSIONS: The incidence and prevalence of lymphangioleiomyomatosis were higher in women than those reported previously. Although the incidence did not change during the 6-year period, the prevalence gradually increased. Moreover, lymphangioleiomyomatosis was observed to be rare in men. The practice of treating patients with lymphangioleiomyomatosis changed across the six years while mortality remained low, at approximately 1%.

Interaction of left ventricular size with the outcome of cardiac resynchronization therapy in Japanese patients.

BACKGROUND: We analyzed the influence of the QRS duration (QRSd) to LV end-diastolic volume (LVEDV) ratio on cardiac resynchronization therapy (CRT) outcomes in heart failure patients classified as III/IV per the New York Heart Association (NYHA) and with small body size. HYPOTHESIS: We proposed the hypothesis that the QRSd/LV size ratio is a better index of the CRT substrate. METHODS: We enrolled 114 patients with advanced heart failure (NYHA class III/IV, and LV ejection fraction >35%) who received a CRT device, including those with left bundle branch block (LBBB) and QRSd ≥120 milliseconds (n = 60), non-LBBB and QRSd ≥150 milliseconds (n = 30) and non-LBBB and QRSd of 120-149 milliseconds (n = 24). RESULTS: Over a mean follow-up period of 65 ± 58 months, the incidence of the primary endpoint, a composite of all-cause death and hospitalization for heart failure, showed no significant intergroup difference (43.3% vs. 50.0% vs. 37.5%, respectively, p = .72). Similarly, among 104 patients with QRSd/LVEDV ≥ 0.67 (n = 54) and QRSd/LVEDV < 0.67 (n = 52), no significant differences were observed in the incidence of the primary endpoint (35.1% vs. 51.9%, p = .49). Nevertheless, patients with QRSd/LVEDV ≥ 0.67 showed better survival than those with QRSd/LVEDV < 0.67 (14.8% vs. 34.6%, p = .0024). CONCLUSION: Advanced HF patients with a higher QRSd/LVEDV ratio showed better survival in this small-body-size population. Thus, the risk is concentrated among those with a larger QRSd, and patients with a relatively smaller left ventricular size appeared to benefit from CRT.

Increased risk of hypocalcemia with decreased kidney function in patients prescribed bisphosphonates based on real-world data from the MID-NET® in Japan: a new-user cohort study.

BACKGROUND: In the post-marketing stage, cases of hypocalcemia associated with bisphosphonate preparations (BPs) have been reported in patients with decreased kidney function, despite warning against use of BPs in such patients in the package insert (PI) of Japan. The purpose of this study was to investigate the safety of BPs in patients with decreased kidney function. METHODS: The cohort study was conducted in patients with osteoporosis and newly prescribed bisphosphonate utilizing real-world data from MID-NET® in Japan. The adjusted hazard ratios (aHRs) for hypocalcemia (a corrected serum Ca level < 8.00 mg/dL) relative to the normal group were calculated in each decreased kidney function group (mild, moderate or severe group). RESULTS: A total of 14,551 patients were included in the analysis, comprising 2,601 (17.88%) with normal (eGFR ≥ 90 mL/min/1.73m2), 7,613 (52.32%) with mild (60 ≤ eGFR < 90 mL/min/1.73m2), 3,919 (26.93%) with moderate (30 ≤ eGFR < 60 mL/min/1.73m2), and 418 (2.87%) with severe kidney function (eGFR < 30 mL/min/1.73m2). The aHRs (95% confidence interval) for hypocalcemia were 1.85 (0.75-4.57), 2.30 (0.86-6.21), and 22.74 (8.37-61.78) in the mild, moderate, and severe groups, respectively. The increased risk of hypocalcemia depending on kidney function was also observed even when calculating the aHR for each specific BP such as alendronate sodium hydrate, minodronic acid hydrate, and sodium risedronate hydrate. Furthermore, similar results were obtained in the sensitivity analysis by altering the outcome definition to a 20% or more reduction in corrected serum Ca level from the baseline, as well as when focusing on patients with more than one laboratory test result per 30 days during the follow-up period. CONCLUSIONS: These findings suggest that the risk of hypocalcemia during BP prescription is higher in patients with decreased kidney function, particularly those with severely decreased kidney function. The quantitative real-world evidence on the safety risk of BPs obtained in this study has led to the PI revision describing a relationship between hypocalcemia risk and decreased kidney function as a regulatory action in Japan and will contribute to promoting the proper use of BPs with appropriate risk management in clinical practice.

Review on epidemiology, disease burden, and treatment patterns of IgA nephropathy in select APAC countries.

BACKGROUND: Immunoglobulin type A (IgA) nephropathy is the most common primary glomerulonephritis (GN) worldwide with higher rates in East and Pacific Asia compared to North America and Europe. Despite high reported prevalence of IgAN in these countries, the overall disease prevalence across Asia is not available. Treatment patterns of IgAN patients across Asian countries have also not been summarized. The aim of this study was to review and summarize evidence on IgA nephropathy prevalence, treatment patterns, and humanistic and economic burden in mainland China, Taiwan, South Korea, Japan, and Australia. METHODS: A targeted literature review was conducted in PubMed and local databases in China (including Taiwan), South Korea, Japan, and Australia between January 2010-December 2021. Website literature searches were conducted using Google Scholar and Baidu. RESULTS: Sixty-nine publications and 3 clinical guidelines were included. Incidence ranged from 0 to 10.7 per 100 000 people per year in Australia, Japan, and Taiwan, and ranged from 6.3 to 24.70% among patients who underwent renal biopsy in mainland China. Prevalence and diagnosis rates ranged from 0 to 72.1% in mainland China, South Korea, Taiwan, Japan, and Australia. Mortality rates in mainland China, South Korea, and Japan varied widely. The top 3 commonly used therapies were angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (0.9-99.6%), corticosteroids (3.5-100%), and immunosuppressants (1.6-85.5%) in Japan, mainland China, and South Korea. Patient quality of life was measured by different tools, and annual hospitalization costs ranged from $1 284.73 to $2 252.12 (2015-2018) in China. CONCLUSIONS: The prevalence of IgA nephropathy among the general population in select countries/regions is not commonly available, despite evidence from studies and clinical guidelines. In addition, it is observed across geographic regions that heterogeneity exists in prevalence rates, and large variations exist in treatment patterns. There is need to fill in these gaps to understand the contributing factors behind the differences through population-based, multi-center, and real-world studies.