Mortality in childhood-onset type 1 diabetes mellitus with onset between 1959 and 1996: A population-based study in Hokkaido, Japan.

Aim: To examine the mortality rate and causes of death in childhood-onset type 1 diabetes in Japan. Methods: For a median 36.7 years, we followed 391 patients under the age of 15 years who developed type 1 diabetes between 1959 and 1996. We calculated the mortality rate per 100,000 person-years and the standardised mortality ratio (SMR) according to risk factors. Results: The mortality rates and SMRs were 823 and 8.8 with onset during 1959-1979, 370 and 5.9 with onset during 1980-1989, and 133 and 3.2 with onset during 1990-1996, respectively. The mortality rates and SMRs were 359 and 8.4 in men, and 235 and 6.0 in women. Mortality rates and SMRs were 452 and 7.3 in patients with diabetes onset before puberty and 514 and 6.3 in patients with onset after puberty. The main causes of death with shorter disease duration were sudden death, accident/suicide, and acute diabetic complications. With a more than 30-year disease duration, the main causes of death were end-stage renal disease and cardiovascular disease. Conclusions: This cohort study revealed a decrease in the mortality rate between 1959-1979 and 1990-1996 in patients with childhood-onset type 1 diabetes in Japan. Patients with onset after puberty had a higher mortality rate than those with onset before puberty.

Antibiotic prescription for outpatients with influenza and subsequent hospitalisation: A cohort study using insurance data.

Background: Whether prophylactic administration of antibiotics to patients with influenza reduces the hospitalisation risk is unknown. We aimed to examine the association between antibiotic prescription in outpatients with influenza infection and subsequent hospitalisation. Methods: We conducted a cohort study using health insurance records of Japanese clinic and hospital visits between 2012 and 2016. Participants were outpatients (age, 0-74 years) with confirmed influenza infection who were prescribed anti-influenza medicine. The primary outcomes were the hospitalisation risk from all causes and pneumonia and the duration of hospitalisation due to pneumonia. Results: We analysed 903,104 outpatient records with 2469 hospitalisations. The risk of hospitalisation was greater in outpatients prescribed anti-influenza medicine plus antibiotics (0.31% for all causes and 0.18% for pneumonia) than in those prescribed anti-influenza medicine only (0.27% and 0.17%, respectively). However, the risk of hospitalisation was significantly lower in patients prescribed peramivir and antibiotics than in those prescribed peramivir only. Patients who received add-on antibiotics had a significantly longer hospital stay (4.12 days) than those who received anti-influenza medicine only (3.77 days). In all age groups, the hospitalisation risk from pneumonia tended to be greater in those who received antibiotics than in those prescribed anti-influenza medicine only. However, among older patients (65-74 years), those provided add-on antibiotics had an average 5.24-day shorter hospitalisation due to pneumonia than those provided anti-influenza medicine only (not significant). Conclusions: In outpatient cases of influenza, patients who are prescribed antibiotics added to antiviral medicines have a higher risk of hospitalisation and longer duration of hospitalisation due to pneumonia.

Association of influenza vaccination or influenza virus infection history with subsequent infection risk among children: The Japan Environment and Children's Study (JECS).

We measured the association between history of influenza vaccination by age 2 years and influenza virus (IFV) infection at ages 3 and 4 years by relative risk reduction. We also examined the association between history of IFV infection by age 2 years and recurrent IFV infection at age 3 years. This study included 73,666 children from a large Japanese birth cohort. Among children vaccinated never, once or twice when aged under 2 years, 16.0%, 10.8% and 11.3%, respectively, had been infected with IFV by age 3 years, and 19.2%, 14.5% and 16.0%, respectively, by age 4 years. Compared with no history of influenza vaccination, vaccination at ages 1 and/or 2 years reduced the risk of IFV infection at age 3 by 30%-32% and at age 4 by 17%-24%. The relative risk of recurrent IFV infection at ages 3 and 4 years increased in proportion to the number of prior infections by age 2. One-season-prior influenza vaccination history reduced the IFV infection risk at age 3 years by 25%-42%. Influenza vaccination most effectively protected children at age 3 who lacked older sibling(s) and did not attend nursery school. One-season-prior IFV infection increased the relative risk of recurrent infection at age 3 years (1.72-3.33). In conclusion, influenza vaccination-induced protection may partly extend to the next season. Owing to the relative risk reduction by influenza vaccination and the increased relative risk of IFV infection from prior-season infection, annual influenza vaccination is recommended.

Gestational age, birth weight, and perinatal complications in mothers with diabetes and impaired glucose tolerance: Japan Environment and Children's Study cohort.

We aimed to determine the risk of perinatal complications during delivery in mothers with non-normal glucose tolerance in a large Japanese birth cohort. We analysed data of 24,295 neonate-mother pairs in the Japan Environment and Children's Study cohort between 2011 and 2014. We included 67 mothers with type 1 diabetes, 102 with type 2 diabetes (determined by questionnaire), 2,045 with gestational diabetes (determined by diagnosis), and 2,949 with plasma glucose levels ≥140 mg/dL (shown by a screening test for gestational diabetes). Gestational age, birth weight, placental weight, and proportions of preterm birth, and labour and neonatal complications at delivery in mothers with diabetes were compared with those in mothers with normal glucose tolerance. Mean gestational age was shorter in mothers with any type of diabetes than in mothers without diabetes. Birth weight tended to be heavier in mothers with type 1 diabetes, and placental weight was significantly heavier in mothers with type 1 and gestational diabetes and elevated plasma glucose levels (all p<0.05). The relative risks of any labour complication and any neonatal complication were 1.49 and 2.28 in type 2 diabetes, 1.59 and 1.95 in gestational diabetes, and 1.22 and 1.30 in a positive screening test result (all p<0.05). The relative risks of preterm birth, gestational hypertension, and neonatal jaundice were significantly higher in mothers with types 1 (2.77; 4.07; 2.04) and 2 diabetes (2.65; 5.84; 1.99) and a positive screening test result (1.29; 1.63; 1.12) than in those without diabetes (all p<0.05). In conclusion, placental weight is heavier in mothers with non-normal glucose tolerance. Preterm birth, gestational hypertension, and jaundice are more frequent in mothers with types 1 and 2 diabetes. A positive result in a screening test for gestational diabetes suggests not only a non-normal glucose tolerance, but also a medium (middle-level) risk of perinatal complications.

Association of the incidence of atopic dermatitis until 3 years old with climate conditions in the first 6 months of life: Japan Environment and Children's Study (JECS).

OBJECTIVE: To determine the climate conditions that affect the incidence of atopic dermatitis from infancy to 3 years old. STUDY DESIGN: We analyzed 100,303 children born from 2011 to 2014 for follow-up until 3 years old using cohort data from the Japan Environment and Children's Study. The study included 15 Regional Centers, including 19 prefectures across Japan. We used meteorological data of the Japan Meteorological Agency. We calculated the hazard ratio (HR) of the standard deviation and low vs. high mean values of several climate conditions in children in their first 6 months of life to determine the incidence of atopic dermatitis. RESULTS: The Kaplan-Meier curve showed that children born in the months of October to December had the highest incidence of atopic dermatitis. Among climate conditions, a one standard deviation increase in the temperature (HR = 0.87), minimum temperature (HR = 0.87), and vapor pressure (HR = 0.87) showed the lowest HRs for the incidence of atopic dermatitis. These results were confirmed by an analysis by strata of the birth season. A low vapor pressure (HR = 1.26, p<0.0001) and the combination of a low mean temperature or low mean minimum temperature and low vapor pressure (HR = 1.26, p<0.0001) were associated with the highest incidence of atopic dermatitis. These results were consistent when they were adjusted for a maternal and paternal history of allergy and the prefecture of birth. CONCLUSION: Among climate conditions, a low vapor pressure is the most strongly associated with a high incidence of atopic dermatitis. Measuring vapor pressure may be useful for preventing atopic dermatitis.

High Incidence of Atopic Dermatitis among Children Whose Fathers Work in Primary Industry: The Japan Environment and Children's Study (JECS).

The hygiene hypothesis assumes a low incidence of allergic diseases in families engaging in farming work. However, a few studies have indicated rural life as a potential risk factor for atopic dermatitis (AD). Using a large Japanese birth cohort dataset, we calculated the accumulated incidence of AD in children aged 6 months and 1, 2, and 3 years by family business and the hazard ratio. We adjusted for confounding factors. The father's job was considered the family business. We analysed data on 41,469 father-child pairs at 6 months of age, 40,067 pairs at 1 year, 38,286 pairs at 2 years, and 36,570 pairs at 3 years. We found the highest accumulated incidence of AD among children with fathers engaged in primary industry, with 2.5% at the age of 6 months, 6.6% at 1 year, 12.0% at 2 years, and 15.4% at 3 years. Among primary industry occupations, forestry was associated with the highest incidence of AD across these ages. The hazard ratio of AD was also highest for children whose family business was primary industry. In conclusion, the highest incidence and hazard ratio of AD were observed among children whose fathers worked in primary industry.

Mother's iodine exposure and infants' hypothyroidism: the Japan Environment and Children's Study (JECS).

In this study, we aimed to determine the association of neonatal/post-neonatal hypothyroidism with mother's iodine exposure, especially povidone iodine disinfection, and hysterosalpingography. Participants were mother-child pairs in a Japanese birth cohort (n = 100,286). Risk factors of hypothyroidism were supplement intake, seaweed intake, other daily iodine intake, povidone iodine disinfection at delivery, and maternal history of hysterosalpingography, thyroid disease (Graves' disease and Hashimoto's thyroiditis), and medication (thiamazole and levothyroxine). Congenital hypothyroidism (CH) at age 1 year was assessed using a questionnaire. Transient hypothyroidism was defined as elevated thyroid stimulating hormone level at birth and absence of CH at age 1 year. The incidence of CH at age 1 year per 100 children was 1.1 for those born at 22-30 weeks' gestation, 0.17 following povidone iodine disinfection, and 0.07, 0.95, 0.81, 1.17, and 1.15 with a maternal history of hysterosalpingography, Graves' disease, Hashimoto's thyroiditis, thiamazole use, and levothyroxine use, respectively. Odds ratios (95% confidence intervals) of CH at age 1 year for povidone iodine disinfection, hysterosalpingography history, maternal Graves' disease, and maternal Hashimoto's thyroiditis were 1.13 (0.71-1.79), 0.47 (0.07-3.36), 7.06 (3.70-13.5), and 5.93 (2.90-12.1), respectively. For transient hypothyroidism for povidone iodine disinfection and hysterosalpingography history, these values were 1.99 (1.51-2.62) and 0.63 (0.20-1.96), respectively. Maternal thyroid disease greatly increased neonatal/post-neonatal hypothyroidism risk. Povidone iodine disinfection may increase transient hypothyroidism risk but not the risk at 1 year of age. Hysterosalpingography does not increase hypothyroidism risk from birth to age 1 year.

Prevention Measures for COVID-19 and Changes in Kawasaki Disease Incidence.

BACKGROUND: Kawasaki disease is suspected to be triggered by previous infection. The prevention measures for coronavirus disease 2019 (COVID-19) have reportedly reduced transmission of certain infectious diseases. Under these circumstances, the prevention measures for COVID-19 may reduce the incidence of Kawasaki disease. METHODS: We conducted a retrospective study using registration datasets of patients with Kawasaki disease who were diagnosed in all 11 inpatient pediatric facilities in Yamanashi Prefecture. The eligible cases were 595 cases that were diagnosed before the COVID-19 pandemic (from January 2015 through February 2020) and 38 cases that were diagnosed during the COVID-19 pandemic (from March through November 2020). Incidence of several infectious disease were evaluated using data from the Infectious Disease Weekly Report conducted by the National Institute of Infectious Diseases. RESULTS: Epidemics of various infectious diseases generally remained at low levels during the first 9 months (March through November 2020) of the COVID-19 pandemic. Moreover, the incidence of COVID-19 was 50-80 times lower than the incidence in European countries and the United States. The total number of 38 cases with Kawasaki disease for the 9 months during the COVID-19 pandemic was 46.3% (-3.5 standard deviations [SDs] of the average [82.0; SD, 12.7 cases] for the corresponding 9 months of the previous 5 years. None of the 38 cases was determined to be triggered by COVID-19 based on their medical histories and negative results of severe acute respiratory syndrome coronavirus 2 testing at admission. CONCLUSION: These observations provide a new epidemiological evidence for the notion that Kawasaki disease is triggered by major infectious diseases in children.

Association of the incidence of atopic dermatitis until 3 years old with birth month and with sunshine duration and humidity in the first 6 months of life: Japan Environment and Children's Study.

OBJECTIVE: To compare the incidence of atopic dermatitis in children aged from 6 months to 3 years across birth seasons and climate conditions. DESIGN: Cohort study. SETTING: Fifteen regional centres across Japan. PARTICIPANTS: A total of 100 304 children born from 2011 to 2014. EXPOSURE: Birth month, and mean sunshine duration (short/long) and humidity (high/low) in the first 6 months of life. PRIMARY OUTCOME MEASURE: Incidence of atopic dermatitis. RESULTS: The highest incidence of atopic dermatitis was in children born in the months of October to December. The lowest incidence of atopic dermatitis was in the months of April to June and in periods with a long duration of sunshine and high humidity. Low humidity was significantly associated with a higher incidence of atopic dermatitis. However, this significant difference disappeared when the birth season and parental history of allergic disease were considered in multivariate analysis. CONCLUSIONS: In Japan, being born in the late autumn to early winter months is associated with a risk of developing atopic dermatitis until the age of 3 years. Sunshine duration and humidity from birth to 6 months of age are not associated with the incidence of atopic dermatitis.

Incidence of childhood type 1 diabetes mellitus in Yamanashi Prefecture, Japan, 1986-2018.

Introduction: Several studies have examined the incidence of childhood T1DM in Japan from the 1970s onwards, but none have been long-term studies using registration data. We estimate the incidence of childhood type 1 diabetes mellitus (T1DM) from 1986 to 2018 in Yamanashi Prefecture, Japan. Methods: We began a population-based, long-term study of childhood T1DM in 1986 involving every hospital paediatrics department in Yamanashi Prefecture. In the Prefecture, every child newly diagnosed with T1DM is referred to a hospital, and therefore, almost 100% of new patients aged <15 years are registered. We calculated the incidence of T1DM among children aged <15 years from 1986 to 2018. All cases met the Japan Diabetes Society diagnostic criteria and were tested for T1DM-related autoantibodies whenever possible. Results: Ninety-nine patients (44 boys and 55 girls) were newly diagnosed with T1DM. The annual incidence among 5- to 9-year-olds increased by 5.35% over the study period (95% confidence interval 2.34%-8.35%, p = .0005), and there was a trend towards increasing 3-year incidence (15.52% increase, p = .0516). There were also trends towards increasing annual and 3-year incidence among 0- to 14-year-olds. However, there were no changes over time in annual or 3-year incidence in the 0-4 year or 10-14 year age groups. Conclusions: The incidence of T1DM in Yamanashi Prefecture increased among children aged 0-14 years over the study period, with the most significant increase occurring among 5- to 9-year-olds. These data suggest that the number of children aged <15 years with T1DM is gradually increasing in one of the local prefectures in Japan, Yamanashi Prefecture and that the age of onset is decreasing.

Encouraging Cross-Disciplinary Collaboration and Innovation in Epidemiology in Japan.

Background: Scientific innovation is often achieved through the intersection of ideas from different fields. However, barriers prevent non-epidemiologists from cultivating interests in epidemiology or undertaking epidemiologic work. In this study, we evaluated changes in the diversity of research topics in an epidemiologic journal over time. We aimed to understand how epidemiologists and non-epidemiologists communicate about epidemiologic data and how this impacts innovation in the field. Methods: We categorized the topics of articles published in the Journal of Epidemiology during the early and late 2010s based on their titles. We calculated the Shannon-Weaver diversity index (H') to measure changes in the diversity of topics addressed by published articles. Results: Comparing 2011-2013 with 2017-2019, there was no significant change in the diversity of article topics (H' = 4.25 and 4.21, respectively) published in the Journal of Epidemiology. Conclusion: To encourage healthcare providers and public administrators to conduct or comment on epidemiologic studies, epidemiologists should present their findings in easily understood language with appropriate and relevant statistical indicators and useful illustrations. Bringing experience from other specialties into epidemiology may yield new findings from epidemiologic data because of the exposure of non-epidemiologists to different values, workplaces, and occupations. Collaboration among professionals from varied backgrounds and with varied occupational experiences may help to promote scientific innovation by broadening perspectives. In addition, a range of professional experiences may enable individuals to solve difficult research questions more easily by themselves.

Effectiveness of influenza vaccination in infants and toddlers with and without prior infection history: The Japan Environment and Children's Study.

We calculated the Poisson-regression-adjusted relative risk (RR) of new influenza infection by vaccination, prior infection, and vaccination after prior infection in a large Japanese birth cohort, using data from ≤89,253 children aged 6 months to 3 years. The effectiveness of risk reduction (1 - RR) by vaccination at ages 1.5-3 years was 21%-31%. The RR of new infection after prior infection vs. no prior infection was 2.58-19.3 at age 1-3 years. An analysis of the 1 - RR data stratified by having at least one senior sibling and/or attending nursery school revealed that vaccination reduced the RR by 22%-40%. The 1 - RR of new infection was 21% in 3-year-old children who were vaccinated after prior infection. All these findings are statistically significant. The results consistently indicate that, regardless of having at least one senior sibling, attending nursery school, and/or being previously infected with influenza, infants and toddlers will benefit from influenza vaccination.

Cause-specific mortality rates in patients with diabetes according to comorbid macro- and microvascular complications: BioBank Japan Cohort.

Objective: This study aimed to compare cause-specific mortality rates in patients with type 2 diabetes with and without various vascular complications. Methods: In Japanese hospitals, we followed up 30 834 patients with a mean age of 64.4 (standard deviation [SD]: 11.1) years. Patients were followed up from 2003 to 2007 for a median of 7.5 (interquartile range: 6.1-9.7) years. We calculated cause-specific mortality rates (number of deaths/1000 person-years) and confounder-adjusted hazard ratios in patients with macrovascular disease and in those with diabetic nephropathy, neuropathy and retinopathy, allowing for overlap of complications. Results: All-cause mortality rate was highest (51.4) in the nephropathy group, followed by the macrovascular disease group (45.2), the neuropathy group (39.5), the retinopathy group (38.7) and the nonvascular complication group (18.1). In the nephropathy group, morality rates of ischaemic heart, cerebrovascular, and infectious diseases and cancer were also highest among the groups. However, the cancer mortality rate was similar among the vascular complication groups. Relative to the nonvascular complication group, covariate-adjusted hazard ratios for ischaemic heart and cerebrovascular disease mortality were triple to quadruple in the macro- and microvascular complication groups. All-cause mortality rates rose exponentially according to age. Conclusion: Highest risks of all-cause, cancer, and ischaemic heart, infectious, and cerebrovascular disease mortality were determined in Japanese patients with diabetic nephropathy. Although cancer is the primary cause of death in Japanese patients with diabetes, cancer mortality rates are similar among those with and without vascular complications.

Primary ovarian insufficiency in a female with phosphomannomutase-2 gene (PMM2) mutations for congenital disorder of glycosylation.

Primary ovarian insufficiency (POI) is a highly heterogeneous condition, and its underlying causes remain to be clarified in a large fraction of patients. Congenital disorders of glycosylation (CDG) are multisystem diseases caused by mutations of a number of genes involved in N-glycosylation or O-glycosylation, and the most frequent form is PMM2-CDG (alias, CDG-Ia) resulting from biallelic mutations in PMM2 encoding phosphomannomutase-2 involved in N-glycosylation. Here, we examined a 46,XX Japanese female with syndromic POI accompanied by an undetectable level of serum anti-Müllerian hormone (AMH). Whole exome sequencing identified biallelic pathogenic mutations of PMM2 (a novel c.34G>C:p.(Asp12His) of maternal origin and a recurrent c.310C>G:p.(Leu104Val) of paternal origin) (NM_000303.3), and N-glycosylation studies detected asialotransferrin and disialotransferrin characteristic of PMM2-CDG, in addition to normally glycosylated tetrasialotransferrin. Clinical assessment showed cerebellar hypotrophy, which is a fairly characteristic and highly prevalent feature in PMM2-CDG, together with multiple non-specific features reported in PMM2-CDG such as characteristic face, intellectual disability, skeletal abnormalities, and low blood antithrombin III value. These results including the undetectable level of serum AMH, in conjunction with previously reported findings suggestive of the critical role of glycosylation in oocyte development and function, imply that PMM2-CDG almost invariably leads to POI primarily because of the defective oogenesis and/or oocyte-dependent early folliculogenesis rather than the compromised bioactivity of FSH/LH with defective glycosylation. Thus, it is recommended to examine PMM2 in patients with syndromic POI, especially in those with cerebellar ataxia/hypotrophy.

All-cause and cardiovascular disease mortality in underweight patients with diabetic nephropathy: BioBank Japan cohort.

We aimed to determine mortality risk in underweight patients with diabetic nephropathy for microalbuminuria or macroalbuminuria. We analyzed mortality and death-cause data from BioBank Japan, with baseline years 2003-2007. We analyzed mortality rates from all causes and ischemic heart disease, according to body mass index (<18.5, 18.5-21.9, 22-24.9 and ≥25 kg/m2 ). The mean (standard deviation) of patient age, body mass index, and glycated hemoglobin at enrollment was 61.6 years (11.7 years), 25.0 kg/m2 (4.4 kg/m2 ) and 7.7% (1.5%), respectively. Hazard ratios of all-cause and ischemic heart disease mortality were highest (1.79 [P = 0.0001] and 2.95 [P = 0.027], respectively) in patients with body mass index <18.5 kg/m2 , as compared with body mass index 22-24.9 kg/m2 . All-cause mortality risk for body mass index <18.5 kg/m2 was similar to that for current smokers (hazard ratio 1.70, P < 0.0001). Underweight could be a predictor of mortality risk in patients with diabetic nephropathy for microalbuminuria or macroalbuminuria.

Increasing secular trends in height and obesity in children with type 1 diabetes: JSGIT cohort.

BACKGROUND: Recently, anthropometric indices in children with type 1 diabetes mellitus (T1DM) have begun to change. OBJECTIVE: To examine secular trends in patients' anthropometric indices. SUBJECTS: Japanese children with T1DM from the 1995, 2000, 2008 and 2013 cohorts of The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes. METHODS: We analysed serum haemoglobin A1c (HbA1c) levels, the incidence of severe hypoglycaemic events, the types and doses of insulin, height standard deviation scores (SDS), body mass index (BMI) percentiles compared with healthy Japanese children and obesity prevalence over time. We also stratified the patients according to glycaemic control levels of <58 mmol/mol (optimal), 58-75 mmol/mol (suboptimal) and ≥75 mmol/mol (high-risk). RESULTS: Data for 513-978 patients from each of the cohorts were analysed. The incidence of severe hypoglycaemic events decreased over time (from 21 to 4.8/100 patient-years), while the proportion of insulin analogue doses increased (14.6% to 98.6%). In addition, patient height SDS (-0.22 to +0.17), BMI percentile (52.1 to 58.7) and obesity prevalence (2.1% to 5.1%) increased. Height SDS increased in all of the glycaemic control subgroups, while BMI percentile and obesity prevalence increased in the suboptimal and high-risk groups. CONCLUSIONS: Since 1995, the average height of children with T1DM has increased in parallel with increasing insulin doses. Clinicians should be aware of increased BMI in these patients and the associated risk of developing cardiovascular disease in the future.

Immune thrombocytopenic purpura risk by live, inactivated and simultaneous vaccinations among Japanese adults, children and infants: a matched case-control study.

This case-control study investigated immune thrombocytopenic purpura (ITP) risk following live, inactivated, and simultaneous vaccination, with a focus on infants aged < 2 years. We matched case patients with ITP to one or two control patients with other diseases by institution, hospital visit timing, sex, and age. We calculated McNemar's pairwise odds ratios (ORs [95% confidence interval]) with 114 case-control pairs. The case group had 27 (44%) males and 22 (35%) infants, and the control group included 49 (43%) males and 42 (37%) infants. For all age groups, the McNemar's OR for ITP occurrence was 1.80 (0.54-6.84, p = 0.64) for all vaccines. Among infants, these were 1.50 (0.17-18.0, p = 0.50) for all vaccines, 2.00 (0.29-22.1, p = 0.67) for live vaccines, and 1.00 (0.01-78.5, p = 0.50) for inactivated vaccines. Sex-adjusted common ORs for simultaneous vaccination were 1.52 (0.45-5.21, p = 0.71) for all vaccines, 1.83 (0.44-7.59, p = 0.40) for inactivated vaccines only, and 1.36 (0.29-6.30, p = 0.69) for mixed live and inactivated vaccines. In infants, these were 1.95 (0.44-8.72, p = 0.38), 1.41 (0.29-6.94, p = 0.67) and 2.85 (0.43-18.9, p = 0.28), respectively. These limited data suggest no significant ITP risk following vaccinations or simultaneous vaccination in any age group, including infants.

Incidence of hospitalisation for severe complications of influenza virus infection in Japanese patients between 2012 and 2016: a cross-sectional study using routinely collected administrative data.

OBJECTIVE: To calculate the incidence of hospitalisation due to acute respiratory failure, pneumonia, acute respiratory distress syndrome (ARDS), febrile seizures and encephalitis/encephalopathy among influenza-positive patients in Japan, where point-of-care tests are routinely used to diagnose influenza. DESIGN: A cross-sectional study using routinely collected data. SETTING: Japanese clinics and hospitals between 2012 and 2016. PARTICIPANTS: Japanese patients aged 0-74 years diagnosed with influenza by a rapid test in employment-related health insurance records. PRIMARY OUTCOME MEASURES: Incidence of hospitalisation per 100 000 influenza-positive episodes. RESULTS: We included over 16 million influenza-positive episodes, 1.0% of whom were hospitalised. Of these, 3361 were acute respiratory failure, 27 253 pneumonia, 18 ARDS, 2603 febrile seizure and 159 encephalitis/encephalopathy. The percentage of hospitalisations by age was 2.96% of patients aged 0-1 years, 0.77% aged 2-5, 0.51% aged 6-12, 0.78% aged 13-18, 1.36% aged 19-44, 1.19% aged 45-64, and 2.21% aged 65-74. The incidence of hospitalisations from these five complications combined was highest in influenza-positive patients aged 0-1 years (943 per 100 000) compared with 307 in those aged 2-5 years and 271 in those aged 65-74 years. For pneumonia, the incidence was highest for influenza-positive patients aged 0-5 years and 65 years or more. There were statistically significant decreasing trends over the years in the incidence of all-cause hospitalisations, pneumonia and febrile seizures. CONCLUSIONS: Japanese administrative data revealed that 1.0% of influenza-positive patients aged under 75 years were hospitalised. Male patients had a higher incidence of pulmonary complications and febrile seizures. Children aged 0-5 years and adults aged 65-74 years were at high risk of being admitted to hospital for pneumonia.