Risk of Lactic Acidosis in Hospitalized Diabetic Patients Prescribed Biguanides in Japan: A Retrospective Total-Population Cohort Study.

Patient data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) are used to assess the effect of biguanide administration on rates of lactic acidosis (LA) in hospitalized diabetes mellitus (DM) patients. In this retrospective cohort study (from April 2013 to March 2016), we compare DM inpatients prescribed biguanides to DM inpatients who were not prescribed biguanides to quantify the association between biguanides and incidence of LA. In total, 8,111,848 DM patient records are retrieved from the NDB. Of the 528,768 inpatients prescribed biguanides, 782 develop LA. Of the 1,967,982 inpatients not prescribed biguanides, 1310 develop LA. The rate ratio of inpatients who develop LA and are administered biguanides to those who developed LA without receiving biguanides is 1.44 (95% CI, 1.32-1.58). Incidence rates and rate ratios for both sexes are elevated in the group prescribed biguanides for patients aged 70 years and older, markedly in those 80 years and older: 40.12 and 6.31 (95% CI, 4.75-8.39), respectively, for men and 34.96 and 5.40 (95% CI, 3.91-7.46), respectively, for women. Biguanides should be used conservatively in patients older than 70 years, particularly for those with comorbidities, and with caution in patients 80 years and older.

The age of death in Japanese patients with type 2 and type 1 diabetes: A descriptive epidemiological study.

This study clarified the age of death in patients with or without diabetes using the largest health insurance database in Japan. This population-based retrospective cohort study was performed using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) data. The ages of death between people with and without diabetes were compared. A total of 142,277,986 patients (74,488,962 women and 67,789,024 men) over 6 years, including 4,647,016 females, and 6,507,817 males with diabetes, were included. 2,786,071 females and 2,975,876 males died over 6 years, including 652,699 females and 954,655 males with diabetes. The average age of death in patients with diabetes was 2.6 years less than that of patients without diabetes. This descriptive epidemiological study illustrated the difference in age at death of patients with and without diabetes.

Tracing all patients who received insured dialysis treatment in Japan and the present situation of their number of deaths.

BACKGROUND: The survival rate of chronic dialysis patients in Japan remains the highest worldwide, so there is value in presenting Japan's situation internationally. We examined whether aggregate figures on dialysis patients in the National Database of Health Insurance Claims and Special Health Checkups of Japan (NDB), which contains data on insured procedures of approximately 100 million Japanese residents, complement corresponding figures in the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR). METHODS: Subjects were patients with medical fee points for dialysis recorded in the NDB during 2014-2018. We analyzed annual numbers of dialysis cases, newly initiated dialysis cases- and deaths. RESULTS: Compared with the JRDR, the NDB had about 6-7% fewer dialysis cases but a similar number of newly initiated dialysis cases. In the NDB, the number of deaths was about 6-10% lower, and the number of hemodialysis cases was lower, while that of peritoneal dialysis cases was higher. The cumulative survival rate at dialysis initiation was approximately 6 percentage points lower in the NDB than in the JRDR, indicating that some patients die at dialysis initiation. Cumulative survival rate by age group was roughly the same between the NDB and JRDR in both sexes. CONCLUSION: The use of the NDB enabled us to aggregate data of dialysis patients. With the definition of dialysis patients used in this study, analyses of concomitant medications, comorbidities, surgeries, and therapies will become possible, which will be useful in many future studies.

Association between dipeptidyl peptidase-4 inhibitors and increased risk for bullous pemphigoid within 3 months from first use: A 5-year population-based cohort study using the Japanese National Database.

AIMS/INTRODUCTION: We assessed the association between dipeptidyl peptidase-4 inhibitors (DPP-4is) and bullous pemphigoid (BP) and time-dependent changes in the risk for developing BP after DPP-4i initiation. MATERIALS AND METHODS: The present population-based, real-world study was carried out using the Japanese National Database dataset collected between 2013 and 2018. To assess independent correlations between DPP-4is and the development of BP, the self-controlled case series method was used. RESULTS: Among the cohort followed up for a median of 1,540 days, 53,027 patients were likely to develop BP. The possible incidence rate of BP in all 150,328,339 patients was 10.4/100,000 person-years. Among the 9,705,814 patients with type 2 diabetes, 15,634 were likely to develop BP. The possible incidence rate of BP in patients with type 2 diabetes was 38.1/100,000 person-years, whereas that in patients with type 2 diabetes who did and did not use DPP-4is was 40.7 and 30.0/100,000 person-years, respectively. Analysis of the 28,705 patients with type 2 diabetes likely to develop BP after initial DPP-4i use showed a risk ratio of 2.15 (95% confidence interval [CI] 1.75-2.63), 1.70 (95% CI 1.37-2.11), 1.44 (95% CI 1.15-1.82), 1.25 (95% CI 0.98-1.59), 0.84 (95% CI 0.63-1.10), 0.84 (95% CI 0.64-1.11) and 1.05 (95% CI 0.92-1.20), for the risk period of ≤30, 31-60, 61-90, 91-120, 121-150, 151-180 and 181-365 days, respectively. CONCLUSIONS: Although DPP-4is were associated with increased risk for BP, the risk was particularly significant within 3 months from first use.

Comparison of Japanese Centenarians' and Noncentenarians' Medical Expenditures in the Last Year of Life.

Importance: Although research has shown that centenarians tend to experience shorter periods of serious illness compared with other age groups, few studies have focused on the medical expenditures of centenarians as a potential indicator of the scale of medical resources used in their last year of life. Objective: To compare Japanese centenarians' and noncentenarians' monthly medical expenditures during the year before death according to age and sex. Design, Setting, and Participants: This retrospective cohort study used linked national health and long-term care insurance data collected from April 2013 to March 2018 in Nara Prefecture, Japan, for residents aged 75 years or older who were insured under the Medical Care System for older adults and died between April 2014 and March 2018. Data were analyzed from April 2013 to March 2018. Exposures: Age of 100 years or older (centenarians) vs 75 to 99 years (noncentenarians). Main Outcomes and Measures: The numbers of unique inpatients and outpatients and medical expenditures related to decedents' hospitalization and outpatient care were extracted and analyzed based on sex and age group. The Jonckheere-Terpstra test was used to identify trends in unadjusted medical expenditures by age group, and generalized estimating equations were used to estimate monthly median expenditures by age group with adjustment for comorbidity burden and functional status. Results: Of 34 317 patients aged 75 to 109 years (16 202 men [47.2%] and 18 115 women [52.8%]) who died between April 2014 and March 2018, 872 (2.5%) were aged 100 to 104 years (131 men [15.0%] and 741 women [85.0%]) and 78 (0.2%) were aged 105 to 109 years (fewer than 10 were men). The analysis of unadjusted medical expenditures in the last year of life showed a significant trend of lower expenditures for the older age groups; the median adjusted total expenditures during the 30 days before death by age group were $6784 (IQR, $4884-$9703) for ages 75 to 79 years, $5894 (IQR, $4292-$8536) for 80 to 84 years, $5069 (IQR, $3676-$7150) for 85 to 89 years, $4205 (IQR, $3085-$5914) for 90 to 94 years, $3522 (IQR, $2626-$4861) for 95 to 99 years, $2898 (IQR, $2241-$3835) for 100 to 104 years, and $2626 (IQR, $1938-$3527) for 105 to 109 years. The proportion of inpatients among all patients in the year before death also decreased with increasing age: 4311 of all 4551 patients aged 75 to 79 years (94.7%); 43 of all 78 patients aged 105 to 109 years (55.1%); 2831 of 2956 men aged 75 to 79 years (95.8%); 50.0% of men aged 105 to 109 years (the number is not reported owing to the small sample size); 1480 of 1595 women aged 75 to 79 years (92.8%); and 55.7% of women aged 105 to 109 years (the number of women is not reported to prevent back-calculation of the number of men). Specifically, 274 of 872 patients aged 100 to 104 years (31.4%) and 35 of 78 patients aged 105 to 109 years (44.9%) had not been admitted to a hospital in the year before death. Conclusions and Relevance: This cohort study found that medical expenditures in the last year of life tended to be lower for centenarians than for noncentenarians aged 75 years or older in Japan. The proportion of inpatients also decreased with increasing age. These findings may inform future health care services coverage and policies for centenarians.

Incidence of lower limb amputation in people with and without diabetes: a nationwide 5-year cohort study in Japan.

INTRODUCTION: This study was conducted to investigate the incidence and time trend of lower limb amputation (LLA) among people with and without diabetes. RESEARCH DESIGN AND METHODS: This retrospective population-based cohort study was based on the national claims data in Japan, comprising a total population of 150 million. Data of all individuals who had LLA from April 2013 to March 2018 were obtained. We analysed the sex-adjusted and age-adjusted annual LLA rate (every fiscal year) in people with and without diabetes for major and minor amputation. To test for time trend, Poisson regression models were fitted. RESULTS: In the 5-year period, 30 187 major and 29 299 minor LLAs were performed in Japan. The sex-adjusted and age-adjusted incidence of major and minor LLAs was 9.5 (people with diabetes, 21.8 vs people without diabetes, 2.3, per 100 000 person-years) and 14.9 (people with diabetes, 28.4 vs people without diabetes, 1.9, per 100 000 person-years) times higher, respectively, in people with diabetes compared with those without. A significant decline in the annual major amputation rate was observed (p<0.05) and the annual minor amputation rate remained stable (p=0.63) when sex, age and people with and without diabetes were included as dependent variables. CONCLUSIONS: This is the first report of the national statistics of LLAs in Japan. The incidence of major and minor LLAs was 10 and 15 times higher, respectively, in people with diabetes compared with those without. A significant decline in the major amputation rate was observed, and the annual minor amputation rate remained stable during the observation period. This information can help to create an effective national healthcare strategy for preventing limb amputations, which affect the quality of life of patients with diabetes and add to the national healthcare expenditure.

Association between influenza and the incidence rate of new-onset type 1 diabetes in Japan.

AIM: This study aimed to determine whether there is an association between influenza and new-onset type 1 diabetes. MATERIALS AND METHODS: This population-based retrospective cohort study used data from the National Database of Health Insurance Claims and Specific Health Check-ups of Japan. Influenza was defined based on drug prescriptions and the onset of type 1 diabetes was defined using specific medical codes indicating a diagnosis of type 1 diabetes. The incidence rate ratio of new-onset type 1 diabetes within 180 days after an influenza diagnosis was calculated and it was compared with that at other times using Poisson regression and generalized estimating equations. Sensitivity analyses were performed to confirm the robustness of this finding. RESULTS: The data of 10,400 patients with new-onset type 1 diabetes were analyzed, including 2,196 (952 male 1,244 female) patients diagnosed with influenza between 1 September 2014 and 31 August 2017. Although only patients with type 1 diabetes were included, adjusted analysis showed that individuals had a 1.3-fold (95% confidence interval: 1.15-1.46) higher risk of developing type 1 diabetes in the first 180 days after influenza diagnosis than that at other times. CONCLUSIONS: In this Japanese population-based cohort, the risk of new-onset type 1 diabetes may increase after the diagnosis of influenza. These results, which must be confirmed in other populations, suggest that influenza may be a causal factor for new-onset type 1 diabetes. The molecular mechanisms underlying the potential etiological relationship between influenza and type 1 diabetes should be elucidated.

Long-term prognosis of enteral feeding and parenteral nutrition in a population aged 75 years and older: a population-based cohort study.

BACKGROUND: Enteral feeding and parenteral nutrition (PN) using gastrostomy (GS) and a nasogastric tube feeding (NGT) and PN should be initiated for older patients based on their prognoses. This study aimed to investigate the long-term prognosis of patients aged ≥75 years who underwent enteral feeding via GS and NGT as well as PN. METHODS: A population-based cohort study was conducted using Japan's universal health insurance claims in the Nara Prefecture. This study enrolled 3,548 patients aged ≥75 years who received GS (N=770), NGT (N=2,370), and PN (N=408) during hospital admissions between April 2014 and March 2016. The GS group was further categorized into secondary GS (N=400) with preceding NGT or PN within 365 days and primary GS (N=370) without preceding NGT or PN groups. In the secondary GS group, 356 (96%) patients received NGT (versus PN). The outcome was mortality within 730 days after receiving GS, NGT, and PN. Cox regression analyses in cases with or without malignant diseases, adjusted for sex, age, comorbidity, and hospital type, were performed to compare mortality in the groups. RESULTS: Of the 3,548 participants, 2,384 (67%) died within 730 days after the initiation of GS and NGT and PN. The 2-year mortality rates in the secondary GS, primary GS, NGT, and PN groups were 58%, 66%, 68%, and 83% in patients without malignancies and 67%, 71%, 74%, and 87% in those with malignancies, respectively. In the non-malignant group, Cox regression analysis revealed that secondary GS (hazard ratio (HR) = 0.43, 95% CI: 0.34-0.54), primary GS (HR = 0.51, 95% CI: 0.40-0.64), and NGT (HR = 0.71, 95% CI: 0.58-0.87) were statistically significantly associated with lower mortality compared with PN. CONCLUSIONS: Approximately 58% to 87% patients aged ≥75 years died within 730 days after initiation of nutrition through GS, NGT, or PN. Patients with non-malignant diseases who received secondary GS exhibited better 2-year prognosis than those who received NGT or PN. Healthcare professionals should be aware of the effectiveness and limitations of enteral feeding and PN when considering their initiation.

Incidence and seasonality of type 1 diabetes: a population-based 3-year cohort study using the National Database in Japan.

INTRODUCTION: To investigate the incidence of type 1 diabetes by age group (0-19, 20-39, 40-59, ≥60 years) in Japan and whether there is seasonality in this incidence. RESEARCH DESIGN AND METHODS: The incidence of type 1 diabetes from September 2014 to August 2017 was estimated using 2013-2018 data from the National Database of Health Insurance Claims and Specific Health Check-ups of Japan. The incidence rate was analyzed using Tango's Index and the self-controlled case series method. RESULTS: Overall, 10 400 of the 79 175 553 included individuals were diagnosed with type 1 diabetes. The incidence of type 1 diabetes from September 2014 to August 2017 was 4.42/100 000 person-years. The incidence rates for men aged 0-19, 20-39, 40-59, and ≥60 years were 3.94, 5.57, 5.70, and 3.48, respectively. Among women, the incidence rates for the same age ranges were 5.22, 4.83, 4.99, and 3.31, respectively. Tango's index showed that the incidence rate of type 1 diabetes was significantly associated with seasons among those aged 0-19 years. Further, the self-controlled case series method showed a significant interaction between age and season, with the incidence of type 1 diabetes being higher in spring for patients younger than 20 years of age. CONCLUSIONS: In Japan, men aged 40-59 years and women aged 0-19 years are the groups with the highest incidence of type 1 diabetes. Further, the incidence of younger-onset diabetes in Japan was higher in spring (from March to May).

Data regarding fracture incidence according to fracture site, month, and age group obtained from the large public health insurance claim database in Japan.

The National Database of Health Insurance Claims and Specific Health Checkups of Japan includes all health insurance claims submitted in Japan and is considered representative of almost all health claims in Japan. Data regarding fracture incidence, based on the documented diagnoses in the claims and relevant procedure codes, were extracted from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. This data paper includes fracture incidence according to fracture site, month, and age group for the population in Kanto area (Tokyo and surrounding areas), which consists of approximately 42 million people. These data provide supplementary material to be interpreted for the article "Variation in Fracture Risk by Season and Weather: A Comprehensive Analysis across Age and Fracture Site Using a National Database of Health Insurance Claims in Japan" Hayashi et al., and serve as one of the largest epidemiological datasets regarding seasonal differences in fracture incidence according to fracture site and age group.

Variation in fracture risk by season and weather: A comprehensive analysis across age and fracture site using a National Database of Health Insurance Claims in Japan.

Although age- and season-specific effects on fracture risk have been reported, the effects of seasonality across different age groups and for different fracture sites have not yet been clarified. Therefore, our study aimed to comprehensively investigate the effects of seasonality on fracture risk across age and fracture sites using a large-scale population database of fracture incidence. Fracture data were accumulated over a 3-year period in the region of Tokyo and in surrounding areas, which accounts for a total population of 42 million. Information on fracture occurrence, fracture site, and patient demographics were obtained from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). Over the study period, 508,051 fractures were identified across the following five age groups: 0-19, 20-39, 40-64, 65-79, and 80+ years. The incidence rate for fractures in 10 site groups was calculated. Fracture risk was the highest in the spring and autumn for children aged 0-19 years and was the highest in the winter for elderly individuals (65-79 and 80+ years). Toe fractures, which occurred more frequently in the summer, were the most notable exception. The risk of fracture of the distal radius and hip was associated with daily temperature and rainfall and was elevated on days with a mean temperature higher than that of the previous day. Fracture risk exhibited seasonal variations that differed between children and elderly individuals and between toe fractures and fractures at other sites. These findings can help us understand the epidemiology of fractures and develop preventive strategies, as well as aid in the allocation of healthcare resources.