Stages of a Transtheoretical Model as Predictors of the Decline in Estimated Glomerular Filtration Rate: A Retrospective Cohort Study.

BACKGROUND: The transtheoretical model (TTM) is composed of the multiple stages according to patient's consciousness and is believed to lead people to realize the importance of healthier behaviors. We examined the association of TTM stages with the decline of estimated glomerular filtration rate (eGFR). METHODS: We used the annual health checkup data and health insurance claims data of the Japan Health Insurance Association in Kyoto Prefecture between April 2012 and March 2016. TTM stages of change obtained from questionnaires at the first health checkup and categorized into six groups. The primary outcome was defined as a more than 30% decline in eGFR from the first health checkup. We fitted multivariable Cox proportional-hazards model for time-to-event analyses adjusting for age, sex, eGFR, body mass index, blood pressure, blood sugar, dyslipidemia, uric acid, urinary protein, and existence of kidney diseases at first health checkup. RESULTS: We analyzed 239,755 employees and the mean follow-up was 2.9 (standard deviation, 1.2) years. As compared with the stage 1 group, the risk of eGFR decline was significantly low in the stage 3 group (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.65-0.91); stage 4 group (HR 0.80; 95% CI, 0.65-0.98); and stage 5 group (HR 0.79; 95% CI, 0.66-0.95). CONCLUSION: Compared with the precontemplation stage (stage 1), the preparation, action and maintenance stages (stages 3, 4, and 5), were associated with a lower risk of eGFR decline.

Effects of periodontal management for patients with type 2 diabetes on healthcare expenditure, hospitalization and worsening of diabetes: an observational study using medical, dental and pharmacy claims data in Japan.

AIMS: To investigate the effects of regular periodontal management for people with type 2 diabetes on total healthcare expenditure, hospitalization and the introduction of insulin. MATERIALS AND METHODS: We collected data of individuals who were prescribed diabetes medications during the fiscal year 2015 from the claims database of a prefecture in Japan. We fitted generalized linear models that had sex, age, comorbidities and the status of periodontal management during the previous two years as predictors. RESULTS: A total of 16,583 individuals were enrolled. The annual healthcare expenditure in the third year was 4% less (adjusted multiplier 0.96, 95% confidence interval [CI] 0.92-1.00) in the group receiving periodontal management every year. The adjusted odds ratio (aOR) for all-cause hospitalization was 0.90 (95% CI: 0.82-0.98). The aOR of introducing insulin in the third year for those who had not been prescribed insulin during the previous two years (n = 13,222) was 0.77 (95% CI: 0.64-0.92) in the group receiving periodontal management every year. CONCLUSION: Regular periodontal management for diabetic people was associated with reduced healthcare expenditure, all-cause hospitalization and the introduction of insulin therapy.

Early impact of school closure and social distancing for COVID-19 on the number of inpatients with childhood non-COVID-19 acute infections in Japan.

Many countries have implemented school closures as part of social distancing measures intended to control the spread of coronavirus disease 2019 (COVID-19). The aim of this study was to assess the early impact of nationwide school closure (March-May 2020) and social distancing for COVID-19 on the number of inpatients with major childhood infectious diseases in Japan. Using data from the Diagnosis Procedure Combination system in Japan, we identified patients aged 15 years or younger with admissions for a diagnosis of upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), influenza, gastrointestinal infection (GII), appendicitis, urinary tract infection (UTI), or skin and soft tissue infection (SSTI) between July 2018 and June 2020. Changes in the trend of the weekly number of inpatients between the two periods were assessed using interrupted time-series analysis. A total of 75,053 patients in 210 hospitals were included. The overall weekly number of inpatients was decreased by 52.5%, 77.4%, and by 83.4% in the last week of March, April, and May 2020, respectively, when compared on a year-on-year basis. The estimated impact was a reduction of 581 (standard error 42.9) inpatients per week in the post-school-closure period (p < 0.001). The main part of the reduction was for pre-school children. Remarkable decreases in the number of inpatients with URI, LRTI, and GII were observed, while there were relatively mild changes in the other groups.Conclusion: We confirmed a marked reduction in the number of inpatients with childhood non-COVID-19 acute infections in the post-school-closure period. What is Known: • Most countries have implemented social distancing measures to limit the spread of the novel coronavirus disease 2019 (COVID-19). • A large decrease in pediatric emergency visits has been reported from several countries after the social distancing. What is New: • Based on administrative claims data, a marked reduction in the number of inpatients for childhood non-COVID-19 acute infections was found in the post-school-closure period in Japan. • The magnitude of the reduction was different between the disease groups.

Surgical volume reduction and the announcement of triage during the 1st wave of the COVID-19 pandemic in Japan: a cohort study using an interrupted time series analysis.

PURPOSE: The coronavirus disease (COVID-19) pandemic has caused unprecedented challenges for surgical staffs to minimize exposure to COVID-19 or save medical resources without harmful patient outcomes, in accordance with the statement of each surgical society. No research has empirically validated declines in surgical volume in Japan, based on the usage of surgical triage. We aimed to identify whether the announcement of surgical priorities by each Japanese surgical society may have affected the surgical volume decline during the 1st wave of this pandemic. METHODS: We extracted 490,719 available cases of patients aged > 15 years who underwent elective major surgeries between July 1, 2018, and June 30, 2020. After the categorization of surgical specialities, we calculated descriptive statistics to compare the year-over-year trend and conducted an interrupted time series analysis to validate the decline of each surgical procedure. RESULTS: Monthly surgical cases of eight surgical specialities, especially ophthalmology and ear/nose/throat surgeries, decreased from April 2020 and reached a minimum in May 2020. An interrupted time series analysis showed no significant trends in oncological and critical surgeries. CONCLUSION: Non-critical surgeries showed obvious and statistically significant declines in case volume during the 1st wave of the COVID-19 pandemic according to the statement of each surgical society in Japan.

Integration of large heterologous DNA fragments into the genome of Thermococcus kodakarensis.

In this study, a transformation system enabling large-scale gene recombination was developed for the hyperthermophilic archaeon Thermococcus kodakarensis. Using the uracil auxotroph T. kodakarensis KU216 (∆pyrF) as a parent strain, we constructed multiple host strains harboring two 1-kbp DNA regions from the genomes of either the hyperthermophilic archaeon Pyrococcus furiosus or Methanocaldococcus jannaschii. The two regions were selected so that the regions between them on the respective genomes would include pyrF genes, which can potentially be used for selection. Transformation using these host strains and genomic DNA from P. furiosus or M. jannaschii were carried out. Transformants with exogenous pyrF were obtained only using host strains with regions from P. furiosus, and only when the distances between the two regions were relatively short (2-5 kbp) on the P. furiosus genome. To insert longer DNA fragments, we examined the possibilities of using P. furiosus cells to provide intact genomic DNA. A cell pellet of P. furiosus was overlaid with that of T. kodakarensis so that cells were in direct contact. As a result, we were able to isolate T. kodakarensis strains harboring DNA fragments from P. furiosus with lengths of up to 75 kbp in a single transformation step.

Developing and validating a multivariable prediction model for in-hospital mortality of pneumonia with advanced chronic kidney disease patients: a retrospective analysis using a nationwide database in Japan.

BACKGROUND: The prognosis of pneumonia in patients with advanced stage chronic kidney disease (CKD) remains unimproved for years. We attempt to develop a simple and more useful scoring system for predicting in-hospital mortality for advanced CKD patients with pneumonia. METHODS: Using the Diagnosis Procedure Combination database, we identified the in-hospital adult patients both with a record of pneumonia and stage 5 or 5D CKD as a comorbidity on admission between April 1, 2012 and March 31, 2016. Predictive variable selection was analyzed by multivariable logistic regression analysis, stepwise method, LASSO method and random forest method, and then develop a new simple scoring system seeking for highest c-statistics combination of variables in one sample data set for model development. Finally, we compared c-statistics of univariate logistic regression about new scoring system with c-statistics about "A-DROP" in the other sample data set. RESULT: We identified 8402 patients in 707 hospitals, and the total in-hospital mortality was 11.0% (437 patients) in development data set. Seven variables were selected, which includes age (male ≥ 70 years, female ≥ 75 years), respiratory failure, orientation disturbance, low blood pressure, the need of assistance in feeding or bowel control, severe or moderate thinness and CRP 200 mg/L or extent of consolidation on chest X-ray ≥ 2/3 of one lung. The c-statistics of univariate logistic regression was 0.8017 using seven variables, while that was 0.7372 using "A-DROP" CONCLUSION: In advanced CKD patients, if we select appropriate variables for predicting in-hospital mortality, simple scoring system may have better discrimination than "A-DROP".

Association between renal outcome and the number of steroid pulse therapies after tonsillectomy in patients with IgA nephropathy.

BACKGROUND: Tonsillectomy performed on patients with Immunoglobulin A glomerulonephritis (IgAN) improved the clinical remission rate as defined by urinary protein. But the number of times steroid pulse therapies (SP) should be administered remained poorly understood. METHOD: Multicenter, observational, retrospective cohort study at four hospitals in the Tokyo metropolitan area between March 1981 and December 2013. We divided patients into two groups: those treated with SP three times and those treated without SP or with SP only once or twice, and we analyzed standard Cox proportional hazard model unadjusted and adjusted the confounding covariates to estimate the hazard ratio for the primary outcome, the 30% estimated decline in glomerular filtration rate, in four models: model 1, unadjusted; model 2, adjusted for age, sex, body mass index, estimated glomerular filtration rate, biopsy year, proteinuria, hematuria, Japanese historical grade, systolic blood pressure, smoking history, and diabetes as a comorbidity; model 3, adjusted for propensity score, which was estimated by multiple logistic regressions; model 4, multilevel mixed-effects parametric survival models, whose facilities comprise the second level. RESULTS: Patients that received three times SP therapy were significantly associated with better renal outcome compared with patients with less number of SP therapy (HR 0.66; 95% CI 0.37-1.17 in model 1, 0.40 (0.20-0.78) in model 2, 0.46 (0.25-0.88) in model 3, 0.36 (0.18-0.71) in model 4). CONCLUSIONS: For treatment of IgAN, SP administered three times after tonsillectomy was associated with better renal prognosis compared with SP administered only once or twice.

Renal histology and MRI in a 25-year-old Japanese man with nephronophthisis 4
.

We investigated a 25-year-old Japanese man who had polycystic kidneys and end-stage renal failure without a positive family history. Ultrasonography revealed enlarged kidneys with increased echogenicity and multiple cystic lesions. MRI showed replacement of both kidneys by cystic lesions without definite walls. Renal biopsy demonstrated interstitial fibrosis, especially at the corticomedullary junction. The residual tubular system showed starfish-like disruption. Tubules with cystic dilation were mainly the distal loop of Henle and the distal tubules since immunohistochemical staining was positive for cytokeratin 7 (the distal loop of Henle and the distal tubule) and Tamm-Horsfall protein (the distal loop of Henle), while being negative for aquaporin 3 (the collecting duct) and CD10 (proximal tubule). Comprehensive genetic analysis identified compound heterozygous missense mutations of NPHP4 with autosomal recessive inheritance since his asymptomatic parents each had a single heterozygous missense mutation of NPHP4. In conclusion, MRI and immunohistochemical analysis of renal biopsy specimens may be useful for evaluation of this disease.
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Anti-RNA polymerase III antibody-associated scleroderma renal crisis in a patient with limited cutaneous systemic sclerosis: A case report.

A 69-year-old Japanese man was presented with hypertensive crisis. Renal histology revealed malignant nephrosclerosis, including an onion skin pattern with fibrinoid necrosis of the small arteries from arterioles up to interlobular arteries. Immunological investigation clarified positive anti-RNA polymerase (RNAP) III antibody, and limited cutaneous systemic sclerosis (Lc SSc) was diagnosed by skin biopsy as the underlying disease causing scleroderma renal crisis (SRC). Angiotensin covering enzyme (ACE) inhibitor therapy and calcium antagonist were effective for his renal condition. Although an association between SRC and anti-RNAP III antibody has already been reported in patients with diffuse cutaneous SSc (Dc SSc), this case indicates that SRC with hypetensive emergency with malignant nephrosclerosis can also be diagnosed on patients with Lc SSc patients by the examination of anti-RNAP III antibody.

Renal histology and MRI findings in a 37-year-old Japanese patient with autosomal recessive polycystic kidney disease
.

A 37-year-old Japanese man with a serum creatinine level of 2.5 mg/dL and hepatomegaly was admitted to our hospital for investigation of renal failure. Magnetic resonance imaging (MRI) showed hepatomegaly with small cystic lesions that had high signal intensity on T2-weighted images. There was no splenomegaly, and the kidneys were nearly normal in size with a few small cystic lesions. Renal biopsy revealed that interstitial fibrosis and tubular atrophy affected 60% of the cortex. There was cystic tubular dilation, mainly affecting the distal loop of Henle and distal tubules, since immunohistochemical staining of the dilated tubules was positive for cytokeratin 7 and Tamm-Horsfall protein but was negative for aquaporin 3 and CD10. Immunofluorescence microscopy and electron microscopy did not demonstrate any immune deposits. Genetic analysis identified two different heterozygous missense variants of PKHD1, while the patient's asymptomatic parents were each heterozygous for a single PKHD1 mutation. Accordingly, autosomal recessive polycystic kidney disease (-ARPKD) due to compound heterozygous PKHD1 mutation was diagnosed. The renal biopsy findings of this patient may be nonspecific, but they were different from the typical renal histology of infantile ARPKD. In conclusion, the renal features of adult-onset ARPKD may differ from those of infantile disease.
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Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations.

Somatic mutations in KCNJ5 gene have been identified in patients with adrenal aldosterone-producing adenomas (APAs). We previously reported that Japanese patients with APAs had distinct characteristics from patients in Western countries; i.e. they had a high frequency of KCNJ5 mutations and exhibited a frequent association with cortisol co-secretion. Therefore, APAs among Japanese patients may have different features from those in Western countries. We added recent cases, examined 47 cases (43% male) of APAs, including clinicopathological features, KCNJ5 mutations, and the mRNA levels of several steroidogenic enzymes, and compared the results obtained to those reported in other countries. While the prevalence of KCNJ5 mutations is approximately 40% in Western countries, 37 APA cases (78.7%) showed mutations: 26 with p.G151R and 11 with p.L168R. Although a significant gender difference has been reported in the frequency of KCNJ5 mutations in Europe, we did not find any gender difference. However, the phenotypes of Japanese patients with mutations were similar to those of patients in Western countries; patients were younger and had higher plasma aldosterone levels, lower potassium levels, and higher diastolic blood pressure. Reflecting these phenotypes, APAs with mutations had higher CYP11B2 mRNA levels. However, in contrast to APAs in Western countries, Japanese APAs with mutations showed lower CYP11B1, CYP17A1, and CYP11A1 mRNA levels. These findings demonstrated that Japanese APA patients may have distinct features including a higher prevalence of KCNJ5 mutations, no gender difference in the frequency of these mutations, and characteristics similar to the zona glomerulosa.

The use of cinacalcet hinders the diagnosis of parathyroid carcinoma in a chronic dialysis patient: a case report.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a common complication in patients receiving chronic dialysis therapy. Although cinacalcet can control parathyroid function and bone turnover, preventing ectopic calcification remains challenging. Cinacalcet can also suppress PTH secretion due to parathyroid carcinoma in the same way as it does for parathyroid hyperplasia in the uremic condition. We present a case of parathyroid carcinoma partially controlled by cinacalcet, in which tumorous calcinosis was successfully resolved by total parathyroidectomy. CASE PRESENTATION: A female patient in her forties who had received dialysis for 12 years was referred to our hospital for painful ectopic calcifications on her right hip joint and both knees. Although she had been treated with alfacalcidol and cinacalcet for 2 years, this therapy had been discontinued 6 months earlier as a result of hypercalcemia. The patient exhibited normocalcemia (2.37 mmol/L) and hyperphosphatemia (2.42 mmol/L) with elevated intact parathyroid hormone (707,000 µg/L). Ultrasonography revealed an enlarged parathyroid gland on the left lower side of the thyroid gland. The otolaryngologist surgeons had to perform an en bloc excision to remove this parathyroid gland because of tight adhesions. Histological examination revealed that parathyroid cells had invaded the surrounding skeletal muscle through fibrous capsules, consistent with parathyroid carcinoma. Her joint pain disappeared 2 weeks after parathyroidectomy, and the tumorous calcinosis had largely resolved after 1 year. CONCLUSIONS: Parathyroid carcinoma is a rare cause of hyperparathyroidism in end-stage kidney disease. Our case indicates that the use of cinacalcet hinders the diagnosis of parathyroid carcinoma in a chronic dialysis patient. When uncontrolled hypercalcemia and/or hyperphosphathemia develop during cinacalcet administration, parathyroidectomy should be considered to prevent a vicious exacerbation of ectopic calcification.

IgA nephropathy featuring massive wire loop-like deposits in two patients with alcoholic cirrhosis.

BACKGROUND: Various renal manifestations are known to develop in patients with liver disease, including chronic hepatitis and cirrhosis. CASE PRESENTATION: We evaluated renal disease in two 47-year-old Japanese men with liver cirrhosis and chronic alcoholism for 34 years and 27 years, respectively. Renal biopsy demonstrated massive wire loop-like deposits in the subendothelial space of the glomerular basement membrane and in the mesangium. However, immunofluorescence was only positive for IgA and C3, and electron microscopy did not reveal any organized structures in the electron-dense deposits. IgA nephropathy was diagnosed, although the features were different from primary IgA nephropathy. Both patients had portosystemic shunts associated with liver cirrhosis. Their renal deposits and proteinuria resolved completely after 1 year of steroid therapy. CONCLUSION: Alcohol abuse may have contributed to development of secondary IgA nephropathy in these two patients, probably via their portosystemic shunts.

Impact of policy alterations on elective percutaneous coronary interventions in Japan.

OBJECTIVE: Establishing appropriate percutaneous coronary intervention (PCI) in stable angina pectoris (SAP) has become a distinctive performance measure worldwide. Clinical guidelines call for documenting ischaemia in patients with SAP prior to elective PCI. The Japanese Ministry of Health, Labour and Welfare introduced a new reimbursement policy in April 2018 to promote the appropriate and judicious implementation of PCI. The 2018 reimbursement changes clarified the required proof of ischaemia. Tests to evaluate functional ischaemia and coronary stenosis have been added as a requirement for reimbursement. We examined whether this reimbursement revision had an impact on PCI procedures for SAP in Japan. METHODS: We used administrative claims data in Japan's Diagnosis Procedure Combination database from April 2014 through March 2020. We used interrupted time series analyses with a control to ascertain the impacts on elective PCI procedures before and after the Japanese reimbursement revision. The primary outcome was the change in elective PCI procedures per month. Emergent PCI procedures served as a control group. RESULTS: A total of 773 240 PCI procedures were identified between April 2014 and March 2020: 388 817 and 180 462 elective PCIs before and after the reimbursement revision, respectively. After the 2018 reimbursement revision, significant trend changes were found in elective PCI procedures per month (-106.3, 95% CI -155.8 to -56.8, p<0.01), while the number of emergent PCIs remained stable throughout the study period. CONCLUSIONS: After revising the reimbursement tariff for elective PCIs in 2018, there was a significant reduction in elective PCI procedures per month.

The Japanese Guide affected the prescription of steroids for COVID-19 inpatients during the COVID-19 epidemic in Japan.

Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, guidance ("Japanese Guide") has been published by a working group of several academic societies and announced by the Ministry of Health, Labour, and Welfare. Steroids as a candidate treatment for COVID-19 were noted in the Japanese Guide. However, the prescription details for steroids, and whether the Japanese Guide changed its clinical practice, were unclear. This study aimed to examine the impact of the Japanese Guide on the trends in the prescription of steroids for COVID-19 inpatients in Japan. We selected our study population using Diagnostic Procedure Combination (DPC) data from hospitals participating in the Quality Indicator/Improvement Project (QIP). The inclusion criteria were patients discharged from hospital between January 2020 and December 2020, who had been diagnosed with COVID-19, and were aged 18 years or older. The epidemiological characteristics of cases and the proportion of steroid prescriptions were described on a weekly basis. The same analysis was performed for subgroups classified by disease severity. The study population comprised 8603 cases (410 severe cases, 2231 moderate II cases, and 5962 moderate I/mild cases). The maximum proportion of cases prescribed with dexamethasone increased remarkably from 2.5 to 35.2% in the study population before and after week 29 (July 2020), when dexamethasone was included in the guidance. These increases were 7.7% to 58.7% in severe cases, 5.0% to 57.2% in moderate II cases, and 1.1% to 19.2% in moderate I/mild cases. Although the proportion of cases prescribed prednisolone and methylprednisolone decreased in moderate II and moderate I/mild cases, it remained high in severe cases. We showed the trends of steroid prescriptions in COVID-19 inpatients. The results showed that guidance can influence drug treatment provided during an emerging infectious disease pandemic.

The relationship between new PCR positive cases and going out in public during the COVID-19 epidemic in Japan.

The suppression of the first wave of COVID-19 in Japan is assumedly attributed to people's increased risk perception after acquiring information from the government and media reports. In this study, going out in public amidst the spread of COVID-19 infections was investigated by examining new polymerase chain reaction (PCR) positive cases of COVID-19 and its relationship to four indicators of people going out in public (the people flow, the index of web searches for going outside, the number of times people browse restaurants, and the number of hotel guests, from the Regional Economic and Social Analysis System (V-RESAS). Two waves of COVID-19 infections were examined using cross-correlation analysis. In the first wave, all four indicators of going out changed to be opposite the change in new PCR positive cases, showing a lag period of -1 to +6 weeks. In the second wave, the same relationship was only observed for the index of web searches for going outside, and two indicators showed the positive lag period of +6 to +12 weeks after the change in new PCR positive cases. Moreover, each indicator in the second wave changed differently compared to the first wave. The complexity of people's behaviors around going out increased in the second wave, when policies and campaigns were implemented and people's attitudes were thought to have changed. In conclusion, the results suggest that policies may have influenced people's mobility, rather than the number of new PCR positive cases.

Trends, Treatment Approaches, and In-Hospital Mortality for Acute Coronary Syndrome in Japan During the Coronavirus Disease 2019 Pandemic.

AIM: The coronavirus disease 2019 (COVID-19) pandemic has left negative spillover effects on the entire health care system. Previous studies have suggested significant declines in cases of acute coronary syndrome (ACS) and primary percutaneous coronary intervention (PCI) during the COVID-19 pandemic. METHODS: We performed a quasi-experimental, retrospective cohort study of ACS hospitalisations by using a multi-institutional administrative claims database in Japan. We used interrupted time series analyses to ascertain impacts on cases, treatment approaches, and in-hospital mortality before and after Japan's state of emergency to respond to COVID-19. The primary outcome was the change in ACS cases per week. RESULTS: A total of 30,198 ACS cases (including 21,612 acute myocardial infarction and 8,586 unstable angina) were confirmed between 1st July 2018 and 30th June 2020. After the state of emergency, an immediate decrease was observed in ACS cases per week (-18.3%; 95% confidence interval, -13.1 to -23.5%). No significant differences were found in the severity of Killip classification (P=0.51) or cases of fibrinolytic therapy (P=0.74). The impact of the COVID-19 pandemic on in-hospital mortality in ACS patients was no longer observed after adjustment for clinical characteristics (adjusted odds ratio, 0.93; 95% confidence interval, 0.78 to 1.12; P=0.49). CONCLUSIONS: We demonstrated the characteristics and trends of ACS cases in a Japanese population by applying interrupted time series analyses. Our findings provide significant insights into the association between COVID-19 and decreases in ACS hospitalisations during the pandemic.