Publications by authors named "Nobuaki Michihata"

114 Publications

Safety of topical ophthalmic antibiotics in pregnant women with hordeola, chalazia, blepharitis, or bacterial conjunctivitis: propensity score analyses.

Eye (Lond) 2021 May 25. Epub 2021 May 25.

Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan.

Objective: To investigate the association between exposure to topical ophthalmic antibiotics during pregnancy and adverse neonatal outcomes.

Methods: In this retrospective cohort study, we identified pregnant women with hordeola, chalazia, blepharitis, or bacterial conjunctivitis from 2005 to 2018 using the Japanese Medical Data Centre Claims Database. From the eligible women, we extracted women who were dispensed no topical antibiotics during the first trimester (non-antibiotic group), women who were dispensed topical fluoroquinolones alone at least once (fluoroquinolone alone group), and women who were dispensed any single type of antibiotic (single-antibiotic group). We compared the frequency of congenital anomalies (CA), preterm birth (PB), low birth weight (LBW), and the composite outcome of these three between the fluoroquinolone and non-antibiotic groups and between the single-antibiotic and non-antibiotic groups, using propensity score adjustment.

Results: A total of 891 eligible women were identified. In the fluoroquinolone (n = 409) and non-antibiotic (n = 309) groups, CA occurred in 6.8% and 6.8%, PB in 2.4% and 3.2%, LBW in 2.9% and 3.2%, and the composite outcome in 10.5% and 11.3%, respectively. Analysis using propensity score adjustment showed no significant difference between the groups in the frequency of CA (adjusted odds ratio, 1.15; 95% confidence interval, 0.61-2.18), PB (0.80; 0.30-2.17), LBW (1.08; 0.45-2.63), or the composite outcome (1.12; 0.67-1.87). Comparison of the single-antibiotic and non-antibiotic groups showed similar results.

Conclusions: Topical ophthalmic antibiotics for hordeola, chalazia, blepharitis, or bacterial conjunctivitis during the first trimester were not associated with increased adverse neonatal outcomes.
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http://dx.doi.org/10.1038/s41433-021-01586-yDOI Listing
May 2021

Association Between Blood Pressure Classification Using the 2017 ACC/AHA Blood Pressure Guideline and Retinal Atherosclerosis.

Am J Hypertens 2021 May 19. Epub 2021 May 19.

The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

Background: We aimed to explore the association between the blood pressure (BP) classification defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline and the prevalence of retinal atherosclerosis.

Methods: This study was a retrospective observational cross-sectional analysis using the JMDC Claims Database. We analyzed 280,599 subjects not taking any antihypertensive medications. According to the 2017 ACC/AHA guideline, each subject was categorized as having normal BP (n=159,524), elevated BP (n=35,603), stage 1 hypertension (n=54,795), or stage 2 hypertension (n=30,677) using the BP value at the initial health check-up. Retinal photographs were assessed according to the Keith-Wagener-Barker system.

Results: The median age was 46 years, and 50.4% subjects were men. Retinal atherosclerosis, defined as Keith-Wagener-Barker system grade ≥1, was observed in 3.2% in normal BP, 5.2% in elevated BP, 7.7% in stage 1 hypertension, and 18.7% in stage 2 hypertension. Compared with normal BP, elevated BP (OR;1.30, 95% CI;1.23-1.38), stage 1 hypertension (OR;1.71, 95% CI;1.64-1.79), and stage 2 hypertension (OR;4.10, 95% CI;3.93-4.28) were associated with a higher prevalence of retinal atherosclerosis. Among 92,121 subjects without obesity, high waist circumference, diabetes mellitus, dyslipidemia, cigarette smoking, and alcohol consumption, elevated BP (OR;1.34, 95% CI;1.19-1.51), stage 1 hypertension (OR;1.79, 95% CI;1.61-1.98), and stage 2 hypertension (OR;4.42, 95% CI;4.00-4.92) were associated with a higher prevalence of retinal atherosclerosis. This association was observed in all subgroups stratified by age or sex.

Conclusions: Our investigation suggests that retinal atherosclerosis could start even in individuals with elevated BP and stage 1 hypertension.
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http://dx.doi.org/10.1093/ajh/hpab074DOI Listing
May 2021

Sodium-containing versus sodium-trace preparations of IVIG for children with Kawasaki disease in the acute phase.

Eur J Pediatr 2021 May 10. Epub 2021 May 10.

Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan.

Kawasaki disease (KD) is an acute systemic vasculitis that most commonly causes acquired cardiac disease in children in developed countries. The most highly recommended treatment for KD is 2 g/kg intravenous immunoglobulin (IVIG). There are two types of IVIG, sodium-containing (high-Na) and sodium-trace (low-Na) preparations. However, few studies have compared the effects of these two preparations for superiority. The purpose of this study was to compare outcomes between high and low-Na IVIG preparations in KD children using a national inpatient database in Japan. We used the Diagnostic Procedure Combination database to identify KD patients treated with IVIG between 2010 and 2017. We identified those receiving high and low-Na preparations of IVIG as an initial treatment. Outcomes included proportion of coronary artery abnormalities (CAA), IVIG resistance, adverse effects, length of stay, and medical cost. Propensity score-matched analyses were conducted to compare the outcomes between the two groups. Instrumental variable analyses were performed to confirm the results. We identified 42,345 patients with KD. There were significant differences in proportions of CAA (2.8% vs. 3.2%; p = 0.031) and IVIG resistance (17% vs. 18%, p = 0.001) between the two groups. However, there were no significant differences in length of stay or medical cost. The instrumental variable analysis confirmed the same results as the propensity score analysis.Conclusion: The present study suggests that high-Na IVIG is potentially effective for reducing the proportion of CAA in KD patients. Prospective studies are warranted to confirm the effectiveness observed in this study. What is Known: • For treatments of Kawasaki Disease in acute phase, intravenous immunoglobulin have been the most recommended to reduce fever early and prevent complications of coronary artery abnormalities. There are two types of IVIG preparations, sodium-containing IVIG and sodium-trace IVIG. However, few studies have performed comparisons to determine which preparation of IVIG is superior. What is New: • The present findings suggest that high-Na IVIG is associated with reductions in the proportions of CAAs and IVIG resistance in KD patients.
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http://dx.doi.org/10.1007/s00431-021-04096-xDOI Listing
May 2021

Clinical features and early post-operative complications of isolated C2 odontoid fractures: a retrospective analysis using a national inpatient database in Japan.

Eur Spine J 2021 May 6. Epub 2021 May 6.

Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showa, Maebashi, Gunma, 371-8511, Japan.

Purpose: To examine the clinical features and post-treatment complications in patients with isolated C2 odontoid fractures.

Methods: We extracted data for all patients who were admitted with C2 odontoid fractures from the Japanese Diagnosis Procedure Combination database between July 2010 and March 2017. We then compared the post-treatment complications during hospitalization according to treatment types: conservative treatment (with or without use of halo-vest) and surgery (anterior or posterior spinal fixation).

Results: A total of 3167 patients (1533 men, 1634 women; mean age, 70 years) with isolated C2 odontoid fractures were identified, including 1124 patients (35%) aged ≥ 80 years. Among the total patients, 2476 (78%) received conservative treatment (with halo-vest, 728; without halo-vest, 1748). The remaining 691 patients (22%) underwent surgery (anterior surgery, 129; posterior surgery, 556; combined surgery, 6). There were no differences between the conservative treatment and surgery groups in baseline characteristics and preexisting comorbid conditions except for age (71 vs. 69 years, p = 0.042). In-hospital death occurred in 136 patients (4.3%). There was no significant difference in in-hospital mortality between the two groups (overall, conservative treatment 4.6% vs. surgery 3.0%, p = 0.066; age ≥ 80 years, conservative treatment 7.2% vs. surgery 5.4%, p = 0.34). Use of halo-vest was not associated with increased mortality (with halo-vest 3.7% vs. without halo-vest 5.0%, p = 0.15).

Conclusion: The great majority of isolated odontoid fractures occurred in elderly patients. Conservative treatment and surgery had similarly low in-hospital mortality. Use of halo-vest was not associated with an increase in mortality.
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http://dx.doi.org/10.1007/s00586-021-06862-9DOI Listing
May 2021

Impact of proton pump inhibitors on mortality and severe esophageal injury after catheter ablation for atrial fibrillation: a nationwide retrospective study using propensity score matching.

Heart Vessels 2021 Apr 30. Epub 2021 Apr 30.

Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Studies on the protective effects of proton pump inhibitors (PPIs) on mortality and severe esophageal injury after catheter ablation for atrial fibrillation are lacking. However, some reports have recommended use of PPIs for prophylaxis against esophageal injury. We investigated the effects of PPIs on mortality and severe esophageal injury after ablation. We retrospectively extracted data for adult in-patients who received catheter ablation with a diagnosis of atrial fibrillation from July 2010 to March 2018. The patients were divided into two groups: with PPI (PPI group) and without PPI (non-PPI group) administration before or on the day of ablation. The primary composite outcome was all-cause 30-day mortality and incidence of severe esophageal injury with complication (cardiac tamponade, ischemic stroke, or sepsis) within 30 days of ablation. Secondary outcomes included incidence of cardiac tamponade, ischemic stroke, and sepsis within 30 days of ablation. Propensity score matching was performed to compare the primary and secondary outcomes between the two groups. We identified 141,649 eligible patients, comprising 62,558 in the PPI group and 79,091 in the non-PPI group. Propensity score-matching analysis showed that PPI use was not associated with reduced proportion of the primary outcome (adjusted odds ratio 1.02; 95% confidence interval 0.71-1.47). PPI use may not be beneficial for reducing mortality or severe complications.
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http://dx.doi.org/10.1007/s00380-021-01860-9DOI Listing
April 2021

Risk of drug-induced interstitial lung disease in hospitalised patients: a nested case-control study.

Thorax 2021 Apr 22. Epub 2021 Apr 22.

Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Introduction: Information on drug-induced interstitial lung disease (DILD) is limited due to its low incidence. This study investigated the frequencies of drug categories with potential risk in patients developing DILD during hospitalisation and analysed the risk of developing DILD associated with each of these drugs.

Methods: Using a Japanese national inpatient database, we identified patients without interstitial pneumonia on admission who developed DILD and required corticosteroid therapy during hospitalisation from July 2010 to March 2016. We conducted a nested case-control study; four controls from the entire non-DILD patient cohort were matched to each DILD case on age, sex, main diagnosis, admission year and hospital. We defined 42 classified categories of drugs with 216 generic names as drugs with potential risk of DILD, and we identified the use of these drugs during hospitalisation for each patient. We analysed the association between each drug category and DILD development using conditional logistic regression analyses.

Results: We retrospectively identified 2342 patients who developed DILD. After one-to-four case-control matching, 1541 case patients were matched with 5677 control patients. Six drug categories were significantly associated with the increased occurrence of DILD. These included epidermal growth factor receptor inhibitors (OR: 16.84, 95% CI 9.32 to 30.41) and class III antiarrhythmic drugs (OR: 7.01, 95% CI 3.86 to 12.73). Statins were associated with reduced risk of DILD (OR: 0.68, 95% CI 0.50 to 0.92).

Conclusions: We demonstrated significant associations between various drug categories and DILD. Our findings provide useful information on drug categories with potential risk to help physicians prevent and treat DILD.
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http://dx.doi.org/10.1136/thoraxjnl-2020-215824DOI Listing
April 2021

Association of Blood Pressure Classification Using the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline With Risk of Heart Failure and Atrial Fibrillation.

Circulation 2021 Jun 22;143(23):2244-2253. Epub 2021 Apr 22.

Department of Cardiovascular Medicine (H. Kaneko, H.I., H. Kiriyama, T.K., K.F., N.T., H.M., I.K.), University of Tokyo, Japan.

Background: Heart failure (HF) and atrial fibrillation (AF) are growing in prevalence worldwide. Few studies have assessed to what extent stage 1 hypertension in the 2017 American College of Cardiology/American Heart Association blood pressure (BP) guidelines is associated with incident HF and AF.

Methods: Analyses were conducted with a nationwide health claims database collected in the JMDC Claims Database between 2005 and 2018 (n=2 196 437; mean age, 44.0±10.9 years; 58.4% men). No participants were taking antihypertensive medication or had a known history of cardiovascular disease. Each participant was categorized as having normal BP (systolic BP <120 mm Hg and diastolic BP <80 mm Hg; n=1 155 885), elevated BP (systolic BP 120-129 mm Hg and diastolic BP <80 mm Hg; n=337 390), stage 1 hypertension (systolic BP 130-139 mm Hg or diastolic BP 80-89 mm Hg; n=459 820), or stage 2 hypertension (systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg; n=243 342). Using Cox proportional hazards models, we identified associations between BP groups and HF/AF events. We also calculated the population attributable fractions to estimate the proportion of HF and AF events that would be preventable if participants with stage 1 and stage 2 hypertension were to have normal BP.

Results: Over a mean follow-up of 1112±854 days, 28 056 incident HF and 7774 incident AF events occurred. After multivariable adjustment, hazard ratios for HF and AF events were 1.10 (95% CI, 1.05-1.15) and 1.07 (95% CI, 0.99-1.17), respectively, for elevated BP; 1.30 (95% CI, 1.26-1.35) and 1.21 (95% CI, 1.13-1.29), respectively, for stage 1 hypertension; and 2.05 (95% CI, 1.97-2.13) and 1.52 (95% CI, 1.41-1.64), respectively, for stage 2 hypertension versus normal BP. Population attributable fractions for HF associated with stage 1 and stage 2 hypertension were 23.2% (95% CI, 20.3%-26.0%) and 51.2% (95% CI, 49.2%-53.1%), respectively. The population attributable fractions for AF associated with stage 1 and stage 2 hypertension were 17.4% (95% CI, 11.5%-22.9%) and 34.3% (95% CI, 29.1%-39.2%), respectively.

Conclusions: Both stage 1 hypertension and stage 2 hypertension were associated with a greater incidence of HF and AF in the general population. The American College of Cardiology/American Heart Association BP classification system may help identify adults at higher risk for HF and AF events.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052624DOI Listing
June 2021

Comparisons of postoperative outcomes after breast cancer surgery in patients with and without renal replacement therapy: a matched-pair cohort study using a Japanese nationwide inpatient database.

Breast Cancer 2021 Apr 10. Epub 2021 Apr 10.

Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Although patients receiving renal replacement therapy (RRT) have more comorbidities and higher mortality and morbidity risks than the general population, surgery during breast cancer treatment is crucial because of limitations in anticancer agents for patients with renal insufficiency. We aimed to compare the short-term postoperative outcomes between patients with and without RRT.

Methods: Patients who underwent surgery for stages 0-III breast cancer between July 2010 and March 2017 were retrospectively identified in a Japanese nationwide inpatient database and divided into those with RRT (RRT group, n = 1547) and those without RRT (control group, n = 364,047). We generated a 1:4 matched-pair cohort matched for age, institution, and fiscal year at admission. We conducted multivariable regression analyses to compare postoperative complications, 30-day readmission, and anesthesia duration between the two groups.

Results: The RRT group was more likely to have comorbidities (95.0% vs. 24.1%) and undergo total mastectomy (64.2% vs. 47.0%) than the control group. The RRT group was not significantly associated with complications (odds ratio 1.18; 95% confidence interval [CI] 0.89-1.56) and 30-day readmission (odds ratio 0.88; 95% CI 0.65-1.18), but was associated with shorter anesthesia duration (difference, - 6.8 min; 95% CI - 10.7 to - 3.0 min) compared with the control group.

Conclusions: The matched-pair cohort analyses revealed no significant differences in postoperative complications after breast cancer surgery between patients with and without RRT. Breast cancer surgery in patients with RRT may be as safe as that in patients without RRT, if comorbidities other than chronic renal failure are adequately addressed.
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http://dx.doi.org/10.1007/s12282-021-01248-7DOI Listing
April 2021

Outcomes of Nonoperative Treatment for Gastroduodenal Ulcer Perforation: a Nationwide Study of 14,918 Inpatients in Japan.

J Gastrointest Surg 2021 Apr 6. Epub 2021 Apr 6.

Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Gastroduodenal ulcer perforation is a common abdominal emergency that may be curable without surgical repair in non-elderly patients with localized and stable symptoms. However, the outcomes of nonoperative approaches have rarely been described.

Methods: Using a Japanese national inpatient database, we identified 14,918 patients with gastroduodenal ulcer perforation who were hospitalized and received nonoperative treatment from July 2010 to March 2017. We categorized these patients into three groups according to age: 18 to 64 years (young group, n=8407), 65 to 74 years (old group, n=2616), and ≥75 years (old-old group, n=3895). We investigated the characteristics, treatments, and outcomes in each group.

Results: Most of the patients were men (71%), and the median patient age was 62 years (interquartile range, 47-75 years). The old and old-old groups had more comorbidities than the young group. Whereas most patients were administered proton pump inhibitors and various antibiotics (96% and 90%, respectively), only 58% of patients underwent gastric tube placement. Surgical repair >3 days after admission was performed in 7.1% of all patients (6.3% vs. 7.9% vs. 5.5%, P<0.001). The old and old-old groups showed higher mortality (1.4% vs. 8.3% vs. 18%, P<0.001) and morbidity (6.6% vs. 15% vs. 17%, P<0.001) than the young group. The median length of stay was almost 2 weeks (13 vs. 17 vs. 20 days, P<0.001).

Discussion: Unlike previous studies, many patients aged >65 years received nonoperative treatment in this nationwide cohort. Our findings provide useful information for clinicians and patients hospitalized for gastric ulcer perforation.
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http://dx.doi.org/10.1007/s11605-021-05003-3DOI Listing
April 2021

Characteristics and Outcomes of Super-Elderly Patients (Aged ≥90 Years) Hospitalized for Heart Failure - Analysis of a Nationwide Inpatient Database.

Circ Rep 2020 Jul 7;2(8):393-399. Epub 2020 Jul 7.

Department of Cardiovascular Medicine, The University of Tokyo Tokyo Japan.

Although the aged population is increasing in developed countries, clinical evidence on super-elderly heart failure (HF) patients is scarce. This study determined the characteristics and outcomes of Japanese hospitalized super-elderly HF patients (aged ≥90 years) using a nationwide inpatient database. A comprehensive analysis was performed of 447,818 HF patients in the Diagnosis Procedure Combination database who were hospitalized and discharged between January 2010 and March 2018. Among the study population, 243,028 patients (54.3%) were aged ≥80 years and 64,628 patients (14.4%) were aged ≥90 years. The percentage of elderly patients increased over time. Elderly patients were more likely to be female and had a higher New York Heart Association functional class at admission. Invasive and advanced procedures were rarely performed, whereas infectious complications were more common in patients with older age. Length of hospital stay and in-hospital mortality increased with age. Multivariable logistic regression analysis fitted with a generalized estimating equation showed higher in-hospital mortality in patients aged ≥80 and ≥90 years (odds ratios 1.99 and 3.23, respectively) compared with those aged <80 years. The number of hospitalized super-elderly HF patients has increased, and these patients are associated with worse clinical outcomes. The results of this study may be useful in establishing an optimal management strategy for super-elderly HF patients in the era of HF pandemic.
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http://dx.doi.org/10.1253/circrep.CR-20-0053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819647PMC
July 2020

Transcatheter Aortic Valve Implantation and Surgical Aortic Valve Replacement for Aortic Stenosis in Japan - Analysis of a Nationwide Inpatient Database.

Circ Rep 2020 Dec 1;2(12):753-758. Epub 2020 Dec 1.

Department of Cardiovascular Medicine, The University of Tokyo Tokyo Japan.

Nationwide data on transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) in Japan are scarce. Using a nationwide inpatient database, we analyzed patients undergoing TAVI (n=8,338) or SAVR (n=16,298) due to aortic stenosis between 2014 and 2017. The annual number of TAVI increased rapidly from 2014 to 2017, particularly in older patients. In-hospital deaths were lower and the length of hospital stay was shorter for patients undergoing TAVI than SAVR. TAVI has been penetrating in Japan as an alternative therapeutic option for aortic stenosis and is associated with acceptable clinical outcomes.
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http://dx.doi.org/10.1253/circrep.CR-20-0116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937519PMC
December 2020

Initial symptoms and diagnostic delay in children with brain tumors at a single institution in Japan.

Neurooncol Pract 2021 Feb 6;8(1):60-67. Epub 2020 Oct 6.

Center for Postgraduate Education and Training, National Center for Child Health and Development, Tokyo, Japan.

Background: A prolonged interval between onset of symptoms and diagnosis of childhood brain tumor is associated with worse neurological outcomes. The objectives of this study are to determine factors contributing to diagnostic delay and to find an interventional focus for further reduction in the interval between symptom onset and diagnosis in Japan.

Methods: We retrospectively analyzed 154 patients younger than 18 years with newly diagnosed brain tumors who visited our institution from January 2002 to March 2013.

Results: The median age at diagnosis was 6.2 years and the median total diagnostic interval (TDI) was 30 days. Patients with low-grade tumors and cerebral midline tumor location had significantly long TDI. Durations between the first medical consultation and diagnosis (diagnostic interval, DI) were exceedingly longer for patients with visual, hearing, or smelling abnormalities as the first symptom (median, 303 days). TDI and DI of patients who visited ophthalmologists or otolaryngologist for the first medical consultation were significantly longer. Among these patients, longer DI was associated with worse visual outcome.

Conclusion: Raising awareness of brain tumor diagnosis among ophthalmologists and otolaryngologists may reduce diagnostic delay and may improve the neurological impairment of children with brain tumors in Japan.
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http://dx.doi.org/10.1093/nop/npaa062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906264PMC
February 2021

Association of Hospital Procedural Volume With Outcomes of Percutaneous Left Atrial Appendage Occlusion.

JACC Cardiovasc Interv 2021 Mar 1;14(5):554-561. Epub 2021 Mar 1.

Division of Cardiology, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio, USA. Electronic address:

Objectives: The aim of this study was to examine the association between percutaneous left atrial appendage occlusion (LAAO) procedural volume and in-hospital outcomes.

Background: Several studies have demonstrated an inverse volume-outcome relationship for patients undergoing invasive cardiac procedures. Whether a similar association exists for percutaneous LAAO remains unknown.

Methods: Patients undergoing LAAO in 2017 were identified in the Nationwide Readmissions Database. Hospitals were categorized into 3 groups on the basis of tertiles of annual procedural volume: low (5 to 15 cases/year), medium (17 to 31 cases/year), and high (32 to 211 cases/year). Multivariate hierarchical logistic regression and restricted cubic spline analyses were performed to examine the association of hospital LAAO volume and outcomes. The primary outcome was in-hospital major adverse events (MAE), defined as a composite of mortality, stroke or transient ischemic attack, bleeding or transfusion, vascular complications, myocardial infarction, systemic embolization, and pericardial effusion or tamponade requiring pericardiocentesis or surgery.

Results: This study included 5,949 LAAO procedures performed across 196 hospitals with a median annual procedural volume of 41 (interquartile range: 25 to 67). Low-volume hospitals had higher rates of in-hospital MAE (9.5% vs. 5.6%; p < 0.001), stroke or transient ischemic attack (2.1% vs. 1.3%; p = 0.049), and bleeding or transfusion (6.1% vs. 3.5%; p = 0.002) compared with high-volume hospitals. No differences were noted for other components of MAE and index length of stay. On multivariate analysis, higher procedural volume was associated with lower rates of in-hospital MAE, with an adjusted odds ratio for medium versus low volume of 0.69 (95% confidence interval: 0.46 to 1.04; p = 0.08) and for high versus low volume of 0.55 (95% confidence interval: 0.37 to 0.82; p = 0.003).

Conclusions: Higher hospital procedural volume is associated with better outcomes for LAAO procedures. Further studies are needed to determine if this relationship persists for long-term outcomes.
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http://dx.doi.org/10.1016/j.jcin.2020.11.029DOI Listing
March 2021

Predictors of performance on the pediatric board certification examination.

BMC Med Educ 2021 Feb 22;21(1):122. Epub 2021 Feb 22.

Center for Postgraduate Education and Training, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, Japan.

Background: Examining the predictors of summative assessment performance is important for improving educational programs and structuring appropriate learning environments for trainees. However, predictors of certification examination performance in pediatric postgraduate education have not been comprehensively investigated in Japan.

Methods: The Pediatric Board Examination database in Japan, which includes 1578 postgraduate trainees from 2015 to 2016, was analyzed. The examinations included multiple-choice questions (MCQs), case summary reports, and an interview, and the predictors for each of these components were investigated by multiple regression analysis.

Results: The number of examination attempts and the training duration were significant negative predictors of the scores for the MCQ, case summary, and interview. Employment at a community hospital or private university hospital were negative predictors of the MCQ and case summary score, respectively. Female sex and the number of academic presentations positively predicted the case summary and interview scores. The number of research publications was a positive predictor of the MCQ score, and employment at a community hospital was a positive predictor of the case summary score.

Conclusion: This study found that delayed and repeated examination taking were negative predictors, while the scholarly activity of trainees was a positive predictor, of pediatric board certification examination performance.
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http://dx.doi.org/10.1186/s12909-021-02515-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898761PMC
February 2021

Possible association between eating behaviors and cardiovascular disease in the general population: Analysis of a nationwide epidemiological database.

Atherosclerosis 2021 03 27;320:79-85. Epub 2021 Jan 27.

The Department of Cardiovascular Medicine, The University of Tokyo, Japan.

Background And Aims: Epidemiological evidence on the relationship between eating behaviors, including breakfast skipping, late night dinner, and bedtime snacking, and cardiovascular disease (CVD) events among the general population is scarce. We sought to explore the association of eating behaviors with subsequent CVD using a nationwide epidemiological database.

Methods And Results: Medical records of 1,941,125 individuals without prior history of CVD were extracted from the Japan Medical Data Center contracting with more than 60 insurers from multiple regions in Japan, mainly including employed working-age individuals. Skipping breakfast <3 times per week, late night dinner <3 times per week, and bedtime snacking <3 times per week were defined as optimal eating behaviors. Median age was 45 (interquartile range 39-53) years, and 1,138,676 were men. Median follow-up period was 978 (interquartile range 481-1790) days. Among them, 948,805 individuals (48.9%) had optimal eating behaviors, whereas 647,383 individuals (33.4%), 283,017 individuals (14.6%), and 61,920 individuals (3.2%) had single, double, and triple non-optimal eating behaviors, respectively. Individuals with non-optimal eating behaviors were younger and more likely to be men. Obesity and high waist circumference were more commonly observed in those with non-optimal eating behaviors. Multivariable Cox regression analysis showed that, compared with no non-optimal eating behavior, having non-optimal eating behaviors would have higher risk of myocardial infarction, angina pectoris, stroke, and heart failure. However, the dose-response relationship was not clear in the association between the number of non-optimal eating behaviors and incident CVD. Multivariable Cox regression analysis after multiple imputation for missing values also showed the association between non-optimal eating behaviors and incident CVD.

Conclusions: Using a nationwide epidemiological database, we found a possible relationship between eating behaviors including skipping breakfast, late night dinner, and bedtime snacking, and subsequent cardiovascular events among the general population, suggesting the potential importance of maintaining optimal eating behaviors for the primordial and primary CVD prevention in the general population.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.01.022DOI Listing
March 2021

Metabolically Healthy Obesity and the Risk of Cardiovascular Disease in the General Population - Analysis of a Nationwide Epidemiological Database.

Circ J 2021 May 5;85(6):914-920. Epub 2021 Feb 5.

Department of Cardiovascular Medicine, The University of Tokyo.

Background: Obesity and metabolic disorders frequently coexist, and both are established risk factors for cardiovascular disease (CVD). Although the phenotype of obesity without metabolic disorders, referred to as metabolically healthy obesity (MHO), is attracting clinical interest, the pathophysiological impact of MHO remains unclear.Methods and Results:Using the Japan Medical Data Center database, we studied 802,288 subjects aged ≥20 years without any metabolic disorders or a prior history of CVD. MHO, defined as obesity (body mass index ≥25 kg/m) with no metabolic disorders, was observed in 9.8% of the study population. The subjects' mean (±SD) age was 42.8±9.4 years and 44.7% were men. The mean follow-up period was 1,126±849 days. Multivariable Cox regression analysis showed that MHO alone did not significantly increase the risk of any CVD. However, abdominal obesity alone increased the risk of heart failure and atrial fibrillation. Moreover, the coexistence of MHO and abdominal obesity increased the risk of myocardial infarction, angina pectoris, heart failure, and atrial fibrillation. The incidence of stroke was not associated with the presence of MHO and abdominal obesity.

Conclusions: Among individuals with no metabolic disorders, MHO alone did not significantly increase the subsequent CVD risk. However, individuals with comorbid MHO and abdominal obesity had a higher risk of myocardial infarction, angina pectoris, heart failure, and atrial fibrillation, suggesting the prognostic importance of abdominal obesity in subjects with MHO.
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http://dx.doi.org/10.1253/circj.CJ-20-1040DOI Listing
May 2021

Effect of the urgency and landing zone on rates of in-hospital death, stroke, and paraplegia after thoracic endovascular aortic repair in Japan.

J Vasc Surg 2021 Feb 4. Epub 2021 Feb 4.

Division of Vascular Surgery, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address:

Objective: The present study used data from the Japanese Committee for Stentgraft Management's national registry, which contains unique surgical data, including surgical timing, anatomic factors, and pathologic factors, to determine the generalized community experience with thoracic endovascular abdominal aortic repair (TEVAR).

Methods: The medical background and short-term outcomes were reviewed for patients who had undergone TEVAR for a thoracic aortic aneurysm (TAA; 14,235 cases) or aortic dissection (AD; 990 type A and 4259 type B) from 2008 to 2015. TEVAR for AD was separated from that for TAAs; only the background and short-term outcomes were evaluated. The technical outcomes of TEVAR for TAA were also evaluated. All the cases were categorized as follows: elective, urgent (within 24 hours after admission), or emergent (immediately after admission). The outcomes included in-hospital mortality and persistent stroke and paraplegia diagnosed at discharge. The number of debranching bypasses, proximal landing zone (0, 1, 2, ≥3), and zone length were included in the logistic regression analysis.

Results: The mortality, stroke, and paraplegia rates in the TAA and AD groups were 4.4%, 4.6%, and 3.7% and 4.0%, 2.9%, and 2.8%, respectively. After analyzing the TAA cohort, we found that urgent and emergent cases were associated with all adverse outcomes. The rate of paraplegia increased drastically in the patients with stent graft coverage that extended for six or more zones. Massive atheroma was associated with stroke and paraplegia. The cumulative survival rate of the TAA group was stratified by the urgency (ie, elective, urgent, emergent; P < .001). We found that the more proximal (0, 1, and 2) the landing zone, the greater the risk of stroke. Likewise, the longer (six or more zones) the coverage, the greater the risk of paraplegia.

Conclusions: Urgency was strongly associated with mortality, stroke, and paraplegia, and the classification of urgent and emergent, according to the surgical timing after admission, successfully stratified the population in the long-term overall survival analysis. A proximal landing zone involving the aortic arch and debranching bypasses were associated with the occurrence of stroke, and the length of stent graft coverage for six or more zones was associated with paraplegia. Identifying these risk factors will help operators of TEVAR develop appropriate operative strategies to mitigate patient risk.
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http://dx.doi.org/10.1016/j.jvs.2020.12.091DOI Listing
February 2021

Impact of hospital volume on clinical outcomes of hospitalized heart failure patients: analysis of a nationwide database including 447,818 patients with heart failure.

BMC Cardiovasc Disord 2021 01 25;21(1):49. Epub 2021 Jan 25.

The Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Hospital volume is known to be associated with outcomes of patients requiring complicated medical care. However, the relationship between hospital volume and prognosis of hospitalized patients with heart failure (HF) remains not fully understood. We aimed to clarify the impact of hospital volume on clinical outcomes of hospitalized HF patients using a nationwide inpatient database.

Methods And Results: We studied 447,818 hospitalized HF patients who were admitted from January 2010 and discharged until March 2018 included in the Japanese Diagnosis Procedure Combination database. According to the number of patients, patients were categorized into three groups; those treated in low-, medium-, and high-volume centers. The median age was 81 years and 238,192 patients (53%) were men. Patients who had New York Heart Association class IV symptom and requiring inotropic agent within two days were more common in high volume centers than in low volume centers. Respiratory support, hemodialysis, and intra-aortic balloon pumping were more frequently performed in high volume centers. As a result, length of hospital stay was shorter, and in-hospital mortality was lower in high volume centers. Lower in-hospital mortality was associated with higher hospital volume. Multivariable logistic regression analysis fitted with generalized estimating equation indicated that medium-volume group (Odds ratio 0.91, p = 0.035) and high-volume group (Odds ratio 0.86, p = 0.004) had lower in-hospital mortality compared to the low-volume group. Subgroup analysis showed that this association between hospital volume and in-hospital mortality among overall population was seen in all subgroups according to age, presence of chronic renal failure, and New York Heart Association class.

Conclusion: Hospital volume was independently associated with ameliorated clinical outcomes of hospitalized patients with HF.
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http://dx.doi.org/10.1186/s12872-021-01863-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836495PMC
January 2021

Potassium Concentration in Initial Fluid Therapy and In-Hospital Mortality of Patients with Diabetic Ketoacidosis.

J Clin Endocrinol Metab 2021 Apr;106(5):e2162-e2175

Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Context: Guidelines worldwide recommend potassium replacement of 10 to 40 mmol/L in the initial fluid therapy for patients with diabetic ketoacidosis. However, evidence is lacking as to the association between infused potassium concentration and mortality.

Objective: We aimed to determine the association between infused potassium concentration and in-hospital mortality.

Methods: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified inpatients admitted for treatment of diabetic ketoacidosis from July 2010 to March 2018. Patients with kidney dysfunction or serum potassium abnormalities were excluded. We evaluated the association of the potassium concentration in the total infused solutions in the first 2 days of hospitalization with 28-day in-hospital mortality using multivariable regression analysis with a cubic spline model. We also assessed the association between potassium concentration and occurrence of hyperkalemia.

Results: We identified 14 216 patients with diabetic ketoacidosis and observed 261 deaths. The quartile cut-points for potassium concentration were 7.7, 11.4, and 16.1 mmol/L. Within the range of approximately 10 to 40 mmol/L, potassium concentration was not associated with occurrence of hyperkalemia or death. Lower potassium concentrations were associated with higher 28-day in-hospital mortality; the odds ratio for patients receiving 8 mmol/L was 1.69 (95% CI, 1.03 to 2.78; reference: 20 mmol/L), and the odds ratio increased monotonically as potassium concentration decreased further.

Conclusion: Patients receiving potassium replacement at concentrations of 10 to 40 mmol/L had similar in-hospital mortality rates, whereas lower concentrations were associated with higher mortality.
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http://dx.doi.org/10.1210/clinem/dgab029DOI Listing
April 2021

Fasting plasma glucose and subsequent cardiovascular disease among young adults: Analysis of a nationwide epidemiological database.

Atherosclerosis 2021 02 16;319:35-41. Epub 2021 Jan 16.

The Department of Cardiovascular Medicine, The University of Tokyo, Japan.

Background And Aims: Using a nationwide epidemiological database, we aimed to clarify the association of fasting plasma glucose (FPG) with subsequent cardiovascular disease (CVD) risk among young adults.

Methods And Results: Medical records of 1,180,062 young adults (20-49 years old) without a prior history of CVD and who were not taking antidiabetic medications were extracted from the Japan Medical Data Center. We categorized the study population into four groups: normal, FPG level<100 mg/dL (1,007,747 individuals), normal-high, FPG level of 100-109 mg/dL (126,602 individuals), impaired fasting glucose (IFG), FPG level of 110-125 mg/dL (32,451 individuals), and diabetes mellitus (DM), FPG level ≥126 mg/dL (13,262 individuals). The mean age was 39.7 ± 6.9 years, and 57.0% of the study population were men. Mean follow-up period was 1201 ± 905 days on average. Multivariable Cox regression analysis showed that IFG (hazard ratio [HR]; 1.38) and DM (HR; 2.09) increased the risk of myocardial infarction. Normal-high (HR; 1.11), IFG (HR; 1.18), and DM (HR; 1.59) groups had an elevated angina pectoris risk. DM (HR; 1.31) increased the risk of stroke compared to normal FPG levels. Normal-high levels (HR; 1.10), IFG (HR; 1.22) and DM (HR; 1.58) elevated the risk of heart failure. DM (HR; 1.69) increased the risk of atrial fibrillation.

Conclusions: Our analysis of a nationwide epidemiological database demonstrated a close association of the FPG category with subsequent CVD risk. Our results exemplify the importance of optimal FPG maintenance for the primary prevention of CVD in young adults.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.12.024DOI Listing
February 2021

Association between nutritional guidance or ophthalmological examination and discontinuation of physician visits in patients with newly diagnosed diabetes: A retrospective cohort study using a nationwide database.

J Diabetes Investig 2021 Jan 18. Epub 2021 Jan 18.

Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Aims/introduction: Discontinuation of diabetes care has been studied mostly in patients with prevalent diabetes and not in patients with newly diagnosed diabetes, whose dropout risk is highest. Because enrolling patients in a prospective study will influence adherence, we retrospectively examined whether guideline-recommended practices, defined as nutritional guidance or ophthalmological examination, can prevent patient discontinuation of diabetes care after its initiation.

Materials And Methods: We retrospectively identified adults with newly screened diabetes during checkups using a large Japanese administrative claims database (JMDC, Tokyo, Japan) that contains laboratory data and lifestyle questionnaires. We defined discontinuation of physician visits as a follow-up interval exceeding 6 months. We divided the patients into those who received guideline-recommended practices (nutritional guidance or ophthalmology consultation) within the same month as the first visit and those who did not. We calculated propensity scores and carried out inverse probability of treatment weighting analyses to compare discontinuation between the two groups.

Results: We identified 6,508 patients with at least one physician consultation for diabetes care within 3 months after their checkup, including 4,574 patients without and 1,934 with guideline-recommended practices. After inverse probability of treatment weighting, patients with guideline-recommended practices had a significantly lower proportion of discontinuation than those without (17.2% vs 21.8%; relative risk 0.79, 95% confidence interval 0.69-0.91).

Conclusions: This study is the first to show that after adjustment for both patient and healthcare provider factors, guideline-recommended practices within the first month of physician consultation for diabetes care can decrease subsequent discontinuation of physician visits in patients with newly diagnosed diabetes.
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http://dx.doi.org/10.1111/jdi.13510DOI Listing
January 2021

Early Initiation of Feeding and In-Hospital Outcomes in Patients Hospitalized for Acute Heart Failure.

Am J Cardiol 2021 04 14;145:85-90. Epub 2021 Jan 14.

The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

Extensive data on early nutrition support for patients requiring critical care are available. However, whether early initiation of feeding could be beneficial for patients hospitalized for acute heart failure (HF) remains unclear. We sought to compare outcomes of early and delayed initiation of feeding for hospitalized patients with acute HF using a nationwide inpatient database. We retrospectively analyzed data from the Diagnosis Procedure Combination database. We included patients hospitalized for HF between January 2010 and March 2018. We excluded patients with length of hospital stay ≤2 days, those patients who underwent major procedures under general anesthesia, and those requiring advanced mechanical supports within 2 days after admission including intubation, intra-aortic balloon pumping, and extracorporeal membrane oxygenation. Propensity score matching and instrumental variable analyses were conducted to compare in-hospital mortality, complications and length of stay between the early and delayed feeding groups. Among 432,620 eligible patients, 403,442 patients (93%) received early initiation of feeding (within 2 days after admission) and 29,178 patients (7%) received delayed initiation of feeding. Propensity score matching created 29,153 pairs and delayed initiation of feeding was associated with higher in-hospital mortality (odds ratio 1.32; 95% confidence interval 1.26 to 1.39), longer hospital stay and higher incidence of pneumonia and sepsis. The instrumental variable analysis also showed patients with delayed initiation of feeding had higher in-hospital mortality (odds ratio 1.34; 95% confidence interval 1.28 to 1.40). In conclusion, our analysis suggested a potential benefit of early initiation of feeding for in-hospital outcomes in hospitalized patients hospitalized for acute HF. Further investigations are required to confirm our results and to clarify the underlying mechanisms.
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http://dx.doi.org/10.1016/j.amjcard.2020.12.082DOI Listing
April 2021

In-Hospital Complications After Surgery in Elderly Patients with Asymptomatic or Minor Symptom Meningioma: A Nationwide Registry Study.

World Neurosurg 2021 Apr 11;148:e459-e470. Epub 2021 Jan 11.

Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Background: Asymptomatic or minor symptom meningiomas (AMSMs) in the elderly are incidental findings, with no consensus reached on the optimal management strategy. In the present study, we aimed to determine the surgical risk factors for elderly patients with AMSMs using a nationwide registry database in Japan.

Methods: We identified patients with surgically treated AMSMs using the Diagnosis Procedure Combination database from 2010 to 2015 and reviewed the medical records for age (<65 years; pre-elderly, 65-74 years; and elderly, ≥75 years), sex, Barthel index (BI) score, medical history, tumor location, and complications. An AMSM was defined by a BI score of 100 points at admission. The risk factors for all stroke complications, BI deterioration at discharge, and in-hospital mortality were determined using multivariate logistic regression analyses.

Results: From a total of 10,535 patients with meningioma, 6628 were included. Advanced age was a significant risk factor (odds ratio, 3.54; 95% confidence interval, 2.80-4.46) for BI deterioration but not for all-stroke complications or in-hospital mortality. Midline and posterior fossa tumors, diabetes mellitus, and chronic heart disease were significant risk factors for in-hospital mortality.

Conclusions: For elderly patients with surgically treated AMSMs, advanced age was a prominent risk factor for functional decline at discharge. Our study identified several factors that should be evaluated before proceeding with surgery for AMSMs in elderly and pre-elderly patients. These findings could, not only improve decision-making among clinicians treating patients with AMSMs, but also help in predicting the results of surgery for elderly patients with AMSMs.
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http://dx.doi.org/10.1016/j.wneu.2021.01.001DOI Listing
April 2021

Comparison of short-term surgical outcomes between men and women with breast cancer: a retrospective study using nationwide inpatient data in Japan.

Breast Cancer Res Treat 2021 Apr 5;186(3):731-739. Epub 2021 Jan 5.

Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: Although long-term survival is similar between men and women, little is known about the short-term outcomes following breast cancer surgery in men. This study was performed to compare postoperative outcomes adjusted for background factors between men and women with breast cancer using a Japanese nationwide inpatient database.

Methods: This study included 2126 men and 363,468 women who underwent surgery for stage 0-III breast cancer from July 2010 to March 2017. We generated a 1:4 matched-pair cohort matched for age, institution, and fiscal year at admission. We then conducted multivariable regression analyses to compare postoperative complications, 30-day readmission, duration of anesthesia, length of hospitalization, and total hospitalization costs between the sexes.

Results: Men were older, more likely to have comorbidities and advanced cancer, and more likely to undergo total mastectomy and axillary dissection than women. There were no significant differences in postoperative complications between the sexes, but men showed a lower risk of 30-day readmission (odds ratio 0.74; 95% confidence interval [CI] 0.57-0.95), shorter duration of anesthesia (difference - 22.0 min; 95% CI - 2.1 to - 0.5), shorter length of hospitalization (difference - 1.3 days; 95% CI - 2.1 to - 0.5), and lower total hospitalization costs (difference - 506 US dollars; 95% CI - 668 to - 334) than women.

Conclusions: The matched-pair cohort analyses revealed no significant differences in postoperative complications between men and women with breast cancer. However, men showed better outcomes than women in terms of 30-day readmission, duration of anesthesia, length of hospitalization, and total hospitalization costs.
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http://dx.doi.org/10.1007/s10549-020-06069-4DOI Listing
April 2021

Association between ambulance use and hospitalization costs among heart failure patients.

Heart Vessels 2021 May 3;36(5):654-658. Epub 2021 Jan 3.

Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan.

Heart failure is the main cause of hospitalization, which burdens the healthcare system. Although many hospitalizations for heart failure follow ambulance use, it is unknown whether ambulance use increases hospitalization costs. Using the Diagnosis Procedure Combination database in Japan, we examined all hospitalizations of patients with heart failure from April 2014 to March 2015. Patients were divided into those with and those without ambulance use. We performed a multiple regression analysis to examine the association between ambulance use and total hospitalization costs, adjusting for age, sex, length of day, and activities of daily living. We identified 126,067 hospitalizations for heart failure. The percentages of ambulance use were 29%, 27%, 30%, and 50% among patients with NYHA Functional Classification I, II, III, and IV, respectively. For patients categorized as NYHA I (n = 9,700), multiple linear regression analysis revealed that ambulance use was significantly associated with higher hospitalization cost (coefficient 723 USD; 95% confidence interval 109-1337; p = 0.021). Even for heart failure patients with NYHA I, ambulances were frequently used. Ambulance use was independently associated with increased hospital costs. Future research is needed on transitional care to limit unnecessary ambulance use.
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http://dx.doi.org/10.1007/s00380-020-01732-8DOI Listing
May 2021

Comparing outcomes of nonoperative treatment for adhesive small bowel obstruction with and without antibiotics.

J Infect Chemother 2021 May 19;27(5):690-695. Epub 2020 Dec 19.

Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan.

Introduction: Some clinicians administer antibiotics in adhesive SBO treatment to prevent bacterial translocation without evidence confirming reduced sepsis and mortality. We aimed to evaluate the effectiveness of preventive antibiotic administration in nonoperative treatment of adhesive small bowel obstruction (SBO) in a retrospective study.

Methods: Using a Japanese national inpatient database, we identified 114,786 eligible patients with adhesive SBO and divided patients into a group who did not receive intravenous antibiotics in the initial 2 consecutive days after admission (control group, n = 71,666) and a group who received intravenous antibiotics ≥2 days after admission (antibiotic group, n = 43,120). To compare the in-hospital mortality, occurrence of sepsis, septic shock, Clostridioides difficile colitis, length of stay, and total costs between the two groups, we performed instrumental variable analyses to adjust for measured and unmeasured confounding factors.

Results: Overall, in-hospital mortality was 2.2%, and the occurrence of sepsis was 0.8%. In the instrumental variable analyses, no significant differences were found for in-hospital mortality, occurrence of sepsis, septic shock, Clostridioides difficile colitis, or total hospitalization costs. The antibiotic group showed a longer length of stay than the control group (coefficient, 1.9 days; 95% confidence interval, 0.6-3.2).

Conclusions: In this large nationwide cohort of patients with adhesive SBO, we found no benefit regarding preventive antibiotic administration in nonoperative treatment; however, antibiotic administration was associated with a longer hospital stay. These results did not support routine administration of antibiotics at admission to prevent bacterial translocation.
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http://dx.doi.org/10.1016/j.jiac.2020.12.005DOI Listing
May 2021

Lipid Profile and Subsequent Cardiovascular Disease among Young Adults Aged < 50 Years.

Am J Cardiol 2021 03 8;142:59-65. Epub 2020 Dec 8.

The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

Epidemiological evidence on the relationship between lipid profile and cardiovascular disease (CVD) events in young adults remains insufficient. Thus, we sought to explore the association of lipid profile with subsequent CVD among young adults. Medical records of 1,451,997 young adults (20 to 49 years old) without prior history of CVD and not taking lipid lowering medications were extracted from the Japan Medical Data Center, a nationwide epidemiological database. We conducted multivariable Cox regression analyses to identify the association between lipid profile and the subsequent risk of CVD and used multiple imputation for missing data on body mass index, waist circumference, hypertension, diabetes mellitus, and cigarette smoking in our database. The mean age was 39.0 ± 7.4 years, and 58.5% were men. After a mean follow-up of 1,148 ± 893 days, myocardial infarction, angina pectoris, stroke, and heart failure developed in 1,638 (0.1%), 15,887 (1.1%), 5,593 (0.4%), and 14,351 (1.0%) subjects, respectively. Multivariable Cox regression analyses including covariates after multiple imputation for missing values demonstrated that LDL-C ≥ 140 mg/dL, HDL-C < 40 mg/dL, and triglycerides ≥ 150 mg/dL were independently associated with the incidence of myocardial infarction, angina pectoris, and heart failure. However, they were not associated with the incidence of stroke. Multivariable Cox regression analyses including the number of abnormal lipid profiles and covariates showed that the incidence of myocardial infarction, angina, and heart failure increased stepwise with the number of abnormal lipid profiles. However, the number of abnormal lipid profiles was not associated with the subsequent risk of stroke. In conclusion, the comprehensive analysis of a nationwide epidemiological database demonstrated a close relationship between lipid profile and subsequent CVD, suggesting the importance of maintaining an optimal lipid profile for the primary prevention of CVD in young generations.
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http://dx.doi.org/10.1016/j.amjcard.2020.11.038DOI Listing
March 2021

Outcomes After Intensive Rehabilitation for Mechanically Ventilated Patients: A Nationwide Retrospective Cohort Study.

Arch Phys Med Rehabil 2021 02 22;102(2):280-289. Epub 2020 Oct 22.

Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan.

Objective: To examine the effects of intensive rehabilitation on mortality and liberation from mechanical ventilation among patients with mechanical ventilation in intensive care units.

Design: Retrospective cohort study using the Diagnosis Procedure Combination inpatient database.

Setting: Patients discharged from acute care hospitals from April 2010 to March 2016.

Participants: Patients (N=46,438) aged 20 years and older who were admitted to intensive care units and who started rehabilitation within 3 days of starting mechanical ventilation.

Intervention: Intensive rehabilitation in intensive care unit in the first 5 days after admission. Amount of rehabilitation was defined as the average number of units per day in the first 5 days after admission and was dichotomized as intensive (≥1.0 unit/d) or nonintensive (<1.0 unit/d) rehabilitation.

Main Outcome Measures: The primary outcome was in-hospital mortality. The secondary outcome was liberation from mechanical ventilation.

Results: We identified 29,982 eligible patients, including intensive (n=7745) and nonintensive (n=22,237) rehabilitation groups. In the propensity score-matched analysis, the intensive rehabilitation group had significantly lower in-hospital mortality (risk difference: -3.4%; 95% CI, -4.9% to -1.9%) and a higher proportion of liberation from mechanical ventilation (subdistribution hazard ratio, 1.08; 95% CI, 1.03-1.13) compared with the nonintensive rehabilitation group.

Conclusions: Patients receiving a higher amount of rehabilitation in intensive care units were less likely to die and more likely to be liberated from mechanical ventilation.
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http://dx.doi.org/10.1016/j.apmr.2020.09.389DOI Listing
February 2021

Serial Changes in Clinical Presentations and Outcomes of 5,740 Patients Requiring Repeated Hospital Admissions (Four or More Times) due to Worsened Heart Failure.

Int Heart J 2020 Nov 13;61(6):1253-1257. Epub 2020 Nov 13.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo.

Heart failure (HF) is a major cause of death and hospitalization worldwide. In particular, hospital readmission due to worsened HF occurs frequently after the onset of HF. However, the association of repeated hospital admission with clinical manifestations and outcomes is unclear. The aim of this study was to clarify the serial changes in presentation and clinical course of patients requiring repeated hospital admission due to worsened HF. Among 466,921 patients who were admitted and discharged between January 2010 and March 2018, with the main discharge diagnosis of HF, we studied 5,740 patients who were hospitalized 4 times or more, using the Diagnosis Procedure Combination database. We evaluated serial changes in continuous data using the Jonckheere trend test, and categorical data using the Cochran-Armitage trend test. The median age of the patients was 78 years, and 3,326 patients (58%) were male. Body mass index and Barthel Index decreased with increased numbers of admissions. Patients requiring respiratory support and hemodialysis increased, whereas patients undergoing intra-aortic balloon pumping decreased with increased numbers of admissions. The length of hospital stay was prolonged and the interval between hospitalizations was shortened with increased numbers of hospital admissions. The in-hospital mortality rate was 8.8% at the fourth admission. In conclusion, this is the first large-scale real-world study on the serial changes in characteristics and outcomes of HF patients requiring repeated hospitalization, suggesting that repeated hospitalization might adversely affect the general status of patients with HF and result in a vicious clinical cycle.
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http://dx.doi.org/10.1536/ihj.20-441DOI Listing
November 2020

Effect of Japanese herbal Kampo medicines on live birth rate in women with recurrent pregnancy loss.

Int J Gynaecol Obstet 2021 Jun 8;153(3):489-495. Epub 2020 Dec 8.

Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan.

Objective: To determine the effectiveness of Japanese Kampo medicines on the overall live birth rate among patients with recurrent pregnancy loss (RPL) in a real-world setting.

Methods: In the current retrospective cohort study, we used the JMDC Claims Database to extract information on women diagnosed with RPL between January 1, 2005 and August 31, 2018. Eligible women were divided into two groups according to Kampo medicines administered as treatments for RPL. The primary outcome was the live birth rate during the study period. Propensity score matching, Kaplan-Meier cumulative incidence plots, log-rank test, and Cox proportional-hazards regression model were used to compare the primary outcome between patients with and without Japanese herbal Kampo medicines.

Results: Among 5517 eligible patients, 1652 used Kampo medicines and 3865 did not. After propensity score matching, the live birth rate at 2.0 years was 15.7% in the Kampo group and 11.2% in the non-Kampo group. At 4.0 years, the difference between the two groups had slightly increased. The overall live birth rate differed significantly between the two groups (hazard ratio 1.32, 95% confidence interval 1.13-1.53; P < 0.001).

Conclusion: Japanese herbal Kampo medicines may improve the live birth rate in patients with RPL.
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http://dx.doi.org/10.1002/ijgo.13477DOI Listing
June 2021