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Background: Immune-related adverse events (irAEs) in patients treated with immune check inhibitors are associated with favourable response rate and survivals in multiple cancers, including renal cell carcinoma (RCC). The aim of this study was to investigate how irAEs were associated with improved survivals in advanced RCC patients treated with nivolumab plus ipilimumab. Materials and methods: This retrospective study included patients who received nivolumab plus ipilimumab between September 2018 and February 2022 at six centres. We assessed associations of the development and the number of irAEs with overall survival (OS) and progression-free survival (PFS). To eliminate immortal time bias, landmark analysis and a Cox model with time-dependent variables were used. Results: This study included 129 patients with a median follow-up of 12.3 months. The 2-year OS and PFS rates were 55% and 42%, respectively. Ninety six patients experienced irAEs. The development of irAEs was positively associated with OS and PFS rates (hazard ratio [HR] 0.328, 95% confidence interval [CI] 0.165–0.648, p = 0.001; HR 0.334, 95% CI 0.151–0.737, p = 0.007). Patients who experienced multiple irAEs had longer OS (HR 0.507, 95% CI 0.235–1.097, p = 0.085 or HR 0.245, 95% CI 0.110–0.544, p < 0.001) and PFS (HR 0.572, 95% CI 0.316–1.036, p = 0.085 or HR 0.267, 95% CI 0.113–0.628, p = 0.002) compared with those who experienced single or zero irAE. Conclusions: Developing irAEs, particularly multiple irAEs, is associated with favourable survivals in advanced RCC patients treated with nivolumab plus ipilimumab.

Nobutaka Hattori,1 Yoshiko Okada,2 Yayoi Kawata,3 Yoshihiko Furusawa,3 Takumi Imai,4 Hisako Yoshida,4 Mihoko Ota,3 Masaki Arai,3 Ayumi Shintani,4 Jovelle Fernandez3 1Department of Neurology, Juntendo University, Tokyo, Japan; 2Japan Parkinson Congress, Tokyo, Japan; 3Japan Medical Office, Takeda Pharmaceutical Company Limited, Tokyo, Japan; 4Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, JapanCorrespondence: Yoshihiko Furusawa, Japan Medical Office, Takeda Pharmaceutical Company Limited, 2 Chome-1-1 Nihonbashihoncho, Chuo City, Tokyo, 103-0023, Japan, Tel +81-3-3278-2111, Fax +81-3-3278-2000, Email yoshihiko.furusawa@takeda.comObjective: The coronavirus disease 2019 (COVID-19) pandemic changed the lives of patients with Parkinson’s disease (PD) and their caregivers. This study aimed to investigate changes in patient behavior and PD symptoms and their effect on caregiver burden resulting from the COVID-19 pandemic in Japan.Methods: This nationwide, observational, cross-sectional survey included patients with self-reported PD and caregivers (members of the Japan Parkinson’s Disease Association). The primary objective was to evaluate changes in behaviors, self-assessed PD symptoms, and caregiver burden from pre–COVID-19 (February 2020) to post–national state of emergency (August 2020 and February 2021).Results: Responses from 1883 patients and 1382 caregivers from 7610 distributed surveys were analyzed. Mean (standard deviation) age of patients and caregivers was 71.6 (8.2) and 68.5 (11.4) years, respectively; 41.6% of patients had a Hoehn and Yahr (HY) scale of 3. Patients (> 40.0%) reported decreased frequency of going out. Most patients (> 70.0%) reported no change in treatment visit frequency, voluntary training, or rehabilitation and nursing care insurance services. Symptoms worsened for approximately 7– 30% of patients; the proportion with HY scale 4– 5 increased from pre–COVID-19 (25.2%) to February 2021 (40.1%). Aggravated symptoms included bradykinesia, walking, gait speed, depressed mood, fatigue, and apathy. Caregivers’ burden increased because of patients’ worsened symptoms and reduced time going out.Conclusion: Control measures during infectious disease epidemics should consider that patients’ symptoms may worsen; therefore, patient and caregiver support is needed to reduce burden of care.Keywords: Parkinson’s disease, COVID-19, questionnaire design, caregiver burden

Background Human cytomegalovirus (HCMV) reactivation occurs in immunosuppressed individuals and is known to increase mortality. Although patients with coronavirus disease 2019 (COVID-19) are often associated with steroid use and intensive care unit (ICU) treatment and may be at risk for comorbid HCMV reactivation, there are still insufficient studies. This study aimed to examine the incidence and potential risk factors of HCMV infection in patients with severe COVID-19 and evaluate the relationship between HCMV infection and mortality. Methods We used administrative claims data from advanced treatment hospitals in Japan to identify and analyze patients with severe or critical COVID-19. We explored potential risk factors for HCMV infection using multivariable regression models and its contribution to mortality in patients with COVID-19. Results Overall, 33,151 patients who progressed to severe or critical COVID-19 illness were identified. The incidence of HCMV infection was 0.3–1.7%. Steroids, immunosuppressants, ICU admission, and blood transfusion were strongly associated with HCMV reactivation. Furthermore, HCMV reactivation was associated with patient mortality independent of the observed risk factors for death. Conclusions HCMV infection is a notable complication in patients with COVID-19 receiving steroids, immunosuppressants, ICU admission, and blood transfusion, and it can significantly increase mortality risk.

BACKGROUND The proportion of adult patients with return of spontaneous circulation (ROSC) following out-of-hospital cardiac arrest (OHCA) remains unchanged since 2012. A better resuscitation strategy is needed. This study evaluated the effectiveness of a regional cerebral oxygen saturation (rSO2)-guided resuscitation protocol without rhythm check based on our previous study. METHODS Because defibrillation is the definitive therapy that should be performed without delay for shockable rhythm, the study subjects were OHCA patients with non-shockable rhythm on hospital arrival at three emergency departments. They were divided into three groups based on their baseline rSO2 value (%): ≥50, ≥40 to

Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Stem cell source or HLA disparity may exert a significant impact on the overall survival (OS) after the development of aGVHD. In order to clarify this point, we performed a retrospective analysis using a database of the Japan Society for HCT. We analyzed the clinical outcomes of 10,035 patients who developed grade II-IV aGVHD. The median age of the patients was 48 years. The probability of 2-year OS after the onset of grade II-IV aGVHD in the study cohort was 54.1%. The multivariate analysis showed that the HLA ≥2-loci mismatched related donor and HLA 1-locus mismatched unrelated donor were significantly associated with an inferior OS after grade II-IV aGVHD. In a subgroup analysis, peripheral blood stem cells and HLA disparity were associated with an inferior OS in patients who received related or unrelated HCT. Thus, the clinical outcome after grade II-IV aGVHD significantly varied as per the combination of the presence of HLA disparity and stem cell source. Further research using other databases is necessary to confirm our findings.

Introduction: In patients requiring both hemodialysis (HD) and apheresis, the 2 treatments can be performed simultaneously. At our hospital, selective plasma exchange (SePE) is often performed along with HD for removal of isoagglutinins before ABO-incompatible (ABOi) kidney transplantation. The 2 treatments can be completed within the HD schedule, which allows the treatment time to be shortened. This approach is also less stressful for patients because fewer punctures are required. In this study, we investigated the safety and efficacy of tandem HD and SePE. Methods: A total of 58 SePE sessions in 30 ABOi kidney transplant recipients were investigated. The SePE circuit was connected in parallel with the HD circuit, and tandem HD and SePE therapy was performed using filtration methods. The SePE sessions were divided into 2 groups: those with SePE monotherapy (group S, n = 20) and those with tandem therapy (group T, n = 38). Changes in transmembrane pressure (TMP), arterial pressure (AP), venous pressure (VP), and decrease in isoagglutinin titers over time were compared between the groups with adjustment for background data. Results: The internal pressures (AP and VP) were higher in group T, and there were significant differences in changes of TMP and AP over time between groups T and S. Membrane exchange was required in 1 case in group T due to coagulation. There was a more significant decrease of immunoglobulin G isoagglutinin titers in group T compared to group S. No case had antibody-mediated rejection after transplantation. Discussion/Conclusion: In HD/SePE tandem therapy, internal pressures were higher and TMP and AP tended to increase more compared to SePE monotherapy, but we were able to perform the 2 treatments without any functional problems. Tandem therapy was also effective in decreasing isoagglutinin titers, which suggests that this may be a beneficial treatment modality as apheresis before ABOi kidney transplantation.

Introduction Several clinical studies have reported the efficacy of favipiravir in reducing viral load and shortening the duration of symptoms. However, the viability of SARS-CoV-2 in the context of favipiravir therapy and the potential for resistance development is unclear. Methods We sequenced SARS-CoV-2 in nasopharyngeal specimens collected from patients who participated in a randomized clinical trial of favipiravir at hospitals across Japan between March and May 2020. Paired genomes were sequenced from those who remained RT-PCR-positive 5–8 days into favipiravir therapy. Daily nasopharyngeal specimens from 69 patients who were RT-PCR-positive at randomization were examined for a cytopathic effect (CPE). Results Some strains early in the trial belonged to clade 19 B, whereas the majority belonged to clade 20 B. The median time from the disease onset to negative CPE was 9 days. CPE was strongly correlated with the time from disease onset, viral load, age, and male sex. Among 23 patients for whom paired genomes were available, all except one had identical genomes. Two mutations were observed in one patient who received favipiravir, neither in the RdRp gene. Conclusions The SARS-CoV-2 genome distribution in this clinical trial conducted in Japan reflected the early influx of strains from China followed by replacement by strains from Europe. CPE was significantly associated with age, male sex, and viral loads but not with favipiravir therapy. There was no evidence of resistance development during favipiravir therapy.

Delta C-peptide derived by the glucagon stimulation test is a reliable value for the evaluation of the pancreatic endocrine function after pancreas transplantation. We examined the associations between delta C-peptide as pancreatic graft endocrine function and donor background factors.Sixty-five cases of pancreatic transplantation from brain-dead donors, which were performed in our facility, were enrolled in this study. Enrolled recipients underwent a glucagon stimulation test within 1 to 3 months after transplantation to evaluate the pancreatic graft endocrine function with delta C-peptide to compare donor background factors.The following factors were associated with significant deterioration of the delta C-peptide: age of 50 years or greater, death from cerebrovascular accident, hemoglobin A1c level of 5.6% or greater, creatinine level of 1.0 mg/dL or greater, C-reactive protein level of 25 mg/dL or greater, and sodium level of 150 mmol/L or greater. In addition, increased numbers of these donor factors indicated significantly greater deterioration of the posttransplant pancreatic endocrine function ( Plt; 0.001).To secure insulin independence after pancreas transplantation, which means maintaining a delta C-peptide level of 1.0 ng/mL or greater on a glucagon stimulation test, the utilization of donors, who possesses more than equal to 3 of the donor factors identified in this study, should be carefully considered.

The use of antiplatelet drugs is thought to increase the risk for intracerebral hemorrhage (ICH) in patients with cerebral microbleeds (CMBs). However, hemodialysis (HD) patients have a high prevalence of CMBs and diverse pathologies that require antiplatelet therapy. In this study, we investigated whether the use of antiplatelet drugs increases the risk for ICH in HD patients with CMBs. Brain magnetic resonance imaging (MRI), including T2*-weighted MRI, was performed in 179 HD patients with no history of cerebrovascular events. CMBs were detected and patients were followed prospectively with a median follow-up period of 5.2 [1.4-6.2] years. To investigate whether the influence of antiplatelet therapy on the development of ICH differs in cases with and without CMBs, the inverse probability of treatment weighting method was used, including an interaction term between the presence or absence of CMBs and use of antiplatelet drugs. As a result, CMBs were detected in 45 patients (25.1%), and antiplatelet drugs were used in 66 patients (36.9%). When the effect of antiplatelet therapy on the incidence of ICH was modified by the presence of CMBs at baseline (P for interaction0.001), the use of antiplatelet drugs was a significant risk factor for ICH in HD patients without CMBs, but not in HD patients with CMBs. Furthermore, the burden of CMBs significantly increased the risk for ICH, but the increase in this risk was slower in antiplatelet drug users as compared to non-antiplatelet drug users (P for interaction = 0.02). The influence of antiplatelet drugs on the development of ICH differed depending on the presence or absence of CMBs. In fact, the use of antiplatelet drugs did not increase the risk for ICH in HD patients with CMBs.

The ability of perioperative fluid management to prevent postoperative recurrence of atrial tachyarrhythmia remains controversial. The aim of the present study was to assess if intraoperative net fluid balance was associated with atrial tachyarrhythmia recurrence after the Cryo-Maze procedure.An observational cohort study.A tertiary care hospital from April 2007 to May 2019.Four hundred forty-four patients undergoing the Cryo-Maze procedure in conjunction with other cardiac surgeries.The Cryo-Maze procedure in conjunction with other cardiac surgeries.The main outcome was early atrial tachyarrhythmia recurrence, consisting of atrial fibrillation, atrial flutter, or atrial tachycardia, within the first three months after surgery. Complete follow-up was achieved in 443 patients (99.8%), of them 127 (28.6%) developed early atrial tachyarrhythmia recurrence. The median intraoperative net fluid balance was 1,627 mL (interquartile range, -215 to 3,557 mL). Multivariate logistic regression showed that intraoperative net fluid balance (p = 0.001), preoperative AF duration (adjusted odds ratio, 1.40; 95% CI, 1.17-1.68; p0.001) and left atrial volume index (aOR, 1.61; 95% CI, 1.06-2.45; p = 0.025) were independent predictors of early atrial tachyarrhythmia recurrence. The adjusted log odds were lowest (-1.52) when net fluid balance was 1,557 mL.There is a significant U-shaped association between intraoperative net fluid balance and early atrial tachyarrhythmia recurrence among patients undergoing the Cryo-Maze procedure.

Introduction: Chronic low back pain (CLBP) is a leading cause of disability, yet there is limited high-quality evidence to identify the most suitable pharmacological therapy. The purpose of this Japanese nationwide, multicenter, prospective study was to compare the effectiveness of four representative drug therapies―acetaminophen, celecoxib, loxoprofen, and a tramadol and acetaminophen (T+A) combination drug―to establish evidence for a drug of choice for CLBP. Methods: Patients with CLBP (N=471) received one of the four treatments and were evaluated, prospectively and comprehensively, once every month for six months using a visual analog scale (VAS) for LBP, the Japanese Orthopedic Association (JOA) score, the JOA Back Pain Evaluation Questionnaire (JOABPEQ), the Roland-Morris Disability Questionnaire (RDQ), the EuroQol five-dimensions three-levels (EQ-5D-3L), and the Short Form-8 item health survey (SF-8). We conducted multivariable linear regression analyses of the four drugs at 1 and 6 months after drug allocation. Differences with P

ObjectiveIstradefylline, a selective adenosine A2A receptor antagonist, is indicated in the US and Japan as adjunctive treatment to levodopa/decarboxylase inhibitors in adults with Parkinson’s disease (PD) experiencing OFF time. This study aimed to observe patterns of dose escalation of levodopa over time in patients initiated on istradefylline.MethodsUsing Japanese electronic health record data, interrupted time series analyses were used to compare levodopa daily dose (LDD, mg/day) gradients in patients before and after initiation of istradefylline. Data were analyzed by period relative to istradefylline initiation (Month 1): pre-istradefylline (Months -72 to 0), early istradefylline (Months 1 to 24), and late istradefylline (Months 25 to 72). Subgroup analyses included LDD before istradefylline initiation (ResultsThe analysis included 4026 patients; mean (SD) baseline LDD was 419.27 mg (174.19). Patients receiving ≥600 mg/day levodopa or not receiving MAO-BIs or COMTIs demonstrated a significant reduction in LDD increase gradient for pre-istradefylline vs late-phase istradefylline (≥600 mg/day levodopa, -6.259 mg/day each month, pConclusionsThis real-world analysis of Japanese prescription data indicated that slowing of LDD escalation was observed in patients initiated on istradefylline, particularly in those receiving ≥600 mg/day levodopa, suggesting istradefylline may slow progressive LDD increases. These findings suggest that initiating istradefylline before other levodopa-adjunctive therapies may mitigate LDD increases, potentially reducing occurrence or severity of levodopa-induced complications in long-term istradefylline treatment.

Background The gut microbiota are reported to be altered in critical illness. The pattern and impact of dysbiosis on prognosis has not been thoroughly investigated in the ICU setting. Aims We aimed to evaluate changes in the gut microbiota of ICU patients via 16S rRNA gene deep sequencing, assess the association of the changes with antibiotics use or disease severity, and explore the association of gut microbiota changes with ICU patient prognosis. Methods Seventy-one mechanically ventilated patients were included. Fecal samples were collected serially on days 1–2, 3–4, 5–7, 8–14, and thereafter when suitable. Microorganisms of the fecal samples were profiled by 16S rRNA gene deep sequencing. Results Proportions of the five major phyla in the feces were diverse in each patient at admission. Those of Bacteroidetes and Firmicutes especially converged and stabilized within the first week from admission with a reduction in α-diversity (p 8 or

Background To evaluate the effectiveness of the nurse-led alcohol guidance to control home blood pressure (HBP) in the morning among male patients with hypertension during outpatient visits. Methods We enrolled 53 male patients with an HBP of ≥135/85 mm Hg with excessive drinking (alcohol ≥210 g/week or ≥60 g/day habitually) among outpatients in a randomized trial. Patients were assigned to a nurse-led alcohol guidance intervention or to the control. The primary outcomes were the mean HBP of 5 consecutive days at 6 months and alcohol consumption. Results Twenty-eight and 25 patients were randomized to intervention and control groups, respectively (mean age; 62.7 years old and 64.5, respectively). At baseline, the groups were well balanced across most characteristics. At 6 months, the mean HBP was 131/82 mm Hg in the intervention group vs. 145/87 mm Hg in the control group (SBP Conclusions We confirmed the effectiveness of the nurse-led alcohol guidance to control the HBP in male patients with hypertension during outpatient visits. Public trials registry number UMIN000017454 (UMIN Clinical Trials Registry).

We investigated the relationship between trunk muscle mass and spinal pathologies by gender. This multicenter cross-sectional study included patients aged ≥ 30 years who visited a spinal outpatient clinic. Trunk and appendicular muscle mass were measured using bioelectrical impedance analysis. The Oswestry Disability Index (ODI), visual analog scale (VAS) score for low back pain, sagittal vertical axis (SVA), and EuroQol 5 Dimension (EQ5D) score were investigated to evaluate spinal pathology. The association between trunk muscle mass and these parameters was analyzed by gender using a non-linear regression model adjusted for patients’ demographics. We investigated the association between age and trunk muscle mass. We included 781 men and 957 women. Trunk muscle mass differed significantly between men and women, although it decreased with age after age 70 in both genders. Lower trunk muscle mass was significantly associated with ODI, SVA, and EQ5D score deterioration in both genders; its association with VAS was significant only in men. Most parameters deteriorated when trunk muscle mass was

BACKGROUND AND OBJECTIVES: Vitamin D receptor activators and calcimimetics (calcium-sensing receptor agonists) are two major options for medical treatment of secondary hyperparathyroidism. A higher serum calcification propensity (a shorter T(50) value) is a novel surrogate marker of calcification stress and mortality in patients with CKD. We tested a hypothesis that a calcimimetic agent etelcalcetide is more effective in increasing T(50) value than a vitamin D receptor activator maxacalcitol. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A randomized, multicenter, open-label, blinded end point trial with active control was conducted in patients with secondary hyperparathyroidism undergoing hemodialysis in Japan. Patients were randomly assigned to receive intravenous etelcalcetide 5 mg thrice weekly (etelcalcetide group) or intravenous maxacalcitol 5 or 10 µg thrice weekly (maxacalcitol group). The primary, secondary, and tertiary outcomes were changes in T(50) value, handgrip strength, and score of the Dementia Assessment Sheet for Community-Based Integrated Care System from baseline to 12 months, respectively. RESULTS: In total, 425 patients from 23 dialysis centers were screened for eligibility, 326 patients were randomized (etelcalcetide, n=167; control, n=159), and 321 were included in the intention-to-treat analysis (median age, 66 years; 113 women [35%]). The median (interquartile range) of T(50) value was changed from 116 minutes (interquartile range, 90–151) to 131 minutes (interquartile range, 102–176) in the maxacalcitol group, whereas it was changed from 123 minutes (interquartile range, 98–174) to 166 minutes (interquartile range, 127–218) in the etelcalcetide group. The increase in T(50) value was significantly greater in the etelcalcetide group (difference in change, 20 minutes; 95% confidence interval, 7 to 34 minutes; P=0.004). No significant between-group difference was found in the change in handgrip strength or in the Dementia Assessment Sheet for Community-Based Integrated Care System score. CONCLUSIONS: Etelcalcetide was more effective in increasing T(50) value than maxacalcitol among patients on hemodialysis with secondary hyperparathyroidism. There was no difference in handgrip strength or cognition between the two drugs. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: VICTORY; UMIN000030636 and jRCTs051180156

Aim Both oxidative stress and inflammation are involved in the pathogenesis of cardiovascular disease (CVD). The serum level of derivatives of reactive oxygen metabolites (d-ROMs) is a measure of the total amount of hydroperoxides serving as a marker of oxidative stress. We investigated whether d-ROMs could predict the clinical outcomes in hemodialysis patients and whether the associations of d-ROMs with the outcomes are independent of a marker of inflammation, C-reactive protein (CRP). Methods This was a prospective cohort study in hemodialysis patients. The key exposures were the serum levels of d-ROMs and CRP. The outcome measures were all-cause mortality and new CVD events. Results A total of 517 patients were analyzed. d-ROMs correlated positively with CRP. During follow-up for 5 years, 107 patients died, and 190 patients experienced new CVD events. In the Kaplan-Meier analyses, both higher d-ROMs and higher CRP levels predicted higher risks for mortality and CVD events. By Cox proportional-hazard regression analysis adjusted for potential confounders excluding CRP, d-ROMs exhibited a significant association with all-cause mortality, but this association was no longer significant after further adjustment for CRP. Using the same model, CRP exhibited a significant association with all-cause mortality, but this association was no longer significant after further adjustment for d-ROMs. When we analyzed new CVD events as the outcome, CRP was a significant predictor, whereas the level of d-ROMs was not. Conclusions Although d-ROMs predicted mortality and CVD events in unadjusted models, the associations of d-ROMs with these outcomes were not independent of CRP. Oxidative stress and inflammation appear to share common causal pathways.

Liberation from mechanical ventilation is of great importance owing to related complications from extended ventilation time. In this prospective multicenter study, we aimed to construct a versatile model for predicting extubation outcomes in critical care settings using obtainable physiological predictors. The study included patients who had been extubated after a successful 30 min spontaneous breathing trial (SBT). A multivariable logistic regression model was constructed to predict extubation outcomes (successful extubation without reintubation and uneventful extubation without reintubation or noninvasive respiratory support) using eight parameters: age, heart failure, respiratory disease, rapid shallow breathing index (RSBI), PaO2/FIO2, Glasgow Coma Scale score, fluid balance, and endotracheal suctioning episodes. Of 499 patients, 453 (90.8%) and 328 (65.7%) achieved successful and uneventful extubation, respectively. The areas under the curve for successful and uneventful extubation in the novel prediction model were 0.69 (95% confidence interval (CI), 0.62–0.77) and 0.70 (95% CI, 0.65–0.74), respectively, which were significantly higher than those in the conventional model solely using RSBI (0.58 (95% CI, 0.50–0.66) and 0.54 (95% CI, 0.49–0.60), p = 0.004 and

Background: The incidence of acute kidney injury (AKI) after open abdominal aortic aneurysm (AAA) repair is reportedly higher than the incidence after general surgery. Amino acid infusion has been shown to increase renal blood flow, thus protecting the kidneys. Therefore, we hypothesized that intraoperative amino acid infusion, which was used to maintain body temperature, is associated with a lower incidence of postoperative AKI. The aim of this study was to validate this hypothesis. Methods: In this retrospective, observational, single-center cohort study, we included patients who underwent open AAA repair between January 2007 and April 2019. Perioperative data were abstracted from medical records. The primary outcome was AKI diagnosed according to Kidney Disease: Improving Global Outcomes criteria. Secondary outcomes were creatinine-AKI diagnosed based on serum creatinine alone and postoperative serum creatinine trajectory. A Fine and Gray proportional hazards regression analysis was conducted to examine the relationship between amino acid infusion and AKI. Similarly, multivariable logistic regression was performed for creatinine-AKI. Postoperative serum creatinine trajectory was assessed using a multivariable non-linear regression model with the Huber-White method.Results: Of 696 patients, 310 patients received an amino acid infusion. Most patients received an amino acid infusion of 20 g. The amino acid group had a lower prevalence of AKI (24.7% vs. 25.3%; adjusted Hazard Ratio (HR)=0.86; 95% CI, 0.67–1.11; P=0.24) and creatinine-AKI (23.5% vs. 19.2%; adjusted odds ratio (OR)=0.84; 95% CI, 0.50–1.43; P=0.52) than the control group, but the differences were not statistically significant. Postoperative serum creatinine levels were significantly lower in the amino acid infusion group on postoperative days 5 and 6.Conclusions: Intraoperative amino acid infusion has a tendency to reduce the incidence of postoperative AKI among patients undergoing open AAA repair. However, we could not show a statistically significant difference.Trial registration: UMIN000038527, 09/11/2019

BACKGROUND Peri-implant tissue condition can result from prosthodontic, surgical and bacteriological factors. PURPOSE This study investigated the effects of prosthodontic factors on peri-implant tissue. MATERIALS AND METHODS Subjects were 140 patients with 310 implants from Osaka University Dental Hospital. Prosthodontic factors examined were the connection type, the suprastructure retention type, the material of the abutment and the mesiodistal and buccolingual prosthetic form of the superstructure as emergence angle. The objective variables were the modified bleeding index (mBI) and marginal bone level (MBL). Statistical analysis was used as a generalized estimation equation. RESULTS The taper joint had a significantly smaller MBL than the butt joint (P

Aim Although nivolumab improves progression-free (PFS) and overall (OS) survival of patients previously treated for metastatic non-small-cell lung cancer (NSCLC), approximately 50% of treated patients experience disease progression within 3 months. As predictive biomarkers of response are not yet established, development of biomarkers to predict longer PFS and OS of patients treated with nivolumab is crucial. Therefore, we analyzed the impact of predictive markers of response to nivolumab and quantified the impact of each factor using nomograms. Patients and methods Clinical data at nivolumab commencement were retrospectively collected from 201 patients treated with nivolumab between December 2015 and July 2016. Immunohistochemistry for programmed cell death ligand 1 (PD-L1) was performed using two assay systems (22C3 and 28-8). OS was calculated from nivolumab treatment initiation. Multivariate Cox regression analysis was conducted to identify independent predictors of OS. A nomogram was constructed to estimate OS. Results The median patient age was 68 years (135 males). Thirty-nine patients had driver mutations (epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement). In 22C3 and 28-8 immunostaining assays, 36.3% and 36.8% patients had PD-L1-negative cells, 17.4% and 14.4% had 1-49% PD-L1-positive cells, 11.9% and 14.9% had ≥50% PD-L1-positive cells, and 34.3% and 33.8% had unknown PD-L1 status, respectively. Kendall's rank correlation coefficient between the staining assays was 0.8414. The median OS of the whole patient cohort was 12.27 months [95% confidence interval (CI)=10.87-15.6]. Performance status ≥2 [hazard ratio (HR)=2.15, 95% CI=1.35-3.42, p=0.001) and high baseline lactate dehydrogenase (HR=1.15, 95% CI=1.05-1.26, p=0.004] were independent predictors of shorter OS. There was no significant correlation between PD-L1 status and OS. We constructed a nomogram to estimate the OS of patients previously treated with nivolumab. Conclusion The multivariate analysis-based nomogram might be useful to estimate the OS of patients previously treated with nivolumab for advanced NSCLC.

Introduction: Chronic low back pain (CLBP) is a major health burden worldwide and requires patient satisfaction with treatment. Consultation length can be an important factor in patient satisfaction, but few studies have investigated the impact of consultation length on satisfaction in patients with CLBP. This study tried to elucidate the impact of consultation length on clinical outcomes in patients with CLBP. Methods: This study is part of an analysis using the database of the nationwide, multicenter cohort for CLBP performed by the Project Committee of the Japanese Society for Spine Surgery and Related Research. A total of 427 patients aged 20-85 years (median age, 73.0 years; female, 58.6%) with CLBP were prospectively followed-up monthly for 6 months. Multivariable nonlinear regression analyses were performed to assess the effect of consultation length on outcome measures including subjective satisfaction score, EuroQol 5-dimension, Japanese Orthopaedic Association (JOA) score, Roland-Morris Disability Questionnaire, JOA Back Pain Evaluation Questionnaire, visual analog scale (VAS) and Medical Outcome Survey short-form 8-item health survey that evaluated at the next phase. Furthermore, we assessed whether the effect of consultation length on patient satisfaction was modified by the baseline Brief Scale for Psychiatric Problems in Orthopaedic Patients (BS-POP) score for patient and physician versions. Results: VAS for CLBP was the only score that correlated significantly with consultation length (P = 0.018). Satisfaction score showed a significant positive correlation with consultation length in patients with the highest baseline BS-POP scores (P < 0.2). Moreover, consultation lengths more than 7.6 min and 15.1 min offered increase of satisfaction if patients show the highest BS-POP scores on patient and physician versions, respectively. Conclusions: These findings suggest that a sufficiently long consultation is an important factor for subjective satisfaction in the patients with CLBP, particularly in patients with psychological problems.

We evaluated the influence of anesthetic management with sevoflurane or propofol on recurrence in patients undergoing breast cancer surgery. This single center, retrospective study, included patients who received either sevoflurane or propofol during primary breast cancer surgery between 2008 and 2012. Our primary outcome was recurrence-free survival (RFS) at 1 year. Recurrence was defined as locoregional recurrence and distal metastasis. Propensity scores were calculated using seven variables (age, sex, body mass index, cancer stage, tumor size, intrinsic subtype, and deviation from standard therapy), and Kaplan–Meier survival curves were constructed from the date of diagnosis of recurrence. Hazard ratios (HRs) were estimated using univariable Cox proportional hazard regression analysis. Two-hundred-twelve patients received sevoflurane and 814 patients received total intravenous anesthesia with propofol. The median follow-up was 59 (interquartile range, 44–75) months. Regional anesthetic techniques were not used. Recurrence occurred in 95 patients (9.26%), with 19 (8.96%) and 76 (9.33%) in the sevoflurane and propofol groups, respectively. The HR was 1.167 (95% confidence interval, 0.681–2.000, p = 0.574) for the use of sevoflurane over propofol. After 1:1 propensity-score matching, 318 patients were analyzed. The 1-year RFS rates were similar between the groups (sevoflurane group: 7.5% [n = 12], propofol group: 8.2% [n = 13]), yielding an HR of 1.002 (95% confidence interval 0.457–2.198, p = 0.995) associated with the use of sevoflurane over propofol. In patients undergoing primary breast cancer surgery, the use of either sevoflurane or propofol without regional anesthesia did not appear to affect the risk of recurrence after 1 year.

Background/aimsTo investigate the chronological corneal changes associated with long-term rigid gas-permeable contact lens (RGP-CL) wear in patients with keratoconus (KC).MethodsClinical records of 405 patients with KC or with KC suspect were retrospectively reviewed. Patients with mild-to-moderate KC and uneventful follow-up were classified into the CL (RGP-CL wear) and non-CL (without CL wear) groups. Inclusion criteria were (1) at least 3-year follow-up and (2) Scheimpflug-based corneal imaging examination at each visit. The anterior (ARC) and posterior (PRC) radius of curvature obtained in a 3.0 mm optical zone, the thinnest pachymetry reading of the corneal thickness (Tmin), and maximum keratometry values (Kmax) were investigated as tomographic parameters.ResultsTwenty-two and 15 patients who met the inclusion criteria were included in the CL and non-CL groups, respectively (31 and 20 eyes, respectively). The mean observation periods were 75 (CL group) and 63 (non-CL group) months. A multivariable non-linear regression analysis to assess the change in tomographic parameters over the follow-up period and difference of the trend between the two groups demonstrated no significant differences in the chronological change in ARC, PRC and Tmin between the CL and non-CL groups (p=0.318, p=0.280 and p=0.874, respectively).ConclusionBased on corneal tomographic evaluation over 5–6 years, the effects of long-term RGP-CL wear had no effect on KC progression.

Background It is uncertain whether health counselling after community-based health checkups for high-risk individuals of lifestyle-related disease enhances their referral to physicians. Methods We performed a clustered randomized controlled trial of untreated high-risk individuals aged 40 to 74 years who were screened from the annual health checkup in 2014 and 2015 under the national health insurance in 43 municipalities around Japan, assigning 21 intervention and 22 usual care municipalities. The high-risk conditions were severe forms of hypertension, diabetes, dyslipidemia (for men), and proteinuria. For the intervention group, the theory-based health counselling was performed to enhance referrals to physicians, while each municipality performed its own standard counselling for the usual care group. Data on clinical visits and risk factors were collected systematically and anonymously from the databases of health insurance qualification, health insurance claims, and annual health checkups. Hypotheses are that the cumulative proportion of seeing physicians (clinical visits) is higher in the intervention than the usual care groups, and that those in the intervention group have lower cumulative incidence of composite outcomes associated with lifestyle-related diseases. Results The numbers of subjects for the analyses were 8,977 in the intervention group and 6,733 in the usual care group. Among them, 6,758 had hypertension, 2,147 had diabetes, 2,861 had dyslipidemia, and 1,221 had proteinuria in the intervention group, with corresponding numbers of 4,833, 1,517, 2,262, and 845, respectively, in the usual care group. There were no material differences in mean levels and proportions of major cardiovascular risk factors between the two groups. Conclusions We expect to provide scientific evidence on the effectiveness of health counselling.

Background While the risk of exceeding the standard range of phosphorus levels has been investigated, the impact of the degree of fluctuations has not been investigated. Methods Data were derived from the Japan Dialysis Active Vitamin D trial, a 4-year prospective, randomized study involving 976 patients without secondary hyperparathyroidism undergoing hemodialysis in Japan. Laboratory data were collected every 6 months and the primary outcome was the time to the occurrence of cardiovascular events. The effect of time-dependent changes in phosphorus levels was assessed using a time-varying Cox proportional hazards regression model. Results The median serum phosphorus levels at baseline and at the final observation were 4.70 mg/dl [interquartile range (IQR) 3.90–5.30] and 5.00 mg/dl (IQR 4.20–5.80), respectively. Over each 6-month period, phosphorus changes ranged from −7.1 to +6.7 mg/dl, with a median value of −0.1 to +0.3 mg/dl. During follow-up, composite cardiovascular events occurred in 103 of 964 patients. Although the P-value for the interaction between serum phosphorus level fluctuations and baseline phosphorus levels was insignificant, the following trends were observed. First, patients with relatively high initial phosphorus levels over a 6-month period showed a trend towards a higher hazard, with greater changes in the phosphorus level over the 6-month period. Second, it was suggested that oral vitamin D receptor activators could contribute to the relationship between fluctuating phosphorus levels and cardiovascular events. Conclusions Our results suggest the importance of maintaining stable phosphorus levels, not only in the normal range, but also without fluctuations, in the risk of cardiovascular events among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis.

Physical inactivity contributes significantly to poor health and the onset of disease. Physical inactivity is also associated with severe economic burdens. Japan’s Ministry of Health, Labor and Welfare (MHLW) cites the provision of various health promotion incentives aimed at health-indifferent groups, which are made up of individuals less interested in health promotion. This study investigated the relationship between medical costs and a pedometer-based walking program providing monetary incentives based on daily step counts. The study sample included 16,816 citizens aged 40–75 years who lived in Takaishi City and were enrolled in the NIH from October 2016 to March 2018. The results of the ordinal logistic regression analysis showed that participation in a walking promotion program with an HPFI was correlated with a reduction in healthcare costs over 1 year in a sample of Takaishi City residents. In fact, there was a difference of 67,077 yen in the average medical cost per person per year between the walking and control groups. With 1,923 walking group participants, the total medical cost reduction was predicted to be at least 12,898,904 yen. In this study, we evaluated the effectiveness of a walking promotion program with incentives. With program context differing widely from region to region and country to country, future investigations are needed to inform the selection of appropriate incentive schemes for programs offered in other regions and countries.

In the Japan Dialysis Active Vitamin D (J-DAVID) trial, oral alfacalcidol numerically, but not significantly, increased the risk of cardiovascular events among patients undergoing hemodialysis. Because the cardiovascular effect of alfacalcidol could be modulated by bone turnover status, this post-hoc analysis of the J-DAVID examined how alkaline phosphatase (ALP), a more precise marker of bone turnover than parathyroid hormone (PTH), modifies the impact of alfacalcidol. The J-DAVID was a 48-month, open-label, randomized controlled trial comparing oral alfacalcidol with no vitamin D receptor activators (VDRAs) use in terms of cardiovascular events among 976 hemodialysis patients without secondary hyperparathyroidism. This post-hoc analysis included 959 patients with available data on baseline ALP. The median [25–75th percentile] baseline ALP level was 234 [183–296] U/L. In a Cox proportional hazards model, ALP did not significantly modify the effect of alfacalcidol on the rate of cardiovascular events or all-cause death (P for effect modification=0.54 and 0.74, respectively). The effect of alfacalcidol on time-series changes in calcium, phosphate, and intact PTH were similar across ALP subgroups. In conclusion, oral alfacalcidol did not significantly affect cardiovascular outcomes irrespective of bone turnover status.

We carried out a randomized controlled trial using ipragliflozin. We analyzed changes in diastolic function using echocardiography in patients with type 2 diabetes and heart failure with preserved ejection fraction.We carried out an open-label, multicenter, randomized, two-arm interventional trial. A total of eligible 68 participants were randomly assigned into two groups (ipragliflozin group n = 36; conventional treatment group n = 32). Primary end-points were the change in E/e' and e'. Secondary end-points were other parameters of echocardiography, plasma NT-proBNP level, New York Heart Association class, hemoglobin A1c and blood pressure.After 24 weeks of follow up, E/e' decreased in both groups (ipragliflozin: 11.0 vs 10.4; conventional treatment 10.5 vs 10.1; multivariate-adjusted P = 0.95). There were no significant differences in the amount of change in E/e', e', echocardiography parameters, plasma NT-proBNP level, New York Heart Association class, hemoglobin A1c and blood pressure between the two groups. In the subgroup analysis, ipragliflozin treatment decreased in left ventricular mass index in patients aged ≥70 years and also decreased in NT-proBNP levels in patients with baseline NT-proBNP ≥400 pg/mL.In this randomized controlled study carried out in patients with type 2 diabetes and heart failure with preserved ejection fraction, 24-week ipragliflozin treatment did not improve left ventricular diastolic function compared with conventional treatment. As the subgroup, ipragliflozin treatment decreased in left ventricular mass index in participants aged ≥70 years. Geriatr Gerontol Int 2022; 22: 298-304.

Pain during cannulation for vascular access is a considerable problem for patients with kidney disease who are undergoing hemodialysis. We examined whether listening to music can reduce cannulation pain in these patients.We conducted a multicenter, single-blind, crossover, randomized trial of 121 patients who reported pain during cannulation for hemodialysis. We compared participants listening to "Sonata for Two Pianos in D Major, K.448" or white noise as control while undergoing the cannulation procedure. The cannulation operator was blinded to the intervention, and the hypothesized superiority of music over white noise was concealed during explanations to the participants. The primary end point was the visual analog scale score for cannulation pain independently evaluated by participants.The primary analysis was on the basis of the modified intention-to-treat principle. The median baseline visual analog scale pain score was 24.7 mm (interquartile range, 16.5-42.3). Median change of the visual analog scale pain score from the "no sound" to the music period was -2.7 mm (interquartile range, -9.2 to 3.6), whereas it was -0.3 mm (interquartile range, -5.8 to 4.5) from "no sound" to white noise. The visual analog scale pain score decreased when listening to music compared with white noise. (Adjusted difference of visual analog scale pain score: -12%; 95% confidence interval, -21 to -2;Listening to music reduced cannulation pain in patients on hemodialysis, although there was no significant effect on anxiety, BP, or stress markers.

PURPOSE: To analyze the causes of debonding of computer-aided design/computer-aided manufacturing (CAD/CAM) indirect resin composite premolar crowns with a focus on the morphological factors of the crown and abutment teeth. METHODS: The clinical courses of 109 CAD/CAM indirect resin composite crowns were observed, and the patients' background characteristics, crown locations, luting methods, types of abutments, distal-most/non-distal-most molars, and types of resin blocks were confirmed. To investigate the influence of the morphology of the crown and abutment teeth, the 1) vertical dimension of the abutment teeth, 2) taper, and 3) thickness of the crown occlusal surface during events were measured from the three-dimensional digital data. The Kaplan-Meier method and multivariable Cox proportional hazard model were used for the statistical analyses. The nonlinearity of the effect of each comparison factor was included in the model. RESULTS: Complications included 21 debonding cases, two crown fractures, five root fractures, and two core debondings. The cumulative no-debonding and no-crown-fracture rate over 1423 days (3 years and 11 months) was 77.4%. The multivariable Cox regression analysis revealed that the abutment teeth type of tooth (first or second premolar) (P = 0.02) and luting materials (P < 0.01) significantly influenced the debonding frequency. All morphological factors (1-3) significantly influenced the debonding. The hazard ratios and nonlinear graph indicated that the crown thickness was less effective than the vertical dimension and taper. CONCLUSION: The combination analysis of clinical outcomes and 3D digital data revealed that preparation of the abutment is important for avoiding crown debonding. ispartof: JOURNAL OF PROSTHODONTIC RESEARCH vol:66 issue:3 pages:402-408 ispartof: location:Japan status: published

Objectives High transprosthetic valvular peak velocity (PV) is indicative of prosthesis–patient mismatch (PPM), which exacerbates mortality and morbidity after surgical aortic valve replacement (AVR). During surgical AVR, a high intraoperative PV sometimes is detected, but whether it affects mortality and morbidity is unknown. The aims of this study were to determine whether intraoperative and postoperative PV were correlated and what factors predicted postoperative PPM. Design Retrospective, observational, cohort study. Setting Tertiary medical center. Interventions None. Measurements and Main Results The study comprised 556 patients who underwent AVR with a bioprosthetic valve. PV was measured intraoperatively, 1 month after surgery, and 1 year after surgery. The occurrence of PPM was defined as an effective orifice area index of less than 0.85 cm2/m2. The associations between PV values at the aforementioned 3 time points were analyzed using a multivariable nonlinear regression model. A multivariable logistic regression model was used to identify the predictors of PPM at 1 year. There was no significant association between intraoperative PV and PV at 1 month (p = 0.419) or 1 year (p = 0.115). The implanted valve type (p Conclusions There was no significant association between intraoperative and postoperative PV values. Implanted valve type and size, but not intraoperative PV, predicted postoperative PPM.

Background Severely burned patients often suffer white blood cell and platelet drop following the injury. Though coagulopathy after burn injury have been reported, the association between leukopenia or thrombopenia and mortality is still unrevealed. To determine whether early drastic drops in white blood cells (WBCs) and platelets following injury can be prognostic markers in patients with major burns. Methods This is a retrospective cohort study setting in a single Burn Center in Japan. Data comprising patients’ characteristics and blood cell counts (red blood cells [RBCs], WBCs including neutrophils, monocytes, and lymphocytes, and platelets) over the first 30 days after burn injury were serially collected from patients suffering major burn injury (≥20% TBSA) from January 1, 2006 to December 31, 2015. To determine blood cell counts affecting 60-day mortality, we used multivariable Cox proportional hazard analysis to assess associations between each blood cell count and mortality, adjusting for age and %TBSA as covariates, and evaluated predicted value of the hazard ratio (HR) of death. Results We enrolled 280 patients. Following burn injury, all blood cell counts were high at admission, then decreased. RBCs diminished progressively and plateaued 2 weeks after injury. WBCs decreased suddenly 2 days after injury, then increased and stabilized. Platelets decreased more rapidly than WBCs to their nadir at 3 days, then continually increased. After covariate adjustment, low RBCs from day 1 (HR: 0.566, 95% C.I. 0.423, 0.759) to day 5 (HR: 0.524, 95% C.I. 0.175, 0.576) were predictors of mortality. Neutrophil count was not a risk factor, but day 3 lymphocyte count (HR: 0.131, 95% C.I. 0.026, 0.646) and day 10 monocyte count (HR: 0.044, 95% C.I. 0.005, 0.396) were risk factors. Low platelet counts from day 3 (HR: 0.545, 95% C.I. 0.300, 0.981) to day 30 following injury were always a predictor of mortality. Conclusions Early thrombopenia and lymphopenia were independent risk factors for 60-day mortality, and prolonged thrombopenia and monocytopenia were independent risk factors for mortality. These findings might shed light on mechanisms of immune response following severe burns.

IntroductionWe investigated trends in the proportion of diabetes treatment and glycemic control, which may be altered by recent advances in insulin and non-insulin drugs, in Japanese patients with type 2 diabetes.Research design and methodsA serial cross-sectional study was performed using a multicenter large-population database from the Japan Diabetes Clinical Data Management study group. Patients with type 2 diabetes who attended clinics belonging to the study group between 2002 and 2018 were included to examine trends in glycated hemoglobin A1c (HbA1c) by treatment group using multivariable non-linear regression model.ResultsThe proportion of patients with insulin only decreased from 15.0% to 3.6%, patients with insulin+non-insulin drugs increased from 8.1% to 15.1%, patients with non-insulin drugs increased from 50.8% to 67.0%, and those with no drugs decreased from 26.1% to 14.4% from 2002 to 2018, respectively. The HbA1c levels of each group, except for no drugs, continued to decrease until 2014 (unadjusted mean HbA1c (%) from 2002 to 2014: from 7.89 to 7.45 for insulin only, from 8.09 to 7.63 for insulin+non-insulin, and from 7.51 to 6.98 for non-insulin) and remained unchanged thereafter. Among insulin-treated patients, use of human insulin decreased, use of long-acting analog insulin increased, and concomitant use of non-insulin drugs increased (from 35.1% in 2002 to 80.9% in 2018), which included increased use of dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide 1 receptor agonists, and the persistently high use of metformin.ConclusionsDuring the past two decades, combined use of insulin and non-insulin drugs increased and glycemic control improved and leveled off after 2014 in Japanese patients with type 2 diabetes. Further studies of the trend in association with age and factors related to metabolic syndrome are necessary to investigate strategies aiming at personalized medicine in diabetes care.

Introduction COVID-19 patients have been reported to have digestive symptoms with poor outcome. Ivermectin, an antiparasitic drug, has been used in COVID-19 patients. The objective of this study was to evaluate whether ivermectin has effects on gastrointestinal complications and ventilator-free days in ventilated patients with COVID-19. Methods COVID-19 patients who were mechanically ventilated in the ICU were included in this study. The ventilated patients who received ivermectin within 3 days after admission were assigned to the Ivermectin group, and the others were assigned to the Control group. Patients in the Ivermectin group received ivermectin 200 μg/kg via nasal tube. The incidence of gastrointestinal complications and ventilator-free days within 4 weeks from admission were evaluated as clinical outcomes using a propensity score with the inverse probability weighting method. Results We included 88 patients in this study, of whom 39 patients were classified into the Ivermectin group, and 49 patients were classified into the Control group. The hazard ratio for gastrointestinal complications in the Ivermectin group as compared with the Control group was 0.221 (95% confidence interval [CI], 0.057 to 0.855; p = 0.029) in a Cox proportional-hazard regression model. The odds ratio for ventilator-free days as compared with the Control group was 1.920 (95% CI, 1.076 to 3.425; p = 0.027) in a proportional odds logistic regression model. Conclusions Ivermectin improved gastrointestinal complications and the number of ventilator-free days in severe COVID-19 patients undergoing mechanical ventilation. Prevention of gastrointestinal symptoms by SARS-Cov-2 might be associated with COVID-19 outcome.

BackgroundThe Japanese Society for Dialysis Therapy (JSDT) published in 2013 inaugural hemodialysis (HD) guidelines. Specific targets include 1.4 for single-pool Kt/V (spKt/V) with a minimum dose of 1.2, minimum dialysis session length of 4 hours, minimum blood flow rate (BFR) of 200 mL/min, fluid removal rate no more than 15 mL/kg/hr, and hemodiafiltration (HDF) therapy for certain identified symptoms. We evaluated the effect of these guidelines on actual practice in the years spanning 2005 – 2018.MethodsAnalyses were carried out to describe trends in the above HD prescription practices from December 2005 to April 2013 (before guideline publication) to August 2018 based on prevalent patient cross-sections from approximately 60 randomly selected HD facilities participating in the Japan Dialysis Outcomes and Practice Patterns Study.ResultsFrom April 2006 to August 2017 continual rises occurred in mean spKt/V (from 1.35 to 1.49), and percent of patients having spKt/V>1.2 (71% to 85%). Mean BFR increased with time from 198.3 mL/min (April 2006) to 218.4 mL/min (August 2017) , along with percent of patients with BFR >200 ml/min (65% to 85%). HDF use increased slightly from 6% (April 2006 and August 2009) to 8% by April 2013, but increased greatly thereafter to 23% by August 2017. In contrast, mean HD treatment time showed little change from 2006-2017, whereas mean UFR declined from 11.3 in 2006 to 8.4 mL/Kg/hour in 2017.ConclusionsFrom 2006 – 2018 Japanese HD patients experienced marked improvement in reaching the spKt/V target specified by the 2013 JSDT guidelines. This may have been due to moderate increase in mean BFR even though mean HD session length did not change much. In addition, HDF use increased dramatically in this time period. Other HD delivery changes during this time, such as increased use of super high flux dialyzers, also merit study. While we cannot definitively conclude a causal relationship between the publication of the guidelines and the subsequent practice changes in Japan, those changes moved practice closer to the recommendations of the guidelines.

Knowledge of statistics is essential for understanding the evidence from clinical trials. In this paper, the principles of blinding, FAS-ITT, pre-specified endpoints, subgroup analysis, missing values, sample size computation, applicability of global studies, non-inferiority trials, and meta-analysis are described. Moreover, the statistical aspects of the recent large-scale clinical trial regarding aducanumab as an Alzheimer's disease treatment will be discussed.

Introduction Cerebral microbleeds (CMBs) are detected on gradient-echo T2*-weighted magnetic resonance imaging (MRI). Clinically, CMBs are often detected after stroke, including in cases of intracerebral hemorrhage and ischemic cerebrovascular disease. Hemodialysis (HD) patients are widely known to have a high incidence of stroke, and HD patients without stroke history have been reported to have a high prevalence of CMBs. In this study, we investigated whether history of stroke affects the prevalence of CMBs in HD patients. Methods A cross-sectional study was performed in 241 HD patients who underwent brain T2*-weighted MRI. We compared the prevalence of CMBs between the patients with and without a history of stroke. Moreover, the relationship between history of stroke and presence of CMBs was examined by multivariate logistic regression analysis. Results Among these patients, 22 (9.1%) had a history of stroke. CMBs were detected in 70 patients (29.0%). The prevalence of CMBs was significantly higher in patients with a history of stroke compared to those without this history (54.5 vs. 26.5%, p = 0.012). In the multivariable analysis adjusted for background characteristics, history of stroke was a significant and independent factor related to CMBs (OR: 3.24, 95%CI: 1.18–8.89, p = 0.02). Discussion/conclusions As has been reported for non-dialysis patients, our results showed a high prevalence of CMBs in HD patients with a history of stroke, and indicated that a history of stroke is significantly and independently associated with CMBs in HD patients.

We describe the results of testing healthcare workers from a tertiary care hospital in Japan, which had experienced a COVID-19 outbreak during the first peak of the pandemic, for SARS-CoV-2 specific antibody seroconversion. Using two chemiluminescent immunoassays and a confirmatory surrogate virus neutralization test, serological testing unveiled that a surprising 42.2% (27/64) of overlooked COVID-19 diagnoses had occurred when case detection had relied solely on SARS-CoV-2 nucleic acid amplification testing. This undetected portion of the COVID-19 iceberg beneath the surface may potentially have led to silent transmissions and triggered the spread. A questionnaire-based risk assessment was further indicative of exposures to specific aerosol-generating procedures, i.e. non-invasive ventilation, having had conveyed the highest transmission risks and served as the origin of outbreak. Our observations are supportive of a multi-tiered testing approach, including the use of serological diagnostics, in order to accomplish exhaustive case detection along the whole COVID-19 spectrum.

BACKGROUND AND AIM Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains the most common and serious adverse event associated with ERCP. Risk factors for PEP have been described in various reports. However, risk factors have not been quantified to date. The aim of this study was to investigate the risk factors for PEP by quantification of pancreatic volume using pre-ERCP images. METHODS Overall, 800 patients were recruited from April 2012 to February 2015 for this study. There were 168 patients who satisfied the inclusion criteria. Measurement of pancreatic volume was achieved using the volume analyzer SYNAPSE VINCENT in all cases and was used to evaluate the risk factors for PEP. RESULTS According to the criteria established by the consensus guidelines (Cotton classification), 17 patients (10.1%) were classified as having mild disease, 4 (2.4%) as having moderate disease, and 5 (3.0%) as having severe disease. Multivariate model analysis showed that a large pancreatic volume was a significant risk factor for PEP (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.06-1.13; P

To translate and validate a Japanese version of the 8-item Contact Lens Dry Eye Questionnaire (CLDEQ-8) among a multicenter sample of Japanese-speaking soft contact lens (SCL) wearers in Japan.The study comprised two phases, 1) forward and backward translation of the CLDEQ-8 into Japanese, 2) cross-sectional validation of Japanese CLDEQ-8 (J-CLDEQ-8) among Japanese spherical disposable SCL wearers (daily disposable, 2 week, or monthly disposable) against their Overall Opinion of SCLs, and 3) repeatability testing in a subset of subjects.300 subjects (118 males and 182 females) completed the J-CLDEQ-8 and anchoring Gestalt SCL questions. The J-CLDEQ-8 had a strong significant linear relationship to Overall Opinion of SCLs and the Self-Assessment of Eye Dryness. The Gestalt Eye Sensitivity question did not translate well in Japanese and the relationship between it and the J-CLDEQ-8 was not linear. A cutoff score of11 points with the J-CLDEQ-8 related best to patients who reported "Excellent" or "Very Good" Overall Opinion of their SCLs, differing slightly from the North American CLDEQ-8 cutoff of12 points. This11 points cutoff yielded accuracy of 0.66, and a sensitivity of 0.67 and specificity of 0.66, very similar to the values for the original CLDEQ-8.The J-CLDEQ-8 was capable of differentiating SCL wearers with different Overall Opinions of their SCLs, comparable to the original CLDEQ-8 in English.

Objective The Risk Assessment Profile (RAP) score is used as a tool of risk prediction in post-traumatic venous thromboembolism (VTE), but this scoring system is complicated to use in clinical settings due to its many variables. The objective of this study was to validate the utility of the RAP model and to develop a simpler risk prediction model for post-traumatic VTE. Methods We conducted an observational study at two emergency and critical care centres in Japan between 2013 and 2016. Consecutive adult trauma patients who survived for 24 h or more after admission to the hospital were enroled. One prediction model (quick RAP model) was created with 6 variables based on clinical utility, experience, and thrombogenic mechanism from 17 variables in the conventional RAP model. We calculated diagnostic performance with 95% confidence interval (95% CI) by exact method. Results We identified and analysed 859 patients. Twenty-six patients (3.0%) had VTE (17 with deep venous thrombosis alone, 2 with pulmonary embolism alone, and 7 with both). In the external validation, the RAP model had a sensitivity of 100% (95% CI, 86.8–100%) and specificity of 37.9% (95% CI, 34.6–41.3%). In contrast, the qRAP model had a sensitivity of 96.2% (95% CI, 80.4–99.9%) and specificity of 56.2% (95% CI, 52.7–59.6%). In the internal validation, receiver-operating characteristic curve analysis showed that the two models had similar area under the curve values that were not significantly different (0.832 and 0.800, respectively; RAP vs qRAP, p = 0.477). Conclusions We developed a practical, modified predictive model for VTE, the qRAP model, which appeared only slightly less accurate than the conventional RAP model and had the advantage of being simpler to use to predict VTE. In our dataset, the conventional RAP model was also evaluated as useful for the prediction of post-traumatic VTE.

Background Anticoagulant therapy has seldom been achieved in randomized trials targeting nonspecific overall sepsis patients. Although the key components to identify the appropriate target in sepsis may be disseminated intravascular coagulation (DIC) and high disease severity, the interaction and relation of these two components for the effectiveness of therapy remain unknown. Objective This article identifies the optimal target of anticoagulant therapy in sepsis. Methods We used a prospective nationwide cohort targeting consecutive adult severe sepsis patients in 59 intensive care units in Japan to assess associations between anticoagulant therapy and in-hospital mortality according to DIC (International Society on Thrombosis and Haemostasis [ISTH] overt and Japanese Association for Acute Medicine DIC scores) and disease severity (Acute Physiology and Chronic Health Evaluation II [APACHE II] and Sequential Organ Failure Assessment scores). Multivariable Cox proportional hazard regression analysis with nonlinear restricted cubic spline including a two-way interaction term (treatment × each score) and three-way interaction term (treatment × ISTH overt DIC score × APACHE II score) was performed. Results The final study cohort comprised 1,178 sepsis patients (371 received anticoagulants and 768 did not). The regression model including the two-way interaction term showed significant interaction between intervention and disease severity as indicated by the ISTH overt DIC score and APACHE II score (p = 0.046 and p = 0.101, respectively). Three-way interaction analysis revealed that risk hazard was suppressed in the anticoagulant group compared with the control group in the most severe subset of both scores. Conclusion Anticoagulant therapy was associated with better outcome according to the deterioration of both DIC and disease severity, suggesting that anticoagulant therapy should be restricted to patients having DIC and high disease severity simultaneously.

Background/objective Reduction of muscle markers, such as creatine phosphokinase (CK), in rheumatic diseases and its association with reduced muscle mass may be of clinical importance in osteoarthritis (OA). Considering the complexity of secondary sarcopenia, clarifying the association between muscle markers and sarcopenia and disentangling the involvement of OA-related conditions are of clinical importance. We investigated the association between serum muscle biomarkers and sarcopenia among patients with OA, considering the presence of pain and inflammation. Methods Overall, 1425 patients with knee and hip OA scheduled for joint replacement surgery were included in a single-center cross-sectional study from Screening for People Suffering Sarcopenia in Orthopedic cohort of Kobe study. Primary outcome was sarcopenia defined by 2 criteria (the Asian Working Group for Sarcopenia and the European Working Group on Sarcopenia in Older People). Pain and inflammation were measured using the numeric rating scale and serum C-reactive protein (CRP) levels, respectively. Associations between the biomarkers (serum CK, aspartate aminotransferase, alanine aminotransferase) and sarcopenia were examined using logistic regression models. Results Sarcopenia by the Asian Working Group for Sarcopenia criteria was present in 4.0% of patients. In adjusted analyses, sarcopenia was negatively associated with higher serum CK levels, but not with serum aspartate aminotransferase or alanine aminotransferase levels independent of pain score and serum CRP. Neither pain score nor serum CRP level was associated with sarcopenia. Similar results were found when the European Working Group on Sarcopenia in Older People criteria were used. Conclusions Serum CK was associated with sarcopenia, suggesting the potential usefulness for sarcopenia detection regardless of pain or inflammation in OA.