Differences in target organ damage between captopril challenge test-defined definitive-positive and borderline-range groups among patients with primary aldosteronism.

The new Japanese guidelines for primary aldosteronism introduce a category in the judgment of functional confirmatory tests that is called the "borderline range," which is rare in the other international guidelines. The clinical characteristics of this borderline group are not yet understood. To investigate whether this borderline group has any significant differences in terms of target organ damage, we used data from a Japanese nationwide registry (JPAS-II) of individuals with primary aldosteronism or essential hypertension to compare the borderline group with the definitive-positive group and the negative group. We analyzed the cases of 1785 patients based on their captopril-challenge test results. Since the JPAS-II database contains plasma aldosterone concentration values obtained based on both radioimmunoassay (n = 1555) and chemiluminescent enzyme immunoassay (n = 230) principles, we converted these values to their equivalents as if measured by chemiluminescent enzyme immunoassay and conducted all analyses under the simulated condition. Multicovariate-adjusted models revealed significant prevalance odds ratios for chronic kidney disease (2.01, 95% confidence interval: 1.13 to 3.61), electrocardiographic abnormalities (1.66, 95% confidence interval: 1.16 to 2.37). No significant difference was observed between the borderline and negative groups in these assessments (odds ratio [95% confidence interval] for chronic kidney disease: 0.73 [0.26 to 2.02] and electrocardiographic abnormalities: 1.01 [0.60 to 1.70]). We confirmed that the prevalence of target organ damage increases linearly as the aldosterone-to-renin ratio rises following the captopril challenge test. These results provide material to consider regarding the significance of the provisionally established borderline group.

Epidemiology, microbiology, and diagnosis of infection in diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: A multicenter retrospective observational study.

AIMS: We investigated the characteristics of infection and the utility of inflammatory markers in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS). METHODS: A multicenter, retrospective observational study in 21 acute-care hospitals was conducted in Japan. This study included adult hospitalized patients with DKA and HHS. We analyzed the diagnostic accuracy of markers including C-reactive protein (CRP) and procalcitonin (PCT) for bacteremia. Multiple regression models were created for estimating bacteremia risk factors. RESULTS: A total of 771 patients, including 545 patients with DKA and 226 patients with HHS, were analyzed. The mean age was 58.2 (SD, 19.3) years. Of these, 70 tested positive for blood culture. The mortality rates of those with and without bacteremia were 14 % and 3.3 % (P-value < 0.001). The area under the curve (AUC) of CRP and PCT for diagnosis of bacteremia was 0.85 (95 %CI, 0.81-0.89) and 0.76 (95 %CI, 0.60-0.92), respectively. Logistic regression models identified older age, altered level of consciousness, hypotension, and higher CRP as risk factors for bacteremia. CONCLUSIONS: The mortality rate was higher in patients with bacteremia than patients without it. CRP, rather than PCT, may be valid for diagnosing bacteremia in hyperglycemic emergencies. TRIAL REGISTRATION: This study is registered in the UMIN clinical trial registration system (UMIN000025393, Registered December 23, 2016).

High-power and high-efficiency operation of 1.3 µm-wavelength InP-based photonic-crystal surface-emitting lasers with metal reflector.

We demonstrate high-output-power and high-efficiency operation of 1.3-µm-wavelength InP-based photonic-crystal surface-emitting lasers (PCSELs). By introducing a metal reflector and adjusting the phase of the reflected light via optimization of the thickness of the p-InP cladding layer, we successfully achieve an output power of approximately 400 mW with the slope efficiency of 0.4 W/A and the wall-plug efficiency of 20% under CW conditions. In addition, this PCSEL exhibits a narrow circular beam with a divergence angle below 1.6° even at high output powers under CW conditions at temperatures from 15°C to 50°C. We have also demonstrated an output power of over 12 W under pulsed conditions at room temperature.

High versus low chloride load in adult hyperglycemic emergencies with acute kidney injury: a multicenter retrospective cohort study.

Hyperglycemic emergencies frequently lead to acute kidney injury (AKI) and require treatment with large amount of intravenous fluids. However, the effects of chloride loading on this population have not yet been investigated. We conducted a multicenter, retrospective, cohort study in 21 acute-care hospitals in Japan. The study included hospitalized adult patients with diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS) who had AKI upon arrival. The patients were classified into high and low chloride groups based on the amount of chloride administered within the first 48 h of their arrival. The primary outcome was recovery from AKI; secondary outcome was major adverse kidney events within 30 days (MAKE30), including mortality and prolonged renal failure. A total of 390 patients with AKI, including 268 (69%) with DKA and 122 (31%) with HHS, were included in the study. Using the criteria of Kidney Disease Improving Global Outcomes, the severity of AKI in the patients was Stage 1 (n = 159, 41%), Stage 2 (n = 121, 31%), and Stage 3 (n = 110, 28%). The analysis showed no significant difference between the two groups in recovery from AKI (adjusted hazard ratio, 0.96; 95% CI 0.72-1.28; P = 0.78) and in MAKE30 (adjusted odds ratio, 0.91; 95% CI 0.45-1.76; P = 0.80). Chloride loading with fluid administration had no significant impact on recovery from AKI in patients with hyperglycemic emergencies.Trial Registration This study was registered in the UMIN clinical trial registration system (UMIN000025393, registered December 23, 2016).

Feasibility and perceptions of a benzodiazepine deprescribing quality improvement initiative for primary care providers in Japan.

BACKGROUND: Quality improvement (QI) initiatives in primary care in Japan are rare. One crucial area for QI is the appropriate prescription of benzodiazepines due to the large and growing elderly population in the country. OBJECTIVE: This study aimed to determine the feasibility and other perceptions of a Benzodiazepine receptor agonist medications (BZRAs) deprescribing QI initiative for primary care providers (PCPs) in Japanese primary care clinics. DESIGN: A qualitative study within a QI initiative. PARTICIPANTS: We recruited 11 semi-public clinics and 13 providers in Japan to participate in a BZRAs deprescribing initiative from 2020 to 2021. After stratifying the clinics according to size, we randomly allocated implementation clinics to either an Audit only or an Audit plus Coaching group. INTERVENTIONS: For the Audit, we presented clinics with two BZRAs-related indicators. We provided monthly web-based meetings for the Coaching to support their QI activities. APPROACH: After the nine-month initiative, we conducted semi-structured interviews and used content analysis to identify themes. We organized the themes and assessed the key factors of implementation using the Consolidated Framework for Implementation Research (CFIR) framework. KEY RESULTS: Audit plus Coaching was perceived as more valuable than Audit only intervention. Participants expressed intellectual curiosity about the QI initiative from resources outside their clinic. However, adopting a team-based QI approach in a small clinic was perceived as challenging, and selecting the indicators was important for meaningful QI. CONCLUSION: The small size of the clinic could be a potential barrier, but enhancing academic curiosity may facilitate QI initiatives in primary care in Japan. Further implementation trials are needed to evaluate the possibility of QI with more various indicators and a more extended period of time.

Clinical profile of patients with diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome in Japan: a multicenter retrospective cohort study.

INTRODUCTION: Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS) are life-threatening complications of diabetes mellitus. Their clinical profiles have not been fully investigated. METHODS: A multicenter retrospective cohort study was conducted in 21 acute care hospitals in Japan. Patients included were adults aged 18 or older who had been hospitalized from January 1, 2012, to December 31, 2016 due to DKA or HHS. The data were extracted from patient medical records. A four-group comparison (mild DKA, moderate DKA, severe DKA, and HHS) was performed to evaluate outcomes. RESULTS: A total of 771 patients including 545 patients with DKA and 226 patients with HHS were identified during the study period. The major precipitating factors of disease episodes were poor medication compliance, infectious diseases, and excessive drinking of sugar-sweetened beverages. The median hospital stay was 16 days [IQR 10-26 days]. The intensive care unit (ICU) admission rate was 44.4% (mean) and the rate at each hospital ranged from 0 to 100%. The in-hospital mortality rate was 2.8% in patients with DKA and 7.1% in the HHS group. No significant difference in mortality was seen among the three DKA groups. CONCLUSIONS: The mortality rate of patients with DKA in Japan is similar to other studies, while that of HHS was lower. The ICU admission rate varied among institutions. There was no significant association between the severity of DKA and mortality in the study population. TRIAL REGISTRATION: This study is registered in the UMIN clinical Trial Registration System (UMIN000025393, Registered 23th December 2016).

Bayesian design of mosaic-based mode multiplexers for various wavelength bands.

Ultracompact mode multiplexers based on mosaic structure for various wavelength bands designed by Bayesian technique are investigated. C-, O-, and C + O band, TE0-TE1 2-mode multiplexers can be designed with the same footprint, by only changing the mosaic-pattern, showing the great flexibility of mosaic-based devices. Bayesian direct binary search method is used for the design, and it is demonstrated that the Bayesian technique is superior to conventional design method in terms of the best-structure search for the same number of iterations. The designed devices are fabricated for Si-waveguide platform, and the proof-of-concept results are obtained. These results indicate that the mosaic-based devices are promising candidates for future compact optical transceivers.

Pre-Extubation Cuffed Tube Leak Test and Subsequent Post-Extubation Laryngeal Edema: Prospective, Single-Center Evaluation of PICU Patients.

OBJECTIVES: We performed our standard air leak, leak percentage, and cuff leak percentage tests in pediatric patients intubated with microcuff pediatric tracheal tubes (MPTTs) just before extubation. We examined the association between test findings and the subsequent occurrence of post-extubation laryngeal edema (PLE). DESIGN: Prospective, single-center, observational study. SETTING: PICU (June 1, 2020 to May 31, 2021). PATIENTS: Pediatric patients intubated and scheduled for extubation during the day shift in the PICU. INTERVENTIONS: Multiple pre-extubation leak tests were performed on each patient immediately before extubation. In our center, the standard leak test is positive if a leak is audible at 30 cm H 2 O applied pressure with the MPTT cuff deflated. Two other tests were calculated in the pressure control-assist control ventilator mode using the following formulas: leak percentage with deflated cuff = (inspiratory tidal volume [V t ]-expiratory V t ) × 100/inspiratory V t ; cuff leak percentage = (expiratory V t with inflated cuff-expiratory V t with deflated cuff) × 100/expiratory V t with inflated cuff. MEASUREMENTS AND MAIN RESULTS: The diagnostic criteria for PLE was made by at least two healthcare professionals and included upper airway stricture with stridor-requiring nebulized epinephrine. Eighty-five pediatric patients (< 15 yr) who had been intubated for at least 12 hours using the MPTT were included. Positive rates for the standard leak, leak percentage (cutoff 10%), and cuff leak percentage (cutoff 10%) tests were 0.27, 0.20, and 0.64, respectively. The standard leak, leak percentage, and cuff leak tests showed sensitivities of 0.36, 0.27, and 0.55, respectively; and specificities of 0.74, 0.81, and 0.35, respectively. PLE occurred in 11 of 85 patients (13%), and there were no instances of needing reintubation. CONCLUSIONS: The pre-extubation leak tests in current practice for intubated pediatric patients in the PICU all lack diagnostic accuracy for PLE.

Association between zinc deficiency and aorta stiffness in non-diabetic hemodialysis patients.

OBJECTIVES: Zinc deficiency (Zn < 60 µg/dL) is known to play an important role for vascular calcification. However, little data is available regarding the association between zinc deficiency and aorta stiffness in dialysis patients. Thus, we studied the relationship between zinc deficiency and aorta stiffness in non-diabetic hemodialysis (HD) patients. METHODS: Of 150 patients receiving maintenance HD at our hospital, we included 79 non-diabetic HD patients (age: 70±11 years, 49 men) after excluding 71 diabetic HD patients. Zinc deficiency was defined as Zn <60 µg/dL during pre-HD blood sampling. The association between zinc deficiency and aorta stiffness was analyzed. Aorta stiffness was evaluated as brachial-ankle pulse wave velocity (baPWV). Other surrogate markers for cardiovascular complications were also measured. RESULTS: The zinc deficiency group (ZD group) included 45 patients (57.0%). Compared to the zinc non-deficiency group (ZND group), patients with ZD group were significantly older, higher levels of CRP and hypoalbuminemia. Moreover, they had significantly higher levels of baPWV, and lower levels of ankle-brachial pressure index (ABI) (p<0.05). After adjusting for hypoalbuminemia, and CRP, multivariate analysis showed that age and zinc level were independent predictors of baPWV. CONCLUSION: The study suggested that zinc deficiency may be an independent risk factor for aorta stiffness, even after adjusting for malnutrition and inflammation.

The Japanese Pediatric Continuous Renal Replacement Therapy (jpCRRT) Registry: Study Protocol.

BACKGROUND: The use of continuous renal replacement therapy (CRRT) in critically ill children is rapidly increasing, but the standard of care has not yet been established and prognosis remains poor. To develop optimal CRRT strategies, we launched a research project generating the Japanese Pediatric CRRT registry, a multicenter registry of CRRT in Japanese pediatric intensive care units (PICUs), to investigate the actual status of CRRT in recent years in PICUs, where data are lacking. METHODS: This manuscript presents a protocol for planning a multicenter prospective registry. As of April 2023, 15 Japanese PICUs are voluntarily participating. Patients enrolled are those <16 years of age who enter the PICUs of the collaborating institutions, require CRRT, and have the guardians' consent. CRRT is defined as anticipated to be required for >24 hours, and CRRT connected to extracorporeal membrane oxygenation is also included. The registry is an online registry system managed by the University Hospital Medical Information Network. The primary outcomes are Pediatric Cerebral Performance Category Scale at PICU discharge and 6 months post-discharge (deaths included), persistent need for dialysis, and PICU readmission within 6 months. The secondary outcomes are adverse events during and immediately after CRRT initiation, and initial circuit life span. CONCLUSIONS: This project will examine the differences in outcomes of CRRT in PICUs in specific patient and treatment groups and will be used to design future interventional studies. We will also aim to establish a platform for a multicenter registry study in Japanese PICUs, considering the current lack of such a platform.

High-power CW oscillation of 1.3-µm wavelength InP-based photonic-crystal surface-emitting lasers.

We demonstrate high-power continuous-wave (CW) lasing oscillation of 1.3-µm wavelength InP-based photonic-crystal surface-emitting lasers (PCSELs). Single-mode operation with an output power of over 100 mW, a side-mode suppression ratio (SMSR) of over 50 dB, and a narrow single-lobe beam with a divergence angle of below 1.2° are successfully achieved by using a double-lattice photonic crystal structure consisting of high-aspect-ratio deep air holes. The double lattice is designed to enhance both the in-plane optical feedback and the surface radiation effects in the photonic crystal. The coupling coefficients for 180 ∘, +90 ∘, and -90 ∘ diffractions are estimated from the measurements of the photonic band structure as κ1D = 417 cm-1, κ2D+ = 135 cm-1, and κ2D- = 65 cm-1, respectively. The stable single-mode, high-beam-quality operation is attributed to these large coupling coefficients introduced by the asymmetric double-lattice structure.

Anti-inflammatory and immune-mediated therapy for a case of febrile infection-related epilepsy syndrome with rapid recurrence.

Febrile infection-related epilepsy syndrome (FIRES) is a disease of unknown etiology, characterized by refractory frequent focal seizures, which require prolonged intensive care. We successfully treated a boy with FIRES with anti-inflammatory and immunosuppressive therapy. This case suggests that an autoimmune mechanism may play a role in the development of FIRES.

[EFFECTIVENESS OF ADD-ON SUBLINGUAL IMMUNOTHERAPY FOR THE TREATMENT OF JAPANESE CEDAR POLLINOSIS-ASSOCIATED ALLERGIC ASTHMA IS IT POSSIBLE TO REDUCE THE DOSE OF INHALED CORTICOSTEROID BY ADDING SUBLINGUAL IMMUNOTHERAPY?]

BACKGROUND: This study investigated the effect of adjuvant sublingual immunotherapy (SLIT) on inhaled corticosteroid (ICS) dose in patients with pollinosis-associated asthma. METHODS: We retrospectively evaluated patients with cedar pollinosis-associated asthma who initiated pharmacotherapy with or without adjuvant SLIT therapy from December 2014 to December 2016 and who continued treatment for 3 years. Changes in ICS dose (fluticasone propionate or its equivalent), antihistamine use, leukotriene antagonist use and intranasal corticosteroid (INCS) use over the 3-year period were compared. RESULTS: The study included 36 and 35 patients in the add-on SLIT and standard treatment groups, respectively. At 3 years, the add-on SLIT group showed a significant decline in ICS dose (p = 0.024). Although leukotriene antagonist use and INCS use did not differ between the two groups, the percentage of patients using antihistamines at 3 years was significantly lower in the add-on SLIT group than in the standard treatment group (p = 0.009); one in three patients on adjuvant SLIT therapy was able to discontinue ICS treatment. Patients who discontinued ICS treatment were younger (44.6±13.3 years vs. 55.0±14.1 years, p = 0.042), had a higher FEV1% predicted (109.9±14.4 vs. 94.8±18.6, p = 0.02), and were on a lower treatment step (2.1±0.7 vs. 3.0±0.8, p = 0.002) than those who did not. CONCLUSION: The addition of SLIT to standard pharmacotherapy resulted in a significant reduction in ICS dose at 3 years.

Physical Restraints in Critically Ill Children: A Multicenter Longitudinal Point Prevalence Study.

OBJECTIVES: We elucidate to investigate the prevalence of and factors associated with the use of physical restraints among critically ill or injured children in PICUs. DESIGN: This was a multicenter, longitudinal point prevalence study. SETTING: We included 26 PICUs in Japan. PATIENTS: Included children were 1 month to 10 years old. We screened all admitted patients in the PICUs on three study dates (in March, June, and September 2019). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We collected prevalence and demographic characteristics of critically ill or injured children with physical restraints, as well as details of physical restraints, including indications and treatments provided. A total of 398 children were screened in the participating PICUs on the three data collection dates. The prevalence of children with physical restraints was 53% (211/398). Wrist restraint bands were the most frequently used means (55%, 117/211) for potential contingent events. The adjusted odds of using physical restraint in patients 1-2 years old was 2.3 (95% CI, 1.3-4.0) compared with children less than 1 year old. When looking at the individual hospital effect, units without a prespecified practice policy for physical restraints management or those with more than 10 beds were more likely to use physical restraints. CONCLUSIONS: The prevalence of physical restraints in critically ill or injured children was high, and significant variation was observed among PICUs. Our study findings suggested that patient age, unit size, and practice policy of physical restraint could be associated with more frequent use of physical restraints.