Use of Japanese Herbal Kampo Medicine in Patients With Acute Cardiovascular Disease　- A 12-Year Nationwide Cohort Analysis.

BACKGROUND: Kampo, a Japanese herbal medicine, is approved for the treatment of various symptoms/conditions under national medical insurance coverage in Japan. However, the contemporary nationwide status of Kampo use among patients with acute cardiovascular diseases remains unknown.Methods and Results: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified 2,547,559 patients hospitalized for acute cardiovascular disease (acute myocardial infarction, heart failure, pulmonary embolism, or aortic dissection) at 1,798 hospitals during the fiscal years 2010-2021. Kampo medicines were used in 227,008 (8.9%) patients, with a 3-fold increase from 2010 (4.3%) to 2021 (12.4%), regardless of age, sex, disease severity, and primary diagnosis. The top 5 medicines used were Daikenchuto (29.4%), Yokukansan (26.1%), Shakuyakukanzoto (15.8%), Rikkunshito (7.3%), and Goreisan (5.5%). From 2010 to 2021, Kampo medicines were initiated earlier during hospitalization (from a median of Day 7 to Day 3), and were used on a greater proportion of hospital days (median 16.7% vs. 21.4%). However, the percentage of patients continuing Kampo medicines after discharge declined from 57.9% in 2010 to 39.4% in 2021, indicating their temporary use. The frequency of Kampo use varied across hospitals, with the median percentage of patients prescribed Kampo medications increasing from 7.7% in 2010 to 11.5% in 2021. CONCLUSIONS: This nationwide study demonstrates increasing Kampo use in the management of acute cardiovascular diseases, warranting further pharmacoepidemiological studies on its effectiveness.

Physician characteristics associated with antiviral prescriptions for older adults with COVID-19 in Japan: an observational study.

OBJECTIVES: Although guidelines recommend antiviral therapy for outpatients with COVID-19 who are at high risk of progressing to severe conditions, such as older adults, many patients do not receive appropriate treatment. Little is known, however, about the physician factors associated with the prescription of guideline-recommended antiviral therapy for patients with COVID-19. DESIGN: A cross-sectional study. SETTING: Data including outpatient visits in primary care clinics in Japan from April to August 2023. PARTICIPANTS: We analysed 30 953 outpatients aged ≥65 years treated with COVID-19 (mean (SD) age, 75.0 (7.6) years; 17 652 women (57.0%)) in 1394 primary care clinics. OUTCOME MEASURES: The primary outcome was the prescription of guideline-recommended antivirals (ie, nirmatrelvir-ritonavir or molnupiravir), adjusted for patient characteristics, months of visits and regions. RESULTS: Antiviral prescriptions were concentrated among a small proportion of physicians; for example, the top 10% of physicians that had the largest number of nirmatrelvir-ritonavir prescriptions accounted for 92.4% of all nirmatrelvir-ritonavir prescriptions. After adjusting for potential confounders, physicians with higher patient volumes were more likely to prescribe guideline-recommended antivirals to their patients (adjusted OR (aOR) for high vs low volume, 1.76; 95% CI 1.31 to 2.38; adjusted p<0.001). We found no evidence that the likelihood of guideline-recommended antiviral prescription differed based on physicians' gender (aOR for women vs men, 1.24; 95% CI 0.88 to 1.74; adjusted p=0.48) or age (aOR for 45-59 vs <45 years, 1.16; 95% CI 0.87 to 1.54; adjusted p=0.48; aOR for ≥60 vs <45 years, 0.88; 95% CI 0.66 to 1.16; adjusted p=0.48). These patterns were similar when examining nirmatrelvir-ritonavir and molnupiravir separately. CONCLUSIONS: Our findings suggest that provider-level factors, such as the clinical experience of treating the patients with COVID-19, play an important role in the appropriate prescription of antiviral medications for COVID-19 in the primary care setting.

Potassium Iodide Use and Patient Outcomes for Thyroid Storm: An Observational Study.

PURPOSE: Iodine, combined with antithyroid drugs, is recommended as an initial pharmacologic treatment for thyroid storm according to some clinical guidelines. However, the clinical efficacy of iodine in managing thyroid storm remains unexplored. This study aimed to determine whether early potassium iodide (KI) use is associated with mortality in patients hospitalized for thyroid storm. METHODS: Using the Japanese Diagnosis Procedure Combination database, we identified patients hospitalized with thyroid storm between July 2010 and March 2022. We compared in-hospital mortality, length of stay, and total hospitalization costs between patients who received KI within two days of admission (KI group) versus those who did not (non-KI group). Prespecified subgroup analyses were performed based on the presence of the diagnosis of Graves' disease. RESULTS: Among 3,188 eligible patients, 2,350 received KI within two days of admission. The crude in-hospital mortality was 6.1% (143/2,350) in the KI group and 7.8% (65/838) in the non-KI group. After adjusting for potential confounders, KI use was not significantly associated with in-hospital mortality (odds ratio [OR] for KI use, 0.91; 95% confidence interval [CI], 0.62-1.34). In patients with the diagnosis of Graves' disease, in-hospital mortality was lower in the KI group than in the non-KI group (OR, 0.46; 95% CI, 0.25-0.88). No significant difference in in-hospital mortality was observed in patients without the diagnosis of Graves' disease (OR, 1.11; 95% CI, 0.67-1.85). Length of stay was shorter (subdistribution hazard ratio, 1.15; 95% CI, 1.05-1.27), and total hospitalization costs were lower (OR, 0.92; 95% CI, 0.85-1.00) in the KI group compared with the non-KI group. CONCLUSION: Our findings suggest that KI may reduce in-hospital mortality among patients hospitalized for thyroid storm with Graves' disease.

StayGold photostability under different illumination modes.

StayGold is a bright fluorescent protein (FP) that is over one order of magnitude more photostable than any of the currently available FPs across the full range of illumination intensities used in widefield microscopy and structured illumination microscopy, the latter of which is a widefield illumination-based technique. To compare the photostability of StayGold under other illumination modes with that of three other green-emitting FPs, namely EGFP, mClover3, and mNeonGreen, we expressed all four FPs as fusions to histone 2B in HeLa cells. Unlike the case of widefield microscopy, the photobleaching behavior of these FPs in laser scanning confocal microscopy (LSCM) is complicated. The outstanding photostability of StayGold observed in multi-beam LSCM was variably attenuated in single-beam LSCM, which produces intermittent and instantaneously strong illumination. We systematically examined the effects of different single-beam LSCM beam-scanning patterns on the photostability of the FPs in living HeLa cells. This study offers relevant guidelines for researchers who aim to achieve sustainable live cell imaging by resolving problems related to FP photostability. We also provide evidence for measurable sensitivity of the photostability of StayGold to chemical fixation.

Association Between Vonoprazan and the Risk of Gastric Cancer After Helicobacter pylori Eradication.

BACKGROUND & AIMS: Potassium-competitive acid blockers (PCABs) have been increasingly used to treat upper gastrointestinal disorders, replacing proton pump inhibitors (PPIs). Whereas PPIs are associated with an increased risk of gastric cancer (GC) after Helicobacter pylori (Hp) eradication, it is uncertain whether PCABs carry the same risk. METHODS: Using a population-based claims database in Japan, we identified patients who were prescribed a clarithromycin-based first regimen of Hp eradication between 2015 and 2018. Patients who failed this regimen and those diagnosed with GC before or within 1 year after Hp eradication were excluded. We compared GC incidence between PCAB users and histamine type-2 receptor antagonist (H2RA) users, matching them on the basis of propensity scores calculated with considerations for age, sex, smoking, alcohol consumption, comorbidities, and co-administered medications. PCABs included only vonoprazan in this study. RESULTS: Among 54,055 patients, 568 (1.05%) developed GC during the follow-up period (mean, 3.65 years). The cumulative incidence of GC was 1.64% at 3 years, 2.02% at 4 years, and 2.36% at 5 years in PCAB users and 0.71% at 3 years, 1.04% at 4 years, and 1.22% at 5 years in H2RA users. The use of PCABs was associated with a higher GC risk (matched hazard ratio, 1.92; 95% confidence interval, 1.13-3.25; P = .016). Longer PCAB use and high-dose PCAB use were significantly associated with higher incidence of GC. Sensitivity analyses showed the risk of GC incidence among PCAB users was comparable with that of PPI users. CONCLUSIONS: The use of PCABs was associated with an increased risk of GC among Hp-eradicated patients, with duration/dose response effects.

Renal outcomes with sodium-glucose cotransporter 2 inhibitors in Japanese people with grade 3 chronic kidney disease and type 2 diabetes: Analysis of medical administrative databases.

AIM: To evaluate whether sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy is associated with a reduction of renal events compared with other glucose-lowering drugs (oGLDs) among Japanese people with type 2 diabetes (T2D) and grade 3 (G3) chronic kidney disease (CKD) in a real-world clinical practice setting. MATERIALS AND METHODS: People with T2D who were newly prescribed an SGLT2i or an oGLD from April 2014 to November 2021 (without prior use of index drugs for ≥ 1 year prior to index date) and G3 CKD (estimated glomerular filtration rate [eGFR] ≥ 30 to < 60 mL/min/1.73 m2) were selected from the Medical Data Vision database (MDV-DB) and the Real-World Data database (RWD-DB). SGLT2i and oGLD users were matched (1:1) using propensity score on patient background characteristics. The primary endpoint was a composite of the development of end-stage kidney disease or a sustained decline in eGFR of 50% or more. Hazard ratios (HRs) were estimated using the Cox proportional hazards model. RESULTS: Overall, 3190 (1595 per group) patients in the MDV-DB and 2572 (1286 per group) patients in the RWD-DB were included in the analyses. The composite outcome was significantly lower in the SGLT2i group than in the oGLD group in the MDV-DB (HR 0.49, 95% confidence interval [CI] 0.33 to 0.74, P < 0.001) and in the RWD-DB (HR 0.57, 95% CI 0.37 to 0.88, P = 0.011). CONCLUSIONS: Japanese people with T2D and G3 CKD initiating an SGLT2i had a lower risk of renal events than people initiating an oGLD.

Spatial frequency-based correction of the spherical aberration in living brain imaging.

Optical errors, including spherical aberrations, hinder high-resolution imaging of biological samples due to biochemical components and physical properties. We developed the Deep-C microscope system to achieve aberration-free images, employing a motorized correction collar and contrast-based calculations. However, current contrast-maximization techniques, such as the Brenner gradient method, inadequately assess specific frequency bands. The Peak-C method addresses this issue, but its arbitrary neighbor selection and susceptibility to the noise limit its effectiveness. In this paper, we emphasize the importance of a broad spatial frequency range for accurate spherical aberration correction and propose Peak-F. This spatial frequency-based system utilizes a fast Fourier transform as a bandpass filter. This approach overcomes Peak-C's limitations and comprehensively covers the low-frequency domain of image spatial frequencies.

Secretory GFP reconstitution labeling of neighboring cells interrogates cell-cell interactions in metastatic niches.

Cancer cells inevitably interact with neighboring host tissue-resident cells during the process of metastatic colonization, establishing a metastatic niche to fuel their survival, growth, and invasion. However, the underlying mechanisms in the metastatic niche are yet to be fully elucidated owing to the lack of methodologies for comprehensively studying the mechanisms of cell-cell interactions in the niche. Here, we improve a split green fluorescent protein (GFP)-based genetically encoded system to develop secretory glycosylphosphatidylinositol-anchored reconstitution-activated proteins to highlight intercellular connections (sGRAPHIC) for efficient fluorescent labeling of tissue-resident cells that neighbor on and putatively interact with cancer cells in deep tissues. The sGRAPHIC system enables the isolation of metastatic niche-associated tissue-resident cells for their characterization using a single-cell RNA sequencing platform. We use this sGRAPHIC-leveraged transcriptomic platform to uncover gene expression patterns in metastatic niche-associated hepatocytes in a murine model of liver metastasis. Among the marker genes of metastatic niche-associated hepatocytes, we identify Lgals3, encoding galectin-3, as a potential pro-metastatic factor that accelerates metastatic growth and invasion.

StayGold variants for molecular fusion and membrane-targeting applications.

Although StayGold is a bright and highly photostable fluorescent protein, its propensity for obligate dimer formation may hinder applications in molecular fusion and membrane targeting. To attain monovalent as well as bright and photostable labeling, we engineered tandem dimers of StayGold to promote dispersibility. On the basis of the crystal structure of this fluorescent protein, we disrupted the dimerization to generate a monomeric variant that offers improved photostability and brightness compared to StayGold. We applied the new monovalent StayGold tools to live-cell imaging experiments using spinning-disk laser-scanning confocal microscopy or structured illumination microscopy. We achieved cell-wide, high-spatiotemporal resolution and sustained imaging of dynamic subcellular events, including the targeting of endogenous condensin I to mitotic chromosomes, the movement of the Golgi apparatus and its membranous derivatives along microtubule networks, the distribution of cortical filamentous actin and the remolding of cristae membranes within mobile mitochondria.

Reverse pH-dependent fluorescence protein visualizes pattern of interfacial proton dynamics during hydrogen evolution reaction.

Reverse pH-dependent fluorescent protein, including dKeima, is a type of fluorescent protein in which the chromophore protonation state depends inversely on external pH. The dependence is maintained even when immobilized at the metal-solution interface. But, interestingly, its responses to the hydrogen evolution reaction (HER) at the interface are not reversed: HER rises the pH of the solution around the cathode, but, highly active HER induces chromophore deprotonation regardless of the reverse pH dependence, reflecting an interface-specific deprotonation effect by HER. Here, we exploit this phenomenon to perform scanning-less, real-time visualization of interfacial proton dynamics during HER at a wide field of view. By using dKeima, the HER-driven deprotonation effect was well discriminated from the solution pH effect. In the electrodes of composite structures with a catalyst, dKeima visualized keen dependence of the proton depletion pattern on the electrode configuration. In addition, propagations of optical signals were observed, which seemingly reflect long-range proton hopping confined to the metal-solution interface. Thus, reverse pH-dependent fluorescent proteins provide a unique tool for spatiotemporal analysis of interfacial proton dynamics, which is expected to contribute to a better understanding of the HER process and ultimately to the safe and efficient production of molecular hydrogen.

Urinary lumirubin excretion in jaundiced preterm neonates during phototherapy with blue light-emitting diode vs. green fluorescent lamp.

Phototherapy converts lipophilic unconjugated bilirubin to hydrophilic bilirubin photoisomers, such as lumirubin. We comparatively used a blue light-emitting diode (LED) and a green fluorescent lamp (FL) as light sources for phototherapy of hyperbilirubinemic preterm neonates with the aim of examining potential differences in urinary lumirubin excretion between these two wavelengths. Urinary lumirubin levels were measured using a fluorescence assay with blue light exposure in the presence of the unconjugated bilirubin-inducible fluorescent protein UnaG, and denoted as urinary UnaG-bound bilirubin (UUB)/creatinine (Cr) (µg/mg Cr). Preterm neonates born at ≤ 33 weeks gestational age and treated with phototherapy were subjected to this study. The maximum UUB/Cr level during phototherapy per device intensity was compared between neonates treated with the blue LED and the green FL. A total of 61 neonates were examined to determine the maximum UUB/Cr levels. The median of maximum UUB/Cr excretion per light intensity of each device (µg/mg Cr/µW/cm2/nm) was 0.83 for the blue LED and 1.29 for the green FL (p = 0.01). Green light was found to be more effective than blue one for bilirubin excretion via urinary lumirubin excretion. This is the first spectroscopic study to compare the efficacy of phototherapy at different wavelengths using fluorescence assay.

Characteristics and in-hospital mortality of patients with COVID-19 from the first to fifth waves of the pandemic in 2020 and 2021 in the Japanese Medical Data Vision database.

Objectives: We aimed to describe patient characteristics, healthcare utilization, and in-hospital mortality among patients with COVID-19 in Japan across waves. Methods: Using a large-scale hospital-based database, we identified patients hospitalized for COVID-19 in the first (January-June 2020), second (June-October 2020), third (October 2020-February 2021), fourth (March-June 2021), and fifth (June-December 2021) waves. We summarized patient characteristics, healthcare utilization, and in-hospital mortality during each wave and performed multivariable logistic regression analyses for in-hospital mortality. Results: From the first to fifth waves, the number of patients (mean age ± standard deviation, years) was 2958 (61.2 ± 22.8), 7981 (55.6 ± 25.3), 18,788 (63.6 ± 22.9), 17,729 (60.6 ± 22.6), and 23,656 (51.2 ± 22.3), respectively. There were 190 (6.4%), 363 (4.5%), 1261 (6.7%), 1081 (6.1%), and 762 (3.2%) in-hospital deaths, respectively. The adjusted odds ratios for in-hospital deaths (95% confidence interval) were 0.78 (0.65-0.95), 0.94 (0.79-1.12), 0.99 (0.84-1.18), 0.77 (0.65-0.92), in the second to fifth waves, respectively, compared with the first wave. Conclusions: In-hospital COVID-19 mortality improved from the first to the second wave; however, during the third and fourth waves, mortality was as serious as in the first wave. Although in-hospital mortality during the fifth wave improved, careful monitoring is needed for upcoming waves, considering changing patient and viral characteristics.

Development of two mouse strains conditionally expressing bright luciferases with distinct emission spectra as new tools for in vivo imaging.

In vivo bioluminescence imaging (BLI) has been an invaluable noninvasive method to visualize molecular and cellular behaviors in laboratory animals. Bioluminescent reporter mice harboring luciferases for general use have been limited to a classical luciferase, Luc2, from Photinus pyralis, and have been extremely powerful for various in vivo studies. However, applicability of reporter mice for in vivo BLI could be further accelerated by increasing light intensity through the use of other luciferases and/or by improving the biodistribution of their substrates in the animal body. Here we created two Cre-dependent reporter mice incorporating luciferases oFluc derived from Pyrocoeli matsumurai and Akaluc, both of which had been reported previously to be brighter than Luc2 when using appropriate substrates; we then tested their bioluminescence in neural tissues and other organs in living mice. When expressed throughout the body, both luciferases emitted an intense yellow (oFluc) or far-red (Akaluc) light easily visible to the naked eye. oFluc and Akaluc were similarly bright in the pancreas for in vivo BLI; however, Akaluc was superior to oFluc for brain imaging, because its substrate, AkaLumine-HCl, was distributed to the brain more efficiently than the oFluc substrate, D-luciferin. We also demonstrated that the lights produced by oFluc and Akaluc were sufficiently spectrally distinct from each other for dual-color imaging in a single living mouse. Taken together, these novel bioluminescent reporter mice are an ideal source of cells with bright bioluminescence and may facilitate in vivo BLI of various tissues/organs for preclinical and biomedical research in combination with a wide variety of Cre-driver mice.

Gene therapy using genome-edited iPS cells for targeting malignant glioma.

Glioblastoma is characterized by diffuse infiltration into the normal brain. Invasive glioma stem cells (GSCs) are an underlying cause of treatment failure. Despite the use of multimodal therapies, the prognosis remains dismal. New therapeutic approach targeting invasive GSCs is required. Here, we show that neural stem cells (NSCs) derived from CRISRP/Cas9-edited human-induced pluripotent stem cell (hiPSC) expressing a suicide gene had higher tumor-trophic migratory capacity compared with mesenchymal stem cells (MSCs), leading to marked in vivo antitumor effects. High migratory capacity in iPSC-NSCs was related to self-repulsive action and pathotropism involved in EphB-ephrinB and CXCL12-CXCR4 signaling. The gene insertion to ACTB provided higher and stable transgene expression than other common insertion sites, such as GAPDH or AAVS1. Ferroptosis was associated with enhanced antitumor immune responses. The thymidylate synthase and dihydroprimidine dehydrogenase expressions predicted the treatment efficacy of therapeutic hiPSC-NSCs. Our results indicate the potential benefit of genome-edited iPS cells based gene therapy for invasive GSCs. Furthermore, the present research concept may become a platform to promote clinical studies using hiPSC.

Two coral fluorescent proteins of distinct colors for sharp visualization of cell-cycle progression.

We cloned and characterized two new coral fluorescent proteins: h2-3 and 1-41. h2-3 formed an obligate dimeric complex and exhibited bright green fluorescence. On the other hand, 1-41 formed a highly multimeric complex and exhibited dim red fluorescence. We engineered 1-41 into AzaleaB5, a practically useful red-emitting fluorescent protein for cellular labeling applications. We fused h2-3 and AzaleaB5 to the ubiquitination domains of human Geminin and Cdt1, respectively, to generate a new color variant of Fucci (Fluorescent Ubiquitination-based Cell-Cycle Indicator): Fucci5. We found Fucci5 provided more reliable nuclear labeling for monitoring cell-cycle progression than the 1st and 2nd generations that used mAG/mKO2 and mVenus/mCherry, respectively.Key words: fluorescent protein, cell cycle, time-lapse imaging, flow cytometry.

Knockout of all ErbB-family genes delineates their roles in proliferation, survival and migration.

The ErbB-family receptors play pivotal roles in the proliferation, migration and survival of epithelial cells. Because our knowledge on the ErbB-family receptors has been largely obtained by the exogenous application of their ligands, it remains unknown to what extent each of the ErbB members contributes to these outputs. We here knocked out each ErbB gene, various combinations of ErbB genes or all ErbB genes in Madin-Darby canine kidney cells to delineate the contribution of each gene. ERK1 and ERK2 (ERK1/2, also known as MAPK3 and MAPK1, respectively) activation waves during collective cell migration were mediated primarily by ErbB1 and secondarily by the ErbB2 and ErbB3 heterodimer. Either ErbB1 or the ErbB2 and ErbB3 complex was sufficient for the G1/S progression. The saturation cell density was markedly reduced in cells deficient in all ErbB proteins, but not in cells retaining only ErbB2, which cannot bind to ligands. Thus, a ligand-independent ErbB2 activity is sufficient for preventing apoptosis at high cell density. In short, systematic knockout of ErbB-family genes has delineated the roles of each ErbB receptor.

Antibiotic Prescription for Outpatients With COVID-19 in Primary Care Settings in Japan.

This cross-sectional study assesses the characteristics of patients and physicians associated with antibiotic prescription for COVID-19.

Bilirubin is produced nonenzymatically in plants to maintain chloroplast redox status.

Bilirubin, a potent antioxidant, is a product of heme catabolism in heterotrophs. Heterotrophs mitigate oxidative stress resulting from free heme by catabolism into bilirubin via biliverdin. Although plants also convert heme to biliverdin, they are generally thought to be incapable of producing bilirubin because they lack biliverdin reductase, the enzyme responsible for bilirubin biosynthesis in heterotrophs. Here, we demonstrate that bilirubin is produced in plant chloroplasts. Live-cell imaging using the bilirubin-dependent fluorescent protein UnaG revealed that bilirubin accumulated in chloroplasts. In vitro, bilirubin was produced nonenzymatically through a reaction between biliverdin and reduced form of nicotinamide adenine dinucleotide phosphate at concentrations comparable to those in chloroplasts. In addition, increased bilirubin production led to lower reactive oxygen species levels in chloroplasts. Our data refute the generally accepted pathway of heme degradation in plants and suggest that bilirubin contributes to the maintenance of redox status in chloroplasts.

In-Hospital Deaths From Ambulatory Care-Sensitive Conditions Before and During the COVID-19 Pandemic in Japan.

Importance: The COVID-19 pandemic may have played a role in the deterioration of access to medical care for ambulatory care-sensitive conditions (ACSCs). Objective: To ascertain whether the number of in-hospital deaths and in-hospital mortality rate associated with ACSC changed after the declaration of the COVID-19 national state of emergency in Japan. Design, Setting, and Participants: This cohort study used a difference-in-differences design to compare outcomes for ACSC in the period before (January 1, 2015, to December 31, 2019) vs the period after (January 1, 2020, to December 31, 2020) Japan declared a national state of emergency for the COVID-19 pandemic. Analyses used discharge summary data from 242 acute care hospitals across Japan. The sample comprised unscheduled hospitalizations of patients with ACSC during the study period (January 1, 2015, to December 31, 2020). Data analyses were performed between August 16 and December 7, 2022. Exposure: The declaration of the COVID-19 national state of emergency announced by the Japanese government in April 2020 was considered to be an exogenous shock. Main Outcomes and Measures: Primary outcomes were the ACSC-associated number of in-hospital deaths, number of hospitalizations, and in-hospital mortality rate. Results: A total of 28 321 ACSC-related hospitalizations were observed involving 15 318 males (54.1%), with a median (IQR) age of 76 (58-85) years. The number of in-hospital deaths was 2117 (7.5%). The number of hospitalizations decreased overall (incidence rate ratio [IRR], 0.84; 95% CI, 0.75-0.94), for chronic conditions (IRR, 0.84; 95% CI, 0.77-0.92), and for vaccine-preventable conditions (IRR, 0.58; 95% CI, 0.44-0.76). However, in-hospital deaths (IRR, 1.66; 95% CI, 1.15-2.39) and in-hospital deaths within 24 hours of hospital arrival (IRR, 7.27 × 106; 95% CI, 1.83 × 106 to 2.89 × 107) increased for acute conditions. The in-hospital mortality rate increased for acute conditions (IRR, 1.71; 95% CI, 1.16-2.54), and the 24-hour in-hospital mortality rates also increased overall (IRR, 1.87; 95% CI, 1.19-2.96), for acute conditions (IRR, 2.15 × 106; 95% CI, 5.25 × 105 to 8.79 × 106), and for vaccine-preventable conditions (IRR, 4.64; 95% CI, 1.28-16.77). Conclusions and Relevance: This cohort study found that in Japan, the number of in-hospital deaths increased after the declaration of the COVID-19 national state of emergency in 2020, particularly for acute ACSC and deaths within 24 hours of hospital admission. This finding suggests that access to good-quality primary care and inpatient care for patients with acute ACSC may have been compromised during the pandemic.

Comparison of Hospital Outcomes for Patients Treated by Allopathic Versus Osteopathic Hospitalists : An Observational Study.

BACKGROUND: The United States has 2 types of degree programs that educate physicians: allopathic and osteopathic medical schools. OBJECTIVE: To determine whether quality and costs of care differ between hospitalized Medicare patients treated by allopathic or osteopathic physicians. DESIGN: Retrospective observational study. SETTING: Medicare claims data. PATIENTS: 20% random sample of Medicare fee-for-service beneficiaries hospitalized with a medical condition during 2016 to 2019 and treated by hospitalists. MEASUREMENTS: The primary outcome was 30-day patient mortality. The secondary outcomes were 30-day readmission, length of stay (LOS), and health care spending (Part B spending). Multivariable regression models adjusted for patient and physician characteristics and their hospital-level averages (to effectively estimate differences within hospitals) were estimated. RESULTS: Of 329 510 Medicare admissions, 253 670 (77.0%) and 75 840 (23.0%) received care from allopathic and osteopathic physicians, respectively. The results can rule out important differences in quality and costs of care between allopathic versus osteopathic physicians for patient mortality (adjusted mortality, 9.4% for allopathic physicians vs. 9.5% [reference] for osteopathic hospitalists; average marginal effect [AME], -0.1 percentage point [95% CI, -0.4 to 0.1 percentage point]; P = 0.36), readmission (15.7% vs. 15.6%; AME, 0.1 percentage point [CI, -0.4 to 0.3 percentage point; P = 0.72), LOS (4.5 vs. 4.5 days; adjusted difference, -0.001 day [CI, -0.04 to 0.04 day]; P = 0.96), and health care spending ($1004 vs. $1003; adjusted difference, $1 [CI, -$8 to $10]; P = 0.85). LIMITATION: Data were limited to elderly Medicare patients hospitalized with medical conditions. CONCLUSION: The quality and costs of care were similar between allopathic and osteopathic hospitalists when they cared for elderly patients and worked as the principal physician in a team of health care professionals that often included other allopathic and osteopathic physicians. PRIMARY FUNDING SOURCE: National Institutes of Health/National Institute on Aging.