Low-Cost, High-Volume Health Services Contribute the Most to Unnecessary Health Spending due to Low-Value Care in Japan.

Importance: As healthcare costs continue to rise, high-income countries-including Japan-face the urgent task of reducing healthcare spending incurred by low-value care. However, evidence is limited as to which low-value care services contribute most to unnecessary healthcare spending outside of the United States.

Objective: To identify which low-value care services contribute the most to unnecessary healthcare spending in Japan.

A unique gating mechanism revealed by the cryo-EM structure of monomeric ATP9A flippase.

Among mammalian P4-ATPase flippases, only ATP9A and ATP9B do not require the auxiliary subunit CDC50 protein. Whilst its yeast homologue, Neo1, is essential for cell survival, little is known about mammalian ATP9A. We present cryo-EM structures of human monomeric ATP9A at a resolution reaching to 2.

Analysis of the Incidence and Severity of Cellulitis During the COVID-19 Pandemic in Japan.

During the COVID-19 pandemic, a decline in various infectious disease cases was observed. However, changes in dermatological infectious diseases, particularly cellulitis, and the potential impact of delayed consultations on severe cases have not been fully explored. To investigate changes in the number of cellulitis patients and severe cases during the COVID-19 pandemic.

Primary Care Physician Characteristics and Low-Value Care Provision in Japan.

Importance: Evidence is limited regarding the physician characteristics associated with the provision of low-value services in primary care, especially outside of the US.

Objective: To measure physician-level use of 10 low-value care services that provide no net clinical benefit and to investigate the characteristics of primary care physicians who frequently provide low-value care in Japan.

Design, Setting, And Participants: This cross-sectional analysis used a nationwide electronic health record database linked with claims data in Japan to assess visits by adult patients (age ≥18 years) to a solo-practice primary care physician from October 1, 2022, through September 30, 2023.

User Profiles of Private Long-term Care Services Not Fully Covered by Public Insurance in Japan.

Introduction: This study aimed to evaluate the characteristics of private long-term care (LTC) service users provided by a company independent from public LTC insurance (LTCI) and to analyze the usage patterns across different types of services.

Methods: We utilized data from 8,046 consultations from the administration data of a private LTC service in Suginami Ward, Tokyo, Japan. We focused on older adults enrolled from February 2016 to October 2019 with follow-up until June 2020.

Molecular Structure of the Na,K-ATPase α4β1 Isoform in Its Ouabain-Bound Conformation.

Na,K-ATPase is the active ion transport system that maintains the electrochemical gradients for Na and K across the plasma membrane of most animal cells. Na,K-ATPase is constituted by the association of two major subunits, a catalytic α and a glycosylated β subunit, both of which exist as different isoforms (in mammals known as α1, α2, α3, α4, β1, β2 and β3). Na,K-ATPase α and β isoforms assemble in different combinations to produce various isozymes with tissue specific expression and distinct biochemical properties.

Human F-ATP synthase as a drug target.

Practical and conceptual barriers have kept human F-ATP synthase out of reach as a target for the treatment of human diseases. Although this situation has persisted for decades, it may change in the near future. In this review the principal functionalities of human F-ATP synthase--proton motive force / ATP interconversion, membrane bending and mitochondrial permeability transition--are surveyed in the context of their respective potential for pharmaceutical intervention.

Last year of life care transitions between long-term care insurance services in Japan: Analysis of long-term care insurance claims data.

Aim: We determined the number of care transitions in the year before death among older adults requiring long-term care (LTC) and those receiving public LTC insurance (LTCI) services in Japan, along with care transition pathways and factors associated with the number of care transitions.

Methods: This study used data from the Japanese LTCI claims, which store national information on certification of needed LTC and LTCI claims data. Services received in the year before death were classified as in-home, facility, mixture of in-home and facility, and not using LTCI services.

Characteristics of first-time users of the nursing small-scale multifunctional home care service: a pooled cross-sectional study using Japanese long-term care insurance claims data from 2012 to 2019.

Objectives: In April 2012, the Japanese government launched a new nursing service called the nursing small-scale multifunctional home care (NSMHC) to meet the nursing care demands of individuals with moderate-to-severe activities of daily living (ADLs) dysfunction and who require medical care, thereby allowing them to continue living in the community. We aimed to preliminarily analyse the characteristics of first-time users of NSMHC service.

Design: This pooled cross-sectional study used the Japanese long-term care insurance (LTCI) claims data from the users' first use of NSMHC (from April 2012 to December 2019).

Association between spatial access and hospitalization for ambulatory care sensitive conditions: A retrospective cohort study using claims data.

Background: Hospitalization for ambulatory care sensitive conditions (ACSCs) is potentially preventable with timely and effective primary care but may increase owing to poor access. Spatial access inequalities exist between Japan and other countries. This retrospective cohort study examined the association between admission for ACSC and spatial accessibility to primary care.

A Na pump with reduced stoichiometry is up-regulated by brine shrimp in extreme salinities.

Brine shrimp () are the only animals to thrive at sodium concentrations above 4 M. Salt excretion is powered by the Na,K-ATPase (NKA), a heterodimeric (αβ) pump that usually exports 3Na in exchange for 2 K per hydrolyzed ATP. express several NKA catalytic α-subunit subtypes.

Specific protonation of acidic residues confers K selectivity to the gastric proton pump.

The gastric proton pump (H,K-ATPase) transports a proton into the stomach lumen for every K ion exchanged in the opposite direction. In the lumen-facing state of the pump (E2), the pump selectively binds K despite the presence of a 10-fold higher concentration of Na. The molecular basis for the ion selectivity of the pump is unknown.

Deep learning driven de novo drug design based on gastric proton pump structures.

Existing drugs often suffer in their effectiveness due to detrimental side effects, low binding affinity or pharmacokinetic problems. This may be overcome by the development of distinct compounds. Here, we exploit the rich structural basis of drug-bound gastric proton pump to develop compounds with strong inhibitory potency, employing a combinatorial approach utilizing deep generative models for de novo drug design with organic synthesis and cryo-EM structural analysis.

An unusual conformation from Na-sensitive non-gastric proton pump mutants reveals molecular mechanisms of cooperative Na-binding.

The Na,K-ATPase (NKA) and non-gastric H,K- ATPase (ngHKA) share ~65 % sequence identity, and nearly identical catalytic cycles. These pumps alternate between inward-facing (E1) and outward-facing (E2) conformations and differ in their exported substrate (Na or H) and stoichiometries (3 Na:2 K or 1 H:1 K). We reported that structures of the NKA-mimetic ngHKA mutant K794S/A797P/W940/R949C (SPWC) with 2 K occluded in E2-P and 3 Na-bound in E1·ATP states were nearly identical to NKA structures in equivalent states.

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.

Three structures of PSI-LHCI from Chlamydomonas reinhardtii suggest a resting state re-activated by ferredoxin.

Photosystem I (PSI) from the green alga Chlamydomonas reinhardtii, with various numbers of membrane bound antenna complexes (LHCI), has been described in great detail. In contrast, structural characterization of soluble binding partners is less advanced. Here, we used X-ray crystallography and single particle cryo-EM to investigate three structures of the PSI-LHCI supercomplex from Chlamydomonas reinhardtii.

Effects of cost sharing on long-term care service utilization among home-dwelling older adults in Japan.

Objectives: This study aimed to examine the effect of increased cost sharing on long-term care (LTC) service utilization among home-dwelling older adults, using nationwide long-term care insurance (LTCI) claims data in Japan.

Methods: In August 2015, the coinsurance rate for Japanese LTCI increased from 10% to 20% for higher-income beneficiaries. We analyzed 27,911,076 person-month observations between April 2015 and July 2016 from 1,983,163 home-dwelling older adults (aged ≥ 65 years).

Structure and function of H/K pump mutants reveal Na/K pump mechanisms.

Ion-transport mechanisms evolve by changing ion-selectivity, such as switching from Na to H selectivity in secondary-active transporters or P-type-ATPases. Here we study primary-active transport via P-type ATPases using functional and structural analyses to demonstrate that four simultaneous residue substitutions transform the non-gastric H/K pump, a strict H-dependent electroneutral P-type ATPase, into a bona fide Na-dependent electrogenic Na/K pump. Conversion of a H-dependent primary-active transporter into a Na-dependent one provides a prototype for similar studies of ion-transport proteins.

Hospitalizations for Ambulatory Care Sensitive Conditions in a Large City of Japan: a Descriptive Analysis Using Claims Data.

Background: Hospitalization for ambulatory care sensitive conditions (ACSCs) is an indicator of the quality of primary care in different health systems. In Japan, where patients can choose any healthcare facility with universal health coverage (UHC), data on these admissions are unknown.

Objective: To describe the current situation of ACSC admissions in a city of Japan.

Structural Basis for Binding of Potassium-Competitive Acid Blockers to the Gastric Proton Pump.

As specific inhibitors of the gastric proton pump, responsible for gastric acidification, K-competitive acid blockers (P-CABs) have recently been utilized in the clinical treatment of gastric acid-related diseases in Asia. However, as these compounds have been developed based on phenotypic screening, their detailed binding poses are unknown. We show crystal and cryo-EM structures of the gastric proton pump in complex with four different P-CABs, tegoprazan, soraprazan, PF-03716556 and revaprazan, at resolutions reaching 2.

Analysis of the diagnosis of Japanese patients with primary ciliary dyskinesia using a conditional reprogramming culture.

Background: Primary ciliary dyskinesia (PCD) is diagnosed through multiple methods, including transmission electron microscopy (TEM), a high-speed video microscopy analysis (HSVA), immunofluorescence (IF), and genetic testing. A primary cell culture has been recommended to avoid the misdiagnosis of secondary ciliary dyskinesia derived from infection or inflammation and improve diagnostic accuracy. However, primary cells fail to differentiate into ciliated cells through repeated passages.

Municipal Characteristics of In-Home Death Among Care-Dependent Older Japanese Adults.

Importance: The provision of in-home and community end-of-life care has emerged as an important policy issue for aging populations around the world. Despite most patients expressing the wish to die at home (as opposed to in the hospital), substantial geographic variation persists in the prevalence of in-home death at the end of life.

Objective: To assess the association of municipal characteristics with variation in the place of death among care-dependent older people in Japan.

National trends in the proportion of in-hospital deaths by cause of death among older adults with long-term care: a nationwide observational study in Japan from 2007 to 2017.

Background: Japan has promoted end-of-life care at home and in long-term care facilities, and the total proportion of in-hospital deaths has decreased recently. However, the difference in trends of in-hospital deaths by the cause of death remains unclear. We investigated the variation in trends of in-hospital deaths among older adults with long-term care from 2007 to 2017, by cause of death and place of care.