Impact of the coronavirus disease 2019 pandemic on primary and metastatic lung cancer treatments in Japan: A nationwide study using an interrupted time series analysis.

BACKGROUND: The coronavirus disease 2019 pandemic prompted healthcare providers to use different approaches from the current standards of care. We aimed to identify the changes in the number of treatments for primary non-small cell lung cancer (NSCLC) and metastatic lung cancer during the pandemic. METHODS: We used nationwide insurance claims data from January 2015 to January 2021, and estimated changes in the number of treatments using an interrupted time series analysis. RESULTS: The number of surgical resections for primary NSCLC significantly decreased in April 2020 (-888; 95% confidence interval [CI]: -1530 to -246) and July 2020 (-1314; 95% CI: -1935 to -694), while the number of stereotactic body radiotherapies (SBRTs) increased in April 2020 (95; 95% CI: 8-182) and July 2020 (111; 95% CI: 24-198). The total number of treatments for primary NSCLC remained unchanged; however, non-significant decreases were observed in 2020. The number of surgical resections for metastatic lung cancer significantly decreased in April 2020 (-201; 95% CI: -337 to -65), but it eventually increased in July 2020 (170; 95% CI: 32-308). Additionally, the number of SBRTs significantly increased in April 2020 (37; 95% CI: 3-71) and October 2020 (57; 95% CI: 23-91). The total number of treatments for metastatic lung cancer was maintained, with an initial decrease in April 2020 followed by a subsequent increase in July and October 2020. CONCLUSION: In Japan, surgical triage for primary and metastatic lung cancer are likely to have been implemented during the pandemic. Despite these proactive measures, patients with primary NSCLC may have been untreated, likely owing to their undiagnosed disease, potentially leading to a deterioration in prognosis. By contrast, patients diagnosed with cancer prior to the pandemic are presumed to have received standard management throughout the course of the pandemic.

Determining Optimal Intervals for In-Person Visits During Video-Based Telemedicine Among Patients With Hypertension: Cluster Randomized Controlled Trial.

BACKGROUND: Introducing telemedicine in outpatient treatment may improve patient satisfaction and convenience. However, the optimal in-person visit interval for video-based telemedicine among patients with hypertension remains unreported in Japan. OBJECTIVE: We determined the optimal in-person visit interval for video-based telemedicine among patients with hypertension. METHODS: This was a cluster randomized controlled noninferiority trial. The target sites were 8 clinics in Japan that had a telemedicine system, and the target patients were individuals with essential hypertension. Among patients receiving video-based telemedicine, those who underwent in-person visits at 6-month intervals were included in the intervention group, and those who underwent in-person visits at 3-month intervals were included in the control group. The follow-up period of the participants was 6 months. The primary end point of the study was the change in systolic blood pressure, and the secondary end points were the rate of treatment continuation after 6 months, patient satisfaction, health economic evaluation, and safety evaluation. RESULTS: Overall, 64 patients were enrolled. Their mean age was 54.5 (SD 10.3) years, and 60.9% (39/64) of patients were male. For the primary end point, the odds ratio for the estimated difference in the change in systolic blood pressure between the 2 groups was 1.18 (90% CI -3.68 to 6.04). Notably, the criteria for noninferiority were met. Patient satisfaction was higher in the intervention group than in the control group. Furthermore, the indirect costs indicated that lost productivity was significantly lesser in the intervention group than in the control group. Moreover, the treatment continuation rate did not differ between the intervention and control groups, and there were no adverse events in either group. CONCLUSIONS: Blood pressure control status and safety did not differ between the intervention and control groups. In-person visits at 6-month intervals may cause a societal cost reduction and improve patient satisfaction during video-based telemedicine. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000040953; https://tinyurl.com/2p8devm9.

Comparison of general satisfaction, oral health-related quality of life, and patient's self-assessment between mandibular single-implant overdentures and experimental removable complete dentures: A randomized crossover clinical trial.

Objective Patient satisfaction with single-implant overdentures (1-IODs) is unclear. This randomized crossover trial aimed to compare the general satisfaction, oral health-related quality of life, and patients' self-assessment between mandibular 1-IODs and experimental removable complete dentures (eRCDs). Methods New mandibular RCDs were fabricated for 22 patients with edentulous mandibles. After adapting to the RCDs, one implant was inserted in the mandibular midline. The participants were then randomly classified into groups 1 and 2. Group 1 received IODs for the first 2 months, while group 2 used eRCDs with a non-loaded implant in the midline. After 2 months, the treatment was switched. Four validated, patient-reported dental outcome measures were assessed: general satisfaction, Japanese version of the Oral Health Impact Profile for edentulous subjects (OHIP EDENT-J), General Oral Health Assessment Index (GOHAI), and Patient's Denture Assessment (PDA). The assessments were performed at the end of the IOD- and eRCD- use periods. Results General satisfaction was significantly higher during the IOD period (p = 0.002). Significant differences were observed in all domains of the OHIP, except orofacial pain (p = 0.084). Further, the total score (p<0.001) and the scores of the physical (p<0.001) and psychosocial functioning (p = 0.001) domains of the GOHAI differed significantly. The total PDA score (p = 0.001) and the scores of the function (p = 0.004), lower denture (p = 0.002), esthetics and speech (p = 0.026), and importance (p = 0.009) domains were significantly higher during the IOD period than during the eRCD period. Conclusion General satisfaction, oral health-related quality of life, and patient self-assessment scores were significantly higher for 1-IODs than for eRCDs. Clinical significance Within the limitations of this study, we found that mandibular single-implant overdentures may be an efficient alternative to mandibular experimental removable complete dentures due to higher general satisfaction, oral health-related quality of life, and patient self-assessment scores of dentures.

A Real-World Comparison of 1-Year Survival and Expenditures for Transcatheter Aortic Valve Replacements: SAPIEN 3 Versus CoreValve Versus Evolut R.

OBJECTIVES: New versions of balloon-expandable and self-expandable valves for transcatheter aortic valve replacement (TAVR) have been developed, but few studies have examined the outcomes associated with these devices using national-level data. This study aimed to elucidate the clinical and economic outcomes of TAVR for aortic stenosis in Japan through an analysis of real-world data. METHODS: This retrospective cohort study was performed using data from patients with aortic stenosis who had undergone transfemoral TAVR with Edwards SAPIEN 3, Medtronic CoreValve, or Medtronic Evolut R valves throughout Japan from April 2016 to March 2018. Pacemaker implantation, mortality, and health expenditure were examined for each valve type during hospitalization and at 1 month, 3 months, 6 months, and 1 year. Generalized linear regression models and Cox proportional hazards models were used to examine the associations between the valve types and outcomes. RESULTS: We analyzed 7244 TAVR cases (SAPIEN 3: 5276, CoreValve: 418, and Evolut R: 1550) across 145 hospitals. The adjusted 1-year expenditures for SAPIEN 3, CoreValve, and Evolut R were $79 402, $76 125, and $75 527, respectively; SAPIEN 3 was significantly more expensive than the other valves (P < .05). The pacemaker implantation hazard ratios (95% confidence intervals) for CoreValve and Evolut R were significantly higher (P < .001) than SAPIEN 3 at 2.61 (2.07-3.27) and 1.80 (1.53-2.12), respectively. The mortality hazard ratios (95% confidence intervals) for CoreValve and Evolut R were not significant at 1.11 (0.84-1.46) and 1.22 (0.97-1.54), respectively. CONCLUSIONS: SAPIEN 3 users had generally lower pacemaker implantation and mortality but higher expenditures than CoreValve and Evolut R users.

Evolving Landscape of New Drug Approval in Japan and Lags from International Birth Dates: Retrospective Regulatory Analysis.

The Pharmaceuticals and Medical Devices Agency (PMDA) has approved hundreds of new drugs in recent years. We retrospectively analyzed the new drugs approved in Japan from 2008 to 2019, and identify the first-in-world approvals and clarify the current drug lag. The new drug and the drug lag were defined as a drug with a new active substance and a difference between the approval date in Japan and the international birth date, respectively. Among 400 new drugs approved in Japan during the last 12 years, 80 (20.0%) were first approved in Japan, and 320 were outside Japan (the United States: 202, 50.5%; Europe: 82, 20.5%; other regions: 36, 9.0%). Of these, 45 new drugs have not yet been approved outside Japan, and the remaining 355 have been globally approved in Japan and overseas. The number of new drug approvals were the largest in oncology followed by metabolic/endocrine and infectious diseases. The median drug lags (year) among all 400 new drugs and 355 new drugs with global approvals were 4.3 and 4.7 in the first tertile (2008-2011), 1.5 and 2.6 in the second tertile (2012-2015), and reduced to 1.3 and 2.2 in the third tertile (2016-2019), respectively. Substantial drug lag remains in neurology, psychiatry, and therapeutic areas where the number of new drug approvals was relatively small. Collectively, one-fifth of the new drugs approved in Japan are first-in-world approvals. Drug lag has been greatly decreased, although it still exists.

The sustainability and the survivability of Kyoto's traditional craft industry revealed from supplier-customer network.

Due to the changes in consumer demand and generational transformations, Kyoto's traditional craft industry has suffered substantial revenue losses in recent years. This research aimed to characterize Kyoto's traditional craft industry by analyzing the supplier-customer network involving individual firms within the Kyoto region. In the process, we clarify the community structure, key firms, network topological characteristics, bow-tie structure, robustness, the vulnerability of the supplier-customer network as crucial factors for sustainable growth. The community and bow-tie structure analysis became clear that the traditional craft industry continues to occupy an important position in Kyoto's industrial network. Furthermore, we clarify the relationship between modern and traditional craft industries' network characteristics and their relative profitability and productivity. It became evident that the traditional craft industry has a different network structure from the modern consumer games and electric machinery industries. The modern industries have the strongly coupled component, and the attendant firms there create high value-added and play a significant role in driving the entire industry, while more traditional craft industries, such as the Nishijin silk fabrics and Kyoto doll industries, do not have this strongly coupled component. Moreover, the traditional crafts industry does not have a central firm or a dense network for integrating information, which is presumed to be a factor in the decline of the traditional craft industry.

Healthcare resources attributable to methicillin-resistant Staphylococcus aureus orthopedic surgical site infections.

The number of orthopedic surgeries is increasing as populations steadily age, but surgical site infection (SSI) rates remain relatively consistent. This study aimed to quantify the healthcare resources attributable to methicillin-resistant Staphylococcus aureus (MRSA) SSIs in orthopedic surgical patients. The analysis was conducted using a national claims database comprising data from almost all Japanese residents. We examined patients who underwent any of the following surgeries between April 2012 and March 2018: amputation (AMP), spinal fusion (FUSN), open reduction of fracture (FX), hip prosthesis (HPRO), knee prosthesis (KPRO), and laminectomy (LAM). Propensity score matching was performed to identify non-SSI control patients, and generalized estimating equations were used to estimate the differences in outcomes between the case and control groups. The numbers of MRSA SSI cases (infection rates) ranged from 64 (0.03%) to 1,152 (2.33%). MRSA SSI-attributable increases in healthcare expenditure ranged from $11,630 ($21,151 vs. $9,521) for LAM to $35,693 ($50,122 vs. $14,429) for FX, and increases in hospital stay ranged from 40.6 days (59.2 vs. 18.6) for LAM to 89.5 days (122.0 vs. 32.5) for FX. In conclusion, MRSA SSIs contribute to substantial increases in healthcare resource utilization, emphasizing the need to implement effective infection prevention measures for orthopedic surgeries.

Differences in healthcare expenditure estimates according to statistical approach: A nationwide claims database study on patients with hepatocellular carcinoma.

AIM: Disease-associated healthcare expenditures are generally calculated using matched comparisons or regression-based analyses, but little is known about their differences in estimates. This aim of this study was to compare the differences between disease-associated healthcare expenditures estimated using these 2 methods. METHODS: In this retrospective cohort study, a matched comparison was first conducted by matching cases with controls using sex, age, and comorbidities to estimate disease-associated expenditures. The cases were then used in a fixed-effects analysis that compared expenditures before and after disease occurrence. The subjects were adults (≥20 years) with primary hepatocellular carcinoma (HCC) who underwent treatment (including surgical resection, locoregional therapy, transcatheter arterial chemoembolization, and transarterial embolization) at a Japanese hospital between April 2010 and March 2018. We calculated the total healthcare expenditures per patient per month according to treatment and disease phase (initial, continuing, and terminal). RESULTS: There were 14,923 cases in the initial/continuing phases and 15,968 cases in the terminal phase. In the initial/continuing phases, 3,552 patients underwent surgical resection only, with HCC-associated expenditures of $5,555 according to the matched comparison and $5,889 according to the fixed-effects analysis (proportional difference: 94.3%). The initial phase expenditures were approximately 9% higher in the fixed-effects analysis, whereas the continuing phase expenditures were approximately 7% higher in the matched comparison. The expenditures in the terminal phase were 93.1% higher in the fixed-effects analysis. CONCLUSIONS: The 2 methods produced similar estimates of HCC-associated healthcare expenditures in the initial/continuing phases. However, terminal phase expenditures were substantially different between the methods.

Comparing Retreatments and Expenditures in Flow Diversion Versus Coiling for Unruptured Intracranial Aneurysm Treatment: A Retrospective Cohort Study Using a Real-World National Database.

BACKGROUND: Flow diverters (FDs) have marked the beginning of innovations in the endovascular treatment of large unruptured intracranial aneurysms, but no multi-institutional studies have been conducted on these devices from both the clinical and economic perspectives. OBJECTIVE: To compare retreatment rates and healthcare expenditures between FDs and conventional coiling-based treatments in all eligible cases in Japan. METHODS: We identified patients who had undergone endovascular treatments during the study period (October 2015-March 2018) from a national-level claims database. The outcome measures were retreatment rates and 1-yr total healthcare expenditures, which were compared among patients who had undergone FD, coiling, and stent-assisted coiling (SAC) treatments. The coiling and SAC groups were further categorized according to the number of coils used. Retreatment rates were analyzed using Cox proportional hazards models, and total expenditures were analyzed using multilevel mixed-effects generalized linear models. RESULTS: The study sample comprised 512 FD patients, 1499 coiling patients, and 711 SAC patients. The coiling groups with ≥10 coils and ≥9 coils had significantly higher retreatment rates than the FD group with hazard ratios of 2.75 (1.30-5.82) and 2.52 (1.24-5.09), respectively. In addition, the coiling group with ≥10 coils and SAC group with ≥10 coils had significantly higher 1-year expenditures than the FD group with cost ratios (95% CI) of 1.30 (1.13-1.49) and 1.31 (1.15-1.50), respectively. CONCLUSION: In this national-level study, FDs demonstrated significantly lower retreatment rates and total expenditures than conventional coiling with ≥ 9 coils.

Healthcare Expenditures for the Treatment of Patients Infected with Hepatitis C Virus in Japan.

AIM: The recently developed direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infections are costly. Cost-effectiveness analyses of DAAs require accurate healthcare expenditure estimates for the various HCV disease states, but few studies have produced such estimates using national-level data. This study utilized nationally representative data to estimate the healthcare expenditure for each HCV disease state. METHODS: We identified all patients infected with HCV between April 2010 and March 2018 from a nationwide administrative claims database in Japan. Monthly patient-level healthcare expenditures were calculated for the following disease states: chronic hepatitis C (CHC), compensated cirrhosis (CC), decompensated cirrhosis (DC), and hepatocellular carcinoma (HCC). The expenditures for the CHC and CC states were also compared before DAA treatment and after sustained virologic response (SVR) was achieved. A longitudinal two-part model was employed to estimate the healthcare expenditures for each state. RESULTS: During the study period, 1,564,043 patients with 146,488,137 patient-months of data met the inclusion criteria. The year of valuation was 2017. The mean monthly healthcare expenditures per patient (95% confidence intervals) for the pre-DAA CHC, CC, DC, and HCC states were US$267 (US$267-268), US$428 (US$427-429), US$666 (US$663-669), and US$969 (US$966-972), respectively. The mean monthly healthcare expenditures per patient for the post-SVR (≥ 2 years) CHC and CC states were US$176 (US$176-177) and US$238 (US$236-240), respectively. Healthcare expenditure increased with increasing age in all disease states (P < 0.05). CONCLUSIONS: These healthcare expenditure estimates from a nationally representative sample have potential applications in cost-effectiveness analyses of DAAs.

A Validation Study of the Remotely Administered Montreal Cognitive Assessment Tool in the Elderly Japanese Population.

Background: In an aging society, neuropsychological testing using video teleconferencing (VTC) is increasingly important. Despite the potential benefit of a VTC-administered Montreal Cognitive Assessment Tool (MoCA) to detect cognitive decline, only a limited number of studies have investigated this tool's reliability. Therefore, we aimed to evaluate the reliability of VTC-administered MoCA compared with face-to-face (FTF)-administered MoCA among elderly Japanese participants. Moreover, we examined participants' satisfaction with VTC-administered MoCA. Methods: Participants ≥60 years of age with and without cognitive impairment (i.e., those with mild cognitive impairment [MCI], those with dementia, and healthy controls [HC]) were assessed with VTC- and FTF-administered MoCA at an interval of >2 weeks and <3 months. The order effect (VTC first vs. FTF first) and time effect (first vs. second testing session), as well as several covariates such as age and years of education were controlled. Intraclass correlation coefficients (ICCs) were calculated using a mixed-effects model to assess the agreement between the two (VTC- vs. FTF-administered) groups. Participants' satisfaction with VTC-administered MoCA was examined using a Likert scale asking seven questions. Results: We included 73 participants in the study (36 men; age, 76.3 ± 7.5 years). The ICC for the MoCA total score was high in the entire sample (0.85), whereas ICCs were moderate to high for the subgroups (MCI: 0.82, dementia: 0.82, and HC: 0.53). Furthermore, we found good overall participant satisfaction with VTC-administered MoCA. Discussion: VTC-administered MoCA appears viable as an alternative to FTF-administered MoCA, although further replication studies with larger sample sizes are needed.

Remote neuropsychological assessment of elderly Japanese population using the Alzheimer's Disease Assessment Scale: A validation study.

INTRODUCTION: Studies have demonstrated the high agreement of several remote neuropsychological tests using video teleconferencing (VTC) with face-to-face (FTF) tests. However, the reliability of the remotely administered Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog), one of the most commonly used neuropsychological tests to detect cognitive decline, has not been substantially elucidated, particularly in Japanese populations. Therefore, this study aimed to evaluate the reliability of the remotely administered ADAS-cog compared with FTF-administered ADAS-cog among elderly Japanese participants. METHODS: Participants aged ≥60 years with and without cognitive impairment, i.e. those with mild cognitive impairment (MCI), those with dementia and healthy controls (HCs), were assessed with the ADAS-cog using VTC and FTF testing at an interval of >2 weeks and <3 months. The assessment order (VTC or FTF) was randomized by participants. Participants' scores were compared among the entire sample, as well as subgroups, using intra-class correlation coefficients (ICCs) in a mixed-effects model. RESULTS: A total of 73 participants were included in the study (36 men; age, 76.3 ± 7.6 years). The ICC for the ADAS-cog total score was high in the entire sample (0.86), whereas ICCs were moderate to high for the subgroups (MCI: 0.63, dementia: 0.80 and HC: 0.74). DISCUSSION: The results indicate that a VTC-administered ADAS-cog could be an alternative for an FTF-administered ADAS-cog, although further replication studies with larger sample sizes and a wider range of cognitive functionalities are warranted.

A model for cooperative gating of L-type Ca2+ channels and its effects on cardiac alternans dynamics.

In ventricular myocytes, membrane depolarization during the action potential (AP) causes synchronous activation of multiple L-type CaV1.2 channels (LTCCs), which trigger the release of calcium (Ca2+) from the sarcoplasmic reticulum (SR). This results in an increase in intracellular Ca2+ (Cai) that initiates contraction. During pulsus alternans, cardiac contraction is unstable, going from weak to strong in successive beats despite a constant heart rate. These cardiac alternans can be caused by the instability of membrane potential (Vm) due to steep AP duration (APD) restitution (Vm-driven alternans), instability of Cai cycling (Ca2+-driven alternans), or both, and may be modulated by functional coupling between clustered CaV1.2 (e.g. cooperative gating). Here, mathematical analysis and computational models were used to determine how changes in the strength of cooperative gating between LTCCs may impact membrane voltage and intracellular Ca2+ dynamics in the heart. We found that increasing the degree of coupling between LTCCs increases the amplitude of Ca2+ currents (ICaL) and prolongs AP duration (APD). Increased AP duration is known to promote cardiac alternans, a potentially arrhythmogenic substrate. In addition, our analysis shows that increasing the strength of cooperative activation of LTCCs makes the coupling of Ca2+ on the membrane voltage (Cai→Vm coupling) more positive and destabilizes the Vm-Cai dynamics for Vm-driven alternans and Cai-driven alternans, but not for quasiperiodic oscillation. These results suggest that cooperative gating of LTCCs may have a major impact on cardiac excitation-contraction coupling, not only by prolonging APD, but also by altering Cai→Vm coupling and potentially promoting cardiac arrhythmias.

Impact of teaching intensity and academic status on medical resource utilization by teaching hospitals in Japan.

Teaching hospitals require excess medical resources to maintain high-quality care and medical education. To evaluate the appropriateness of such surplus costs, we examined the impact of teaching intensity defined as activities for postgraduate training, and academic status as functions of medical research and undergraduate teaching on medical resource utilization. Administrative data for 47,397 discharges from 40 academic and 12 non-academic teaching hospitals in Japan were collected. Hospitals were classified into three groups according to intern/resident-to-bed (IRB) ratio. Resource utilization of medical services was estimated using fee-for-service charge schedules and normalized with case mix grouping. 15-24% more resource utilization for laboratory examinations, radiological imaging, and medications were observed in hospitals with higher IRB ratios. With multivariate adjustment for case mix and academic status, higher IRB ratios were associated with 10-15% more use of radiological imaging, injections, and medications; up to 5% shorter hospital stays; and not with total resource utilization. Conversely, academic status was associated with 21-33% more laboratory examinations, radiological imaging, and medications; 13% longer hospital stays; and 10% more total resource utilization. While differences in medical resource utilization by teaching intensity may not be associated with indirect educational costs, those by academic status may be. Therefore, academic hospitals may need efficiency improvement and financial compensation.

Preoperative assessment of the risk factors that help to predict the prognosis after living donor liver transplantation.

BACKGROUND: The purpose of this study was to analyze various risk factors and to assess the preoperative risk score, which can predict the prognosis after living donor liver transplantation (LDLT). METHODS: From February 2002 to August 2007, 84 adult to adult living donor liver transplantation donors and recipients were analyzed. First, the donor, recipient, and intraoperative factors were examined by univariate and multivariate analyses. We then gave a score of one point for each significant marginal factor (total point scores were called "risk score") and each risk score was examined by univariate analyses. RESULTS: Recipients with the donor age 50 years or older, Model for End-Stage Liver Disease (MELD) score (> or =21), and hepatitis C virus-positive status had a significantly poor survival. Recipients between the risk score of 0 vs. scores of 2 + 3 (p < 0.001, log-rank) and risk score of 1 vs. scores of 2 + 3 (p = 0.003, log-rank) had significantly different survival. CONCLUSIONS: Preoperative assessment of the risk score might help to predict recipient outcomes after living donor liver transplantation.

A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates.

Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Ca(i)) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (I(Ca,L)) and Ca(i) cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35-37 degrees C. Incorporating a minimal seven-state Markovian model of I(Ca,L) that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Ca(i) cycling model, the new model replicates experimentally observed action potential duration and Ca(i) transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing.