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Onychomycosis, a fungal nail infection, is a common dermatological condition in Japan, with a prevalence of approximately 5%-10%. Despite the introduction of new antifungal medications and updated treatment guidelines published in 2019, data on real-world prescription trends and the associated medical costs are limited. This study aimed to investigate the prescription patterns and medical costs of topical and oral antifungal medications for onychomycosis in Japan from fiscal years 2014 to 2021 using the National Database of Health Insurance Claims and Specific Health Checkups of Japan Open Data. We analyzed the annual prescription volumes and medical costs of four antifungal medications: efinaconazole, luliconazole, fosravuconazole, and terbinafine. The prescription volume of efinaconazole, a topical medication launched in 2014, rapidly increased and dominated the market share. Fosravuconazole, an oral medication introduced in 2018, showed an increasing trend, coinciding with a decline in efinaconazole prescriptions. Terbinafine, a well-established oral medication, experienced a substantial decrease in prescription volume. The sex- and age-adjusted prescription volume per 100 000 population was higher among older adults, particularly for efinaconazole. The total medical costs for onychomycosis treatment more than doubled in fiscal year 2015 compared with that for 2014, mainly driven by efinaconazole prescriptions, and exceeded 30 billion Japanese yen in fiscal years 2019-2021. The costs slightly decreased in fiscal years 2020 and 2021, possibly due to the introduction of fosravuconazole. The predominance of topical prescriptions, especially in older adults, raises concerns regarding adherence to the Japanese guidelines that recommend oral antifungals as the first-line treatment for onychomycosis. The substantial increase in medical costs also highlights the economic burden of onychomycosis and the need for cost-effective treatment strategies. This study provides valuable insights into the real-world prescription trends and medical costs of onychomycosis treatment in Japan, suggesting an opportunity to assess potential gaps between guideline recommendations and clinical practice.
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In observational studies, identifying and adjusting for a sufficient set of confounders is crucial for accurately estimating the causal effect of the exposure on the outcome. Even in studies with large sample sizes, which typically benefit from small variances in estimates, there is a risk of producing estimates that are precisely inaccurate if the study suffers from systematic errors or biases, including confounding bias. To date, several approaches have been developed for selecting confounders. In this article, we first summarize the epidemiological and statistical approaches to identify a sufficient set of confounders. Particularly, we introduce the modified disjunctive cause criterion as one of the most useful approaches, which involves controlling for any pre-exposure covariate that affects the exposure, outcome, or both. It then excludes instrumental variables but includes proxies for the shared common cause of exposure and outcome. Statistical confounder selection is also useful when dealing with a large number of covariates, even in studies with small sample sizes. After introducing several approaches, we discuss some pitfalls and considerations in confounder selection, such as the adjustment for instrumental variables, intermediate variables, and baseline outcome variables. Lastly, as it is often difficult to comprehensively measure key confounders, we introduce two statistics, E-value and Robustness value, for assessing sensitivity to unmeasured confounders. Illustrated examples are provided using the National Health and Nutritional Examination Survey Epidemiologic Follow-up Study. Integrating these principles and approaches will enhance our understanding of confounder selection and facilitate better reporting and interpretation of future epidemiological studies.
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We compared the comprehensive clinical outcomes of focal therapy (FT) and robot-assisted radical prostatectomy (RARP) in patients with localized prostate cancer (PC) using a win ratio analysis. After propensity score matching, a win ratio analysis, in which the composite endpoints of failure-free survival (FFS) and the urinary domain of the Expanded Prostate Cancer Index Composite (EPIC) were analyzed, was used for the comparison of the clinical outcomes of FT and RARP for the patients with localized PC. Seventy-two patients were included in each group after propensity score matching. FFS was not significantly different between the groups (p = 0.5044) after 36 months of follow-up. In contrast, the score of the urinary domain of the EPIC in the FT group was significantly better than that in the RARP group (p < 0.0001). The win ratio of FT per RARP was 3.39 (p < 0.0001; 95% confidence interval 2.21-5.20), suggesting a higher comprehensive outcome in the FT group than in the RARP group during short-term follow-up in single institution. Although further randomized trial with long-term follow-up would be needed for the evaluation, the win ratio would be useful to analyze the efficacy of FT according to patient preferences comprehensively.
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Prostatectomía , Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Humanos , Masculino , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Prostatectomía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Puntaje de Propensión , Estudios de SeguimientoRESUMEN
Background: Little is known about the relationship between the disease activity of Behçet disease (BD) and the incidence of inflammatory major organ events. Objectives: In this prospective registry study, we investigated the association between the Behçet Disease Current Activity Form (BDCAF) and incidence of inflammatory major organ events, defined as the inflammation of the ocular, central nervous, intestinal, and vascular systems in BD. Methods: We enrolled participants from Japanese multicenter prospective cohorts. The BDCAF was evaluated annually. BD-related symptoms, including inflammatory major organ events, were monitored. The association between BDCAF and inflammatory major organ events was analyzed by time-to-event analysis. An unsupervised clustering of the participants' BDCAF, therapeutic agents, and multiple serum cytokines was also performed to examine their association with inflammatory major organ events. Results: A total of 260 patients were included. The patients had a median BDCAF score of 2 [Interquartile range, 1-3] at the enrolment and remained disease active at 1- and 2-year follow-ups, indicating residual disease activity in BD. Patients with a BDCAF score of 0 had a longer inflammatory major organ event-free survival at 52 weeks than those with a score of 1 or higher (p=2.2 x 10-4). Clustering analysis revealed that patients who did not achieve remission despite treatment with tumor necrosis factor inhibitors had high serum inflammatory cytokine levels and incidences of inflammatory major organ events. Among the elevated cytokines, IL-6 was associated with inflammatory major organ events. Conclusion: This study suggests that treatment strategies targeting overall disease activity and monitoring residual serum IL-6 may help prevent inflammatory major organ events in BD.
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Síndrome de Behçet , Interleucina-6 , Sistema de Registros , Síndrome de Behçet/sangre , Síndrome de Behçet/epidemiología , Humanos , Masculino , Femenino , Interleucina-6/sangre , Adulto , Estudios Prospectivos , Incidencia , Persona de Mediana Edad , Inflamación/sangre , Biomarcadores/sangre , Japón/epidemiología , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Assessment of male lower urinary tract symptoms (LUTS) needs to identify predictors of symptom outcomes when interventional treatment is planned. OBJECTIVE: To develop a novel prediction model for prostate surgery outcomes and validate it using a separate patient cohort and derive thresholds for key clinical parameters. DESIGN, SETTING, AND PARTICIPANTS: From the UPSTREAM trial of 820 men seeking treatment for LUTS, analysis of bladder diary (BD), International Prostate Symptom Score (IPSS), IPSS-quality of life, and uroflowmetry data was performed for 176 participants who underwent prostate surgery and provided complete data. For external validation, data from a retrospective database of surgery outcomes in a Japanese urology department (n = 227) were used. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Symptom improvement was defined as a reduction in total IPSS of ≥3 points. Multiple logistic regression, classification tree analysis, and random forest models were generated, including versions with and without BD data. RESULTS AND LIMITATIONS: Multiple logistic regression without BD data identified age (p = 0.029), total IPSS (p = 0.0016), and maximum flow rate (Qmax; p = 0.066) as predictors of outcomes, with area under the receiver operating characteristic curve (AUC) of 77.1%. Classification tree analysis without BD data gave thresholds of IPSS <16 and Qmax ≥13 ml/s (AUC 75.0%). The random forest model, which included all clinical parameters except BD data, had an AUC of 94.7%. Internal validation using the bootstrap method showed reasonable AUCs (69.6-85.8%). Analyses using BD data marginally improved the model fits. External validation gave comparable AUCs for logistic regression, classification tree analysis, and random forest models (all without BD; 70.9%, 67.3%, and 68.5%, respectively). Limitations include the significant number of men with incomplete baseline data and limited assessments in the external validation cohort. CONCLUSIONS: Outcomes of prostate surgery can be predicted preoperatively using age, total IPSS, and uroflowmetry data, with prognostic thresholds of 16 for IPSS and 13 ml/s for Qmax. PATIENT SUMMARY: This study identified key preoperative factors that can predict outcomes of prostate surgery for bothersome urinary symptoms, including which patients are at risk of a poor outcome.
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Síntomas del Sistema Urinario Inferior , Próstata , Humanos , Masculino , Síntomas del Sistema Urinario Inferior/diagnóstico , Síntomas del Sistema Urinario Inferior/cirugía , Pronóstico , Calidad de Vida , Estudios Retrospectivos , Reología , Ensayos Clínicos como AsuntoRESUMEN
To establish a safer and more efficient treatment strategy with mini-endoscopic combined intrarenal surgery (ECIRS), the present study aimed to develop models to predict the outcomes of mini-ECIRS in patients with renal and/or ureteral stones. We retrospectively analysed consecutive patients with renal and/or ureteral stones who underwent mini-ECIRS at three Japanese tertiary institutions. Final treatment outcome was evaluated by CT imaging at 1 month postoperatively and stone free (SF) was defined as completely no residual stone or residual stone fragments ≤ 2 mm. Three prognostic models (multiple logistic regression, classification tree analysis, and machine learning-based random forest) were developed to predict surgical outcomes using preoperative clinical factors. Clinical data from 1432 ECIRS were pooled from a database registered at three institutions, and 996 single sessions of mini-ECIRS were analysed in this study. The overall SF rate was 62.3%. The multiple logistic regression model consisted of stone burden (P < 0.001), number of involved calyces (P < 0.001), nephrostomy prior to mini-ECIRS (P = 0.091), and ECOG-PS (P = 0.110), wherein the area under the curve (AUC) was 70.7%. The classification tree analysis consisted of the number of involved calyces with an AUC of 61.7%. The random forest model showed that the top predictive variable was the number of calyces involved, with an AUC of 91.9%. Internal validation revealed that the AUCs for the multiple logistic regression model, classification tree analysis and random forest models were 70.4, 69.6 and 85.9%, respectively. The number of involved calyces, and a smaller stone burden implied a SF outcome. The machine learning-based model showed remarkably high accuracy and may be a promising tool for physicians and patients to obtain proper consent, avoid inefficient surgery, and decide preoperatively on the most efficient treatment strategies, including staged mini-ECIRS.
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Cálculos Renales , Nefrostomía Percutánea , Cálculos Ureterales , Humanos , Ureteroscopía/métodos , Cálculos Renales/diagnóstico por imagen , Cálculos Renales/cirugía , Cálculos Renales/etiología , Estudios Retrospectivos , Nefrostomía Percutánea/métodos , Cálculos Ureterales/diagnóstico por imagen , Cálculos Ureterales/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: The net benefit is an effect measure for any type of endpoint, including the time-to-event outcome, and can provide intuitive and clinically meaningful interpretation. It is defined as the probability of a randomly selected subject from the experimental arm surviving by at least a clinically relevant time longer than a randomly selected subject from the control arm. In oncology clinical trials, an intercurrent event such as treatment switching is common, which potentially causes informative censoring; nevertheless, conventional methods for the net benefit are not able to deal with it. In this study, we proposed a new estimator using the inverse probability of censoring weighting (IPCW) method and illustrated an oncology clinical trial with treatment switching (the SHIVA study) to apply the proposed method under the estimand framework. METHODS: The net benefit can be estimated using the survival functions of each treatment group. The proposed estimator was based on the survival functions estimated by the inverse probability of the censoring weighting method that can handle covariate-dependent censoring. The simulation study was undertaken to evaluate the operating characteristics of the proposed estimator under several scenarios; we varied the shapes of the survival curves, treatment effect, covariates effect on censoring, proportion of the censoring, threshold of the net benefit, and sample size. We also applied conventional methods (the scoring rules by Péron or Gehan) and the proposed method to the SHIVA study. RESULTS: Our simulation study showed that the proposed estimator provided less biased results under the covariate-dependent censoring than existing estimators. When applying the proposed method to the SHIVA study, we were able to estimate the net benefit by incorporating the information of the covariates with different estimand strategies to address the intercurrent event of the treatment switching. However, the estimates of the proposed method and those of the aforementioned conventional methods were similar under the hypothetical strategy. CONCLUSIONS: We proposed a new estimator of the net benefit that can include covariates to account for the possibly informative censoring. We also provided an illustrative analysis of the proposed method for the oncology clinical trial with treatment switching using the estimand framework. Our proposed new estimator is suitable for handling the intercurrent events that can potentially cause covariate-dependent censoring.
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Neoplasias , Cambio de Tratamiento , Humanos , Neoplasias/terapia , Simulación por Computador , Probabilidad , Tamaño de la Muestra , Análisis de SupervivenciaRESUMEN
AIM: The anti-programmed death-ligand 1 antibody atezolizumab and vascular endothelial growth factor-neutralizing antibody bevacizumab in combination (Atezo + Bev) have become the first-line therapy in advanced hepatocellular carcinoma (HCC). Distinct types of tumor immune microenvironment (TIME) and their associations with specific molecular subclasses and driver gene mutations have been identified in HCC; however, these insights are mainly based on surgically resected early-stage tumors. The current study aimed to reveal the biology and TIME of advanced HCC and their significance in predicting clinical outcomes of Atezo + Bev therapy. METHODS: Thirty-three patients with advanced HCC who were scheduled for treatment with Atezo + Bev therapy were included in this study. Pretreatment tumor biopsy, pre- and posttreatment diffusion-weighted magnetic resonance imaging (MRI) with nine b values (0-1500 s/mm2 ), and other clinicopathologic factors were analyzed. RESULTS: Compared with resectable HCC, advanced HCC was characterized by higher proliferative activity, a higher frequency of Wnt/ß-catenin-activated HCC, and lower lymphocytic infiltration. Prognostically, two metabolism-related factors, histopathologically determined tumor steatosis and/or glutamine synthetase (GS) expression, and MRI-determined tumor steatosis, were the most significant prognostic indicators for progression-free survival (PFS) and overall survival after Atezo + Bev therapy. Furthermore, changes in the pre- and posttreatment true diffusion coefficients on MRI, which might reflect changes in TIME after treatment, were significantly associated with better PFS. CONCLUSIONS: The biology and TIME of HCC were strikingly different in advanced HCC compared with those of surgically resected HCC. Two metabolism-related factors, pathologically determined tumor steatosis and/or GS expression, and MRI-determined tumor steatosis, were found to be the most significant prognostic indicators for Atezo + Bev therapy in advanced HCC.
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BACKGROUND: Despite the diversity of thermal ablations, such as radiofrequency ablation (RFA) and microwave ablation (MWA), and non-thermal ablation, such as irreversible electroporation (IRE) cross-comparisons of multiple ablative modalities for hepatocellular carcinoma (HCC) treatment remain scarce. Thus, we investigated the therapeutic outcomes of different three ablation modalities in the treatment of early stage HCC. METHODS: A total of 322 consecutive patients with 366 HCCs (mean tumor size ± standard deviation: 1.7 ± 0.9 cm) who underwent RFA (n = 216, 59.0%), MWA (n = 91, 28.3%), or IRE (n = 15, 4.7%) were included. Local tumor progression (LTP) rates for LTP were compared among the three modalities. Propensity score-matched analysis was used to reduce selection bias. RESULTS: A significant difference in 2-year LTP rates between the IRE and RFA groups (IRE, 0.0% vs. RFA, 45.0%; p = 0.005) was found. There was no significant difference in 2-year LTP rates between the IRE and MWA groups (IRE, 0.0% vs. MWA, 25.0%; p = 0.103) as well as between the RFA and MWA groups (RFA, 18.2% vs. MWA, 20.6%; p = 0.586). CONCLUSION: IRE provides better local tumor control than RFA as a first-line therapeutic option for small perivascular HCC.
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Benefit-risk balance is gaining interest in clinical trials. For the comprehensive assessment of benefits and risks, generalized pairwise comparisons are increasingly used to estimate the net benefit based on multiple prioritized outcomes. Although previous research has demonstrated that the correlations between the outcomes impact the net benefit and its estimate, the direction and magnitude of this impact remain unclear. In this study, we investigated the impact of correlations between two binary or Gaussian variables on the true net benefit values via theoretical and numerical analyses. We also explored the impact of correlations between survival and categorical variables on the net benefit estimates based on four existing methods (Gehan, Péron, Gehan with correction, and Péron with correction) in the presence of right censoring via simulation and application to actual oncology clinical trial data. Our theoretical and numerical analyses revealed that the true net benefit values were impacted by the correlations in various directions depending on the outcome distributions. With binary endpoints, this direction was governed by a simple rule with a threshold of 50% for a favorable outcome. Our simulation showed that the net benefit estimates based on Gehan's or Péron's scoring rule could be substantially biased in the presence of right censoring, and that the direction and magnitude of this bias were associated with the outcome correlations. The recently proposed correction method greatly reduced this bias, even in the presence of strong outcome correlations. The impact of correlations should be carefully considered when interpreting the net benefit and its estimate.
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Ensayos Clínicos como Asunto , Medición de Riesgo , HumanosRESUMEN
BACKGROUND: Chemotherapy-induced peripheral neuropathy can occur in the right and left hand. Studies on prevention treatments for chemotherapy-induced peripheral neuropathy have largely adopted either self-controlled designs or parallel designs to compare two preventive treatments. When three treatment options (two experimental treatments and a control treatment) are available, both designs can be extended. However, no clinical trials have adopted a self-controlled design to compare three prevention treatments for chemotherapy-induced peripheral neuropathy. The incomplete block crossover design for more than two treatments can be extended to compare three treatments in the self-controlled design. In simple extension, some of the participants receive two experimental treatments in both hands; however, it may be difficult to administer different experimental treatments in both hands for practical reasons, such as a concern for the different types of unexpected adverse events. This study proposes a design and analysis method appropriate for the situation where only one experimental treatment is provided to each participant. METHODS: We assume clinical trials to compare each of the two experimental treatments (E1 and E2) with the control treatment (C) and between two experimental treatments only when both experimental treatments are superior to the control treatment. We propose a self-controlled design, which equally randomizes to four arms to adjust for the dominant hand effect: Arm 1: E1 for right hand, C for left hand; Arm 2: C for right hand, E1 for left hand; Arm 3: E2 for right hand, C for left hand; and Arm 4: C for right hand, E2 for left hand. We compare operating characteristics of the proposed design with the three-arm parallel design in which the same treatment is performed in both hands by participants. We also assess three proposed analysis methods for comparisons between experimental treatments in the self-controlled design under several conditions of correlations between right and left hands using simulation studies. RESULTS: The simulation studies showed that the proposed design was more powerful than the three-arm parallel design when correlation was 0.3 or higher. For comparisons between experimental treatments, the methods based on the regression model, including the outcome of hands with C as a covariate, had the highest power under modest to high correlation among the analysis methods in the self-controlled design. CONCLUSION: The proposed design can improve the power for comparing between two experimental treatments and the control treatment. Our design is useful in situations where it is undesirable for participants to receive different experimental treatments in both hands for practical reasons.
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Antineoplásicos , Humanos , Ensayos Clínicos como Asunto , Simulación por ComputadorRESUMEN
In phase I trials of a novel anticancer drug, one of the most important objectives is to identify the maximum tolerated dose (MTD). To this end, a number of methods have been proposed and evaluated under various scenarios. However, the percentages of correct selection (PCS) of MTDs using previous methods are insufficient to determine the dose for late-phase trials. The purpose of this study is to construct an action rule for escalating or de-escalating the dose and continuing or stopping the trial to increase the PCS as much as possible. We show that deep reinforcement learning with an appropriately defined state, action, and reward can be used to construct such an action selection rule. The simulation study shows that the proposed method can improve the PCS compared with the 3 + 3 design, CRM, BLRM, BOIN, mTPI, and i3 + 3 methods.
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Antineoplásicos , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Antineoplásicos/efectos adversos , Simulación por Computador , Oncología Médica , Proyectos de Investigación , Dosis Máxima Tolerada , Relación Dosis-Respuesta a Droga , Teorema de BayesRESUMEN
BACKGROUND/AIM: SEC11A gene encodes the SPC18 protein, which has been implicated in tumour progression by inducing the secretion of various growth factors. We investigated the clinical significance of SEC11A expression in gastric cancer (GC) tissues in patients with locally advanced gastric cancer (LAGC) after curative resection. PATIENTS AND METHODS: We estimated SEC11A expression in cancer tissues from 253 pStage II/III GC patients who underwent curative resection using quantitative polymerase chain reaction (PCR) and investigated the relationship of SEC11A expression with clinicopathological factors and survival. RESULTS: SEC11A expression was significantly related to serosal invasion, lymph node metastasis, lymphatic invasion, and pathological stage. The high-SEC11A expression group had a significantly lower survival rate than the low group (5-year survival 52.3% vs. 75.9%; p<0.005). Furthermore, in multivariate analysis, high-SEC11A expression was an independent factor of poor survival (hazard ratio, 2.010; 95% confidence interval=1.303-3.100; p=0.002). CONCLUSION: SEC11A expression in cancer tissue may be a useful prognostic marker in patients with LAGC after curative resection.
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Neoplasias Primarias Secundarias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirugía , Metástasis Linfática , Análisis Multivariante , Péptido HidrolasasRESUMEN
BACKGROUND: Although there are discussions regarding standards of the analysis of patient-reported outcomes and quality of life (QOL) in oncology clinical trials, that of QOL with death events is not within their scope. For example, ignoring death can lead to bias in the QOL analysis for patients with moderate or high mortality rates in the palliative care setting. This is discussed in the estimand framework but is controversial. Information loss by summary measures under the estimand framework may make it challenging for clinicians to interpret the QOL analysis results. This study illustrated the use of graphical displays in the framework. They can be helpful for discussions between clinicians and statisticians and decision-making by stakeholders. METHODS: We reviewed the time-to-deterioration analysis, prioritized composite outcome approach, semi-competing risk analysis, survivor analysis, linear mixed model for repeated measures, and principal stratification approach. We summarized attributes of estimands and graphs in the statistical analysis and evaluated them in various hypothetical randomized controlled trials. RESULTS: Graphs for each analysis method provide different information and impressions. In the time-to-deterioration analysis, it was not easy to interpret the difference in the curves as an effect on QOL. The prioritized composite outcome approach provided new insights for QOL considering death by defining better conditions based on the distinction of OS and QOL. The semi-competing risk analysis provided different insights compared with the time-to-deterioration analysis and prioritized composite outcome approach. Due to the missing assumption, graphs by the linear mixed model for repeated measures should be carefully interpreted, even for descriptive purposes. The principal stratification approach provided pure comparison, but the interpretation was difficult because the target population was unknown. CONCLUSIONS: Graphical displays can capture different aspects of treatment effects that should be described in the estimand framework.
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Neoplasias , Calidad de Vida , Humanos , Oncología Médica , Neoplasias/terapia , Medición de Resultados Informados por el Paciente , Proyectos de InvestigaciónRESUMEN
Basic and clinical reports have suggested that eicosapentaenoic acid (EPA) exhibits anti-tumor activity. The present study evaluated whether perioperative EPA could improve the survival of patients with localized gastric cancer as a key secondary endpoint of a randomized clinical study. The present study was designed as multicenter, open-label, superiority, randomized trial to confirm the preventive effect of EPA on body weight loss after total gastrectomy for gastric cancer. Eligible patients were randomized to either the standard-diet group (EPA-off group) or EPA-on group by a centralized dynamic method. An EPA-enriched supplement (ProSure®) was given to the EPA-on group in addition to their standard diet. This supplement included 600 kcal with 2.2 g/day of EPA. Among the 126 patients who were randomized, 123 patients (EPA-off group, n=60; EPA-on group, n=63) were examined in the survival analyses. All background factors were well balanced between the two groups. The 3-year and 5-year overall survival rates were 74.6 and 67.8%, respectively, in the EPA-off group, and 77.8 and 76.2% in the EPA-on group. There was no significant difference between the EPA-off and EPA-on groups (hazard ratio, 0.77; P=0.424). In the subgroup analysis, the hazard ratio was 0.39 in patients who received neoadjuvant chemotherapy and 0.57 in patients with nodal metastasis. In conclusion, a clear survival benefit of perioperative EPA was not observed in localized gastric cancer. The value of EPA should be further tested in a future study in patients with unfavorable advanced gastric cancer. Clinical trial number: UMIN000006380; date of registration, September 21, 2011.
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AIM: To compare the diagnostic performance based on the modified CEUS Liver Imaging Reporting and Data System (LI-RADS), which includes Kupffer-phase findings as a major imaging feature, with that of CT and MRI (CT/MRI) LI-RADS for liver nodules in patients at high risk of HCC. METHODS: A total of 120 patients with 120 nodules were included in this retrospective study. The median size of the lesions was 20.0 mm (interquartile range, 14.0-30.8 mm). Of these lesions, 90.0% (108 of 120) were confirmed as HCCs, 6.7% (8 of 120) were intrahepatic cholangiocarcinomas, 1.7% (2 of 120) were metastases, and 1.7% (2 of 120) were dysplastic nodules. All nodules were diagnosed histopathologically. Each nodule was categorized according to the modified CEUS LI-RADS and CT/MRI LI-RADS version 2018. The diagnostic performance and inter-modality agreement of each criterion was compared. RESULTS: The inter-modality agreement for the modified CEUS LI-RADS and CT/MRI LI-RADS was slight agreement (kappa = 0.139, p = 0.015). The diagnostic accuracies of HCCs for the modified CEUS LR-5 and CT/MRI LR-5 were 70.0% (95% confidence interval [CI]: 61.0%, 78.0%) versus 70.8% (95% CI: 61.8%, 78.8%) (p = 0.876), respectively. The diagnostic accuracies of non-HCC malignancies for the modified CEUS LR-M and CT/MRI LR-M were 84.2% (95% CI: 76.4%, 90.2%) versus 96.7% (95% CI: 91.7%, 99.1%) (p = 0.002), respectively. CONCLUSIONS: The diagnostic performance for HCCs on the modified CEUS LR-5 and CT/MRI LR-5 are comparable. In contrast, CT/MRI LR-M has better diagnostic performance for non-HCC malignancy than that of the modified CEUS LR-M.
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Data science plays an important role in many fields. Project-based learning is an effective teaching approach because students can learn data science practices based on real-world problems and real-world data. Because of a pandemic of COVID-19, we provided project-based learning as distance education (synchronic distance education). In this study, we explain how we developed and conducted it and provide survey results from students. The survey showed about 30% of the students found it difficult to communicate with each other and with teachers. However, it suggested that they could communicate to some extent even by remote group work. We found that, in remote communication, it is important to see the faces of all the students (and teachers) on the Zoom screen when they discuss using screen sharing. There remain some challenges such as timing to start talking and casual questions to teachers. Although some issues should be improved, distance education for project-based learning in data science can be implemented effectively. Supplementary Information: The online version contains supplementary material available at 10.1007/s42081-022-00154-2.
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The elder population has increased, introducing the profound medical and social challenge of maintaining health in aging seniors and the need for a medical approach to sustaining physical and mental health. The relationship between diseases and lifestyle-related factors such as diet and exercise are important. A health-conscious lifestyle improves one's health condition from a medical perspective, as indicated by new wellness monitoring using health devices and recent research into the efficacy of functional lunches incorporating utilitarian agricultural, forestry, and fishery products and foods. For a period of 3 months, and solely at lunchtime, 21 participants consumed the contents of a bento (Japanese box lunch), which incorporated functional (healthy) foods. A variety of factors were analyzed, including: weight, weight fluctuation rate, abdominal girth, triglycerides, total cholesterol value, and 8-OHdG (8-hydroxy-2'-deoxyguanosine). The bento comprising functional foods resulted in a reduction in both weight and abdominal girth without calorie restrictions. A reduction over time was observed in 8-OHdG, an oxidative stress marker, as compared to values prior to initiation of the study. Usage of a health device, exercise/dietary advice from a physician and nutritionist, and the availability of meals incorporating functional agricultural products might help prevent lifestyle disease and lead to improved health management.
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Alimentos Funcionales , Almuerzo , Anciano , Dieta , Humanos , Japón , Masculino , Estrés Oxidativo , Proyectos Piloto , PropanolaminasRESUMEN
The aim of this study was to compare the diagnostic performance of Contrast-Enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) version 2017, which includes portal- and late-phase washout as a major imaging feature, with that of modified CEUS LI-RADS, which includes Kupffer-phase findings as a major imaging feature. Participants at risk of hepatocellular carcinoma (HCC) with treatment-naïve hepatic lesions (≥1 cm) were recruited and underwent Sonazoid-enhanced US. Arterial phase hyperenhancement (APHE), washout time, and echogenicity in the Kupffer phase were evaluated using both criteria. The diagnostic performance of both criteria was analyzed using the McNemar test. The evaluation was performed on 102 participants with 102 lesions (HCCs (n = 52), non-HCC malignancies (n = 36), and benign (n = 14)). Among 52 HCCs, non-rim APHE was observed in 92.3% (48 of 52). By 5 min, 73.1% (38 of 52) of HCCs showed mild washout, while by 10 min or in the Kupffer phase, 90.4% (47 of 52) of HCCs showed hypoenhancement. The sensitivity (67.3%; 35 of 52; 95% CI: 52.9%, 79.7%) of modified CEUS LI-RADS criteria was higher than that of CEUS LI-RADS criteria (51.9%; 27 of 52; 95% CI: 37.6%, 66.0%) (p = 0.0047). In conclusion, non-rim APHE with hypoenhancement in the Kupffer phase on Sonazoid-enhanced US is a feasible criterion for diagnosing HCC.
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Estimation of the dose-response curve for efficacy and subsequent selection of an appropriate dose in phase II trials are important processes in drug development. Various methods have been investigated to estimate dose-response curves. Generally, these methods are used with equal allocation of subjects for simplicity; nevertheless, they may not fully optimize performance metrics because of nonoptimal allocation. Optimal allocation methods, which include adaptive allocation methods, have been proposed to overcome the limitations of equal allocation. However, they rely on asymptotics, and thus sometimes cannot efficiently optimize the performance metric with the sample size in an actual clinical trial. The purpose of this study is to construct an adaptive allocation rule that directly optimizes a performance metric, such as power, accuracy of model selection, accuracy of the estimated target dose, or mean absolute error over the estimated dose-response curve. We demonstrate that deep reinforcement learning with an appropriately defined state and reward can be used to construct such an adaptive allocation rule. The simulation study shows that the proposed method can successfully improve the performance metric to be optimized when compared with the equal allocation, D-optimal, and TD-optimal methods. In particular, when the mean absolute error was set to the metric to be optimized, it is possible to construct a rule that is superior for many metrics.