Assessment of clinical relevance of antigen improves diagnostic accuracy of hypersensitivity pneumonitis.

BACKGROUND: Exposure assessment is integral to the diagnosis of hypersensitivity pneumonitis (HP). Although the clinical relevance of exposed antigens is essential for the assessment, many of the previous guidelines or reports have only evaluated simple exposure histories or immunological tests. To overcome this problem, the Exposure Assessment Form (EAF) was developed as an assessment tool for classifying the exposure grade from G0 to G4. The EAF was modified from the description in the Japanese clinical practice guide 2022 for HP published by the Japanese Respiratory Society. METHODS: One hundred and seventy-two consecutive patients with interstitial lung disease who underwent multidisciplinary discussion (MDD) at our hospital were retrospectively examined. We assessed whether the use of the EAF improved the diagnostic performance of the international guideline of HP. We also evaluated whether the exposure grade affected the prognosis of HP. RESULTS: Even when a HP diagnosis was made with a confidence of 70% or higher according to the international guideline, less than half of these cases resulted in a final diagnosis of HP when the exposure grades were lower than G3. When the result of the EAF was integrated into the exposure definition of the international guideline, the specificity of the diagnostic performance improved, while sensitivity was maintained. Furthermore, HP patients with an exposure grade of G3 or higher showed a tendency to take a longer time to initiate medication. CONCLUSIONS: This is the first study to evaluate the clinical relevance of possible antigens using the EAF. Assessing the exposure grade prevents overdiagnosis and improves the diagnostic performance of the international guideline.

Impact of home-visit nursing service use on costs in the last 3 months of life among older adults: A retrospective cohort study.

INTRODUCTION: Considering Japan's aging society, the number of older individuals who die at home is expected to increase. In Japan, there are challenges in utilizing and promoting home-visit nursing services at the end of life for community-dwelling older adults. We examined the use of home-visit nursing services at the end of patients' lives and the recommended use patterns of this service (utilization, timing of initiation, and continuity) that contribute to reducing the medical care and long-term care costs (total costs) in the last 3 months of life. DESIGN: This was a retrospective cohort study. METHODS: We examined 33 municipalities in Japan, including depopulated areas. The analysis included 22,927 people aged 75 or older who died between September 2016 and September 2018. We used monthly medical care and long-term care insurance claims data. Participants were classified into five groups based on their history of home-visit nursing service use: (1) early initiation/continuous use, (2) early initiation/discontinued or fragment use, (3) not-early initiation/continuous use, (4) not-early initiation/fragment use, and (5) no use. Univariate and multivariate linear regression analyses were performed to examine the association between total costs in the last 3 months of life and patterns of home-visit nursing service use. RESULTS: Overall, the median age was 85, and 12,217 participants were men (53.3%). In the last half year before death, 5424 (23.7%) older adults used home-visit nursing services. Multivariable linear regression analysis of the log10-transformed value of total costs revealed that compared with the no use group, the early initiation/continuous use group was estimated to have 0.88 times (95% confidence interval: 0.84, 0.93) the total costs in the last 3 months of life (p < 0.001). CONCLUSION: Early initiation use of home-visit nursing services may contribute to reducing total costs in the last 3 months of life for Japanese people aged 75 years or older living at home as they approach the end of life. CLINICAL RELEVANCE: When approaching the end of life, many older adults require daily life care and palliative care. Policymakers are strengthening end-of-life care for community-dwelling older adults in Japan. Although the current results do not demonstrate the effectiveness of home-visit nursing services, they provide a perspective from which to assess the use of home-visit nursing services and its impact on older adults. The findings can be helpful in considering how to provide nursing care in home-care settings for older adults who prefer to spend their final days at home.

Multimorbidity patterns in the working age population with the top 10% medical cost from exhaustive insurance claims data of Japan Health Insurance Association.

Although the economic burden of multimorbidity is a growing global challenge, the contribution of multimorbidity in patients with high medical expenses remains unclear. We aimed to clarify multimorbidity patterns that have a large impact on medical costs in the Japanese population. We conducted a cross-sectional study using health insurance claims data provided by the Japan Health Insurance Association. Latent class analysis (LCA) was used to identify multimorbidity patterns in 1,698,902 patients who had the top 10% of total medical costs in 2015. The present parameters of the LCA model included 68 disease labels that were frequent among this population. Moreover, subgroup analysis was performed using a generalized linear model (GLM) to assess the factors influencing annual medical cost and 5-year mortality. As a result of obtaining 30 latent classes, the kidney disease class required the most expensive cost per capita, while the highest portion (28.6%) of the total medical cost was spent on metabolic syndrome (MetS) classes, which were characterized by hypertension, dyslipidemia, and type 2 diabetes. GLM applied to patients with MetS classes showed that cardiovascular diseases or complex conditions, including malignancies, were powerful determinants of medical cost and mortality. MetS was classified into 7 classes based on real-world data and accounts for a large portion of the total medical costs. MetS classes with cardiovascular diseases or complex conditions, including malignancies, have a significant impact on medical costs and mortality.

Nutritional Adequacy Assessment of the Japanese Diet Using the Number of Dishes Compared to Existing Dietary Diversity Indices: A Cross-Sectional Analysis from the 2012 National Health and Nutrition Survey, Japan.

The Japanese diet has attracted attention as a factor contributing to the Japanese population's longevity. A typical Japanese meal, traditionally called "ichiju-sansai," is composed of various dishes. This study assessed the nutritional adequacy of the Japanese diet using the number of dishes in all meals (NDAM) compared to existing dietary diversity indices (DDIs). This cross-sectional study used data from the 2012 National Health and Nutrition Survey. A total of 25,976 participants aged ≥20 y were included in this study. NDAM was calculated for whole dishes or single foods (except supplements and beverages) from one-day weighted dietary records. The food variety score (FVS), number of foods, dietary diversity score (DDS), and number of food groups are some of the existing DDIs. NDAM had relatively high positive correlation coefficients with potassium, magnesium, and dietary fiber. The partial correlation coefficients with an indicator of the overall nutrient adequacy of NDAM was 0.42 for men and 0.42 for women. It was almost the same as that of the FVS (men: 0.44, women: 0.42) and DDS (men: 0.44, women: 0.43). On the other hand, NDAM, similar to existing DDIs, was also positively correlated with nutrient restriction in both sexes. These findings indicate that the nutrient adequacy of NDAM is similar to that of the existing DDIs. Because of the higher sodium intake and cholesterol intake in higher NDAM and existing DDIs, the effect of higher NDAM on health outcomes must be investigated in future studies.

Effect-Size Estimation Using Semiparametric Hierarchical Mixture Models in Disease-Association Studies with Neuroimaging Data.

In disease-association studies using neuroimaging data, evaluating the biological or clinical significance of individual associations requires not only detection of disease-associated areas of the brain but also estimation of the magnitudes of the associations or effect sizes for individual brain areas. In this paper, we propose a model-based framework for voxel-based inferences under spatial dependency in neuroimaging data. Specifically, we employ hierarchical mixture models with a hidden Markov random field structure to incorporate the spatial dependency between voxels. A nonparametric specification is proposed for the effect size distribution to flexibly estimate the underlying effect size distribution. Simulation experiments demonstrate that compared with a naive estimation method, the proposed methods can substantially reduce the selection bias in the effect size estimates of the selected voxels with the greatest observed associations. An application to neuroimaging data from an Alzheimer's disease study is provided.

A Progressive Early Mobilization Program Is Significantly Associated With Clinical and Economic Improvement: A Single-Center Quality Comparison Study.

OBJECTIVES: To determine whether a progressive early mobilization protocol improves patient outcomes, including in-hospital mortality and total hospital costs. DESIGN: Retrospective preintervention and postintervention quality comparison study. SETTINGS: Single tertiary community hospital with a 12-bed closed-mixed ICU. PATIENTS: All consecutive patients 18 years old or older were eligible. Patients who met exclusion criteria or were discharged from the ICU within 48 hours were excluded. Patients from January 2014 to May 2015 were defined as the preintervention group (group A) and from June 2015 to December 2016 was the postintervention group (group B). INTERVENTION: Maebashi early mobilization protocol. MEASUREMENTS AND MAIN RESULTS: Group A included 204 patients and group B included 187 patients. Baseline characteristics evaluated include age, severity, mechanical ventilation, and extracorporeal membrane oxygenation, and in group B additional comorbidities and use of steroids. Hospital mortality was reduced in group B (adjusted hazard ratio, 0.25; 95% CI, 0.13-0.49; p < 0.01). This early mobilization protocol is significantly associated with decreased mortality, even after adjusting for baseline characteristics such as sedation. Total hospital costs decreased from $29,220 to $22,706. The decrease occurred soon after initiating the intervention and this effect was sustained. The estimated effect was $-5,167 per patient, a 27% reduction. Reductions in ICU and hospital lengths of stay, time on mechanical ventilation, and improvement in physical function at hospital discharge were also seen. The change in Sequential Organ Failure Assessment score and Sequential Organ Failure Assessment score at ICU discharge were significantly reduced after the intervention, despite a similar Sequential Organ Failure Assessment score at admission and at maximum. CONCLUSIONS: In-hospital mortality and total hospital costs are reduced after the introduction of a progressive early mobilization program, which is significantly associated with decreased mortality. Cost savings were realized early after the intervention and sustained. Further prospective studies to investigate causality are warranted.

Epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge in Japan: An exploratory descriptive study using a nationwide claims database.

BACKGROUND: Little is known about the nationwide epidemiology of the annual rate, causative substance, and clinical course of overdose-related admission. We aimed to describe the epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge to home. METHODS: We assessed all cases of admission due to overdose (21,663 episodes) in Japan from October 2012 through September 2013 using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. RESULTS: The annual rate of overdose admission was 17.0 per 100,000 population. Women exhibited two peaks in admission rates at 19-34 years (40.9 per 100,000) and ≥75 years (27.8 per 100,000). Men exhibited one peak in the admission rate at ≥75 years (23.7 per 100,000). Within 90 days prior to overdose, ≥60% and ≥9% of patients aged 19-49 years received a prescription for benzodiazepines and barbiturates, respectively. In addition, 59% of patients aged ≥75 years received a prescription for benzodiazepines prior to overdose, 47% had a history of congestive heart failure, and 24% had a diagnosis of poisoning by cardiovascular drugs. The proportion of patients with recent psychiatric treatments decreased with age (65.1% in those aged 35-49 years and 13.9% in those aged ≥75 years). CONCLUSIONS: The findings emphasize the need for overdose prevention programs that focus on psychiatric patients aged 19-49 years who are prescribed benzodiazepines or barbiturates and on non-psychiatric patients aged ≥75 years who are prescribed benzodiazepines or digitalis.

Effect of database profile variation on drug safety assessment: an analysis of spontaneous adverse event reports of Japanese cases.

BACKGROUND: The use of a statistical approach to analyze cumulative adverse event (AE) reports has been encouraged by regulatory authorities. However, data variations affect statistical analyses (eg, signal detection). Further, differences in regulations, social issues, and health care systems can cause variations in AE data. The present study examined similarities and differences between two publicly available databases, ie, the Japanese Adverse Drug Event Report (JADER) database and the US Food and Drug Administration Adverse Event Reporting System (FAERS), and how they affect signal detection. METHODS: Two AE data sources from 2010 were examined, ie, JADER cases (JP) and Japanese cases extracted from the FAERS (FAERS-JP). Three methods for signals of disproportionate reporting, ie, the reporting odds ratio, Bayesian confidence propagation neural network, and Gamma Poisson Shrinker (GPS), were used on drug-event combinations for three substances frequently recorded in both systems. RESULTS: The two databases showed similar elements of AE reports, but no option was provided for a shareable case identifier. The average number of AEs per case was 1.6±1.3 (maximum 37) in the JP and 3.3±3.5 (maximum 62) in the FAERS-JP. Between 5% and 57% of all AEs were signaled by three quantitative methods for etanercept, infliximab, and paroxetine. Signals identified by GPS for the JP and FAERS-JP, as referenced by Japanese labeling, showed higher positive sensitivity than was expected. CONCLUSION: The FAERS-JP was different from the JADER. Signals derived from both datasets identified different results, but shared certain signals. Discrepancies in type of AEs, drugs reported, and average number of AEs per case were potential contributing factors. This study will help those concerned with pharmacovigilance better understand the use and pitfalls of using spontaneous AE data.

A flexible spatial scan statistic with a restricted likelihood ratio for detecting disease clusters.

Spatial scan statistics are widely used tools for detection of disease clusters. Especially, the circular spatial scan statistic proposed by Kulldorff (1997) has been utilized in a wide variety of epidemiological studies and disease surveillance. However, as it cannot detect noncircular, irregularly shaped clusters, many authors have proposed different spatial scan statistics, including the elliptic version of Kulldorff's scan statistic. The flexible spatial scan statistic proposed by Tango and Takahashi (2005) has also been used for detecting irregularly shaped clusters. However, this method sets a feasible limitation of a maximum of 30 nearest neighbors for searching candidate clusters because of heavy computational load. In this paper, we show a flexible spatial scan statistic implemented with a restricted likelihood ratio proposed by Tango (2008) to (1) eliminate the limitation of 30 nearest neighbors and (2) to have surprisingly much less computational time than the original flexible spatial scan statistic. As a side effect, it is shown to be able to detect clusters with any shape reasonably well as the relative risk of the cluster becomes large via Monte Carlo simulation. We illustrate the proposed spatial scan statistic with data on mortality from cerebrovascular disease in the Tokyo Metropolitan area, Japan.

[Bayesian approach to indices of regional healthcare expenditure in Japan].

OBJECTIVES: To compare medical expenses among regions in Japan, the "regional difference index" of National Health Insurance has been used. The index is formulated as a ratio of observed to expected numbers. However, it has large variability such as in the standardized mortality ratio (SMR) in small populations. To circumvent this problem, we propose an alternative index based on Bayesian methods. METHODS: Regional medical expenses were assumed to have a log normal distribution and be derived from the conventional regional difference index as a statistical estimator. Under the assumed distribution, we then considered a full Bayes estimator for the index. The data for 2003-2005 were used for a comparison between the proposed Bayesian index and the conventional index. RESULTS: Under the assumed lognormal model, we could define the conventional index as an estimator for the expenditure level in the region. We showed that it has a large variability for small populations. The proposed Bayes estimator could solve this problem. CONCLUSIONS: The proposed index based on Bayesian inference could stably estimate the level of regional medical expenses. We therefore suggest that a more appropriate discussion of regional differences could be given using this Bayesian index than with the conventional one.

[Health care resources and mortality as assessed by "the empirical Bayes estimate of standardized mortality ratio": results for municipalities in Japan].

BACKGROUND AND OBJECTIVE: The standardized mortality ratio (SMR) is frequently used to compare health status among different populations. However, SMR could be biased when based upon communities with small population size such as towns and wards and comparison of SMRs in such cases is not appropriate. The "empirical Bayes estimate of standardized mortality ratio" (EBSMR) is a useful alternative index for comparing mortalities among small populations. The objective of the present study was to use the EBSMR to clarify the relationships between health care resources and mortalities in 3,360 municipalities in Japan. MATERIALS AND METHODS: Health care resource data (number of physicians, number of general clinics, number of general sickbeds, and number of emergency hospitals) and socioeconomic factors (population, birth rate, aged households, marital rate, divorce rate, taxable income per individual under taxes duty, unemployment, secondary, tertiary industrial employment and prefecture) were obtained from officially published reports. EBSMRs for all causes, cerebrovascular disease, heart disease, acute myocardial infarction, and malignant neoplasms were calculated from the 1997-2001 vital statistic records. Multiple regression analysis was used to examine the relationships between EBSMRs and the variables representing health care resources and socioeconomic factors as covariates. Some of the variables were log-transformed to normalize the distribution of variables. RESULTS: The correlation between number of physicians and general sickbeds was very high (Pearson's r = 0.776). So, we excluded the number of general sickbeds. Some of the EBSMRs were inversely associated with the number of physicians per person (all causes in males (beta = -0.042, P = 0.024) and females (beta = -0.150, P < 0.001), cerebrovascular disease in females (beta = -0.074, P < 0.001), heart disease in males (beta = -0.066, P < 0.001) and females (beta = - 0.087, P < 0.001), acute myocardial infarction in females (beta = -0.061, P = 0.003), and malignant neoplasms in females (beta = -0.064, P = 0.001)). In contrast, when there was a higher number of clinics per persons, the EBSMR was higher for all causes in males (beta = 0.053, P = 0.001) and females (beta = 0.115, P < 0.001), cerebrovascular disease in males (beta = 0.047, P = 0.002) and females (beta = 0.070, P < 0.001), heart disease in females (beta = 0.061, P < 0.001), acute myocardial infarction in females (beta = 0.048, P = 0.006), and malignant neoplasms in males (beta = 0.036, P = 0.018) and females (beta = 0.046, P = 0.005). Next, we selected the number of emergency hospitals as the variable representing health care resources. Some of the EBSMRs were inversely associated with the existence of emergency hospitals (all causes in females (beta = -0.085, P < 0.001), cerebrovascular disease in males (beta = -0.032, P = 0.031) and females (beta = -0.059, P = 0.001), and heart disease in females (beta = -0.052, P = 0.008)). CONCLUSION: The results suggested that an appropriate distribution of health care resources such as physicians and emergency hospitals is an important factor associated with mortality in a community.

A flexibly shaped space-time scan statistic for disease outbreak detection and monitoring.

BACKGROUND: Early detection of disease outbreaks enables public health officials to implement disease control and prevention measures at the earliest possible time. A time periodic geographical disease surveillance system based on a cylindrical space-time scan statistic has been used extensively for disease surveillance along with the SaTScan software. In the purely spatial setting, many different methods have been proposed to detect spatial disease clusters. In particular, some spatial scan statistics are aimed at detecting irregularly shaped clusters which may not be detected by the circular spatial scan statistic. RESULTS: Based on the flexible purely spatial scan statistic, we propose a flexibly shaped space-time scan statistic for early detection of disease outbreaks. The performance of the proposed space-time scan statistic is compared with that of the cylindrical scan statistic using benchmark data. In order to compare their performances, we have developed a space-time power distribution by extending the purely spatial bivariate power distribution. Daily syndromic surveillance data in Massachusetts, USA, are used to illustrate the proposed test statistic. CONCLUSION: The flexible space-time scan statistic is well suited for detecting and monitoring disease outbreaks in irregularly shaped areas.

An extended power of cluster detection tests.

Several tests have been proposed to detect spatial disease clustering without prior information on their locations. In order to compare the performance of these tests, most authors employ the usual power, i.e. the rejection probability of the null hypothesis of no clustering due to various reasons. However, the usual power is not always appropriate for evaluating the cluster detection tests since their purpose is to both reject the null hypothesis and identify the cluster areas accurately. In this paper, we propose an extended power of the cluster detection tests, which includes the usual power as a special case. Further, we define the profile of the extended power, which can be expected to play an important role in the evaluation and comparison of several cluster detection tests. The proposed extended power and its profile are demonstrated by two tests--Kulldorff's circular spatial scan statistic and a flexible spatial scan statistic proposed by Tango and Takahashi.

[Health care resources and mortality as assessed by the "empirical Bayes estimate of standardized mortality ratio": results for Fukuoka Prefecture].

BACKGROUND AND OBJECTIVE: The standardized mortality ratio (SMR) is frequently used to compare health status among different populations. However, it may be biased when based upon communities with small population sizes such as towns, cities, and wards. Thus, comparison of SMRs among such small communities is not appropriate. But the "empirical Bayes estimate of standardized mortality ratio" (EBSMR) is, in contrast, a useful index. The objective of the present study was to use the EBSMR to clarify the relationships between health care resources and mortalities in 109 communities in Fukuoka Prefecture. MATERIALS AND METHODS: Data for health care resources (number of physicians, number of general clinics, number of general sickbeds in hospitals, number of emergency hospitals, and proportion of elderly outpatients within their resident' community) and socioeconomic factors (birth rate, inflow or outflow population, aged households, marital status, taxable income per individual under taxes duty, unemployment, primary, secondary, tertiary industrial employment and criminal offense records) were obtained from officially published reports. EBSMRs for all causes, cerebrovascular disease, heart disease, malignant neoplasms, and acute myocardial infarction were calculated from the 1993-1997 vital statistic records. Multiple regression analysis with stepwise variable selection was used to examine the relationships between EBSMRs and the five variables representing health care resources, considering the eleven socioeconomic factors as covariates. Some of the variables were log-transformed to normalize the distribution. RESULTS: Some of the EBSMRs were inversely related to the numbers of physicians per person (acute myocardial infarction in males (P=0.047) and females (P=0.012)), emergency hospitals per person (acute myocardial infarction in females: P=0.001), and general sickbeds per person (all causes in females: P<0.001, cerebrovascular disease in females: P=0.007, heart disease in females: P<0.001, malignant neoplasms in females: P=0.049). In contrast, when the higher the number of clinics per person, the higher the EBSMR in females for all causes (P=0.025), as well as acute myocardial infarction (P=0.006). CONCLUSION: The results suggest that an appropriate distribution of hospital care resources such as physicians, general sickbeds, and emergency hospitals is an important factor related to mortality in a community.