Assessment of anthracycline-induced cardiotoxicity in childhood cancer survivors during long-term follow-up using strain analysis and intraventricular pressure gradient measurements.

BACKGROUND: Cardiac dysfunction due to cardiotoxicity from anthracycline chemotherapy is a leading cause of morbidity and mortality in childhood cancer survivors (CCS), and the cumulative incidence of cardiac events has continued to increase. This study identifies an adequate indicator of cardiac dysfunction during long-term follow-up. PROCEDURE: In total, 116 patients (median age: 15.5 [range: 4.7-40.2] years) with childhood cancer who were treated with anthracycline were divided into three age groups for analysis (C1: 4-12 years of age, C2: 13-18 years of age, C3: 19-40 years of age), and 116 control patients of similar ages were divided into three corresponding groups (N1, N2, and N3). Layer-specific strains were assessed for longitudinal strain (LS) and circumferential strain (CS). The total and segmental intraventricular pressure gradients (IVPG) were also calculated based on Doppler imaging of the mitral inflow using Euler's equation. RESULTS: Conventional echocardiographic parameters were not significantly different between the patients and controls. All layers of the LS and inner and middle layers of the basal and papillary CS in all ages and all IVPGs in C2 and C3 decreased compared to those of corresponding age groups. Interestingly, basal CS and basal IVPG in CCS showed moderate correlation and both tended to rapidly decrease with aging. Furthermore, basal IVPG and anthracycline dose showed significant correlations. CONCLUSIONS: Basal CS and total and basal IVPGs may be particularly useful indicators of cardiotoxicity in long-term follow-up.

The cumulative burden of self-reported, clinically relevant outcomes in long-term childhood cancer survivors and implications for survivorship care: A DCCSS LATER study.

BACKGROUND: The aim of this study is to evaluate how cumulative burden of clinically relevant, self-reported outcomes in childhood cancer survivors (CCSs) compares to a sibling control group and to explore how the burden corresponds to levels of care proposed by existing risk stratifications. METHODS: The authors invited 5925 5-year survivors from the Dutch Childhood Cancer Survivor Study (DCCSS LATER) cohort and their 1066 siblings to complete a questionnaire on health outcomes. Health outcomes were validated by self-reported medication use or medical record review. Missing data on clinically relevant outcomes in CCSs for whom no questionnaire data were available were imputed with predictive mean matching. We calculated the mean cumulative count (MCC) for clinically relevant outcomes. Furthermore, we calculated 30-year MCC for groups of CCSs based on primary cancer diagnosis and treatment, ranked 30-year MCC, and compared the ranking to levels of care according to existing risk stratifications. RESULTS: At median 18.5 years after 5-year survival, 46% of CCSs had at least one clinically relevant outcome. CCSs experienced 2.8 times more health conditions than siblings (30-year MCC = 0.79; 95% confidence interval [CI], 0.74-0.85 vs. 30-year MCC = 0.29; 95% CI, 0.25-0.34). CCSs' burden of clinically relevant outcomes consisted mainly of endocrine and vascular conditions and varied by primary cancer type. The ranking of the 30-year MCC often did not correspond with levels of care in existing risk stratifications. CONCLUSIONS: CCSs experience a high cumulative burden of clinically relevant outcomes that was not completely reflected by current risk stratifications. Choices for survivorship care should extend beyond primary tumor and treatment parameters, and should consider also including CCSs' current morbidity.

Risk factors associated with infection-related mortality of Bacillus cereus bacteremia in hematologic disorders.

The mortality risk factors in B. cereus bacteremia in hematologic disorders are still unknown. In this study, patients with B. cereus bacteremia in hematologic disorders were selected in St. lukes international hospital and from electronic databases. A total of 176 patients [median age, 41 years (3-88 years); 99 (56%) males] were included. Of these patients, 141 (80%) had acute leukemia, and 93 (53%) died. Univariate analysis showed that neutropenia, CNS, gastrointestinal, and respiratory infections/symptoms were significantly associated with infection-related death. Meanwhile, glycopeptide use and management with source control were protective factors. Multivariate logistic regression analysis showed that infection-related death was significantly associated with CNS [odds ratio (OR): 3.49, 95% confidence interval (CI) 1.25-9.80], gastrointestinal (OR: 5.22, 95% CI 1.82-8.99), and respiratory infections/symptoms (OR: 8.98, 95% CI 1.62-49.9), as well as glycopeptide use (OR: 0.10, 95% CI 0.03-0.31) and source control (OR: 0.11, 95% CI 0.03-0.37). In conclusion, early glycopeptide administration and source control should be performed upon detection of infections suspicious for B. cereus.

High whole-body bone mineral density in ossification of the posterior longitudinal ligament.

BACKGROUND CONTEXT: Recent studies suggest that ossification of the posterior longitudinal ligament (OPLL) is exacerbated by systemic metabolic disturbances, including obesity. However, although an increase in bone mineral density (BMD) measured at the lumbar spine has been reported in patients with OPLL, no studies have investigated the systemic BMD of patients with OPLL in detail. PURPOSE: We investigated whether patients with OPLL develop increased whole-body BMD. STUDY DESIGN: Single institution cross-sectional study. PATIENT SAMPLE: Data were collected from Japanese patients with symptomatic OPLL (OPLL [+]; n=99). Control data (OPLL [-]; n=226) without spinal ligament ossification were collected from patients who underwent spinal decompression, spinal fusion, or hip replacement surgery. OUTCOME MEASURES: Demographic data, including age, body mass index (BMI), comorbidities, history of treatment for osteoporosis, and history of vertebral and nonvertebral fractures, was obtained from all participants. In addition, whole-body BMD, including the lumbar spine, thoracic spine, femoral neck, skull, ribs, entire upper extremity, entire lower extremity, and pelvis, were measured in all participants using whole-body dual-energy X-ray absorptiometry. METHODS: Patient data were collected from 2018 to 2022. All participants were categorized based on sex, age (middle-aged [<70 years] and older adults [≥70 years]), and OPLL type (localized OPLL [OPLL only in the cervical spine], diffuse OPLL [OPLL in regions including the thoracic spine]), and OPLL [-]) and each parameter was compared. The factors associated with whole-body BMD were evaluated via multivariable linear regression analysis. RESULTS: Compared with the OPLL (-) group, the OPLL (+) group of older women had significantly higher BMD in all body parts (p<.01), and the OPLL (+) group of older men had significantly higher BMD in all body parts except the ribs, forearm, and skull (p<.01). The factors associated with increased BMD of both the femoral neck (load-bearing bone) and skull (nonload-bearing bone) were age, BMI, and coexisting diffuse OPLL in women and BMI and coexisting localized OPLL in men. CONCLUSIONS: Patients with OPLL have increased whole-body BMD regardless of sex, indicating that it is not simply due to load-bearing from obesity. These findings suggested that OPLL is associated with a systemic pathology.

Projection of morbidity and mortality due to breast cancer between 2020 and 2050 across 42 low- and middle-income countries.

Objective: Aim of the study is to predict trends in morbidity and mortality due to breast cancer in 42 LMICs between 2020 and 2050. Design: and Setting: National level cross-sectional breast cancer related data between 1990 and 2019 were used. Recurrent Neural Network, Long-Short-Term Memory (RNN-LSTM) model was employed to forecast the trend in breast cancer burden. Main outcomes and measures: Age standardized breast cancer incidence, mortality, and disability adjusted life years (DALYs) rates. Results: By 2050, the age standardized breast cancer incidence rate is expected to increase in 38 LMICs with highest incidence rate in Namibia; 127.0 (78.0-176.0) followed by Nigeria 71.1 (53.9-88.3) and Papua New Guinea 70.6 (88.7-74.6). Similarly, the age standardized breast cancer mortality and DALYs rates in 2050 are expected to increase in 33 and 35 LMICs respectively. The highest mortality and DALYs rates in 2050 are expected to be 64.7 (42.6-86.7) in Namibia and 1543.6 (1463.1-1624.1) in Pakistan. The estimated annual percentage change (EAPC) is expected to increase uniformly in all the countries during the same period. Due to considerable variation in exposure risk, such as high plasma glucose level, high body mass index (BMI) and socio-demographic index (SDI), high regional disparity in burden of breast cancer is expected among the countries. Conclusion: and Relevance: Breast cancer burden is expected to increase in most of the LMICs with high regional disparity by 2050. Our study's finding focuses on LMICs with high breast cancer burden that require tailored strategies and effective action plans to ensure prevention from catastrophic consequences in the future. Minimizing the exposure to behavioral and metabolic risk factors such as high plasma glucose, high BMI, along with tackling the issue of low fertility rate would be important in managing breast cancer burden in LMICs.

Effectiveness of the Internet of Things for Improving Working-Aged Women's Health in High-Income Countries: Protocol for a Systematic Review and Network Meta-analysis.

BACKGROUND: Women often experience many unique health issues and conditions throughout their working lives. The Internet of Things (IoT) is a system of interrelated digital devices that can enable data exchanges over a network without human-to-human or human-to-computer interaction. The usage of applications and IoT in improving women's health has recently increased worldwide. However, there has been no consensus on the effectiveness of IoT in improving women's health outcomes. OBJECTIVE: This systematic review and network meta-analysis (NMA) aims to assess and synthesize the role of apps and the IoT in improving women's health and to identify the ranking of interventions for ensuring better results for each stated outcome. METHODS: Our systematic review and NMA will be conducted in accordance with the guidelines of the Cochrane Handbook. We will comprehensively search the following electronic databases: PubMed (including MEDLINE), Cochrane Central Register of Controlled Trials, Embase, Cumulative Index to Nursing and Allied Health Literature (ie, CINAHL), PsycINFO, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry, along with other resources to identify relevant randomized controlled trials that have assessed the effects of various apps and the IoT with regard to improving working-aged women's health in high-income countries. We will segment and analyze the results of the included studies based on age categories (women undergoing a preconception period, those undergoing gestational and postpartum periods, and menopausal and pre- and postmenopausal women) and the medical history (women who have a specific medical condition-eg, cancer or diabetes-and women who do not have them) separately. Two independent reviewers will perform the study selection, data extraction, and quality assessment. Our primary outcomes include health status, well-being, and quality of life. We will perform pairwise meta-analysis and NMA to estimate the direct, indirect, and relative effects of apps and the IoT on women's health outcomes. We will also assess the hierarchy of interventions, statistical inconsistencies, and certainties of evidence for each outcome. RESULTS: We plan to conduct the search in January 2023 and are currently discussing search strategies with the literature search specialists. The final report is planned for submission to a peer-reviewed journal in September 2023. CONCLUSIONS: To the best of our knowledge, this review will be the first to identify the ranking of IoT intervention for ensuring working-aged women's health outcomes. These findings may be of great use to researchers, policy makers, and others with an interest in the field. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42022384620; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=384620. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/45178.

Recent changes in the reporting of STIs in Japan during the COVID-19 pandemic.

OBJECTIVES: The COVID-19 pandemic has had variable effects on the rates of STIs reported across the globe. This study sought to assess how the number of STI reports changed during the pandemic in Japan. METHODS: We used national infectious disease surveillance data from the National Institute of Infectious Diseases (Tokyo, Japan) for the period between January 2013 and December 2021. We compared reported rates of chlamydia, gonorrhoea, condyloma acuminata and genital herpes, as well as total notifications for HIV/AIDS and syphilis during the pandemic versus previous years in Japan. We used a quasi-Poisson regression to determine whether any given week or month between January 2018 and December 2021 had a significant excess or deficit of STIs. Notification values above or below the 95% upper and lower prediction thresholds were considered as statistically significant. The start of the pandemic was defined as January 2020. RESULTS: Chlamydia generally remained within predicted range during the pandemic period. Reporting of gonorrhoea was significantly higher than expected throughout early-to-mid 2021 but otherwise generally remained within predicted range prior to 2021. Condyloma, herpes and HIV/AIDS reporting were transiently significantly lower than expected throughout the pandemic period, but no significant periods of higher-than-expected reporting were detected. Syphilis showed widespread evidence of significantly lower-than-predicted reporting throughout 2020 but eventually reversed, showing significantly higher-than-predicted reporting in mid-to-late 2021. CONCLUSIONS: The COVID-19 pandemic was associated with variable changes in the reporting of STIs in Japan. Higher-than-predicted reporting was more likely to be observed in the later phases of the pandemic. These changes may have been attributable to pandemic-related changes in sexual behaviour and decreased STI clinic attendance and testing, but further research on the long-term impact of the pandemic on STIs is necessary.

Ex-vivo 1.5T MR Imaging versus CT in Estimating the Size of the Pathologically Invasive Component of Lung Adenocarcinoma Spectrum Lesions.

PURPOSE: The purpose of this study was to investigate whether ex-vivo MRI enables accurate estimation of the invasive component of lung adenocarcinoma. METHODS: We retrospectively reviewed 32 patients with lung adenocarcinoma who underwent lung lobectomy. The specimens underwent MRI at 1.5T. The boundary between the lesion and the normal lung was evaluated on a 5-point scale in each three MRI sequences, and a one-way analysis of variance and post-hoc tests were performed. The invasive component size was measured histopathologically. The maximum diameter of each solid component measured on CT and MR T1-weighted (T1W) images and the maximum size obtained from histopathologic images were compared using the Wilcoxon signed-rank test. Inter-reader agreement was evaluated using intraclass correlation coefficients (ICC). RESULTS: T1W images were determined to be optimal for the delineation of the lesions (P < 0.001). The histopathologic invasive area corresponded to the area where the T1W ex-vivo MR image showed a high signal intensity that was almost equal to the intravascular blood signal. The maximum diameter of the solid component on CT was overestimated compared with the maximum invasive size on histopathology (mean, 153%; P < 0.05), while that on MRI was evaluated mostly accurately without overestimation (mean, 108%; P = 0.48). The interobserver reliability of the measurements using CT and MRI was good (ICC = 0.71 on CT, 0.74 on MRI). CONCLUSION: Ex-vivo MRI was more accurate than conventional CT in delineating the invasive component of lung adenocarcinoma.

Salt intake reduction using umami substance-incorporated food: a secondary analysis of NHANES 2017-2018 data.

OBJECTIVE: Excessive salt intake raises blood pressure and increases the risk of non-communicable diseases (NCD), such as CVD, chronic kidney disease and stomach cancer. Reducing the Na content of food is an important public health measure to control the NCD. This study quantifies the amount of salt reduced by using umami substances, i.e. glutamate, inosinate and guanylate, for adults in the USA. DESIGN: The secondary data analysis was performed using data of the US nationally representative cross-sectional dietary survey, the National Health and Nutrition Examination Survey (NHANES) 2017-2018. Per capita daily salt intake corresponding to the NHANES food groups was calculated in the four hypothetical scenarios of 0 %, 30 %, 60 % and 90 % market share of low-Na foods in the country. The salt reduction rates by using umami substances were estimated based on the previous study results. SETTING: The USA. PARTICIPANTS: 4139 individuals aged 20 years and older in the USA. RESULTS: Replacing salt with umami substances could help the US adults reduce salt intake by 7·31-13·53 % (7·50-13·61 % for women and 7·18-13·53 % for men), which is equivalent to 0·61-1·13 g/d (0·54-0·98 g/d for women and 0·69-1·30 g/d for men) without compromising the taste. Approximately, 21·21-26·04 % of the US adults could keep their salt intake below 5 g/d, the WHO's recommendation in the scenario where there is no low-Na product on the market. CONCLUSIONS: This study provides essential information that the use of umami substances as a substitute for salt may help reduce the US adults' salt intake.

Excess deaths from non-COVID-19-related causes in Japan and 47 prefectures from January 2020 through May 2021 by place of death.

Excess deaths, including all-causes mortality, were confirmed for the first time in Japan in April 2021. However, little is known about the indirect effects of COVID-19 on the number of non-COVID-19-related deaths. We then estimated the excess deaths from non-COVID-19-related causes in Japan and its 47 prefectures from January 2020 through May 2021 by place of death. Vital statistical data on deaths were obtained from the Ministry of Health, Labour and Welfare. Using quasi-Poisson regression models, we estimated the expected weekly number of deaths due to all-causes excluding COVID-19 (non-COVID-19) and due to respiratory disease, circulatory disease, malignant neoplasms, and senility. Estimates were made separately for deaths in all locations, as well as for deaths in hospitals and clinics, in nursing homes and elderly care facilities, and at home. We defined a week with excess deaths as one in which the observed number of deaths exceeded the upper bound of the two-sided 95% prediction interval. Excess death was expressed as a range of differences between the observed and expected number of deaths and the 95% upper bound of the two-sided predictive interval. The excess percentage was calculated as the number of excess deaths divided by the expected number of deaths. At the national level, excess deaths from non-COVID-19-related all-causes were observed during April 19 to May 16, 2021. The largest excess percentage was 2.73-8.58% (excess deaths 689-2161) in the week of May 3-9. Similar trends were observed for all four cause categories. The cause-of-death categories which contributed to the excesses showed heterogeneity among prefectures. When stratified by place of death, excess mortality tended to be observed in nursing homes and elderly care facilities for all categories, in hospitals and clinics for circulatory disease, and at home for respiratory disease, malignant neoplasms, and senility. A caution is necessary that for the lastest three months (March-May 2021), adjusted data were used to account for possible reporting delays.

Is young-onset esophageal adenocarcinoma increasing in Japan? An analysis of population-based cancer registries.

BACKGROUND: While esophageal squamous cell carcinoma (ESCC) is the predominant histological type in Japan, concern has been expressed over an increase in the proportion of esophageal adenocarcinoma (EAC), especially in middle-aged populations. This study aimed to assess long-term trends in esophageal cancer incidence by histological type. METHODS: We used data from three population-based cancer registries in Japan with 10,642 esophageal cancer cases diagnosed between 1993 and 2014. The multiple imputation approach was used to impute a specific histological type (ESCC, EAC, and others) for cases with "Unknown" or missing status. We calculated the age-standardized incidence rates by histological type from 1993 to 2014 and fitted age-period-cohort models to estimate the annual percent changes (APCs) and adjusted incidence rate ratios (IRRs). RESULTS: After imputation of missing data, the largest mean APC increase was seen in the incidence of EAC in men aged 40-49 years (7.1%) followed by those aged 50-59 years (5.5%). The age-period-cohort analysis showed that men who were born in the 1960s and later were more likely to develop EAC relative to men who were born in 1950-1959 (1960-1969 cohort, IRR: 1.42; 1970-1974 cohort, IRR: 2.23), with a period effect indicating a constant increase after 2003. For women, no significant trend in EAC incidence was observed. CONCLUSIONS: The incidence of EAC has increased more prominently compared with that of ESCC, especially in men aged 40-59 years, suggesting the impact of increasing obesity in men and a reduction in H. pylori prevalence in Japan.

Projections of disability-adjusted life years for major diseases due to a change in vegetable intake in 2017-2040 in Japan.

BACKGROUND: Low vegetable intake is one of the key dietary risk factors known to be associated with a range of health problems, including cardiovascular diseases (CVDs), cancer, and diabetes and kidney diseases (DKDs). Using data from Japan's National Health and Nutrition Surveys and the Global Burden of Diseases study in 2017, this study aimed to forecast the impact of change in vegetable intake on disability-adjusted life years (DALYs) between 2017 and 2040 for three diseases. METHODS: We generated a three-component model of cause-specific DALYs, including changes in major behavioural and metabolic risk predictors, the socio-demographic index and an autoregressive integrated moving average model to project future DALY rates for 2017-2040 using the data between 1990 and 2016. Data on Vegetable consumption and risk predictors, and DALY rate were obtained from Japan's National Health and Nutrition Surveys and the Global Burden of Diseases Study in 2017. We also modelled three scenarios of better, moderate and worse cases to evaluate the impact of change in vegetable consumption on the DALY rates for three diseases (CVDs, cancer, and DKDs). RESULTS: Projected mean vegetable intake in the total population showed a decreasing trend through 2040 to 237.7 g/day. A significant difference between the reference scenario and the better case scenario was observed with un-overlapped 95% prediction intervals of DALY rates in females aged 20-49 years (- 8.0%) for CVDs, the total population for cancer (- 5.6%), and in males (- 8.2%) and females (- 13.7%) for DKDs. CONCLUSIONS: Our analysis indicates that increased vegetable consumption would have a significant reduction in the burdens of CVDs, cancer and DKDs in Japan. By estimating the disease burden attributable to low vegetable intake under different scenarios of future vegetable consumption, our study can inform the design of targeted interventions for public health challenges.

Prediction of disability-adjusted life years for diseases due to low fruit intake in 2017-2040 in Japan.

OBJECTIVE: The current study aimed to predict disability-adjusted life years (DALY) rate in Japan through 2040 with plausible future scenarios of fruit intake for neoplasms, cardiovascular diseases (CVD) and diabetes and kidney diseases (DKD). DESIGN: Data from National Health and Nutrition Surveys and the Global Burden of Diseases study in 2017 were used. We developed an autoregressive integrated moving average model with four future scenarios. Reference scenario maintains the current trend. Best scenario assumes that the goal defined in Health Japan 21 is achieved in 2023 and is kept constant afterwards. Moderate scenario assumes that the goal is achieved in 2040. Constant scenario applies the same proportion of 2016 for the period between 2017 and 2040. SETTING: DALY rates in Japan were predicted for the period between 2017 and 2040. PARTICIPANTS: Population aged more than than 20 years old. RESULTS: In our reference forecast, the DALY rates in all-ages group were projected to be stable for CVD and continue increasing for neoplasms and DKD. Age group-specific DALY rates for these three disease groups were forecasted to decrease, with some exceptions. Among men aged 20-49 years, DALY attributable to CVD differed substantially between the scenarios, implying that there is a significant potential for reducing the burden of CVD by increasing fruit intake at the population level. CONCLUSIONS: Our scenario analysis shows that higher fruit intake is associated with lower disease burden in Japan. Further research is required to assess which policies and interventions can be used to achieve an increase in fruit intake as modelled in the scenarios of the current study.

Deep Neural Network for Reducing the Screening Workload in Systematic Reviews for Clinical Guidelines: Algorithm Validation Study.

BACKGROUND: Performing systematic reviews is a time-consuming and resource-intensive process. OBJECTIVE: We investigated whether a machine learning system could perform systematic reviews more efficiently. METHODS: All systematic reviews and meta-analyses of interventional randomized controlled trials cited in recent clinical guidelines from the American Diabetes Association, American College of Cardiology, American Heart Association (2 guidelines), and American Stroke Association were assessed. After reproducing the primary screening data set according to the published search strategy of each, we extracted correct articles (those actually reviewed) and incorrect articles (those not reviewed) from the data set. These 2 sets of articles were used to train a neural network-based artificial intelligence engine (Concept Encoder, Fronteo Inc). The primary endpoint was work saved over sampling at 95% recall (WSS@95%). RESULTS: Among 145 candidate reviews of randomized controlled trials, 8 reviews fulfilled the inclusion criteria. For these 8 reviews, the machine learning system significantly reduced the literature screening workload by at least 6-fold versus that of manual screening based on WSS@95%. When machine learning was initiated using 2 correct articles that were randomly selected by a researcher, a 10-fold reduction in workload was achieved versus that of manual screening based on the WSS@95% value, with high sensitivity for eligible studies. The area under the receiver operating characteristic curve increased dramatically every time the algorithm learned a correct article. CONCLUSIONS: Concept Encoder achieved a 10-fold reduction of the screening workload for systematic review after learning from 2 randomly selected studies on the target topic. However, few meta-analyses of randomized controlled trials were included. Concept Encoder could facilitate the acquisition of evidence for clinical guidelines.

Forecasting disability-adjusted life years for chronic diseases: reference and alternative scenarios of salt intake for 2017-2040 in Japan.

BACKGROUND: In Japan, a high-sodium diet is the most important dietary risk factor and is known to cause a range of health problems. This study aimed to forecast Japan's disability-adjusted life year (DALYs) for chronic diseases that would be associated with high-sodium diet in different future scenarios of salt intake. We modelled DALY forecast and alternative future scenarios of salt intake for cardiovascular diseases (CVDs), chronic kidney diseases (CKDs), and stomach cancer (SC) from 2017 to 2040. METHODS: We developed a three-component model of disease-specific DALYs: a component on the changes in major behavioural and metabolic risk predictors including salt intake; a component on the income per person, educational attainment, and total fertility rate under 25 years; and an autoregressive integrated moving average model to capture the unexplained component correlated over time. Data on risk predictors were obtained from Japan's National Health and Nutrition Surveys and from the Global Burden of Disease Study 2017. To generate a reference forecast of disease-specific DALY rates for 2017-2040, we modelled the three diseases using the data for 1990-2016. Additionally, we generated better, moderate, and worse scenarios to evaluate the impact of change in salt intake on the DALY rate for the diseases. RESULTS: In our reference forecast, the DALY rates across all ages were predicted to be stable for CVDs, continuously increasing for CKDs, and continuously decreasing for SC. Meanwhile, the age group-specific DALY rates for these three diseases were forecasted to decrease, with some exceptions. Except for the ≥70 age group, there were remarkable differences in DALY rates between scenarios, with the best scenario having the lowest DALY rates in 2040 for SC. This represents a wide scope of future trajectories by 2040 with a potential for tremendous decrease in SC burden. CONCLUSIONS: The gap between scenarios provides some quantification of the range of policy impacts on future trajectories of salt intake. Even though we do not yet know the policy mix used to achieve these scenarios, the result that there can be differences between scenarios means that policies today can have a significant impact on the future DALYs.

The diagnostic role of diffusional kurtosis imaging in glioma grading and differentiation of gliomas from other intra-axial brain tumours: a systematic review with critical appraisal and meta-analysis.

PURPOSE: We aim to illustrate the diagnostic performance of diffusional kurtosis imaging (DKI) in the diagnosis of gliomas. METHODS: A review protocol was developed according to the (PRISMA-P) checklist, registered in the international prospective register of systematic reviews (PROSPERO) and published. A literature search in 4 databases was performed using the keywords 'glioma' and 'diffusional kurtosis'. After applying a robust inclusion/exclusion criteria, included articles were independently evaluated according to the QUADAS-2 tool and data extraction was done. Reported sensitivities and specificities were used to construct 2 × 2 tables and paired forest plots using the Review Manager (RevMan®) software. A random-effect model was pursued using the hierarchical summary receiver operator characteristics. RESULTS: A total of 216 hits were retrieved. Considering duplicates and inclusion criteria, 23 articles were eligible for full-text reading. Ultimately, 19 studies were eligible for final inclusion. The quality assessment revealed 9 studies with low risk of bias in the 4 domains. Using a bivariate random-effect model for data synthesis, summary ROC curve showed a pooled area under the curve (AUC) of 0.92 and estimated sensitivity of 0.87 (95% CI 0.78-0.92) in high-/low-grade gliomas' differentiation. A mean difference in mean kurtosis (MK) value between HGG and LGG of 0.22 (95% CI 0.25-0.19) was illustrated (p value = 0.0014) with moderate heterogeneity (I2 = 73.8%). CONCLUSION: DKI shows good diagnostic accuracy in the differentiation of high- and low-grade gliomas further supporting its potential role in clinical practice. Further exploration of DKI in differentiating IDH status and in characterising non-glioma CNS tumours is however needed.

Long-term Trends in Prostate Cancer Incidence by Stage at Diagnosis in Japan Using the Multiple Imputation Approach, 1993-2014.

BACKGROUND: This study aimed to assess long-term trends in the incidence of prostate cancer by stage at diagnosis before and after the introduction of population-based PSA screening. METHODS: We used data from three population-based cancer registries in Japan. A total of 29,458 malignant prostate cancer cases diagnosed between 1993 and 2014 were used for the analysis. Multiple imputation with chained equations was used to impute a specific stage at diagnosis for cases with "unknown" and missing status. We estimated the age-standardized incidence rates by stage at diagnosis from 1993 to 2014, and used joinpoint linear regression models to assess changes in trend. RESULTS: Joinpoint analyses after imputation showed that localized cancer was stable from 1993 to 2000, followed by a pronounced but insignificant increase through 2003 (from 12.1 per 100,000 in 2001 to 34.1 per 100,000 in 2003), and a significant increase thereafter [annual percentage change (APC), 4.1%]. For regional cancer, the imputed data showed that the increasing trend lasted from 1993 to 2006 (APC, 12.5%), then leveled off through 2014. For distant prostate cancer, the imputed data showed the increasing trend continued from 1993 to 2004 (APC, 2.4%), and started to marginally decline thereafter (APC, -2.2%). CONCLUSIONS: Our study confirmed a significantly rapid increase in localized prostate cancer after the spread of PSA screening in Japan, with a marginal decrease in distant prostate cancer after 2004. IMPACT: Evaluation of the effectiveness of PSA screening would require a comprehensive analysis of changes in mortality, survival, and treatment practices over time.

Limited alignment of publicly competitive disease funding with disease burden in Japan.

OBJECTIVE: The need to align investments in health research and development (R&D) with public health needs is one of the most important public health challenges in Japan. We examined the alignment of disease-specific publicly competitive R&D funding to the disease burden in the country. METHODS: We analyzed publicly available data on competitive public funding for health in 2015 and 2016 and compared it to disability-adjusted life year (DALYs) in 2016, which were obtained from the Global Burden of Disease (GBD) 2017 study. Their alignment was assessed as a percentage distribution among 22 GBD disease groups. Funding was allocated to the 22 disease groups based on natural language processing, using textual information such as project title and abstract for each research project, while considering for the frequency of information. RESULTS: Total publicly competitive funding in health R&D in 2015 and 2016 reached 344.1 billion JPY (about 3.0 billion USD) for 32,204 awarded projects. About 49.5% of the funding was classifiable for disease-specific projects. Five GDB disease groups were significantly and relatively well-funded compared to their contributions to Japan's DALY, including neglected tropical diseases and malaria (funding vs DALY = 1.7% vs 0.0%, p<0.01) and neoplasms (28.5% vs 19.2%, p<0.001). In contrast, four GDB disease groups were significantly under-funded, including cardiovascular diseases (8.0% vs 14.8%, p<0.001) and musculoskeletal disorders (1.0% vs 11.9%, p<0.001). These percentages do not include unclassifiable funding. CONCLUSIONS: While caution is necessary as this study was not able to consider public in-house funding and the methodological uncertainties could not be ruled out, the analysis may provide a snapshot of the limited alignment between publicly competitive disease-specific funding and the disease burden in the country. The results call for greater management over the allocation of scarce resources on health R&D. DALYs will serve as a crucial, but not the only, consideration in aligning Japan's research priorities with the public health needs. In addition, the algorithms for natural language processing used in this study require continued efforts to improve accuracy.

Parallel repulsive logic regression with biological adjacency.

Logic regression, an extension of generalized linear models with Boolean combinations of binary variables as predictors, is a useful tool in exploring interactions among single-nucleotide polymorphisms (SNPs) in genome-wide association studies. However, since the search space defined by all possible combinations of SNPs, their complements, and logical operators in Boolean expressions can be exceedingly large in such studies, objective function optimization is slow and likely to be trapped in many local solutions, resulting in model over-fitting. We introduce a new search algorithm, parallel repulsive logic regression (PRLR), to efficiently estimate parameters of a logic regression to find a best model within the large space of SNP interactions by incorporating: (i) relevant biological adjacency matrix between SNPs to define similarity of estimation paths or trees, which are derived from physical SNP positions on chromosomes and/or memberships in biological gene pathways; and (ii) two repulsive forces to counter the similarity between and within estimation paths considered in parallel, which are introduced as penalty terms in the objective function. We compare our method's performance for identifying biologically-meaningful SNP interactions through simulations and with real genetic-epidemiological data. PRLR's detection-accuracy measures outperform existing approaches, especially in terms of positive predictive value and sensitivity for detecting SNP-SNP interactions.

Late-onset anorectal disease and psychosocial impact in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

BACKGROUND: The prevalence and associated psychosocial morbidity of late-onset anorectal disease after surgery and radiotherapy for the treatment of childhood cancer are not known. METHODS: A total of 25,530 survivors diagnosed between 1970 and 1999 (median age at cancer diagnosis, 6.1 years; age at survey, 30.2 years) and 5036 siblings were evaluated for late-onset anorectal disease, which was defined as a self-reported fistula-in-ano, self-reported anorectal stricture, or pathology- or medical record-confirmed anorectal subsequent malignant neoplasm (SMN) 5 or more years after the primary cancer diagnosis. Piecewise exponential models compared the survivors and siblings and examined associations between cancer treatments and late-onset anorectal disease. Multiple logistic regression with generalized estimating equations was used to evaluate associations between late-onset anorectal disease and emotional distress, as defined by the Brief Symptom Inventory 18 (BSI-18), and health-related quality of life, as defined by the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). RESULTS: By 45 years after the diagnosis, 394 survivors (fistula, n = 291; stricture, n = 116; anorectal SMN, n = 26) and 84 siblings (fistula, n = 73; stricture, n = 23; anorectal neoplasm, n = 1) had developed late-onset anorectal disease (adjusted rate ratio [RR] for survivors vs siblings, 1.2; 95% confidence interval [CI], 1.0-1.5). Among survivors, pelvic radiotherapy with ≥30 Gy within 5 years of the cancer diagnosis was associated with late-onset anorectal disease (adjusted RR for 30-49.9 Gy vs none, 1.6; 95% CI, 1.1-2.3; adjusted RR for ≥50 Gy vs none, 5.4; 95% CI, 3.1-9.2). Late-onset anorectal disease was associated with psychosocial impairment in all BSI-18 and SF-36 domains. CONCLUSIONS: Late-onset anorectal disease was more common among childhood cancer survivors who received higher doses of pelvic radiotherapy and was associated with substantial psychosocial morbidity.