Efficacy of anifrolumab in long-term intractable alopecia due to discoid lupus erythematosus.

Alopecia associated with lupus erythematosus is broadly classified into reversible nonscarring alopecia seen in the acute phase, such as worsening of systemic lupus erythematosus (SLE) and cicatricial alopecia seen in chronic cutaneous lupus erythematosus represented by discoid lupus erythematosus (DLE). In DLE-induced alopecia, early therapeutic intervention before developing scarring alopecia is important, but the condition is often resistant to conventional treatment. Anifrolumab (ANI), a novel therapeutic agent for SLE that inhibits type I interferon activity, has been shown to be effective against acute skin lesions, including alopecia, in patients with SLE. However, there are very few reports on the effect of ANI on alopecia due to DLE. We report on a 27-year-old Japanese woman with SLE whose alopecia due to chronic DLE was refractory to topical therapy and systemic therapy with oral glucocorticoid, multiple immunosuppressants and belimumab for approximately 8 years after onset, and whose alopecia improved with ANI. ANI can be considered to be an effective treatment option in lupus patients presenting with alopecia due to DLE, even in the chronic refractory stage.

Travel burdens to access care among children with cancer between 2016 and 2019: Analysis of a national population-based cancer registry in Japan.

BACKGROUND: Centralization of cancer care increases survival but increases the travel burden (i.e., travel durations, distances, and expenditures) in visiting hospitals. This study investigated the travel burdens to access cancer care for children aged 18 years and younger in Japan. METHODS: The study population comprised 10,709 patients diagnosed between 2016 and 2019 obtained from a national population-based cancer registry in Japan. Their residences were classified as urban or rural. We counted the number of patients treated at specialized hospitals and investigated the treatment centralization across diagnostic groups by Pareto plot. Travel burdens to access care were estimated using a route-planner web service and summarized using median values. A multivariable logistic model was performed to investigate factors associated with the events of car travel duration exceeding 1 h. RESULTS: Of the patients, 76.7% lived in urban areas, and 82.5% received treatment in designated hospitals for childhood cancer. The Pareto plot suggested that the top five hospitals treated 63.5% of patients with retinoblastoma. The estimated travel burdens for all patients were 0.62 h (0.57 h in urban areas and 1.00 h in rural areas), 16.9 km, and 0.0 dollars of toll charges. Regarding travel duration, 21.7% of patients had travel exceeding 1 h, and rural areas, retinoblastoma, malignant bone tumors, and childhood cancer-hub hospitals were associated with travel duration exceeding 1 h (adjusted odds ratios of 6.93, 3.59, 1.94, and 1.91, respectively). CONCLUSIONS: Most patients were treated in specialized hospitals and the treatments for specific diseases were centralized. However, most patients were estimated to travel less than 1 h, and the travel burden tended to increase for patients in rural areas, those with specific diseases, and those going to specialized hospitals. Cancer control measures in Japan have steadily improved centralized treatment while keeping the travel burden relatively manageable.

Aging-associated changes of optical coherence tomography-measured ganglion cell-related retinal layer thickness and visual sensitivity in normal Japanese.

PURPOSE: To report aging-associated change rates in circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and macular ganglion cell-inner plexiform layer and complex thickness (MGCIPLT, MGCCT) in normal Japanese eyes and to compare the data in linear scaled visual field (VF) sensitivity of central 4 points of Humphrey Field Analyzer (HFA) 24-2 test (VF4TestPoints) to that in MGCIPLT in four 0.6-mm-diameter circles corresponding to the four central points of HFA 24-2 adjusted for retinal ganglion cell displacement (GCIPLT4TestPoints). STUDY DESIGN: Prospective observational study METHODS: HFA 24-2 tests and spectral-domain optical coherence tomography (SD-OCT) measurements of cpRNFLT, MGCIPLT, MGCCT and GCIPLT4TestPoints were performed every 3 months for 3 years in 73 eyes of 37 healthy Japanese with mean age of 50.4 years. The time changes of SD-OCT-measured parameters and VF4TestPoints were analyzed using a linear mixed model. RESULTS: The aging-associated change rates were -0.064 µm/year for MGCIPLT and and -0.095 for MGCCT (P=0.020 and 0.017), but could not be detected for cpRNFLT. They accelerated with aging at -0.009µm/year/year of age for MGCIPLT (P<0.001), at 0.011 for MGCCT (P<0.001) and at 0.013 for cpRNFLT(0.031). The aging-associated decline of -82.1 [1/Lambert]/year of VF4TestPoints corresponded to -0.095 µm/year of GCIPLT4TestPoints. CONCLUSION: We report that aging-associated change rates of cpRNFLT, MGCIPLT and MGCCT in normal Japanese eyes were found to be significantly accelerated along with aging. Relationship between VF sensitivity decline rates and SD-OCT measured GCIPLT decline rates during physiological aging in the corresponding parafoveal retinal areas are also documented.

Suicide risk among patients with cancer by sex in Japan: A population-based study.

BACKGROUND: In Japan, few studies have examined suicide risk for five-year relative survival rates for cancer sites. Since five-year relative survival rates differ by sex, we aim to examine suicide risk for patients with cancer separately for men and women. METHODS: We estimated the risk of suicide among patients with cancer by sex in Japan compared to the general population, using standardized mortality ratios (SMRs). Patients with cancer diagnosed between January 1, 1985-December 31, 2013 and registered in the Osaka Cancer Registry were followed-up with for up to 10 years. The outcome was suicide death. In addition, cancer sites were classified into three prognosis groups based on five-year relative survival rates: good (> 70%), moderate (40-70%), poor (< 40%). RESULTS: Among 623 995 patients with cancer observed for 2 349 432 person-years, 1210 patients died by suicide (867 men and 343 women). The SMRs were almost equal for men (1.66, 95% CI, 1.55-1.77) and women (1.65, 95% CI, 1.48-1.83). SMRs for cancer prognosis groups were 1.01 (95% CI, 0.84-1.22) for men and 1.47 (95% CI, 1.24-1.73) for women in the good group, 1.53 (95% CI, 1.39-1.68) for men and 1.74 (95% CI, 1.47-2.05) for women in the moderate group, and 2.54 (95% CI, 2.27-2.85) for men and 1.87 (95% CI, 1.43-2.46) for women in the poor group. CONCLUSIONS: In this population, both sexes had higher suicide risk with poor prognosis, but the difference in SMRs between the good and poor groups was smaller for women than men.

Characteristics and Risk of Diabetes in People With Rare Glucose Response Curve During an Oral Glucose Tolerance Test.

CONTEXT: Existing differences in persons with lower 30- or 60-minute plasma glucose (PG) levels during 75-g oral glucose tolerance test (OGTT) than fasting PG remain unclear. OBJECTIVE: To clarify the characteristics of persons whose PG levels decrease after glucose administration during OGTT and their risk of incidence of diabetes in a Japanese general population. METHODS: In this cohort study, a total of 3995 men and 3500 women (mean age 56.7 years) without diabetes were classified into 3 groups: (1) PG at both 30 and 60 minutes ≥ fasting PG; (2) PG at 30 minutes ≥ fasting PG and PG at 60 minutes < fasting PG; (3) PG at 30 minutes < fasting PG. The characteristics and the risk of diabetes onset were analyzed using ordered logistic regression and Cox proportional hazard regression, respectively. RESULTS: Among 7495 participants, the numbers of individuals in the group 1, 2, and 3 were 6552, 769, and 174, respectively. The glucose response curve of the group 3 was boat shaped. Group 3 had the youngest age, lowest percentage of men, and best health condition, followed by groups 2 and 1. Among 3897 participants analyzed prospectively, 434 developed diabetes during the mean follow-up period of 5.8 years. The hazard ratio for diabetes onset in the group 2 was 0.30 with reference to the group 1. No-one in group 3 developed diabetes. CONCLUSION: People with lower 30-minute PG than fasting PG tended to be women, young, healthy, and at low risk of diabetes onset.

Risk of Parkinson's disease-related death in cancer survivors: A population-based study in Japan.

BACKGROUND: The risk of Parkinson's disease (PD)-related death in patients with cancer largely unexplored. METHODS: We analyzed data from the Neoplasms ANd other causes of DEath (NANDE) study, which investigates the causes of death in patients with cancer in Japan. Standardized mortality ratios (SMRs) were calculated to compare the risk of PD-related deaths in patients with cancer to that of the general population. Poisson regression models were employed to estimate the relative risk of PD-related death in the subgroups. RESULTS: The cohort included 548,485 patients with cancer, yielding 2,047,398 person-years at risk from 1995 to 2013. During the study period, 242,250 patients died and 145 deaths were attributable to PD. The SMR for PD-related death was 2.34 (95% confidence interval [CI]: 1.99-2.75). Patients who were diagnosed with cancer before 70 years of age had a high SMR (>5) for PD-related deaths. The SMR of patients with mouth-to-stomach cancers (lip, oral cavity, pharynx, esophagus, and stomach cancers) was 3.72 (95% CI: 2.84-4.86), while that of those with other cancers was 1.93 (95% CI: 1.57-2.37). The multivariate Poisson regression model revealed that patients with mouth-to-stomach cancers were more likely to die of PD than those without (relative risk 2.07, 95 % CI; 1.46-2.93). CONCLUSIONS: Patients with cancer are at a high risk of PD-related death; particularly, mouth-to-stomach cancers and potentially obstructing medication for PD are attributable to a high mortality risk. Careful management, including adequate PD treatment, would benefit cancer survivors with PD and reduce the risk of PD-related death.

Lifestyle factors associated with a rapid decline in the estimated glomerular filtration rate over two years in older adults with type 2 diabetes-Evidence from a large national database in Japan.

BACKGROUND: The present study investigated lifestyle risk factors from metabolic syndrome-related lifestyles for a rapid decline in the estimated glomerular filtration rate (eGFR) among adults aged 40-74 years with treated and untreated type 2 diabetes. METHODS AND RESULTS: This study analyzed data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan, encompassing the period from fiscal year (FY) 2017 to FY2020. We established FY2018 as our baseline year. The subjects of this study were adults aged 40-74 in FY2018(baseline) who had type 2 diabetes and underwent specific health checkups in FY2020. We excluded adults with a medical record of kidney dialysis between FY2017 and FY2018, records of suspected type 1 diabetes between FY2017 and FY2020, or a baseline eGFR >85 mL/min/1.73 m2 or missing eGFR data as of FY2020. Eventually we analyzed 573,860 individuals. The outcome variable was a rapid decline in eGFR (≥30%) during the follow-up. Exposure lifestyle factors included skipping breakfast, late-night dinners, regular smoking, a high alcohol intake, non-refreshing sleep, and a lack of habitual exercise. Logistic regression models were stratified by age (40-59 and 60-74 years) and baseline eGFR levels (60-85, 30-59, and <30 mL/min/1.73 m2). Covariates included sex, a history of heart disease, a history of stroke, a history of renal failure, anemia, low-density lipoprotein, systolic blood pressure, hemoglobin A1C, body mass index, antidiabetic medications, antihypertension drugs, lipid-lowering drugs, the oral adsorbent Kremezin, non-steroidal anti-inflammatory drugs, and drugs for the treatment of renal anemia. A rapid decline in eGFR was detected in approximately 1.3% of participants (7,683 cases). In the baseline eGFR >30 subgroups (60-85 or 30-59 mL/min/1.73 m2), skipping breakfast and regular smoking were associated with a rapid decline in eGFR in both age groups, while a lack of habitual exercise and late-night dinners in the 60-74 age group and non-refreshing sleep in the 40-59 age group were identified as risk factors. Additionally, skipping breakfast was a risk factor for a rapid decline in eGFR in the 60-74 age group regardless of baseline eGFR levels. In the baseline eGFR <30 mL/min/1.73 m2 subgroup, skipping breakfast and non-refreshed sleep were risk factors for a rapid decline in eGFR. CONCLUSIONS: We found specific lifestyle risk factors were associated with a rapid eGFR decline among people with type 2 diabetes from a nationwide database in Japan. The associations varied by baseline eGFR level, age, and sex. Lifestyle modifications may effectively prevent the aggravation of diabetic kidney disease.

Heart Disease Mortality in Cancer Survivors: A Population-Based Study in Japan.

BACKGROUND: Data on the risk of cardiovascular-related mortality in patients with cancer are limited. METHODS AND RESULTS: This retrospective cohort study used data from the Osaka Cancer Registry and vital statistics in Japan between 1985 and 2013. The causes of death were investigated, and the risk of fatal heart disease was analyzed. Standardized mortality ratios were calculated to compare the risk of fatal heart disease between patients with cancer and the general population. Fine and Gray competing risk regression models were used to assess the risk of fatal heart disease among patients with cancer. In total, 682 886 patients with cancer were included in the analysis, and 335 635 patients died during the study period. Heart disease was the leading cause of noncancer deaths, with 10 686 deaths. Among the patients who died of heart disease, 5017 had ischemic heart disease, 3598 had heart failure, 356 had hypertensive disease, and 1715 had other heart diseases. The standardized mortality ratio for heart disease was 2.80 (95% CI, 2.74-2.85). The standardized mortality ratio for ischemic heart disease, heart failure, and hypertensive disease were 3.26 (95% CI, 3.17-3.35), 2.69 (95% CI, 2.60-2.78), and 5.97 (95% CI, 5.38-6.63), respectively. The risk of fatal heart disease increased over time after cancer diagnosis. Men were more likely to die of heart disease than women (subdistribution hazard ratio, 1.08 [95% CI, 1.02-1.16]). The risk of fatal heart disease among cancer survivors has decreased in recent years. CONCLUSIONS: Cancer survivors have a higher risk of fatal heart disease than the general population.

A dominant negative 14-3-3 mutant in Schizosaccharomyces pombe distinguishes the binding proteins involved in sexual differentiation and check point.

The homothallic fission yeast Schizosaccharomyces pombe undergoes sexual differentiation when starved, but sam (skips the requirement of starvation for mating) mutants such as those carrying mutations in adenylate cyclase (cyr1) or protein kinase A (pka1) mate without starvation. Here, we identified sam3, a dominant negative allele of rad24, encoding one of two 14-3-3 proteins. Genetic mapping and whole-genome sequencing showed that the sam3 mutation comprises a change in nucleotide at position 959 from guanine to adenine, which switches the amino acid at position 185 from glutamic acid to lysine (E185K). We generated the rad24-E185K integrated mutant and its phenotype was similar to that of the sam3 mutant, including calcium sensitivity and UV non-sensitivity, but the phenotype is different from that of the Δrad24 strain. While the UV-sensitive phenotype was observed in the Δrad24 mutant, it was not observed in the sam3 and rad24-E185K mutants. The expression of the rad24-E185K gene in wild type cells induced spore formation in the nutrient rich medium, confirming rad24-E185K is dominant. This dominant effect of rad24-E185K was also observed in Δras1 and Δbyr2 diploid mutants, indicating that rad24-E185K generate stronger phenotype than rad24 null mutants. Ste11, the key transcription factor for sexual differentiation was expressed in sam3 mutants without starvation and it predominantly localized to the nucleus. The Rad24-E185K mutant protein retained its interaction with Check point kinase1 (Chk1), whereas it reduced interaction with Ste11, an RNA binding protein Mei2, and a MAPKKK Byr2, freeing these proteins from negative regulation by Rad24, that account for the sam phenotype and UV non-sensitive phenotype. Glucose depletion in rad24-E185K or Δpka1 Δrad24 double mutation induced haploid meiosis, leading to the formation of spores in haploid. The position of glutamic acid 185 is conserved in all major 14-3-3s; hence, our finding of a dominant negative allele of 14-3-3 is useful for understanding 14-3-3s in other organisms.

Trends of travel burdens to access cancer care among children with cancer: analysis of a population-based cancer registry data in Aichi, Japan.

Centralization of childhood cancer treatment in specialized hospitals is necessary for quality treatment and care, but imposes a time and cost burden for patients and their families. We investigated the 20-year trend in the patients' car travel burden to reach cancer-care hospitals in Aichi Prefecture, Japan. From the Aichi population-based cancer registry data, 1,741 cases diagnosed in 1998-2017 under 15 years of age were extracted and assigned to three treatment groups: invasive treatment (n = 697), radiotherapy (n = 371), or chemotherapy groups (n = 1,462), allowing for duplicate assignment. Their travels to access each treatment hospital were estimated and summarized as the estimated travel times (ETT), estimated travel distances (ETD), and direct distances (DD). The ETTs were compared using the Brunner-Munzel test. The average cases per year for each hospital were plotted. The annual trends during 1998-2017 on ETT, ETD, and DD were investigated using Joinpoint regression models. The ETTs were 0.38-0.45 hours on median for three periods (1998-2005, 2006-2012, and 2013-2017) in three treatment groups and increased by 0.02-0.07 hours from 2006-2012 to 2013-2017, with a statistically significant difference in the radiotherapy group (0.07 hours, P = 0.037). The average cases per year increased for the top hospital in each group, and regression model analyses showed no joinpoint on the annual median trend. In conclusion, the increases in travel times were small and not considered clinically significant, and treatment centralization was observed from 2006-2012 to 2013-2017.

The number of erupted teeth as a risk factor for dental caries in eighteen-month-old children: a cross­sectional study.

BACKGROUND: Dental caries is one of the most common chronic diseases worldwide, affecting lifelong as well as children. Therefore, it is important to clarify factors related to early childhood caries (ECC) in a younger population in terms of caries prevention. However, the prevalence of ECC is low in developed countries in the twenty-first century and a large-scale survey is needed to clarify the risk factors. Furthermore, earlier tooth eruption is not taken into consideration in most studies of ECC, even though it may be a factor of ECC. The present study investigated the prevalence and risk factors of dental caries in children aged 18 months in a core city of Japan. METHODS: Findings from a total of 7351 children aged 18 months were analyzed. Anthropometric measurements of height and weight, as well as an oral examination and a microbiological caries-risk test, were performed. Additionally, a structured interview sheet was provided to the parents or guardians. Findings of dental caries at 18 months of age were evaluated using a logistic regression model. RESULTS: Of the enrolled children, 1.2% had experienced dental caries. Multivariable logistic regression analysis results indicated a significant association with dental caries at 18 months of age for the following factors: second child (OR = 1.78; 95% CI:1.08-2.93, P < 0.05), third and later child (OR = 2.08; 95% CI:1.12-3.89, P < 0.05), 12 or fewer erupted teeth (OR = 0.47; 95% CI:0.24-0.96, P < 0.05), 17 or more erupted teeth (OR = 4.37; 95% CI:1.63-11.7, P < 0.01), Cariostat score (+ + +) (OR = 3.99; 95% CI:1.29-12.31, P < 0.05), daily eating before bed (OR = 2.62; 95% CI: 1.55-4.45, P < 0.001), three or more snacks per day (OR = 2.03; 95% CI:1.15-3.58, P < 0.05), and breastfeeding (OR = 3.30; 95% CI:2.00-5.44, P < 0.001). CONCLUSIONS: These results suggest that the number of erupted teeth, as well as birth order, eating habits, and breastfeeding, are significant factors in dental caries occurrence at 18 months of age.

Examining normative values using the Cambridge neuropsychological test automated battery and developmental traits of executive functions among elementary school-aged children in Japan.

The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a computerized and child-friendly neuropsychological assessment battery that includes subtests aimed at evaluating some aspects of executive functions. Using the CANTAB, this study aims to establish normative values based on the aspects of executive functions among school-aged children in Japan. The participants included 234 children (135 boys and 99 girls aged 6-12 years) enrolled in regular classes, without any clinical records of developmental disorders or educational support. The participants were grouped according to age (6-7, 8-9, and 10-12 years). Four CANTAB subtests, including spatial working memory (SWM) to assess spatial working memory, Stockings of Cambridge (SOC) to evaluate planning, intra/extradimensional set shift (IED) to evaluate attentional set shifting and flexibility, and stop signal task (SST) to evaluate inhibition, were administered to each participant. The results showed that performance in all the CANTAB subtests administered changed with age. Among the subtests, compared with performances in the SOC and IED, those in the SWM and SST improved earlier, thereby indicating that spatial working memory and inhibition develop earlier than planning as well as attentional set shifting and flexibility. Additionally, in the SST subtest, girls made fewer errors than boys did in the 6-7 years group. This study presents normative data of four CANTAB subtests according to age and sex among school-aged children in Japan. We expect that the findings will be used to develop effective tools for the early detection of and support for children with executive dysfunction.

Prognostic impact of the presence or absence of prior cancer in patients with cancer using cure models: A population-based study.

Developing a subsequent cancer is one of the major concerns for cancer survivors; however, whether prior cancer could affect their prognosis is unknown. We therefore aimed to analyze how prognosis varies depending on prior cancer in patients with newly developed cancer, focusing on cancer that had been "cured." We used the record-linked database of the Osaka Cancer Registry and Vital Statistics to select 186,798 patients with stomach, colorectal, or lung cancer aged ≥40 years from 1995 to 2009 in Osaka, Japan. These cancers were defined as index cancers. We classified the patients into two groups according to whether they had a prior cancer diagnosis within 10 years before the index cancer diagnosis. The cured proportion was defined as the proportion of cancer patients with the same mortality as the general population and was estimated using the parametric mixture cure model. The cured proportion of patients with prior cancer by sex and age group was not significantly lower than those without prior cancer, except for patients with stomach cancer aged ≥65 years. According to the index cancer stage in the localized stomach or colorectal cancer, the cured proportion in patients with prior cancer was lower than in those without prior cancer. However, at any stage of lung cancer, the proportion of patients with prior cancer who had been cured was similar to patients without prior cancer, therefore prior cancer had a prognostic impact only in some patient groups based on the characteristics of their index cancer.

Age-Dependent Causes of Death among Patients with Breast Cancer Based on Osaka Cancer Registry and Vital Statistics in Japan.

We aimed to clarify the differences in causes of death among patients with breast cancer according to age at diagnosis and years elapsed since diagnosis. Using data from the Osaka Cancer Registry and Vital Statistics databases, 40,690 female patients diagnosed with primary breast cancer between 1985 and 2006 were included in this study. The statistics on all deaths between 1985 to 2016 were collected, and the observation period was 10 years (2006-2016). Mortality hazards according to age at diagnosis and years elapsed since diagnosis were estimated using a flexible parametric estimation. Of the 40,690 patients, 13,676 (34%) died from all-cause death, and the 10-year survival rate was 65.74% (95% confidence interval: 65.28-66.21). The proportions of deaths were 10,531 (77%) from breast cancer, 1048 (8%) from other cancers, and 2097 (15%) from non-cancer causes. The mortality hazard for deaths from breast cancer was initially high and then declined, whereas that for deaths from other cancers and non-cancer causes was initially low and then increased. The more likely causes of death 5 years after breast cancer diagnosis were other cancers or non-cancer causes among patients aged ≥70 years.

Major Causes of Death among Older Adults after the Great East Japan Earthquake: A Retrospective Study.

This retrospective study investigated the 3-year impact of the Great East Japan Earthquake (GEJE) of 2011 on deaths due to neoplasm, heart disease, stroke, pneumonia, and senility among older adults in the primarily affected prefectures compared with other prefectures, previous investigations having been more limited as regards mortality causes and geographic areas. Using death certificates issued between 2006 and 2015 (n = 7,383,253), mortality rates (MRs) and risk ratios (RRs) were calculated using a linear mixed model with the log-transformed MR as the response variable. The model included interactions between the area category and each year of death from 2010 to 2013. The RRs in the interaction significantly increased to 1.13, 1.17, and 1.28 for deaths due to stroke, pneumonia, and senility, respectively, in Miyagi Prefecture in 2011, but did not significantly increase for any of the other areas affected by the GEJE. Moreover, increased RRs were not reported for any of the other years. The risk of death increased in 2011; however, this was only significant for single-year impact. In 2013, decreased RRs of pneumonia in the Miyagi and Iwate prefectures and of senility in Fukushima Prefecture were observed. Overall, we did not find evidence of strong associations between the GEJE and mortality.

Cause of Death among Long-Term Cancer Survivors: The NANDE Study.

Survival information for Japanese patients with cancer is based only on survival status and the cause of death among these patients remains unclear. In this study, Osaka Cancer Registry data (1985-2014) and vital statistics data (1985-2016) were linked to create a database, permitting the extraction of data on the causes of death. In total, 522,566 subjects diagnosed with cancer between 1995 and 2011 were analyzed. Follow-up for vital status was conducted 5 and 10 years after cancer diagnosis. To evaluate the three causes of death (index cancer, non-index cancer, and non-cancer death), cause-specific hazard and cumulative incidence functions were estimated using a life table and Gray's methods. The number of deaths owing to any of the causes in the observation period (median: 3.51 years, mean: 4.90 years) was 394,146. The 5- and 10-year cancer-specific survival rate was 48.56% and 39.92%, respectively. Immediately after cancer onset, the hazard of index cancer death was high. The proportion of non-index cancer deaths was high in patients with mouth and pharynx cancers. The hazard of index cancer death remained constant for breast and liver cancers. In prostate, breast, and laryngeal cancers with good prognosis, the hazard of non-index cancer and non-cancer death constantly increased.

A novel "five-in-one" comprehensive medical care framework for rehabilitation and nursing.

With the evolution of society, the world has entered a moderate stage of aging. Not surprisingly, the aging problem in the world is getting more intense, resulting in the increasing demand for higher-quality and well-organized medical and elderly care services. To cope with that, many researchers have dedicated themselves to advancing the medical care system based on data or platforms. However, they have ignored the life cycle, health service and management and the inevitable shift of living scenarios for the elderly. Therefore, the study aims to improve health conditions and enhance senior citizens' life quality and happiness index. In this paper, we build a unified body for people in their old age, bridging the disconnection between medical care and elderly care and constructing the "five-in-one" comprehensive medical care framework. It should be mentioned that the system takes the human life cycle as its axis, relies on the supply side and supply chain management, integrates medicine, industry, literature and science as methods, and takes health service management as a requirement. Furthermore, a case study on upper limb rehabilitation is elaborated along the "five-in-one" comprehensive medical care framework to confirm the effectiveness of the novel system.

Recent advancements in digital health management using multi-modal signal monitoring.

Healthcare is the method of keeping or enhancing physical and mental well-being with its aid of illness and injury prevention, diagnosis, and treatment. The majority of conventional healthcare practices involve manual management and upkeep of client demographic information, case histories, diagnoses, medications, invoicing, and drug stock upkeep, which can result in human errors that have an impact on clients. By linking all the essential parameter monitoring equipment through a network with a decision-support system, digital health management based on Internet of Things (IoT) eliminates human errors and aids the doctor in making more accurate and timely diagnoses. The term "Internet of Medical Things" (IoMT) refers to medical devices that have the ability to communicate data over a network without requiring human-to-human or human-to-computer interaction. Meanwhile, more effective monitoring gadgets have been made due to the technology advancements, and these devices can typically record a few physiological signals simultaneously, including the electrocardiogram (ECG) signal, the electroglottography (EGG) signal, the electroencephalogram (EEG) signal, and the electrooculogram (EOG) signal. Yet, there has not been much research on the connection between digital health management and multi-modal signal monitoring. To bridge the gap, this article reviews the latest advancements in digital health management using multi-modal signal monitoring. Specifically, three digital health processes, namely, lower-limb data collection, statistical analysis of lower-limb data, and lower-limb rehabilitation via digital health management, are covered in this article, with the aim to fully review the current application of digital health technology in lower-limb symptom recovery.

Effect of the Diabetic Nephropathy Aggravation Prevention Program on medical visit behavior in individuals under the municipal national health insurance.

AIMS/INTRODUCTION: We aimed to clarify the effectiveness of the Diabetic Nephropathy Aggravation Prevention Program in Japan by comparing the diabetes-related medical visit behavior of individuals under the municipal national health insurance according to insurers' effort levels. MATERIALS AND METHODS: We assessed changes in medical visit behavior according to insurers' effort levels, "Full Efforts," "Some Efforts" and "No Effort," using longitudinal data from the National Database of Health Insurance Claims and Specific Health Checkups before 2015 and after 2018 regarding the national health insurance programs in Japan. We analyzed the effect of the Diabetic Nephropathy Aggravation Prevention Program using a generalized linear mixed model for 208,388 participants with diabetes. RESULTS: The additive effect on medical visit behavior was significantly higher for insurers with "Full Efforts" than for those with "No Effort;" the coefficient (log odds ratio) was 0.159 (95% confidence interval 0.063-0.256). The additive effects on medical visit behavior sizes for the people with hemoglobin A1c ≥7.0%, positive urinary protein and systolic blood pressure ≥140 mmHg were 0.508, 0.402 and 0.232, respectively, which were larger than the overall effect size (0.159) for insurers with "Full Efforts." CONCLUSIONS: Our findings showed that insurer efforts had an additive effect on the increase in the number of medical visits, suggesting that this national program could reduce the number of end-stage renal failures or dialysis in Japan.