Factors associated with the introduction of visiting-pharmacist services in older adults in Japan: A nested case-control study.

AIM: To investigate the factors associated with introducing visiting-pharmacist services for community-dwelling older adults in Japan. METHODS: We conducted a nested case-control study using claims data in a cohort from a city in Tokyo. Patients aged ≥65 years who received visiting-pharmacist services for the first time between April 2014 and March 2020 were considered case patients. A maximum of four controls to each case patient were randomly selected on the basis of sex, age, health insurance systems, and month-year. Medical and long-term care service usage and patient condition were assessed using claims data from the index and preceding months, along with long-term care needs certification data. Multivariable conditional logistic regression analysis was conducted to estimate the adjusted odds ratios with 95% confidence intervals for factors associated with visiting-pharmacist service introduction. RESULTS: A total of 22 949 participants (4591 cases and 18 358 controls) were included, with a median age of 85 years; 59.3% were women. The adjusted odds ratios (95% confidence intervals) of the three most related factors were 27.61 (23.98-31.80) for physicians' home visits, 5.83 (5.08-6.70) for hospitalization, and 4.97 (4.16-5.95) for designated-facility admission. Factors such as prescribing ≧10 medications, visiting nursing, and cancer were positively associated. In contrast, low household income and a high need for support due to cognitive function or disability were negatively associated. CONCLUSIONS: This study provides insights into the introduction of visiting-pharmacist services for older adults in Japan. Geriatr Gerontol Int 2024; 24: 344-351.

Analyzing Patient-Sharing Network Using an Administrative Claim Database in Japan.

We analyzed the behavior of patient with a focus on patient-sharing based on the methodology of network analysis. We used an administrative healthcare claims database from September of the years 2008-2020 to identify shared patients with hypertension. The patients' behavior of visiting multiple medical facilities was extracted as graphical data, and we calculated density and centrality as indicators to evaluate the structure of the patient sharing network. Our findings indicate that density, reciprocity, and transitivity increased over time, and that centrality and PageRank were correlated.

Changes in Demand Volume and Patient/Health Care Provider Characteristics of First-Time Telehealth Users: A Comparative Analysis Before and After the COVID-19 Policy Response Using the Administrative Claims Database.

Introduction: The COVID-19 pandemic has led to a decrease in demand for medical services in Japan, but the utilization of telehealth, which the Japanese government has recently promoted, has seen a temporary increase. This study aims to analyze the trend of telehealth utilization and changes in patient characteristics following the policy response to COVID-19. Methods: This retrospective study analyzed data from 26,152 adult patients who used telehealth for the first time between April 2019 and April 2021 in Mie Prefecture, Japan. An interrupted time series analysis was conducted to evaluate changes in the number of first-time patients before and after April 2020. Results: The number of telehealth users increased by 111.87% after April 2020, but the trend showed a declining slope thereafter. Patient characteristics and disease types showed different trends. The percentage of patients choosing a hospital over a clinic increased for the first time. Conclusions: After the policy response to COVID-19, the number of first-time telehealth users overall increased immediately, but gradually showed a declining trend. However, some diseases have shown both an immediate increase and a continued upward trend in telehealth utilization. Patients with these diseases may be candidates for adopting telehealth services in clinical settings.

Association of the Japanese herbal kampo medicine kakkonto with antibiotic use and surgical drainage for noninfectious mastitis: A nationwide database study.

AIM: Kakkonto, a Japanese herbal kampo medicine, is empirically prescribed to improve milk stasis and ameliorate breast inflammation in patients with noninfectious mastitis. We investigated whether early use of kakkonto is associated with a reduction in antibiotic use and surgical drainage in patients with noninfectious mastitis. METHODS: We identified 34 074 patients with an initial diagnosis of noninfectious mastitis within 1 year of childbirth between April 2012 and December 2022 using the nationwide administrative JMDC Claims Database. Patients were divided into the kakkonto (n = 9593) and control (n = 9648) groups if they received and did not receive kakkonto on the day of the initial diagnosis of noninfectious mastitis, respectively. Antibiotic administration and surgical drainage within 30 days after the initial diagnosis of noninfectious mastitis in the two groups were compared using propensity score-stabilized inverse probability of treatment weighting analysis. RESULTS: The frequency of antibiotic administration within 30 days after the initial diagnosis of noninfectious mastitis was significantly lower in the kakkonto group than in the control group (10% vs. 12%; odds ratio, 0.88 [95% confidence interval, 0.80-0.96]). The frequency of antibiotic administration during 1-3 and 4-7 days after the initial diagnosis were also significantly lower in the kakkonto group than in the control group. The frequency of surgical drainage did not differ significantly between the two groups. CONCLUSIONS: Kakkonto was associated with reduced administration of antibiotics for noninfectious mastitis, making it a potential treatment option for relieving breast inflammation and promoting antimicrobial stewardship.

Optimal allocation of physicians improves accessibility and workload disparities in stroke care.

BACKGROUND: Inequalities in access to stroke care and the workload of physicians have been a challenge in recent times. This may be resolved by allocating physicians suitable for the expected demand. Therefore, this study analyzes whether reallocation using an optimization model reduces disparities in spatial access to healthcare and excessive workload. METHODS: This study targeted neuroendovascular specialists and primary stroke centers in Japan and employed an optimization model for reallocating neuroendovascular specialists to reduce the disparity in spatial accessibility to stroke treatment and workload for neuroendovascular specialists in Japan. A two-step floating catchment area method and an inverted two-step floating catchment area method were used to estimate the spatial accessibility and workload of neuroendovascular specialists as a potential crowdedness index. Quadratic programming has been proposed for the reallocation of neuroendovascular specialists. RESULTS: The reallocation of neuroendovascular specialists reduced the disparity in spatial accessibility and the potential crowdedness index. The standard deviation (SD) of the demand-weighted spatial accessibility index improved from 125.625 to 97.625. Simultaneously, the weighted median spatial accessibility index increased from 2.811 to 3.929. Additionally, the SD of the potential crowdedness index for estimating workload disparity decreased from 10,040.36 to 5934.275 after optimization. The sensitivity analysis also showed a similar trend of reducing disparities. CONCLUSIONS: The reallocation of neuroendovascular specialists reduced regional disparities in spatial accessibility to healthcare, potential crowdedness index, and disparities between facilities. Our findings contribute to planning health policies to realize equity throughout the healthcare system.

Regional disparity in the provision of rehabilitation services using the open data from the Japanese national claims database: an ecological study.

OBJECTIVES: There are few reports on regional differences in the supply/utilisation balance and provision of rehabilitation services. This study analysed those regional differences in Japan to help policymakers provide more uniform and efficient rehabilitation services and optimally allocate related resources. DESIGN: An ecological study. SETTING: 47 prefectures and 9 regions in Japan in 2017. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary measures were 'supply/utilisation (S/U) ratio', calculated by dividing rehabilitation supply converted to service units, by rehabilitation utilisation and 'utilisation/expected utilisation (U/EU) ratio', calculated by dividing utilisation by EU. The EU was defined as utilisation expected from the demography in each area. Data required to calculate these indicators were collected from open sources such as the National Database of Health Insurance Claims and Specific Health Checkups of Japan Open Data Japan. RESULTS: The S/U ratios were higher in Shikoku, Kyusyu, Tohoku and Hokuriku regions, and lower in Kanto and Tokai regions. The number of rehabilitation providers per population was higher mostly in the western part of Japan and lower mostly in the eastern part. The U/EU ratios were also higher mostly in the western part, and lower mostly in the eastern part such as Tohoku and Hokuriku regions. The same trend was seen for cerebrovascular disease and musculoskeletal disorder rehabilitation, which accounted for approximately 84% of rehabilitation services. For disuse syndrome rehabilitation, such a trend did not exist, and the U/EU ratio differed by prefectures. CONCLUSIONS: The large surplus in rehabilitation supply in the western part was attributed to the greater number of providers, while the smaller surplus in Kanto and Tokai regions was due to the smaller amount of supply. The number of rehabilitation services used was lesser in the eastern part such as Tohoku and Hokuriku regions, indicating regional differences in the provision of rehabilitation services.

Predicting demand for long-term care using Japanese healthcare insurance claims data.

BACKGROUND: Driven by the rapid aging of the population, Japan introduced public long-term care insurance to reinforce healthcare services for the elderly in 2000. Precisely predicting future demand for long-term care services helps authorities to plan and manage their healthcare resources and citizens to prevent their health status deterioration. METHODS: This paper presents our novel study for developing an effective model to predict individual-level future long-term care demand using previous healthcare insurance claims data. We designed two discriminative models and subsequently trained and validated the models using three learning algorithms with medical and long-term care insurance claims and enrollment records, which were provided by 170 regional public insurers in Gifu, Japan. RESULTS: The prediction model based on multiclass classification and gradient-boosting decision tree achieved practically high accuracy (weighted average of Precision, 0.872; Recall, 0.878; and F-measure, 0.873) for up to 12 months after the previous claims. The top important feature variables were indicators of current health status (e.g., current eligibility levels and age), risk factors to worsen future healthcare status (e.g., dementia), and preventive care services for improving future healthcare status (e.g., training and rehabilitation). CONCLUSIONS: The intensive validation tests have indicated that the developed prediction method holds high robustness, even though it yields relatively lower accuracy for specific patient groups with health conditions that are hard to distinguish.

Potent and Selective PTDSS1 Inhibitors Induce Collateral Lethality in Cancers with PTDSS2 Deletion.

SIGNIFICANCE: This study identifies a specific dependency on PTDSS1 for phosphatidylserine synthesis following PTDSS2 deletion and introduces novel PTDSS1 inhibitors as a therapeutic option to induce collateral lethality in cancer with PTDSS2 loss.

The Association Between Telehealth Utilization and Policy Responses on COVID-19 in Japan: Interrupted Time-Series Analysis.

BACKGROUND: Telehealth using telephones or online communication is being promoted as a policy initiative in several countries. However, there is a lack of research on telehealth utilization in a country such as Japan that offers free access to medical care and regulates telehealth provision-particularly with respect to COVID-19. OBJECTIVE: The present study aimed to clarify telehealth utilization, the characteristics of patients and medical institutions using telehealth, and the changes to telehealth in Japan in order to support the formulation of policy strategies for telehealth provision. METHODS: Using a medical administrative claim database of the National Health Insurance and Advanced Elderly Medical Service System in Mie Prefecture, we investigated patients who used telehealth from January 2017 to September 2021. We examined telehealth utilization with respect to both patients and medical institutions, and we determined their characteristics. Using April 2020 as the reference time point for COVID-19, we conducted an interrupted time-series analysis (ITSA) to assess changes in the monthly proportion of telehealth users to beneficiaries. RESULTS: The number of telehealth users before the reference time point was 13,618, and after the reference time point, it was 28,853. Several diseases and conditions were associated with an increase in telehealth utilization. Telehealth consultations were mostly conducted by telephone and for prescriptions. The ITSA results showed a sharp increase in the proportion of telehealth use to beneficiaries after the reference time point (rate ratio 2.97; 95% CI 2.14-2.31). However, no apparent change in the trend of increasing or decreasing telehealth use was evident after the reference time point (rate ratio 1.00; 95% CI 1.00-1.01). CONCLUSIONS: We observed a sharp increase in telehealth utilization after April 2020, but no change in the trend of telehealth use was evident. We identified changes in the characteristics of patients and providers using telehealth.

Prevalence of hypertensive diseases and treated hypertensive patients in Japan: A nationwide administrative claims database study.

We investigated the prevalence of hypertensive patients and treated hypertensive patients using a Japanese nationwide administrative claims database. We analyzed national database data from 2014, including all claims data, provided by the Ministry of Health, Labour and Welfare of Japan. Hypertensive diseases were identified using Japanese standardized disease codes. Among hypertensive patients, treated hypertensive patients were defined by the prescription of any antihypertensive medication, identified using national health insurance price listing codes. We calculated and compared the number and age-adjusted prevalence of hypertensive patients and treated hypertensive patients by prefecture and the proportion of these patients by the size of medical facilities. In 2014, approximately 27 million Japanese people were identified as hypertensive, among which 89.6% were treated. The age-adjusted prevalence of hypertensive patients (per 100,000 persons) among women and men was 21,414 and 21,084, respectively. The age-adjusted prevalence of treated hypertensive patients (per 100,000 persons) among women and men was 19,118 and 18,974, respectively. While the prevalence of hypertensive and treated hypertensive patients varied geographically, the prevalence remained similar between the sexes. Approximately 59% of hypertensive patients visited clinics (0 to 19 beds) in Japan. In Japan, 27 million people were diagnosed with hypertensive diseases, and approximately 90% of these patients were treated with any antihypertensive medication in 2014. The distribution of hypertensive patients varied geographically throughout Japan.

Current status of delirium assessment tools in the intensive care unit: a prospective multicenter observational survey.

Delirium is a critical challenge in the intensive care unit (ICU) or high care unit (HCU) setting and is associated with poor outcomes. There is not much literature on how many patients in this setting are assessed for delirium and what tools are used. This study investigated the status of delirium assessment tools of patients in the ICU/HCU. We conducted a multicenter prospective observational study among 20 institutions. Data for patients who were admitted to and discharged from the ICU/HCU during a 1-month study period were collected from each institution using a survey sheet. The primary outcome was the usage rate of delirium assessment tools on an institution- and patient-basis. Secondary outcomes were the delirium prevalence assessed by each institution's assessment tool, comparison of delirium prevalence between delirium assessment tools, delirium prevalence at the end of ICH/HCU stay, and the relationship between potential factors related to delirium and the development of delirium. Result showed that 95% of institutions used the Intensive Care Delirium Screening Checklist (ICDSC) or the Confusion Assessment Method for the ICU (CAM-ICU) to assess delirium in their ICU/HCU, and the remaining one used another assessment scale. The usage rate (at least once during the ICU/HCU stay) of the ICDSC and the CAM-ICU among individual patients were 64.5% and 25.1%, and only 8.2% of enrolled patients were not assessed by any delirium assessment tool. The prevalence of delirium during ICU/HCU stay was 17.9%, and the prevalence of delirium at the end of the ICU/HCU stay was 5.9%. In conclusion, all institutions used delirium assessment tools in the ICU/HCU, and most patients received delirium assessment. The prevalence of delirium was 17.9%, and two-thirds of patients had recovered at discharge from ICU/HCU.Trial registration number: UMIN000037834.

Monthly trends and seasonality of hemodialysis treatment and outcomes of newly initiated patients from the national database (NDB) of Japan.

BACKGROUND: The numbers of patients treated with hemodialysis (HD) in Japan are currently quantified by manual survey. As this method requires much effort from medical institutions and cannot achieve 100% response, a more practical method is required. We aimed to establish a novel method for determining the static and dynamic numbers of patients treated with HD. METHODS: This observational study used the national medical billing database (termed NDB) of Japan, based on the records of the universal healthcare insurance system. Medical billing data registered in the NDB between April 2011 and March 2015 were analyzed. From 130 billion records, we extracted and analyzed records of patients who had undergone HD at least once per month. Patients' monthly condition was classified as newly initiated HD, chronic HD, or presumed death, using conditional expressions. We also investigated renal outcome and presumed survival in newly initiated HD patients. RESULTS: In the last month of the study period, 274,100 patients were identified as receiving chronic HD, which is estimated as > 95% of the number of these patients identified in the manual survey so far. The monthly data showed clear seasonality in the incidence of transient HD, which increased in winter and decreased in summer. CONCLUSION: Analysis of a large national database revealed a significant increase in transient HD in winter and decrease in summer. Applied to additional epidemiological exploratory studies or clinical research, this analytical technique would enable collection of the dynamics of almost all HD patients nationwide.

Projecting supply and demand for pharmacists in pharmacies based on the number of prescriptions and system dynamics modeling.

BACKGROUND: Pharmacists play an important role in promoting people's health in Japan, which has an aging population. Hence, it is necessary that the distribution of pharmacists meets the population's needs in each region. This study projects the future supply and demand for pharmacists in pharmacies to consider an optimal distribution of pharmacists. METHODS: The future supply of pharmacists working in pharmacies in Hokkaido is projected using system dynamics modeling, according to their career path. The demand is projected based on the number of prescriptions, sourced from publicly available sources. The analysis period is 2015-2040. The estimated demand is converted into the number of pharmacists and the sufficiency is evaluated using sufficiency ratio (supply/demand ratio). Sensitivity analyses of the sufficiency ratio were conducted to estimate the effects of changes in parameters such as national exam pass rate, enrollments, attrition rates, the number of prescriptions per pharmacist, and diffusion of newly licensed pharmacists. RESULTS: The projected supply, in 2025 and 2040, is 1.24 and 1.56 times, respectively, as that in 2015 and the demand is 1.11 and 0.98 times, respectively. In 2015, although the sufficiency ratio in Hokkaido overall is 1.19, the ratios are higher in urban medical areas and lower than 1 in rural medical areas, such as Minamihiyama, Emmon, and Nemuro. By 2040, the sufficiency ratios are greater than 1 for all areas except for Emmon and higher than 2 in some areas. The sensitivity analyses found that the sufficiency ratio was most sensitive to diffusion of newly licensed pharmacists and the number of prescriptions per pharmacist. CONCLUSION: Optimal distribution should be considered, as the results reveal a possible shortage in the number of pharmacists in rural medical areas in 2015-2025. Conversely, as the demand is projected to decrease after 2025 with a population decrease, future supply should be determined in order not to cause an oversupply after 2025. Refinements of the projection model should be conducted since the related factors such as the roles of pharmacists will change over time.

Cost-Effectiveness of a Continuous Glucose Monitoring Mobile App for Patients With Type 2 Diabetes Mellitus: Analysis Simulation.

BACKGROUND: Apps for real-time continuous glucose monitoring (CGM) on smartphones and other devices linked to CGM systems have recently been developed, and such CGM apps are also coming into use in Japan. In comparison with conventional retrospective CGM, the use of CGM apps improves patients' own blood glucose control, which is expected to help slow the progression of type 2 diabetes mellitus (DM) and prevent complications, but the effect of their introduction on medical costs remains unknown. OBJECTIVE: Our objective in this study was to perform an economic appraisal of CGM apps from the viewpoint of assessing public medical costs associated with type 2 DM, using the probability of developing type 2 DM-associated complications, and data on medical costs and utility value to carry out a medical cost simulation using a Markov model in order to ascertain the cost-effectiveness of the apps. METHODS: We developed a Markov model with the transition states of insulin therapy, nephrosis, dialysis, and cardiovascular disease, all of which have a major effect on medical costs, to identify changes in medical costs and utility values resulting from the introduction of a CGM app and calculated the incremental cost-effectiveness ratio (ICER). RESULTS: The ICER for CGM app use was US $33,039/quality-adjusted life year (QALY). CONCLUSIONS: Sensitivity analyses showed that, with the exception of conditions where the transition probability of insulin therapy, utility value, or increased medical costs increases, the ICER for the introduction of CGM apps was below the threshold of US $43,478/QALY used by the Central Social Insurance Medical Council. Our results provide basic data on the cost-effectiveness of introducing CGM apps, which are currently starting to come into use.

Cost comparison between open radical cystectomy, laparoscopic radical cystectomy, and robot-assisted radical cystectomy for patients with bladder cancer: a systematic review of segmental costs.

BACKGROUND: Robot-assisted radical cystectomy is becoming a common treatment for bladder carcinoma. However, in comparison with open radical cystectomy, its cost-effectiveness has not been confirmed. Although few published reviews have compared total costs between the two surgical procedures, no study has compared segmental costs and explained their impact on total costs. METHODS: A systematic review was conducted based on studies on the segmental costs of open, laparoscopic, and robot-assisted radical cystectomy using PubMed, Web of Science, and Cochrane Library databases to provide insight into cost-effective management methods for radical cystectomy. The segmental costs included operating, robot-related, complication, and length of stay costs. A sensitivity analysis was conducted to determine the impact of the annual number of cases on the per-case robot-related costs. RESULTS: We identified two studies that compared open and laparoscopic surgeries and nine that compared open and robotic surgeries. Open radical cystectomy costs were higher than those of robotic surgeries in two retrospective single-institution studies, while robot-assisted radical cystectomy costs were higher in 1 retrospective single-institution study, 1 randomized controlled trial, and 4 large database studies. Operating costs were higher for robotic surgery, and accounted for 63.1-70.5% of the total robotic surgery cost. Sensitivity analysis revealed that robot-related costs were not a large proportion of total surgery costs in institutions with a large number of cases but accounted for a large proportion of total costs in centers with a small number of cases. CONCLUSIONS: The results show that robot-assisted radical cystectomy is more expensive than open radical cystectomy. The most effective methods to decrease costs associated with robotic surgery include a decrease in operating time and an increase in the number of cases. Further research is required on the cost-effectiveness of surgeries, including quality measures such as quality of life and quality-adjusted life years.

Forecasting maldistribution of human resources for healthcare and patients in Japan: a utilization-based approach.

BACKGROUND: Hokkaido's demographic trend of population decrease with aging population is remarkable even in Japan. Although healthcare policy decision-makers need to appropriately allocate resources while grasping regional demands, not much is available on whether medical demand would increase or not for future. In addition, little is known about what impact will current situation have on future demand-supply balance and equality by regions. This study aims to support decision-making in human resource planning for coping with changing population structure by forecasting future demand, and evaluation those regional maldistributions. METHOD: We set patients with acute myocardial infarction or cerebral stroke, and all medical care as study subjects and analyzed for 2015, 2025, and 2035 in Hokkaido and each Secondary Medical Care Area. We used a utilization-based approach to estimate the healthcare supply-demand balance in the future. Moreover, we evaluated the regional maldistribution of demand-supply balance by calculating Herfindahl-Hirschman Index, Gini Coefficients, the number of physicians/specialists per patient. Moreover, we conducted sensitivity analysis to evaluation impact on aspects of demand-supply balance by uncertainty of utilization for future. RESULTS: Our results displayed that concentration of patients will progress, while regional distribution will shrink in all subject. However, from comparison based on all medical care, Gini Coefficients of acute myocardial infarction and cerebral stroke has always been high. This suggest that the resource allocation of them has room for improvement. In addition, our analysis showed the change in this balance will differ in each region in the future. Moreover, demographic change will not consistent with the number of patient change from 2015 to 2035. CONCLUSION: These results suggest policy planners should use the number of patient by disease, by region as indicator of demand, instead of provider-to-population ratios being in use today. The result of our sensitivity analysis show two findings. First, the range of each indicator have possible for future. Second, increase of utilization, for instance lowing barrier in the use by development operation of patient transportation in AMI/CS, would improve maldistribution of opportunity for resident to get emergency medical services.

A Cost-Effectiveness Simulation of Specialist Dispatching System in Japan for Treatments of Patients with Acute Ischemic Stroke Using a Geographic Information System.

Regional disparities in the implementation rates of recombinant tissue-type plasminogen activator and endovascular thrombectomy treatments have been reported in Japan. We simulated the cost-effectiveness of specialist dispatching system in Hokkaido, Japan using Geographic Information System. In the system a qualified specialist is dispatched to another hospital for endovascular thrombectomy. Since the system improved patient accessibility, and the cost- effectiveness was excellent, the system could help enhance the equality and cost-effectiveness of ischemic stroke treatments in Hokkaido.

Cost Effectiveness of Drive and Retrieve System in Hokkaido for Acute Ischemic Stroke Patient Treatment Using Geographic Information System.

BACKGROUND AND PURPOSE: Although endovascular thrombectomy combined with recombinant tissue-type plasminogen activator is effective for treatment of acute ischemic stroke, regional disparities in implementation rates of those treatments have been reported. Drive and retrieve system, where a qualified neurointerventionist travels to another primary stroke center for endovascular thrombectomy, has been practiced in parts of Hokkaido, Japan. This study aims to simulate the cost effectiveness of the drive and retrieve system, which can be a method to enhance equality and cost effectiveness of treatments for acute ischemic stroke. MATERIALS AND METHODS: The number of patients who had acute ischemic stroke in 2015 is estimated. Those patients are generated according to the population distribution, and thereafter patient transport time is analyzed in the 3 scenarios (1) 60-minute drive scenario, (2) 90-minute drive scenario, in which the drive and retrieve system operates within 60-minute or 90-minute driving distance (3) without the system, using geographic information system. Incremental cost-effectiveness rate, quality-adjusted life years, and medical and nursing care costs are estimated from the analyzed transport time. FINDINGS: The incremental cost-effectiveness rate by implementing the system was dominant. Cost reductions of $213,190 in 60-minute drive scenario, and $247,274 in the 90-minute scenario were expected, respectively. Such benefits are the most significant in Soya, Emmon, Rumoi, and Kamikawahokubu medical areas. CONCLUSIONS: The drive and retrieve system could enhance regional equality and cost effectiveness of ischemic stroke treatments in Hokkaido, which can be achieved using existing resources. Further studies are required to clarify its cost effectiveness from hospital perspective.

Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway.

Activation of tumor suppressors for the treatment of human cancer has been a long sought, yet elusive, strategy. PTEN is a critical tumor suppressive phosphatase that is active in its dimer configuration at the plasma membrane. Polyubiquitination by the ubiquitin E3 ligase WWP1 (WW domain-containing ubiquitin E3 ligase 1) suppressed the dimerization, membrane recruitment, and function of PTEN. Either genetic ablation or pharmacological inhibition of WWP1 triggered PTEN reactivation and unleashed tumor suppressive activity. WWP1 appears to be a direct MYC (MYC proto-oncogene) target gene and was critical for MYC-driven tumorigenesis. We identified indole-3-carbinol, a compound found in cruciferous vegetables, as a natural and potent WWP1 inhibitor. Thus, our findings unravel a potential therapeutic strategy for cancer prevention and treatment through PTEN reactivation.

Effect of the Combination of Whole-Body Neuromuscular Electrical Stimulation and Voluntary Exercise on Metabolic Responses in Human.

PURPOSE: Since neuromuscular electrical stimulation (NMES) can recruit high-threshold motor units and enhance glucose metabolism, the combination of NMES and voluntary low-intensity exercise would induce both anerobic and aerobic energy consumptions and this type of exercise could be more efficient and effective than conventional exercise regimens. We aimed to investigate metabolic responses and muscle fatigue during whole body NMES (WB-NMES), voluntary exercise, and their combination. METHODS: The blood lactate concentration and maximal voluntary contraction were measured before and after specified exercises: WB-NMES (E), voluntary exercise (V), and their combination (VE), and expired gas was sampled during the exercises in thirteen healthy young men. Each exercise was conducted for 15 min and interval between exercise was > 48h. RESULTS: Energy expenditure and V ˙ O 2 relative to the body mass during VE were significantly higher than during V and E (p < 0.05). The Respiratory gas exchange ratio (RER) during both E and VE was higher than during V (p < 0.05), and the blood lactate concentration after VE was significantly higher than after V and E (p < 0.05). Although V ˙ O 2 relative to the body mass was 18.6 ± 3.1 ml/min/kg and the metabolic equivalent was 5.31 ± 0.89 Mets, the blood lactate concentration reached 7.5 ± 2.7 mmol/L after VE. CONCLUSION: These results suggest that the combination of WB-NMES and voluntary exercise can enhance the metabolic response to a level equivalent to high intensity exercise under the net physiological burden of low-middle intensity exercises.