Innovative device for surgical wound irrigation: a preclinical testing and pilot clinical validation study.

INTRODUCTION: Surgical site infection (SSI) poses a substantial postoperative challenge, affecting patient recovery and healthcare costs. While surgical wound irrigation is pivotal in SSI reduction, consensus on the optimal method remains elusive. We developed a novel device for surgical wound irrigation and conducted preclinical and clinical evaluations to evaluate its efficacy and safety. METHODS: Two preclinical experiments using swine were performed. In the washability test, two contaminated wound model were established, and the cleansing rate between the device and the conventional method were compared. In the contamination test, the irrigation procedure with a fluorescent solution assessed the surrounding contamination of drapes. Subsequently, a clinical trial involving patients undergoing abdominal surgery was conducted. RESULTS: The washability test demonstrated significantly higher cleansing rates with the device method (86.4% and 82.5%) compared to the conventional method (65.2% and 65.1%) in two contamination models. The contamination test revealed a smaller contaminated region with the device method than the conventional method. In the clinical trial involving 17 abdominal surgery cases, no superficial SSIs or adverse events related to device use were observed. CONCLUSIONS: Our newly developed device exhibits potential for achieving more effective and safe SSI control compared to conventional wound irrigation.

Usefulness of Self-Selected Scenarios for Simple Triage and Rapid Treatment Method Using Virtual Reality.

BACKGROUND: Repeated triage training is necessary to maintain and improve the accuracy of simple triage and rapid treatment (START), a popular triage method. Virtual reality (VR) may be more effective than conventional training methods. This study aimed to verify the educational usefulness of START using VR originally developed for students. METHODS: A VR was initially developed with a function that allowed students to select the triage procedure and its evaluation. Triage was performed using a simple modified START method, and eight scenarios were developed. The participants included 70 paramedic students classified into VR and live lecture groups. They took a 20-question written test that evaluated their academic ability before the course. After the course, a practical test and a 20-question written test were conducted. The total score of the practical test was 43 points. Triage procedure (1 point), observation and evaluation (1-5 points), and triage categories (1 point) were evaluated in this test. RESULTS: The VR and live lecture groups consisted of 33 and 29 participants, respectively. No significant differences were observed pre- and post-test. In the practical test, the median (interquartile range) score was 29 (26-32) and 25 (23-29) for the VR and live lecture groups, respectively, with the VR group scoring significantly higher (P=0.03). CONCLUSION: Our results confirmed the educational usefulness of selective VR for active learning of START. Therefore, VR combined with live lectures and simulations would be an optimal educational technique.

Atrial fibrillation and mortality after ischemic stroke: An observational study using an insurance claim database.

OBJECTIVES: In this study, we aimed to examine the association between atrial fibrillation and mortality after ischemic stroke and evaluate the use of anticoagulation therapy for atrial fibrillation before stroke onset in patients who experienced stroke. METHODS: In this retrospective observational study, we used a combined database of medical and long-term care insurance claims data from one prefecture in Japan. The data of 25,352 patients aged ≥ 65 years who were hospitalized in acute care hospitals with a diagnosis of ischemic stroke between April 2012 and March 2015 were extracted. Cox proportional hazard modeling, with adjustment for age, sex, comorbidities, and long-term care dependency level (based on the activities of daily living), was performed to evaluate the relationship between mortality and atrial fibrillation. RESULTS: The prevalence of atrial fibrillation was 21.8% in the study population. A significant association was noted between mortality and atrial fibrillation (adjusted hazard ratio: 1.28, 95% confidence interval: 1.16-1.41, p < 0.001). Anticoagulant drugs were used in 32.2% of the patients with atrial fibrillation. CONCLUSIONS: These results indicate that atrial fibrillation is associated with mortality after stroke; however, the use of anticoagulation therapy for atrial fibrillation is unsatisfactory. Efforts to improve the use of atrial fibrillation therapy are required in Japan.

Clinical characteristics in patients with non-alcoholic steatohepatitis in Japan: a case-control study using a 5-year large-scale claims database.

OBJECTIVES: To examine the clinical characteristics of patients with non-alcoholic steatohepatitis (NASH) and associated comorbidities. DESIGN: A case-control study using the national health insurance and the long-term elderly health insurance claims database. SETTING: Eligible patients diagnosed with NASH (ICD-10 K-75.8, other inflammatory liver disease or K-76.0, other fatty liver) between April 2015 and March 2020 were included. PARTICIPANTS: Patients who met the diagnostic definitions for NASH (n=545) were matched with non-NASH controls (n=185 264) and randomly selected according to sex, birth year and residential area. INTERVENTIONS: No interventions were made. PRIMARY AND SECONDARY OUTCOME MEASURES: ORs were estimated for the relationship between patient background, such as age and sex, body mass index (BMI), NASH-related comorbidities and lifestyle-related diseases. RESULTS: In total, 545 patients with NASH (38.3% men) and 185 264 non-NASH controls (43.2% men) were identified, with median ages of 68 (IQR 63.0-75.0) and 65 (IQR 44.0-74.0) years, respectively. BMI was significantly higher in patients with NASH than in controls (25.8 kg/m2 vs 22.9 kg/m2, p<0.001). The proportions of women, patients with hypertension, patients with dyslipidaemia and patients with type 2 diabetes were higher in the NASH group. In addition, NASH was associated with an increased risk of hepatic cirrhosis (OR 28.81 (95% CI 21.79 to 38.08)), followed by liver cancer (OR 18.38 (95% CI 12.56 to 26.89)). There was no significant association between NASH and risk for depression (OR 1.11 (95% CI 0.87 to 1.41)), insomnia (OR 1.12 (95% CI 0.94 to 1.34)) or chronic kidney diseases (OR 0.81 (95% CI 0.58 to 1.12)). CONCLUSIONS: In the daily medical care of patients, it is necessary to consider sex and age differences and to pay close attention to the risk of liver cancer, as well as other lifestyle-related comorbidities associated with NASH.

Seeking Treatment Profile of Male Shift Workers With Hypertension and Diabetes.

OBJECTIVE: This study was identified seeking treatment for hypertension and diabetes among male shift workers. METHOD: This retrospective cohort study included nine large companies in Japan. Data were collected from health checkup, health insurance records, and self-administered questionnaires in 2017 and 2020. Data were analyzed using Kaplan-Meier curves and Cox regression. RESULT: Person-days shift workers and day workers seeking treatment for hypertension were 41,604 and 327,301, respectively and, for diabetes, were 7326 and 60,735, respectively. The log ranks were statistically significant. Shift workers were 46% and 56% less likely to seek treatment for hypertension and diabetes, respectively, than day workers were after adjustment for age, marital status, education level, and intention to modify lifestyle (model 2) ( P < 0.01). CONCLUSIONS: Male shift workers are less likely to seek treatment for hypertension and diabetes compared with day workers.

Stochastic Optimal Linear Control for Generalized Cost Functions With Time-Invariant Stochastic Parameters.

This study presents the design of feedback controllers for generalized cost functions to deal with stochastic optimal control problems. Target linear systems contain time-invariant stochastic parameters that describe system uncertainty. The cost functions involve nonlinear mappings and polynomial forms of the system states and inputs to express various performance metrics. Unfortunately, these properties cause difficulties in solving the problems. Conventional methods, such as the principle of optimality, are not employed to solve such problems owing to the time-invariant parameters. As opposed to the well-known quadratic functions, handling the generalized cost functions is a complicated task. This study overcomes these challenges by deriving an explicit relation between the cost function and the linear feedback gain of a controller. The derived relation enables the feedback gain to be optimized via a gradient method. A theoretical analysis ensures the convergence of the proposed gradient method. A suboptimal feedback controller is obtained to solve the problem, even for the generalized cost. Furthermore, the controller guarantees robust stability of the feedback system even with the stochastic parameters. It is demonstrated that the proposed cost function can express an expectation of a quadratic cost, risk-sensitive cost, polynomial cost, and input-to-state gain. A numerical simulation shows the effectiveness of the proposed method.

Development of a Machine Learning Model to Predict Cardiac Arrest during Transport of Trauma Patients.

BACKGROUND: Trauma is a serious medical and economic burden worldwide, and patients with traumatic injuries have a poor survival rate after cardiac arrest. The authors developed a prediction model specific to prehospital trauma care and used machine learning techniques to increase its accuracy. METHODS: This retrospective observational study analyzed data from patients with blunt trauma injuries due to traffic accidents and falls from January 1, 2018, to December 31, 2019. The data were collected from the National Emergency Medical Services Information System, which stores emergency medical service activity records nationwide in the United States. A random forest algorithm was used to develop a machine learning model. RESULTS: The prediction model had an area under the curve of 0.95 and a negative predictive value of 0.99. The feature importance of the predictive model was highest for the AVPU (Alert, Verbal, Pain, Unresponsive) scale, followed by oxygen saturation (SpO2). Among patients who were progressing to cardiac arrest, the cutoff value was 89% for SpO2 in nonalert patients. CONCLUSIONS: The machine learning model was highly accurate in identifying patients who did not develop cardiac arrest.

A Study on Points of Respiratory Assist Devices Using in Pre-Hospital Care Respiratory Assist Devices in Pre-Hospital Care.

BACKGROUND: In Japan, increasing the number of ambulance requests, the case with the use of respiratory assistance devices in prehospital care by paramedics is also increasing1. When patient experiences respiratory failure, the first responders frequently select a respiratory assist device (RAD) such as Bag Valve Mask (BVM), Jackson Rees (JR), or BVM with Gas Supply Valve® (BVM+GSV). This is based on both evaluation and experience as there is no study indicating which RAD is the best choice at the pre-hospital emergency site. This study clarified the precautions when using BVM, JR, and BVM+GSV in pre-hospital emergency medical care with healthy volunteers. METHODS: Twenty healthy adults were fitted with a RAD while breathing spontaneously, and changes in vital signs and ETCO2 were observed. RESULTS: The level of ETCO2 became elevated after each RAD was attached. The value was significantly higher in the JR group than in the others. CONCLUSIONS: The study showed that even in the presence of spontaneous breathing, ETCO2 increased markedly with the application of respiratory assist devices that are used in pre-hospital care for conditions such as hypoxemia and ventilatory disturbance. The increase in ETCO2 was particularly significant in the JR group, suggesting the need for caution when selecting JRs for pre-hospital care. As the number of subjects was only 20 for each RAD, studies with a larger sample size are needed.

Estimation of the Number of Patients With Mitochondrial Diseases: A Descriptive Study Using a Nationwide Database in Japan.

BACKGROUND: To provide a better healthcare system for patients with mitochondrial diseases, it is important to understand the basic epidemiology of these conditions, including the number of patients affected. However, little information about them has appeared in Japan to date. METHODS: To gather data of patients with mitochondrial diseases, we estimated the number of patients with mitochondrial diseases from April 2018 through March 2019 using a national Japanese health care claims database, the National Database (NDB). Further, we calculated the prevalence of patients, and sex ratio, age class, and geographical distribution. RESULTS: From April 2018 through March 2019, the number of patients with mitochondrial diseases was 3,629, and the prevalence was 2.9 (95% confidence interval [CI], 2.8-3.0) per 100,000 general population. The ratio of females and males was 53 to 47, and the most frequent age class was 40-49 years old. Tokyo had the greatest number of patients with mitochondrial diseases, at 477, whereas Yamanashi had the fewest, at 13. Kagoshima had the highest prevalence of patients with mitochondrial diseases, 8.4 (95% CI, 7.1-10.0) per 100,000 population, whereas Yamanashi had the lowest, 1.6 (95% CI, 0.8-2.7). CONCLUSION: The number of patients with mitochondrial diseases estimated by this study, 3,269, was more than double that indicated by the Japanese government. This result may imply that about half of all patients are overlooked for reasons such as low severity of illness, suggesting that the Japanese healthcare system needs to provide additional support for these patients.

Analysis of the risk factors of mortality in elderly patients with hip fracture using a combined database of medical and long-term care insurance claims data.

BACKGROUND: The present study evaluated the risk of mortality in elderly hip fracture, focusing on comorbidities and nursing care levels. METHODS: The present study was an observational cohort study that used a combined database of medical and long-term care insurance (LTCI) claims data from one prefecture in Japan between 2011 and 2016. In total, 6125 patients aged 65 years and older were selected from acute care hospitals with a diagnosis of "hip fracture" between March 2011 and March 2012. The impact of long-term care insurance claim evaluation levels and comorbidities at recruitment time was investigated using this dataset. These patients were followed up monthly until March 2016. Based on this person-month dataset, survival analysis was performed with death as the endpoint. Cases in which receipt data were missing during the middle of the observation period and cases in which the patient survived at the end of the observation period were censored. RESULTS: The number of deaths during the observation period was 635 (10.4%). The impact of comorbidities and nursing care level on mortality were both significant as follows: high nursing care level before the fracture (hazard ratio: 1.09, P < 0.001), comorbidities of malignant diseases (HR: 1.45, P < 0.001), heart disease (hazard ratio: 1.20, P = 0.037), pneumonia (hazard ratio: 1.27, P < 0.001), chronic obstructive pulmonary disease (hazard ratio: 1.28, P = 0.026), renal failure (hazard ratio: 1.44, P < 0.001), and dementia (hazard ratio: 1.27, P = 0.013). CONCLUSION: The results of this study showed that a high level of nursing care and presence of comorbidities such as malignant diseases, heart diseases, pneumonia, chronic obstructive pulmonary disease, renal failure, and dementia increased mortality in elderly patients with hip fracture. Furthermore, this study showed the usefulness of a combined database of medical and LTCI claims data for clinical and health service-related research in the field of orthopedics.

High-frequency HbA1c testing among older patients with diabetes in Japan: a longitudinal analysis using medical claims data.

Aims: We aimed to determine the rate of high-frequency HbA1c testing among older Japanese patients (≥ 75 years) with type 2 diabetes who did not have diabetic complications and were not using insulin, and to explore its influencing factors and association with the number of hospital admissions. Methods: A retrospective, longitudinal observation study design based on medical claims data between 2015 and 2020 was adopted. We tracked patients for 3 years to describe the annual rate and determine factors associated with high-frequency HbA1c testing using a hierarchical logistical model. We employed a zero-inflated Poisson model to examine the association between frequency of HbA1c testing and the number of hospitalizations. Results: Among 6594 patients included (mean age 80.4 years), the rates of high-frequency HbA1c testing in the first, second, and third year were 10.2%, 4.8%, and 4.7%, respectively. Follow-up year [odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.49-0.59];insulin use (OR = 1.63, 95% CI = 1.26-2.11); multi facility for HbA1c testing (OR = 5.51, 95% CI = 4.66-6.51); more than 48 outpatient days per year (OR = 2.13, 95% CI = 1.81-2.51); hospitalizations (OR = 0.66, 95% CI = 0.55-0.79); two or more classes of antidiabetic agents at baseline (OR = 1.32, 95% CI = 1.11-1.56); and dementia at baseline (OR = 0.70, 95% CI = 0.51-0.97) were significantly associated with high-frequency HbA1c testing. No significant association between frequent HbA1c testing and the number of all-cause hospitalizations was found. Conclusions: We revealed a high rate of HbA1c testing among older Japanese patients with type 2 diabetes in ambulatory care and indicated that high-frequency HbA1c testing was more likely to result from the decentralized healthcare system and its structure.

Clinical application of a highly sensitive digital PCR assay to detect a small fraction of IDH1 R132H-mutant alleles in diffuse gliomas.

The current World Health Organization classification of diffuse astrocytic and oligodendroglial tumors requires the examination of isocitrate dehydrogenase 1 (IDH1) or IDH2 mutations. Conventional analysis tools, including Sanger DNA sequencing or pyrosequencing, fail in detecting these variants of low frequency owing to their limited sensitivity. Digital polymerase chain reaction (dPCR) is a recently developed, highly sensitive, and precise quantitative rare variant assay. This study aimed to establish a robust limit of quantitation of the dPCR assay to detect a small fraction of IDH1 R132H mutation. The dPCR assays with serially diluted IDH1 R132H constructs detected 0.05% or more of mutant IDH1 R132H in samples containing mutant DNA. The measured target/total value of the experiments was proportional to the dilution factors and was almost equal to the actual frequencies of the mutant alleles. Based on the average target/total values, together with a twofold standard deviation of the normal DNA, a limit of quantitation of 0.25% was set to secure a safe margin to judge the mutation status of the IDH1 R132H dPCR assay. In clinical settings, detecting IDH1 R132H using dPCR assays can validate ambiguous immunohistochemistry results even when conventional DNA sequencing cannot detect the mutation and assure diagnostic quality.

The differences of the economic losses due to presenteeism and treatment costs between high-stress workers and non-high-stress workers using the stress check survey in Japan.

OBJECTIVES: This study sought to examine differences in the economic losses due to presenteeism and costs of medical and dental treatment between high-stress workers and non-high-stress workers using the stress check survey. METHODS: We conducted a cross-sectional study from April 1, 2018 to March 31, 2019 in a pharmaceutical company. High-stress workers were classified with the Brief Job Stress Questionnaire using two methods: the sum method and the score converted method. The incidence of presenteeism and its costs were determined using a questionnaire. The costs of medical and dental treatment were calculated according to claims. We compared the costs between high-stress and non-high-stress workers using Wilcoxon's rank-sum test. RESULTS: Of 3910 workers, 6.3% were classified as high-stress using the sum method and 6.6% were classified as high-stress using the score converted method. The costs associated with presenteeism and medical treatment among high-stress workers were higher than the costs among non-high-stress workers, whereas the costs associated with dental treatment were not. CONCLUSIONS: To motivate employers to improve stressful work environments, it is recommended that presenteeism measurement items be added to the stress check survey, and that the methods used in this study be used to calculate the loss associated with high-stress workers in Japanese companies. However, we must be careful in interpreting absolute presenteeism loss amounts because they are poorly reliable and valid.

Evaluation of cholecystectomy in older individuals using real-world data: a multilevel analysis based on a nationwide administrative database in Japan.

BACKGROUND: In the present study, we aimed to evaluate the clinical outcomes of cholecystectomy in older individuals. METHODS: In this retrospective study, data from the Japanese Diagnosis Procedure Combination database on 96,620 patients who had undergone cholecystectomy at 1060 hospitals from 2018 to 2020 were analyzed. Patients were divided into five age groups: < 75, 75-79, 80-84, 85-89, and ≥ 90 years. Associations between postoperative outcomes and age group were investigated by logistic regression analysis. Mean differences between age groups in time to postoperative recovery and cost were also compared. RESULTS: Older patients had higher rates of poor scores for activities of daily living and preoperative comorbidity. Compared with the youngest age group (< 75 years), the odds ratios for in-hospital mortality were 3.00 (95% confidence interval, 1.74-5.19), 7.54 (4.73-12.01), 13.47 (8.21-22.14), and 27.64 (15.56-49.09), in the 75-79, 80-84, 85-89, and ≥ 90-year-old age group, respectively (all p < 0.001). Furthermore, the length of postoperative hospital stay and rates of postoperative complications, postoperative reintubation, and reoperation with general anesthesia increased significantly in parallel with increasing age, the highest rates being in the ≥ 90 year-old age group. CONCLUSIONS: Our real-world data highlight the worse postoperative outcomes, including a higher mortality rate, in older patients undergoing cholecystectomy. Care should be taken when considering the indications for surgery in such patients.

Epidemiological Study of Hospital Admissions for Food-Induced Anaphylaxis Using the Japanese Diagnosis Procedure Combination Database.

BACKGROUND: Food allergies are common among children, and food-induced anaphylaxis (FIA) is a serious disease with a risk of death; however, there is yet to be a large-scale epidemiological study on causative foods in Japan. The purpose of this study was to identify foods that cause FIA in Japan. METHODS: We identified 9,079 patients from the Japanese Diagnosis Procedure Combination Database who were admitted for treatment for FIA from April 1, 2014 through March 31, 2017. We extracted data on patient sex, age, use of epinephrine injections on the first day, prescription for epinephrine self-injection on the day of discharge, length of stay, readmission, and causative foods. RESULTS: The most common causative food was eggs, followed by wheat, milk, peanuts, and buckwheat. The most common causative food in each age group was eggs among 0-3-year-olds, milk among 4-6-year-olds, peanuts among 7-19-year-olds, and wheat among those aged 20 years and older. Epinephrine was used at admission among about 40%, 50%, and over 60% of cases in which the causative food was eggs; wheat, milk and peanuts; and buckwheat, respectively. The proportion of cases with a prescription for epinephrine self-injection at discharge was highest among those in which the causative food was wheat, followed by peanuts, buckwheat, milk, and eggs. CONCLUSIONS: FIA due to peanuts has become as common in Japan as it is in the West. These results suggest the importance of taking measures to prevent peanut allergies because children cannot make adequate decisions regarding food.

Eribulin prolongs survival in an orthotopic xenograft mouse model of malignant meningioma.

Meningioma is the most common intracranial tumor, with generally favorable patient prognosis. However, patients with malignant meningioma typically experience recurrence, undergo multiple surgical resections, and ultimately have a poor prognosis. Thus far, effective chemotherapy for malignant meningiomas has not been established. We recently reported the efficacy of eribulin (Halaven) for glioblastoma with a telomerase reverse transcriptase (TERT) promoter mutation. This study investigated the anti-tumor effect of eribulin against TERT promoter mutation-harboring human malignant meningioma cell lines in vitro and in vivo. Two meningioma cell lines, IOMM-Lee and HKBMM, were used in this study. The strong inhibition of cell proliferation by eribulin via cell cycle arrest was demonstrated through viability assay and flow cytometry. Apoptotic cell death in malignant meningioma cell lines was determined through vital dye assay and immunoblotting. Moreover, a wound healing assay revealed the suppression of tumor cell migration after eribulin exposure. Intraperitoneal administration of eribulin significantly prolonged the survival of orthotopic xenograft mouse models of both malignant meningioma cell lines implanted in the subdural space (P < .0001). Immunohistochemistry confirmed apoptosis in brain tumor tissue treated with eribulin. Overall, these results suggest that eribulin is a potential therapeutic agent for malignant meningiomas.

Evaluation of outcomes after EMS-witnessed traumatic out-of-hospital cardiac arrest caused by traffic collisions.

AIM: The survival rate of patients with traumatic cardiac arrest is 3% or lower. Cardiac arrest witnessed by emergency medical services (EMS) accounts for approximately 16% of prehospital traumatic cardiac arrests, but the prognosis is unknown. We aimed to compare the 1-month survival rate of cardiac arrest witnessed by EMS with that of cardiac arrest witnessed by bystanders and unwitnessed cardiac arrest in traffic trauma victims; further, the time from injury to cardiac arrest was assessed. METHODS: This analysis used the Utstein Registry in Japan and included data of 3883 patients with traumatic cardiac arrest caused by traffic collisions registered between 2014 and 2019 in Japan. RESULTS: The 1-month survival rate was 10.9% in the EMS-witnessed cardiac arrest group; this was significantly higher than that in the bystander-witnessed (7.2%) and unwitnessed (5.6%) cardiac arrest groups (P < 0.01). The median time from injury to cardiac arrest was 18 min (25% quartile: 12, 75% quartile: 26). CONCLUSION: The 1-month survival rate was significantly higher in the EMS-witnessed cardiac arrest group than in the bystander-witnessed and unwitnessed cardiac arrest groups. It is important to prevent progression to cardiac arrest in trauma patients with intact respiratory function and pulse rate at the time of contact with EMS. A system for early recognition of severe trauma is needed, and a doctor's car or helicopter can be requested as needed. We believe that early recognition and prompt intervention will improve the prognosis of prehospital traumatic cardiac arrest.

Diabetes severity measured by treatment control status and number of anti-diabetic drugs affects presenteeism among workers with type 2 diabetes.

BACKGROUND: The number of people with diabetes is increasing and resulting in major economic losses. Presenteeism accounts for the majority of economic losses, so measures against presenteeism are important. This study investigated the relationship between severity of type 2 diabetes and presenteeism. METHODS: A cross-sectional study was conducted among workers over 40 years of age. Participants were classified as normal group or diabetic treatment group using their medical examination results and health insurance claims data. Diabetic treatment groups were described by degree of treatment control: Good (HbA1c < 7%), Intermediate (7% ≤ HbA1c < 8%), and Poor (8% ≤ HbA1c). Therapy type was also divided into monotherapy and combination therapy. Logistic regression analysis was performed to predict presenteeism loss using the Quantity and Quality method. RESULTS: Data on 13,271 workers were analyzed. Presenteeism loss was significantly higher in all treatment control groups compared with the normal group, particularly for the intermediate and poor control groups. The monotherapy group did not differ from the normal group, but presenteeism loss was significantly higher in the combination therapy group than the normal group. CONCLUSIONS: Presenteeism loss in workers with diabetes may be affected by diabetes severity, and even if treatment control were good, presenteeism loss could occur when the number of anti-diabetic drugs was high. Therefore, it is important to provide early intervention and continuous support as a preventive measure against not only diabetes and diabetes-related complications but also presenteeism.

TERT promoter mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic glioma with molecular features of glioblastoma.

The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) update 3 recommends that histologic grade II and III IDH-wildtype diffuse astrocytic gliomas that harbor EGFR amplification, the combination of whole chromosome 7 gain and whole chromosome 10 loss (7 + /10 -), or TERT promoter (pTERT) mutations should be considered as glioblastomas (GBM), World Health Organization grade IV. In this retrospective study, we examined the utility of molecular classification based on pTERT status and copy-number alterations (CNAs) in IDH-wildtype lower grade gliomas (LGGs, grade II, and III). The impact on survival was evaluated for the pTERT mutation and CNAs, including EGFR gain/amplification, PTEN loss, CDKN2A homozygous deletion, and PDGFRA gain/amplification. We analyzed 46 patients with IDH-wildtype/pTERT-mutant (mut) LGGs and 85 with IDH-wildtype/pTERT-wildtype LGGs. EGFR amplification and a combination of EGFR gain and PTEN loss (EGFR + /PTEN -) were significantly more frequent in pTERT-mut patients (p < 0.0001). Cox regression analysis showed that the pTERT mutation was a significant predictor of poor prognosis (hazard ratio [HR] 2.79, 95% confidence interval [CI] 1.55-4.89, p = 0.0008), but neither EGFR amplification nor EGFR + /PTEN - was an independent prognostic factor in IDH-wildtype LGGs. PDGFRA gain/amplification was a significant poor prognostic factor in IDH-wildtype/pTERT-wildtype LGGs (HR 2.44, 95% CI 1.09-5.27, p = 0.03, Cox regression analysis). The IDH-wildtype LGGs with either pTERT-mut or PDGFRA amplification were mostly clustered with GBM by DNA methylation analysis. Thus, our study suggests that analysis of pTERT mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic gliomas with molecular features of glioblastoma. The PDGFRA status may help further delineate IDH-wildtype/pTERT-wildtype LGGs. Methylation profiling showed that IDH-wildtype LGGs without molecular features of GBM were a heterogeneous group of tumors. Some of them did not fall into existing categories and had significantly better prognoses than those clustered with GBM.

A cross-sectional study of socioeconomic status and treatment interruption among Japanese workers during the COVID-19 pandemic.

OBJECTIVES: The COVID-19 pandemic has caused interruptions to chronic disease and non-emergency treatment. The purpose of this study is to examine which socioeconomic status groups are most at risk of treatment interruption among Japanese workers. METHODS: This cross-sectional internet monitor study was conducted among Japanese workers on December 22-26, 2020. Out of a total of 33 302 participants in the survey, 9510 (5392 males and 4118 females) who responded that they required regular treatment or hospital visits were included in the analysis. A multilevel logistic model nested in the prefecture of residence was used to estimate the odds ratio (OR) for treatment disruption. We examined separate multivariate models for socioeconomic factors, health factors, and lifestyle factors. RESULTS: During a period of rapid COVID-19 infection, about 11% of Japanese workers who required regular treatment experienced interruptions to their treatment. The OR of treatment interruption associated with not being married compared with being married was 1.44 (95%CI: 1.17-1.76); manual labor work compared with desk work was 1.30 (95%CI: 1.11-1.52); loss of employment when the COVID-19 pandemic started and continued unemployment compared with being employed over the entire pandemic period was 1.62 (95%CI: 1.13-2.31) and 2.57 (95%CI: 1.63-4.07), respectively; and feeling financially unstable was 2.92 (95%CI: 2.25-3.80). CONCLUSION: Treatment interruption is a new health inequality brought about by COVID-19 with possible medium- and long-term effects, including excess mortality, morbidity, and productivity loss due to increased presenteeism. Efforts are needed to reduce treatment interruptions among workers who require regular treatment.