Safety of Boron Neutron Capture Therapy with Borofalan(10B) and Its Efficacy on Recurrent Head and Neck Cancer: Real-World Outcomes from Nationwide Post-Marketing Surveillance.

BACKGROUND: This study was conducted to evaluate the real-world safety and efficacy of boron neutron capture therapy (BNCT) with borofalan(10B) in Japanese patients with locally advanced or locally recurrent head and neck cancer (LA/LR-HNC). METHODS: This prospective, multicenter observational study was initiated in Japan in May 2020 and enrolled all patients who received borofalan(10B) as directed by regulatory authorities. Patient enrollment continued until at least 150 patients were enrolled, and adverse events attributable to drugs, treatment devices, and BNCT were evaluated. The patients with LA/LR-HNC were systematically evaluated to determine efficacy. RESULTS: The 162 patients enrolled included 144 patients with squamous cell carcinoma of the head and neck (SCCHN), 17 patients with non-SCCHN (NSCCHN), and one patient with glioblastoma. Treatment-related adverse events (TRAEs) were hyperamylasemia (84.0%), stomatitis (51.2%), sialoadenitis (50.6%), and alopecia (49.4%) as acute TRAEs, and dysphagia (4.5%), thirst (2.6%), and skin disorder (1.9%) as more common late TRAEs. In patients with LA/LR-HNC, the overall response rate (ORR) was 72.3%, with a complete response (CR) in 63 (46.0%) of 137 patients with SCCHN. Among 17 NSCCHN patients, the ORR was 64.7%, with eight cases (47.1%) of CR. One- and two-year OS rates in patients with recurrent SCCHN were 78.8% and 60.7%, respectively. CONCLUSIONS: This post-marketing surveillance confirmed the safety and efficacy of BNCT with borofalan(10B) in patients with LA/LR-HNC in a real-world setting.

Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies.

BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium. METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction. RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions. CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.

Prospective cohort study on potato intake and mortality from cardiovascular diseases: the Japan Collaborative Cohort Study (JACC study).

PURPOSE: The association between potato intake and risk of cardiovascular diseases is unknown. This study aimed to examine the association between potatoes intake and mortality from stroke and coronary heart disease among Japanese. METHODS: The study included 74,750 participants of the Japan Collaborative Cohort Study, aged 40-79, who were initially free of cardiovascular diseases or cancer at baseline (1988-1990) and provided information on their potato intake. Hazard ratios and 95% confidence intervals were estimated by fitting a Cox proportional hazards model according to the frequency of potatoes intake (0, 0.4, 1.5, 3.5 and 7 servings per week) adjusting for geographic location, age, body mass index, drinking status, smoking status, perceived mental stress, education level, walking time, dietary intakes of total energy, meat, fish, vegetables, fruit, dairy products, cakes, and salt. RESULTS: Over a median of 19.2 years of follow-up, 4908 deaths from cardiovascular diseases were identified: 1019 from coronary heart diseases and 2153 from strokes (738 ischemic strokes and 495 hemorrhagic strokes). After adjustment for potential confounding factors, the hazard ratio of mortality from cardiovascular diseases for daily potato intake compared with no potato intake was 0.82 (95% confidence interval: 0.70, 0.95) among women, and 1.01 (0.88, 1.16) among men. Among women, the multivariable hazard ratios were 0.67 (0.48, 0.96) for coronary heart disease, 0.83 (0.66-1.05) for total stroke, 0.70 (0.43-1.15) for hemorrhagic stroke, and 0.75 (0.49-1.13) for ischemic stroke. CONCLUSION: We found an inverse association of potato intake with mortality from total cardiovascular diseases, especially that from coronary heart disease, among Japanese women. To our knowledge, this is the first report to show an inverse association between potato intake and total cardiovascular diseases.

Clinical report of six-month follow-up after cementing PEEK crown on molars.

We conducted a six-month clinical follow-up on computer-aided design/computer-aided manufacturing-fabricated molar polyetheretherketone PEEK crowns to investigate their therapeutic effect. Only the PEEK crowns were examined as our study focused on short-term clinical evaluation of the new PEEK material. Twenty-three cases of PEEK crowns placed on the molars of 20 subjects (7 males and 13 females, mean age: 60.6 ± 14.2 years) were included in the study. The evaluation items were the condition of the crowns at the time of cementation and after six months, patient satisfaction, masticatory ability, and occlusal force. Mann-Whitney U tests with a significance level of 5% were used to examine the difference in glucose concentration by masticatory ability, occlusal pressure, and occlusal force, with and without PEEK crowns. The occlusion, margin fit, and contact of all 23 cases at the time of cementing were good. Six months after cementation, there was no crown desorption, fracture or crack, and prosthodontics was not needed in the 22 cases (one patient dropped out). No wear of the dental antagonist was observed. Patient satisfaction was generally high. There was no significant difference in masticatory ability between the groups with and without PEEK crowns. The subject's occlusal force was within the normal range. PEEK crowns used on molars can replace metal crowns and hold promise for an appropriate and effective treatment.

The global response: How cities and provinces around the globe tackled Covid-19 outbreaks in 2021.

Background: Tackling the spread of COVID-19 remains a crucial part of ending the pandemic. Its highly contagious nature and constant evolution coupled with a relative lack of immunity make the virus difficult to control. For this, various strategies have been proposed and adopted including limiting contact, social isolation, vaccination, contact tracing, etc. However, given the heterogeneity in the enforcement of these strategies and constant fluctuations in the strictness levels of these strategies, it becomes challenging to assess the true impact of these strategies in controlling the spread of COVID-19. Methods: In the present study, we evaluated various transmission control measures that were imposed in 10 global urban cities and provinces in 2021- Bangkok, Gauteng, Ho Chi Minh City, Jakarta, London, Manila City, New Delhi, New York City, Singapore, and Tokyo. Findings: Based on our analysis, we herein propose the population-level Swiss cheese model for the failures and pitfalls in various strategies that each of these cities and provinces had. Furthermore, whilst all the evaluated cities and provinces took a different personalized approach to managing the pandemic, what remained common was dynamic enforcement and monitoring of breaches of each barrier of protection. The measures taken to reinforce the barriers were adjusted continuously based on the evolving epidemiological situation. Interpretation: How an individual city or province handled the pandemic profoundly affected and determined how the entire country handled the pandemic since the chain of transmission needs to be broken at the very grassroot level to achieve nationwide control. Funding: The present study did not receive any external funding.

Peripheral Immune Activation in Mice Elicits Unfolded Protein Responses Independent on MyD88 Pathway in the Liver but not the Hypothalamus and Hippocampus.

Neuroimmune interactions between the immune system and CNS as well as peripheral organs such as the liver play a key role in the pathophysiological state of diseases. Unfolded protein responses (UPRs), which are activated by cells in response to endoplasmic reticulum stress, have been linked to the occurrence of inflammation diseases, neurodegenerative diseases, and metabolic disorders such as type 2 diabetes. Peripheral injection of lipopolysaccharide (LPS) is known to induce a systemic inflammatory response, along with fever, anorexia, and depressive behaviors. LPS also elicits UPRs, although the underlying physiological mechanism remains unclear. In the present study, we investigated whether peripheral activation of the immune system can elicit UPRs in the CNS and liver. Peripheral injection of LPS is known to elevate pro-inflammatory cytokines in the liver, hypothalamus and hippocampus. We report that LPS-induced systemic inflammation elicits UPRs in the liver, but not the hypothalamus. Injection of LPS upregulated the expression levels of glucose-regulated protein 78 and pro-apoptotic transcription factor C/EBP homologous protein, along with increased splicing of X-box binding protein one mRNA in the liver, but not in the hypothalamus and hippocampus. Myeloid differentiation primary response 88 (MyD88), an adaptor protein, is known to play a key role in the signal transduction of LPS mediated by Toll-like receptor 4. Using MyD88 deficient mice, we found that LPS-induced UPRs occurred independently of MyD88 expression. In summary, peripheral activation of the immune system elicits UPRs in the liver, but not the hypothalamus and hippocampus, which may have implications for the pathophysiology of diseases.

Efficacy and limitations of additional steroid pulse therapy in IgA nephropathy patients whose hematuria did not remit on tonsillectomy and protocol steroid pulse therapy.

BACKGROUND: Hematuria is the essential symptom of IgA nephropathy that has been suggested to be associated with long-term renal prognosis, Tonsillectomy and steroid pulse therapy (TSP), which is widely practiced in Japan, is effective for achieving hematuria remission. However, some cases are refractory to TSP, and additional steroid pulse therapy (SP) administered to these cases to achieve remission of hematuria. Nonetheless, the clinical significance of additional SP is unknown. METHODS: In this retrospective study, we enrolled 99 patients from Okubo Hospital whose hematuria persisted following TSP. Patients were divided into the hematuria remission and non-remission groups. A multivariate regression analysis was performed on the factors that contributed to hematuria remission. RESULTS: Following TSP, 103 of 403 patients (32.3%) did not achieve hematuria remission. Additional SP were performed in 99 of these patients, and remission of hematuria was achieved in 57 (57.6%). Patients with a greater degree of improvement in hematuria with TSP were significantly more likely to have remission of hematuria with additional SP (p = 0.0084*). Even in the hematuria non-remission group, both hematuria and proteinuria improved after additional SP. CONCLUSION: In IgA nephropathy, additional SP could induce hematuria remission and reduce proteinuria.

Purinergic P2X7 receptor antagonist ameliorates intestinal inflammation in postoperative ileus.

Postoperative ileus (POI) is a postsurgical gastrointestinal motility dysfunction caused by mechanical stress to the intestine during abdominal surgery. POI leads to nausea and vomiting reduced patient quality of life, as well as high medical costs and extended hospitalization. Intestinal inflammation caused by macrophages and neutrophils is thought to be important in the mechanism of POI. Surgery-associated tissue injury and inflammation induce the release of adenosine triphosphate (ATP) from injured cells. Released ATP binds the purinergic P2X7 receptor (P2X7R) expressed on inflammatory cells, inducing the secretion of inflammatory mediators. P2X7R antagonists are thought to be important mediators of the first step in the inflammation process, and studies in chemically induced colitis models confirmed that P2X7R antagonists exhibit anti-inflammatory effects. Therefore, we hypothesized that P2X7R plays an important role in POI. POI models were generated from C57BL/6J mice. Mice were treated with P2X7R antagonist A438079 (34 mg/kg) 30 min before and 2 hr after intestinal manipulation (IM). Inflammatory cell infiltration and gastrointestinal transit were measured. A438079 ameliorated macrophage and neutrophil infiltration in the POI model. Impaired intestinal transit improved following A438079 treatment. P2X7R was expressed on both infiltrating and resident macrophages in the inflamed ileal muscle layer. The P2X7R antagonist A438079 exhibits anti-inflammatory effects via P2X7R expressed on macrophages and therefore could be a target in the treatment of POI.

Nd:YVO4 laser groove treatment can improve the shear bond strength between dental PEEK and adhesive resin cement with an adhesive system.

The purpose of this study was to investigate the effect of various surface treatments on the shear bond strength between dental polyetheretherketone (PEEK) and adhesive resin cement. Two hundred and forty specimens were randomly classified into four groups: no treatment, sandblasted, sulfuric-acid-etched, and laser-grooved treatment. Each group was classified into two adhesive resin cement subgroups. Surface roughness, water contact angle, shear bond strength, and failure mode were measured; SEM and XPS results were obtained. The data were statistically analyzed using one-way or two-way analysis of variance and Tukey's honest significant difference test (α=0.05). Laser-grooved PEEK surface showed regular grooves and carbonization by thermal degradation; the surface roughness as well as water contact angle of were the highest in all groups. Shear bond strength values were significantly higher in the laser-groove-treated and sulfuric-acid-etched groups. Laser-groove-treated specimens showed cohesive failure. Laser-grooved treatment can improve shear bond strength between PEEK and adhesive resin cement.

Hemodialysis patients with coronavirus disease 2019: reduced antibody response.

BACKGROUND: Because patients on maintenance hemodialysis (HD) have an impaired immune response to pathogens, they are at higher risk of severe coronavirus disease 2019 (COVID-19). However, data on antibody production among HD patients with COVID-19 is scarce. Thus, we performed a retrospective cohort study evaluating severe acute respiratory syndrome coronavirus two antibody (SARS-CoV-2) production within 1 month after COVID-19 onset in hospitalized patients on HD. METHODS: SARS-CoV-2-specific immunoglobulin (Ig) G levels were quantified using an iFlash 3000 Chemiluminescence Immunoassay analyzer (Shenzhen YHLO Biotech Co., Ltd.) to detect IgG antibodies specific for the S1 subunit of the spike protein (IgG-S1). Propensity score matching was used to balance covariate distribution in HD and non-HD patients. From April 2020 to February 2021, antibody testing was performed on 161 hospitalized patients with symptomatic COVID-19. Of them, 34 HD patients were matched to 68 non-HD patients. RESULTS: After propensity score matching, the median levels of IgG-S1 in the HD patients at 7-13 days after symptom onset were significantly lower than in non-HD patients, especially in those with severe disease. Among all patients, those with severe disease produced lower levels of IgG-S1 at 7-13 days compared with non-severe patients. CONCLUSION: COVID-19 patients with severe disease, especially those undergoing HD, had lower IgG-S1 production in the second week of the disease. Thus, the increased risk of severe COVID-19 in HD patients may be, in part, due to a slow and reduced antibody response.

Outcomes of hypertrophic cardiomyopathy in Japanese children: a retrospective cohort study.

There has been no multicenter study on the prognosis of pediatric hypertrophic cardiomyopathy (HCM) in Japan. Therefore, we conducted a retrospective multicenter observational study on the long-term survival rate in patients diagnosed with HCM under the age of 18 between 1990 and 2014. Twenty institutions participated. A total of 180 patients were identified. The median age at diagnosis was 5.8 years old and median duration of observation was 8.3 years. Although six patients (3%) deteriorated into the dilated phase of HCM, no patient received heart transplantation. Freedom from death at 1, 5, 10, and 20 years were 97%, 92%, 84%, and 80%, respectively. There were 26 deaths. Among them, 11 patients died suddenly, presumably due to arrhythmia, and 15 patients died of heart failure. The presence of heart failure symptoms and a greater cardiothoracic ratio were significant risk factors for heart failure-related death. There were no significant risk factors identified for arrhythmia-related death. In conclusion, the prognosis of pediatric HCM in Japan is good and similar to those reported in population-based studies in the United States and Australia. Significant risk factors for heart failure-related death were identified in pediatric patients with HCM in Japan.

Systematic analysis of authorship demographics in global surgery.

BACKGROUND: Global surgery has recently gained prominence as an academic discipline within global health. Authorship inequity has been a consistent feature of global health publications, with over-representation of authors from high-income countries (HICs), and disenfranchisement of researchers from low-income and middle-income countries (LMICs). In this study, we investigated authorship demographics within recently published global surgery literature. METHODS: We performed a systematic analysis of author characteristics, including gender, seniority and institutional affiliation, for global surgery studies published between 2016 and 2020 and indexed in the PubMed database. We compared the distribution of author gender and seniority across studies related to different topics; between authors affiliated with HICs and LMICs; and across studies with different authorship networks. RESULTS: 1240 articles were included for analysis. Most authors were male (60%), affiliated only with HICs (51%) and of high seniority (55% were fully qualified specialist or generalist clinicians, Principal Investigators, or in senior leadership or management roles). The proportion of male authors increased with increasing seniority for last and middle authors. Studies related to Obstetrics and Gynaecology had similar numbers of male and female authors, whereas there were more male authors in studies related to surgery (69% male) and Anaesthesia and Critical care (65% male). Compared with HIC authors, LMIC authors had a lower proportion of female authors at every seniority grade. This gender gap among LMIC middle authors was reduced in studies where all authors were affiliated only with LMICs. CONCLUSION: Authorship disparities are evident within global surgery academia. Remedial actions to address the lack of authorship opportunities for LMIC authors and female authors are required.

Outcomes of Dilated Cardiomyopathy in Japanese Children　- A Retrospective Cohort Study.

BACKGROUND: There has been no nationwide survey on the prognosis of pediatric dilated cardiomyopathy (DCM) in Japan. Therefore, we designed this retrospective multicenter study to investigate the long-term survival rate in pediatric patients with DCM in Japan.Methods and Results:In this multicenter retrospective observational study, data were reviewed for 106 patients aged <18 years who had been diagnosed with DCM at any 1 of 18 Japanese institutions between 1990 and 2014. The median age at diagnosis was 2.0 years and the median duration of observation was 3.3 years. Most DCM patients were diagnosed because of symptoms of heart failure. On echocardiography, the median left ventricular end-diastolic dimension z score was 5.4 and fractional shortening was 0.10. Freedom from death or transplantation rates at 1, 3, 5, 10, and 20 years after diagnosis were 76%, 66%, 64%, 58%, and 43%, respectively. Freedom from death rates at 1, 5, 10, and 20 years after diagnosis were 81%, 75%, 72%, and 53%, respectively. The incidence of heart transplantation at 1, 5, 10, and 20 years after diagnosis was 6%, 15%, 20%, and 20%, respectively, suggesting that only 15% of patients in Japan underwent heart transplantation within 5 years of diagnosis. CONCLUSIONS: In Japan, the prognosis of pediatric DCM is poor and the rate of heart transplantation is low.

Quasi-cluster randomized trial of a six-month low-intensity group-based resistance exercise for hemodialysis patients on depression and cognitive function: a 12-month follow-up.

OBJECTIVE: This study aimed to examine the effects of a six-month group-based low-intensity resistance exercise program on depression and the cognitive function of hemodialysis patients. METHOD: We conducted a quasi-cluster randomized, open-label controlled study from October 2017 to December 2018. Forty-two patients undergoing hemodialysis completed the trial over six months; half participated in the resistance exercise group (n = 21, mean = 74.90 years of age, SD = 2.23, 66.67% female) and the other half were in a stretching control group (n = 21, mean = 72.57 years of age, SD = 2.26, 28.57% female). Depressive symptoms and cognitive function were the primary outcome measures. Behavioral and psychological problems associated with cognitive decline (NPI-Q), subjective insomnia, and exercise self-efficacy were secondary outcomes. Outcomes were measured at baseline, three-month (mid-intervention), six-month (end of intervention), and 12-month (six months after intervention) follow-ups. Linear mixed model analyses were used to determine short-term (immediately after intervention) and long-term (six months after intervention) effects. RESULTS: In depression, cognitive function, and the NPI-Q, there were no significant effects. In subjective insomnia, a short-term group-by-time interaction in the intervention group compared to the control group was found (ES = .43). However, the effect had disappeared by the 12-month follow-up. In exercise self-efficacy, short- and long-term group-by-time interactions were found. A significant short-term increase in the resistance exercise and a significant decrease in the stretching control was observed (ES = -.83). However, the effect was weakened in the long term (ES = -.38). CONCLUSION: The results showed that low-intensity group resistance exercise would reduce subjective insomnia and improve exercise self-efficacy, but the effect was not maintained by six months after the program.Trial registration: This study was registered on the University Hospital Medical Information Network Clinical Trials Registry (UMIN000029372). Trial registration: UMIN Japan identifier: UMIN000029372.

Potentially harmful excipients in neonatal medications: a multicenter nationwide observational study in Japan.

BACKGROUND: A multicenter investigation of neonate exposure to potentially harmful excipients (PHEs) in neonatal intensive care units (NICUs) in Japan has not been conducted. METHODS: A multicenter nationwide observational study was conducted. Neonate patient demographic data and information on all medicines prescribed and administered during hospitalization on 1 day between November 2019 and March 2021 were extracted from the medical records. Nine PHEs, paraben, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol, benzalkonium chloride, and aspartame, were selected. PHEs were identified from the package insert and the Interview Form. The quantitative daily exposure was calculated if quantitative data were available for each product containing the PHE. RESULTS: Prescription data was collected from 22 NICUs in Japan. In total, 343 neonates received 2360 prescriptions for 426 products containing 228 active pharmaceutical ingredients. PHEs were found in 52 (12.2%) products in 646 (27.4%) prescriptions for 282 (82.2%) neonates. Benzyl alcohol, sodium benzoates, and parabens were the most common PHEs in parenteral, enteral, and topical formulations, respectively. Quantitative analysis showed that 10 (10%), 38 (42.2%), 37 (94.9%), and 9 (39.1%) neonates received doses exceeding the acceptable daily intake of benzyl alcohol, polysorbate 80, propylene glycol, and sorbitol, respectively. However, due to the lack of quantitative information for all enteral and topical products, accurate daily PHE exposure could not be quantified. CONCLUSIONS: Neonates admitted to NICUs in Japan were exposed to PHEs, and several of the most commonly prescribed medicines in daily clinical practice in NICUs contained PHEs. Neonate PHE exposure could be reduced by replacing these medicines with available PHE-free alternatives.

Possible Involvement of MyD88 in Regulating Stress Response in Mice.

Myeloid differentiation primary response 88 (MyD88) is an adapter protein of the toll-like receptor (TLR) family that regulates innate immune function. Here, we identified a novel role of MyD88 in regulating stress response. MyD88 deficiency decreased immobility time in the forced swim test without affecting locomotor activity in mice. Immobilization stress-induced production of serum corticosterone was also completely inhibited by MyD88 deficiency. Stress induced decrease in glucocorticoid receptor in the hippocampus. On the other hand, stress exposure in MyD88 deficient mice did not cause decrease in its level in the hippocampus. Furthermore, immobilization stress-induced reduction of brain-derived neurotrophic factor (BDNF) levels in the hippocampus was ameliorated by MyD88 deficiency. These results suggest that MyD88 deficiency attenuates depression-like behavior by regulating corticosterone and BDNF levels. Overall, these results indicate the key role of MyD88 in regulating stress response in mice.

Medical costs of Japanese lung cancer patients during end-of-life care.

OBJECTIVE: The medical costs associated with cancer treatment have increased rapidly in Japan; however, little data exist on actual costs, especially for end-of-life care. Therefore, this study aimed to examine the medical costs of lung cancer patients during the last 3 months before death and to compare the costs with those of initial anticancer treatment. METHODS: We retrospectively evaluated all patients who died from lung cancer at the Japanese Red Cross Medical Center between 1 January 2008 and 31 August 2019. Patients were classified into three cohorts (2008-2011, 2012-2015 and 2016-2019) according to the year of death; the medical costs were evaluated for each cohort. Costs were then divided into outpatient and inpatient costs and calculated per month. RESULTS: Seventy-nine small cell lung cancer and 213 non-small cell lung cancer patients were included. For small cell lung cancer and non-small cell lung cancer patients, most end-of-life medical costs were inpatient costs across all cohorts. The median monthly medical costs for the last 3 months among both small cell lung cancer and non-small cell lung cancer patients did not differ significantly among the cohorts, but the mean monthly costs for non-small cell lung cancer tended to increase. The monthly medical costs for the last 3 months were significantly higher than those for the first year in SCLC (P = 0.013) and non-small cell lung cancer (P < 0.001) patients and those for the first 3 months in non-small cell lung cancer patients (P = 0.005). CONCLUSIONS: The medical costs during the end-of-life period for lung cancer were high and surpassed those for initial treatment.

Medical costs of lung cancer care in Japan during the first one or two years after initial diagnosis.

OBJECTIVES: Japan's healthcare expenditures, especially on oncology, are rapidly growing; however, there are scant data on actual costs and cost-effectiveness in the real world. The aim was to assess the medical costs and outcomes of patients with advanced lung cancer. METHODS: We retrospectively investigated all patients who were diagnosed with advanced lung cancer at the Japanese Red Cross Medical Center between 1 January 2008 and 31 December 2018. Patients were classified into three cohorts according to the year of diagnosis-Cohort 1: 2008-2010, Cohort 2: 2011-2014 and Cohort 3: 2015-2018-and assessed for medical costs and outcome. Medical costs were divided into outpatient and inpatient costs and were calculated on a monthly basis. RESULTS: Ninety-five patients with small cell lung cancer (SCLC) and 330 with nonsmall cell lung cancer (NSCLC) were included. There was a trend toward increased costs during the first two years after diagnosis in NSCLC patients, without changes in monthly costs, reflecting improved survival. Compared to Cohort 1, Cohort 3 patients with NSCLC had longer survival (median: 24 versus 12 months, P < 0.001), with a median incremental cost of Japanese Yen 6 million during the initial two years. The proportion of outpatient costs increased over time, especially for NSCLC patients (P < 0.001). No changes in costs or survival were observed in SCLC patients. CONCLUSIONS: In NSCLC patients, medical costs increased with prolonged survival during the last decade. The costs on a monthly basis did not change. The proportion of outpatient costs increased.

Association between buccal mucosa ridging and oral feature/symptom and its effects on occlusal function among dentate young adults in a cross-sectional study of Japan.

Objective: The purpose of this study was to assess the distinction in oral features/symptoms and occlusal function between young dentate individuals with and without buccal mucosa ridging (BMR). Methods: This cross-sectional study included 200 young adults. The outcome variable was BMR state. The predictor variables were oral features/symptoms (torus palatinus, torus mandibularis, temporomandibular joint noise, bruxism, tongue thrusting habit, number of teeth present, and occlusal vertical dimension) and oral function (occlusal force, occlusal contact area, occlusal pressure, tongue pressure). These variables were compared among participants with and without BMR using univariate and multiple logistic regression analysis. Results: There were 119 participants with BMR and 81 without BMR. Multiple logistic regression analysis revealed that BMR was closely associated with bruxism, occlusal vertical dimension, and occlusal pressure. Discussion: Oral/occlusal changes of increased bruxism, lower occlusal vertical dimension, and lower occlusal pressure constitute the major causes of BMR.