Elevated Levels of the Cancer Marker Neuron-Specific Enolase in a Patient With Coexisting Silicosis and Sarcoidosis.

In a periodical medical checkup, a 39-year-old Mongolian underground miner was diagnosed with silicosis based on chest radiography, computed tomography (CT), and work history. Chest radiography showed diffuse bilateral rounded nodules in both lung fields, with upper lobe dominance and large opacities in the right upper zone. Chest CT presented conglomerated massive changes in the right upper lobe and the coalescence of small nodules in the left upper lung. In the blood test, serum levels of the lung cancer marker neuron-specific enolase (NSE) were elevated (24.58 ng/mL). Carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) levels were within the reference range. Subsequent to the suspicion of a tumour in the right upper lobe, a right upper lobectomy was performed. The histopathological examination of the lung specimen revealed the coalescence of numerous silica nodules, accompanied by indications of associated sarcoidosis. The histological features suggested the presence of two concurrent pathological processes: silicosis and sarcoidosis. This case demonstrated the combination of three clinical conditions diagnosed in one patient, including complicated silicosis associated with sarcoidosis and elevated serum NSE levels. This case report may serve as a foundation for future investigations exploring the potential of NSE as a marker for silicosis.

Children's injuries in legislated types child-care institutions.

BACKGROUND: Severe injuries in child-care institutions are an important social issue. However, no reports on this matter have been made in Japan. This study examined trends in severe injuries at child-care institutions, including the impact of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted a serial cross-sectional study and interrupted time-series (ITS) analysis with a linear regression model to assess trends in the incidence rate of severe injuries using Japanese national open data between January or April 2017 and December 2021. Participants were individuals utilizing legislated types child-care institutions. The outcomes were annual and monthly incidence rates of severe injuries in legislated types child-care institutions. RESULTS: The number of legislated types child-care institutions increased from 32,793 facilities in 2017 to 38,666 facilities in 2021, and the number of participants rose from 2,802,228 in 2017 to 3,059,734 in 2021. The annual incidence rate of severe injuries in 2021 was 58.3 cases per 100,000 person-years, which is twofold higher than that in 2017. The ITS for the monthly incidence rate demonstrated an increasing trend before the COVID-19 pandemic. CONCLUSIONS: Before the COVID-19 pandemic, the monthly incidence rate of severe injuries in legislated types child-care institutions increased. The annual incidence rate in Japan may have also increased during the observation period.

Medical care costs according to the stage and subtype of breast cancer in a municipal setting: a case study of Hachioji City, Japan.

BACKGROUND: It is important to assess whether the early detection of breast cancer affects medical care costs. However, research remains scant on the actual medical care costs associated with breast cancer treatment in Japan. This study aimed to determine the medical care costs of breast cancer treatment based on its stage using national health insurance claims data. METHODS: This was an observational study including patients with breast cancer who had undergone breast cancer treatment, as defined by the disease name and related treatment codes. Between August 2013 and June 2016, patients who underwent surgical treatment without axillary lymph node dissection and other radical treatment were classified as the curable group, while those who underwent palliative treatment were classified as the non-curable group. Patients were further stratified by subtype. The total and treatment-specific medical care costs for the five years were calculated using the national health insurance claims data of Hachioji City between August 2013 and May 2021. RESULTS: The mean total medical care costs for the curable and non-curable groups for the 5 years were JPY 3958 thousand (standard deviation 2664) and JPY 8289 thousand (8482), respectively. The mean medical care costs for specific breast cancer treatment for the curable and non-curable groups were JPY 1142 (728) thousand and JPY 3651 thousand (5337), respectively. Further, human epidermal growth factor receptor 2 + , Hormone + patients had the highest mean cost over the 5 years. CONCLUSIONS: The results suggest that the early detection of breast cancer may reduce medical care costs at the patient level.

Internet-Based Inquiries From Users With the Intention to Overdose With Over-the-Counter Drugs: Qualitative Analysis of Yahoo! Chiebukuro.

BACKGROUND: Public concern with regard to over-the-counter (OTC) drug abuse is growing rapidly across countries. OTC drug abuse has serious effects on the mind and body, such as poisoning symptoms, and often requires specialized treatments. In contrast, there is concern about people who potentially abuse OTC drugs whose symptoms are not serious enough to consult medical institutions or drug addiction rehabilitation centers yet are at high risk of becoming drug dependent in the future. OBJECTIVE: Consumer-generated media (CGM), which allows users to disseminate information, is being used by people who abuse (and those who are trying to abuse) OTC drugs to obtain information about OTC drug abuse. This study aims to analyze the content of CGM to explore the questions of people who potentially abuse OTC drugs. METHODS: The subject of this research was Yahoo! Chiebukuro, the largest question and answer website in Japan. A search was performed using the names of drugs commonly used in OTC drug abuse and the keywords overdose and OD, and the number of questions posted on the content of OTC drug abuse was counted. Furthermore, a thematic analysis was conducted by extracting text data on the most abused antitussive and expectorant drug, BRON. RESULTS: The number of questions about the content of overdose medications containing the keyword BRON has increased sharply as compared with other product names. Furthermore, 467 items of question data that met the eligibility criteria were obtained from 528 items of text data on BRON; 26 codes, 6 categories, and 3 themes were generated from the 578 questions contained in these items. Questions were asked about the effects they would gain from abusing OTC drugs and the information they needed to obtain the effects they sought, as well as about the effects of abuse on their bodies. Moreover, there were questions on how to stop abusing and what is needed when seeking help from a health care provider if they become dependent. It has become clear that people who abuse OTC drugs have difficulty in consulting face-to-face with others, and CGM is used as a means to obtain the necessary information anonymously. CONCLUSIONS: On CGM, people who abused or tried to abuse OTC drugs were asking questions about their abuse expectations and anxieties. In addition, when they became dependent, they sought advice to quit their abuse. CGM was used to exchange information about OTC drug abuse, and many questions on anxieties and hesitations were posted. This study suggests that it is necessary to produce and disseminate information on OTC drug abuse, considering the situation of those who abuse or are willing to abuse OTC drugs. Support from pharmacies and drugstores would also be essential to reduce opportunities for OTC drug abuse.

Associations between Sleep-Disordered Breathing and Serum Uric Acid and Their Sex Differences: The Nagahama Study.

Sleep-disordered breathing (SDB) is often accompanied by noncommunicable diseases (NCDs), including gout. However, the association between serum uric acid (sUA) levels and NCDs is complicated in patients with SDB. We aimed to clarify this issue utilizing large-scale epidemiological data. This community-based study included 9850 inhabitants. SDB and its severity were assessed by a 3% oxygen desaturation index (3% ODI) corrected for sleep duration using wrist actigraphy. The associations between sUA and moderate to severe SDB (MS-SDB) and sUA and NCDs in patients with MS-SDB were analyzed. A total of 7895 subjects were eligible. In females, the prevalence of MS-SDB increased according to an elevation in sUA levels even after adjusting for confounders, and sUA ≥ 5 mg/dL was the threshold. These were not found in males. There was a positive interaction between sUA ≥ 5 mg/dL and female sex for MS-SDB. In females with MS-SDB, the prevalence of diabetes mellitus (DM) increased according to an elevation in sUA levels, and those with sUA ≥ 5 mg/dL showed a higher prevalence of DM than their counterparts. There is a clear correlation between sUA levels and the severity of SDB, and elevated sUA poses a risk for DM in females with MS-SDB.

Status of screening and preventive efforts against diabetic kidney disease between 2013 and 2018: analysis using an administrative database from Kyoto-city, Japan.

Background: Japan has the second highest prevalence of dialysis use in the world. Approximately 40% of patients who begin dialysis have diabetic kidney disease (DKD). Local governments and medical facilities are required to provide preventive measures against worsening diabetes mellitus (DM). However, the percentage of patients with DM who receive such screening or interventions for DKD is unclear. This study aimed to reveal to what extent screening for DKD and preventive measures against worsening DKD are performed in patients with DM, using an administrative database in a municipality. Methods: This was a cross-sectional study that used the Kyoto-city's administrative medical and long-term care database. Patients with a diagnosis of DM and receiving antidiabetic medication between 2013 and 2018 were defined as patients with DM and included. Patients with DKD were defined as those diagnosed with diabetic nephropathy or those with chronic kidney disease. We described the characteristics of patients with DM, diabetic complications, and extent of DKD screenings and preventive efforts against worsening of DM by fiscal year. Results: Across fiscal years, 25.8% to 27.5% of patient with DM had DKD. More than 3% of patients were on dialysis due DM in each fiscal year; approximately 15% started receiving dialysis that year. The percentage of patients who were regularly prescribed antidiabetic medication and received glycosylated hemoglobin testing ranged from 64.0% to 67.2% and from 30.6% to 36.5%, respectively. Urine microalbuminuria testing at least once a year occurred in 9.3% to 10.0%. The percentage of patients who received nutritional guidance ranged from 19.0% to 21.0%. Approximately 1% of patients received guidance for preventing DM from progressing to a disease that requires dialysis each fiscal year. Conclusion: This study from Japan, where a super-aging society has developed, using an administrative database in a municipality covering most of the elderly population clearly demonstrated an evidence-practice gap in efforts to prevent worsening of DKD. Strengthening cooperation between government and medical facilities and support for providing preventive measures against DKD are urgently needed.

The role of critical care nurses in shared decision-making for patients with severe heart failure: A qualitative study.

AIM: Patients with severe heart failure undergo highly invasive and advanced therapies with uncertain treatment outcomes. For these patients, shared decision-making is necessary. To date, the nursing perspective of the decision-making process for patients facing difficulties and how nurses can support patients in this process have not been fully elucidated. This study aimed to clarify the perceptions of critical care nurses regarding situations with patients with severe heart failure that require difficult decision-making, and their role in supporting these patients. METHODS: Individual semi-structured interviews were conducted with 10 certified nurse specialists in critical care nursing at nine hospitals in Japan. A qualitative inductive method was used and the derived relationships among the themes were visually structured and represented. RESULTS: The nurses' perceptions on patients' difficult situations in decision-making were identified as follows: painful decisions under uncertainties; tense relationships; wavering emotions during decision-making; difficulties in coping with worsening medical conditions; patients' wishes that are difficult to realize or estimate; and difficulties in transitioning from advanced medical care. Critical care nurses' roles were summarized into six themes and performed collaboratively within the nursing team. Of these, the search for meaning and value was fundamental. Two positions underpin the role of critical care nurses. The first aims to provide direct support and includes partnerships and rights advocacy. The second aims to provide a holistic perspective to enable necessary adjustments, as indicated by situation assessments and mediation. By crossing various boundaries, co-creating, and forming a good circular relationship in the search for meaning and values, the possibility of expanding treatment and recuperation options may be considered. CONCLUSIONS: Patients with severe heart failure have difficulty participating in shared decision-making. Critical care nurses should collaborate within the nursing team to improve interprofessional shared decision-making by providing decisional support to patients that focuses on values and meaning.

Misregulation of cell cycle-dependent methylation of budding yeast CENP-A contributes to chromosomal instability.

Centromere (CEN) identity is specified epigenetically by specialized nucleosomes containing evolutionarily conserved CEN-specific histone H3 variant CENP-A (Cse4 in Saccharomyces cerevisiae, CENP-A in humans), which is essential for faithful chromosome segregation. However, the epigenetic mechanisms that regulate Cse4 function have not been fully defined. In this study, we show that cell cycle-dependent methylation of Cse4-R37 regulates kinetochore function and high-fidelity chromosome segregation. We generated a custom antibody that specifically recognizes methylated Cse4-R37 and showed that methylation of Cse4 is cell cycle regulated with maximum levels of methylated Cse4-R37 and its enrichment at the CEN chromatin occur in the mitotic cells. Methyl-mimic cse4-R37F mutant exhibits synthetic lethality with kinetochore mutants, reduced levels of CEN-associated kinetochore proteins and chromosome instability (CIN), suggesting that mimicking the methylation of Cse4-R37 throughout the cell cycle is detrimental to faithful chromosome segregation. Our results showed that SPOUT methyltransferase Upa1 contributes to methylation of Cse4-R37 and overexpression of UPA1 leads to CIN phenotype. In summary, our studies have defined a role for cell cycle-regulated methylation of Cse4 in high-fidelity chromosome segregation and highlight an important role of epigenetic modifications such as methylation of kinetochore proteins in preventing CIN, an important hallmark of human cancers.

Female sexual dysfunction and lower urinary tract symptoms associated with vulvovaginal atrophy symptoms: Results of the GENJA study.

OBJECTIVES: To investigate the main symptoms of female sexual dysfunction (FSD) and lower urinary tract symptoms associated with vulvovaginal atrophy (VVA) symptoms as the core symptoms of genitourinary syndrome of menopause. METHODS: We extracted the data of 4134 Japanese women aged 40-79 years who participated in the GENitourinary syndrome of menopause in JApanese women (GENJA) study. All participants responded to web-based questionnaires assessing their health situation, including the Vulvovaginal Symptoms Questionnaire, the Female Sexual Function Index (FSFI), and the Core Lower Urinary Tract Symptom Score. Multivariable regression and multivariable logistic regression analyses were applied to analyze the association between VVA symptoms and FSD, and between VVA symptoms and lower urinary tract symptoms. RESULTS: Multivariable regression analysis revealed that VVA symptoms were associated with lower scores for arousal, lubrication, orgasm, satisfaction, and pain domains in the FSFI in sexually active women (p < 0.01). Regression coefficients were higher for lubrication and pain domains than for the other domains. Multivariable logistic regression analysis revealed that women reporting VVA symptoms were more likely to have increased daytime urinary frequency, nocturia, urgency, slow stream, straining to void, feeling of incomplete emptying, bladder pain, and feeling a bulge/lump from or in the vagina (p < 0.05). Adjusted odds ratios were particularly high for straining to void, feeling of incomplete emptying, and bladder pain. CONCLUSIONS: Vulvovaginal atrophy symptoms were significantly associated with decreased lubrication and dyspareunia in FSD, and urinary symptoms of straining to void, feeling of incomplete emptying, and bladder pain.

Relationship of Ethinylestradiol/Drospirenone Prescription on Work Productivity and Activity Impairment Among Women With Menstruation-Related Symptoms: A Multicenter Prospective Observational Study.

OBJECTIVE: The aim of the study is to examine changes in work productivity and daily activity impairment among women by starting ethinylestradiol (EE)/drospirenone (DRSP) for perimenstrual symptoms. METHODS: Participants were women who were newly prescribed EE/DRSP at 25 gynecological clinics in Japan. Eligible participants recorded daily intake of EE/DRSP and the Work Productivity Activity Impairment Questionnaire General Health every 2 weeks for 3 months by smartphone app. A linear mixed-effects model was used to see changes in work productivity impairment and activity impairment relative to baseline. RESULTS: A total of 222 participants were eligible. Work productivity impairment recovered by 20.0% (95% confidence interval, 14.1%-26.0%) at 1 m and maintained for 2 months. Activity impairment recovered by 20.1% (95% confidence interval, 15.5%-24.7%) at 1 m and thereafter. CONCLUSIONS: Improvements in work productivity and daily activities were observed at 1 m after EE/DRSP initiation, with a sustained effect thereafter.

Dysfunction of Foxp3+ Regulatory T Cells Induces Dysbiosis of Gut Microbiota via Aberrant Binding of Immunoglobulins to Microbes in the Intestinal Lumen.

Foxp3+ regulatory T (Treg) cells prevent excessive immune responses against dietary antigens and commensal bacteria in the intestine. Moreover, Treg cells contribute to the establishment of a symbiotic relationship between the host and gut microbes, partly through immunoglobulin A. However, the mechanism by which Treg cell dysfunction disturbs the balanced intestinal microbiota remains unclear. In this study, we used Foxp3 conditional knockout mice to conditionally ablate the Foxp3 gene in adult mice and examine the relationship between Treg cells and intestinal bacterial communities. Deletion of Foxp3 reduced the relative abundance of Clostridia, suggesting that Treg cells have a role in maintaining Treg-inducing microbes. Additionally, the knockout increased the levels of fecal immunoglobulins and immunoglobulin-coated bacteria. This increase was due to immunoglobulin leakage into the gut lumen as a result of loss of mucosal integrity, which is dependent on the gut microbiota. Our findings suggest that Treg cell dysfunction leads to gut dysbiosis via aberrant antibody binding to the intestinal microbes.

Survival and medical costs of non-small cell lung cancer patients according to the first-line treatment: An observational study using the Kyoto City Integrated Database.

BACKGROUND: Lung cancer is the primary cause of cancer mortality and non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases. New drug treatments have been developed since 2010 but there are concerns about the increase in medical costs. This study aimed to compare survival and medical costs among patients with NSCLC according to their initial treatment to estimate the impact of early NSCLC detection. METHODS: Patients with primary NSCLC who filed insurance claims between April 2013 and March 2019 were identified using the Kyoto City Integrated Database. Patients were divided into two groups depending on their initial treatment: the resection group and drug or radiation group. The survival and medical costs were calculated. RESULTS: A total of 2609 patients with primary NSCLC were identified. Among them, 1035 patients underwent resection. The 5-year survival was 75% for the resection group while below 25% for the drug or radiation group. At 6 months of survival, the median cumulative total cost was 2409 thousand yen (interquartile range [IQR] 1947-4012 thousand yen) in the resection group and 2951 thousand yen (IQR 1600-4706 thousand yen) in the drug or radiation group. At 4 years of survival, the cumulative median total cost was 5257 thousand yen (IQR 3808-8243 thousand yen) in the resection group and 10 202 thousand yen (IQR 4845-20 450 thousand yen) in the drug or radiation group. CONCLUSIONS: As a first-line therapy in newly diagnosed patients with NSCLC, surgical resection is associated with longer survival and lower medical costs than pharmacotherapy or radiotherapy.

Chronic Diseases and Sociodemographic Characteristics Associated With Online Health Information Seeking and Using Social Networking Sites: Nationally Representative Cross-sectional Survey in Japan.

BACKGROUND: In an aging society, worsening chronic diseases increase the burden on patients and the health care system. Using online health information including health information via social networking sites (SNSs), such as Facebook and YouTube, may play an important role in the self-management of chronic diseases and health promotion for internet users. OBJECTIVE: This study aims to improve strategies for promoting access to reliable information for the self-management of chronic diseases via the internet, and to identify populations facing barriers to using the internet for health, we examined chronic diseases and characteristics associated with online health information seeking and the use of SNSs. METHODS: This study used data from the INFORM Study 2020, which was a nationally representative cross-sectional postal mail survey conducted using a self-administered questionnaire in 2020. The dependent variables were online health information seeking and SNS use. Online health information seeking was assessed using 1 question about whether respondents used the internet to find health or medical information. SNS use was assessed by inquiring about the following 4 aspects: visiting SNSs, sharing health information on SNSs, writing in an online diary or blog, and watching a health-related video on YouTube. The independent variables were 8 chronic diseases. Other independent variables were sex, age, education status, work, marital status, household income, health literacy, and self-reported health status. We conducted a multivariable logistic regression model adjusted for all independent variables to examine the associations of chronic diseases and other variables with online health information seeking and SNS use. RESULTS: The final sample for analysis comprised 2481 internet users. Hypertension or high blood pressure, chronic lung diseases, depression or anxiety disorder, and cancer were reported by 24.5%, 10.1%, 7.7%, and 7.2% of respondents, respectively. The odds ratio of online health information seeking among respondents with cancer was 2.19 (95% CI 1.47-3.27) compared with that among those without cancer, and the odds ratio among those with depression or anxiety disorder was 2.27 (95% CI 1.46-3.53) compared with that among those without. Further, the odds ratio for watching a health-related YouTube video among those with chronic lung diseases was 1.42 (95% CI 1.05-1.93) compared with that among those without these diseases. Women, younger age, higher level of education, and high health literacy were positively associated with online health information seeking and SNS use. CONCLUSIONS: For patients with cancer, strategies for promoting access to websites with reliable cancer-related information as well as access among patients with chronic lung diseases to YouTube videos providing reliable information may be beneficial for the management of these diseases. Moreover, it is important to improve the online environment to encourage men, older adults, internet users with lower education levels, and those with low health literacy to access online health information.

Trend of anticoagulant therapy in elderly patients with atrial fibrillation considering risks of cerebral infarction and bleeding.

The introduction of direct oral anticoagulants (DOACs) has greatly changed the use of anticoagulant therapy in patients with non-valvular atrial fibrillation (Af). Therefore, this study aimed to examine changes in the proportions of oral anticoagulant prescriptions in patients with non-valvular Af aged ≥ 65 years, taking into consideration the risk of cerebral infarction and bleeding. Anticoagulant prescriptions in outpatients aged ≥ 65 years with Af were temporally analyzed using the nationwide claims database in Japan. Trends in anticoagulant prescriptions were examined according to cerebral infarction and bleeding risk. The proportion of anticoagulant prescriptions for 12,076 Af patients increased from 41% in 2011 to 56% in 2015. An increase in DOAC prescriptions was accompanied by an increase in the proportion of anticoagulant prescriptions in each group according to the CHA2DS2-VASc and HAS-BLED scores. The proportion of anticoagulant prescriptions for patients with a high risk of developing cerebral infarction and bleeding showed a marked increase. Trends in anticoagulant prescriptions in Af patient with a CHA2DS2-VASc score ≥ 2 and HAS-BLED scores ≥ 3 showed a marked increase in DOAC prescriptions. The widespread use of DOACs greatly changes the profile the prescription of anticoagulant therapy in patients with Af.

Sleep disordered breathing and haemoglobin A1c levels within or over normal range and ageing or sex differences: the Nagahama study.

Recently an association between blood glucose dysregulation and sleep disruption was suggested. The association between sleep disordered breathing, most of which is due to obstructive sleep apnea (OSA) in the general population, and diabetic severity, as well as the impact of antidiabetic treatment, remains unclear. This study aimed to investigate these associations as well as age and sex differences. This cross-sectional study evaluated 7,680 community participants as the main cohort (population-based cohort). OSA was assessed by the 3% oxygen desaturation index from pulse oximetry, which was corrected for sleep duration obtained by wrist actigraphy. For arguing the limitations for using pulse oximetry, 597 hospitalised patients, who were assessed by the apnea-hypopnea index from attended polysomnography, were also evaluated as the validation cohort (hospital-based cohort). Moderate-to-severe OSA was more prevalent as haemoglobin A1c (HbA1c) levels increased (<5.6%/5.6%-<6.5%/6.5%-<7.5%/≥7.5%, respectively) in both cohorts (p < 0.001), but only in those without antidiabetic treatment. The HbA1c level was an independent factor for moderate-to-severe OSA (population-based cohort, odds ratio [OR] 1.26, 95% confidence interval [CI] 1.10-1.45; hospital-based cohort, OR 1.69, 95% CI 1.22-2.33, per 1% increase). These associations were more prominent in the middle-aged (aged <60 years) than in the elderly (aged ≥60 years) and in women than in men in both cohorts. The prevalence of moderate-to-severe OSA in patients with antidiabetic treatment in the hospital-based cohort was ≥75% regardless of HbA1c levels. In conclusion, an association between the prevalence of OSA and HbA1c level even within or over the normal range was found only in patients without antidiabetic treatment and was more prominent in the middle-aged and in women.

Evaluation of factors affecting epidermal growth factor receptor tyrosine kinase inhibitor-induced hepatotoxicity in Japanese patients with non-small cell lung cancer: a two-center retrospective study.

BACKGROUND: Gefitinib and erlotinib, are epidermal growth factor receptor tyrosine kinase inhibitors, and are currently recommended for non-small cell lung cancer stage IV in the elderly and in patients with decreased performance status in the Japanese Lung Cancer Society Guideline, but they occasionally caused severe hepatotoxicity requiring postponement or modification of treatment. However, little is known about the risk factors for hepatotoxicity in patients receiving gefitinib and erlotinib. In this study, we investigated the factors influencing hepatotoxicity in Japanese non-small cell lung cancer (NSCLC) patients treated with gefitinib or erlotinib monotherapy. METHODS: Japanese patients with NSCLC who started gefitinib or erlotinib monotherapy from January 2005 to December 2017 at Kanazawa University Hospital or Kanazawa Medical University Hospital were included in this study. Factors affecting hepatotoxicity were retrospectively investigated by multiple logistic regression analysis. RESULTS: A total of 102 patients who received gefitinib and 95 patients who received erlotinib were included in the analysis. In the gefitinib group, a body mass index (BMI) ≥ 25 was associated with an increased risk of hepatotoxicity (OR = 4.571, 95% CI = 1.486-14.056, P = 0.008). In the erlotinib group, concomitant use of acid-suppressing medications (AS), namely proton pump inhibitors or histamine-2 receptor antagonists, was associated with a reduced risk of hepatotoxicity (OR = 0.341, 95% CI = 0.129-0.900, P = 0.030). CONCLUSIONS: BMI ≥ 25 in patients treated with gefitinib increased the risk of hepatotoxicity. In contrast, AS combination with erlotinib reduced the risk of hepatotoxicity. Thus, because different factors influence the risk of hepatotoxicity, monitoring for adverse events should take into account patient background factors and concomitant medications.

Risk assessment of accidental falls in patients taking trazodone, quetiapine, or risperidone for insomnia: A single-center, case-control study.

AIM: No consensus has been reached on the association between the risk of falls and antipsychotic and antidepressant drug use. In this study, we evaluated the risk of falls with trazodone, risperidone, and quetiapine, which are recommended for use at Kanazawa Medical University Hospital. METHODS: We reviewed all patients who were admitted to Kanazawa Medical University Hospital between January 1st and December 31st, 2018. We excluded those aged <20 years and those admitted to pediatric, intensive care, and psychiatric wards. Finally, 9273 patients were included. We reviewed the incidence in these patients of accidental falls reported to the medical safety department. We noted whether these patients received trazodone, quetiapine, or risperidone. We also observed whether they were taking a benzodiazepine receptor agonist, which is a known risk factor. We further examined each patient's age, sex, the department they were visiting, and their diseases. Patients were considered to have taken medication if it was administered within 24 hours before an accidental fall. Multiple logistic regression analysis was used to evaluate the risk of accidental fall. RESULTS: Multivariate analysis showed that the adjusted odds ratios (OR) for each medication (with 95% confidence intervals) were: trazodone (OR, 0.47 [0.27-0.80]), quetiapine (OR, 1.06 [0.46-2.46]), and risperidone (OR, 0.82 [0.41-1.63]). CONCLUSION: The association of risperidone and quetiapine with accidental falls was unclear. Interestingly, however, trazodone may help reduce the risk, which makes it a potential pharmacologic treatment option for insomnia in patients at high risk for accidental falls.

Tracheostomy decannulation rates in Japan: a retrospective cohort study using a claims database.

Despite the exponential increase in the use of tracheostomy worldwide, rates of tracheostomy decannulation are unknown. We conducted a retrospective cohort study to investigate tracheostomy decannulation rates among adult patients over a two-year period and explored factors associated with prolonged tracheostomy. A health insurance claims database including 3,758,210 people in Japan was used. The primary outcome was time to decannulation. Assessed patient and hospital factors included age, sex, emergency endotracheal intubation, disease, and hospital size. A total of 917 patients underwent tracheostomy, and 752 met the eligibility criteria. Decannulation rates were 40.8% (95% confidence interval 36.8-44.9) at 3 months, 63.9% (58.4-69.0) at 12 months, and 65.0% (59.2-70.3) at 24 months. Hazard ratios of patient and hospital factors for tracheostomy decannulation were 0.44 for age (65-74 years) (95% confidence interval 0.28-0.68), 0.81 (0.63-1.05) for female sex, and 0.59 (0.45-0.76) for emergency endotracheal intubation. Cerebrovascular disease, head injuries, and cardiac arrest had lower hazard ratios compared to other diseases. Decannulation rates among adult patients in Japan increased rapidly up to 3 months after tracheostomy, reaching a plateau after 12 months. Older age, female sex, emergency endotracheal intubation, cerebrovascular disease, head injuries, and cardiac arrest were associated with prolonged tracheostomy.

Evaluation of Clinical Practice Guidelines for Rare Diseases in Japan.

Introduction: The insufficient quantity and quality of clinical epidemiological evidence in the field of rare diseases have posed methodological challenges to develop clinical practice guidelines (CPGs). Guideline development groups struggle to provide patients and their families with beneficial guidance, such as that for medical care and in complex circumstances. Motivated by the challenges, we focused on information on resources for supporting the daily and social life to improve the CPGs for users. We aimed to assess the methodological quality of CPGs for rare diseases in Japan and to evaluate information on resources to support the daily and social life in the CPGs. Methods: We conducted a systematic search using PubMed, three electronic Japanese databases, and two hand-searched sources in Japan. The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument with six domains was used to assess the methodological quality of the CPGs. A content analysis of the CPG text was conducted using five keywords as information on non-medical resources, e.g., "Intractable Disease Consultation Support Center," "Japan Intractable Disease Information Center," and "Patient Association." Results: A total of 55 CPGs met the inclusion criteria. Among four domains of AGREE II with low scores (Stakeholder Involvement, Rigor of Development, Applicability, and Editorial Independence), Rigor of Development had the lowest median score. As for information on non-medical resources, 41 CPGs included at least 1 of the 5 keywords, while 14 CPGs included none. Conclusions: At the Rigor of Development domain, methodological challenges may have resulted in an insufficient description of items regarding the translation evidence to recommendations. As the sufficiency of five keywords as information on non-medical resources could be improved, the information will be advocative as clues to provide pragmatic guidance, particularly for rare diseases with limited medical evidence.

Depressive symptoms homophily among community-dwelling older adults in japan: A social networks analysis.

Late-life depression is one of the most common mental illnesses that cause serious consequences, but the majority do not reach out for mental health services and relapses are common. The present study investigated profiled similarity of older adults' social networks in terms of depressive symptoms. In 2017, we distributed questionnaires inquiring about confidants in the community, depressive symptoms based on the 15-item Geriatric Depression Scale (GDS-15), and demographic and functional characteristics to all the community-dwelling older adults under the national insurance system in Wakuya City (Miyagi prefecture, Japan). Applying the Exponential Random Graph Model, we estimated the likelihood of a confidant relational tie by the similarity of overall and specific depressive symptoms within 217,470 potential ties among 660 respondents eligible for analysis. The overall depressive symptom homophily was marginally significant (p < 0.10), indicating that the likelihood of a confidant relational tie between two community-dwelling older adults was decreased by 5%, with one point increase in their difference in the total number of depressive symptoms (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.90-1). Focusing on specific domains of depressive symptoms, we found significant apathy homophily (p < 0.05) but no significant suicidal ideation of homophily. The results indicated that there is a 19% decrease in the likelihood of a confidant relational tie between two community-dwelling older adults by one point increase in their difference in the total number of apathy symptoms (OR, 0.81; 95%CI, 0.67-0.98) but no change by increasing the difference in their total number of suicidal ideation symptoms (OR, 1; 95%CI, 0.87-1.14). These findings suggest depressive symptom homophily, particularly with respect to apathy domains, in confidant social networks of community-dwelling older adults, and the importance of network intervention in preventing late-life depression.