Dose-dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracil.

Agranulocytosis is a serious adverse effect of methimazole (MMI) and propylthiouracil (PTU), and although there have been reports suggesting a dose-dependent incidence in relation to both drugs, the evidence has not been conclusive. The objective of our study was to determine whether the incidences of agranulocytosis induced by MMI and PTU exhibit dose-dependency. The subjects were 27,784 patients with untreated Graves' disease, 22,993 of whom were on an antithyroid drug treatment regimen for more than 90 days. Within this subset, 18,259 patients had been treated with MMI, and 4,734 had been treated with PTU. The incidence of agranulocytosis according to dose in the MMI group was 0.13% at 10 mg/day, 0.20% at 15 mg/day, 0.32% at 20 mg/day, and 0.47% at 30 mg/day, revealing a significant dose-dependent increase. In the PTU group, there were 0 cases of agranulocytosis at doses of 125 mg/day and below, 0.33% at 150 mg/day, 0.31% at 200 mg/day, and 0.81% at 300 mg/day, also revealing a significant dose-dependent increase. The incidence of agranulocytosis at MMI 15 mg and PTU 300 mg, i.e., at the same potency in terms of hormone synthesis inhibition, was 0.20% and 0.81%, respectively, and significantly higher in the PTU group. Our findings confirm a dose-dependent increase in the incidence of agranulocytosis with both drugs, but that at comparable thyroid hormone synthesis inhibitory doses PTU has a considerably higher propensity to induce agranulocytosis than MMI does.

Thyroid Dysfunction Risk After Iodinated Contrast Media Administration: A Prospective Longitudinal Cohort Analysis.

CONTEXT: Iodinated contrast media (ICM) is a common source of excess iodine in medical settings, given the common use of iodinated radiologic procedures. OBJECTIVE: To determine the long-term risks of thyroid dysfunction following iodinated contrast administration in a prospective study. DESIGN, SETTING, PARTICIPANTS: A longitudinal cohort study was conducted of patients in the U.S. Veterans Affairs medical system who received ICM. MAIN OUTCOME MEASURES: Serum thyroid function, thyroid antibody, and inflammatory markers were measured at baseline. Thyroid function tests were repeated at 1 month, 3 months, and every 6 months thereafter until 36 months. Risk of thyroid dysfunction and longitudinal changes in thyroid hormone levels were assessed using mixed effect models. RESULTS: There were 122 participants (median age, 70.0 [IQR 62.2-74.0] years; 98.4% male). At baseline, six subjects had subclinical thyroid dysfunction prior to ICM receipt. During median follow-up of 18 months, iodine-induced thyroid dysfunction was observed in 11.5% (14/122); six (4.9%) developed hyperthyroidism (including one with overt hyperthyroidism) and eight (6.6%) subclinical hypothyroidism. At last follow-up, ten of 20 subjects with thyroid dysfunction (14 new-onset cases and six with preexisting thyroid dysfunction) had persistent subclinical hyperthyroidism or hypothyroidism. There were also subtle changes in thyroid hormones observed longitudinally within the reference ranges in the overall cohort. CONCLUSIONS: There is a rare long-term risk of an excess iodine load on thyroid dysfunction even among individuals from an overall iodine-sufficient region, supporting the need for targeted monitoring following iodinated contrast administration.

Depression Onset After a Spouse's Cardiovascular Event.

Importance: Although cardiovascular disease (CVD) is a known risk factor for depression, evidence is lacking regarding whether and to what extent a spouse's CVD is associated with the subsequent mental health of individuals. Objective: To examine the association between CVD onset in spouses and subsequent depression. Design, Setting, and Participants: This cohort study examined 277 142 matched married couples enrolled in the Japan Health Insurance Association health insurance program between April 2015 and March 2022, covering approximately 40% of the working-age population in Japan. Index individuals (primary insured) whose spouses (dependent) experienced incident CVD between April 2016 and March 2022 were 1:1 matched to controls whose spouses did not experience CVD. Matching was based on age, sex, income, or the onset date of the spouses' CVD. Data analysis was conducted from April 2016 to March 2022. Exposure: Spousal onset of CVD between fiscal years 2016 and 2021. The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes were used to identify the composite CVD outcomes (stroke, heart failure, and myocardial infarction). Main Outcomes and Measures: Multivariate Cox proportional hazards models were used to investigate the association between spouses' new-onset CVD and individuals' depression, adjusting for sociodemographic characteristics and comorbidities of index individuals (diabetes, hypertension, and CVD) and spouses (diabetes, hypertension, and depression). Subgroup analyses were conducted according to sex, age, income levels, and history of CVD. Results: Among 277 142 matched pairs of married couples, 263 610 (95.1%) had a male index individual; the mean (SD) age of index individuals was 58.2 (10.2) years. A new onset of depression was observed in 4876 individuals (1.8%). In multivariable Cox models, there was an association between the spouse's CVD and the individuals' depression (hazard ratio, 1.13 [95% CI, 1.07-1.20]). The subgroup analysis found no evidence of heterogeneity in sex, age, income level, or CVD history. The results were consistent when additionally adjusted for health behaviors (smoking, alcohol consumption, physical activity, and use of antihypertensive drugs) and objectively measured physical health conditions (body mass index, blood pressure, cholesterol levels, glucose levels, and estimated glomerular filtration rate) (hazard ratio, 1.16 [95% CI, 1.06-1.28]). Conclusions and Relevance: In this nationwide cohort study of matched couples, a spouse's onset of CVD was associated with an increased risk of an individual's depression. These findings highlight the importance of preventive care for mental health disorders in individuals whose spouses experience incident CVD.

Cardiovascular Outcomes of KCNJ5 mutated Aldosterone-Producing Adenoma: A Systematic Review.

BACKGROUND: While clinical features of KCNJ5-mutated aldosterone-producing adenoma (APA) have been reported, evidence of its clinical outcomes is lacking. We aimed to synthesize available literature about the associations between KCNJ5 mutation with cardiovascular and metabolic outcomes among patients with APA. METHODS: In this systematic review of observational studies, MEDLINE and EMBASE were searched through August 2022. Two independent authors screened the search results and extracted data from eligible observational studies investigating cardiovascular or metabolic outcomes between KCNJ5-mutated APAs and KCNJ5-non-mutated APAs. Risk of Bias In Non-randomized Studies of Interventions was used to assess the quality of the included studies. RESULTS: A total of 573 titles/abstracts were screened and after the expert opinion of the literature, 20 were read the full text, of which 12 studies were included. Across three studies comparing the baseline or change in the cardiac function between KCNJ5-mutated APAs and KCNJ5-non-mutated APAs, all studies reported the association between impaired cardiac functions and KCNJ5 mutation status. Among six studies evaluating the cure of hypertension after surgery, all studies showed that KCNJ5 mutation was significantly associated with the cure of hypertension. In quality assessment, seven studies were at serious risk of bias, while the remaining studies were at moderate risk of bias. CONCLUSIONS: This systematic review provided evidence of the significant association between KCNJ5 mutation and unfavorable cardiovascular outcomes in patients with primary aldosteronism. Further research is needed to improve the quality of evidence on this topic and elucidate the underlying mechanisms of the potential burden of KCNJ5 mutation.

Income Level and Impaired Kidney Function Among Working Adults in Japan.

Importance: Chronic kidney disease (CKD) is a major public health issue, affecting 850 million people worldwide. Although previous studies have shown the association between socioeconomic status and CKD, little is known about whether this association exists in countries such as Japan where universal health coverage has been mostly achieved. Objective: To identify any association of income-based disparity with development of impaired kidney function among the working population of Japan. Design, Setting, and Participants: This was a nationwide retrospective cohort study of adults aged 34 to 74 years who were enrolled in the Japan Health Insurance Association insurance program, which covers approximately 40% of the working-age population (30 million enrollees) in Japan. Participants whose estimated glomerular filtration rate (eGFR) had been measured at least twice from 2015 to 2022 were included in the analysis, which was conducted from September 1, 2021, to March 31, 2023. Exposure: Individual income levels (deciles) in the fiscal year 2015. Main Outcomes and Measures: Odds ratios were calculated for rapid CKD progression (defined as an annual eGFR decline of more than 5 mL/min/1.73 m2), and hazard ratios, for the initiation of kidney replacement therapy (dialysis or kidney transplant) by income level deciles in the fiscal year 2015. Results: The study population totaled 5 591 060 individuals (mean [SD] age, 49.2 [9.3] years) of whom 33.4% were female. After adjusting for potential confounders, the lowest income decile (lowest 10th percentile) demonstrated a greater risk of rapid CKD progression (adjusted odds ratio, 1.70; 95% CI, 1.67-1.73) and a greater risk of kidney replacement therapy initiation (adjusted hazard ratio, 1.65; 95% CI, 1.47-1.86) compared with the highest income decile (top 10th percentile). A negative monotonic association was more pronounced among males and individuals without diabetes and was observed in individuals with early (CKD stage 1-2) and advanced (CKD stage 3-5) disease. Conclusions and Relevance: The findings of this retrospective cohort study suggest that, even in countries with universal health coverage, there may be a large income-based disparity in the risk of rapid CKD progression and initiation of kidney replacement therapy. These findings highlight the importance of adapting CKD prevention and management strategies according to an individual's socioeconomic status, even when basic health care services are financially guaranteed.

Harnessing Causal Forests for Epidemiologic Research: Key Consideration.

Assessing heterogeneous treatment effects (HTEs) is an essential task in epidemiology. The recent integration of machine learning into causal inference has provided a new, flexible tool for evaluating complex HTEs: causal forest. Jawadekar et al. (Am J Epidemiol. 2023) introduce this innovative approach and offer practical guidelines for applied users. Building on their work, this commentary provides additional insights and guidance to promote the understanding and application of causal forest in epidemiologic research. We start with conceptual clarifications, differentiating between honesty and cross-fitting, and exploring the interpretation of estimated conditional average treatment effects. We then delve into the following practical considerations not addressed by Jawadekar et al., including motivations for estimating HTEs, calibration approaches, and ways to leverage causal forest output with examples from simulated data. We conclude by outlining challenges to consider for future advancements and applications of causal forest in epidemiological research.

Estimating the joint association of adverse childhood experiences and asthma with subsequent depressive symptoms: a marginal structural modelling approach.

BACKGROUND: The relationship between adverse childhood experiences (ACEs) and depression risk has been well documented. However, it remains unclear whether stress-related chronic conditions associated with ACEs, such as asthma, increase the long-term mental health burden of ACEs. OBJECTIVE: To investigate the joint association of ACEs and asthma with subsequent depressive symptoms among US adults. METHODS: This study used data from the Behavioural Risk Factor Surveillance System 2010, including 21 544 participants over 18 years old from four states where participants were questioned about ACEs. We used logistic regression models to calculate the adjusted OR (aOR) for elevated depressive symptoms evaluated by Patient Health Questionnaire-8 according to ACEs and asthma, along with marginal structural models (MSM) to consider ACE-related confounders between asthma and depression. We evaluated the additive interaction between ACEs and asthma on depressive symptoms with the relative excess risk due to interaction (RERI). FINDINGS: Of the 21 544 participants (mean age: 56, women: 59.5%), 52.3% reported ≥1 ACEs, 14.9% reported a history of asthma and 4.0% had depressive symptoms. ACEs and asthma were independently associated with elevated depressive symptoms (aORs (95% CI) were 2.85 (2.30 to 3.55) and 2.24 (1.50 to 3.27), respectively). Furthermore, our MSM revealed an additive interaction between ACEs and asthma for depressive symptoms (RERI (95% CI)=+1.63 (0.54 to 2.71)). CONCLUSIONS: These findings suggest that asthma amplifies the risk of depressive symptoms associated with ACEs. CLINICAL IMPLICATIONS: Prevention and treatment of asthma, along with establishing preventive environments and services against ACEs, are effective in mitigating the potential burden of ACEs on mental health.

Machine Learning Detects Heterogeneous Effects of Medicaid Coverage on Depression.

In 2008, Oregon expanded its Medicaid program using a lottery, creating a rare opportunity to study the effects of Medicaid coverage using a randomized controlled design (Oregon Health Insurance Experiment). Analysis showed that Medicaid coverage lowered the risk of depression. However, this effect may vary between individuals, and the identification of individuals likely to benefit the most has the potential to improve the effectiveness and efficiency of the Medicaid program. By applying the machine learning causal forest to data from this experiment, we found substantial heterogeneity in the effect of Medicaid coverage on depression; individuals with high predicted benefit were older and had more physical or mental health conditions at baseline. Expanding coverage to individuals with high predicted benefit generated greater reduction in depression prevalence than expanding to all eligible individuals (21.5 vs. 8.8 percentage point reduction; adjusted difference [95%CI], +12.7 [+4.6,+20.8]; P=0.003), at substantially lower cost per case prevented ($16,627 vs. $36,048; adjusted difference [95%CI], -$18,598 [-$156,953,-$3,120]; P=0.04). Medicaid coverage reduces depression substantially more in a subset of the population than others, in ways that are predictable in advance. Targeting coverage on those most likely to benefit could improve the effectiveness and efficiency of insurance expansion.

Measuring functional ability in Healthy Ageing: testing its validity using Japanese nationwide longitudinal data.

BACKGROUND: The United Nations Decade of Healthy Ageing 2021-2030 suggests nations should monitor functional ability as an indicator of healthy ageing progress. Functional ability is the attribute of people to do something they value and consists of five domains. We examined its validity in terms of a construct, cross-validation across multiple waves' data, and predictivity for subsequent well-being. METHODS: Using panel data from 35,093 community-dwelling adults aged ≥65 years from the Japan Gerontological Evaluation Study, we performed factor analyses to explore the construct of functional ability domains in both 2013 and 2016. A modified Poisson regression analysis was employed to test their associations with well-being (subjective health and happiness) in 2019. RESULTS: The mean age (standard deviation) of participants was 72.1 (5.0) years, and 52.0% were women. A total of 85.0% reported good subjective health, and 50.6% reported high happiness levels. Factor analyses with 31 logically checked candidate items from 2016 data suggested a three-factor model comprising 24 items, which were compatible with the 2013 data results. Based on the World Health Organization's original domains, we named domains as domain #1: ability to build and maintain relationships; domain #2: ability to meet basic needs + ability to move around and domain #3: ability to learn, grow and make decisions + ability to contribute. All three domains predicted both subjective health and happiness in 2019. CONCLUSIONS: Empirical data from Japan supports the functional ability concept among older individuals. Validating this concept with data from other nations is warranted.

Clinical Factors Affecting Daily Dosage of Desmopressin Orally Disintegrating Tablets in Arginine Vasopressin Deficiency.

CONTEXT: Desmopressin orally disintegrating tablets (ODTs) are widely used to treat arginine vasopressin deficiency (AVP-D). However, limited information is available on the dosage regimen; the dosage for each patient is selected based on their response to the initiation dose. OBJECTIVE: To investigate the relationships between clinical characteristics and the daily dose of ODTs and to identify factors that affect ODT dosages. METHODS: This retrospective study included 209 adult patients with AVP-D. Patients were administered ODTs sublingually and instructed to restrict eating and drinking for 30 minutes after taking ODTs using a patient leaflet. ODT dose titration was conducted during hospitalization with close monitoring of urine output, body weight, and serum sodium levels. Multivariable linear regression models were applied to identify clinical factors associated with the daily dose of ODTs at discharge. We also evaluated the dosage at 1 year in 134 patients who were followed up in our hospital. RESULTS: The median daily dose of ODTs at discharge was 90 µg (IQR 60-120 µg). Multivariable linear regression models identified sex, age, and estimated creatinine clearance (eCCr) as significant factors associated with the daily dose of ODTs, with eCCr having the strongest effect. After excluding patients recovering from AVP-D, 71% of those followed up at our hospital took the same daily dose at 1 year after discharge. CONCLUSION: To achieve the safe and stable treatment of AVP-D, the daily dose of ODT needs to be selected based on a patient's sex, age, and eCCr under appropriate sublingual administration by patient education.

Prevalence, Incidence, and Clinical Characteristics of Thyroid Eye Disease in Japan.

Background: Although thyroid eye disease (TED) can impact social and psychological well-being, the epidemiological evidence of TED is lacking in Japan. Methods: Nationwide claims databases provided by JMDC Inc. and Medical Data Vision Co., Ltd. and national population statistics are used. Three TED definitions ranging from a strict definition only including a TED diagnosis to a broad definition including a TED diagnosis and considering ocular symptoms are considered. The proportion of patients by severity and disease activity are estimated based on definitions that would allow identification of those patients within the claims data. Results: The incidence rate per 100 000 person-years ranged from 7.3 to 11.1 for the strict and broad TED definitions, respectively. For fiscal year 2020 (April 2020 to March 2021) the prevalence rate ranged between 24.65 (strict TED) and 37.58 (broad TED) per 100 000 persons. These correspond to 25 383 and 38 697 patients for the strict and broad TED definitions, respectively. Regardless of the definition used, a predominance of female patients was observed, and the highest burden of the disease was seen in the age group of 35 to 59. Mild and inactive forms of TED were predominant (about 85% and 74%, respectively). Conclusion: The incidence and prevalence of TED in Japan were 7.3 to 11.1 per 100 000 person-years and 24.65 to 37.58 per 100 000 persons, respectively. The robust results of this database study add valuable real-world evidence on the incidence and prevalence of TED in Japan.

Identifying primary aldosteronism patients who require adrenal venous sampling: a multi-center study.

Adrenal venous sampling (AVS) is crucial for subtyping primary aldosteronism (PA) to explore the possibility of curing hypertension. Because AVS availability is limited, efforts have been made to develop strategies to bypass it. However, it has so far proven unsuccessful in applying clinical practice, partly due to heterogeneity and missing values of the cohorts. For this purpose, we retrospectively assessed 210 PA cases from three institutions where segment-selective AVS, which is more accurate and sensitive for detecting PA cases with surgical indications, was available. A machine learning-based classification model featuring a new cross-center domain adaptation capability was developed. The model identified 102 patients with PA who benefited from surgery in the present cohort. A new data imputation technique was used to address cross-center heterogeneity, making a common prediction model applicable across multiple cohorts. Logistic regression demonstrated higher accuracy than Random Forest and Deep Learning [(0.89, 0.86) vs. (0.84, 0.84), (0.82, 0.84) for surgical or medical indications in terms of f-score]. A derived integrated flowchart revealed that 35.2% of PA cases required AVS with 94.1% accuracy. The present model enabled us to reduce the burden of AVS on patients who would benefit the most.

Kinematic analysis of damaged capsulolabral structure in patients with anterior shoulder instability using cine-magnetic resonance imaging.

Background: We assessed damaged anterior capsulolabral motion during axial shoulder rotation in patients with anterior shoulder instability. Methods: Twenty-nine shoulders of 28 patients with anterior shoulder instability who underwent cine-magnetic resonance imaging during axial rotation of the adducted arm were included. The motion was captured after an intra-articular injection of saline solution (10-20 mL). During imaging, the shoulder was rotated passively from maximum internal rotation to maximum external rotation in the first 10 s and then back to maximum internal rotation in the subsequent 10 s. We assessed the rotational angles of the damaged labrum during compressing and pulling the humeral head against the glenoid. Evaluation of the rotational angles was performed on a series of axial images through the humeral head center. Results: The mean angles that damaged labrum compressed and pulled off against the glenoid were 12.0 ± 19.1° and 2.8 ± 21.2°, respectively. Additionally, seven of the 29 shoulders showed that the damaged labrum compressed on the glenoid rim before the rotational angle exceeded 0° during external rotation. In 13 shoulders, the damaged labrum could remain repositioned on the glenoid rim over the neutral position during internal rotation. In two shoulders, the damaged labrum was not compressed against the glenoid at the maximum external rotation. The injected saline moved from the posterior to the anterior side of the glenohumeral joint during internal rotation in each shoulder. Conclusion: The damaged labrum could be positioned on the glenoid when the arm was in a traditional internal immobilization.

Urinary cortisol and cardiovascular events in women vs. men: The multi-ethnic study of atherosclerosis.

Research suggests that women experience greater cardiovascular ischemic effects from stress than men. Visceral adiposity is an endocrine tissue that differs by sex and interacts with stress hormones. We hypothesized that urinary cortisol would be associated with increased cardiovascular events and change in coronary artery calcium score (CAC) in women, and these relationships would vary by central obesity. In the Multi-Ethnic Study of Atherosclerosis Stress Ancillary study, cortisol was quantified by 12-h overnight urine collection. Central obesity was estimated by waist-hip ratio (WHR). Multivariable Cox models estimated the relationship between cortisol and cardiovascular events and assessed for moderation by WHR. The relationship between cortisol and change in CAC Agatston score was assessed by Tobit regression models. 918 patients were analyzed with median follow up of 11 years. There was no association between urinary cortisol and cardiovascular events in the cohort. However, in individuals with below median WHR, higher urinary cortisol levels (upper tertile) were associated with higher cardiovascular event rates in the full cohort, women, and men, but not in groups with above median WHR. There was significant moderation by WHR in women, but not men, whereby the association between elevated cortisol and increased cardiovascular events diminished as WHR increased. Urinary cortisol was associated with increased change in CAC in women (P = 0.003) but not men, without moderation by WHR. Our study highlights associations between cortisol and subclinical atherosclerosis in women, and moderation of the relationship between cortisol and cardiovascular events by central obesity in both genders.

Iodine-Induced Hypothyroidism and Long-Term Risks of Incident Heart Failure.

Background Although most individuals can adapt to a large iodine load and remain euthyroid, hypothyroidism can develop after iodine exposure. Hypothyroidism is associated with adverse cardiovascular consequences, including heart failure. This study was performed to investigate the relationships between iodine-induced hypothyroidism and incident heart failure. Methods and Results This cohort study of the US Veterans Health Administration (1998-2021) included adults aged ≥18 years with a serum thyroid-stimulating hormone (thyrotropin) <60 days of iodine contrast administration, and <1 year of a baseline normal serum thyroid-stimulating hormone. Cox proportional hazards regression ascertained risk of incident heart failure following iodine-induced hypothyroidism, adjusting for age, sex, race and ethnicity, body mass index, and history of coronary heart disease, dyslipidemia, diabetes, and hypertension. Of 45 470 veterans (mean±SD age, 61.1±14.1 years; 88% men), 3361 (7.4%) developed iodine-induced hypothyroidism. Heart failure developed in 5685 (12.5%) individuals over a median follow-up of 3.6 years (interquartile range, 1.9-7.2 years). Adjusted for risk factors, iodine-induced hypothyroidism was associated with increased risk of heart failure, compared with those who remained euthyroid after iodine exposure (adjusted hazard ratio [HR], 1.11 [95% CI, 1.01-1.22]). Women were at greater risk than men (adjusted HR: women, 1.65 [95% CI, 1.13-2.40]; men, 1.08 [95% CI, 0.98-1.19]; P for interaction, 0.02). Conclusions In the largest US study of this topic, hypothyroidism following iodine exposure was associated with an increased risk of incident heart failure, particularly in women. These findings support the need for further research to address the clinical significance of this issue, including the possible sex-specific risks of incident heart failure in more diverse data sets and study populations.

Incidence and risk factors for Graves' orbitopathy in patients who underwent anti-inflammatory and immunosuppressive treatment during medical treatment for Graves' disease: investigation of 1,553 cases with newly diagnosed Graves' disease and proposal of a predictive score.

Appropriate administration of anti-inflammatory and immunosuppressive treatment (AIIST) is important for patients with Graves' orbitopathy (GO). This study aimed to clarify the incidence and risk factors for GO treated with AIIST and propose a predictive score, among newly diagnosed Graves' disease (GD) patients in Japan. A total of 1,553 GD patients who were newly diagnosed during the year 2011 were investigated. AIIST included local and/or systemic glucocorticoid administration and retrobulbar irradiation. A multivariable Cox proportional hazards model was used to investigate the risk factors for GO underwent AIIST during medical treatment, including at diagnosis, of GD. Then, a GO score was created by summing each point assigned to risk factors based on their coefficient obtained in the Cox model. AIIST was administered to 107 patients (6.9%). The risk factors and hazard ratios for GO underwent AIIST were: age (per 10 years), 1.32 (95% confidence interval: 1.16-1.50), p < 0.0001; TSH binding inhibitory immunoglobulin (TBII) (per 10 IU/L), 1.33 (1.15-1.54), p = 0.0001; and thyroglobulin antibody (TgAb) negativity, 2.98 (1.96-4.59), p < 0.0001. The GO score, ranging from 0 to 8 points, showed moderate performance (area under the curve: 0.71, cut-off value: 5 points, sensitivity: 0.76, specificity: 0.59, positive predictive value: 0.12, negative predictive value: 0.97). AIIST was performed for patients with active manifestations of GO in 6.9% of newly diagnosed GD patients. The risk factors for GO underwent AIIST were higher age, higher TBII, and TgAb negativity. The GO score based on these factors may be useful in managing GO.

Per- and polyfluoroalkyl substances and sleep health in U.S. adults, NHANES 2005-2014.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that induce oxidative inflammatory responses and disrupt the endocrine and central nervous systems, all of which can influence sleep. OBJECTIVE: To investigate the association between PFAS exposure and sleep health measures in U.S. adults. METHODS: We analyzed serum concentration data of four PFAS [perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)] reported for 8913 adults in NHANES 2005-2014. Sleep outcomes, including trouble sleeping, having a diagnosis of sleep disorder, and recent daily sleep duration classified as insufficient or excessive sleep (<6 or >9 h/day) were examined. Weighted logistic regression was used to estimate the association between the sleep outcomes and each PFAS modeled continuously (log2) or in exposure tertiles. We applied quantile g-computation to estimate the effect of the four PFAS as a mixture on the sleep outcomes. We conducted a quantitative bias analysis to assess the potential influence of self-selection and uncontrolled confounding. RESULTS: We observed some inverse associations between serum PFAS and trouble sleeping or sleep disorder, which were more consistent for PFOS (e.g., per log2-PFOS (ng/ml) and trouble sleeping OR = 0.93, 95%CI: 0.89, 0.98; sleep disorder OR = 0.89, 95%CI: 0.83, 0.95). Per quartile increase of the PFAS mixture was inversely associated with trouble sleeping and sleep disorder. No consistent associations were found for sleep duration across analyses. Our bias analysis suggests that the finding on sleep disorder could be explained by a moderate level of self-selection and negative confounding effects. CONCLUSIONS: We found no evidence to suggest exposure to four legacy PFAS worsened self-reported sleep health among U.S. adults. While some inverse associations between specific PFAS and sleep disorder were observed, self-selection and uncontrolled confounding biases may play a role in these findings.

The effect of poverty on the relationship between household education levels and obesity in U.S. children and adolescents: an observational study.

Background: Although ample evidence has shown the link between childhood obesity and socioeconomic status including family income and household education levels, the mediating role of poverty in the association between household education levels and childhood obesity is unclear. This study aimed to quantify the extent to which family poverty levels contribute to the association between household education levels and obesity among US children and adolescents. Methods: This cohort study used the nationally representative data of 21,754 US children and adolescents aged 6-17 years (National Health and Nutrition Examination Survey 1999-2018). We applied mediation analysis of the association between household education levels (less than high school, high school, and college or above) and obesity mediated through poverty (≤138% vs. >138% federal poverty level), adjusting for demographic characteristics of household head and their offspring. Obesity was defined as age- and sex-specific body mass index in the 95th percentile or greater using the 2000 Centers for Disease Control and Prevention growth charts. Findings: Among 21,754 children and adolescents (weighted N = 43,544,684; mean age, 11.6 years; female, 49%), 9720 (weighted percentage, 33.0%) were classified as living in poverty and 4671 (weighted percentage, 19.1%) met the criteria for obesity. Low household education level (less than high school) showed increased risks of poverty (adjusted relative risk [95% CI], 5.82 [4.90-6.91]) and obesity (adjusted relative risk [95% CI], 1.94 [1.68-2.25]) compared to high household education level (college or above). We also quantified that poverty mediated 18.9% of the association between household education levels and obesity among children and adolescents. The mediation effect was consistently observed across age, gender, and race/ethnicity. Interpretation: Poverty mediated the association between the low educational status of household heads and their offspring's obesity. Our findings highlight the importance of reducing obesity risk among the low-income population to minimize the burden of intergenerational health disparities due to socioeconomic status. Funding: Japan Society for the Promotion of Sciences (22K17392).

Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models.

A complete resection of tongue cancer is often difficult. We investigate the usefulness of administering G47Δ (teserpaturev), a triple-mutated oncolytic herpes simplex virus type 1, prior to resection. G47Δ exhibits good cytopathic effects and replication capabilities in all head and neck cancer cell lines tested. In an orthotopic SCCVII tongue cancer model of C3H/He mice, an intratumoral inoculation with G47Δ significantly prolongs the survival. Further, mice with orthotopic tongue cancer received neoadjuvant G47Δ (or mock) therapy with or without "hemilateral" resection, the maximum extent avoiding surgical deaths. Neoadjuvant G47Δ and resection led to 10/10 survival (120 days), whereas the survivals for G47Δ alone and resection alone were 6/10 and 5/10, respectively: all control animals died by day 11. Furthermore, 100% survival was achieved with neoadjuvant G47Δ therapy even when the resection area was narrowed to "partial," providing insufficient resection margins, whereas hemilateral resection alone caused death by local recurrence in half of the animals. G47Δ therapy caused increased number of tumor-infiltrating CD8+ and CD4+ cells, increased F4/80+ cells within the residual tongues, and increased expression of immune-related genes in and around the tumor. These results imply that neoadjuvant use of G47Δ is useful for preventing local recurrence after tongue cancer surgery.