Postoperative delirium (POD) is associated with complications following cardiovascular surgery, and its psychomotor subtypes differ in clinical course and treatment responsiveness, underscoring the importance of personalized preventive strategies. We aimed to investigate preoperative neurophysiological characteristics associated with POD and its psychomotor subtypes in patients undergoing cardiovascular surgery. This prospective, single-center study included 209 patients undergoing cardiovascular surgery. Preoperative frontal electroencephalography (EEG) was recorded using a patch-type device with three electrodes (left, center, and right). Standardized mean power spectral density of the following frequency bands was calculated: theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz), gamma1 (30-59 Hz), and gamma2 (61-75 Hz). Delirium and its psychomotor subtypes were assessed until postoperative day 7. EEG features were compared between patients with and without POD and among psychomotor subtypes, with adjustment for multiple comparisons. POD occurred in 70 patients (33.5%). No significant differences in preoperative EEG power were observed between patients with and without POD. However, patients with the hyperactive-or-mixed subtype demonstrated significantly higher theta and lower alpha activity than those with the hypoactive or no motor subtypes. These findings may identify neurophysiological markers associated with underlying psychomotor symptoms in delirium and may inform preoperative subtype risk stratification.Trial registration: UMIN-CTR (ID: UMIN000049390).

Introduction:Energy-based therapies for genitourinary syndrome of menopause (GSM) remain controversial, and evidence for vaginal high-intensity focused ultrasound (HIFU) is limited. The aim of this study was to evaluate the safety and exploratory efficacy of vaginal HIFU in women with GSM. Methods:In this prospective, single-arm, exploratory study, women with GSM underwent vaginal HIFU and were followed for 24 weeks. Women with prior gynecologic surgery or treated malignancy were eligible if ≥6 months had elapsed and clinical stability was confirmed. Patient-reported outcomes included visual analog scale (VAS) scores for GSM symptoms, the Vulvovaginal Symptoms Questionnaire (VSQ), the Female Sexual Function Index (FSFI), and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Objective measures included the Vaginal Health Index (VHI), vaginal pressure, pelvic organ prolapse quantification, vaginal pH, and vaginal microbiome profiling. The primary endpoint was the percent change from baseline to 12 weeks in the VAS score of the participant-identified most bothersome GSM symptom. Results:Eighteen women comprised the full analysis set. The primary endpoint showed a reduction in symptom severity (mean percent change -67.7%; 95% confidence interval [CI], -87.6% to -47.7%). Individual VAS scores decreased over time and were generally maintained throughout follow-up. The VSQ improved at 24 weeks (-40.4%; 95% CI, -64.6% to -16.2%), and the ICIQ-SF improved at 12 weeks (-29.0%; 95% CI, -54.6% to -3.4%), although this improvement was not sustained at 24 weeks. Total FSFI scores did not change. Improvements were observed in VHI and vaginal pressure, while vaginal pH and microbiome composition remained stable. No Grade ≥3 adverse events occurred. Discussion:In this exploratory study, vaginal HIFU was associated with improvements in the most bothersome GSM symptom and selected objective measures without serious adverse events. However, given its single-arm design and small sample size, no definitive conclusions regarding its efficacy or safety can be drawn, and further studies are needed to elucidate the mechanisms of action, optimize treatment parameters, characterize the safety profile, and determine the clinical utility of vaginal HIFU.

Objective: Adult-type granulosa cell tumors of the ovary (aGCTs) show ambiguous morphology and may be misdiagnosed as other tumors. Recently, heterozygous FOXL2 C402G mutations and TERT promoter C228T mutation have been reported as diagnostic and prognostic biomarkers of aGCTs. The objective of this study was to identify the characteristics of true aGCT cohort using these biomarkers in 72 aGCT samples. Methods: FOXL2 and TERT promoter mutational statuses of 64 primary and matched 8 recurrent aGCT samples were assessed. Non-aGCTs were excluded by the combination of FOXL2 mutational analysis and the pathological review. The characteristics and prognosis of molecularly/pathologically confirmed aGCTs (MP-aGCTs) were analyzed. Results: Of 18 FOXL2 wild-type (WT) tumors, 3 were excluded as they were of other histotype. None of 20 samples with the FOXL2 C402G mutation include other histotype. Clinical stage and age were prognostic factors for recurrence. Of the 61 MP-aGCTs, 46 harbored FOXL2 C402G mutation (44 heterozygous, 2 homozygous/hemizygous) and 15 had WT FOXL2. The presence of the FOXL2 mutation was associated with a worse prognosis. The mutational status of the TERT promoter in MP-aGCTs was 10 heterozygous and 51 WT. The TERT promoter mutation was highly identified in older patients and in larger tumors but had no prognostic impact. Conclusion: This is the first study to clearly demonstrate its practical application of FOXL2 in the diagnosis of aGCTs. Application of the molecular analysis to a large aGCT cohort is crucial for understanding true characteristics and establishing novel treatment strategy of this disease.

Pregnant women with Graves' disease (GD) who have undergone thyroidectomy or radioactive iodine therapy can have high levels of thyroid-stimulating hormone (TSH) receptor antibodies, which are transferred to the fetus via the placenta, posing a risk for fetal GD. This retrospective observational study, conducted at two high-level perinatal medical centers in Tokyo and Osaka, Japan, aimed to identify predictors of fetal GD in pregnant women with GD who had undergone thyroidectomy or radioactive iodine therapy. In total, 65 women were included, and 79 singleton pregnancies and fetuses were analyzed. Fetal GD occurred in 17.7% of the 79 fetuses. Women in the fetal GD group had higher levels of TSH receptor antibodies and a higher prevalence of ophthalmopathies than did women in the non-fetal GD group. The receiver operating characteristic curve cutoff values of maternal TSH-binding inhibitory immunoglobulin (hereafter referred to as TRAb [TSH receptor antibody from a narrow perspective]) and thyroid-stimulating antibody (TSAb) levels predictive of fetal GD development were as follows: TRAb, 12.8 and 10.2 IU/L at 10 and 20 gestational weeks (GW), respectively; TSAb, 975.4% and 1,259.0% at 10 and 20 GW, respectively. Ophthalmopathy was a predictor of fetal GD; nonetheless, combining the ophthalmopathy and TRAb cutoff values did not improve predictive accuracy. A cutoff value of TRAb ≥10.2 IU/L at 20 GW (highest diagnostic accuracy found) could be a predictor of fetal GD risk for pregnant women with GD who undergo thyroidectomy or radioactive iodine therapy; thus, appropriate fetal monitoring should begin at around 20 GW.

AIM:The present study aimed to estimate the total numbers of obstetric diseases diagnosed, total amounts of medical expenses claimed for obstetric diseases, their averages per livebirth, and yearly trends in Japan. METHODS:This is a secondary analysis of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) (data from 2015 to 2019). The target population was women of reproductive age (15-49 years old) with diseases in pregnancy, childbirth, and the puerperium, defined by having O codes according to the International Classification of Diseases 10th Revision. We calculated the numbers of obstetric diseases diagnosed, amounts of medical expenses claimed for obstetric diseases marked with the "main injury/disease decision flag," and the totals divided by the annual numbers of livebirths, by year and women's age group. RESULTS:From 2015 to 2019, both the numbers of obstetric diseases diagnosed and amounts of medical expenses claimed for obstetric diseases per livebirth were on an upward trend, whereas the total numbers of obstetric diseases diagnosed were decreased. Women in advanced age groups had a higher number of diagnoses and a higher amount of medical expenses for obstetric diseases per livebirth. "Preterm labour without delivery" had the highest amounts of medical expenses claimed for and the second highest numbers of diagnoses throughout the study period. CONCLUSIONS:This study suggests that pregnant women in Japan would have an increasing number of obstetric complications and necessary medical expenses year by year. Further study is warranted to elucidate these trends and identify possible mitigation measures.

Evidence regarding chemosensitivity to different therapeutic regimens in epithelial ovarian cancer (EOC) remains limited. This study aimed to investigate EOC implementation in daily clinical practice and reveal favorable regimens for EOC among Japanese patients. We retrospectively collected clinical data of patients newly diagnosed with EOC from 2012 to 2021 at our affiliated institutions. We evaluated overall survival (OS) and progression-free survival (PFS) of conventional paclitaxel plus carboplatin (TC) vs. dose-dense TC (ddTC) according to the eligibility of GOG262 and JGOG3016 and those with bevacizumab (BEV) vs. without BEV based on GOG218. Further, we evaluated OS and PFS of ddTC and ddTC + BEV to TC + BEV among patients with stage III/IV. The ddTC group (n = 402) demonstrated longer PFS and OS than the TC group (n = 165) (adjusted hazard ratios [aHRs] [95

Associations between delirium and postoperative adverse events in cardiovascular surgery have been reported and the preoperative identification of high-risk patients of delirium is needed to implement focused interventions. We aimed to develop and validate machine learning models to predict post-cardiovascular surgery delirium. Patients aged ≥ 40 years who underwent cardiovascular surgery at a single hospital were prospectively enrolled. Preoperative and intraoperative factors were assessed. Each patient was evaluated for postoperative delirium 7 days after surgery. We developed machine learning models using the Bernoulli naive Bayes, Support vector machine, Random forest, Extra-trees, and XGBoost algorithms. Stratified fivefold cross-validation was performed for each developed model. Of the 87 patients, 24 (27.6%) developed postoperative delirium. Age, use of psychotropic drugs, cognitive function (Mini-Cog < 4), index of activities of daily living (Barthel Index < 100), history of stroke or cerebral hemorrhage, and eGFR (estimated glomerular filtration rate) < 60 were selected to develop delirium prediction models. The Extra-trees model had the best area under the receiver operating characteristic curve (0.76 [standard deviation 0.11]; sensitivity: 0.63; specificity: 0.78). XGBoost showed the highest sensitivity (AUROC, 0.75 [0.07]; sensitivity: 0.67; specificity: 0.79). Machine learning algorithms could predict post-cardiovascular delirium using preoperative data. Trial registration: UMIN-CTR (ID; UMIN000049390).

Background. Peer learning has been recognized for its effectiveness in health professional education. However, its effects on clinical research education are not clear and were explored qualitatively in this study. Methods. The peer-learning method was implemented in a clinical research education seminar for early-career physicians at a children’s and mothers’ hospital in 2019. We conducted semistructured interviews with participants about peer-learning experience and qualitatively analyzed verbatim transcripts using Engeström’s “activity theory” framework. Results. From framework analysis, learning processes were extracted mainly in four domains, namely, (a) instrument and its usage: research design and its match with research question, (b) outcome: research result, (c) community: seminar, and (d) division of labor: roles of participants and staff. Conclusions. In this report of a peer-learning trial in postgraduate clinical research education, the following two pathways of peer-learning effects were abstracted. The indirect pathway was the presentations by experienced participants providing concrete examples of research processes. The direct pathway was the questions from experienced participants to beginners about specific and concrete questions. There were also two points to consider in peer learning in clinical research education: gaps in premise knowledge and beginners’ frustration about expected outcomes. We believe that these extracted pathways and points imply the significance and considerations for continuing the peer-learning trial in clinical research education. Future tasks are to promote clinical research education with a view to the learning effects, not only on individuals, but also on groups.

Background:Fetal growth restriction is associated with perinatal morbidity and mortality. Early identification of women having at-risk fetuses can reduce perinatal adverse outcomes. Objectives:To assess the predictive performance of existing models predicting fetal growth restriction and birthweight, and if needed, to develop and validate new multivariable models using individual participant data. Design:Individual participant data meta-analyses of cohorts in International Prediction of Pregnancy Complications network, decision curve analysis and health economics analysis. Participants:Pregnant women at booking. External validation of existing models (9 cohorts, 441,415 pregnancies); International Prediction of Pregnancy Complications model development and validation (4 cohorts, 237,228 pregnancies). Predictors:Maternal clinical characteristics, biochemical and ultrasound markers. Primary outcomes:fetal growth restriction defined as birthweight <10th centile adjusted for gestational age and with stillbirth, neonatal death or delivery before 32 weeks' gestation birthweight. Analysis:First, we externally validated existing models using individual participant data meta-analysis. If needed, we developed and validated new International Prediction of Pregnancy Complications models using random-intercept regression models with backward elimination for variable selection and undertook internal-external cross-validation. We estimated the study-specific performance (c-statistic, calibration slope, calibration-in-the-large) for each model and pooled using random-effects meta-analysis. Heterogeneity was quantified using τ2 and 95% prediction intervals. We assessed the clinical utility of the fetal growth restriction model using decision curve analysis, and health economics analysis based on National Institute for Health and Care Excellence 2008 model. Results:Of the 119 published models, one birthweight model (Poon) could be validated. None reported fetal growth restriction using our definition. Across all cohorts, the Poon model had good summary calibration slope of 0.93 (95% confidence interval 0.90 to 0.96) with slight overfitting, and underpredicted birthweight by 90.4 g on average (95% confidence interval 37.9 g to 142.9 g). The newly developed International Prediction of Pregnancy Complications-fetal growth restriction model included maternal age, height, parity, smoking status, ethnicity, and any history of hypertension, pre-eclampsia, previous stillbirth or small for gestational age baby and gestational age at delivery. This allowed predictions conditional on a range of assumed gestational ages at delivery. The pooled apparent c-statistic and calibration were 0.96 (95% confidence interval 0.51 to 1.0), and 0.95 (95% confidence interval 0.67 to 1.23), respectively. The model showed positive net benefit for predicted probability thresholds between 1% and 90%. In addition to the predictors in the International Prediction of Pregnancy Complications-fetal growth restriction model, the International Prediction of Pregnancy Complications-birthweight model included maternal weight, history of diabetes and mode of conception. Average calibration slope across cohorts in the internal-external cross-validation was 1.00 (95% confidence interval 0.78 to 1.23) with no evidence of overfitting. Birthweight was underestimated by 9.7 g on average (95% confidence interval -154.3 g to 173.8 g). Limitations:We could not externally validate most of the published models due to variations in the definitions of outcomes. Internal-external cross-validation of our International Prediction of Pregnancy Complications-fetal growth restriction model was limited by the paucity of events in the included cohorts. The economic evaluation using the published National Institute for Health and Care Excellence 2008 model may not reflect current practice, and full economic evaluation was not possible due to paucity of data. Future work:International Prediction of Pregnancy Complications models' performance needs to be assessed in routine practice, and their impact on decision-making and clinical outcomes needs evaluation. Conclusion:The International Prediction of Pregnancy Complications-fetal growth restriction and International Prediction of Pregnancy Complications-birthweight models accurately predict fetal growth restriction and birthweight for various assumed gestational ages at delivery. These can be used to stratify the risk status at booking, plan monitoring and management. Study registration:This study is registered as PROSPERO CRD42019135045. Funding:This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/148/07) and is published in full in Health Technology Assessment; Vol. 28, No. 14. See the NIHR Funding and Awards website for further award information.

Objective To predict birth weight at various potential gestational ages of delivery based on data routinely available at the first antenatal visit.Design Individual participant data meta-analysis.Data sources Individual participant data of four cohorts (237 228 pregnancies) from the International Prediction of Pregnancy Complications (IPPIC) network dataset.Eligibility criteria for selecting studies Studies in the IPPIC network were identified by searching major databases for studies reporting risk factors for adverse pregnancy outcomes, such as pre-eclampsia, fetal growth restriction, and stillbirth, from database inception to August 2019. Data of four IPPIC cohorts (237 228 pregnancies) from the US (National Institute of Child Health and Human Development, 2018; 233 483 pregnancies), UK (Allen et al, 2017; 1045 pregnancies), Norway (STORK Groruddalen research programme, 2010; 823 pregnancies), and Australia (Rumbold et al, 2006; 1877 pregnancies) were included in the development of the model.Results The IPPIC birth weight model was developed with random intercept regression models with backward elimination for variable selection. Internal-external cross validation was performed to assess the study specific and pooled performance of the model, reported as calibration slope, calibration-in-the-large, and observed versus expected average birth weight ratio. Meta-analysis showed that the apparent performance of the model had good calibration (calibration slope 0.99, 95% confidence interval (CI) 0.88 to 1.10; calibration-in-the-large 44.5 g, -18.4 to 107.3) with an observed versus expected average birth weight ratio of 1.02 (95% CI 0.97 to 1.07). The proportion of variation in birth weight explained by the model (R2) was 46.9% (range 32.7-56.1% in each cohort). On internal-external cross validation, the model showed good calibration and predictive performance when validated in three cohorts with a calibration slope of 0.90 (Allen cohort), 1.04 (STORK Groruddalen cohort), and 1.07 (Rumbold cohort), calibration-in-the-large of -22.3 g (Allen cohort), -33.42 (Rumbold cohort), and 86.4 g (STORK Groruddalen cohort), and observed versus expected ratio of 0.99 (Rumbold cohort), 1.00 (Allen cohort), and 1.03 (STORK Groruddalen cohort); respective pooled estimates were 1.00 (95% CI 0.78 to 1.23; calibration slope), 9.7 g (-154.3 to 173.8; calibration-in-the-large), and 1.00 (0.94 to 1.07; observed v expected ratio). The model predictions were more accurate (smaller mean square error) in the lower end of predicted birth weight, which is important in informing clinical decision making.Conclusions The IPPIC birth weight model allowed birth weight predictions for a range of possible gestational ages. The model explained about 50% of individual variation in birth weights, was well calibrated (especially in babies at high risk of fetal growth restriction and its complications), and showed promising performance in four different populations included in the individual participant data meta-analysis. Further research to examine the generalisability of performance in other countries, settings, and subgroups is required.Trial registration PROSPERO CRD42019135045

Introduction:coronavirus disease 2019 (COVID-19) transmission dynamics in the communities of low- and middle-income countries, particularly sub-Saharan African countries, are still not fully understood. This study aimed to determine the characteristics of COVID-19 secondary transmission during the first wave of the epidemic (March-October 2020) in Lusaka, Zambia. Methods:we conducted an observational study on COVID-19 secondary transmission among residents in Lusaka City, between March 18 and October 30, 2020. We compared the secondary attack rate (SAR) among different environmental settings of contacts and characteristics of primary cases (e.g, demographics, medical conditions) by logistic regression analysis. Results:out of 1862 confirmed cases of COVID-19, 272 primary cases generated 422 secondary cases through 216 secondary transmission events. More contacts and secondary transmissions were reported in planned residential areas than in unplanned residential areas. Households were the most common environmental settings of secondary transmission, representing 76.4% (165/216) of secondary transmission events. The SAR in households was higher than the overall events. None of the environmental settings or host factors of primary cases showed a statistically significant relationship with SAR. Conclusion:of the settings considered, households had the highest incidence of secondary transmission during the first wave in Lusaka, Zambia. The smaller proportion of contacts and secondary transmission in unplanned residential areas might have been due to underreporting of cases, given that those areas are reported to be vulnerable to infectious disease outbreaks. Continuous efforts are warranted to establish measures to suppress COVID-19 transmission in those high-risk environments.

IntroductionThere is still controversy or a lack of evidence regarding the efficacy of dose-dense paclitaxel plus carboplatin (ddTC) and bevacizumab (BEV) for epithelial ovarian cancer (EOC) among Japanese and Westerners. We aimed to compare the survival outcomes between conventional paclitaxel plus carboplatin (TC) with BEV and ddTC with or without BEV among Japanese.MethodsWe retrospectively analyzed the data from patients newly diagnosed with EOC between 2012 and 2021 at our institutions. The target population was patients with stage III and IV EOC except for poly (adenosine diphosphate-ribose) polymerase inhibitors users. Overall survival (OS) and progression-free survival (PFS) of patients treated with ddTC and ddTC with BEV (ddTC+BEV) were compared to those of patients treated with TC with BEV (TC+BEV). We used Cox proportional hazard models adjusted for patients’ backgrounds.ResultsThere were 75, 259, and 117 patients treated with TC+BEV, ddTC, and ddTC+BEV, respectively. The three groups had similar backgrounds such as histopathology and staging. For PFS, adjusted hazard ratios (aHRs) [95% confidence intervals (95%CIs)] were 1.09 [0.79, 1.50] in ddTC and 0.74 [0.52, 1.08] in ddTC+BEV compared to TC+BEV. For OS, aHRs (95%CIs) were 0.89 [0.59, 1.34] in ddTC and 0.73 [0.50, 1.05] in ddTC+BEV compared to TC+BEV.Conclusion/ImplicationsWe previously confirmed that ddTC was associated with favorable PFS and OS, and BEV could prolong PFS using the data from 1333 EOC patients at our institution. The present study further suggested that ddTC+BEV had favorable survival outcomes and might be a candidate for a clinical trial.

Introduction:Postoperative delirium (POD) is common and life-threatening, however, with intensive interventions, a potentially preventable clinical syndrome. Although electroencephalography (EEG) is a promising biomarker of delirium, standard 20-leads EEG holds difficulties for screening usage in clinical practice.Objective:We aimed to develop an accurate algorithm to predict POD using EEG data obtained from portable device.Methods:We recruited 128 patients who underwent scheduled cardiovascular surgery. Cognitive function assessments were conducted, and portable EEG recordings were obtained prior to surgery.Results:Among the patients, 47 (36.7%) patients with POD were identified and they did not significantly differ from patients without POD in sex ratio, age, cognitive function, or treatment duration of intensive care unit. However, significant differences were observed in the preoperative EEG power spectrum densities at various frequencies, especially gamma activity, between patients with and without POD. POD was successfully predicted using preoperative EEG data with a machine learning algorithm, yielding accuracy of 86% and area under the receiver operating characteristic curve of 0.93.Discussion:This study provides new insights into the objective and biological vulnerability to delirium. The developed algorithm can be applied in general hospitals without advanced equipment and expertise, thereby enabling the reduction of POD occurrences with intensive interventions for high-risk patients.

We retrospectively analyzed spatial factors for coronavirus disease 2019 (COVID-19)-associated community deaths i.e., brought-in-dead (BID) in Lusaka, Zambia, between March and July 2020. A total of 127 cases of BID with geocoordinate data of their houses were identified during the study period. Median interquartile range (IQR) of the age of these cases was 49 (34-70) years old, and 47 cases (37.0%) were elderly individuals over 60 years old. Seventy-five cases (75%) of BID were identified in July 2020, when the total number of cases and deaths was largest in Zambia. Among those whose information regarding their underlying medical condition was available, hypertension was most common (22.9%, 8/35). Among Lusaka’s 94 townships, the numbers (median, IQR) of cases were significantly larger in those characterized as unplanned residential areas compared to planned areas (1.0, 0.0-4.0 vs 0.0, 0.0-1.0; p=0.030). The proportion of individuals who require more than 30 minutes to obtain water was correlated with a larger number of BID cases per 105 population in each township (rho=0.28, p=0.006). The number of BID cases was larger in unplanned residential areas, which highlighted the importance of targeted public health interventions specifically to those areas to reduce the total number of COVID-19 associated community deaths in Lusaka. Brought-in-dead surveillance might be beneficial in monitoring epidemic conditions of COVID-19 in such high-risk areas. Furthermore, inadequate access to water, sanitation, and hygiene (WASH) might be associated with such distinct geographical distributions of COVID-19 associated community deaths in Lusaka, Zambia.

Background Although prevalence of low birth weight has increased in the last 3 decades in Japan, no studies in Japanese women have investigated whether birth weight is associated with the risk of pregnancy complications, such as pregnancy-induced hypertension (PIH) and gestational diabetes mellitus (GDM). Methods We used data from the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT), a population-based cohort study in Japan that launched in 2011. In the main analysis, we included 46,365 women who had been pregnant at least once, for whom information on birth weight and events during their pregnancy was obtained using a self-administered questionnaire. Women were divided into five categories according to their birth weight, and the relationship between birth weight and risk of PIH and GDM was examined using multilevel logistic regression analyses with place of residence as a random effect. Results Compared to women born with birth weight of 3,000–3,999 grams, the risk of PIH was significantly higher among women born <1,500 grams (adjusted odd ratio [aOR] 1.60; 95% confidence interval [CI], 1.17–2.21), 1,500–2,499 grams (aOR 1.16; 95% CI, 1.03–1.30), and 2,500–2,999 grams (aOR 1.13; 95% CI, 1.04–1.22). The risk of GDM was significantly higher among women born 1,500–2,499 grams (aOR 1.20; 95% CI, 1.02–1.42), albeit non-significant association among women in other birthweight categories. Conclusions We observed an increased risk of PIH among women born with lower birth weight albeit non-significant increased risk of GDM among Japanese women.

Background Health-care needs change throughout the life course. It is thus crucial to assess whether health systems provide access to quality health care for all ages. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019), we measured the Healthcare Access and Quality (HAQ) Index overall and for select age groups in 204 locations from 1990 to 2019. Methods We distinguished the overall HAQ Index (ages 0-74 years) from scores for select age groups: the young (ages 0-14 years), working (ages 15-64 years), and post-working (ages 65-74 years) groups. For GBD 2019, HAQ Index construction methods were updated to use the arithmetic mean of scaled mortality-to-incidence ratios (MIRs) and risk-standardised death rates (RSDRs) for 32 causes of death that should not occur in the presence of timely, quality health care. Across locations and years, MIRs and RSDRs were scaled from 0 (worst) to 100 (best) separately, putting the HAQ Index on a different relative scale for each age group. We estimated absolute convergence for each group on the basis of whether the HAQ Index grew faster in absolute terms between 1990 and 2019 in countries with lower 1990 HAQ Index scores than countries with higher 1990 HAQ Index scores and by Socio-demographic Index (SDI) quintile. SDI is a summary metric of overall development. Findings Between 1990 and 2019, the HAQ Index increased overall (by 19.6 points, 95% uncertainty interval 17.9-21.3), as well as among the young (22.5, 19.9-24.7), working (17.2, 15.2-19.1), and post-working (15.1, 13.2-17.0) age groups. Large differences in HAQ Index scores were present across SDI levels in 2019, with the overall index ranging from 30.7 (28.6-33.0) on average in low-SDI countries to 83.4 (82.4-84.3) on average in highSDI countries. Similarly large ranges between low-SDI and high-SDI countries, respectively, were estimated in the HAQ Index for the young (40.4-89.0), working (33.8-82.8), and post-working (30.4-79.1) groups. Absolute convergence in HAQ Index was estimated in the young group only. In contrast, divergence was estimated among the working and post-working groups, driven by slow progress in low-SDI countries. Interpretation Although major gaps remain across levels of social and economic development, convergence in the young group is an encouraging sign of reduced disparities in health-care access and quality. However, divergence in the working and post-working groups indicates that health-care access and quality is lagging at lower levels of social and economic development. To meet the needs of ageing populations, health systems need to improve health-care access and quality for working-age adults and older populations while continuing to realise gains among the young. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

IMPORTANCE:The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE:To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW:The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS:In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE:The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

Background: Panayiotopoulos syndrome (PS) is a common benign epilepsy in childhood, characterized by predominantly autonomic symptoms such as emesis, pallor, and seizures, which are often prolonged. In an emergency room (ER), particularly when unconsciousness is prolonged, differentiating PS from acute encephalopathy is challenging. In this study, we aimed to elucidate the differences in clinical features of patients with PS and acute encephalopathy who visited our ER. Methods: We retrospectively reviewed 18 patients who were transferred to our ER because of status epilepticus later diagnosed as PS, and 30 patients with acute encephalopathy, between July 2012 and July 2017. We compared patient demographics, clinical characteristics, and treatment. Results: Most patients (90%) with acute encephalopathy had convulsive seizures of greater than or equal to 15 min, whereas only three patients (17%) with PS had convulsive seizures of greater than or equal to 15 min (P < 0.001). In addition, seizures were treatable in all patients with PS with a small dose of midazolam (0.1 mg/kg), but all patients with acute encephalopathy required midazolam at 0.3 mg/kg or more (P < 0.001). More patients with PS had autonomic symptoms compared to those with acute encephalopathy (e.g., vomiting [78% vs. 3%, P < 0.001]). Non-convulsive status epilepticus was observed in 22% of PS patients, but not in any acute encephalopathy patients. In contrast, fever was observed in all patients with acute encephalopathy (100%), but less frequently in those with PS (11%, P < 0.001). Conclusion: PS was characterized by 1) convulsive seizures shorter than 15 min, 2) seizures treatable with small doses of midazolam, and 3) autonomic symptoms. PS could be differentiated from acute encephalopathy in the early stages of the syndrome. (c) 2022 The Japanese Society of Child Neurology Published by Elsevier B.V. All rights reserved.