The study was aimed at investigating the alterations of local spontaneous brain activity in preschool boys with autism spectrum disorders (ASD).Based on regional homogeneity (ReHo), the acquired resting state functional magnetic resonance imaging (fMRI) data sets, which included 86 boys with ASD and 54 typically developing (TD) boys, were used to detect regional brain activity. Pearson correlation analysis was used to study the relationship between abnormal ReHo value and the Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC), developmental quotient, and age.p < 0.05, false discovery rate correction). We did not find a correlation between the results of brain regions and the CARS, ABC, and age.In the ASD group, we found increased ReHo in the right calcarine as well as decreased ReHo in the opercular part of the left inferior frontal gyrus, the left middle temporal gyrus, the left angular gyrus, and the right medial orbital frontal cortex (Our study found spontaneous activity changes in multiple brain regions, especially the visual and language-related areas of ASD, that may help to further understand the clinical characteristics of boys with ASD. Autism spectrum disorders (ASD) have social disorders, communication difficulties, repetitive and stereotyped behaviors, and limited and narrow interests as the core symptoms. These neurodevelopmental disorders occur early in childhood. The latest large-scale global survey has estimated that the incidence rate of ASD is about 1–2%, and it has been steadily increasing . AlthougIn recent years, the development of neuroimaging provides a new platform for the study of the neural changes of ASD. Autism spectrum disorders has always been considered to be a disease characterized by early changes in brain development, as early as 6–12 months of age, where there is excessive growth of the cortical surface area . With thIn addition, more studies have begun to focus on sex differences in ASD. Although the morbidity of ASD is two to five times more common in men than in women , sex difTherefore, our study intended to acquire resting-state fMRI data based on ReHo analysis from a relatively large sample size of preschool boys (3–6 years old) to specifically explore the alterations of local spontaneous activity in younger children with ASD and analyze its correlation with the severity of symptoms in patients with ASD. Based on a literature review, we speculated that there might be abnormal spontaneous neural activity in the visual cortex and semantic system–related brain areas in young children with ASD.We recruited 86 ASD preschool boys and 54 age-matched TD boys from Shenzhen Children’s Hospital. Healthy boys were recruited into the TD group through advertisement. All data sets were collected from November 2016 to August 2018. The study was approved by the ethics committee of Shenzhen Children’s Hospital. The guardian of each subject was asked to sign informed consent forms on the premise of fully understanding the purpose of the study. Before the scans, all children with ASD and TD who met the following criteria were excluded: neurological disorders , genetic disorders , or psychiatric disorders . Children with a history of severe physical illness, a history of loss of consciousness for more than 5 min, or who were currently taking psychoactive drugs were also excluded.All ASD subjects were co-diagnosed by two associate chief physicians of pediatrics and psychiatry, met the ASD DSM-V criteria and cutoffs on all the Childhood Autism Rating Scale (CARS)  and AutiImage data acquisition was performed by two experienced radiographers. Each child received 0.5% chloral hydrate 0.5 ml/kg (maximum dose 10 ml) and was sedated by a certified nurse. During the entire scan, each participant was required to have a caregiver and guardian present.MRI data were collected by a 3T Siemens Skyra scanner from the radiology department of Shenzhen Children’s hospital. Each participant was in the supine position, and the head was fixed firmly on a foam pad to prevent head movement. Adhesive earmuffs were also used to plug the ears to protect hearing. Then the resting-state fMRI data set was obtained using the gradient echo-planar imaging sequence. Resting-state fMRI collection parameters were as follows: repeat time (TR)/echo time (TE): 2000 ms/30 ms; flip angle: 90°; thickness/interval: 3.6 mm/0.72 mm; field of view (FOV): 230 × 230 mm; matrix: 64 × 64, and layers: 35. In 8 min, 240 volumes were obtained. After the MRI scan, images of each participant were examined to ensure that they met the experimental requirements. Meanwhile, a T1-weighted sequence of magnetization-prepared rapid-acquisition gradient echo (MPRAGE) prepared by three-dimensional magnetization covering the whole brain  was obtained. The corresponding acquisition parameters were set as TR: 2300 ms, TE: 2.26 ms, TI: 900 ms, flip angle: 8°, acquisition matrix: 256 × 256, FOV: 256 × 256 mm, and layer thickness was 1 mm.1). For each participant, the first 10 time points were discarded due to transient signal changes before magnetization reached a stable state and the participant adapted to the fMRI noise. To minimize the influence of head movement, subjects with maximum displacement greater than 1.5 mm and angle movement greater than 1.5° during the whole fMRI scan were excluded. No subjects were deleted in this step. Then, the resting-state fMRI data were corrected for intra-volume acquisition delay and co-registered together with anatomical scanning. The co-registered anatomical images were divided into gray matter, white matter, and cerebrospinal fluid. Then, all data spaces were normalized to the whole brain template of the Montreal Neurological Institute standard space (age 4.5–8.5 years) with an isotropic voxel size 3 mm × 3 mm × 3 mm .Two independent-sample, nonparametric tests were used to assess the age difference between ASD boys and TDs. To explore the differences in ReHo between ASD boys and TDs, the REST-State fMRI Data Analysis Toolkit (REST 1.8) was used to conduct a two-sample All of the data of the ASD and TD groups were retained after processing. There was no significant difference in age between the two groups. The values of the ABC, CARS, and DQ of the ASD group were consistent with the ASD standard as shown in Resting-state fMRI analysis showed that, compared with the TD group, ASD boys had increased ReHo in the right calcarine as well as decreased ReHo in the opercular part of the left inferior frontal gyrus (IFG operc), left middle temporal gyrus (MTG), left angular gyrus (AG), and right medial orbital frontal cortex (mOFC) , 2.The ReHo values of the five brain regions and the values of the ABC, CARS, DQ, and age were in accordance with normal distribution; hence, Pearson correlation analysis was used. However, we did not find a significant correlation between any of the five brain regions and ASD-related scales or age.In this study, based on a large sample size of resting-state fMRI, we used ReHo analysis to explore the alterations of spontaneous neural activity in the brain of ASD preschool boys. The results show that the ReHo value in the right calcarine of the primary visual cortex was increased in preschool boys with ASD, and the ReHo value in the language-related brain region  and right mOFC was decreased. No significant correlation was found between the abnormal brain regions and the score on the ASD scale.We found that the ReHo value of the right calcarine increased, suggesting that there was an increase in local spontaneous neural activity in the right calcarine. The calcarine is an important part of the primary visual cortex, and abnormal visual processing in patients with ASD has been the focus of the research on a mechanism of ASD. Among them, many recent studies attributed the enhancement of the primary visual cortex of ASD patients to the functional compensation of semantic dysfunction ; in factSimultaneously, we found that there was a decrease of spontaneous neural activity in the left IFG operc and left MTG in preschool boys with ASD. The former is a part of Broca’s area, which is an important area related to semantic expression and comprehension , whereasIn this study, decreased local spontaneous neural activity in the left AG was also found. The AG is considered an important brain region responsible for episodic memory. The AG may play a particular role in behaviors requiring fluent conceptual combination, such as sentence comprehension, discourse, problem solving, and planning . Some reThe decreased local spontaneous neural activity in the right mOFC was observed in this study as well. The mOFC, as a part of the prefrontal cortex, is thought to be associated with complex emotions and reward and punishment processing, which are essential for social behavior . Based oWe did not find a correlation between the ASD preschool boys’ abnormal brain regions and the ASD score scale. Possible reasons may be that  our studThere are some limitations in our study. First, we only investigated the ReHo of preschool boys with ASD although ASD has atypical brain development trajectories  and sex Finally, based on resting-state fMRI data, the brain regions with functional abnormalities in preschool boys with ASD were found by using ReHo analysis. We suggest that increased spontaneous activity of the primary visual cortex might be a potential primary disorder of boys with ASD. In addition, some brain regions  may partly explain the core symptoms of ASD, such as social dysfunction and stereotyped behavior(s). Given that more than 60% of children with ASD are prescribed for any clinical indication and that more than 41% of them are taking more than one psychotropic drug with limited effect , these rThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of Shenzhen Children’s Hospital. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.ZL: validation, formal analysis, investigation, writing – original draft, and visualization. SX: software, investigation, resources, and funding acquisition. YW: methodology and software. LX, KH, and McL: methodology. ML and YY: software. CL, SH, and YF: validation. GJ: conceptualization, data curation, writing – review and editing, supervision, project administration, and funding acquisition. TW: formal analysis, data curation, writing – review and editing, and funding acquisition. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


BackgroundThe aim of the present study was to compare the clinical outcome of the David operation and the Bentall operation in patients with Stanford type A acute aortic dissection (AADA) from the viewpoint of hemostasis.MethodsBetween April 2016 and April 2020, 235 patients underwent emergent surgery for AADA. Of them, 38 patients required aortic root replacement . The mean age was 59.3±12.6 years. In the present series, the David operation was the first choice for relatively young people, and the Bentall operation was performed for relatively elderly patients and cases in which valve-sparing seemed impossible.ResultsBetween the David and the Bentall group, the 30-day mortality rate did not differ significantly. However, hemostasis time , defined as the interval from the cessation of cardio-pulmonary bypass (CPB) to the end of the operation, and total operation time  were significantly shorter in the David group than in the Bentall group, and the amount of blood transfusion was less in the David group than in the Bentall group .ConclusionDavid operation offers a shorter hemostasis time and consequently shorter operation time than the Bentall operation in the setting of AADA, probably due to double suture lines, despite its surgical complexity. Some patients with acute aortic dissection type A (AADA) require aortic root replacement (ARR) because of the enlarged aortic root, extensive tissue destruction of the aortic root, and/or intimal tears located in the aortic root. In such patients, the Bentall operation using a composite graft with a vascular prosthesis and an artificial valve used to be the gold standard -3, but iThere are two modalities of VSRR, i.e., the re-implantation technique by David  and the The study protocol was reviewed and approved by our institutional review board, and the need for additional informed consent was waived .Between April 2016 and April 2020, 235 patients underwent emergency surgery for AADA. Of them, 38 patients who needed ARR were retrospectively evaluated in the present study; their mean age was 59.3±12.6 years, and 31 (81.6%) were male. The David operation was performed in 17 patients, and the Bentall operation was performed in 21 patients . The standard indications for ARR in the setting of AADA are extensive tissue destruction, the presence of a concomitant aortic root aneurysm ≥4.5 cm, or a known connective tissue disorder. In the present series, the David operation was the first choice for young people, and the Bentall operation was performed for elderly patients and cases in which self-valve-sparing seemed impossible.All patients were intubated under general anesthesia, and they were maintained on mechanical ventilation during the operation. A standard median sternotomy was performed, and cardiopulmonary bypass (CPB) was instituted. The arterial cannula was inserted into the femoral artery or into the ascending aorta using the Seldinger technique. The venous cannula was generally inserted through the right atrial appendage, but selective bi-caval venous cannulation was performed in some cases. A venting cannula was inserted through the right superior pulmonary vein to the left ventricle. The ascending aorta was clamped if there was no thick thrombus in the false lumen. Otherwise, the ascending aorta was not clamped, and myocardial protection was achieved at the time of the hypothermic circulatory arrest. Myocardial protection was achieved by intermittent antegrade and/or retrograde administration of hypothermic blood cardioplegia. The hypothermic circulatory arrest was induced at a rectal temperature of 25 °C. All three arch vessels were cannulated, and antegrade selective cerebral perfusion was started. Entry resection was the standard procedure in our institute, and partial arch replacement with the reconstruction of the brachiocephalic trunk with or without reconstruction of the left common carotid artery, or total arch replacement was done according to the location of the entry. Technical details of the David operation and the Bentall operation have been described elsewhere. The Carrel patch was the first choice for coronary reconstruction, but the Cabrol method or coronary artery bypass grafting was added if needed.Follow-upFollow-up information on all patients was collected through planned outpatient visits in the course of regular clinical follow-up. The follow-up rate was 100%, and the mean duration of follow-up was 435±433 days.Statistical analysisResults are expressed as means±standard deviation. Statistical analysis was performed using Student’s t-test for continuous variables or chi-square tests (Fisher’s exact tests if n<5) for categorical variables. Kaplan-Meier analysis was used to compare late mortality between groups. A P-value less than 0.05 was considered significant. All statistical analyses were performed using SPSS 22.0 software .The average age of the patients was 51.4±8.6 years in the David group and 65.7±12.1 years in the Bentall group (p<0.001), and more than 80% of them were male. Generally, the Bentall group had a more critical preoperative condition than the David group, such as malperfusion  and cardiac tamponade with shock . Malperfusion of organs in the Bentall group was frequently presented in the cerebrum  and coronary . Moreover, preoperative blood tests showed lower platelet , and extended APTT  in the Bentall group. The value of other coagulation factors, serum acidosis, and serum lactate was similar between the groups. As for the indications for ARR, the David group had more root enlargement , but the rate of rupture of the aortic root and entry in the aortic root was similar in the two groups. The demographic characteristics of the groups are summarized in Table Operative data are shown in Table Short-term outcomes are shown in Table During the follow-up period, two patients in the David group (both within 30 days) and seven patients in the Bentall group  died. The survival curves are shown in Figure The crucial findings of the present study were: (1) the David operation can be performed with acceptable results in selected patients having AADA and (2) despite its surgical complexity, the David operation offers shorter hemostasis time and consequently shorter operation time than the Bentall operation in the setting of AADA, probably due to double suture lines.The surgical approach for AADA differs between western countries and Japan. In general, aortic root surgery is more common in western countries, and aortic arch surgery is more common in Japan. Regarding aortic root surgery in patients with AADA, the frequency of root replacement was about 30% in Europe and the United States , whereasIn the present series, about 16% of patients with AADA underwent root replacement, and the rate is obviously higher than the Japanese average, but almost half of the average of Europe and the United States. However, among those patients who underwent ARR, about 60% underwent total arch replacement or partial arch replacement with a reconstruction of at least one arch vessel, and the rate was similar to the Japanese average, but almost four times higher than the average of Europe and the United States. In such an aggressive strategy, hemostasis, i.e., control of surgical bleeding and non-surgical coagulopathy, is very important.However, it is sometimes difficult to distinguish surgical bleeding due to technical issues from stitch-hole bleeding due to coagulopathy, especially in patients with AADA, because many patients have coagulopathy preoperatively, and hypothermic circulatory arrest worsens this coagulopathy ,13. In tDespite its surgical complexity, many previous studies have suggested the non-inferiority of the David operation to the Bentall operation in patients with AADA -16. For LimitationsThere are several limitations to the present study. First, this was a retrospective study of a single center's experience with a relatively small sample size. Moreover, the two groups in the present study had different patient backgrounds, with younger patients in the David group (p<0.001), and more severe cases, e.g., malperfusion (p=0.004) and cardiac tamponade with shock (p=0.018), low platelet (p=0.0023), extended APTT (p=0.0001) in the Bentall group. These factors are said to be higher the perioperative mortality -19. TherThe present study demonstrated that the David operation offers a shorter hemostasis time and consequently a shorter operation time than the Bentall operation in the setting of AADA, probably due to double suture lines, despite its surgical complexity. Therefore, especially for younger patients, this valve-sparing fashion seems valuable in terms of clinical benefits.


Objective: Medical errors or near misses (MENM) may cause serious negative outcomes for the patients. However, medical professionals with MENM may also be secondary victims. Although the association between MENM and depression among medical professionals has been explored in several previous studies, the possible causal relationship has been explored less, especially in China. In this study, our first aim was to determine the prevalence of MENM among Chinese medical professionals. We also wanted to explore the causal effect of MENM on depressive symptoms based on a propensity-score matching analysis. Methods: A cross-sectional study was conducted among medical professionals in Chinese public general hospitals, and 3426 medical professionals were analyzed in this study. The Center for Epidemiologic Studies Depression (CES-D) scale was used to assess depressive symptoms. Social support was measured by the Multidimensional Scale of Perceived Social Support (MSPSS). MENM, social-demographic variables, occupational characteristics, and physical disease were also evaluated in this study. Results: The one-year prevalence of perceived MENM was 2.9% among medical professionals in Chinese public general hospitals. The results of logistic regressions showed that working hours/week  and depressive symptoms  were associated with MENM. After propensity score matching, depressive symptoms were associated with MENM  among medical professionals. The associations between occupational characteristics, physical disease, social support, and MENM were not supported by this study. Conclusions: The one-year prevalence of MENM was low in Chinese public general hospitals, and based on our propensity score matching analyses, the occurrence of MENM may cause depressive symptoms in medical professionals. A bigger effort by health systems and organizations may be helpful for reducing MENM. It is well known that medical professionals play very important roles in patient care and safety, and any medical errors or near misses (MENM) may result in serious negative outcomes for the patients. In the United States (US), medical errors have been the third-leading cause of death . AlthougAlthough we know that MENM can cause serious negative outcomes for patients, we should understand that MENM is inevitable, because medical professionals are imperfect humans ,6. ThereIndeed, there are many studies that support the association between MENM and negative psychological problems, such as depression , burnoutTo address these gaps in our understanding, a cross-sectional study was conducted among medical professionals in public general hospitals in Shandong province, China. The first aim for this study was to investigate the one-year prevalence of perceived MENM among medical professionals, and the second aim was to explore the possible effect of MENM on depressive symptoms among them. Propensity score matching is an emerging matching technique for causal inference in observational research . It has This study was conducted among medical professionals working in public general hospitals in Shandong province, China. Shandong province is in the east of China, where the size of the population and the number of medical workers are ranked second and first for all Chinese provinces, respectively ,23. To rThe survey for this study was performed between December 2018 and January 2019. Medical professionals received the questionnaires individually. The questionnaires were filled out anonymously, and there was no reward for these medical professionals. We also asked two trained postgraduate students in the hospital to answer the questions and collect the questionnaires on the survey date.MENM was assessed with the question, “have you ever made any MENM in the last year?” The answers were yes (1) and no (0). Medical professionals with positive responses were considered as making a MENM in the last year. This assessment method for MENM has been used in previous studies ,25.The Chinese version of the Center for Epidemiologic Studies Depression (CES-D) scale was used to evaluate depressive symptoms in this study ,27. The Gender was coded as male (1) and female (0). Age was calculated according to the medical professionals’ date of birth, which was analyzed as a continuous variable. Marital status was assessed by a choice between single, married, divorced, widowed, and others. Since there were only a few medical professionals that were divorced, widowed, or others, we recoded this status as single (1), married (2), and others (3). Education was evaluated according to the medical professionals’ academic degree. Since most of medical professionals reported either a doctor, master’s, or bachelor’s degree, we recoded education as doctor (1), master (2), bachelor degree (3), and others (4).The types of medical staff included in this study were doctor (1), nursing (2), and medical technician (3). Professional title was ranked as senior (1), vice-senior (2), intermediate (3), and junior and others (4). Manager status was evaluated with a question about the medical professionals’ administrative function in their hospitals. Working hours was determined with a question about the average working hours/week for the medical professionals, and it was analyzed as a continuous variable.The question, “if you have been diagnosed with any physical disease?” was used to evaluate physical disease for the medical professionals. The answer was yes (1) and no (0).Social support was measured by the Chinese version of the Multidimensional Scale of Perceived Social Support (MSPSS) . It contIn this study, IBM SPSS Statistics 24.0 (web edition) and R (version 3.2.5) were used to perform the data analyses. A Student’s T-test or a one-way ANOVA was conducted to analyze the factors associated with MENM. A logistic regression was conducted to further examine the factors associated with MENM. To explore the causal effect of MENM on depressive symptoms, propensity score matching was conducted based on a 1:3 matching ratio for medical professionals.p-value of ≤0.05 was considered as statistically significant.A logistic model was used to calculate the propensity scores with MENM as the dependent variable, and the covariates included the following 10 variables: gender, age, marital status, education level, type of medical staff, professional title, manager, physical disease, working hours/week, and social support. All of the tests were two-tailed and a p < 0.01), education level (p < 0.01), professional title (p < 0.05), working hours/week (p < 0.01), social support (p < 0.001), and depressive symptoms (p < 0.001) were associated with MENM. Propensity score matching was also performed to analyze the association between MENM and depressive symptoms. p > 0.05), and only depressive symptoms was associated with MENM (p < 0.001). The detailed results for the pre-matching and post-matching are shown in In this study, we analyzed a total of 3426 medical professionals that worked in Chinese public general hospitals. There were 99 medical professionals (2.9%) who perceived MENM in the last year. Single analyses supported that marital status (p < 0.05), and depressive symptoms  were associated with MENM before propensity score matching among medical professionals. After propensity score matching, depressive symptoms was also associated with MENM  among medical professionals.In In this study, there are several critical findings for MENM among medical professionals in Chinese public general hospitals. The first concerns the prevalence of perceived MENM, which we found affected 2.9% of medical professionals in the last year. We also found that the number of working hours per week and depressive symptoms were associated with MENM among medical professionals. The results of propensity score matching analyses further supported a causal effect of MENM on depressive symptoms. The other interesting finding was that none of the other analyzed factors were associated with MENM, with the exception of working hours per week and depressive symptoms.For the one-year prevalence of MENM, our finding was 2.9%, which was much lower than other studies from around the world. Previous studies have reported a wide range for the prevalence of MENM. A Study among US physicians reported that the prevalence of medical errors was 10.5% in last three months , and anoThe other main aim for this study was to identify the association between MENM and depressive symptoms, and we also wanted to explore the causal effect of MENM on depressive symptoms using propensity score matching analyses. Both hypotheses were supported in this study. For the association between MENM and depressive symptoms, it has been reported by several studies for different kinds of medical professionals ,40,41. IIn this study, a positive correlation between longer working hours per week and MENM was also observed. This association has been reported by previous studies ,43,44, wThe other interesting findings of this study concerned the association between occupational characteristics, physical disease, social support, and MENM. We found that all of these factors were not associated with MENM after we controlled for working hours per week and depressive symptoms. Although we should be cautious about concluding that these factors are not associated with MENM, previous studies have shown that most MENM are the result of system issues , and thaThere were some limitations, which should be considered when interpreting the results of this study. Firstly, this is a cross-sectional study. Although propensity score matching analyses may identify causal relationships, we should be cautious about the strength of these causal relationships. Some longitudinal studies should be conducted to confirm the causal relationship between MENM and depressive symptoms. Secondly, since the prevalence of MENM, and the factors analyzed by this study, were self-evaluated by medical professionals, it may underestimate the prevalence of MENM and introduce a bias to the findings of this study. Thirdly, all participants were medical professionals working in Chinese public general hospitals, and the findings may be not relevant to other kinds of hospitals in other countries. Fourthly, only depressive symptoms were analyzed in this study, while other variables, such as health-related quality of life and quality of medical care, were not analyzed.Considering these limitations, this study provides some critical findings and implications for understanding the prevalence of MENM and its effect on depressive symptoms. Firstly, the one-year prevalence of MENM was low in Chinese public general hospitals. Secondly, the occurrence of MENM may cause depressive symptoms in medical professionals. Thirdly, the efforts of health systems and organizations could help to reduce MENM. These findings indicate that medical professionals that have experienced MENM are at a higher risk for depressive symptoms, and they will need help, so they can be considered a “second victim”.


Cervical, thoracic spines, first ribs, aortic arch, heart, rib cage, and soft tissue of thorax and flank seemed to be the most crucial activated regions in the age prediction model. The sex prediction model demonstrated an AUC of >0.99. Conclusion: Deep learning can accurately estimate age and sex based on CXRs.Background: The performance of chest radiography-based age and sex prediction has not been well validated. We used a deep learning model to predict the age and sex of healthy adults based on chest radiographs (CXRs). Methods: In this retrospective study, 66,643 CXRs of 47,060 healthy adults were used for model training and testing. In total, 47,060 individuals  were included. By using chronological ages as references, mean absolute error (MAE), root mean square error (RMSE), and Pearson’s correlation coefficient were used to assess the model performance. Summarized class activation maps were used to highlight the activated anatomical regions. The area under the curve (AUC) was used to examine the validity for sex prediction. Results: When model predictions were compared with the chronological ages, the MAE was 2.1 years, RMSE was 2.8 years, and Pearson’s correlation coefficient was 0.97 ( Predicting age and sex using various medical imaging modalities has been implemented for decades. In forensic medicine, dental and manubrium with age correlation ,2 and coThe advantages for medical imaging to predict age and sex may have roots in the fact that age and sex are not simply one single concept. In fact, image findings may reflect the overall effects of chronological, biological, and/or pathological changes ,14,15. CNumerous advances have been implemented in conventional ML for bone age ,17 or neChronological age has been widely used in various studies to predict disease and treatment prognosis. However, biological age may better reflect the impacts of lifestyle, nutrition, multiple risk factors, and environmental factors, which, in turn, can benefit the prediction of disease and prognosis both theoretically and practically ,25,26. AThis study was approved by the Far Eastern Memorial Hospital Institutional Review Board (FEMH 107094-E), and the requirement to obtain informed consent was waived due to its retrospective nature. The participant records were anonymized and deidentified before analysis. This project was supported by Quanta Computer Inc. . The data and analysis were controlled by authors independent of Quanta Computer (C.-Y. Y. and K.-H. K.). Three authors  are employees of Quanta Computer but had no control of data presented in this study.n = 71,878) for health screening from January 2008 to December 2017 at Far Eastern Memorial Hospital. To train the model purely based on physiological age change, an in-house deep learning screening model was used to exclude all images revealing any kind of lung diseases, acute traumatic lung, surgical conditions, or any type of implants. In total, 66,643 images from 47,060 individuals were used for model training and testing , validation (n = 6664), and test (n = 6664) sets. Multiple images from the same participant at different timepoints were selected only for the training set, rather than for the validation or test sets  who underwent frontal chest radiograph studies  and 24,916 women (52.9%)) were included. Image-based demographics are summarized in https://github.com/keras-team/keras/blob/master/keras/applications/inception_resnet_v2.py; accessed on 1 July 2021) [The neural network architecture used in this study was Inception-ResNet-v2 (ly 2021) , which ily 2021)  and incely 2021) ,30,31. RBefore being fed into the network, the images were resized to a resolution of 512 × 512 pixels. Grayscale values were normalized from  to  by dividing the values by 127.5 and then subtracting 1.0. We used a CNN architecture (InceptionResNetV2)  with parThe codomain of sigmoid is ; therefore, the outputs were interpreted as min-max normalized ages. Specifically, If The oldest and youngest ages in the dataset were normalized to 0.9 and 0.1, respectively. In our case, the youngest age was 21, whereas the oldest was 93. After these values were substituted into Equation (2), a = 12 and b = 102, i.e., the predicted age range of our model was 12–102 years.https://www.tensorflow.org/; accessed on 1 July 2021) was used to train and evaluate the algorithms.For data augmentation, a rotation of up to 5° degrees was applied for each image in the training set before being fed into the model. The loss function of the age prediction model was the mean absolute error (MAE), and the model training goal was to minimize loss. The overall model performance was also evaluated using MAE. We used an adaptive moment estimation (ADAM) optimizer with a default parameter setting: β1 = 0.9 and β2 = 0.999. The model was trained with minibatches of a size of 32 and an initial learning rate of 0.0001. The open-source deep learning framework Tensorflow (We used gradient-weighted class activation mapping (Grad-CAM) to visually explain the most activated region produced by the model . AlthougTo visualize the activated region variance across diverse age levels, individuals were divided into separate 5-year age groups as follows: the bounding box coordinates containing the chest region of each individual were obtained using an in-house object detection model developed based on YOLOv3  to detecr) between chronological and predicted ages, the MAE, and root mean square error (RMSE). A Bland-Altman plot was used to distinguish paired differences of the model estimate from the chronological age over the paired means. The area under the receiver-operating characteristic curve (AUC) and standard errors were calculated to examine the validity of chest radiographs in sex prediction. The absolute errors and squared errors between different sex groups were compared using the Student’s t-test. A p-value less than 0.05 was considered significant, and Bonferroni adjustment was conducted in the case of multiple comparisons. The statistical analysis was performed using R (version 3.5.3).Data are presented as means and standard deviations for continuous variables and as percentages for categorical variables. The reported performance assessment of the model used age predictions on the test set. The model performance was evaluated by calculating the Pearson correlation coefficient  .This study developed a deep learning model for age and sex estimation based on chest radiographs from a healthy adult cohort in a hospital-based real-world clinical dataset. By using CNNs, our model predicted age and sex with high accuracy  and the mean of the differences between model estimates of age and the ground truth was close to 0 years. In addition, the modified Grad-CAM method with SAM demonstrated the variance across different age groups in the most activated anatomical regions, containing critical features for the age prediction model.N = 2001) with an MAE > 4 years and RMSE > 5 years. Although speculative, it seems possible that our model, demonstrating greater accuracy, may extract more relevant features for age prediction from the chest radiographs than those extracted in brain MR images.Under the assistance of a CNN, and using regression method, our chest radiography-based age prediction model resulted in an MAE and an RMSE of <3 years and showed a strong correlation between predicted and chronological ages. With a similar method, Larson et al.  developeAll prior studies predicting age and sex were based on open datasets, which have been criticized for mislabeled or poor-quality images ,38. In tFor age prediction, we demonstrated a series of SAMs for people of different age groups . We usedThe model can be particularly useful when a person’s name and age/sex are unknown or unreliable, for instance, when a police officer or healthcare provider tries to help a person who has lost their memory or when a patient needs rapid imaging services at an emergency department with their name or age being unknown. Additionally, the model can be used in various forensic fields for subjects of unknown ages and sexes . Chest rThe other significance is that age information in images is derived not only from chronological change, but also from the cumulative effects of biological and/or pathological change. Although our model could predict very accurately overall, the differences between predicted age and chronological age differed across individuals, which may contain information from changes from environmental factors, lifestyle, or diseases overtime for this individual. In fact, image-based age predictions have frequently been used to evaluate clinical conditions. For instance, bone age studies from hand and wrist radiographs are commonly used to evaluate the degree of skeletal maturity and diagnose growth disorders or to predict final adult height in children. In various brain diseases, neuroimaging-derived age predictions have been studied and the differences between the predicted brain and chronological ages are potentially related to the accumulation of age-related changes in pathological conditions ,9,10,11 In conclusion, the present study developed a deep learning model which can estimate age and sex in chest radiographs with a high accuracy than that in other radiographic methods. Future research to compare the accuracy of age and sex prediction models based on other imaging modalities and to further explore the relevance of CXR- age as an imaging biomarker is warranted.Our study has several limitations. First, we used a dataset comprising healthy Asian individuals from a single institution, which might introduce some potential biases in data collection. Therefore, the generalizability of our study should be addressed with additional studies on populations of different ethnicities, geographical regions, and socioeconomic levels. Additional representative image data with reasonable variation for training should also be considered to minimize such biases. Moreover, the deep learning model tendentiously underestimated age in individuals aged >60 years, potentially because a relatively low number of individuals from this age group were in the training set. Furthermore, the age-related features learned from the dataset might not be expressed as much as expected in older ages. Further investigation on a more balanced dataset may aid in clarifying this issue. Finally, although our model had a 2.1-year MAE and a 2.8-year RMSE, a more accurate and precise estimate for an individual is needed in the clinical settings. Further research with optimization of data manipulation or deep learning algorithms to reduce the error rate and to include different datasets to explore the relevance of CXR-age as a clinical imaging biomarker is warranted.


N = 327) with normal vaginal delivery were selected purposively for this study. Data were collected through face-to-face interviews using a structured questionnaire based on the Disrespectful and Abusive Scale by Bowser and Hill. All women had experienced at least one type of disrespect and/or abuse during labor and delivery, most common being non-consented care (100%), non-dignified care (72%), and non-confidential care (66.6%), respectively. Discriminatory care and physical abuse were experienced by 32.33% and 13.23%, respectively. Ethnicity, religion, place of delivery, and numbers of living children were the main predictors of reporting disrespect and abuse. Overall, the occurrence of disrespect and abuse during institutional delivery was found to be very high.Worldwide, a large number of women experience disrespectful and abusive behavior from care providers during childbirth. This violates the rights of women to attain respectful care. This study aimed to find out the women’s experience of disrespect and abuse during institutional delivery. A cross-sectional study was conducted in two hospitals of Morang district situated in eastern Nepal. Two hundred eighteen women from a public hospital and 109 women from a private hospital ( The provision of respectful and satisfactory maternity care is essential for promoting timely care-seeking behavior and ultimately ensuring the health and well-being of mothers and their babies. Disrespectful and abusive behavior from health care providers has been recognized as one of the barriers to seeking timely maternity health services . Every wDisrespectful and abusive care includes impoliteness of care providers, inappropriate reprimands, shouting at the client, lack of empathy, refusal to assist, threatening clients for their non-compliance, and denying clients opportunities to choose or give an opinion on the care they are receiving . Based oGlobally, many women experience mistreatment during childbirth, including abusive anddisrespectful care.Women aremistreatedacross all income levels and at alllocations. Previous studies conducted in various countries have shown that 27.2% to 98% of women experienced at least one type of disrespectful and abusive behavior from care providers during facility-based childbirth ,7,8,9,10Maternal and child mortality rates are still high in Nepal. The recent maternal mortality ratio (MMR) is 186 deaths per 100,000 live births, neonatal mortality rate is 19.8deaths per 1000 live births, infant mortality rate is 25.6 deaths per 1000 live births, and child mortality rate is 30.8 deaths per 1000 live births . SustainWhite Ribbon Alliance claims that in Nepal, women in childbirth routinely experience disrespect and abuse in health facilities. The problem is pervasive and does not spare anyone, regardless of social, geographic, or economic background. The overall disrespect and abuse was reported by 70.1% of the women in a study conducted in Pokhara, Nepal . This isThere is a lack of adequate studies in Nepal that address the prevalence and factors associated with disrespect and abuse of women in facility-based childbirth. Disrespectful and abusive behaviors might be associated with, e.g., ethnicity, religion, and/or education level. Thus, this study was conducted to learn more about the women’s experiences and factors related to reporting disrespect and abuse during childbirth as a quest for respectful maternity care in Nepal.A cross-sectional study was conducted in one public and one private hospital in Biratnagar, Morang district, situated in Province 1, Nepal. Public hospitals in Nepal have low resources compared to private hospitals. Maternal and child health services are free of cost in public hospitals of Nepal. Besides, women receive transportation costs when they deliver in a health facility whereas, women must pay for the services in private hospitals. The professional background of the care providers is similar in both hospitals. Generally, normal deliveries in both hospitals are conducted by nurses. One of the reasons for selecting these sites was to compare the women’s experience of disrespect and abuse in two different settings. Moreover, the study site is a home for populations from various socio-demographic characteristics and backgrounds. In addition, large numbers of women from the adjoining region visit public and private hospitals located in the study site, seeking maternal health services. Thus, these places have been selected purposefully to fulfill the objectives of the study.Women admitted to the postnatal ward after normal vaginal deliveries were included in the study. Based on the prevalence of disrespect and abuse in a previous study performed in Gujrat, Pakistan , prevaleA structured questionnaire was designed based on the Disrespect and Abuse (D & A) scale according to Bowser and Hill’s landscape evidence review. The authors adopted this scale as it has comprehensive points to find out the abuse faced by women during facility-based childbirth. The D & A scale includes seven categories of disrespect and abuse in childbirth: (1) physical abuse, (2) non-consented care, (3) non-confidential care, (4) non-dignified care, (5) discrimination based on specific patient attributes, (6) abandonment of care, and (7) detention in facilities. These categories of disrespect and abuse during facility-based childbirth were adopted from the above-mentioned scale and 28 items under these categories were developed based on extensive literature review. Items were categorized into binary choice: yes/no to find out whether the women experienced disrespect and abuse or not. All the items are presented in Data collection was performed from September to October 2020. The first author collected the data using the face-to-face interview technique. Different understanding and expectations of non-confidential care, non-dignified care, discrimination, and abandonment of care might occur.So, the author asked the questions of the respondents in local and understandable language. All interviews were conducted in the postnatal ward on the day of discharge in a separate room to maintain privacy and confidentiality.The outcome variable for this study was experiences of disrespect and abuse during labor and delivery based on 28 indicators classified into 7 categories, Independent variables were: socio-demographic characteristics  and obstetric characteristics .p-value < 0.05).Collected data were coded, entered, and analyzed using a statistical package for social science (SPSS) version 20. Descriptive statistics such as frequency, percentage, mean, and standard deviation were used to describe the socio-demographic and obstetric characteristics of the participants as well as prevalence of disrespect and abuse in childbirth. Women who reported experiencing one or more subcategories of disrespect were included in the overall prevalence measure. The sum score of experiencing D&A for each woman was calculated (varying from 0 to 28) and this variable was used as the outcome variable. Mann–Whitney U and Kruskal–Wallis tests were performed to identify the factors associated with experience of disrespect and abuse. Multiple linear regressions were calculated to identify the strength of association. Statistical significance level was set at 95% , and ethical clearance was obtained from the Ethical Review Board of NHRC (Ref. No. 2088). A proposal was also submitted to concerned authorities of both the hospitals and written permission for data collection was obtained from both the hospitals. To maintain anonymity of the hospitals, the name of the hospitals has not been disclosed anywhere. Each respondent received an explanation about the purpose of the study and written informed consent was taken from each respondent before the interview.p ≤ 0.05).Sociodemographic information of the respondents is presented in p ≤ 0.05).Multiple linear regression analysis was performed to identify the strength of association , Muslim religion (β = 1.095), having delivered in a private hospital (β = 2.285), and having two or more living children (β = 0.904) with p-value < 0.05. Despite this, most women who want to have more children reported intending to deliver again at the same facility as they have no other better choice.Mann–Whitney U and Kruskal–Wallis were performed to identify the factors associated with disrespect and abuse . Disrespociation . It reveProviding respectful maternity care and increasing institutional delivery are the focus of health programs of the Nepal government. Promoting respectful maternity care during childbirth is a vehicle to utilize maternal health care and prevent maternal and child morbidity and mortality rate. Disrespectful and abusive behaviors during childbirth and maternity care have been documented throughout the world, making this truly a global agenda. This study aimed to find out the prevalence of disrespectful and abusive behavior during institutional delivery.In this study, all women reported at least one category of disrespect and abuse during labor and delivery, the most common being non-consented care, non-confidential care, and non-dignified care. Similar studies conducted in Pakistan and Nigeria also found that almost all women  experienced at least one type of abusive behavior during childbirth ,7. HowevIn the present study, 100% of women experienced non-consented care, 72.2% of women experienced non-dignified care, and 66.6% of women experienced non-confidential care, which was similar to a study conducted in Gujrat, Pakistan in which it is mentioned that the most commonly experienced disrespect and abuse was non-consented care and lack of informed choice (99.7%) followed by non-confidential care 58.6%), and non-dignified care (45.6%) [8.6%, andIn our study, abandonment of care (neglected) was experienced by 35.6% which was also consistent with the findings of studies conducted in Nigeria and Pakistan in which 29.1% and 32% of women reported experience of abandonment of care, respectively ,8. In thOverall, physical abuse such as beating, slapping, pinching, and rough touch was reported by 12.23% of women in this study which was almost similar to studies conducted in Pakistan and Ethiopia where 15% and 13.6% of women had reported physical abuse, respectively ,17. Howeβ = 2.45 and 3.27, respectively), delivered in private hospital (β = 2.28). In this study, women with more than one living child were more likely to report disrespect and abuse compared to women with only one child. This is in contrast with a study conducted in southwest Ethiopia in which parity two or above women were nearly 72% less likely ) to report disrespect and abuse compared to parity one woman [β = 2.285 with 95% CI = 1.806, 2.763) to experience disrespect and abuse. In contrast, a study conducted in Pakistan found that the risk of reporting disrespect and abuse was twice in public health facilities as compared to private [Disrespect and abuse during labor and delivery were significantly associated with ethnicity, religion, level of education, number of living children, and place of delivery on univariate analysis. The finding was consistent with studies conducted in Pakistan and southern Mozambique and in which ethnicity, educational level, and parity were the predictors of disrespect and abuse ,9. Howevne woman . The difHowever, there are minimal studies related to women’s experience of disrespect and abuse during institutional delivery in Nepal. The findings of the study might be the basis for intervention to enhance respectful maternity services. The findings of the study might be useful to maternity care providers. The limitations of this study are a small sample size and non-probability sampling. Since this is a sensitive and subjective issue, the response might be under- or over-reported. The findings of the study are based on women’s reports only. Different understanding and expectations of non-confidential care, non-dignified care, discrimination, and abandonment of care might occur. Cultural and social practices shape self-understanding and how women understand themselves as being neglected or discriminated against. These value-loaded concepts could also have been investigated with qualitative research methods and ethnography in order to understand these women’s expectations, thinking, and needs. Thus, further studies among women as well as health care workers, using qualitative research design, are planned.Findings of the study revealed that the prevalence of disrespect and abuse during labor and delivery is high in institutional delivery both in public as well as private hospitals. Disrespect and abuse during labor and delivery were significantly associated with ethnicity, religion, level of education, number of living children, and place of delivery. Despite this, most women who want to have more children reported intending to deliver again at the same facility, as they have no other better choice. Thus, measures to enhance respectful maternity care are essential. To reduce the disrespect and abuse of women during institutional delivery, respectful maternity care components should be incorporated in the nursing and medical education curricula so that the care providers will be prepared for this from the pre-service period. Guidelines on respectful maternity care should be formulated and communicated to all the maternity care providers.


No differences in LOS were found between groups . Women in the ChroPreg group reported being more satisfied with maternity care measured by the Pregnancy and Childbirth Questionnaire (PCQ) compared with the Standard Care group . In conclusion, the ChroPreg intervention did not reduce LOS. However, women in the ChroPreg group were more satisfied with maternity care.The proportion of childbearing women with pre-existing chronic medical conditions (CMC) is rising. In a randomized controlled trial, we aimed to evaluate the effects of a midwife-coordinated maternity care intervention (ChroPreg) in pregnant women with CMC. The intervention consisted of three main components: (1) Midwife-coordinated and individualized care, (2) Additional ante-and postpartum consultations, and (3) Specialized known midwives. The primary outcome was the total length of hospital stay (LOS). Secondary outcomes were patient-reported outcomes measuring psychological well-being and satisfaction with maternity care, health utilization, and maternal and infant outcomes. A total of 362 women were randomized to the ChroPreg intervention ( Worldwide the population of pregnant women living with chronic medical conditions (CMC) is increasing ,2,3, andQualitative evidence suggests that women with CMC also experience pregnancy and childbirth as fragmented with insufficient attention given to the women’s individual needs and the normal aspects of the childbearing experience .Evidence from previous randomized controlled trials (RCTs) including pregnant women with obstetric risk factors suggests that midwifery continuity of care models ,18,19, cThis trial used a two-arm parallel-group randomized trial design (1:1). The methods applied and a detailed description of the intervention have been published previously . The repThe trial was conducted at the Department of Obstetrics, Rigshospitalet, Copenhagen University Hospital from October 2018–August 2020, with follow-up completion by October 2020. The Department is a tertiary referral center with ≥5000 births annually. Pregnant women with a single fetus, one or more CMCs before pregnancy, aged ≥ 18 years, and who understood written and spoken Danish were eligible to participate. We defined CMC as any prolonged medical condition diagnosed >6 months before pregnancy, with continued reoccurrence and a need for medical treatment ,28. An oRandomization was performed in a 1:1 ratio between the ChroPreg intervention and Standard Care. The randomly generated allocation sequence was computer-generated with concealed varying block sizes. Allocation to study group was centrally administered by the online clinical trial management and randomization software EasyTrial . In Denmark, maternity care is tax-financed and free of charge, and most women give birth at public hospitals (97%) . AntenatWomen in the Standard Care group were referred to an obstetrician. An individual care plan was designed dependent on the character and severity of the respective CMC and the pregnancy-associated risks. Participants were also referred to a midwife for standard care antenatal consultations scheduled around weeks 14–18, 28, 35, 38, and 40. Consultations include physical examination, discussion about lifestyle and physical and mental well-being, symptoms of normal and complicated pregnancies, and breastfeeding-related issues. Antenatal classes consisted of two group sessions in an auditorium (90 min) delivered by midwives. Intrapartum care was provided by the midwives on call on the labor ward. Postnatal care was delivered by midwives, nurses, and obstetricians on the maternity ward. According to individual needs, postpartum consultations could be scheduled after hospital discharge at the woman’s request. This could be a debriefing session with a midwife, or, for women who had experienced severe or unexpected complications, a postnatal consultation with an obstetrician was offered.additional ante-and postpartum consultations, and (3) specialized known midwives  and two months after birth. Psychological well-being was assessed by the World Health Organization Well-being Index (WHO-5) , the Edi weeks anSecondary healthcare utilization outcomes and maternal and infant outcomes were collected from electronic medical records and described in detail in the study protocol . Data are presented by median values with Inter Quartile Ranges (IQR) and counts with percentages as appropriate. The power calculation was described in the study protocol . ExpectiThe secondary patient-reported outcomes  were compared at 33–37 weeks of gestation and two months postpartum. The comparisons were performed using a covariance pattern model, including the baseline measurement as an outcome. The models included the interaction between allocation group and time (baseline/33–37 weeks/two months postpartum) with the constraint that the means at baseline are equal due to randomization . An unstIn response to the global Covid-19 Pandemic , from 13n = 6608). Of these, 357 women were invited to participate. After verbal and written information, 63 women declined to participate. Between invitation and randomization, 32 women were excluded. In total, 262 women were randomized to either the ChroPreg intervention (n = 131) or Standard Care (n = 131). In each group, one woman withdrew consent after randomization. Moreover, the screening process had failed to identify that two women had pre-existing type 2 diabetes and they were therefore excluded. Thus, 258 women were included in the Intention-to-treat (ITT) analysis . Most women had one CMC, and the most prevalent types were endocrinological conditions, neurological conditions, and rheumatological conditions .Women in the ChroPreg intervention had a median of six antenatal consultations with their midwife, 90% participated in the postpartum telephone follow-up, and 85% in the debriefing session. The optional intervention components of weekly telephone hours and e-mail consultation were utilized by 27% and 33% of the ChroPreg participants, respectively . p = 0.97). When adjusting for age and parity, women in the ChroPreg group had 1.8% higher LOS (95%CI −5.0–9.1%) than the Standard Care group. In the ChroPreg group, 84/130 (65%) women had LOS ≤ 3 days compared with 75/128 (59%) in the Standard Care group (p = 0.32). We found no differences in LOS between the two allocation groups. The median LOS during the study period was three days in both groups . Women ip < 0.0001). A higher level of satisfaction was also found concerning the two domains of the pregnancy subscale; women in the ChroPreg group scored 3.3 points higher in Personal treatment  and 2.0 points higher in Information/education . We found no difference in the delivery subscale.The overall response rate to the online questionnaires was 96.5% in the 3rd trimester and 94.6% two months postpartum. We found no differences in any patient-reported outcomes measuring psychological well-being or health-related quality of life . An incrWe found no differences in maternal and infant outcomes between groups . p = 0.10). Due to a higher proportion of multipara in the ChroPreg group, an adjusted analysis was performed, and parity could not explain this tendency (p = 0.11). A non-significant difference was found in the mode of birth, where 98 women in the ChroPreg group had a vaginal birth compared with 84 women in the Standard Care group  planned consultations with midwives and obstetric doctors vs. 9 (IQR 8–12) in the Standard Care group . Women iIn this randomized controlled trial, we found no evidence to support that a midwifery-coordinated maternity care intervention could reduce the total LOS for childbearing women with CMC. Women in the ChroPreg group were, however, more satisfied with the maternity care they had received. Women in the ChroPreg group were especially satisfied with the care received during pregnancy in relation to the two domains, Personal treatment and Information, and education. The intervention was found to be safe, and adherence was high.Worldwide, the average LOS during pregnancy and childbirth has gradually declined . In 2001In line with other studies on midwife-led maternity care interventions ,19,49,50Recruitment of participants for the current trial progressed according to plan, and eligible women with CMC were interested in participating (81%). Adherence to all intervention elements was overall high, indicating that the women found the intervention meaningful and relevant.We had access to complete data on the primary outcome and all other outcomes collected from electronic medical records, ensuring a high internal validity. High response rates were also obtained for self-reported data collected through electronic questionnaires. We used validated psychometric tools to measure the patient-reported outcomes . The PCQAnother strength of the intervention is the potential reduction in the need to transfer pregnant women to other care teams. The experience from this trial showed that only one woman in the ChroPreg group (vs. 15 in the Standard Care group) needed a referral to other specialist midwives. This is in line with findings from a previous review of interventions of integrated maternity care .However, some limitations of the study design and methods should be discussed. First, we chose LOS as our primary outcome for this trial. Based on studies in mixed populations and populations with women of high risk that found a reduction of LOS in midwife-led interventions, we wished to assess if an intervention given to a population of women with CMC would reduce overall LOS. We hypothesized that, through improved self-reported psychological well-being and health-related QoL, women would feel empowered and more ready to cope with everyday life in pregnancy and the immediate postpartum period . HoweverSecondly, we excluded women with cardiac conditions, diabetes mellitus, substance abuse disorders, and psychiatric conditions as only CMC, because these women had already received maternity care which included some of the elements included in the ChroPreg intervention. Therefore, standard care would differ between these women and women with other CMCs. These conditions are, however, associated with risk of severe adverse maternal and neonatal outcomes ,59, and We included a wide variety of CMCs. According to national recommendations, to be eligible for the trial the pregnant woman should have at least one CMC that needed tertiary obstetrician-led care . By inclThird, we were not able to test a full scale midwife continuity of care intervention that also included intrapartum care. At the recruiting hospital it was not an organizational option of care at the time of the trial, but future studies should assess the effect of a midwife continuity of care model for women with CMC.Generalizing the findings from this trial to other populations of childbearing women with CMC must be done cautiously. It is necessary to consider that the study population was well-educated, averagely weighted, and non-smoking. Therefore, the results may not be generalizable to pregnant women with less advantageous characteristics. Blinding of participants and specialized midwives was not possible and introduced a risk of bias. We can, therefore, not preclude a degree of researcher or social desirability bias. We aimed to reduce this risk of bias by measuring outcomes with validated instruments and introducing an objectively measurable primary endpoint. For this trial, it was not possible to conduct a full-scale economic evaluation of the cost-effectiveness of the intervention ,61, as wChildbearing women with CMC are considered to have high-risk pregnancies, and maternity care for this population requires a high level of flexibility and specialization to ensure optimal outcomes. To our knowledge, this RCT was the first to compare a midwife-coordinated maternity care intervention with Standard Care for women with CMC. We found no difference in the LOS between the groups. We did, however, find that women in the ChroPreg group were overall more satisfied with maternity care. The intervention was feasible, safe, and easy to implement in a clinical setting. Further studies among women with CMC should consider measures of satisfaction with postpartum care and explore the effects of continuity of midwife-led care throughout the childbearing experience, including intrapartum care.


Objective: Disseminated intravascular coagulation plays a key role in the pathophysiology of sepsis. Thrombomodulin is essential in the protein C system of coagulation cascade, and functional polymorphisms influence the human thrombomodulin gene (THBD). Therefore, we conducted a multicenter study to evaluate the influence of such polymorphisms on the pathophysiology of sepsis.Methods: A collaborative case-control study in the intensive care unit (ICU) of each of five tertiary emergency centers. The study included 259 patients (of whom 125 displayed severe sepsis), who were admitted to the ICU of Chiba University Hospital, Chiba, Japan between October 2001 and September 2008 (discovery cohort) and 793 patients (of whom 271 patients displayed severe sepsis), who were admitted to the five ICUs between October 2008 and September 2012 . To assess the susceptibility to severe sepsis, we further selected 222 critically ill patients from the validation cohort matched for age, gender, morbidity, and severity with the patients with severe sepsis, but without any evidence of sepsis.Results: We examined whether the eight THBD single nucleotide polymorphisms (SNPs) were associated with susceptibility to and/or mortality of sepsis. Higher mortality on severe sepsis in the discovery and combined cohorts was significantly associated with the CC genotype in a THBD promoter SNP  [odds ratio [OR] 2.709 (1.067–6.877), P = 0.033 and OR 1.768 (1.060–2.949), P = 0.028]. Furthermore, rs2239562 SNP was associated with susceptibility to severe sepsis .Conclusions: The data demonstrate that rs2239562, the THBD promoter SNP influences both the outcome and susceptibility to severe sepsis. Sepsis is a global public death emergency, affecting millions of people worldwide, and representing one of the greatest global causes of mortality . CurrentTHBD.Recently, precision medicine has gained attention, particularly for multifactorial diseases in the critical care field, and disseminated intravascular coagulation (DIC) in the pathophysiology of sepsis has of late been increasingly recognized to play a key role as well as to be a therapeutic target . ThromboTHBD single nucleotide polymorphisms (SNPs) are associated with susceptibility to and/or mortality of sepsis. In addition, the present study aimed to evaluate the role of thrombomodulin in the pathophysiology of sepsis through a genetic association study with Japanese multicenter cohorts, focusing on the THBD gene polymorphisms.Accordingly, we postulated that some of the The subjects were recruited as part of a prospective, observational study of adults admitted during 2001–2012 into a network of Japanese intensive care units (ICUs). The study using these subjects has been reported elsewhere . The proIn total, 259 critically ill patients admitted to the ICU of Chiba university hospital in Chiba, Japan, between October 2001 and September 2008 were included . The incIn the multicenter validation cohort, 793 critically ill patients admitted to the general ICU of each of the five tertiary emergency centers of Kurume University Hospital, Tokyo Medical University Hachioji Medical Center, Hyogo College of Medicine, Kimitsu Chuo Hospital, and Chiba University Hospital (updated permission number 457) from October 2008 to September 2012 were included . The incTHBD genotypic distributions in whole blood genomic DNA from the critically ill patients with severe sepsis vs. non-sepsis with similar age, gender, severity of illness, and mortality to assess the genetic association for susceptibility to sepsis between the similar severity of critically ill patients. The patients with sepsis tend to die than the patients with non-sepsis do. Therefore, propensity score matching was implemented to compare THBD genotypic distributions between the severe sepsis and non-sepsis having similar severity, such as mortality. Controls were matched as follows: the participating centers submitted similar blood samples from critically ill patients who were not known to have sepsis. All the patients who did not meet severe sepsis criteria were placed into the matching pool, and those who had any evidence of sepsis were then excluded. Each patient with sepsis was tentatively matched with all the patients in the pool of the same gender and hospital discharge status . Then, each patient with severe sepsis was matched with one patient from its set of potential non-sepsis matches. The patient selection above was performed employing the propensity score matching method with a Greedy 5-to-1 digit-matching algorithm for the clinical factors, that is, age, gender, severity scores, and hospital discharge status. Once all the propensity-score matching was performed, we compared the baseline covariates between the two groups. Ultimately, 444 patients (222 with severe sepsis/septic shock (SS) while 222 displayed non-sepsis) were selected (We conducted a case-cohort study to compare the selected .The baseline characteristics (age and gender) and clinical data, such as length of ICU stay, Sequential Organ Failure Assessment (SOFA) scores , Acute PTHBD . Eight SNPs distributed in THBD and its promoter region  were investigated. We were able to assign the genotype in >95% of typed samples. To verify the genotypes of the SNPs, some were tested in a set of earlier Japanese samples . The genotyped SNPs can be found at dbSNP (http://www.ncbi.nlm.nih.gov/SNP/). The SNP genotyping matching rate was 100%, according to the earlier results (Genomic DNA was isolated from the banked whole blood specimens collected on ICU admission. We genotyped eight markers from the region surrounding THBD . GenotypTHBD SNP. Hardy–Weinberg equilibrium (HWE) for the population distribution of the variant alleles was determined according to the approach described by Guo and Thompson . Significant differences in the mean ± SD or median  values between the two groups were evaluated by using the Student's t-test or Mann–Whitney U-test, depending on the variables. The statistical analyses were performed using the GraphPad PRISM 8, version 8.3.0  for Windows. We considered differences to be significant at P <.05.The primary endpoint was a mortality of severe sepsis, and the secondary endpoint was susceptibility to severe sepsis concerning the Thompson . The alln = 259) and the multicenter validation cohort (n = 793). Mortality and the SOFA and APACHE II scores were significantly higher in the SS group than those in the non-sepsis group in both the cohorts , which indicated that there was no marked difference in severity in the SS patients between the two cohorts. In the validation cohort, trauma, heart failure, and intracranial diseases were overrepresented in the non-sepsis group.THBD, which are associated with the mortality of severe sepsis, genotyping of these polymorphisms was performed in the discovery cohort. The observed allele frequencies and genotypic distributions for the investigated polymorphisms are summarized in 3 , and 4 (combined cohort). The distributions of genotypes for all the investigated polymorphisms conformed to the HWE test (P > 0.01).To determine the frequencies of eight SNPs of P = 0.005, THBD promoter SNP  was found to be most significantly associated with mortality of SS group in the discovery cohort [odds ratio (OR) 2.709 , P = 0.033 in a dominant model with the trend test, OR 1.446 (0.782–2.675), P = 0.249, OR 1.768 (1.060–2.949), P = 0.028 in a dominant model with the trend test, The genotype call rate of the eight SNPs was 96.3–100%, although the genotypic distributions in rs1042579 diverged from the HWE in the studied subjects (THBD promoter SNP (rs2239562) and the THBD exon 1 SNP (rs41348347) were significantly different between the SS and non-sepsis groups with similar severity of illness [OR 1.593 (1.086–2.338), P = 0.017 and OR 0.107 (0.013–0.853), P = 0.011, respectively in a dominant model with the trend test, Because of the retrospective nature of the study, the baseline imbalances between the SS and non-sepsis existed; therefore, we identified 222 subjects from each of the SS and non-sepsis groups from the validation cohort by propensity score matching (17) to equalize morbidity of severe sepsis and severity of illness of both the cohorts . Figure  1 SNP rs1348347 wTHBD promoter SNP, rs2239562, had a significant influence on the outcome as well as the progress of severe sepsis/septic shock. First, we determined the worse outcome of severe sepsis to be associated with the CC (major) allele homozygotes of rs2239562. Intriguingly, the frequency of the CC carriers was also augmented in the SS in a propensity-matched patient cohort. In the pathophysiology of sepsis, THBD promotor may influence the thrombomodulin-guided APC function and limit endothelial cell damage   , caused rategies . Furtherh sepsis . The aboTHBD genetic association was relatively weak because the patient characteristics were very heterogeneous, such that it was challenging to show the influence on an outcome with the present sample volume. Interestingly, a recent study demonstrates that phenotype γ and δ reveals the characteristics of hematologic dysfunctions, such as coagulopathy  can be found in the article/The studies involving human participants were reviewed and approved by the Ethics Committee of Chiba University School of Medicine (permission number 205), the Ethical Committee of Kurume University (bioethics permission number 49), the Medical Research Ethics Committee of Tokyo Medical University, the Ethics Review Board of Hyogo College of Medicine (permission number 208), and the Ethics Committee of Kimitsu Chuo Hospital (permission number 120). The patients/participants provided their written informed consent to participate in this study.EW, MH, and SO: conceived and designed the experiments. YT, MO, and AT: performed the experiments. EW, YT, MO, BM, and MH: analyzed the data. OT, TS, TI, JK, NK, and EMS: contributed reagents, materials, and analysis tools. EW and GH: wrote the paper. All authors contributed to the article and approved the submitted version.The present study is partly funded by Asahi Kasei Pharma Corporation, which had no influence on the results of the present study (EW). Funded also by A-STEP (Adaptive and Seamless Technology transfer Program) through targetdriven R&D; AS251Z02001P) (EW). MO was the recipient of a Therapeutics Research Initiative Grant from Chiba University School of Medicine 2018-S3.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


P < 0.0001) and 2018  and in the pre-education answers between years . Praziquantel mass drug administration attendance improved, rising from 64% to 91% (P < 0.0001), alongside improved latrine use, from 89% to 96% (P = 0.005). This community-consulted and -engaged SEP resulted in substantial improvements in children’s understanding of schistosomiasis, with improvements in praziquantel uptake and latrine use. Socioculturally tailored education programs can help gain schistosomiasis control. Continued investment in SEP will help promote the future well-being of children through increased participation in control and treatment activities.Schistosomiasis control requires multisectoral approaches including praziquantel treatment, access to safe water, sanitation and hygiene, and health education. Community input can help ensure health education programs are culturally appropriate to effectively direct protective behavior change. This study reports on the three-stage development of an education program for Malagasy children, with an impact evaluation on their knowledge, attitudes, and practices (KAP) related to intestinal schistosomiasis. A cross-sectional study took place in 2017 with follow-up in 2018 in the hard-to-reach Marolambo district, Madagascar. A novel schistosomiasis education program (SEP) was designed in collaboration with researchers, stakeholders, and local community and included cartoon books, games, songs, puzzles, and blackboard lessons, costing $10 USD per school. KAP questionnaires were completed by 286 children pre-SEP and 273 children post-SEP in 2017, and by 385 and 337 children pre-SEP and post-SEP, respectively, in 2018. Improvements were observed in responses to all questions between pre- and post-education answers in 2017 (53–77%,  Here, miracidia are released from the eggs and infect certain freshwater snails. The obligatory intermediate snail hosts in turn release numerous cercariae into fresh water, where they can come into contact with humans.Schistosomiasis is a NTD that affects approximately 290 million people worldwide and results in 1.4 million disability-adjusted life years lost each year.,,–Optimal disease prevention, control, and acceptance of regular PZQ treatment relies on sustained and appropriate knowledge, attitude, and practices (KAP) in the community.S. mansoni infection and high burden of disease among school-age children,–Marolambo is a highly remote and hard-to-reach rainforest district in Madagascar, hyperendemic for intestinal schistosomiasis, with an 88% to 98% prevalence of This study was carried out in six villages in the Marolambo district: Marolambo, Ampasimbola, Ambohitelo, Marofatsy, Vohidamba, and Betampona. Marolambo is a remote district in the east of Madagascar , with an estimated population of 215,000, although limited anthropometric data exist. The villages were chosen purposively based on the advice from local officials that the safety of the team could not be guaranteed in other villages in the region. In each study village selected, there is a single government school, overseen by district education officials in Marolambo village. In the Marolambo village, private schools exist in addition to the government school. Altogether, there are 290 schools across 190 villages in the district. There are no formal government-led education programs on schistosomiasis or MDA in Madagascar.Malagasy and French are the official languages of Madagascar and are taught in schools, including in rural villages of Marolambo where a local dialect, Betsimisaraka Atsimo, is also commonly spoken. Communities in the Marolambo District rely on environmental water from the Nosivolo River for drinking, cooking, washing, and transport . There are gravitational water supply systems that provide water through a series of pipes from streams to the villages. However, these are prone to environmental damage and are rarely repaired, meaning they are unreliable sources of water. Villages and schools have simple pit latrines, built from mud, sticks, or concrete .S. mansoni in the six villages, the Ministry of Health, Madagascar, has provided MDA to all school-age children in the district. Before this, there had not been an MDA in the Marolambo district since 2008.Following our research in 2015 showing a high prevalence of S. mansoni prevalence and infection intensity in response to MDA, using repeated annual cross-sectional studies in the same villages, the methodology of which has been previously published.This schistosomiasis education study was a nested component of a research program on A pilot KAP questionnaire was designed with input from Malagasy medical students and local leaders in 2015. It was written in English  and translated into Betsimisaraka Atsimo  by three Malagasy doctors who reached a consensus with the translation. The pilot KAP was pretested among children aged 5 to 14 in Marolambo in 2016, and corrections to both the content and delivery in language were made using informal feedback from participants, interviewers, and teachers. An effort was made to minimize scientific terms and use easily understandable phrases so it could be understood by all targeted age groups; the only scientific word, “schistosomiasis,” was translated into the local vernacular “Bilharziose.”The formal KAP questionnaires were completed by participants the day before and after delivery of the SEP in each village in June 2017 and June 2018. Questions were read from the questionnaire by the Malagasy researchers and verbal responses recorded in Malagasy, then back-translated into English. Participants were not time pressured, and questions were rephrased to facilitate understanding, particularly in young or illiterate participants. Each child was asked away from the presence of others to limit external influence and thereby reduce bias. Each answer was marked as correct or incorrect by a single investigator (to prevent interobserver variation) and checked by a second investigator to ensure agreement and prevent misclassification. If there was a discrepancy in marking, the original answer was reviewed again and a consensus reached. Participant answers relating to questions on attendance to the previous year’s MDA were verified by checking local MDA attendance registers.To establish a control group, MDA register data were collected post hoc from six comparable schools in the Marolambo district that did not participate in this MADEX-SEP study: Lycée Marolambo, Center d’Enseignement Général Marolambo, École FLM 1, École FLM 2, CESAM, and École Papillion. MDA attendance from these nonparticipating (SEP-naïve) schools was compared with MDA attendance from SEP-participating schools to determine the impact of the SEP on MDA attendance.The design, development, and delivery of the education program involved three stages  in partn,Baseline understanding and prior perceptions about disease were ascertained from the 2016 pilot KAP survey and used to guide key messages of the SEP. After this, focus group discussions (FGDs) were held in 2016 in each of the six villages, which included representatives of the local communities: all local traditional and elected leaders attended as well as all school teachers and health workers. Community members, parents, and children were also invited to attend through convenience sampling after village announcements. Discussions in the FGDs established the importance of schistosomiasis education and highlighted that misconceptions of PZQ treatment jeopardized attendance to MDA.1.A.Posters and puzzles B.Blackboard classroom teaching C.Scolly the Schisto Bug; Supplemental Figure 7)Cartoon book (D.S. mansoni parasites).Playground game (based on the lifecycle of the Schistosomiasis transmission and prevention (with teaching on parasite lifecycle) using infographics, traditional education tools, and gameplay:2.E.Schistosomiasis songSchistosomiasis treatment (and mass drug administration) using music:The education program was designed through collaboration with the University of Manchester, Madagascar Ministry of Health, students and doctors from the University of Antananarivo, peer community members, local doctors, and teachers. A combination of didactic, interactive and kinesthetic learning methods were created so that the program catered to different ages and learning modalities. The education program used the following educational tools to teach on schistosomiasis transmission, prevention, and treatment:In June 2017 and June 2018, teaching was delivered by both Malagasy members of the MADEX team and local teachers. First, local teachers were taught how to teach the SEP by MADEX doctors and scientists. Local teachers then delivered the SEP to all children in the local dialect, observed by Malagasy team members. All children rotated through each of the five educational activities. Because of the logistical demands of the research expedition in such a remote environment, the SEP delivery was limited to 1 day in each village. Head teachers were instructed how to train new teachers, and all teachers were encouraged to continue teaching the SEP when appropriate thereafter.The overall cost for each pack was $10 (USD) per village, $7.50 for materials and $2.50 for printing and binding. All resources were left in schools of each village to allow for future use and continuity, including the lyrics for the songs to allow them to be easily relearned if forgotten.S. mansoni. Participants were provided with a single sterile stool container to provide a single fecal sample. Two thick smears (containing 41.7 mg of stool) were prepared from each stool sample using the Kato-Katz  method.S. mansoni eggs.S. mansoni eggs. To ensure reliability one in every 10 slides was reexamined by a second researcher who was blinded to the findings from the first reading. If a difference was identified, the slide was reexamined and a consensus reached. S. haematobium was not tested for because a previous study demonstrated that this species is not endemic in the Marolambo district.Parasitological examinations were performed in June 2017  to determine the number of study participants infected with Ethical approval was granted by the University of Manchester Research Ethics Committee (UREC3 #16153) and the Ministère de la Santé Publique de Madagascar (No. 621/001/2016-CEER/INSPC). Written consent for participation in the study was obtained from the child and their parent/guardian. All data were anonymized.Questionnaires were completed on paper, and answers were transferred to Microsoft Excel . Statistical analyses were performed using StataCorp 2017 . chi-square analyses were used to 1) examine infection prevalence between groups of children when stratified by river contact behavior, 2) assess for differences in the percentage of correct responses in questionnaire data between years, and 3) compare MDA attendance among children from the six MADEX SEP-participating schools to children from six nonparticipating SEP-naïve schools. Matched McNemar’s chi-square analyses were performed on paired within-year questionnaire data (comparing pre- versus posteducation KAP responses). Kolmogorov-Smirnov tests were used to test for differences in male and female answers and Spearman’s rank to assess for correlation between age and percentage of correct responses.There were 286 of 300 (95%) respondents for the preeducation questionnaire in 2017 of whom 273 of 286 (95%) returned to complete the posteducation questionnaire. In 2018, 385 of 400 (96%) children attended the preeducation questionnaire, and 337 of 385 (88%) completed the post-questionnaire .P < 0.0001, odds ratio [OR]: 3.05, 95% confidence interval [CI]: 2.68–3.46) and 2018 . The percentage of correct preeducation answers also improved between 2017 and 2018 from 53% to 72% .The knowledge- and attitudes-related questions revealed variable and mixed answers in the preeducation questionnaire in 2017; the percentage of correct answers ranged from 11% and 79% . Improver = 0.45, P < 0.0001; 2017 posteducation: r = 0.49, P = 0.0001; 2018 preeducation: r = 0.51, P < 0.001; 2018 posteducation: r = 0.30, P < 0.0001).Older children were more likely to provide correct answers .There were no differences in scores between male and female participants . After the delivery of the SEP in 2017, the 91% attendance from SEP-participating schools was significantly higher than the 42% attendance rate among children from SEP-naïve schools . Among SEP-naïve schools, the decline in MDA attendance from 74% to 42% was significant .Questions relating to practices—namely, MDA attendance, river contact behavior, and place of defecation—were only asked in the preeducation questionnaires each year. Among the SEP-participating children, there was an increase in MDA attendance from 64%  to 91% , and the percentage reporting to defecating on the ground reduced from 10% to 3% , and the percentage with no contact with the river decreased from 24% to 5%  of children. Among children who had no contact with the Nosivolo River, the prevalence of egg-patent infection was 61% ; this waThis is the first study to attempt and successfully implement a three-stage design with community consultation, engagement, and participation, to deliver a socioculturally appropriate SEP in a hard-to-reach area. In addition, this is the first assessment of KAP relating to intestinal schistosomiasis in a hyperendemic area of Madagascar. Our initial assessments in 2017 demonstrated large gaps in knowledge of schistosomiasis, similar to reports elsewhere.,,,,Children from SEP-participating schools had 91% MDA attendance after the SEP—more than double the attendance rates compared with children from SEP-naïve schools. Among SEP-naive schools, MDA attendance fell from 74% (2016) to 42% (2017), which likely reflects misconceptions regarding PZQ, fears of side effects, and lack of perceived benefits in the absence of education, as ascertained during the focus group discussions and reported in studies elsewhere in Africa.S. mansoni than those with no river contact. Our work with this community highlights the dependence on the river and supports renewed community-directed efforts to ensure access to clean water in this area. Despite our educational efforts, there was an increase in reported contact with infested water between 2017 and 2018. This observation does not negate the use of our education program and may simply reflect changing infrastructure. For example, the number of gravitational water sources in the six villages fell from 27 to nine between 2017 and 2018 as a result of environmental damage and the lack of resources available for repairs to be made. Similar studies in Egypt, Zimbabwe, and Ethiopia showed that improved knowledge did not always result in reduced water contact, particularly where safe water supplies were not available.S. mansoni cercariae in both rice paddies and freshwater sources.,Our data highlight that frequent water contact is concerning, showing that children who had contact with the river had a higher likelihood of infection with ,–This SEP consisted of five educational tools, including didactic and interactive school-based blackboard lessons, group activities solving puzzles and jigsaw, songs, games, and cartoon books. Previous research has demonstrated improvements in schistosomiasis knowledge after a similar range of educational activities.Although there was no control comparator for knowledge assessments, we believe improvements in schistosomiasis understanding are likely to be related to our teaching program because there were no other health education programs in this area before or during the study. Our KAP questionnaire may have be subject to responder or observer bias, although we attempted to limit this in our methodology. The cross-sectional study design assesses the impact of the SEP intervention on school populations. Although there may have been variability in the teaching standards between schools, all teaching was observed to minimize this. Despite these limitations, this health engagement study puts forward the first data on a successful community participation in a context-appropriate health education program in rural Madagascar, with promising findings that can help benchmark future health education delivery in rural areas and offer feasible inclusion in the school curriculum in endemic regions.,,Previous studies have shown how local involvement in health education helps interrupt transmission of schistosomiasis.,,The SEP was delivered by community peer members, who can help with approachability, acceptability, and reach of both health education and research projects.The SEP was designed to be low-cost, durable, sustainable, and easily maintained by the community. Educational tools such as the song and the game were zero cost and can continue to be played by the children after the SEP. School teachers were also trained in delivery of the education program. This allows for the repetition of key educational messages over time and helps to retain knowledge. Enhanced awareness of infection among children may further improve knowledge in the wider community due to dialogue between children and their families, leading to wider changes in the area. Previous work on education awareness has shown that immigrant communities have been empowered to share newly learned knowledge with their families, that teachers often feel enabled to continue sharing new knowledge independently,Successful scale-up of education activities will require attention to the culture, ethnicity, and language of the target population. This is likely to be a particular challenge in countries comprising multiple ethnic and cultural groups, such as Madagascar. The three-stepped, community-engaged methodological approach discussed in this study provides a framework that can be followed to adapt the SEP to allow for scale-up to other communities and can also enable expansion to tackle the information and education of other neglected tropical diseases.This health education strategy resulted in a positive impact on understanding of intestinal schistosomiasis among schoolchildren. Importantly, MDA attendance improved among children who attended the SEP in contrast to a fall in MDA attendance among SEP-naïve children in the same district. Continued investment in SEP is required to promote future well-being of children through increased participation in disease control and treatment activities. It is also vital for schistosomiasis control programs to ensure that there is sufficient access to safe water, sanitation, and hygiene, in addition to the necessary health education, treatment, and snail control in high-transmission, hyperendemic zones such as this.Supplemental materials