Obesity is associated with the presence of low-grade inflammation even during childhood. The dysregulation in the secretion of adipokines, such as leptin, which occurs in obesity states, could be associated with an increase in inflammatory factors already at an early age. In this cross-sectional study, we aimed to investigate the role of leptin levels in the association between body mass index (BMI) and high-sensitivity C-reactive protein (hs-CRP) in healthy schoolchildren. Leptin and hs-CRP levels were analyzed in two pediatric cohorts comprising 684 prepubertal children and 763 adolescents. hs-CRP concentrations correlated significantly with BMI and leptin levels in prepubertal males and females as well as in adolescents. However, after adjusting for leptin concentration, no significant correlation was observed between hs-CRP and BMI in prepubertal children, while the correlations remained significant in adolescents. The same differences were observed when analyzed BMI according to hs-CRP tertile after adjusting for leptin; mean BMI was not significantly different between hs-CRP tertile in prepubertal children but was significantly different in adolescents. In conclusion, the fact that leptin concentrations determine the association of BMI with hs-CRP levels in prepubertal children, but not in adolescents, suggests a role for leptin in low-grade inflammation at early ages, while other factors seem to contribute to hs-CRP levels later in life. Obesity was related to the presence of a systemic low-grade inflammatory state, even during childhood ,2. C-reaThe dysregulation of adipocytokine secretion that occurs in obesity states was consistently associated with an increased secretion of a number of inflammatory factors, as these adipocytokines that are secreted from adipose tissue are involved in inducing the production of CRP . AdiposeAmong the adipokines secreted by adipose tissue, leptin was consistently associated with the development of obesity-related complications . It was Using a cross-sectional epidemiologic design, the aim of the present study was to analyze the potential influence of leptin levels in the association between body mass index and hs-CRP concentrations in two cohorts of children, prepubertal children (age 6 to 8 years) and adolescents between the ages of 12 and 17 years.We analyzed two population-based samples comprising 684 prepubertal children (6-to-8-year-olds) and 763 adolescents with ages between 12 and 17 years. This was a sub-study of the Four Provinces Study, a cross-sectional study designed to analyze cardiovascular risk factors in children. A more detailed information on the study design is available in previous publications . The selThe study protocol was approved by the Clinical Research Ethics Committee of the Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD). This investigation was carried out in accordance with the principles of the Declaration of Helsinki and subsequent reviews, as well as the prevailing Spanish legislation on clinical research in human participants .Children who, according to parents’ reports, suffered from metabolic, endocrine, hepatic, or renal disorders were excluded, due to possible alterations in the values of the variables of interest . SpecialOral presentations of the study were carried out at each center selected in the sample and a letter was sent to the parents of the children invited to participate in the study with information on the objectives and procedures of the same. Then, all parents were required to give written consent for their children to be included.In each center, the information was collected by a field team made up of a doctor, a nurse and a group of people trained in completing the food consumption frequency questionnaire, obtaining information from the mothers of the children or the people in charge of preparing the menu.2) was calculated from these parameters [Measurements (weight and height) were taken with children barefoot and wearing light clothing as reported . Height rameters .Venous blood samples were obtained early in the morning, after a 12 h fasting period, by venipuncture into Vacutainer tubes containing EDTA-Na2 as anticoagulant. Then, samples were placed on ice bath, and centrifuged at low speed. The plasma was separated and frozen for future biochemical determinations.Plasma leptin levels were determined by ELISA using a commercially available kit  . C-reactDiet information was available in the cohort of pre-pubertal children of our study. As reported previously , food anStatistical analyses were performed using the SPSS software package, version 26.0  and the GraphPad Prism statistical software . The Kolmogorov–Smirnov test was used to determine whether the variables under study were normally distributed. Spearman correlation and partial correlation analyses were performed to evaluate the association between the variables under study in both cohorts of children. Analysis of variance (ANOVA) and the Games–Howell post hoc test were used to compare body mass index and leptin levels by hs-CRP tertile. Univariate analyses of variance were performed to analyze the associations between body mass index and hs-CRP by age group and sex after adjusting for leptin levels.Our population comprised 327 6-to-8-year-old males and 357 females of the same age as well as 358 males and 405 females within a range of the ages between 12 and 17 years. The average age of the participants in our study was 7.2 ± 0.6 years in the prepubertal group and 14.4 ± 0.8 years in the group of adolescents. No significant differences between sexes were observed.The values of hs-CRP were below or equal to the detection limit in 33% of 6–8-year-old children and in 26% of 12–16-year-old children .p < 0.001), as well as between body mass index and hs-CRP concentrations in both males (p < 0.01) and females (p < 0.001) of the younger cohort. However, the correlation between body mass index and hs-CRP was not significant in these children after adjusting for leptin levels (p < 0.001) for body mass index with leptin and hs-CRP concentrations. In this group, the correlations between body mass index and hs-CRP remained significant after adjusting for leptin concentration (A significant positive correlation was found between body mass index and leptin levels (n levels . In 12-tntration .p < 0.001) differences between tertiles at both ages. Leptin levels also varied significantly across hs-CRP categories in both prepubertal boys (p < 0.001) and girls (p < 0.01) and in 12-to-17-year-old boys (p < 0.001) and girls (p < 0.01), showing a significant increase across hs-CRP tertiles  and girls (p < 0.01)  c but sho < 0.01) c.We previously described an inverse association of fruit and vegetable intakes with hs-CRP concentrations in the prepubertal females; thus, we decided to analyze the potential influence of these intakes on the association between body mass index and hs-CRP concentrations in the cohort of 6-to-8-year-old children of our study. No significant results were found.Previous research on cardiovascular risk factors in Spain using the same cohort of prepubertal children described here found that leptin concentration influenced the association between obesity and features of insulin resistance . In the Leptin seems to regulate proinflammatory immune responses and was related to CRP secretion . CRP is Leptin levels were associated with IL-6 in a study investigating the relationship of these adipocytokines with overweight and obesity in participants at different ages . InteresAlong with these previous reports, our findings reporting that the correlation between body mass index and hs-CRP disappeared when we adjusted for leptin levels in prepubertal children, while the association remained significant after the adjustment in adolescents, may indicate an important role of leptin in the earlier phases of obesity-related inflammation. The role of leptin in the pathogenesis of inflammatory responses was established ,28, and The seemingly unessential role of leptin in older children suggests the existence of other mediators of hs-CRP levels. CRP was found to be increased in both liver and adipose tissue in obese patients . It was A relationship between diet and hs-CRP concentrations was previously reported by our group in adults  as well Unfortunately, data on IL-6 concentrations were lacking from our study, as we were unable to measure this parameter. As a result of this primary limitation to our study, further research taking into consideration IL-6 levels is needed to clarify these findings. An additional important limitation is the lack of information on fat mass, which would have enabled us to compare this aspect between the two pediatric cohorts.Further research is required to clarify the role of leptin in inflammation.The association of body mass index with hs-CRP concentrations in prepubertal children seems to be mediated by leptin levels, while the increased hs-CRP concentrations associated with higher body mass index in adolescents appears to remain independent of plasma leptin concentrations and may be related to other factors.


Plant-parasitic nematodes (PPN), especially sedentary endoparasitic nematodes like root-knot nematodes (RKN), pose a significant threat to major crops and vegetables. They are responsible for causing substantial yield losses, leading to economic consequences, and impacting the global food supply. The identification of PPNs and the assessment of their population is a tedious and time-consuming task. This study developed a state-of-the-art deep learning model-based decision support tool to detect and estimate the nematode population. The decision support tool is integrated with the fast inferencing YOLOv5 model and used pretrained nematode weight to detect plant-parasitic nematodes (juveniles) and eggs. The performance of the YOLOv5-640 model at detecting RKN eggs was as follows: precision = 0.992; recall = 0.959; F1-score = 0.975; and mAP = 0.979. YOLOv5-640 was able to detect RKN eggs with an inference time of 3.9 milliseconds, which is faster compared to other detection methods. The deep learning framework was integrated into a user-friendly web application system to build a fast and reliable prototype nematode decision support tool (NemDST). The NemDST facilitates farmers/growers to input image data, assess the nematode population, track the population growths, and recommend immediate actions necessary to control nematode infestation. This tool has the potential for rapid assessment of the nematode population to minimise crop yield losses and enhance financial outcomes. While the majority of nematodes in the soil are free-living and beneficial to plant growth , plant pTo mitigate the problem caused by PPN, farmers commonly use a range of traditional and mechanical methods such as crop rotation, resistant cultivars, and destruction of crop root remnants ,11. PPN Effective and efficient application of pesticides can eliminate pests while minimising soil damage and environmental contamination, thus maximising crop productivity. This can be facilitated by the accurate identification and quantification of PPN. Traditionally, PPN are identified and counted using a manual microscope. Although this method is relatively simple, it is laborious and time consuming. Alternative approaches to the manual identification and quantification of nematodes include methods based on Deoxyribonucleic Acid (DNA) ,15, morpGlobodera pallida and Globodera rostochiensis morphological features (stylet length) . Th. Th70]. Django is a Python server-side framework that facilitates Model-View-Controller (MVC) architecture and supports relational databases . The MVCThe MySQL database was used to store NemDST data. Three main modules for the preliminary testing of PPN detection and counting NemDST were designed . The EntThe pest detection module uses the YOLOv5 model as a background process to classify and count the number of PPN and FLN. For juvenile detection, this module employs the YOLOv5 weight file computed from the RKN detection model . It facin is the number of classes and kAP is the average precision of class k.In machine learning, a confusion matrix is an arrangement of actual and predicted classes of objects in rows and columns . The evan denotes the number of samples, iy represents the actual value, iŷ denotes the predicted value, and iȳ is the mean value of the actual value for i = 1 ….. n.The coefficient of determination (Equation (3)) is a dimensionless measurement of the proportion of variance in the dependent variable that can be computed from independent variables .(3)R2=1y is the actual value, y′ is the predicted value, and n is the number of samples.Mean absolute percentage error (Equation (4)) is defined as the proportion of actual values and predicted value to the actual value taken for the n number of data points .(4)MAPEAfter training three YOLO models, they are subsequently assessed on the validation set. The result of nematode egg detection on the test set is shown in 2 = 0.964 and MAPE = 3.582, whereas YOLOv6-480 showed the lowest correlation of manual and machine counting with R2 = 0.957 and MAPE = 2.978. The lowest correlation was due to an increase in the number of false positives, as the YOLOv6 model detected soil particles as RKN eggs. This might be caused by insufficient training data. The YOLOv7-640 surpassed the outcome of RKN egg detection using conventional image processing and computer vision methods [The machine and manual counting results of RKN eggs are shown in  methods . YOLOv7- methods . YOLOv5- methods  and accuMost nematode studies are limited to the identification task ,27,29; nEven though YOLOv5-640 achieved the highest accuracy in terms of detecting nematodes, this model can be modified in terms of the loss function and optimisation criteria to attain greater accuracy in nematode detection and counting. In addition, the YOLOv5-640 model can be compared to several other convolution neural networks for nematode detection. Further, these models can be utilised to assess different datasets of nematodes from a wider range of geographical locations and growing conditions or even detect microorganisms and pests. In addition, this study can be further explored by utilising the latest YOLOv8 model to estimate the nematode population.Once the user submits the plant-parasitic nematode images, the DST system displays the detection of nematodes and their quantity as shown in This study explored a deep learning-based decision support tool for plant-parasitic nematode management that holds promising applications in modern agriculture. By implementing state-of-the-art deep learning techniques and integrating them with the YOLOv5 model, this tool offers a great advantage in rapidly estimating nematode populations, particularly their juveniles and eggs. The performance of the YOLOv5 model exhibited significant application in pest management. This tool enables farmers to assess nematode populations efficiently, enabling timely intervention and minimising crop yield losses. The implications of this innovation extend beyond improved yields; it has the potential to enhance financial outcomes, ensure food security, and reduce the environmental impact caused by unnecessary pesticide use. In comparison to conventional machine learning methods like random forest ,82, suppWhen compared with similar studies in the context of plant diseases in tropical crops, this research has significant applications. Plant diseases can have catastrophic effects on tropical crops, where climatic conditions often favour the proliferation of pests and diseases ,85. WhilThis study built a new prototype decision support tool (NemDST) integrated with a deep learning-based detection model that facilitates rapid and innovative methods for plant parasitic nematode identification and assesses the magnitude of nematode infestation. The NemDST utilises the state-of-the-art YOLOv5 to classify and count plant parasitic nematodes at juvenile and egg stages. The system provides fast and efficient tools to estimate the plant-parasitic nematode population and provide information about nematode management tactics. Further, the NemDST stores nematode data in the database, helps the farmer keep track of the nematode population for future studies, and applies appropriate nematode management practices. The NemDST can be further extended to develop integrated pest management (IPM) using machine learning and deep learning technologies.


The fecal immunochemical test (FIT) is the most widely used test for colorectal cancer (CRC) screening. RAID-CRC Screen is a new non-invasive test based on fecal bacterial markers, developed to complement FIT by increasing its specificity. The test was previously clinically evaluated in FIT-positive patients , in which it reduced the proportion of false positive results by 16.3% while maintaining most of FIT20’s sensitivity. The aim of this study was to compare the sensitivity and specificity of a CRC screening program using RAID-CRC Screen in addition to FIT20 as a triage test in a European screening population undergoing screening colonoscopy with a CRC screening program with FIT20 alone in the same cohort. A cohort of 2481 subjects aged > 55 years from the German screening colonoscopy program was included. The colonoscopy findings were used as the gold standard in calculating the diagnostic capacity of the tests and included 15 CRC and 257 advanced neoplasia cases. RAID-CRC Screen added to FIT20 provided the same sensitivity as FIT20 alone (66.7%) in detecting CRC and a significantly higher specificity . The positive predictive value was 11.9% when using RAID-CRC Screen and 9.5% with FIT20 alone, and the negative predictive value was 99.8% in the two scenarios. For advanced neoplasia detection, the use of RAID-CRC Screen yielded significantly lower sensitivity than with FIT20 alone , and the overall specificity was significantly higher when using RAID-CRC Screen compared with FIT20 alone . Our findings confirm the results obtained in previous clinical studies in a CRC screening setting, showing the potential of RAID-CRC Screen to increase the overall specificity of FIT-based screening. Colorectal cancer (CRC) is the third most-frequently diagnosed cancer and the second in mortality worldwide, accounting for more than 935,000 deaths in 2020 . CRC is Most European countries offer CRC screening to average-risk populations from the age of 50 years, based on a two-step approach in which non-invasive tools are used as a triage test to determine who should proceed to a confirmatory colonoscopy . Widely The use of lower cut-off values of FIT enables a higher detection rate of colorectal tumoral lesions. However, this comes at the expense of reduced specificity, generating a higher false-positive rate and, therefore, increasing the number of unnecessary colonoscopies which, in turn, may result in potential adverse events and additional healthcare costs. An alternative strategy might be to increase the effectiveness and efficiency of population-based screening programs. To this end, a new tool called RAID-CRC Screen was developed to improve the specificity of FIT, thereby reducing the false-positive rate as part of a three-step approach to the CRC screening program .Gemella morbillorum and Bacteroides fragilis as opportunistic pathogens; Faecalibacterium prausnitzii [Subdoligranulum variabile), and B48  as butyrate-producing bacteria [RAID-CRC Screen is a non-invasive tool for CRC screening based on a specific fecal bacterial signature that, used in addition to a positive FIT result, increases the overall specificity and positive predictive value (PPV) of both CRC and advanced neoplasia (advanced adenoma and/or CRC) detection by selecting for colonoscopy only patients with a positive fecal bacterial signature in addition to a positive FIT result . The fecusnitzii , B46  in which 172 patients with a positive FIT were enrolled , adding RAID-CRC Screen reduced the proportion of false positive FIT20 results by 34% (32/94), while maintaining 100% and 94% of FIT20’s sensitivity for CRC and advanced neoplasia (AN), respectively [The aim of this study was to compare the sensitivity and specificity of a CRC screening program using RAID-CRC Screen in addition to FIT20 as a triage test in a European screening program undergoing screening colonoscopy with a CRC screening program with FIT20 alone in the same cohort.The analysis is based on data from the BLITZ study, a large ongoing study conducted in the context of the German screening colonoscopy program in which blood and stool samples are collected from average-risk persons before a routine screening colonoscopy. The German screening colonoscopy program offers colonoscopy as a primary screening examination for men and women aged ≥ 55 years (in 2019 the starting age for men was lowered to 50 years). Screening colonoscopies are mostly conducted in gastroenterology practices, and the program has implemented rigorous quality control measures. The study was approved by the ethics committee of the Heidelberg Medical Faculty of Heidelberg University. Written informed consent including usage of stored samples for future studies was obtained from each participant. Further details of the BLITZ study have been previously reported –14.Fecal samples collected before bowel cleansing from participants aged ≥ 55 years recruited in 2012–2016 were retrospectively selected for inclusion in this analysis. We excluded samples from participants who had a personal history of CRC, colorectal adenomas, colorectal polyposis, or inflammatory bowel disease, a positive fecal occult blood test in the six months before fecal sample collection, had undergone colonoscopy or flexible sigmoidoscopy in the five years prior to study recruitment, had received antibiotic treatment within one month or chemotherapy and/or radiotherapy within 6 months of fecal sample collection, had severe comorbidities, or other diseases and/or surgery that compromised the transit of the digestive system, or pregnancy at the time of fecal sample collection.vs. FIT20 alone. Two one-sided McNemar tests with a significance level of 0.05 (estimated proportions of discordant pairs of 10%) was used. With an estimated 10% advanced neoplasm prevalence, approximately 2480 samples were included retrospectively to achieve a sufficient number of positive colonoscopies.A minimum of 248 fecal samples from subjects with advanced colorectal neoplasm , and 1507 fecal samples from participants with negative colonoscopy  were required to achieve 80% power to demonstrate both non-inferiority in sensitivity and superiority in specificity of the RAID-CRC Screen approach in situ, sessile serrated adenoma ≥1 cm, or any other finding with high-grade dysplasia.Colonoscopy and histology reports were reviewed by trained investigators who were blinded to the fecal testing results. Each participant was classified according to the most advanced finding at colonoscopy. Adenomas were defined as advanced if they matched any of the following features: size ≥1 cm, tubulovillous or villous architecture, or high-grade dysplasia. Advanced Neoplasia (AN) include CRC, advanced adenoma, pTis neoplasia and adenocarcinoma Stool samples were collected at home using sterile feces container before study participants started bowel preparation for the colonoscopy. Samples were stored by the participant in the freezer  and brought to the gastroenterology practice in a temperature isolated bag on the day of the colonoscopy. Thereafter, the samples were stored at -20ºC, sent in a cooling chain to a central laboratory, and finally stored at -70ºC in the German Cancer Research Center (DKFZ).For this analysis, 100 mg aliquots obtained from the deep-frozen stool samples at the DKFZ biobank were transported in frozen conditions to GoodGut .Fecal samples were thawed to collect samples with the FIT collector for the FIT analysis and to extract DNA. FIT was performed using OC-Sensor IO  48 hours after sample thawing. DNA was extracted using the DNeasy Powersoil Pro kit  according to the manufacturer’s instructions and eluted to 100 μl final volume and stored at -20ºC until use.F. prausnitzii (FPRA), G. morbillorum (GMLL), and B. fragilis (BCTF) [The specific bacterial sequences targeted were those included in RAID-CRC Screen: Eubacteria (EUB), B46, B48, s (BCTF) . Biomarkt value obtained outside the dynamic range, i.e. the interval of relative abundance in which a given bacterial marker can exist.In the qualitative analysis, the absence of a biomarker was defined as a CInvestigators analyzing the samples were blinded to the participants’ diagnoses.The RAID-CRC Screen algorithm had previously been defined in a proof-of-concept study (study code RAID-CRC 20202015) in 172 subjects who participated in the Catalan CRC screening program and had a FIT- positive result [Sensitivity, specificity, overall accuracy, positivity rate, positive and negative likelihood ratios, and positive and negative predictive values of a CRC screening program using RAID-CRC Screen in addition to FIT as a triage test were compared with those of a CRC screening program using FIT alone, using in both cases the FIT cut-off value recommended by the manufacturer . The diagnostic accuracy was determined using the results of the screening colonoscopy as the gold standard. Endpoints evaluated were (i) detection of AN; and (ii) detection of CRC.Differences in sensitivity, specificity, accuracy, and the positivity rate between the use or not of RAID-CRC Screen together with FIT as a triage test were evaluated for statistical significance by the McNemar test; statistical significance was defined as a p-value <0.05 in a two-sided test. Differences in likelihood ratios were evaluated using a regression model  with a 0To evaluate the concordance of our results with those of other studies in independent cohorts that were based on FIT positive participants only , we addiIn the 2481 screening colonoscopy participants , advanced neoplasms were detected in 257 (10.3%) participants, and 84 (3.4%) were classified as positive when using RAID-CRC Screen in addition to FIT20 as a triage test. When RAID-CRC Screen was applied in addition to FIT20 it yielded an overall sensitivity of 17.5% and specificity of 98.2% for the detection of AN and a sensitivity of 66.7% and specificity of 97% for CRC detection.For the detection of AN, RAID-CRC Screen added to FIT20 had significantly higher specificity than FIT20 alone  and significantly-lower sensitivity . No significant differences were observed regarding the PPV or positive likelihood ratio (LR) and only marginal differences were found for the NPV and negative LR .For the detection of CRC, RAID-CRC Screen combined with FIT20 had significantly-higher specificity than FIT20 alone  and equal sensitivity (66.7%). The PPV and positive LR were marginally higher for the RAID-CRC Screen and FIT20 combination, whereas no differences were observed for the NPV and negative LR .post-hoc analysis considering only FIT20 positive patients (N = 105). In the subgroup of FIT20 positive patients (N = 105), 45 out of 56 participants with AN and 10 out of 10 participants with CRC also had a positive RAID-CRC Screen . These results are in line with and confirm previous results obtained in a clinical study which was restricted to participants preselected by a positive FIT in clinical practice [The gain in specificity and reduction in unnecessary colonoscopies of approximately 20% estimated for the additional use of RAID-CRC Screen in our study, should be weighed against the loss in sensitivity of approximately 20% in detecting advanced neoplasms. An additional consideration is the time course of colorectal carcinogenesis. The development from advanced neoplasm to CRC typically takes many years, and a substantial proportion of advanced neoplasms will not develop into clinically manifest CRC during screenees’ lifetime . The lowAs stated by the Colorectal Cancer Screening Committee of the World Endoscopy Organization, when considering the introduction of a new test and its clinical accuracy in the screening context, the effect on other variables in the screening pathway should be considered . In partWhile the bacterial signature of RAID-CRC Screen was shown to increase specificity in our study, its use should be further compared with alternative approaches to increase specificity, such as an increase or decrease in FIT positivity cut-offs , 29 or tOne of the RAID-CRC Screen medical device characteristics is that it is based on the fecal bacterial signature, which suggests that this signature could not be a universal panel since the dietary products and the associated eating habits and geographical provenance of individuals all have an influence on gut microbiota diversity , 33. AltThe study has strengths and weakness. Major strengths are the large overall sample size in an average-risk screening population, and the availability of screening colonoscopy results for all participants. However, despite the large overall size, the number of participants with CRC was still rather small (n = 15) which reflects the low prevalence of CRC in screening settings. Estimates of sensitivity for CRC detection and the impact of adding RAID-CRC Screen to FIT20 on that sensitivity, therefore, need to be interpreted with caution. Likewise, the results were restricted to the use of RAID-CRC Screen in the FIT20 cut-off of one specific FIT brand only. Future studies should assess the performance of the combination of RAID-CRC Screen with other FIT brands and other positivity thresholds. In particular, based on the data obtained it would be promising to explore the combination when the FIT cut-off is lowered. In such a scenario, it is expected that the increased sensitivity provided by FIT and the potential higher specificity achieved when adding RAID-CRC Screen as a triage test would lead to higher detection rates with greater precision, thus requiring fewer colonoscopies than when using FIT alone. Even though the results were highly consistent with those from a preliminary Spanish clinical study , furtherOur results suggest that a three-step approach using the combination of FIT20 and RAID-CRC Screen as a triage test to select subjects for colonoscopy may potentially avoid a significant number of unnecessary colonoscopies compared with a two step approach where FIT is used alone. Further research should address the effectiveness and cost-effectiveness of using RAID-CRC Screen along with FIT-based screening compared with existing and alternative screening options in order to best define its potential use for enhanced CRC screening.S1 Checklist(DOCX)Click here for additional data file.


Radar-based personal identification and fall detection have received considerable attention in smart healthcare scenarios. Deep learning algorithms have been introduced to improve the performance of non-contact radar sensing applications. However, the original Transformer network is not suitable for multi-task radar-based applications to effectively extract temporal features from time-series radar signals. This article proposes the Multi-task Learning Radar Transformer (MLRT): a personal Identification and fall detection network based on IR-UWB radar. The proposed MLRT utilizes the attention mechanism of Transformer as its core to automatically extract features for personal identification and fall detection from radar time-series signals. Multi-task learning is applied to exploit the correlation between the personal identification task and the fall detection task, enhancing the performance of discrimination for both tasks. In order to suppress the impact of noise and interference, a signal processing approach is employed including DC removal and bandpass filtering, followed by clutter suppression using a RA method and Kalman filter-based trajectory estimation. An indoor radar signal dataset is generated with 11 persons under one IR-UWB radar, and the performance of MLRT is evaluated using this dataset. The measurement results show that the accuracy of MLRT improves by 8.5% and 3.6% for personal identification and fall detection, respectively, compared to state-of-the-art algorithms. The indoor radar signal dataset and the proposed MLRT source code are publicly available. Due to the rapidly increasing aging population and the COVID-19 pandemic, assisted living systems with intelligent personal identification have become concerning issues in IoT-based smart healthcare systems. Additionally, correctly identifying a person involved in a falling incident and providing timely warnings to nursing workers can help prevent severe injuries. Contact devices such as electrocardiogram (ECG) monitors and photoplethysmograph (PPG)-based wearable devices are commonly used for person identification. However, these devices have limitations and low adaptability in daily living conditions and movement  as they Radar fulfills these unobtrusiveness requirements as a non-contact sensor, which is privacy-preserving and able to detect both body and cardiorespiratory movements. To enable personal healthcare in an indoor environment, different radar-based methods have been researched in recent years for personal identification. Ref.  designedAs for fall detection, most existing radar-based methods rely on extracting a set of features ,9 from tIn indoor environments, it is beneficial to determine the identities of different individuals while also detecting falls to enhance personalized monitoring performance. As a result, several methods ,15,16 haInspired by the Transformer and self-attention mechanisms, we propose the Multi-task Learning Radar Transformer (MLRT): a personal Identification and fall detection network based on IR-UWB radar as shown in 1. To deal with different persons in different environments, a multi-task learning radar Transformer network is proposed for both personal identification and fall detection to utilize the radar time-series signals. MLRT takes a “backbone-discriminator” multi-task learning network to exploit the correlation between the personal identification task and the fall detection task, thus enhancing the performance of discrimination. The proposed method is more robust and has better performance on radar signals than state-of-the-art methods.2. Considering the signal distortions from moving persons and background noises which can affect the performance of MLRT, a signal processing method is applied on radar signals before feeding forward into the network. After Direct Current (DC) removal and bandpass filtering, a Running-Average (RA) method is applied for clutter suppression. A Kalman filter is applied for trajectory estimation.https://github.com/bupt-uwb/MLRT (accessed on 23 March 2023).3. A dataset is generated with an IR-UWB radar for personal identification and fall detection. The radar data are generated in the indoor environment with a total of 11 persons × 10 min. The experiments are performed in the zone in front of the UWB radar sensor, approximately 5 m × 5 m. Radar data are collected from a person who suddenly falls while walking randomly. The proposed MLRT and other existing methods are evaluated on this dataset. This dataset is now available at The rest of this paper is organized as follows. t is the pulse accumulative time, IR-UWB radar periodically transmits narrow impulse signals with wide bandwidth. The received signal can be expressed as the sum of the channel’s response and variations caused by vital signs:R represents the n-th received frame with M fast time sampling points  and their variants, such as Long Short-Term Memory (LSTM) and Gated Recurrent Unit (GRU), are specifically designed to model and retain temporal correlations in time-series signals. However, these networks operate sequentially, which can result in information loss for long sequences and hinder parallel computation. Transformer networks, on the other hand, overcome this limitation by leveraging self-attention mechanisms, which have gained recognition for their ability to handle time-series data. However, directly applying Transformer networks to radar signals may yield suboptimal results. Therefore, it is essential to adapt the architecture of Transformer networks to suit the characteristics of radar signals and their specific applications.The fast-time dimension, which represents the spatial dimension of the radar signal matrix, covers a wide range of distances. However, the echo signals reflected from the target person only occupy a relatively small portion of this dimension, indicating that some unnecessary or redundant features may be extracted. To address this, a CNN layer can be employed to compress information along the fast-time dimension and extract spatial features simultaneously. To preserve the time-dependent features along the slow-time dimension of radar signals, the same convolutional operations with identical parameters need to be applied to each individual fast-time slice, which corresponds to each row of the radar signal matrix. To achieve this, a Time-distributed CNN layer is proposed. This layer consists of a 1D Convolutional layer, which performs convolution calculations on each row of the radar signal matrix independently in time. Along the slow-time dimension, the parameters of the convolutional kernel remain unchanged until the entire time-series radar signal is processed. To extract effective spatial features from the radar signal, the size of the convolutional kernel should be close to or slightly smaller than the size of the target to be detected. In the experimental settings of this article, one person occupies approximately 30 columns in the radar signal matrix. Hence, a 1D Convolutional layer with a kernel size of 20 and padding of 2 is utilized in the Time-distributed CNN layer.Q), Key (K) and Value (V). The three matrices are obtained by linear transformation through the same input. Then, the attention score is calculated asQ. The final output is obtained by multiplying the score matrix and V.After the Time-distributed CNN layer and a dropout layer to address overfitting concerns, the attention mechanism from Transformer is employed to assign appropriate weights to the time-series radar signal, highlighting its temporal features. In contrast to traditional manual feature extraction methods, the attention mechanism effectively concentrates on valuable features, allowing neural networks to focus on subsets of features that are most informative. The multi-head attention mechanism is derived from the encoder module in Transformer. It captures time-related information from the features and finds widespread application in machine translation, natural language processing, and other domains. This mechanism resolves the issue of the model excessively attending to its own position when encoding information about the current position. The module is formed through the combination of several self-attention operations. The key is matrix Query , a similar architecture called “backbone-discriminator” is employed. This architecture is used because both personal identification and fall detection tasks involve classification, but with different numbers of classes.To apply multi-learning on both fall detection and personal identification, a joint loss function should be designed. The joint loss function of two classification tasks can be expressed as:The value of The whole architecture and parameters of MLRT is shown as In the experiment, a Xethru X4M03 radar  is used for data collection. The experiments include identification and fall activities running in parallel, as seen in The experiments are divided into three parts: fall events, non-fall events, and daily activities. During a 20-s fall event, the target subject freely walks for the first 10 s and then falls down perpendicular to the radar line of sight at a distance of 2 m from the radar. Each event has a duration of approximately 20 s, and the fall occurs randomly within the last 10 s of the event.Personal identification and fall detection are performed simultaneously from the moment the target enters the experiment zone until the end of the experiment. In non-fall events, the target subject walks randomly for 20 s without falling.Each person’s experiment is repeated 30 times, including 15 fall events and 15 non-fall events. Additionally, to further evaluate the method’s effectiveness in real scenarios, five specific daily activities are included: squatting down, sitting, turning around (the target continuously rotates), waving arms (the target raises and rotates the arms freely), and lying down. The locations and movements of the targets are not fixed during data collection, and the targets maintain slight random body movements to simulate normal human behavior. These daily living activities consist of a total of 160 samples. Each sample has a duration of 20 s, similar to the falling samples, and the activity occurs randomly within the last ten seconds of each sample.A sliding window approach is applied to each 20-s sample with a window length of 10 s and a step size of 0.5 s. The signals within each window are preprocessed as described in . All the methods are trained for 50 epochs equally with a batch size of 64.To demonstrate the effectiveness of the proposed MLRT in identification, comparisons with other methods are carried out on the dataset in this article. One is the LSTM network based on LIDAR . A two-lThe personal identification accuracy is calculated using ten-fold cross-validation in which the training set and test set are divided by a certain ratio randomly. The performances are investigated to distinguish 11 persons with different proportions of training sets which are presented in This article introduces the MLRT method for personal identification and fall detection in indoor living environments. It addresses challenges posed by signal distortions from moving individuals and background noise through signal processing techniques. Preprocessing steps include DC removal, bandpass filtering, clutter suppression using RA, and trajectory estimation with a Kalman filter. This mitigates interference and enhances signal quality. The MLRT framework utilizes a multi-task learning radar Transformer network that handles personal identification and fall detection tasks simultaneously. It adopts a “backbone-discriminator” architecture to leverage the inherent correlation between these tasks. Experimental results using a dataset from 11 individuals in an indoor environment demonstrate outstanding performance. MLRT achieves an average personal identification accuracy of 98.7%, surpassing state-of-the-art methods. Fall detection accuracy with MLRT is 96.5%, outperforming other approaches. These results validate MLRT’s effectiveness in accurately identifying individuals and detecting falls. Future work will extend MLRT to incorporate vital signs monitoring for personalized healthcare. Additionally, research efforts will focus on recognizing human activities and gestures.


Long-acting injectable antipsychotics (LAIA) have provided a significant improvement in the treatment of schizophrenia. Although there is already significant clinical experience with paliperidone palmitate, it is important to evaluate the clinical response of patients to this new 6-monthly presentation, so descriptive studies based on real clinical evidence can be very useful for this purpose.The main objective of the study is to describe the use of 6-monthly paliperidone palmitate in routine clinical practice, providing variables that objectify the evolution such as the number of admissions and visits to the emergency room.Retrospective descriptive study with a sample selected by non-probabilistic consecutive sampling, retrospective type, in a time interval of 12 months (n=40). The patients selected were all those who received 6-monthly paliperidone palmitate treatment, with a diagnosis of schizophrenia, in 12 months of use at Hospital Universitario Infanta Elena. A descriptive analysis was performed. Mean and standard deviation were calculated for quantitative variables and N and percentage for categorical variables.A total of 40 administrations of 6-monthly paliperidone palmitate were performed in the study. None of the patients presented adverse reactions related to the administration of the drug, not reporting local pain or inflammation of the puncture area, except for the characteristic discomfort of an intramuscular puncture. Regarding the efficacy of 6-monthly paliperidone palmitate, none of the patients presented a psychotic decompensation after its administration, maintaining psychopathological stability after the change. The switch to 6-monthly paliperidone palmitate was made from both 1-monthly paliperidone palmitate and 3-monthly paliperidone palmitate, both showing the same efficacy. Regarding tolerability, all the patients who were administered 6-monthly paliperidone palmitate were previously treated with the monthly and quarterly presentation of the same molecule, having presented good tolerability to it, maintaining said tolerability after treatment. change to 6-monthly paliperidone palmitate, with no adverse reaction being recorded after the change. The adherence presented by the patients was very good, performing 100% of the administrations of 6-monthly paliperidone palmitate6-monthly paliperidone palmitate may be an effective and well-tolerated treatment for the treatment of schizophrenia. In the present study, the use of said LAIA in a group of 40 patients is objectified, showing excellent efficacy and tolerability. All study patients were already stable with the 1-monthly and 3-monthly paliperidone palmitate formulations, maintaining said psychopathological stability when switching to the 6-monthly paliperidone palmitate formulation, with excellent adherence and adverse effect profile .None Declared


Older adults living in long-term care facilities (LTCF) have been severely affected by COVID-19. Hospice care (HC) facilities and palliative care are essential in treating patients dying from COVID-19. In Italy, little is known about the impact of COVID-19 on deaths in LTCF and the care provided in HC to COVID-19 patients.To assess overall and case-specific mortality in 2020 in LTC and HC facilities in comparison to the previous five years (2015–2019).We performed a descriptive study using data derived from the Italian national “Cause of Death” registry—managed by the Italian National Institute of Statistics—on deaths occurred in LTC and HC facilities during 2020 and the period 2015–2019.Number of deaths significantly increased in 2020 compared with 2015–2019 in LTCF  and slightly decreased in hospices . COVID-19 caused 12.5% of deaths in LTCF and only 2% in hospices. Other than COVID-19, in 2020, cancer accounted for 77% of all deaths that occurred in HC, while cardiovascular diseases (35.6%) and psychotic and behavioral disorders (10%) were the most common causes of death in LTCF. Overall, 22% of the excess mortality registered in Italy during 2020 is represented by the deaths that occurred in LTCF.LTCF were disproportionally affected by COVID-19, while the response to the pandemic in HC was limited. These data can help plan strategies to limit the impact of future epidemics and to better understand residential care response to COVID-19 epidemic.The online version contains supplementary material available at 10.1007/s40520-023-02426-7. COVID-19 poses a direct threat to older adults, who are intrinsically more at risk of adverse outcomes , are usuOlder adults in long-term care facilities represent a population that has been particularly affected by COVID-19 due to the intrinsic vulnerability of the residents, who are often institutionalized because of the higher prevalence of multiple health conditions and disability , 8, 9. AHospice care facilities are designed to provide multidimensional care, aiming to reduce physical, psychological, social, and spiritual suffering , 16. TheWith this work, we aimed to assess case-specific mortality in 2020 in long-term care and hospice care facilities compared to the previous five years (2015–2019), with a specific focus on COVID-19. We also aimed to evaluate excess mortality by cause in these settings.www.iris-institute.org, accessed on 23 November 2022), which attributes ICD codes for approximately 80% of cases; the remaining 20% are reviewed by expert personnel. For each case, the underlying cause of death defined by the World Health Organization (WHO) as “the condition that initiated the train of morbid events leading to death” was selected. COVID-19 coding was performed by the latest recommendations by the WHO [Deaths of the Italian resident population that occurred in 2015–2020 were analyzed. We compared different causes of death observed in 2020 in the Italian resident population to the ones observed in the previous five years (2015–2019), in terms of the mean number of casualties. Causes of death were derived from the national Cause of Death registry, managed by the Italian National Institute of Statistics, which collects copies of death certificates completed by the medical certifiers for all deaths occurring in Italy. All causes reported on the death certificate are classified according to the International Classification of Diseases, 10th Revision (ICD10) , using t the WHO .The present study considered only deaths in patients who received care in a hospice or long-term care facilities (including care homes and nursing homes). The number of beds available and patients admitted to HC facilities and the number of beds available in long-term care facilities during the study's period are presented in Supplementary Materials (Supplementary Table S1).In Italy, hospice care is provided by the National Healthcare System . The “Sistema Sanitario Nazionale” fully covers the costs of care. The number of palliative care units has continuously expanded since the mid-2000s and provides advanced home care, hospice, and consulting services. For this study, only hospice care is considered.Case di Riposo”) are assisted living facilities for older adults who are partially self-sufficient and present primarily social needs. Nursing homes provide residential healthcare and social support to individuals with different clinical conditions including chronic patients who are not autonomous .Long-term care facilities in Italy cover care homes and nursing homes. Care homes , consistent in both semesters analyzed. Conversely, a slight reduction was documented in the number of fatalities occurred in hospice care facilities , especially during the second semester of 2020. The number of deaths that occurred in long-term care facilities due to COVID-19 was 10,395 . Deaths due to causes other than COVID-19 also increased in 2020 as compared with the 2015–2019 period (+ 16% deaths). COVID-19 seemed to have a minimal impact on deaths in hospice care facilities, with only 790 deaths due to COVID-19 .Table Finally, a comparison between the mean number of cause-specific deaths that occurred in the period 2015–2019 and the year 2020 is presented in Table We conducted a descriptive study to assess case-specific mortality in long-term care and hospice care facilities during the year 2020 in comparison to the previous five-year time (2015–2019), with a specific focus on COVID-19. We have underlined that COVID-19 had a relevant impact on deaths that occurred in LTCF, while hospice care facilities were less significantly affected by this condition. Residents who died during 2020 in long-term care facilities were on average older than those in hospice facilities and, more often, females. In Italy, independently of the study settings, an excess mortality of 108,178 deaths during the whole of 2020 compared to the previous five-year time was registered . Based oEspecially during the first wave of the pandemic, long-term care facilities have been disproportionally affected by COVID-19, accounting for almost 50% of COVID-19-related deaths , and fraNoticeably a substantial increment of deaths that occurred in long-term care facilities due to respiratory diseases was observed in the first semester of 2020. This finding can be due to the lack of SARS-CoV-2 diagnostic tests in the first period of the pandemic. Therefore, many patients may have been classified as dying by respiratory diseases  rather than by COVID-19.The response to the pandemic in hospice care facilities was very limited, even if efforts to standardize palliative care for COVID-19 patients were made on a national scale. Hospice care facilities rarely activated an admission path for patients positive for SARS-CoV-2 infection. Italian hospices continued to register mainly cancer-related deaths while COVID-19-related deaths were extremely low. A survey conducted in the U.S. on hospice agencies underlined how healthcare professionals found that inadequate supplies of PPE had an essential impact on the delivery of care during the first year of the pandemic especially, as well as the reduced number of personnel in hospices insufficient to respond to the increase in family bereavement needs efficiently. More importantly, almost one-third of respondents reported adverse effects on patient outcomes, such as inadequate symptom management and negative psychosocial effects which can be explained by shorter visitations of healthcare providers and family members to reduce probabilities of contact . The numIn conclusion, the data we have presented describe the scenario experienced in two different types of residential care facilities in Italy, during the first year of COVID-19 Pandemic. These data can help understand the strategies adopted in the first epidemic phase, when the National Healthcare System was unprepared to face the challenges posed by COVID-19 and to plan strategies to limit the impact of future epidemics.Supplementary file1 (DOCX 14 KB)Below is the link to the electronic supplementary material.


Attention-deficit/hyperactivity disorder (ADHD) is a chronic neuropsychiatric disorder, that typically manifests itself during childhood and persists in a majority of the affected individuals into adulthood, negatively affecting physical and mental health. Previous studies have shown detrimental effects of the COVID-19 pandemic on mental health in individuals with ADHD. Thus, telemedicine could be a useful tool for optimizing treatment-outcomes in adult ADHD by improving treatment adherence and persistence. However, data on telemedical treatment outcomes in adult patients with ADHD is scarce.We report here the sub-cohort analysis of a naturalistic cohort of adult patients (N = 254) recruited between April 2020–April 2021, comparing the effects of telemedical treatment on participants either clinically diagnosed with depression (N = 54) or ADHD (N = 67). Participants were asked to fill out the WHO-5 repetitively during >12 weeks of telemedical treatment. Furthermore scores of WHO-5, SCL-90R and BDI-II, psychopathology, psychosocial functioning, sociodemographic data, medical records and a feedback survey were analyzed for both groups and compared. Participants with ADHD were further stratified according to the development of well-being during the study period in order to identify factors associated with a satisfactory treatment outcome.p = 0.03, Mann–Whitney-U-Test), suggesting successful treatment was hampered by the combination of ADHD and depressive symptoms. Furthermore, female sex among ADHD patients was correlated with an unfavorable treatment outcome during the course of the study  as well as living with children .Participants with depression reported a significant improvement of well-being during the course of the study, while no such effect could be seen in participants with ADHD on a group level. Despite the good outcome, participants with depression were more severely affected at baseline, with significantly worse psychopathology and a more precarious labor and financial situation. A detailed analysis of ADHD participants without clinical improvement revealed significantly higher BDI-II scores than for ADHD participants with a satisfactory outcome (Besides screening for depressive symptoms before telemedical treatment, future research should address the specific needs of female ADHD patients as these patients may be at a particularly high risk of being overburdened with family work. AtteThe COVID-19 pandemic was associated with high rates of symptoms of insomnia, anxiety, depression and psychological distress in the general population , with yoAt the initial stages of the COVID-19 pandemic, telemedicine was - despite limited evidence - considered as an additional means of expanding the delivery of mental health services to patients with ADHD  and faciThe current analysis - building on the sample of the exploratory study mentioned above  – invest2.2.1.Here, we report the analysis of a sub-cohort of our recently published study . This moRecently, we determined a robust and favorable response to telemedical treatment among patients with depressive disorders in this patient cohort, whereas patients with chronic neurodevelopmental disorders like ADHD did not experience significant improvement at a group level . Therefo2.2.All participants analyzed in this study (N = 67 with ADHD and N = 54 with depression) gave informed consent to analyze their medical records, including sex, age and sociodemographic data as well as their psychiatric history and standardized professional ratings of psychopathology for the purpose of the study. As described previously , all men2.3.2.3.1.We used the WHO-5 for the assessment of overall well-being during telepsychiatric counseling. The WHO-5 is a short self-administered measure of well-being, covering the last 2 weeks before completion of the questionnaire . The WHO2.3.2.The SCL-90-R by Derogatis  measures2.3.3.During the second or third online survey via REDCap participants could also complete the BDI-II. 19 (35.2%) of the participants diagnosed with depression and 33 (49.3%) of the participants diagnosed with ADHD completed the BDI-II. The BDI-II is a widely used 21-item instrument, validated for the self-report of depressive symptoms experienced during the past 2 weeks , 36. Ind2.3.4.While the WHO-5, SCL-90-R and the BDI-II are self-report questionnaires focusing on the subjective perception of overall well-being and different symptom domains, the GAF and CGI were used as clinician-rated scales to document the global impairment due to patients’  health conditions. CGI  scores i2.3.5.Thirty-two (59.3%) of the participants with depression and 45 (67.2%) of the participants with ADHD completed an evaluation questionnaire asking for feedback concerning technical details . Moreover, patients were asked for their overall satisfaction with telepsychiatric consultations. Participants were asked how helpful they found the telemedical interventions during the study period and if they were comparable to conventional face to face consultations. Patients were also requested to state their preference about using telepsychiatry in the future again. Participants were also asked if and how the COVID-19 Pandemic had influenced their mental well-being.2.4.All data acquired during surveys and from medical records were entered into an Excel master file and then translated to SPSS Version 27 and R Version 4.2.0.1. for further analysis. The descriptive statistics of the sample were computed for the sociodemographic characteristics, consisting of frequencies and percentages for categorical values and mean and standard deviations (SD) and for scale variables. Differences between two groups of patients (patients with depression vs. ADHD patients or ADHD patients with or without improvement on the WHO-5 well-being index) were assessed using the Mann-Witney-U test for the different non-parametric clinical scale variables or the Chi-Square tests for frequencies of the categories in the sociodemographic parameters.r. For all tests, a value of p of less than 0.05 was considered statistically significant.A paired Wilcoxon signed-rank test was used to assess differences in the levels of mental health variables, e.g., the results of the WHO-5 during subsequent inquiries. To this end, only data from subjects was included, who had participated in all inquiries .3.We previously reported that telemedical treatment in a naturalistic patient cohort N = 254) during the COVID-19 pandemic supported mental well-being as measured by the WHO-5 well-being index and the SCL-90-R  and 8–12 weeks . In contrast, ADHD patients without children benefited more from telemedical treatment during the COVID-19 pandemic than ADHD patients who were living together with children during the study period . Further analyses, examining correlations between the outcome on the WHO-5 and different sociodemographic factors  were not conclusive (Thirty-three patients with ADHD (49.3% of the participants diagnosed with ADHD) also completed the BDI-II. Participants with ADHD and no improvement or even a further decline on the WHO-5 during the course of the study , had sighe WHO-5 . Female nclusive .4.The data presented here builds on an earlier exploratory study that aimed at describing the changes of symptoms of psychiatric outpatients during telemedical treatment during the COVID-19 pandemic, identifying patient groups with beneficial or less favorable treatment outcomes, determining sociodemographic factors with an impact on the effectiveness of telepsychiatric treatment, and specifying patients’ experiences with telepsychiatric consultations compared to conventional face to face treatment by mental health experts. The objective of the current analysis was to identify factors that distinguish patients with a depressive disorder, who experienced the best treatment outcome, from patients with poorer treatment results on a group level, namely patients with ADHD. Secondly, the data was screened for factors that allowed for a better differentiation between ADHD patients with a satisfactory treatment outcome and ADHD patients with a stagnating or even worsening mental health status.Comparing the two groups of patients that experienced the highest and the least improvement in well-being during telemedical psychiatric treatment in our study, namely patients with either clinically confirmed depression or ADHD, patients with depression more frequently reported financial debt and unemployment. At the same time patients with ADHD were more likely to have children. Nevertheless, sociodemographic characteristics could not explain the significant difference in treatment outcomes between both groups. Clinical diagnoses of depression and ADHD were mirrored by clinicians’ standardized ratings of psychopathology, substantiating the validity of diagnostic procedures during telemedical treatment. Patients with depression reported a significantly greater impairment in well-being on the WHO-5 index and a higher burden of psychopathology on the SCL-90-R in combination with a lower clinician-rated global functioning on the GAF and CGI scales at baseline. However, during the course of the study, patients with depression experienced a substantial improvement of well-being, while ADHD patients’ well-being scores stagnated or even deteriorated on a group level. There was a statistically non-significant tendency of patients with ADHD to engage in less telemedical appointments than their depressed counterparts. However, patients with depression and participants with ADHD were equally satisfied with the treatment they received. Stratification of patients with ADHD according to the development of well-being during the study period revealed no differences in well-being, psychopathology and global functioning at baseline between patients with an improvement in well-being and those without. Hence, patients with ADHD who experienced improvement during telemedical treatment were not already less impaired at the beginning of treatment. The frequency of telemedical consultations was also evenly distributed between both groups of patients. Yet, ADHD patients with a lack of improvement or even a further decline of well-being during the study reported a higher load of depressive symptoms on the BDI-II than ADHD patients with a favorable treatment outcome. Furthermore, female patients with adult ADHD and patients living with children were more likely to experience an unfavorable treatment outcome.Generally, quality of life is significantly reduced in patients with ADHD compared to their healthy peers . DepressAttention-deficit/hyperactivity disorder research on psychiatric treatment and support during the COVID19 pandemic has largely neglected adults, older adults and females as well as minority groups . On the On a general level, our findings basically corroborate results from an earlier study that found female children and adolescents with a mental illness during the COVID-19 pandemic to be at a higher risk for psychological burden than their mentally healthy peers . Yet, inIn this context, it has to be emphasized that the presence of depressive symptoms on the BDI-II does not necessarily imply the clinical diagnosis of depression . FurtherFinally, the results of our study overall corroborate earlier findings that remote communication for psychiatric assessment and treatment during the COVID-19 pandemic was found useful, effective, reliable and satisfactory by adult patients with ADHD , albeit There are several limitations that have to be taken into account concerning the interpretation of the above mentioned data. Due to the pandemic situation, a randomization of participants to different treatment modalities (face to face vs. telemedicine) was not feasible. Furthermore, treatment choices were purely guided by patients’ preferences and experienced clinicians’ advice and experience. Thus, heterogeneity in treatment modalities during the course of telemedical treatment, e.g., the administration of behavior-therapy oriented and mindfulness-based interventions vs. generic counseling in combination with psychopharmacological treatment, cannot be excluded. Furthermore, women with mental disorders may have higher odds of COVID-19 infection than males with the strongest gender disparity for ADHD . Partici5.When assigning adult patients with ADHD to telemedical treatment options in clinical practice, special attention needs to be paid to monitoring the development of symptomatology and treatment outcomes. A change to face to face treatment should be a low-threshold offer despite patients’ subjective satisfaction with telemedical treatment modalities. Women with ADHD, patients living with children and ADHD patients with a high load of depressive symptoms and/or diagnosed with a depressive disorder might not respond adequately to telemedical treatment. Therefore, such treatment options should be considered with caution during the treatment of patients with the aforementioned characteristics.Future cross-sectional and longitudinal research should focus on sex differences in ADHD symptoms and treatment outcomes and the development of responsive interventions , aiming The original contributions presented in the study are included in the article/The studies involving humans were approved by Ethics committee II of the medical faculty Mannheim, University of Heidelberg approved under license no. 2020-562 N. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.A-SW and PP designed the study. TR, PP, and A-SW acquired the data. AB developed the online survey tool. A-SW and TP analyzed the data. OH, HT, and AM-L advised and discussed the data. PP, TP, and A-SW wrote the manuscript with the help of all authors. All authors contributed to the article and approved the submitted version.


The hepatitis C virus (HCV) prevalence rate among injection drug users (IDUs) in North America is 55.2%, with 1.41 million individuals estimated to be HCV-antibody positive. Studies have shown the effectiveness of syringe service programs (SSPs) alone, medications for opioid use disorder (MOUD) alone, or SSP+MOUD combination in reducing HCV transmission among opioid IDUs.To evaluate the cost-effectiveness of SSP alone, MOUD alone, and SSP + MOUD combination in preventing HCV cases among opioid IDUs in the United States.We used a decision tree analysis model based on published literature and publicly available data. Effectiveness was presented as the number of HCV cases avoided per 100 opioid IDUs. A micro-costing approach was undertaken and included both direct medical and nonmedical costs. Cost-effectiveness was assessed from a public payer perspective over a 1-year time horizon. It was expressed as an incremental cost-effectiveness ratio (ICER) and an incremental cost savings per HCV case avoided per 100 opioid IDUs compared with cost savings with “no intervention.” Costs were standardized to 2019 U.S. dollars.The incremental cost savings per HCV case avoided per 100 opioid IDUs compared with no intervention were as follows: SSP + MOUD combination = $347,573; SSP alone = $363,821; MOUD alone = $317,428. The ICER for the combined strategy was $4,699 compared with the ICER for the SSP group. Sensitivity analysis showed that the results of the base-case cost-effectiveness analysis were sensitive to variations in the probabilities of injection-risk behavior for the SSP and SSP + MOUD combination groups, probability of no HCV with no intervention, and costs of MOUD and HCV antiviral medications.The SSP + MOUD combination and SSP alone strategies dominate MOUD alone and no intervention strategies. SSP had the largest incremental cost savings per HCV case avoided per 100 opioid IDUs compared with the no intervention strategy. Public payers adopting the SSP + MOUD combination harm-reduction strategy instead of SSP alone would have to pay an additional $4,699 to avoid an additional HCV case among opioid IDUs. Although these harm-reduction programs will provide benefits in a 1-year time frame, the largest benefit may become evident in the years ahead. What is already known about this subjectHarm-reduction strategies such as syringe service programs (SSPs) or medications for opioid use disorder (MOUD) are effective in reducing the risk of hepatitis C virus (HCV) acquisition.Using these harm-reduction strategies in combination is more effective than using them separately.What this study addsThe SSP + MOUD combination intervention dominated both MOUD and “no intervention” strategies when a public payer perspective was undertaken.All harm-reduction strategies yielded significant cost savings when compared with a no intervention strategy over a 1-year period.Among opioid injection drug users in the United States, the SSP + MOUD combination intervention is cost-effective if payers are willing to pay $4,699 or more per HCV case avoided.4 According to the Centers for Disease Control and Prevention (CDC), the estimated number of new HCV cases was 44,700 in 2017. The rate of acute HCV reported had increased from 0.7 per 100,000 people in 2013 to 1.0 per 100,000 people in 2017.5 The HCV prevalence rate among injection drug users (IDUs) in North America is 55.2%, and about 1.41 million are estimated to be HCV-antibody positive.6 Approximately 2.4 million people in the United States are living with HCV infection.7 In 2017, there were 17,253 HCV-related deaths in the United States, which is about 4.13 deaths per 100,000 people.Hepatitis C virus (HCV) is the leading cause of chronic liver disease, liver transplantation, and liver-related mortality and morbidity in the United States.9 In 2018, the total economic cost of the opioid crisis was estimated at $696 billion (3.4% of the gross domestic product) and more than $2.5 trillion from 2015 to 2018.10IDUs are at greater risk of developing HCV infection, and the growing number of HCV cases in the United States is attributed largely to opioid misuse.11 SSP programs can be implemented in a fixed or nonfixed setting on a local community level. While there is very low-quality and insufficient evidence on the effect of SSP on HCV acquisition risk in North America, there is evidence of reduced HCV acquisition risk with SSPs by 56% in Europe, after stratification by region.13 MOUD such as methadone or buprenorphine are used in an effort to decrease illicit opioid use or misuse as well as injection-risk behaviors.14 MOUD programs have been shown to reduce HCV acquisition risk by 50%.12 Recent studies have suggested that a combination of SSP and MOUD programs has an additive effect in reducing HCV and HIV transmission. The combination of harm-reduction strategies resulted in a 6- to 7-fold decrease in the risk of HCV seroconversion and a 2- to 3-fold decrease in the risk of HIV seroconversion.17 A study by Turner et al. (2011) in the United Kingdom suggested that the combination of SSP and MOUD reduced the odds of new HCV infections by almost 80%.18 Despite these results, no study in the United States has examined the cost-effectiveness in terms of the incremental cost savings per HCV case avoided compared with cost savings with “no intervention.”HCV infections can be reduced through syringe service programs (SSPs) and medications for opioid use disorder (MOUD). SSPs involve the distribution of sterile syringes and other injecting equipment to patients, increasing the number of clean syringes in circulation and reducing the number of contaminated syringes, consequently reducing the risk of acquisition of HCV and other diseases acquired by needle sharing.The purpose of this project was to develop an economic model comparing the costs and effectiveness of SSP and MOUD as standalone interventions and SSP + MOUD in combination as harm-reduction strategies for the prevention of HCV infection in opioid IDUs. The study was conducted from a public payer perspective and considered both direct medical and nonmedical costs associated with injection-risk behaviors. The analysis was done to assist local community and public payers in decision making regarding adoption of harm-reduction strategies to prevent HCV infections and reduce the burden associated with HCV.The target population studied in this analysis consisted of opioid IDUs in the United States not currently engaged in any harm-reduction strategy. The model considered a hypothetical population of patients and was designed using prevalence-based model inputs. A 1-year time period was chosen to capture the time patients engaged in the intervention, antiviral treatment, and antiviral retreatment in cases of treatment failures.21The primary outcome measure used in this cost-effectiveness study was the number of HCV cases avoided per 100 patients in the SSP, MOUD, and SSP + MOUD combination groups compared with the no intervention group. Several cost-effectiveness studies on infectious diseases similarly assessed their outcomes in terms of “cases of infection avoided or averted.”A decision tree analytic model was built in Microsoft Excel 2016 , as pictured in 22 The probability of injection-risk behaviors for each intervention was obtained from systematic literature reviews and meta-analyses and secondary sources.26The outcomes data for this analysis were obtained from a PubMed literature search using the following search terms: “needle exchange programs,” “syringe exchange programs,” “needle and syringe programs,” “opioid substitution treatment,” “injection drug users,” “opioid or opioids,” “people who inject drugs,” and “hepatitis C,” in various combinations. Additional articles were included after reviewing the literature search. Clinical data from randomized controlled trials, cost-effectiveness studies, systematic reviews and meta-analyses, and review articles were included in the analysis. Data retrieved from the literature search pertaining to the effectiveness of harm-reduction strategies were summarized in Both costs and effectiveness measures were estimated from a public payer perspective to capture the public payer’s interest in the growing issue of opioid misuse, given that interventions were likely to be sponsored by a public entity.Opioid IDUs who developed HCV incurred the following costs: HCV screening, biopsy, computerized tomography (CT), magnetic resonance imaging (MRI), antiviral treatment, antiviral treatment complication, HCV treatment monitoring, hepatitis A-B vaccine (3 doses). On the other hand, opioid IDUs who did not develop HCV did not incur these costs. We assumed that those engaging in injection-risk behaviors and those in the no intervention group also incurred the direct nonmedical costs due to injection drug use-related crime.34 The per-person-per annum cost of SSP and MOUD were obtained from literature sources.29 Direct costs of CT and MRI were obtained from the 2019 National Physician Fee Schedule, while the cost of hepatitis A-B vaccine for 3 doses was obtained from the CDC.30 Other direct medical costs such as costs of HCV screening, biopsy, HCV antiviral, and HCV treatment monitoring were obtained from literature sources, including recently published cost-effectiveness studies.32 Similar to the approach of previous studies and due to the perspective chosen for this study, the base-case analysis considered direct nonmedical costs such as criminal justice expenditures related to substance use.31 The public payer perspective analyses included the costs associated with the criminalization of substance use, comprising the costs of policing, court, corrections, and criminal victimization. These cost inputs were obtained from a retrospective, administrative data-based cohort study with comprehensive information on drug treatment and criminal justice system interactions.33 All costs were standardized to 2019 U.S. dollars, using the medical Consumer Price Index.35Cost data were collected from public data sources, primary literature sources, and recently published cost-effectiveness studies .27-34 ThIn developing the model, several assumptions were made. Considering the natural prevalence of HCV in patients with opioid IDU (70%), we postulated the following:The probability of no HCV with no intervention is 0.30, the proportion of patients who do not seem to be infected by HCV virus or naturally clear the virus from the body. We also assumed that all participants (100%) receiving no intervention were engaging in injection-risk behaviors and were exposed to HCV.Opioid IDUs enrolled in one of the harm-reduction strategies and still engaging in injection-risk behaviors had the same probability of developing HCV as those receiving no intervention since injection-risk behaviors are the primary means by which HCV is transmitted. If the injection-risk behavior is not decreased, then the risk of HCV is not decreased.Opioid IDUs enrolled in one of the harm-reduction strategies no longer engaging in injection-risk behaviors had a lower probability of developing HCV when compared with those in the no intervention group.31Similar to the study by Stevens et al. (2019), we assumed that patients were retreated with antivirals for treatment failures.Those engaging in injection-risk behaviors incurred the cost of injection drug use-related crimes.12 As a result, we assumed a conservative estimate of 60% to avoid other key probabilities in the model from falling outside a reasonable range .Although the risk reduction of HCV for the SSP + MOUD combination group was estimated at 74%, the confidence interval was broad from 11% to 93%.The cost-effectiveness findings were expressed in terms of cost per IDU and per 100 IDUs, number of HCV cases per 100 IDUs, number of HCV cases avoided per 100 IDUs, cost per HCV case avoided per 100 IDUs, incremental cost savings per HCV case avoided (per 100 IDUs) compared with no intervention, and incremental cost-effectiveness ratio (ICER).36A 1-way sensitivity analysis was conducted on all cost inputs considered in the model to test the robustness of the base-case cost-effectiveness analysis. The risk reduction of HCV for SSP, MOUD, and SSP + MOUD combination; the probabilities of injection-risk behavior for SSP, MOUD, and SSP + MOUD combination; the probability of no HCV infection with no intervention; and all cost inputs were varied by ± 50%, according to accepted modeling research practices.Results of the base-case cost-effectiveness analysis are shown in The sensitivity analysis varied all cost and clinical variables using the ranges presented in 18 The base-case analysis suggested that (a) the combination strategy, compared with SSP alone, would cost $4,699 to avoid an additional HCV case; (b) the combination and the SSP-alone groups dominated both the MOUD-alone and no intervention groups; and (c) the MOUD-alone group dominated the no intervention group.This study indicates that the SSP+MOUD combination program is an effective harm-reduction strategy to prevent HCV cases among opioid IDUs and is cost-effective if payers are willing to pay $4,699 or more per avoided case of HCV. There is evidence to support the effectiveness of these harm-reduction strategies in reducing injection-risk behaviors as well as reducing HCV and HIV transmission.39 To date, studies have not examined the cost-effectiveness of these harm-reduction strategies in terms of incremental cost savings per HCV case avoided, and none has undertaken a public payer perspective in the United States.Most of the recent studies on the cost-effectiveness of SSP and MOUD alone and in combination were conducted outside the United States, were conducted from a societal or health care system perspective, did not directly compare the interventions used in the base case, had moderate evidence of the cost-effectiveness in some sites, estimated the outcome in terms of quality-adjusted life years, and did not examine the number of cases avoided in a 1-year time horizon.41 The savings associated with these interventions would allow public institutions to redirect funds toward other health care services or public service investments. In addition, the results indicated that all the harm-reduction strategies were less costly and more effective than no intervention even though they required some up-front investments. It is also important to point out that the largest benefits could occur in the future. This is because HCV-related liver disease such as cirrhosis and hepatocellular carcinoma may take several years to occur, and SSPs are associated with reducing the risk of other diseases transmitted via needle sharing, such as HIV.26Based on the analysis, the combination of MOUD and SSP appears to be the most effective policy, from a public health perspective. By including both the direct medical and nonmedical costs due to injection drug use-related crime in the calculation, the combination program will save public payers $347,573 per HCV case avoided compared with costs for no intervention. SSP-alone and MOUD-alone interventions will also save public payers $363,821 and $317,428, respectively. Given that the total direct economic burden of HCV-related liver disease in the United States is estimated to be $6.5 billion ($4.3 to $8.2 billion) annually and 2.4 million people in the United States live with an HCV infection, these interventions could dramatically reduce HCV-related annual costs.The 1-way sensitivity analysis shows that the base-case cost effectiveness analysis was sensitive to the probabilities of injection-risk behavior for the SSP and SSP+MOUD combination groups, probability of no HCV with no intervention, and costs of MOUD and HCV antivirals. Despite varying the model parameters by ± 50%, the base-case ICER was not sensitive to a majority of the key variables in the model. Considering that the cost for the combination intervention was assumed to be the sum of the costs of the SSP and MOUD individual interventions, our results can be considered as conservative estimates, given that in reality, savings and economies of scale can be achieved by a combination of efforts.26 However, varying this variable by ± 50% resulted in an ICER between SSP and combination interventions that ranged from $4,429 to $7,454 compared with the base-case ICER of $4,699. The micro-costing approach of this cost-effectiveness study could have omitted other important cost inputs. There is also weak and insufficient data on the effect of SSP on HCV transmission in North America and the effectiveness of combination programs in reducing injection risk behaviors; thus, we used outcomes data from Europe. Finally, not all populations in the studies from which our input estimates came were the same.Several limitations could affect the results of this analysis. Given the lack of evidence on the probability of HCV among opioid IDUs who are receiving no intervention, we assumed that 30% would not have HCV since they would naturally clear the HCV.42 The cost-effectiveness of harm-reduction strategies could also be examined in nonopioid IDUs. Finally, future studies should also examine the cost-effectiveness of these harm-reduction strategies from a societal perspective by including indirect costs such as costs due to lost productivity.This research reports the cost-effectiveness of several harm-reduction strategies: SSP alone, MOUD alone, and SSP + MOUD combination program, compared with no intervention in preventing HCV cases in the United States during a 1-year time horizon. Additional research should be performed on the cost-effectiveness of other harm-reduction strategies to examine their role in preventing HCV cases among opioid IDUs. These include antiretroviral therapy, condom programs for IDUs and their sexual partners, and targeted information, education, and communication.This study provides evidence that compared with no intervention, SSP, MOUD, and the SSP and MOUD combination are cost-effective and cost-saving harm-reduction strategies. The base-case scenario of the model found the combination program to be cost-effective if payers were willing to pay $4,699 or more per case of HCV avoided. Although these harm-reduction programs will provide benefits in a 1-year time frame, the largest benefit may become evident in the years ahead.


There were 56 (24%) fetuses with extracardiac anomalies. Extracardiac anomalies were present in 20 (22%) fetuses in the V group, 22 (45%) fetuses of the UV group and in 14 (14%) fetuses in the control group (p < 0.01). Our study has proved that maternal COVID-19 infection can affect the fetal physiology and mild cardiac and extracardiac markers detected by fetal ultrasonography and echocardiography. Moreover, maternal vaccination results in lower occurrence of these findings in fetuses.Most obstetrical studies have focused on maternal response to the SARS-CoV-2 virus but much less is known about the effect of COVID-19 on fetal physiology. We aimed to evaluate the effect of the maternal SARS-CoV-2 infection on the fetal homeostasis with the use of detailed ultrasonography and echocardiography and consideration of the effect of vaccination. This was a multi-center study of fetuses who had prenatal detailed ultrasound and echocardiographic examinations performed by fetal cardiology specialists. The subjects were divided based on the COVID vaccination status . We evaluated the ultrasound and echocardiography results obtained. The study group included 237 gravidas from four prenatal cardiology centers. In the group of fetuses with normal heart anatomy, normal cardiovascular function had 147 (81%) fetuses and functional cardiovascular anomalies were present in 35 (19%) cases. Functional cardiovascular anomalies were present in 11 (16%) fetuses in the V group, 19 (47%) fetuses in the UV group and 5 (8%) fetuses in the control group ( The SARS-CoV-2 coronavirus belongs to the group of coronaviruses (coronaviridae). This is a group of viruses that by the end of the twentieth century caused infections mainly in animals and a few species also in humans. They involved mainly mild infections of the upper respiratory tract and sometimes the gastrointestinal tract. So far, about 15–30% of mild seasonal “colds” have been caused by coronaviruses. At the turn of 2002 and 2003, a new subspecies of coronavirus appeared in China and some people were affected by the symptoms of acute respiratory failure—this virus was called SARS-CoV (severe acute respiratory syndrome). The restrictions related to the SARS-CoV-2 pandemic and the COVID-19 disease are slowly disappearing, but it seems that the virus has not yet said the last word and its next mutations will stay with us forever, like the flu virus. The course of infections caused by subsequent mutations will be less severe and more dangerous only for immunodeficient people, the elderly and pregnant women. Vaccination will protect against severe infection. Vaccination recommendations against the influenza virus has already been included in the pregnancy schedule. We would like such recommendations also to be adopted in relation to vaccination against COVID-19. In December 2019, a novel corona virus called SARS-CoV-2 emerged in China and caused significant public health and economic problems. COVID-19 still remains a challenging problem for clinicians because of its acute and chronic effects ,5. Pregnwww.orpkp.pl) (accessed on 20 October 2022), which means that they are referral centers  and perform referral fetal echocardiography and”genetic” ultrasonography examinations [This was a multi-center study of fetuses who had detailed prenatal ultrasound and echocardiographic examinations performed by fetal cardiology specialists . The study was conducted in four Polish centers  from October 2021 to May 2022. These centers sent a protocol from examinations to the main center. The Polish centers of prenatal cardiology have rank C or B in the prenatal cardiology system in Poland (inations . The datExclusion criteria included: (1) no fetal echocardiography; (2) improper technique of echocardiography or poor quality of examination; (3) lack of vital data. We excluded cases with maternal urogenital infections. Cardiac functional abnormalities included tricuspid insufficiency, pericardial effusion, myocardial hypertrophy, bright spot, mild cardiomegaly, abnormal foramen ovale blood flow, reversal flow in the ductus arteriosus or mild arrhythmia. Extracardiac anomalies included a thick, edematous placenta, an umbilical cord around the fetal neck, oligohydramnios, polihydramnios, pyelectasis, hiperechogenic bowels, a renal cyst, a lung cyst, hiperechogenic lungs, bowels distension, hydrops testis, mild ventriculomegaly, a visible bronchogram, a vacuolised or thick placenta > 5 cm.The study group included 237 gravidas from four prenatal cardiology centers. There were 88 vaccinated gravidas who did not have COVID-19 (group V), 49 unvaccinated gravidas who had COVID-19 (group UV) and 100 unvaccinated gravidas (control group) who did not have COVID-19. The mean age of the gravidas was 31 ± 5 years  (p < 0.01) (There were 182 (76%) fetuses with a normal heart anatomy and 55 (23%) fetuses with a congenital heart defect . In the  < 0.01) . More de < 0.01) . More dePrenatal Cardiology Journal hypothesizes that an increase in fetal-isolated pericardial effusion coincided with the period of massive COVID-19 immunization, as a result of a transient fetal inflammatory response to SARS-CoV-2 immunization [Maternal COVID-19 infection can affect the fetal physiology and mild cardiac and extracardiac markers detected by fetal ultrasonography and echocardiography. Maternal vaccination results in lower occurrence of these findings in fetuses. Diverse viruses are known to cause fetal infections. Rubella, cytomegalovirus (CMV), herpes simplex virus (HSV), and human immunodeficiency virus (HIV) could enter the amniotic cavity even if amniotic membranes are intact. Others could enter the fetus via the hematogenous route. Herpes simplex virus (HSV), varicella zoster virus (VZV), and Coxsackievirus are among those viruses which can cross the placental barrier and infect the fetus . Viral inization .Our results showed that in the V group (vaccinated), there was only one case of fetal pericardial effusion  but in tIn our country, the National Society of Gynecologists and Obstetricians recommends the COVID-19 vaccination . COVID-1There are some important clinical implications resulting from our study. Recommendations for vaccination against the influenza virus have already been included in the schedule of vaccinations for pregnant women. This study may contribute to an elaboration of recommendations for vaccination against COVID-19. It is very important due to the fact that there have been many myths about the COVID-19 vaccination in our society. The increase in the awareness of patients about possible benefits of the COVID-19 vaccination may make patients more willing to be vaccinated and thus decrease the side-effects of any complications following COVID-19 infection.A key strength of this paper is that is includes a large study group of carefully selected patients. This study shows a current problem that covers the psychosomatic space and the unforeseen long-term effects of COVID-19 on the health of people. The authors determine the impact of maternal SARS-CoV-2 infection on fetal homeostasis with the use of detailed ultrasound and echocardiographic examinations as well as a maternal vaccination. The awareness of the presence of the above-described ultrasound and echocardiographic markers may increase the attention of specialists and patients and prepare a plan for further diagnosis and procedures. This study demonstrates that fetal ultrasonography and echocardiography constitute excellent non-invasive tools for assessing the overall condition of the fetus in terms of any anomalies resulting from the maternal COVID-19 infection. Ultrasonographic and echocardiographic screening can be successfully used in daily practice in patients following the SARS-CoV-2 infection.In spite of the large amount of data, there are also some limitations that need to be addressed. The most important one is the still small group of patients and the number of clinics participating in the study. Another limitation may be the awareness of people and their beliefs about the negative effects of vaccination. However, these limitations can be considered in further studies.Maternal COVID-19 infection seems to affect the fetal physiology alterations and mild cardiac and extracardiac markers detected by fetal ultrasonography and echocardiography. Maternal vaccination results in lower occurrence of these findings in fetuses. Further studies are needed to establish the direct influence of the SARS-CoV-2 infection on the fetal cardiac function.