The harmonization of front-of-pack nutritional declaration is in the heart of food and nutrition policy discussions in Europe. The Nutri-Score system has been proposed by many countries as a potential candidate but its suitability for use across Europe is still under consideration. The current study aimed to evaluate the performance and discriminatory capacity of Nutri-Score in Greece and to test its alignment with the national food-based dietary guidelines.n = 4,002) in the Greek branded food composition database HelTH. Each food content in fruits, vegetables, pulses, nuts and oils was manually estimated from the ingredients list. The Nutri-Score algorithm was used both as a continuous (FSAm-NPS Score) and a categorical variable [Grades (A)–(E)].Data on the energy, saturated fat, total sugars, sodium, protein, and fiber content per 100°g or ml were extracted for all foods available  were graded from (A) to (C), while most beverages (59.2%) were graded (E). More than 50% of food categories were populated with foods in all Nutri-Score grades, indicative of a good discriminatory capacity. The system scores favorably vegetables, pulses, and low-fat dairy products and unfavourablly sweets and processed meats showing in this way good alignment with the national guidelines. Eggs and seafood scored preferably compared to meat products. Animal fats received less favorable scores and so did cereal products that were highly processed.Nutri-Score showed good capacity to inform consumers toward better food choices in line with the national guidelines. It showed a potential to guide consumers and manufacturers toward less energy dense and more nutrient dense options and highlighted areas of improvement in the food supply. The creation of a unified Front-of-Pack (FOP) labeling system is at the core of European discussions for the past years . GloballFront-of-Pack (FOP) labeling has been proposed as a cost-effective tool for consumer education at the point of sale, linked to both improvements in dietary behaviors and in industry practices . HoweverSince 2018, a number of European countries, namely France, Belgium, Germany, Luxembourg, Netherlands, and Spain have decided upon the adoption of Nutri-Score as the new FOP labeling system . The NutThe Nutri-Score algorithm, is currently the strongest candidate for application across Europe; however there are concerns raised by some Mediterranean countries that the algorithm has not taken into account the specificities of the food system in the region –18. The A new tool that could facilitate the investigation of Nurti-Score in Greece, is the Hellenic Food Thesaurus (HelTH). HelTH is a BFCD launched in 2019 by the Agricultural University of Athens, which collects and analyses all nutritional and quality data provided on labels of branded food products  of Greece.Food composition data were extracted from HelTH, a dynamic dataset that compiles data on the nutritional composition and quality characteristics of branded foods available in Greek supermarkets.n = 4,002 food products. In brief, HelTH includes information on the nutritional composition of foods, extracted from food labels available on the e-shops of large supermarket chains in Greece. Data on any health and/or nutrition claims made on pack, and information on any other quality claims written on pack  and the nutritional declaration was checked for quality by two independent researchers and curated in the database. A detailed description of the methodology and structure of HelTH has been published previously (Hellenic food thesaurus (HelTH) started as an initiative in 2018 and in its first version 11/2019), used in this analysis, contained data for , used inn = 139) as they are not included in the scope of the Nutri-Score according to the European regulation .The latest Nutri-Score algorithm was used in this analysis . In brieAn overall score ranging from −15 to +40 was calculated by subtracting the “positive nutrients” score from the “negative nutrients” score. More specifically, fiber and FV scores were subtracted for all products, but the protein score was subtracted only in products with “negative nutrients” score < 11, those with an FV score > 5 or for cheeses.The FSAm-NPS score was translated to Nutri-Score based on the following criteria : (A) wasAll nutrient contents were based on the labeled nutritional composition declaration. FV% was estimated based on the ingredient list in a two-step process. Firstly, all foods were screened to assess the presence of at least 40% content in fruits, vegetables, pulses, nuts and rapeseed, walnut, and olive oils, which is the minimum content required. Then for the products that met this minimum requirement a thorough quantification was carried out.n = 778) were excluded, as no Nutri-Score could be calculated. Missing nutrient values could be due to lack of nutritional declaration or low-quality images obtained from the specific foods. On the contrary for “positive nutrients” missing information were imputed as zero.For the purpose of the study, products that did not contain any data about their energy, saturated fat, total sugar or sodium content . Nutritional composition data (content per 100 g or 100 mL of product) and the FSAm-NPS score were analyzed as continuous variables. Data were tested for normality using the Kolmogorov-Smirnov test. None of the variables followed the normal distribution. Therefore, variables were expressed as median (interquartile range). We assessed the distribution of prepacked products across different NS grades for main categories and subcategories and displayed this information in boxplots emphasizing median, 25th, and 75th percentiles. Discriminating ability was considered good when the food group comprised at least three different NS grades .Statistical analysis was carried out using IBM SPSS Statistics S grades , 13. Difp < 0.001). Vegetables had the lowest average score among all groups , followed by ready meals, eggs, and fruits which all received similar Nutri-Score . Sugar products had the highest FSAm-NPS Score compared to all food categories (p < 0.001 data not shown), followed by meat products, fats and oils, miscellaneous foods and non-milk beverages .A total of 3,224 products were included in the final analysis with grain and grain products being the largest food category followed by dairy products and imitations and then non-milk beverages, sugar products and miscellaneous foods . The medThe distribution of FSAm-NPS Score across all categories is shown in Overall, 100% of egg products, 95.2% of vegetables products, 77.6% of ready meals, 67.5% of fruit products, and 48.6% of milk and milk products categories were graded as (A) or (B). On the contrary, 85.8% of meat products, 90.3% of sugar products, 65.1% of fats and oils, and 56.8% of miscellaneous foods were graded as (D) or (E). The same was true for beverages with 74.9% of all beverages being graded as (E) , Table 2In 8 out of the 13 food categories there was at least one product in every Nutri-Score grade. The categories with the lowest variability were egg products and fats and oils, in that order.In terms of the distribution in subcategories within the milk products, milk and yogurt had the highest number of products rated (A) or (B), 93.5 and 86.8% respectively. On the other hand, cheeses were graded mostly (D) (78.6%), however a small proportion of cheeses (< 2%) were graded (A) and (B) . Imitatin < 10)  for all subcategories. Preserved meats and meat dishes showed some variability in Nutri-Score but the absolute numbers are very small (n < 10) . In the Grains and grain products, the largest food category, showed great variability in Nutri-Score. As the largest and most versatile food category, this variability was also seen among its subcategories with pasta, breads, rice, and cereal milling products receiving Nutri-Scores across the spectrum with larger numbers at the lower scores . On the Jams, non-chocolate confectionary, condiments and prepared food products were subcategories where Nutri-Score (D) was the dominant grade and that was more pronounced in the sweet options rather than the savory options. In general, those subcategories represent mainly sweet and savory snack foods. Sweet snacks are predominantly graded as (D) with the exception of chocolates with 89.6% of all products graded as (E). For savory snacks the main volume of products is split between grades (C) and (D).More complex food products as they are represented by the composite dishes in the ready-to-eat and frozen foods subcategories receive overall positive grades, with > 70% of all products in (A) and (B). Semi-prepared dishes performed better than ready-to-eat products but even then, ready-to-eat foods were equally split between (A) and (B).Finally, almost all juices and nectars (98%) were graded as (E), while for the remaining non-alcoholic beverages a quarter of the products were graded as (B) which is the lowest Nutri-Score for beverages other than water.p < 0.001, data not shown). Sweets are overall unflavored and graded as (D) and (E), as are juices.In terms of agreement with the national food-based guidelines, Nutri-Score shows a preliminary good agreement as shown in p < 0.01). More specifically cereal products in Nutri-Score grades (D) and (E) had an average fiber content of 3.91 ± 2.7 and 2.50 ± 1.2 g/100°g respectively, as opposed to products graded (A) to (C) which had an average content of 5.24 ± 4.6 g/100°g. The majority of wholegrain/non-refined cereals (76%) were graded either (A) or (B) which indicates a greater capacity to highlight the differences in the nutritional composition of this subcategory.Fats, oils and nuts are mentioned as food groups to be consumed in moderation and with close consideration in their nutritional composition, in the case of Nutri-Score grading all food groups that contained the statement in moderation did not receive any grade below (C), which could be considered in agreement with the guideline. In the case of grains and cereals, Nutri-Score showed a wide variability but an analysis of the fiber content showed that foods graded as (D) and (E) had significantly lower fiber content compared to all other Nutri-Score grades . On the other hand, although the National FBGs include a mention on avoiding sweetened dairy products, only a few products (namely sweetened condensed milk) received a Nutri-Score grade above (C). Sweetened yogurts (either kid’s yogurts or yogurt desserts) were graded as (B) or (C) even when sweetened with fruit juices/jams.The Greek food-based guidelines mention a preference toward dairy foods that are low in fat naturally, meaning a prioritization of milks, yogurts which is documented in the Nutri-Score performance in the dairy subcategories. Only a small number of cheeses were graded as (A) or (B) but there was good discriminatory capacity among cheeses as all Nutri-Score grades were populated. In dairy products, increasing Nutri-Score was associated with increasing energy, SFA, sodium, and total sugars content  and (C) (FSAm-NPS Score = 1) with a second peak at FSAm-NPS Score = 11, the cut-off point between grades (C) and (D). That shows that although currently 27.9% of all products are graded (D) and 16.5% are graded (C), it is possible for a substantial proportion of those foods to improve without extensive reformulation. In fact, 9.5% of all foods have an FSAm-NPS score = 11–12 and 7.1% of all foods have scores at FSAm-NPS = 1–2. Similar results were seen in the Netherlands  in FrancIn the case of Greece, Nutri-Score managed to successfully identify “healthier” options for consumers in all food categories and subcategories allowing for product substitutions up to two Nutri-Score grades below. The agreement of our findings with previous analyses in other countries also adds to the discussion of the potential for extrapolation of the findings across Europe and even in other regions, suggesting that Nutri-Score performance is rather homogenous in multiple settings.As FOP labeling’s main purpose is consumer information on healthier food choices, a key stage in its validation is testing its alignment with national and international guidelines , 25, 26.A similar explanation could be offered for the unfavorable grading of the meat and meat products group, which in the case of HelTH is mainly populated by sausages, cured or dried meats which are discouraged both as potential carcinogens and for their high fat and sodium content , 28. WheThe lowest discriminatory capacity was seen among sweets and more so among chocolates. Although discriminatory capacity is always better to help identify “healthier” options in the case of those food subcategories, the lack of discriminatory capacity is in line with national and international guidelines that call for a reduction in sugar intake and the avoidance of sweets to a maximum of one portion per week , 30.Finally, a key consideration for Nutri-Score in Greece is its performance vis-à-vis fats and oils. In the case of our analysis, the dataset used did not include any data on vegetable oils , as suchLimitations of the current study linked to the nature of the HelTH dataset have already been mentioned in the relevant sections. Although HelTh is the only available branded food composition database for Greece and covers an important part of the market, it is still in need of targeted expansions as for the case of oils and potentially novel foods like plant-based meat alternatives etc. Despite, its gaps the use of branded food composition databases is linked with substantial improvement in the relevance of the results for the consumer and the food industry as it is a direct reflection of the marketplace as compared to analyses performed on generic food composition data , 32.This study also faced issues with missing data, especially for positive nutrients like protein and fiber. Although data completeness is relatively high for protein, fiber is only declared in food categories that are relevant or in foods that carry a nutrition claim for the specific nutrient . In the The hardest part of the Nutri-Score calculation is the calculation of the Fruits, Vegetables, Nuts, Pulses, and Oils component. This calculation has to be done manually and it is always linked to underestimation. Especially, in the context of the Mediterranean foodscape the importance of this component is vital as both national and Mediterranean Diet guidelines suggest that foods that contain vegetables or pulses and use olive oil as their main fat should be preferred , 33. AnoIn the case of testing the alignment with existing FBDGs there are additional limitations to be considered. These include issues like the misalignment of the food categories as mentioned in the guidelines as opposed to the food categories proposed by systems like Langual or FoodEx2. For example, although the guidelines considered fine bakery ware to be considered sweets from a food technology point of view these foods are more likely to be classified as cereal-based foods. Similarly, the guidelines often refer to decreased intake of trans-fatty acids and increased intake of fiber and wholegrains, however this information is not mandatory as part of the nutritional declaration in EU and is often missing or it needs to be manually estimated from the ingredients list.Although, this work offers evidence on the alignment of Nutri-Score with national FBDGs, it is important for Nutri-Score to be tested against dietary patterns with a documented beneficial effect on health. The Mediterranean Diet Pyramid is such a pattern and its principles expand beyond the nutritional composition of foods to cover elements of locality, tradition, seasonality, culinary, and cultural elements. Testing the alignment of Nutri-Score with dietary patterns like the Mediterranean Diet would require targeted analysis and testing. Future work should aim to directly test the alignment of Nutri-Score with these guidelines as it will allow to answer questions around the type of reformulation that Nutri-Score will promote in the Mediterranean and whether the traditional cooking techniques will be favored and what the impact of Nutri-Score would be on the Mediterranean agri-food value chain.Overall, this study is the first to report the performance and discriminatory capacity of Nutri-Score in the Greek foodscape using a branded food composition database. It highlights an overall good discriminatory capacity and satisfactory agreement with the national FBDGs. However, the evaluation of an upcoming food policy requires further data on the consumer perception and likelihood for adoption, as well as an analysis of the alignment with the existing agricultural policies and agroeconomic strategies. After this complete description of the risks and benefits a roadmap of implementation could be developed.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.AV: formal analysis and writing—original draft preparation. AV and AK: investigation and data curation. MK: resources and supervision. All authors have conceptualization, methodology, writing—review and editing, read, and agreed to the published version of the manuscript.


The COVID-19 pandemic has generated an avalanche of information, which, if not properly addressed, generates uncertainty and limits healthy decision-making. On the other hand, the pandemic has exacerbated mental health problems among young people and adolescents, causing a worsening of their wellbeing. Previous studies have found that digital health literacy has a positive impact on people's attitudes toward the disease. This study aimed to analyze the association between digital health literacy on COVID-19 with subjective wellbeing in university students.A cross-sectional study was developed in 917 students from Ecuador. Subjective wellbeing was measured with the World Health Organization WellBeing Scale. Digital health literacy was assessed using the Spanish-translated version of the Digital Health Literacy Instrument adapted to the context of the COVID-19 pandemic. Bivariate and multivariate linear regressions were performed.p-value <0.001). This correlation persisted after adjust by demographic and socioeconomic variables.Digital health literacy and subjective wellbeing proofed to be significantly higher among males and among students with higher social status. The association between digital health literacy and subjective wellbeing was significant; for each increase of one point in the digital health literacy scale, an average increase of 9.64 points could be observed on the subjective wellbeing scale (IC 95% 5.61 – 13.67, Improving digital health literacy in health would improve the subjective wellbeing of university students. It is suggested strengthen the digital health literacy through public and university policies that promote access, search skills and discernment of digital information. Socioeconomic and gender inequalities related to digital health literacy need to be further investigated. The current COVID-19 pandemic has become a global societal challenge, causing an unprecedented public health crisis that in turn has led to a real economic catastrophe for many countries. COVID-19 is a new disease, and new knowledge is constantly being gained about its etiology, treatment, and prevention. Therefore, there is a high need for evidence-based, reliable, and trustworthy health information and sources.The presence of the internet and its ability to massively and instantly spread information becomes an invaluable help in the fight against COVID-19, but it has also proved to be an obstacle by facilitating the fast spread of misinformation, falsehoods and myths . This “ivia health professionals and authorized publications. However, during the COVID-19 crisis a large amount of information on social networks and online media has been available that can overwhelm lay persons and professionals alike  is defined as “a set of fundamental skills that underlie the use of health-oriented information and communication technologies” . This alp < 0.001), adducing a positive longitudinal association between digital literature and health    on digitd-hl.eu) , 17, 18.d-hl.eu)  found a d-hl.eu) . Howeverhttps://covid-hl.eu)  and settings  (d-hl.eu) .A cross-sectional study performed in the confinement period due to COVID-19, with data collected from June 4 through 29 of 2020.This study was conducted in Ecuador, a country where the first confirmed case of COVID-19 was recorded on February 29, 2020. It was the third country in Latin America to confirm COVID-19 cases, after Brazil and Mexico. COVID-19 cases spread rapidly throughout the country's provinces, making it one of the countries in Latin America hit hardest by the pandemic .During the data collection period of the COVID-HL university student survey, from June 4 to 29, 2020, cases of COVID-19 had spread throughout the Ecuadorian territory, reaching 53,424 confirmed cases, with 8,026 deceased . RegardiThe present study was carried out in two universities in Quito, the capital of Ecuador: the Central University of Ecuador (UCE) and the Pontifical Catholic University of Ecuador (PUCE). The public university (UCE) receives students from all over the national territory and from all socioeconomic classes. The private university (PUCE) receives students mostly from medium and medium-high socioeconomic classes.https://www.unipark.com/). This software allows 10,000 respondents per project from each country, with high standards for data protection and security. All data are transmitted via an encrypted connection using the secure encryption protocol.Undergraduate, graduate and postgraduate university students from the UCE and the Quito headquarters of PUCE were invited to participate in an online survey. The online survey was applied through the platform Enterprise Feedback Suite survey tool by Tivian, software Unipark . The sample was calculated from the following information: a size of the known universe of 17,000 students, an expected percentage of sufficient digital literature in university students of 49%, based on a previous study  Wellbeing Scale , 24. ThiThe independent variable was Digital Health Literacy with respect to COVID-19 (DHLI). It was measured with the Spanish-translated version of the Digital Health Literacy Instrument (COVID-DHLI-Spanish) used by the Global COVID-HL Consortium , and basIn accordance with previous literature that shows an association between wellbeing and socioeconomic and demographic variables , 18, 19,In order to collect information on the variables described above, the online survey administered to university students contained the following: socioeconomic and demographic characteristics, the WHO wellbeing scale, and the Digital Health Literacy Instrument questionnaire adapted to Spanish (COVID- DHLI-Spanish). The entire survey was administered in Spanish, it was verified that the survey has adequate internal and construct validity . To redup < 0.25 were entered in the multivariate analysis . There were also significant age differences in the mean digital health literacy scores with older students showing a higher digital health literacy (3.0 SD ± 0.4 for students 23 years or older) as opposed to those of younger age . Moreover, those students from life and health sciences and basic sciences had a significantly lower digital health literacy compared to students from technological sciences and engineering .On a scale from 1 to 4, the mean value digital health literacy across all dimensions was 2.9 . A higher subjective social status was positively associated with a higher COVID-19-related digital health literacy. For each point of increase in subjective social status, there was an average increase of 0.05 on the digital health literacy scale   . After ap < 0.001) (p 0.01). Moreover, the wellbeing mean value was significantly higher for students in the public university enrolled at a private university . Similarly, there are significant lower wellbeing means for social science students as compared to those of technological sciences and engineering . Students with chronic diseases also reported a lower subjective wellbeing score than those respondents without a chronic condition .On a 0 to 100 scale, subjective well-being reached a mean of 53.2 SD ± 20.7 . Males r< 0.001) . Studentp<0.001 than females. Moreover, compared to respondents from private universities, public university students reported a 11.12 points higher subjective well-being . Life and health sciences and Basic sciences students had a subjective well-being score that was 15.39 points lower . These associations remained significant after multivariate adjustment . Having a chronic health condition decreased the subjective wellbeing score by an average of 4.34 points . The relationship with subjective wellbeing remained significant in the multiple linear regression . This association remained significant after adjusting for the covariates, i.e., the correlation between digital health literacy and subjective wellbeing is independent of gender, age, university, study area, subjective social status, and the presence or absence of chronic illness . In Germany, levels of digital health literacy in health reported during 2020 reached a 49.9% for sufficient DHL, 34.9% for problematic, and 15.2%for inadequate DHL , and it This study showed significantly higher levels of digital health literacy in male students than in female respondents, which coincides with previous studies in Palestine  and PortBetter digital health literacy was found among university students older than 23 years, which is consistent with other studies , 42; howOn the other hand, higher scores in digital health literacy were found in students who reported better subjective social status, which can be considered a proxy for socioeconomic status, which is consistent with previous findings , 12. ThiRegarding subjective wellbeing, higher scores were found in male students. Other studies carried out during the period of the COVID-19 pandemic reveal a greater deterioration in psychological wellbeing in women, which is observed along with a greater burden of domestic work, greater job losses, and a reduction in economic income –46. PartThe population in this study is university students, which has certain advantages over other population groups due to the level of education they have attained. Adil and colleagues have found that educational level is the main factor for the uneven response toward digital health literacy . In thisp < 0.001), and positively with Health-Related Quality of Life  in a (include country) study with (include population) . However, the authors emphasize that this finding may be due to socioeconomic status (p < 0.001)  , 52. On c status . Other r< 0.001) .These results would imply that people with higher digital health literacy use certain digital sources, such as social media, less often and are better able to find and use high-quality health information that is beneficial in protecting them from infection with the coronavirus and help them to promote your wellbeing.An interesting observation is that although the pandemic has been managed differently all around the world and COVID-19 prevalence is very different between countries; the experience of college students may be comparable between the countries. Gender differences in COVID-19-related concerns have been demonstrated, with female college students scoring significantly higher than male students on depression, anxiety, and stress do during the early stages of the pandemic . This stAlthough the evidence shows gender and social status differences in stress and anxiety prior to the pandemic , the panFor this reason, it is considered important to improve digital health literacy of university students. Access to high quality information from reliable sources, and digital literacy that is adequate to distinguish between fake news and information with scientific evidence, are essential. It is important that university students and the general public are able to analyze, evaluate and apply the information they find in digital media, and consequently, protect their health and that of their family and community. Additionally, digital literacy may well be considered as a fundamental part of people's responsibility and social conscience , 6, bothThis research has several limitations: first, the survey was conducted three and a half months after the rapid spread of COVID-19 in Ecuador, which could have intensified fear and decreased the student's satisfaction with life. Another limitation has to do with the respondents and convenience sampling; most of the responses were from health and life sciences students, which could generate a bias in the results obtained, since they, in general terms, have more information on health-related topics. In this study, wellbeing was measured through a subjective assessment in the last 2 weeks, and other variables that could be related to wellbeing, such as grief, mental health illnesses, job layoffs, family support, etc., were not considered. The low response rate in this study may be due to the technical difficulties encountered at the beginning of the pandemic to gain better acceptance among students, such as access to technical resources and the use of online surveys, which they were not familiar with.https://covid-hl.eu)  . This wiAccess to quality digital information and the skills to search for useful information, as well as their discernment for making health decisions, are key elements in protecting and promoting health , 9, 10. In this study, the subjective wellbeing perceived by university students in Ecuador was significantly associated with digital health literacy related to COVID-19. This finding could suggest that efforts to improve digital literature in university students could potentially be related to improving their well-being, and vice versa.It is necessary to make visible the importance of digital health literacy for the promotion and prevention of health, particularly in the current pandemic. Coordinated public and private efforts are required to reinforce digital health literacy in health among adults and young adults, by recognizing the importance of skills to navigate the internet and other digital environments in order to promote both personal and community health. Special attention must be devoted to the university population, as well as socioeconomic and gender inequalities must be addressed. This study also suggests gender and socioeconomic inequalities related to digital health literacy, so further research on these gaps is required. This analysis will be part of a future investigation that the authors plan to carry out.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material.The studies involving human participants were reviewed and approved by Ethics Committee for Research in Human Beings of the Pontifical Catholic University of Ecuador. The patients/participants provided their written informed consent to participate in this study.MR designed and executed the study, developed the data analysis model, and wrote the preliminary draft. CS helped with study design, coordinated data collection, and contributed to writing the preliminary draft. JC-G performed the validation of the scales and the statistical analysis and participated in the writing of the draft. LA, JC, AT-C, MM-V, KD, and OO developed the instrument and overall study design, coordinated data collection, and made important contributions to writing this scientific article. All authors contributed to the article and approved the submitted version.


The purpose of this study was to determine whether virtual reality-based sensory stimulation has the ability to improve the level of consciousness in pediatric disorders of consciousness compared with general rehabilitation.n = 15) and a control group (n = 15). Subjects in the VR group received both general rehabilitation and exposure to VR videos; the control group received only general rehabilitation. The Glasgow Coma Scale (GCS), Coma Recovery Scale-Revised (CRS-R), and amplitude-integrated electroencephalogram (EEG) (aEEG) were used to measure the clinical behavioral response and neuroelectrophysiology before and after the treatment. The Glasgow Outcome Scale Extended Pediatric Revised (GOS-E Peds) was used to measure the social and personal functional ability after 3 months.Thirty subjects were divided into a virtual reality (VR) group (p = 0.003) and GCS (p = 0.045). There were no significant differences on aEEG in the two groups after treatment. According to the GOS-E Peds, the improvement of social and personal functional ability had no significant differences in the two groups. Additionally, there were no obvious adverse reactions in the two group during the treatment.After 2 weeks of treatment, the CRS-R and GCS improved in both groups. However, the VR group had better results than the control group in the CRS-R (This pilot study indicates potential benefit from the addition of VR to standard rehabilitation in pediatric disorders of consciousness. To further explore the efficacy of VR, a large-sample randomized controlled trial is warranted. With the rapid development of emergency and critical care medicine and the continuous improvement of medical technology, the survival rate of brain injury due to various causes has greatly improved. However, many patients still have varying degrees of disorders of consciousness (DOC), such as coma, vegetative state (VS), and minimally conscious state (MCS). One cause of DOC in children is craniocerebral trauma as a result of events such as traffic accidents and falls. Non-traumatic causes include viral encephalitis and hypoxic ischemic encephalopathy. Children with DOC not only bring difficulties to nursing but are also prone to complications such as lung infection, urinary tract infection, joint contracture, skin acne, and malnutrition, which place heavy psychological and economic burdens on families of children who have had lengthy hospitalizations. Therefore, the treatment of pediatric DOC is one of the issues that intensive care unit and rehabilitation facility pay close attention to.Some studies have reported the use of dopaminergic agonists , 2, γ-amA VR system, which is defined as an interactive system that includes computers and media peripherals, can be used to create an environment that is similar to the real world, providing both audio and video stimuli to users . VR has The game elements of virtual reality can increase a child's motivation for participation and treatment compliance. VR has been reported to have the ability to improve cognitive function in children with autism and motor function in children with cerebral palsy, and to offer pain relief –16. Howen = 0) or Minimally Conscious State (MCS) ; and (b) stable vital signs. Patients were excluded if they had any of the following: (a) use of psychotropic drugs within 1 day; (b) suffered from neurological disorder or serious mental illness before brain injury; (c) severe visual and hearing impairment before or after brain injury; (d) poor treatment compliance; and (f) other severe complications during observation. A research flowchart is shown in n = 15; 8 male; 7 female) and the control group .Patients between 2 and 16 years of age hospitalized in the rehabilitation department, PICU and SICU of Nanjing Children's Hospital from January 2020 to December 2021 were recruited. The inclusion criteria were as follows: (a) according to the JFK Coma Recovery Scale-Revised (CRS-R) scores: Vegetative State (VS) . The registration number in the Chinese Clinical Trial Registry is ChiCTR2000034517.The demographic and clinical characteristics of the participants are listed in The HTC Vive  was usedAll participants received general therapy including physical therapy, exercise therapy, and repetitive transcranial magnetic stimulation. In addition to general therapy, the VR group watched VR videos for 30 min per day for 2 weeks. Patients with continuous eye closure were subjected to pain stimulation  for 1 min before therapy. To customize the stimulus to make sense to the individual, we asked the child's family and friends about their interests and habits prior to the DOC onset before the experiment began. All patients in the VR group watched personalized videos (for 15 min) first and then panoramic videos (for 15 min).In the first stage, patients in the VR group watched personalized videos for 15 min, mainly providing visual and auditory stimuli. At the beginning of the personalized videos, children's parents called their names repeatedly and described interesting stories in a gentle tone. Parents also showed their daily life in the video, with activities such as cooking, attending parties, or visiting with friends. The personalized videos included videos recorded before the DOC. This part of the videos contained children's pictures, voices, and impressive events, which helped to reproduce scenes and were conducive to refresh their memories.In the second stage, patients in the VR group watched panoramic videos for 15 min, which provided visual, auditory, and vestibular stimuli.“Live in Your Music,” which is a music visualization game, allows patients to choose favorite songs and themes . When the patients put on a head mounted display, they can see a music environment with the theme they choose. Like the pink butterfly theme, the center of the field is a varied pattern of many pink butterflies. When the head is turned in any direction, the butterflies can be seen dancing, and the size and position of the butterflies change with the rhythm and sound level of the music.“VR Roller Coaster at Global Wonders,” it includes multiple scenes , and each scene contains different classical music. After wearing a head-mounted display, patients become a virtual character who rides on a roller coaster to experience different scenes. The patients can enjoy the scenery when the roller coaster is moving slowly, and experience the excitement when the roller coaster is speeding up.“Submarine VR,” it is a game full of adventure under the sea. When the patients put on a head mounted display, patients are disguised as submarine drivers who are depicted as diving slowly into the deep sea and sailing on an endless ocean. When the submarine dives to the bottom, patients can see sunken ships, coral reefs, clownfish and mysterious sea creatures. And when the submarine nears the surface, patients can see rough waves, leaping dolphins and blue skies.CRS-R and GCS scores were evaluated by a trained clinician before and after treatment, and the Glasgow Outcome Scale Extended Pediatric Revised (GOS-E Peds) was used to evaluate social and personal functional abilities after 3 months. And the EEG signals were monitored before and after treatment.For children ages 2–5 the pediatric GCS was used, and for those older than 5 years the GCS was used . The scan = 0, and arousal ≤ 2. For the diagnosis of MCS, the scores are auditory, 3–4; visual, 2–5; motor, 3–5; verbal, 3; and communication, 1. The following scores indicate emergence from MCS (EMCS), the scores are: motor = 6 or communication = 2  consists of 23 items with six subscales addressing auditory, visual, motor, verbal, communication, and arousal functions , 20. Thetion = 2 . This totion = 2 .In this study, the amplitude-integrated EEG (aEEG) were recorded as objective indices. According to Naqeeb et al.aEEG is divided into 3 grades: grade I, normal amplitude (aEEG upper edge >10 μV and aEEG lower edge >5 μV); grade II, mild abnormal amplitude ; and grade III, suppressed amplitude (upper edge <10 μV and lower edge <5 μV) .We used the GOS-E Peds to measure social and personal functional ability before and after treatment, which provides an age-appropriate and effective neurologic measure for infants and children under 18 years of age . The lisp < 0.05 was reflected statistically significant. Bonferroni was applied to multiple comparison correction in the study.Data were analyzed using IBM SPSS Statistics 22.0. Results were summarized as frequencies and percentages for categorical variables, median and interquartile ranges for duration of disease, age, GCS, and CRS-R. Mann–Whitney U test was used to compare the change of aEEG and functional grade, GCS, and CRS-R. Chi-square test was used to compare the classification of consciousness levels before and after treatment. The p > 0.05). During the treatment, there were no obvious adverse reactions in the two groups. Only three children in the VR group showed mild irritability at the last stage of watching VR videos, which could be calmed after a short rest, while the other children did not show similar symptoms or other adverse reactions.Thirty-two children were enrolled, but two failed to complete the EEG and were omitted. Thirty patients completed all treatment and evaluation follow-up tasks. As shown in p = 0.109) and GCS (p = 0.069) between the two groups before treatment. Patients who received general rehabilitation and exposure to VR videos got higher score in GCS (p = 0.045) and CRS-R (p = 0.003). And after the correction of Bonferroni, there was significant difference in CRS-R but no significant difference in GCS.As shown in p-values by Bonferroni, there was no significant difference before and after treatment in two groups.The classification of consciousness levels pre and post treatment can be seen in p = 0.203).Both groups had the same ratio prior to intervention, as shown in p = 1.000). Three months after the end of treatment, the proportion of patients with no functional defects in the VR group was higher than that in the control group. Moderate functional defects in the two groups were the same, while the number in the VR group with severe functional defects was lower than that in the control group. However, there has no significant difference between groups (p = 0.073).As shown in To the best of our knowledge, this study is the first to use immersive VR to provide sensory stimulation for children with DOC in an attempt to improve the level of consciousness. The VR program involves visual, auditory, and vestibular stimuli to form multi-sensory stimuli, as well as a combination of music and memory therapy. We found that VR combined with general rehabilitation significantly increased the CRS-R score [auditory function from 1 0–2) to 3  system based on virtual reality. The theoretical system uses 3D modeling to create a virtual environment equipped with head-mounted displays, 3D trackers, stereo systems, olfactory stimulation devices, wearable tactile displays, and computers, which can provide strong visual, auditory, tactile, and olfactory stimulation . HoweverIn this study, we used VR to create immersive environments to produce multimodal sensory stimuli. For the panoramic video, the programs “Live in Your Music” and “Submarine VR” provided patients with visual, auditory, and vestibular stimuli; the personalized videos also provided patients with visual, auditory, and emotional stimuli. Environmental (sensory) deprivation has been reported to adversely affect synaptic remodeling . PreviouUnfortunately, we did not conduct a questionnaire survey on virtual sickness (side/adverse effects) because the children in this study lacked accurate communication and poor coordination. Brooks et al.  stated tThere are some limitations to this study: Firstly, this was a pilot study and the sample size was small; therefore, any inferences based on the results should be made with caution. Secondly, despite attempts to limit the use of potentially psychotropic drugs for patients hospitalized in PICU or SICU, such drugs were used frequently. Exposure to psychotropic drugs may affect the therapeutic effect of VR or general rehabilitation. To reduce the acute impact of medications, no psychotropic medications were administered in the 24 h preceding treatment. However, in order to eliminate the drugs interference, future studies will include larger sample size and accounting for drug administration. Thirdly, we compared general rehabilitation and virtual reality combined with general rehabilitation, so we could not determine the degree to which the benefits of virtual reality are independent of or synergistic with such general rehabilitation. In the future, we need to take large sample study that compare only general rehabilitation and virtual reality to determine which one gives the main benefit in the further. Finally, this study used several scales mainly for clinical evaluation, and reactivity EEG (EEG-R) and aEEG were also used to objectively evaluate the changes of behavioral responses. However, the statistical comparison of EEG-R was not performed due to the lack of data before treatment. In addition to aEEG and EEG-R, more objective indicators should be taken to evaluate the curative effect such as body surface evoked potentials, brainstem auditory evoked potentials, event-related potentials, transcranial magnetic stimulation combined with EEG, and electromyography in the future studies.This pilot study indicates potential benefit from the addition of VR to standard rehabilitation in pediatric disorders of consciousness. Through this study, we have provided preliminary evidence to support that VR can improve the level of consciousness in pediatric DOC. The exact efficacy of VR is worthy of future randomized controlled trial studies with large sample sizes.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.This study was approved by the Ethics Committee of the Children's Hospital of Nanjing Medical University (batch number: 201912253-1). The registration number in the Chinese Clinical Trial Registry is ChiCTR2000034517. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin. Written informed consent was obtained from the individual(s), and minor(s)' legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.XZ and PL conceptualized the idea and designed experiment. PL, SL, and LR contributed to clinical data collection and assessment. PL and HX contributed to statistical analysis. PL wrote the manuscript. XZ approved the final manuscript. All authors read and approved the final manuscript.This work was supported by National Natural Science Foundation of China (81501946), Jiangsu Women and Children Health Association Scientific Research Foundation (FYX202013), and Nanjing Medical Science and Technology Development Foundation (YKK18144).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This review was intended to determine the effectiveness of physical and cognitive training (PCT) on falls and fall-related factors and cognitive function among community-dwelling elderly people with mild cognitive impairment (MCI). A systematic literature search was performed of the MEDLINE, CINAHL, Web of Sciences, Scopus, ProQuest, Embase, and Google Scholar databases for articles published from 2010 to 2020. The studies that combined PCT to assess their impacts on fall outcomes both directly and indirectly were included. Study quality was assessed using the standardized JBI Critical Appraisal Tool for RCTs. The standardized data extraction tool from JBI-MAStARI was used to extract data of included studies. Seven RCTs involving 740 participants were included. The overall fall incidence did not significantly decrease after the interventions. However, PCT significantly impacted the cognitive function and physical activities of elderly people with MCI, particularly improving their balancing ability, gait speed, muscular strength, and executive functions. This study indicated that combining PCT improves balance ability, gait speed, and executive functioning in the elderly with MCI, which may help to minimize fall occurrence. The elderly with cognitive impairment are prone to falls ,2, and tSince elderly people with cognitive impairment are often excluded from general fall-prevention programs for the elderly in local communities , a fall-The primary goal of this study was to summarize the current evidence of RCTs on the efficacy of combining physical and cognitive interventions in preventing falls and fall risk factors, such as balance, muscular strength, gait, and cognitive function. The finding of this review may help to address optimal intervention for fall prevention in community-dwelling elderly with MCI. To comprehensively and unbiasedly synthesize the effects of PCT on fall prevention in the elderly with MCI, we used guidelines for confirming the quality of a study for systematic reviews of randomized controlled trials (RCTs). Previous studies have utilized these guidelines, and both above-mentioned studies used the 10-item Joanna Briggs Institute Reviewers’ Manual instrument to select the studies . In the Studies were selected based on the PICO model : (1) TarThis review only included randomized controlled clinical trials and experimental studies that had been reported on in English. The MEDLINE, CINAHL, Web of Science, Embase, Scopus, Google Scholar, and ProQuest databases were searched for relevant articles. The following Boolean search string was used for the search: (“cognitive training” OR “cognitive intervention” OR “brain training” OR “cognitive exercise” OR “memory training”) AND  AND (“aged” OR “older people” OR “elderly”) AND (“MCI”). The full texts of articles included in this study needed to be available for evaluation and published between January 2010 and December 2020. Non-original research, protocol studies, and intervention development studies were excluded.One investigator performed the review independently (H.M.B.). It primarily consisted of reading over the titles and abstracts of all studies found through database searches. Second, according to the inclusion or exclusion criteria, two investigators (H.M.B. and J.K.) independently evaluated the obtained full-text studies. Studies that did not meet the inclusion criteria were excluded, and selected studies were agreed upon by two investigators and evaluated for quality in the following phase. Study quality was assessed using the standardized JBI Critical Appraisal Tool for RCTs  This is Quantitative data were extracted from the articles included in the review using the standardized data extraction tool from JBI-MAStARI. The extracted data contained detailed information on the population’s characteristics, intervention features, outcomes, and measures . Due to The search process identified 2835 published and unpublished studies for potential inclusion in the review. Screening the publication titles resulted in 2707 articles being excluded. The remaining 128 articles were then consolidated, with 26 duplicates removed and 56 articles excluded after abstract screening. The full manuscripts of the remaining 46 articles were obtained for full-text reading, which resulted in 38 articles being excluded for various reasons as listed in The total number of participants in all the included studies was 740. The mean age of these participants ranged from 69.5–79.2 years. All participants had MCI identified via diagnosis or cognitive screening test results. The seven included studies comprised two conducted in the United States, and the remaining ones were conducted in France, South Korea, Japan, Taiwan, and the Philippines. p-values could not be interpreted as estimates of type I and type II error probabilities [bilities . Finallybilities .The articles in this review measured falls either directly or indirectly. Direct measures included the number of falls, number of fallers, or fall rate, and indirect outcomes included physical and cognitive risk factors .p = 0.152) and 36 weeks (p = 0.954). Shimada et al. (2018) reported that falls in daily life did not differ significantly between the intervention and control groups after 40 weeks .Overall, the number of falls did not decrease significantly after the intervention. However, the fall outcomes were only measured in two studies: in one as a major outcome  and the Physical outcomes: three outcomes were repeatedly reported to be associated with fall risk across the included studies: balance, gait, and muscular strength. p < 0.01) [p = 0.001) [Overall, after the interventions, dynamic balance and functional mobility improved and positively changed in the combined-intervention group. The timed-up-and-go (TUG) test ,19,20 an < 0.01) ; (2) the= 0.001) .p < 0.05) [Gait performance was measured in four studies, of which two measured it in three conditions: (1) single-task walking, (2) complex walking, and (3) dual-task walking. The findings indicated that complex walking capacities had a larger range of improvement in the PCT group than in the groups in the first study that engaged in a single training . In the  < 0.05) . In the  < 0.05) ,23.p < 0.05) [To evaluate lower limb muscular strength, sit-to-stand time, and a 30-second chair-stand test was used to measure the effectiveness of the combined interventions in two studies. Only one found that the sit-to-stand time improved significantly compared with the control group following 24 weeks of intervention . The oth < 0.05) .p < 0.01) [p < 0.001) [The findings of our included studies also indicated that daily step counts and physical activity intensity in the combined intervention group improved compared with the control group during the study periods of 24 weeks ( < 0.01)  and 40 w< 0.001) .Global cognitive functions were mostly measured using the Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and modified Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Overall, the combined interventions exerted mixed effects on general cognitive functions. The combined intervention group showed significantly greater differences between scores on the MMSE  and ADASp < 0.05) after 24 weeks of intervention. Donnezan et al. (2018) also reported improvements in attention capacity and working memory for all groups except the control after 12 weeks, and working memory was still improved relative to the baseline after 6 months for the PT and PCT participants. The Stroop test was used in four out of seven studies that evaluated inhibitory control. This assesses the ability of a subject to inhibit an automatic behavior (reading a word) and perform a controlled behavior (saying the front color of the word). Overall, the PCT improved the ability to inhibit executive functions at 12 weeks to 6 months after the intervention. Anderson-Hanley et al. (2018) found that the Stroop test score improved significantly in both the exer-tour  = −2.6, p = 0.049) and exer-score  = −5.5, p = 0.001) groups over 6 months. However, after 3 months, the exer-tour group experienced a significant and moderate effect, while the exer-score group experienced the little effect, as did a game-only condition. Liao et al. (2019) found that both the VR and PCT groups exhibited significant improvements in Stroop test scores, but there was no significant difference between the groups. Donnezan et al. (2018) indicated an improvement in Stroop test scores after combined PCT, but the difference was not statistically significant (p = 0.06).Numerous neuropsychological tests were used to evaluate the executive functions in different cognitive function domains, including the Stroop test, symbol-digit substitution test, the color trails test, the digit span test (DST), the trail-making test (TMT), Rey’s auditory verbal learning test, and the verbal fluency test. Of these, the TMT was commonly used to evaluate attention domain outcomes in four studies ,18,21,23This study is the systematic review that combined PCT intervention for preventing falls and identified the effects. Seven studies were selected for review when using the JBI tool to assess the quality of included studies . The objA PCT intervention was found to be useful for improving cognitive and physical function in the elderly with MCI  and seemA training program developed using VR was found to improve the cognitive and physical functions of the elderly with MCI . In anotTwo of the reviewed studies directly measured the frequency of fall occurrence ,20, but Instead of directly measuring fall incidence, many studies measured variables such as balance, mobility, and gait related to falls, which were also used in many studies with interventions aimed at enhancing physical activity to prevent falls. Various types of intervention also induced significant changes in fall-related variables. For balance measurements, sway was measured using a wearable sensor. In one included study, the intervention group showed better sway results than the control group . MeasuriThe tools used frequently to measure differences in cognitive function before and after a program were the Stroop test ,21,22, MThe continuation of each intervention activity is important for preventing falls in the elderly with cognitive impairment. In this regard, it is also important to determine whether an intervention activity is easy to perform in daily life so that the subject can practice it over the long term. It is therefore important to develop a program that can be easily performed by the elderly in the community and that can be continued after the intervention concludes. Only two studies followed up after the intervention period ,20, but The limitations of this study were as follows: The number of reviewed studies was small due to combining PT and CT and selecting interventions targeting MCI. This approach made it difficult to pool the study results to carry out a meta-analysis. In addition, the effect size could not be measured since the outcomes in the reviewed studies were too heterogeneous. This was because the measurement variables related to falls and the variables measuring cognitive function were both diverse. However, this study has implications that can be referred to when planning a program to prevent falls among the community-dwelling elderly with MCI. This was systematic review studies including to directly and indirectly observe the effects of PCT on fall outcomes in community-dwelling elderly with MCI. Although the combined intervention did not induce a direct decrease in fall rates, it did exert a strong indirect effect on reducing fall risk factors for the elderly with MCI, including their balance, gait speed, muscular strength, and cognitive function. However, we still cannot infer that the combined intervention reduced the fall incidence compared with the single intervention because only two of the included studies reported fall rates in their respective trials. Therefore, additional studies on the direct effect of this intervention on fall rates in elderly people with MCI are needed. Our findings also add to the existing understanding of the impact of PCT on most physical and cognitive domains. Finally, it is advised that when implementing a physical activity intervention program combined with CT in the future, the same tools as those used in previous research should be used in the analysis.


The hepatitis B virus (HBV) is a blood-borne virus that can be transmitted by percutaneous and mucocutaneous contact with infected bodily fluid. Healthcare workers (HCWs) are more exposed to HBV infection. They must have a thorough understanding of HBV infection since they can contract and spread the virus. In this study, we systematically reviewed all published evidence on the seroprevalence of Hepatitis B virus (HBV) infection among HCWs. and synthesize evidence on the association between knowledge and awareness with HBV infection.We searched PubMed, EMBASE, Cochrane Library and Scopus for studies reporting on HBV seroprevalence from January 1997 to September 2021 among healthcare workers. We used random-effects meta-analyses to estimate the pool prevalence of HBV infection.We identified 25 studies that met our inclusion criteria, with data on 10,043 adults from 11 countries and two regions: Africa and Asia. The overall seroprevalence of HBV was 5.0% , with Africa reporting higher estimates  than Asia population . The highest pooled prevalence estimate in African countries came from studies published in the Cameroon region  while the lowest came from Ethiopia . The overall seroprevalence estimates in the African population were significantly higher than those in the Asian group. Studies in Africa found that the average knowledge and seroprevalence were 1.4% and 11.0%, respectively where, eight studies (53.3%) reported good knowledge and seven studies (46.7%) reported average knowledge. In Asia, two studies (40.0%) reported good knowledge, one study (20.0%) reporting average knowledge, and two studies (40.0%) reporting poor knowledge. African studies demonstrated good knowledge despite the fact that their HBV infection rate was higher than 6.7%.Africa and Asia have the highest seroprevalence of HBV infection. Improving the comparability of epidemiological and clinical studies constitutes an important step forward. More high-quality data is needed to improve the precision of burden estimates.PROSPERO CRD42021279905. Hepadnaviridae family, has only one known natural host: humans. The virus enters the liver through the bloodstream and replicates in the tissue of the liver (The Hepatitis B virus (HBV) is a bloodborne virus that has become a major global public health concern. HBV, which belongs to the he liver . Acute hhe liver . Globallhe liver . Accordihe liver , and apphe liver . Hepatithe liver –8. Furthhe liver .Healthcare workers are four times more likely to be infected with HBV compared to the general population . This maAlthough HCWs are more aware of Hepatitis B, several countries lack a comprehensive grasp of the disease biology, transmission methods, risk of transmission, clinical characteristics, and vaccination availability . HepatitWe conducted a systematic review by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)  and GuidA comprehensive systematic literature search was conducted in electronic databases  to identify relevant studies from inception to September 2021. A search strategy was developed for PubMed  and adapWe included studies according to the following criteria; Population/Intervention/Comparator/Outcome/Study Design (PICOS) approach. For this review, we included HCWs (P) defined as individuals such as doctors, dentists, nurses, midwives, medical personnel, medical assistant or laboratory scientists who are in direct contact with the following: (i) patient bodily fluids or biological samples such as blood, saliva, sperm, sweat and stool, (ii) new-born delivery process in which mother-to-child transmission was possible via a transplacental route, and (iii) people who were exposed sexually, and (iv) sharp or needle-stick injuries. Instead of an intervention (I), we included observational studies that report the seroprevalence of HBV with either one or both of the components of knowledge or awareness in relation to HBV seroprevalence. There was no comparator (C), and lastly, the determined outcome (O) was seroprevalence of hepatitis B infection. We considered all articles published in English language. When numerous studies with the same cohort were conducted, the research with the most detailed information on the participants or the largest number of participants was chosen.We excluded abstracts, letters to the editor, reviews, commentaries, editorials, and studies without either primary data or described study methods. We excluded systematic reviews, non-empirical studies, conference, abstracts, editorials, commentaries, book reviews, and abstracts not accompanied by a full text.Two review authors (NHM and NAM) independently screened all titles and abstracts to look for potential studies found through the search and coded them as “retrieve”  or “do not retrieve”. Two more review authors (NSMD and MHAM) independently retrieved full-text study reports/publications to identify studies for inclusion, and to identify and record reasons for studies' exclusion. When there were disagreements, a consensus was obtained through discussion with a third reviewer (MRAH).Two review authors (FNL and TA) independently evaluated each included study ‘s methodological quality and extracted data using a piloted form; discrepancies were resolved through discussion with a third review author (NML). Data on the year of publication, country of origin, study design, sample size, sampling procedure (if available), study period, and setting (country/continent/region) were extracted using a standardized data collection form.To assess the risk of bias for each study, a domain-based questionnaire developed from the Newcastle-Ottawa Scale (NOS) was used to assess methodological quality  Supplem. In the 2 statistics and Cochran's Q Test  independently assessed the quality of the included studies using an adapted version of the NOS for prevalence studies. The quality of evidence was rated as low to begin with, due to the non-randomized nature of the study. The quality of evidence in the outcomes were based on the NOS criteria, where a maximum score of 4 stars for selection, 2 stars for comparability, and 3 stars for exposure and outcome assessment. Studies with fewer than 2 stars were considered low quality; 2 to 6 stars, moderate quality; and 7 stars and more, high quality. Twenty-one studies were observed to be of good quality (NOS score 7 and above), and four studies were identified as fair quality (NOS score between 2 and 6 inclusive) .2 = 94.6%, P = 0.001). The study was divided into two parts: Africa and Asia. In Asia, the overall pooled seroprevalence of Hepatitis B was 4.0% (95% CI: 0.01–0.07) with a high-level of heterogeneity between studies      (As shown in = 0.001) , whereas= 0.001) . The sub= 0.001) . In Nige= 0.001) . Ethiopi = 0.19) . Cameroo = 0.03) .There were twenty studies that reported findings on seroprevalence and knowledge, with fifteen from Africa and five from Asia. Some of the studies mentioned the knowledge level  in the publication. In Africa, the majority of the studies found that participants have a strong knowledge of hepatitis B infection, with eight studies (53.3%) reporting good knowledge and seven studies (46.7%) reporting average knowledge. In Asia, five studies reported seroprevalence and knowledge findings, with two studies (40.0%) reporting good knowledge, one study (20.0%) reporting average knowledge, and two studies (40.0%) reporting poor knowledge. Seven studies in Africa found that the average knowledge and seroprevalence were 1.4 and 11.0%, respectively. Surprisingly, few African studies demonstrated good knowledge despite the fact that their HBV infection rate was higher than 6.7% , 42, 45.There were eleven studies that found an association between seroprevalence and participants' level of awareness, including nine (81.8%) from Africa and two (18.2%) from Asia. Some of the studies mentioned the participants' level of awareness . The scale for awareness level was adopted from Vaishali et al.  for thosHealthcare workers have a higher risk of contracting HBV infection than the general population. Simultaneously, they play a vital role in preventing and controlling HBV infection by disseminating and transmitting HBV knowledge to the public, as well as assisting in behavior changes that may aid in infectious diseases prevention . After uIn comparison to other regions, the current study found that African countries have a high seroprevalence of HBV infection , 4. MediDespite the high seroprevalence observed in a few studies, other publications claimed good knowledge or awareness of HBV infection , 43, 46.A few approaches to increase an awareness of HBV infection among HCWs include strengthening immunization program, regularly screen the HBsAb and HBsAg of HCWs, media involvement, continuous medical educations, and provide trainings to the HCWs , 46, 50.The present study had limitations. First, we were unable to locate reports on the HBV seroprevalence and levels of knowledge or awareness in the developing countries. Thus, we were unable to compare the findings worldwide. Second, in some research, differences in score and inability to score on the level of knowledge or awareness may result in inconsistent conclusions that are either good, average, or poor. As a result, we were unable to determine some research' scores and compare them to seroprevalence.In conclusion, hepatitis B virus was shown to be present in 4.0–5.0 % of the population tested, with an apparent higher prevalence in African countries than in Asian countries. Some HCWs were still infected with HBV despite having strong knowledge and awareness of HBV infection. Improved epidemiological data collection can help determine and identify key risk factors for a more effective public health response. Thus, if enough people are exposed to Hepatitis B virus knowledge, awareness, attitude, and practice, the goal of eliminating viral hepatitis by 2030 may be achieved.The original contributions presented in the study are included in the article/NHM and NAM carried out the study design, study selection, data extraction, and statistical analysis and drafted the manuscript. NSMD and MHAM participated in the study selection and data extraction and drafted the manuscript. FNL and TA evaluated the quality of included studies. MRAH and NML participated in the discussion for any discrepancies and supervised the study. All authors read and approved the final manuscript.The open-access publication fee was supported by the National Institutes of Health, Ministry of Health, Malaysia.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This study aims to observe the effect of optimized individualized nursing care applied to intensive care unit (ICU) patients with severe pneumonia (SP).  440 patients with SP admitted to the ICU of our hospital from January 2019 to June 2020 were provided with routine nursing care (group A), and 550 patients with SP admitted from July 2020 to December 2021 were provided with optimized individualized nursing care (group B). The blood lactate index and acute physiology and chronic health evaluation (APACHE II) scores before and after care were compared between the two groups. The WBC count recovery time, mechanical ventilation time, antipyretic time, and length of hospital stay of the two groups were recorded. The complication rate of the two groups during the nursing care period was compared. The prognosis effect of the two groups after 6 and 12 months of discharge was followed up with the Seattle angina pectoris questionnaire (SAQ). P < 0.05). After care, APACHE II scores were lower in both groups than before care, and lower in group B than in group A (P < 0.05). After care, the WBC count recovery time, mechanical ventilation time, antipyretic time, and length of hospital stay were shorter in group B than in group A (P < 0.05). During the nursing care period, the complication rate was lower in group B (5.82%) than in group A (11.59%) (P < 0.05). 6 and 12 months after discharge, the SAQ scores were higher in group B than in group A (P < 0.05).  After care, the lactate level and lactate clearance rate were higher in both groups than before care, and the lactate level in group B was lower than that in group A and the lactate clearance rate was higher than that in group A ( Optimized individualized nursing care applied to ICU SP patients can effectively improve the patients' physiological indicators, reduce complications, improve the prognosis of quality of life, and have a positive effect on the patients' speedy recovery. ICU monitoring is often used in the clinic to improve the treatment effect [Severe pneumonia (SP) is a common acute and critical illness, mostly in the elderly. Patients are severely ill, progress rapidly, and have a poor prognosis, and some patients may even suffer from complications, such as infectious shock , acute rt effect . Martin-t effect  believe P > 0.05), which is comparable  for SP  and weremparable .Patients in both groups received symptomatic support treatment, such as routine oxygenation, sputum evacuation, anti-infection, nutritional support, correction of water-electrolyte disturbances, acid-base balance, and active treatment of underlying diseases.① Environmental care: nursing staff should keep the air in the ward clean with appropriate room temperature and humidity and regular ventilation. Also, ensure that the beds are neat and clean, the room is disinfected regularly, and the quietness of the ward is maintained. ② Daily care: healthcare workers should make detailed observations and records of changes in the patient's condition, advise the patient to take medication on time, arrange rest time reasonably, conduct daily vital sign checks for the patient, and perform regular oral, nasal, and suction care. ③ Health education: health care staff should develop relevant health education programmes in a targeted manner. For those with a high literacy level, they could communicate with patients by using the treatment means of the disease, the nursing programme, and precautions as entry points; for those with a low literacy level, the nursing staff should explain the knowledge of the disease in a simple and easy-to-understand manner to help patients establish a correct mindset towards the disease. ④ Discharge instruction: instruct patients to take appropriate physical exercise to improve their physical fitness and quality of life.2 below 90%, elevated airway pressure and sputum sounds, and the patient's vital signs and parameters were closely monitored during aspiration. For older, weaker coughs and severe conditions, postural drainage might be used. For patients on ventilator-assisted ventilation, airway humidification should be enhanced to dilute sputum to prevent blockage of the tube. ② Oxygen therapy care: for patients with symptoms of hypoxia, blood oxygen saturation should be monitored, and an appropriate oxygen inhalation mode should be selected according to the results. Oxygen flow should be controlled at 5 L/min. For patients with CO2 retention, oxygen should be maintained at a low flow rate and be continuous, with an oxygen concentration of 30%–35% being appropriate. Also, during oxygen therapy care, the nurse must closely monitor the patient's respiratory rate and state of consciousness. ③ Bacterial culture and drug sensitivity test: bacterial cultures were regularly performed on airway secretions, and drug sensitivity tests were conducted on isolated pathogenic bacteria to keep track of changes in pathogenic bacteria and to select sensitive antibacterial drugs, pay attention to the duration of each use of antibacterial drugs within 8 d, and change the type of antibacterial drugs when appropriate to reduce bacterial resistance. ④ Complication prevention and control care: if patients develop cardiac insufficiency, they should be promptly treated with oxygen and sedation to control their condition. If there was no significant improvement in symptoms and the patient became agitated and cyanotic, appropriate resuscitation measures should be taken to prevent heart failure from developing. If patients develop symptoms of renal insufficiency, caregivers must closely monitor the patient's progress. ⑤ Psychological care and health education: SP patients often had symptoms, such as chest tightness and wheezing, and were accompanied by a sense of near-death, which, together with being in an ICU environment, further aggravated the patients' psychological burden and fear. Patients were provided with reasonable psychological guidance and health education, introduced to the purpose of various treatments and examinations and the methods of cooperation so that they could have a scientific understanding of their condition, reduce unnecessary psychological pressure, alleviate their anxiety and tension, and improve compliance with treatment.① Enhance respiratory management: help the patient lie flat and pad the neck and back, and pay attention to clearing the oral and nasal secretions at any time to keep the respiratory tract unblocked. For those whose sputum was thick and difficult to cough up, Mucosolvan and normal saline were given for atomization inhalation to dilute the sputum. Sputum aspiration could be performed on anyone with SpOBefore and after care, a blood gas biochemistry analyser  was used to measure lactate levels in both groups and to calculate the lactate clearance rate. Lactate clearance rate = /initial lactate level × 100%.Before and after care, APACHE II scores were tallied for both groups. It consists of 3 parts: the acute physical status score, age, and chronic health status score, with a total score of 71, 0–15 being nonserious, and >15 being serious, with lower scores indicating a less serious condition.The WBC count recovery time, mechanical ventilation time, antipyretic time, and length of hospital stay of the two groups were recorded.The occurrence of complications  during care was recorded in both groups.The prognosis effect of the two groups after 6 and 12 months of discharge was followed up with the SAQ. The assessment dimensions include activity limitation, disease onset, and quality of life, all of which are scored out of 100, with higher scores indicating better survival status.s) were tested by independent samples t-test. Count data n (%) was tested by χ2. A difference of P < 0.05 was considered statistically significant.SPSS 22.0 was used for data analysis. The measurement data (±P < 0.05). . .P < 0.05). . .P < 0.05). . .P < 0.05).  than in group A (11.59%); the difference was statistically significant (< 0.05). .P < 0.05). . .Pneumonia is an inflammation of lung tissue , caused by different etiologies and different pathogenic bacteria in different settings with similar or identical pathophysiological processes, all of which can deteriorate and worsen into SP when they develop into certain disease stages, causing multiorgan dysfunction or even being life-threatening, with a mortality rate of up to 30%–50% . SP is pPatients with SP have congested and oedematous lung tissue, as well as increased respiratory secretions, which can lead to fine bronchial and bronchial obstruction, causing respiratory distress . LactateAPACHE II score is an internationally used method to classify and assess the condition of critical patients and predict the prognosis, and it is also applicable to the assessment of the severity and prognosis of ICU patients . Also, tICU SP is mostly seen in elderly patients, whose immune systems are low and whose organ reserve function is relatively poor. Once the disease progresses, it can lead to rapid failure of all organ functions that are barely in equilibrium in a short period of time, and can easily lead to various complications and seriously affect the patient's prognosis , 19. BasSAQ is a recognized, effective index to evaluate the results of clinical treatment measures and has been widely used in the evaluation of the quality of life of patients with coronary heart disease . In thisIn summary, the optimized individualized nursing care applied to ICU SP patients can effectively improve the patients' physiological indicators, reduce complications, improve the prognosis of quality of life, and have a positive effect on the patients' speedy recovery.


These results revealed that platelet activation in viral respiratory tract infections in children, as measured by MPV, is related to the vit D level, with differences between influenza and non-influenza infection.Apart from their classical roles, both platelets and vitamin D play important roles in inflammation and infectious diseases. This study evaluated the platelet response to viral respiratory tract infection in children aged 4–16 years, 32 with influenza, 27 with non-influenza viral infection tested by nasopharyngeal swab and 21 healthy children of the same age. Blood count, including platelet count (PLT), mean platelet volume (MPV) and other platelet indices, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and vitamin D (vit D) levels were compared. The influenza group showed lower PLT and platelet mass (PLTViral respiratory tract infection in children can diminish the platelet size most likely by suppressing the platelet activation. This response is associated with low levels of vit D. Whether the vit D status is associated with the virus-platelet immune/inflammatory process needs further investigation. Acute respiratory tract infections (RTIs) are the most common infections worldwide . In a stThe incidence of RTIs related to influenza virus is higher among children aged <3 years, reaching 179/1,000 .The complete blood count (CBC) is the most frequently used laboratory test during an infection process . The chaThe primary function of platelets is haemostatic, but recently, their role in inflammation and immunogenicity has also been evaluated. They show the ability to recruit leukocytes and release proinflammatory and anti-inflammatory factors . SeveralThe main role of vitamin D (vit D) is in bone homeostasis, but in recent years its role in infections , inflammIn this study we investigated the platelet changes during influenza and non-influenza RTIs in children, and the possible role of vit D in the process.The study population consisted of Caucasian children, aged 4–16 years presenting with symptoms of RTI in the emergency department (ED) of a regional hospital in Greece during a 6-month period (September 2019–February 2020). The exclusion criteria were comorbidities, need for hospital admission, vit D supplement during the preceding 3 months, a diagnosis of bacterial infection, and administration of medication other than antipyretics. A control group was selected from children of the same age attending the pediatric outpatient clinic of the same hospital for a well-child visit, during the same time period. Similar exclusion criteria were applied for the control subjects. Children with even minor infections on the day of examination were excluded. The study was approved by the hospital ethics committee. Written, informed consent was provided by parents'care givers of all the children in the study.Testing for Influenza A and B by a nasopharyngeal swab was performed on each child on arrival in the ED. The demographic characteristics of each child, and the duration and height of fever and the presence of cough were documented. A sample of venous blood was drawn for analysis of (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and the level of vit D. The CBC was performed in a Unicel DxH 600 Coulter Cellular Analysis System by Beckman Coulter. The blood samples for CBC were obtained by ethylenediaminetetraacetic acid (EDTA) and were analyzed within 1 h after collection in order to prevent platelet swelling.The influenza viruses were identified by a rapid immunochromatographic test for the qualitative detection of influenza antigens in nasopharyngeal swab. Vit D (25(OH)D) was measured by ELISA method, using 25OH Vitamin D Total ELISA Kit . All the determinations were done according to the manufacturers' instructions.t-test or the non-parametric Mann-Whitney test. Categorical variables were presented as counts and percentages, which were compared using χ2-statistics or Fisher's exact test. Statistical significance was defined as P < 0.05.SPSS 25 was used for statistical analyses. Normal distribution for continuous variables was assessed with the Kolmogorov–Smirnov normality test. Continuous variables were expressed as mean ± standard deviation (SD) or median (Percentile 25–75), and they were compared using an unpaired Student's A total of 80 children were included in the study. The patients with RTI were divided into 2 groups: those diagnosed with influenza (32 children), and those ones with a negative influenza test (27 children). The healthy control group comprised 21 children.p < 0.01), although both groups recorded a maximum temperature above 39°C. The duration of fever was lower in children with influenza compared to non-influenza group, but the difference was not statistically significant. The presence of cough was similar in both groups, around two thirds.The demographic characteristics and the symptoms of the study children are shown in The laboratory values are reported in 3/ml vs. 306 × 103/ml), although thrombocytopenia with PLT <150 × 103 cells/ml was observed in only one patient, in the non-influenza group. The platelet indices were examined further among the groups. The platelet count (PLT) showed significant differences between groups. The children diagnosed with influenza had lower PLT (233 × 10p = 0.005)  . The PDW= 0.005) . The sen*PLT) showed significant differences between the groups, being greatest in the control group and least in the influenza group: influenza vs. control , and influenza vs. non-influenza .The platelet mass (MPVp = 0.013]. The median level of vit D was slightly lower in the influenza group than in control group [23.97 (13.88–52.69) vs. 26 (16.25–79.6)], but the difference did not reach the level of statistical significance (p = 0.108). Additionally, several complex parameters resulting from the multiplication of the vit D level with MPV, PLT and PDW, respectively, are lower in the non-influence than in the control group and this difference is statistically significant.With regard to vit D levels, the non-influenza group showed significantly lower levels of vit D compared to the control subjects [21.49 (15.47–36.2) vs. 26 (16.25–79.6), The aim of this study was to evaluate the platelet response to viral RTI in children by identifying the differences in PLT and platelet indices among children suffering from influenza and other viral RTI, compared with healthy control subjects, and exploring the impact of vit D on platelet parameters. Moreover, we intended to evaluate the role of platelet indices, specifically of MPV as a potential factor to differentiate influenza by other viral RTI. The early etiological diagnosis of RTI may be difficult in certain location. The PLT indices can offer useful information and they are already determined and available through complete blood count (CBC).3 cells/ml. Vit D deficiency, with vit D levels <20 mg/dl, was observed in 7/32 children in the influenza group, 7/27 in the non-influenza group and 3/21 in the control group. None of the children had very low levels of vit D of <10 mg/dl.None of the children with influenza developed thrombocytopenia, while only one from the non-influenza group had PLT 123 × 10The two groups with RTI had similar clinical characteristics, regarding the duration of the illness, measured by the days of fever, although those in the influenza group developed higher fever, and the presence of cough. The inflammation indices CRP and ESR were similar in the two groups with RTI, and higher in both than in the control group.p = 0.7, 0.96, 0.98, respectively). A higher MPV occurs as a result of increased platelet activity and thus of more intense inflammation as a result of a certain infection  that are not different in the two groups (nfection .The mechanism of low PLT can be explained by studying further the platelet parameters, MPV and PDW. The MPV in the influenza group showed no difference from the control group, while the PDW was higher, but not to a statistically significant degree. This means that in response to influenza, the platelets maintain their size, but have increased variability, compared to the control subjects. In the non-influenza RTI group, the PLT showed no difference, but the platelet size was significantly lower compared to the control group, but with stable PDW, i.e., no significant size variability.To explain these findings, we must review the platelet response to inflammation/infection. The platelets are cytoplasmic fragments of megakaryocytes. The MPV has been extensively evaluated, both in healthy subjects and in several medical conditions . The regWith regard to viral infections, several different mechanisms of PLT modulation have been proposed , and theThe defense mechanism mediated by platelets is very complex, involving activation and recruitment of leukocytes. The platelet-leucocyte activation results in vascular inflammation. Finally, platelets are also implicated in the resolution of inflammation .In the case of influenza, the platelets play an important role in the host immune defense, and the inflammation process, and live viruses have been identified inside the platelets . It has In the current study, the children with non-influenza RTI had low MPV, but the PLT remained stable, suggesting diminished platelet activation. The platelets are not activated and consequently they are not consumed at the sites of inflammation. This may be a direct effect of the viral strains on the platelet response, or due to alterations in the innate host immunity.*MPV was lower than in the control subjects, due to decreased PLT.With regard to the children with influenza, their mean PLT was lower than that of the control group, but with no differences in MPV. Their mean PDW was minimally elevated, but the difference did not reach statistical significance. These findings suggest platelet activation and consumption at the inflammatory sites. A dysregulation of platelet mass was observed, as PLTThe differences in platelet indices between the two groups with RTI, influenza and non-influenza, cannot be explained by the degree of inflammation as this was documented to be similar by the clinical symptoms and the levels of the inflammatory indices ESR and CRP. The only notable difference between the two groups was the vit D level, which was significantly lower in the non-influenza group compared to the control group.The immunomodulatory effect of vit D has been described in several illnesses , 46, 47.The low vit D levels could be a result of insufficient dietary intake of vit D compared to increased demand of vit D as a consequence of the infection in the non-influenza patients. It is of note that our series consists of patients who were brought to the ED with symptoms severe enough to alarm their parents. It is not clear whether the lower vit D levels led to an increase in symptom severity, resulting in the ED visit, or if the severity of the symptoms was due to the virulence of the microorganisms. In addition, the vit D status could be a cofounder to viral susceptibility.The main strength of the paper is the demonstration of an influence of influenza virus on platelet reaction and the establishment of a direct relationship virus-platelet immune process. This study was limited to a specific age range, 4–16 years, and younger children and infants were not included. In addition, none of the children were diagnosed with severe vit D deficiency. The children were examined within the first 2 days of the beginning of illness. It would be interesting to evaluate the platelet parameters during the course of their disease. Further studies are needed to confirm our findings, and to extend the evaluation to the clinical outcome of those patients with low vit D levels and platelet inactivation.The major limitation of this study was the small sample size of children. Our study was designed to be conducted over 2 flu seasons, 2019–2020 and 2020–2021. Unfortunately, the appearance of the pandemic, did not give us the opportunity to continue the study. Shortly after WHO declared the SARS-CoV-2 pandemic, the cases of influenza showed a sudden decrease, and the “flu season” ended earlier than usual. Next year, due to the introduction of the measures to limit SARS-CoV-2 transmission, a decrease in respiratory viral infections has been observed in children.This study has identified alterations of platelet indices in patients with influenza and other respiratory viral illnesses in association with vit D levels. Measures of molecules secreted by activated platelets and platelets functional studies should be performed to verify the relationship of platelet parameters with the platelet activation.In conclusion, the present study showed that viral RTI in children can diminish the platelet size probably by suppressing the platelet activation. Also, we found that MPV acted as a positive acute phase reactant in children with influenza RTI, and MPV levels were significantly elevated in these children. This response is associated with low levels of vit D, which probably alters the virus-platelet-immune/inflammatory process.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Scientific Commission of General Hospital of Amaliada, Greece. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.GF, VV, IB, and MZ: conceptualization. GF, RP, IB, and MZ: methodology. GF, VV, and IB: analysis and writing—original draft preparation. GF, RP, and IB: investigation. GF, VV, IB, LS, and MZ: writing—review and editing. LS, AB, and MZ: supervision. GF and MZ: project administration. All authors read and agreed to the published version of the manuscript.This work was supported by PhD Grant 1300/24/13.01.2017, University of Medicine and Pharmacy, Iuliu Hatieganu, Cluj Napoca, Romania.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.