Hyperbaric oxygen therapy (HBOT) is a professional medical regimen with a wide range of clinical applications in various research fields. In addition to treating diving decompression sickness and air embolism, HBOT is used as an adjuvant in the management of various diseases. A large number of studies have been published to confirm its efficacy. Although HBOT has been clinically applied to the treatment of many diseases, the effectiveness of these treatments remains controversial. Exploring and evaluating HBOT will contribute to the future development of research in this field. Through a quantitative analysis of the literature, this paper explores the citation relevance and collaboration map and their impact on research outcomes. This study used bibliometric and cartographic techniques with VOSviewer to identify the most influential countries and scholars using this treatment, based on syndrome differentiation. It also provides continuous quality evaluation and lean management of the medical expenses associated with HBOT. Hyperbaric oxygen therapy (HBOT) is a recognized treatment for diving decompression sickness (DCS)  and air In the past, most of the academic research on HBOT has focused on its treatment mechanisms and therapeutic effects on a disease . HoweverIn summary, this study’s aims were to obtain more evidence of HBOT research trends from the information in the database through a visual bibliometric method, so as to point out the shortcomings of past research and the directions of future research.WOS platforms make up one of the largest scientific citation index databases on the world. The comprehensive academic information resources consist of six online indexes that include more than 8700 core academic journals in various fields such as medical science, biomedicine, engineering, humanities and social sciences. In the data mining process, digital system parameters were searched from WOS citation indexes . The field retrieval of information was “title” and “topic”. The digital system parameter search term setting of “hyperbaric oxygen therapy” was used for this study. The document type was limited to “article”. Articles were excluded if their primary focus was not HBOT, even if the topic was peripherally discussed. Furthermore, publications such as meetings and commentaries, letters to the editor, editorials and abstracts were excluded. Since this study is concerned with the development trend of HBOT in recent years, 1999–2021 is used as the time interval for analysis. According to the stated inclusion and exclusion principles, 5944 articles on HBOT were obtained.VOSviewer tools (version 1.6.15) were used in this study. They were developed by the Centre for Science and Technology Studies at the University of Leiden. VOSviewer is a free access visualization tool that can quickly render numerical data visually to make published content stand out. Additionally, VOSviewer is able to recognize any patterns in large bibliometric datasets, including Europe PMC, Microsoft Academic, Open Citations, Crossref and PubMed . This maIn this study, we assessed the various functional options of the system and accurately analysed the growth of publications and research hotspots related to HBOT. The results of this analysis will contribute to the development of HBOT. Details on the steps for this study are shown in The VOSviewer clustering technique is based on the connections between its cluster function  and the strength among objects of interest (the body of scientific literature) . This viIn this paper, we determined the most influential journals, authors and countries publishing HBOT research. Additionally, the visualization map  was constructed in this study, and based on this, the theoretical foundation for the visualization platform research was established.n = 238), the UK (n = 186), Australia (n = 176), Taiwan (n = 176), Israel (n = 156), Germany (n = 154) and Italy (n = 136).In addition, the USA has a link strength of 12,741 with 30,669 citations; the USA ranks significantly higher than other countries in total link strength, which is expected because of their number of publications. China and Turkey are second to the United States in total link strength; China’s link strength is at 3860, with 4568 citations, while Turkey’s link strength is 3679 with 3872 citations. Interestingly, the scientific research production related to HBOT is concentrated in the northern hemisphere, with little representation from the southern hemisphere, which includes Indonesia and South Africa.The results of the author co-citation analysis and the investigation of the interrelationships among individual authors in the academic field are presented in Undersea and Hyperbaric Medicine have been co-cited 2843 times, and have a total link strength of 105,698. Other journals with high citations and overall link strength include the Journal of Applied Physiology and Brain Research; the Journal of Applied Physiology has a total of 1728 citations and a total link strength of 59,549, while Brain Research has a total of 1443 citations and a total link strength of 59,541. It is noteworthy that these well-known journals are focused on the clinical applications on orthopaedics, plastic surgery, neurology, rheumatology and neurosurgery. This shows that these clinically oriented journals can influence future research directions.The results of this study reveal information from most publications in the WOS. The findings show that the citation analysis of journals reflects the research domains of HBOT . ArticleStructural analysis of keywords helps to identify important research topics in the field. Visualization co-occurrence keyword analysis is an efficient tool providing insight into the most popular topics in publications in a specific research field and how their frequency varies with time .Results show that from the bibliographic database of 5594 articles with the minimum occurrence pre-set at 10, there are 8744 keywords in 433 articles that meet the threshold. The total link strength of each keyword was calculated, and is shown in The findings show that HBOT research focuses on its mechanisms, indications and treatment risks. These data can help researchers speculate on the future directions of HBOT research. In addition, the management of HBOT remains the most important research topic.As shown in the overlay visualization in Co-occurrence network analysis was used to examine the relationships in and structure of HBOT research .It can be observed that the keyword with the highest co-occurrence frequency density and total link strength is “hyperbaric oxygen”, with values of 912 and 4459, respectively. The “treatment” of co-occurrence frequency is 672 and the total link strength is 3406. Lastly, the “hyperbaric oxygen therapy” of co-occurrence frequency is 635, and its total link strength is 2421. The remaining keywords have lower co-occurrence frequency and total link strength.This also subtly shows that the keywords showed a research concentration on the risks and benefits of HBOT. This can be partly attributed to attention from the academic community, and it is still an important subtopic in HBOT research.According to the results of the visualization analysis of HBOT publications, we propose the following implications for HBOT research and trends in coming years.Bibliometric analysis is based on constructing graphical databases with various citation metrics. It is frequently used in the field of library and information science . The gloThe UHMS is an international non-profit organization that is the primary source of scientific information for hyperbaric medicine in relation to physiology and diving . In addiBased on the number of journals and authors mentioned above, there is strong competition globally to contribute to HBOT. This study confirms the use of bibliometric analysis to examine the status of international academic cooperation and identify core research groups. The USA is a core country with a dynamic comparative advantage; it also has technological spillover, and is a leader in HBOT research and innovation.The article that received the most citations has also exerted a positive and profound influence on current research . As in tR. E. Marx is another researcher who has made important contributions in HBOT. He pioneered new concepts and treatments for oral pathologies, and made valuable contributions to the use of hyperbaric oxygen after radiation therapy. He indicated the benefits of hyperbaric oxygen therapy, including vascular improvement, maintenance of intact mucosa, expedited healing of osteoradionecrosis and skin over all bone and better tolerance to surgical wounding prior to oral surgery . In addiThe next most important contributor on HBOT is T. K. Hunt. He is dedicated to curing age-related diseases through biotechnology. T. K. Hunt has long been immersed in the development of trauma services and the cell biology of wound healing . In explUndersea and Hyperbaric Medicine journal is the most important in the HBOT field, having received 2843 citations, and has a co-citation strength of 105,698. This journal is receptive to new scientific information on this topic and has great publication strength, which has contributed to conceptual research and opinions on future research directions for HBOT. The Journal of Applied Physiology focuses on the theories, methods and applications of scientific concepts and publishes techniques in physiology. Brain Research is devoted to fundamental research on the brain and neuroscience. It publishes articles on nervous system structure and function, diagnoses of brain injuries and experiments and clinical trials for diseases that are the relevant for HBOT and of general interest to the international community of neuroscientists. Other journals, such as the Stroke and The Lancet, also play an important role in HBOT research.The analysis of journals that have published papers on HBOT shows publishers that engage with similar subjects. The Undersea and Hyperbaric Medicine is the most frequently cited journal in our analysis . Although some journals do not have many publications, they have a very high number of co-citations. It is also worth noting that based on the co-journal analysis, the Unersea and Hyperbaric Medicine journal predominates, especially in terms of the exceptional quality of its research articles. It makes a substantial scientific contribution and has a far more positive impact and the greatest effect on academic HBOT research compared to any other journal. In the classification of the top five journals related to HBOT, relevant subjects included plastic surgery, neurological medicine, physiology and neurosurgery. Higher co-citations and effects on the modern-day health system show that journals add strength and value to research that positively impacts the lives of people.These topics not only provide new scientific perspectives, theoretical foundations and clinical applications in hyperbaric medicine, but also seek to address urgent topics in society, such as human health and major environmental events. Notably, We summarize our arguments as follows. The collaborative network of authors and journals shown in the bibliometric analysis contributes to highlighting lesser-known disciplines and identifies potential competitors. Capable scientists are necessary for improving these theories, monitoring the future of HBOT, contributing to solutions to recent global issues and combining creative imagination with true scholarship.Co-keyword analysis can effectively measure the relatedness of topics and quantitative knowledge structure . It is aFrom the analysis results of important keywords, hyperbaric oxygen therapy, oxidative stress and expression are the research topics that attract attention. The bibliometric analysis highlighted some of the beneficial effects of HBOT. The data that indicate the therapeutic effects of hyperoxia have been demonstrated often, but this research topic still attracts a wide range of public opinions. For example, HBOT is currently used off-label to treat COVID-19 pneumonia patients. An overly active immune response generating inflammation is a direct cause of the pathogenesis of the SARS-CoV2 virus. These studies have shown that HBOT has a reliable threshold value on oxygen absorption and its delivery into blood vessels and tissue, thereby increasing oxygen saturation . Recent In addition, among the indications not covered by health insurance, there is empirical medical evidence of their auxiliary effects of sudden deafness, skin flap transplantation , poorly At present, governments, as medical advocates and policymakers, should formulate future guidelines and academic research directions for HBOT, seek to find common ground with other countries and reach agreements to resolve issues and conflicts of common concern. Although considerable progress has been made in this field in recent years, more research and evidence are needed to establish the status of HBOT in 21st century medicine. More importantly, a clearer strategic direction and broader development space for HBOT should be formulated to stimulate the development of the medical field and improve the quality of medical care.Broadly, there is growing evidence that HBOT substantially contributes to the treatment of disease, both in primary management and as an adjuvant. Therefore, the focus of future research could be determining whether HBOT has benefits in the treatment of diseases such sudden deafness, Parkinson’s syndrome, dementia, cancer and other diseases, and even currently prevalent diseases such as COVID-19. This study confirms the mechanisms underlying HBOT and provides indications for treatment through statistics and analysis of evidence from extensive literature databases and information platforms. In this way, it provides a reference for the payment of medical insurance in various countries and application of limited medical resources to the most appropriate and necessary medical behaviours. Finally, although some interesting results were obtained through the bibliometric analysis and visualization of publications related to HBOT, there were also several research limitations to this process. The data sources for the study were archives downloaded from the WOS SSCI and Science Citation Index Extended databases. More than 99% of these articles are written in English, which leads to an underestimation of the research literature and authors in other languages. In the future, researchers can use other software  for classification, comparison and analysis. This approach can make bibliometric analysis more objective and efficient. There are also opportunities for cross-certification in terms of the proofreading and interpretation of academic progress. The results of this study provide clinically correct uses of HBOT, can provide indications and can enable medical benefits to be applied to patients who are most in need.


It’s pathophysiological markers such as overproduction along with the accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFT) are posing a serious challenge to novel drug development processes. A model which simulates the human neurodegenerative mechanism will be beneficial for rapid screening of potential drug candidates. Due to the comparable neurological network with humans, zebrafish has emerged as a promising AD model. This model has been thoroughly validated through research in aspects of neuronal pathways analogous to the human brain. The cholinergic, glutamatergic, and GABAergic pathways, which play a role in the manifested behavior of the zebrafish, are well defined. There are several behavioral models in both adult zebrafish and larvae to establish various aspects of cognitive impairment including spatial memory, associative memory, anxiety, and other such features that are manifested in AD. The zebrafish model eliminates the shortcomings of previously recognized mammalian models, in terms of expense, extensive assessment durations, and the complexity of imaging the brain to test the efficacy of therapeutic interventions. This review highlights the various models that analyze the changes in the normal behavioral patterns of the zebrafish when exposed to AD inducing agents. The mechanistic pathway adopted by drugs and novel therapeutic strategies can be explored  The neuronal loss is predominantly due to intra-neuronal deposits and extra-neuronal deposits of abnormal protein, which constitute the irregularly phosphorylated tau protein and the insoluble beta amyloid protein, respectively , an advancing multifaceted neurodegenerative disorder, is the leading cause for 70% of dementia worldwide . The numectively . Furtherectively . The manectively . The neuehavior] . These tehavior] .Previously, AD animal models were developed to reproduce the brain lesions formed due to Aβ plaques and NFTs with the assumption that the models would authentically reproduce the human clinical condition. However, many therapeutics which have shown promise in the animal models have failed to show efficacy in clinical trials . The chaDanio rerio) which belongs to the infraclass of teleost fishes is found to have certain features that makes it a suitable model for the study of AD and evaluation of therapeutic agents. Zebrafish possesses the following features; genes orthologous to the genes known to be involved in AD  volumes (in vitro cellular model). Compounds added to water containing zebrafish, undergo the processes of absorption, distribution, metabolism and excretion similar to an in vivo model  and the internal organs like heart, liver and kidney develop 96 hpf. The development of the zebrafish can be visualized  volumes  , midbrain, hind brain (posterior most part) and a spinal cord . These dThe midbrain  of the zebrafish is important for vision and hearing . It liesThe hindbrain  of the zebrafish is composed of the posteriorly located medulla oblongata, the ventro-anterior pons and the dorso-anterior cerebellum . The cerFunctionally analogous regions in the brains of zebrafish and humans are illustrated and outlined in AD in humans is caused by excessive neuronal loss predominantly in the hippocampus and the cerebral cortex resulting into cognitive dysfunction, memory loss and behavioral changes in the patient. The symptoms of this disease are exacerbated when there is a massive loss of cholinergic neurons that synthesize Ach, a neurotransmitter involved in memory consolidation . The curSome AD patients exhibit extrapyramidal symptoms suggesting a loss of dopaminergic neurons . Aβ plaqThe differences and similarities in the metabolic and synthetic routes of these neurotransmitters in zebrafish and mammals are well reviewed by Ach is a significant neurotransmitter that is quite widespread in the human central nervous system (CNS) . It is eGlutamatergic pathway involving the NMDA receptor is one of the important excitatory pathways in vertebrates and is essential in learning, memory, and synaptic plasticity . HoweverGlutamate is a ligand to some classes of metabotropic receptors and ionotropic receptors. Human ionotropic glutamate receptors (iGluRs) include, NMDA, amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainate receptors . Among iReports on a family of excitatory amino acid transporters (EAATs) in humans, which transport the glutamate away from the synapse, have indicated that, neutralization of excess glutamate could reduce the excitotoxicity of the neuroreceptor . The previa modulating the activity of postsynaptic cells . Administration of drugs and chemicals can modify the neurotransmission pathways by targeting various molecular mechanisms. Several compounds induce AD in mammals Multiple studies have discovered that in FAD autosomal dominant mutations are mainly in three genes that are presenilin 1 (PS1), presenilin 2 (PS2), and Aβ precursor protein (APP) . The expSymptoms of AD in humans span from cognitive deficits , abnormal motor movements  to behavioral and emotional issues  . The zebOver the last couple of decades, there has been a significant rise in interest in the behavioral features of zebrafish. However, the current protocols are based on reinforcement/reward or avoidance and have long training periods. The advantages of Y-maze are that, it is simple and has quick training sessions, allowing specific training of memory as it does not include conditioned learning. It also minimizes factors that might influence performance such as emotional and motivational states. This task assesses the natural tendency of the fish to explore a novel arm when the mnemonic demand is less. As the retention time does last for more than a couple of hours, the performance of the fish can be evaluated multiple times . Advancevia inducers such as scopolamine) zebrafishes, it has been observed that they have a lower intention of exploration and tend to float around in a particular arm. To create an unbias environment with regards to the cues the maze is rotated for each experiment . After allowing the fishes to acclimatize in both the compartments, an electric shock is given in the dark compartment for about 5 s and then the fish is returned to its home tank . The folFor several animals, including zebrafish, new surroundings can be anxiogenic. This test has been considerably used in the modeling of anxiety and assessing the effects of anxiolytics. As this test is based on the idea of a novel surrounding, it is equivalent to the open field test generally performed in rodents. In this test, the initial response of an adult zebrafish is to stay at the bottom of the tank until they get accustomed to the rest of the tank .In this method, the fishes are paired and transferred into a behavioral examination tank. After holding the fishes in the behavioral tanks, they are transferred into separate 100 ml beakers containing 25–30 mL water for immediate transportation into observational tanks. After the transfer, the fishes are observed in the new environment. The ability of the fishes to explore the novel tank is investigated. The more amount of time a fish spends at the bottom of the tank indicates high anxiety levels, which is a common manifestation in neurodegenerative disease models .The light-dark test is commonly used in the quantification of anxiety in rodents but in recent years has been also used for screening adult zebrafish. This model uses the nature of phototaxis displayed in fishes to evaluate the anxiety . It is aZebrafish larvae when exposed to abrupt stimuli of unexpected touch (tactile), loud sound (acoustic), or sudden bright light  tend to react by a swimming burst to escape from the threatening stimuli . Startlevia high-throughput methods will be able to provide observations required for testing and identification of neuroactive compounds. Recent research by This behavioral model is important for neuropharmacological research to observe if the drugs being administered can restore the normal response to startling stimulus in larvae . LocomotThe optokinetic response is first observed in zebrafish 73 h post-fertilization and it slowly develops until 4 days post fertilization where it reaches to 9/10th of an adult goldfish . Around via chemicals that affect the central nervous system allows the study of Alzheimer’s induction and treatment by considering this response as an analysis parameter (Effect on the optokinetic response arameter . This bearameter .When exposed to a new environment animals tend to have a natural tendency of moving to the periphery of the novel environment. This behavior, also known as the wall-hugging behavior, is used to estimate anxiety and it is conserved across all species . ZebrafiThis test can be used to study anxiety-like behavior in the zebrafish . Thus, uZebrafish can be exposed to aversive and non-aversive visual cues on an LCD screen monitor. For responsive cues, 15 zebrafish larvae are placed in a single petri dish and then placed on a monitor. The zebrafish is exposed to moving red and white stripes 5 days post-fertilization . The dirAfter hatching, zebrafish embryos start swimming toward the prey, a behavior that is essential for survival . To testin vivo, exploration of behavioral and pharmaceutical in both larvae and adults (The zebrafish model is a robust system for the physiological and genetic study of AD . The advd adults . Over thd adults . Due to d adults . The lard adults . The artd adults . Zebrafid adults . FurtherGK and AU visualized the presented idea, contributed to the manuscript writing, supervised the project and corrected, revised, and approved the manuscript. MB, SB-P, and AS contributed equally to doing literature searches and in the preparation of the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.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.


To assess whether scales of physical functional performance and the surprise question (“Would I be surprised if this patient died in 6 months?”) predict life support limitations and mortality in critically ill nonsurgical patients.We included 114 patients admitted from the Emergency Department to an intensive care unit in this prospective cohort. Physical functional performance was assessed by the Palliative Prognostic Score, Karnofsky Performance Status, and the Katz Activities of Daily Living scale. Two intensivists responded to the surprise question.The proposed physical functional performance scores were significantly lower in patients with life support limitations and those who died during the hospital stay. A negative response to the surprise question was more frequent in the same subset of patients. Adjusted univariable analysis showed an increased odds ratio for life support limitations and death regarding the activities of daily living scale  and a negative response for the surprise question ; with a p < 0.05 for all results.All physical functional performance scales showed lower scores in nonsurvivors and patients with life support limitations. The activities of daily living score and the surprise question increased the odds of life support limitations and mortality in our cohort of nonsurgical intensive care unit patients admitted from the Emergency Department. The maintenance of full medical treatment (FMT) is relatively straightforward for previously healthy patients with a treatable or curable disease and who have a reasonable chance of survival. However, the increasing prevalence of chronic diseases, coupled with an increase in the age of the population, might significantly worsen the prognosis of acute critical diseases. Patients with a low likelihood of surviving with an acceptable quality of life may be eligible for withholding and/or withdrawing futile therapeutic measures. Thus, the estimation of outcomes, in addition to being necessary, is an important challenge for intensive care physicians.In recent decades, advances in the management of critically ill patients have greatly contributed to a decrease in mortality in the intensive care unit (ICU). Comorbid conditions are also often associated with clinically relevant results. The Charlson Comorbidity Index (CCI) has been the most extensively studied and most widely used comorbidity index in medical literature when mortality is the outcome of interest. These scoring systems have some disadvantages, such as a large number of input variables (which might lead to missing data), lack of calibration to different ICU populations, and overestimation of the risk of death.,5 They are also not designed to predict life support limitations (LSLs) and may not achieve precise clinical decisions in individualized patients.Scoring systems have been widely used to predict the chance of death in the ICU. For example, the Simplified Acute Physiology Score 3 (SAPS 3) and the Acute Physiology and Chronic Health Evaluation II (APACHE II) use data from physiologic parameters, admission diagnosis, and chronic health conditions to predict ICU mortality. Originally developed for patients with sepsis, the Sequential Organ Failure Assessment (SOFA) assesses disease severity during ICU stay and has also been used as a predictor of mortality. The Karnofsky Performance Status (KPS) scale classifies patients according to the degree of their functional disabilities and loss of autonomy. The KPS scale is widely used in oncology to determine the ability of a patient to tolerate chemotherapy. The Katz Activities of Daily Living (ADL) scale was originally designed to evaluate performance in self-care activities in elderly patients.,9 The Palliative Prognostic Score (PaP) was originally developed to predict the 30-day mortality of patients with solid tumors referred to palliative care centers. Moreover, clinical intuition may improve the precision of objective prognostic models utilizing the surprise question. The attending physicians were asked if they would be surprised if the patient died within the next 6 months. A negative response  to the surprise question predicts 6-month mortality, combined with objective scores.,12There are several physical functional performance (PFP) scales that are useful to predict outcomes in clinical contexts other than the ICU.In this study, we hypothesized that the scales used in other clinical situations, namely, the KPS, the ADL, the PaP score, and a negative response to surprise question, would be able to predict LSL and mortality in critically ill patients admitted to a medical ICU. Our objective was to assess whether scales of physical functional performance and the surprise question (“Would I be surprised if this patient died in 6 months?”) predict life support limitations and mortality in critically ill nonsurgical patients.This was a prospective, observational cohort study carried out from August 2018 to February 2019 in an adult ICU of a tertiary public university hospital in the city of Campinas (SP), Brazil. The ICU is composed of ten beds dedicated to the care of nonsurgical patients admitted from the Emergency Department. The nursing technician-to-patient ratio was 2:1, the nurse-to-patient ratio was 5:1, and the doctor-to-patient ratio was 10:1. All adult patients over 18 admitted to the ICU during the study period were eligible for inclusion after they or their relatives signed the informed consent form. A family member or guardian signed the informed consent form when the patient was not in clinical condition to do it independently. Exclusion criteria included nonconsent to participate in the study, pregnant women (as they are referred to another facility), and patients with potential follow-up difficulties, such as indigenous people and prisoners.Universidade Estadual de Campinas, according to CAAE 87042318.8.0000.5404, approved this prospective cohort study.The research Ethics Committee of the The data were collected from medical records and transferred to a form designed exclusively for this research . The mai,9The patient’s functional status before hospitalization was measured using scales that assess PFP, such as the KPS and ADL. The KPS is a score ranging from zero to 100% in which every ten point drop is related to a specific autonomy and performance loss, and ADL consists of six questions, including information about bathing, dressing, toileting, transferring, eliminating, and feeding. A score closer to six indicates better function.A score including measures of the physical condition of patients in palliative care (PaP) was calculated. This score predicts 30-day survival based on the KPS and five other criteria, such as dyspnea, anorexia, clinical prediction of survival in weeks, total white blood count (WBC), and lymphocyte percentage. It ranges from zero to 17.5, with higher scores predicting a lower chance of survival.The main author also consulted two intensivists responsible for the daily routine, who provided additional information, such as the decision of LSL during the stay in the ICU and the response to surprise questions. They did not have access to the scores, and clinical and ethical decisions were based on their clinical experiences, as well as discussions in multidisciplinary teams and daily rounds with students, residents, and ICU medical teachers. The most complex cases were referred for discussion at the weekly clinical bioethics meeting, which brought together the ICU multiprofessional team, undergraduate students, resident doctors, bioethics department professors, and chaplains. At this meeting, the technical aspects , ethical aspects , and affective aspects  were reviewed. The team deliberated and decided the course of the therapeutic plan, which could be revised if the patient presented relevant changes in their clinical status.http://www.raosoft.com/samplesize.html) with 95% confidence level, a margin of error of 7%, a population size of 230 (average of patients admitted to our ICU in the 6 months prior to the beginning of our study), and a 50% response distribution. The sample size was estimated at 107 subjects.Continuous variables are expressed as means and standard deviations or medians and percentiles, as appropriate. Mann-Whitney test and Kruskal-Wallis test were used to assess the scales between categorical variables. A univariable analysis was conducted for the four individual scales and two dependent variables: death during hospitalization, and limitations of life support. Subsequently, the models were adjusted by SAPS3 score, CCI score, and age. The level of significance for the study was 5%. For statistical analysis, the Statistical Analysis System (SAS) for Windows, version 9.4  was used. Sample size calculation was performed using Raosoft® online calculator , multiorgan failure (eight patients), and poor neurologic outcomes (seven patients). The average ICU stay was 14 days and greatly varied between patients. Seventeen patients from our cohort were discussed at the bioethics meeting.The patients on LSL had worse scores on the PaP, KPS, and ADL scales than those who received FMT. The deceased patients had worse scores on the scales and were older. The characteristics of the patients according to the outcome are shown in The same assessment was performed to assess the odds ratio (OR) of the three studied PFP scales and the surprise question for death. Additionally, for this outcome, the ADL scale and the surprise question were associated with death during hospitalization .In our analysis, we aimed to use scales that would reproduce a more detailed anamnesis regarding the degree of functional capacity loss reported. Thus, we sought to include data from the patient’s previous functional history , chronic diseases (CCI), physiological laboratory data , and the subjective analysis of the attending physician about the prognosis through the surprise question. Although both diseased patients and those with LSL had significantly worse PFP scores, our adjusted analysis found that ADLs and a negative response to the surprise question were related to increased odds of both outcomes.A seminal European study including thirty-seven ICUs in 17 countries showed that the most frequent reasons for the limitation of curative therapies were the lack of response to FMT, severe neurological damage, chronic diseases limiting life quality and expectancy, and multiorgan failure. Thus, despite the small number of patients in our cohort, we observed the same pattern. In our study, most patients had an ADL score above four, and even so, mortality was significantly higher when there was a loss of independence for any of the components of this scale. In this regard, a study with 223 patients observed that the functional decline assessed by ADL lower than three was related to a fourfold likelihood of having a nosocomial infection and that half of these infections occurred within 12 days of hospitalization. As nosocomial infections increase hospital mortality, it is possible to trace a cause-and-effect relationship between functional decline, susceptibility to sepsis, and worsening prognosis. This result points to the need for a detailed understanding of daily activities, from simpler to more complex ones. Since we observed that a decrease in the ADL score was a predictor of LSL and hospital mortality in both unadjusted and adjusted univariate analyses, this scale seems to be suitable not only for recognizing patients with increased odds of dying during the hospital stay but also for considering LSL, especially in situations in which the patient is not responding to the treatment.A multicenter study with adults over 80 years of age admitted to European ICUs showed that almost one-third of the 3,920 patients included had an important prior functional decline, assessed by the ADL scale of less than four. This subset of patients had significantly fewer chances of surviving after a month of hospitalization. The same occurred when both doctors and nurses were asked and gave a negative response to the surprise question in different clinical settings, such as primary care, oncology, and hemodialysis clinics.,18Although the surprise question is considered a subjective assessment, several studies suggest that it can improve the accuracy of prognostic indices. A survey of patients admitted to the medical ICU of a large academic medical center showed that, when associated with prognostic models, the negative response to surprise question showed strong discrimination to predict hospital mortality. The first system can act as an alarm to something that is not right and that could be related to the results we obtained from the surprise question, both with LSL and an increased chance of death. The surprise question requires an immediate categorical response (yes or no), in which intensive care providers take into account their intuition, built from their previous experiences, associated with the amount of information available about the patient . Thus, this information reinforces the interaction of the first system (the immediate response to surprise question) with the second .The explanation may lie in how clinical reasoning works, which, according to dual-process theory, is composed of two systems. The first, considered intuitive, is the result of the observer’s experiences and uses the recognition of environmental and patient-related factors, which together constitute patterns that generate subconsciously processed automatic responses. The second system, called analytical, works consciously and actively. In this case, the assessment is conscious and based on stimuli and constituents of the environment and the patient. Regarding clinical reasoning, these two systems operate freely in an interdependent and complementary way.Therefore, a better individual therapeutic plan might be reached, including the odds of LSL and death. However, despite our significant results concerning both the progression to LSL and the increased risk of death, we do not advocate the idea of using the surprise question alone for decision-making in the care of critically ill patients. It should serve as an increased risk alert for these outcomes.Our results suggest that the surprise question, along with the ADL scale, could not only be incorporated into the collection of clinical history with patients and family members but could also serve as an inspiration for clinicians to learn more about patients’ biographies.A strength of our study is its prospective design in a nonsurgical ICU, where most patients were of advanced age and diagnosed with sepsis, a common profile worldwide. Another strong point includes the participation of two intensivists with more than 10 years of experience who work in the ICU, one in the morning and another in the afternoon, adding a workload of 30 hours each per week.Our study had some important limitations. First, it was performed in a single center and with a small number of patients, as half of the sample was excluded for not signing the informed consent form. Thus, the results may not apply to other institutions, and studies with larger sample sizes and longer follow-up periods are needed to be clinically useful and scientifically reliable. Second, the duration of the follow-up was short, and the long-term outcomes could not be assessed. Third, despite being the most studied measure of functional status in the literature, frailty syndrome was not evaluated in our cohort.The assessment of functional capacity, especially employing the activities of daily living scale and the surprise question (with a negative response), were both associated with therapeutic limitation and an increased chance of death during hospitalization. Our results may assist in the development of future prognostic and screening systems in the intensive care unit.


Many individuals with autism spectrum disorders (ASD) demonstrate some challenges with personal narrative writing. Sentence completion tests (SCT) is a class of semi-structured projective techniques and encourage respondents to disclose their private narratives. Even in SCT, only providing beginning of sentences is inadequate to compensate atypicalities in their creativity and imagination, and self-disclosure is difficult for many individuals with ASD. It is reported that many individuals with ASD often achieve a higher degree of task engagement through interactions with robots and that robotic systems may be useful in eliciting and promoting social communication such as self-disclosure for some individuals with ASD. There is a possibility that exemplification by android robots in place of human interviewers can result in a higher degree of task engagement for individuals with ASD. The objective of this study was to investigate whether additional exemplifications by android robots in the SCT can prompt self-disclosure for individuals with ASD. We compared the difference in disclosure statements and subjective emotion in the testing paper of the SCT in additional exemplification by an android robot and a human interviewer. In addition, we assessed the disclosure statements and subjective emotions in the SCT, for which exemplifications were written on testing paper to make the comparison. Our quantitative data suggested that exemplification by android robot promoted more self-disclosure, especially about the negative topic compared to exemplification by a human interviewer and that written on test paper. In addition, the level of participant embarrassment in response to exemplification by the android robot seemed to be lower compared to that in the human interviewer condition. In the assessment and support for individuals with ASD, eliciting self-disclosure is a pressing issue. It is hoped that the appropriate use of robots will lead to a better understanding and support for their application. Self-disclosure is the process by which people reveal personal information about themselves to others and is important in all types and stages of social relationships . IndividSentence completion test (SCT) –8 is a cIndividuals with ASD tend to show impoverished creativity as well as deficient imagination . PreviouIndividuals with ASD often achieve a higher degree of task engagement through interactions with robots than through interactions with humans –24. RoboAn android robot is a humanoid robot with an appearance and movements resembling those of an actual human. It can exhibit facial expressions  during speech and provide subtle non-verbal cues. It can potentially simulate actions that are performed in daily life to some extent. It is very similar to humans but, since it is a robot, it is still much simpler than humans. There is increasing anecdotal evidence for the fact that individuals with ASD may have unique opportunities to use android robots to assist them. A previous study reported a novel intervention using android robots to reduce social anxiety , 26. It The objective of this study was to investigate whether additional exemplifications by android robots in the SCT can prompt self-disclosure for individuals with ASD. We compared the difference in disclosure statements and subjective emotion in the testing paper of the SCT in additional exemplification by an android robot and a human interviewer. In addition, we assessed the disclosure statements and subjective emotions in the SCT, for which exemplifications were written on testing paper to make the comparison. We also investigated the relationship between individual characteristics and self-disclosure statements. A greater understanding of the relationship could provide insight into developing a future therapeutic android robot to manage self-disclosure difficulties for individuals with ASD.The present study was approved by the ethics committee of Kanazawa University. Participants were recruited by flyers that explained the content of the experiment. All procedures involving human participants were conducted in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. After receiving a complete explanation of the study, all participants and their guardians agreed to participate. Written informed consent was obtained from participants and/or from minor participants' legal guardian for the publication of any potentially identifiable images or data included in this article. The inclusion criteria included  from theAll participants completed the Autism Spectrum Quotient-Japanese version (AQ-J) , which hFull-scale IQ scores were measured by either the Wechsler Intelligence Scale for Children—Fourth Edition, the Wechsler Adult Intelligence Scale–Third Edition or the Japanese Adult Reading Test (JART) . The latThe participants' severity of social anxiety symptoms was measured using the Liebowitz Social Anxiety Scale (LSAS) . This clThe Adolescent/Adult Sensory Profile [AASP ] is a seThe android robot used in this study was A-Lab android ST  A-Lab C. The andWe used the first 30 questions in the Japanese version of SCT called the SEIKEN SCT . In this study, unlike the standard SCT, which presents the beginning of sentences, additional short exemplifications were presented. The procedure for making short exemplifications was as follows. First, two psychologists chose sample responses from the SCT, which are listed in the manual. Second, they drafted short exemplifications while referencing sample responses independently. Then, they revised the draft so that individuals with ASD whose IQ was above 70 could understand the meaning. Finally, we confirmed that they can understand the meaning of short examples in our preliminary experiment. Please refer to At the close of the session, participants completed a self-report survey using a 7-point Likert scale to rank their level of stress, embarrassment, boredom, and enjoyment in each session. Two professional psychologists counted the number of words indicating self-disclosure that were written on the testing paper in each condition. The psychologists also assessed the number of topics about positive and negative self-disclosure. Positive self-disclosure was defined as the expression of positive narratives in the past, present, and future. Negative self-disclosure was defined as the expression of negative narratives in the past, present, and future. In addition, the two professional psychologists evaluated the items of positive and negative self-disclosures separately, and items that were rated in agreement by both psychologists were adopted.We performed statistical analysis using SPSS version 24.0 . Differences in the number of words and topics about positive and negative disclosure written on the testing paper of SCT as well as self-report ratings between exemplification by android robot vs. human interviewer and exemplification by android robot vs. written passages on testing paper were analyzed using the Wilcoxon signed-rank test. Spearman's rank correlation coefficients were used to explore the relationships among demographic data , the number of words, and number of topics related to positive and negative self-disclosure written on testing paper in the case of exemplification by android robot, by a human interviewer, and in a written passage on testing paper. An alpha level of 0.05 was used for these analyses.In total, 21 individuals with ASD took part in the study. The details are presented in p = 0.443) and between the conditions of exemplification by the android robot vs. in a written passage on testing paper (p = 0.663). Significant trends were observed between exemplification by the android robot vs. the human interviewer in the number of topics signifying positive disclosure (p = 0.030). There were no significant differences in the number of topics signifying positive disclosure between exemplification by the android robot vs. in a written passage on paper (p = 0.218). Significant differences were observed between exemplification by the android robot vs. the human interviewer in the number of topics signifying negative disclosure (p = 0.020). Significant differences were also observed between exemplification by the android robot vs. in a written passage on paper in the number of topics signifying negative disclosure (p = 0.021). The details are presented in We performed multiple comparison corrections for the number of words written on the testing paper of the SCT, the number of topics signifying positive disclosure, and the number of topics signifying negative disclosure using the Bonferroni method. The significance level after correction by the Bonferroni method was 0.025 each. There were no significant differences in the number of words written on the testing paper of the SCT between the conditions of exemplification by the android robot vs. the human interviewer (p = 0.023). There were no significant differences in the Likert scale to rank the participants' level of embarrassment between exemplification by the android robot vs. in a written passage on the test paper of SCT (p = 0.064). There were no significant differences in the Likert scale in their rankings of stress level (p = 0.576), boredom (p = 0.888), and enjoyment (p = 0.820) between exemplification by the android robot vs. the human interviewer. There were no significant differences in the Likert scale in the rankings of their level of stress (p = 0.518), boredom (p = 0.781), and enjoyment (p = 0.268) between exemplification by the android robot vs. in a written passage on the test paper. The details are presented in We performed multiple comparison corrections for the Likert scale to rank the participants' level of stress, embarrassment, boredom, enjoyment using the Bonferroni method. The significance level after correction by the Bonferroni method was 0.025 each. In the self-report survey to rank their level of embarrassment on a 7-point Likert scale, significant differences were observed between exemplification by the android robot and the human interviewer  and full IQ . We found a positive relationship between the number of topics signifying negative disclosure for exemplification by android robot and AQ score  and full IQ . There were no significant relationships between the number of topics signifying positive disclosure for exemplification by human interviewer and AQ score , between the number of positive disclosure topics and full IQ , between exemplification provided in a written passage on test paper and AQ score , between exemplification in a written passage on test paper and full IQ . There were also no significant relationships between the number of topics of negative disclosure for exemplification by human interviewer and AQ score , between the number of negative disclosure topics and full IQ , between exemplification provided in a written passage on test paper and AQ , between exemplification provided in a written passage on test paper and full IQ .In Spearman's rank correlation coefficients, there were no significant relationships between the number of topics about positive disclosure for exemplification by android robot and AQ score ; however, we judged that 15 min per session would be appropriate to meet the specific needs of individuals with ASD. In addition, all our participants were able to complete the trial. Third, we only included individuals with ASD. To elucidate the relationship between exemplifications by android robots and self-disclosure more clearly, it is important to study individuals without ASD and compare their data with those of individuals with ASD. At the time of this experiment, the Japanese government declared a state of emergency due to the spread of COVID-19, so we could not ask controls to participate in the experiment. Given that eliciting self-disclosure is a pressing issue for individuals with ASD, we had to conduct pilot studies even without controls. Additionally, their level of social anxiety is high. Although the level of social anxiety among individuals with ASD without intellectual disability is estimated to be higher than that of individuals with typical development , and socDespite limitations, all participants were able to complete the study procedures, and the results suggest the usefulness of exemplification by android robots to promote self-disclosure for individuals with ASD. In the assessment and support for individuals with ASD, eliciting self-disclosure is a pressing issue. It is hoped that the appropriate use of robots will lead to a better understanding and support for their application.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 Ethical committee, Kanazawa University. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.HK designed the study, conducted the experiment, carried out the statistical analyses, analyzed and interpreted the data, and drafted the manuscript. TM, YY, YM, KT, HI, and MM conceived of the study, participated in its design, assisted with data collection and the scoring of behavioral measures, analyzed and interpreted the data and were involved in drafting the manuscript, and critically revising it for important intellectual content. MM was involved in approving the final version to be published. All authors read and approved the final manuscript.This work was supported in part by Moonshot R&D Grant Number JPMJMS2011.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.


Self-rated health, a subjective health outcome that summarizes an individual’s health conditions in one indicator, is widely used in population health studies. However, despite its demonstrated ability as a predictor of mortality, we still do not full understand the relative importance of the specific health conditions that lead respondents to answer the way they do when asked to rate their overall health. Here, education, because of its ability to identify different social strata, can be an important factor in this self-rating process.The aim of this article is to explore possible differences in association pattern between self-rated health and functional health conditions , chronic diseases, and mental health (depression) among European women and men between the ages of 65 and 79 according to educational attainment .n = 27,230).Classification trees , an established machine learning technique that has only recently started to be used in social sciences, are used to predict self-rated health outcomes. The data about the aforementioned health conditions among European women and men aged between 65 and 79 comes from the sixth wave of the Survey of Health, Ageing and Retirement in Europe (SHARE) (It is confirmed the high ability to predict respondents’ self-rated health by their reports related to their chronic diseases, IADLs, ADLs, and depression. However, in the case of women, these patterns are much more heterogeneous when the level of educational attainment is considered, whereas among men the pattern remains largely the same.The same response to the self-rated health question may, in the case of women, represent different health profiles in terms of the health conditions that define it. As such, gendered health inequalities defined by education appear to be evident even in the process of evaluating one’s own health status. Self-rated health as an indicator of an individual’s health status has received considerable attention because of its demonstrated ability as a predictor of mortality , 2. AlthA number of studies have sought to shed light on the nature of the relationship between this indicator and specific aspects of health, including chronic conditions , functioDespite this evidence pointing to the influence of certain objective health conditions, self-rated health cannot be fully understood without analyzing the subjective processes that lead people to respond the way they do when questioned about their overall health. Of note here is the contribution of Jylhä  who idenWhen comparing people with similar sociodemographic characteristics, there is probably a process of homogenization of the subjective conception of health within the same group. This process, known as social comparison, permits to understand the more optimistic assessment of health in general of older population, among whom the normalization of negative health situations has led to a more favorable evaluation of their own health . Social The aim of this article is to explore possible differences in association pattern between self-rated health and functional health conditions , chronic diseases, and mental health (depression) among European between the ages of 65 and 79 and whether this association varies according to educational attainment , separately for women and men. Education was chosen due to its ability to establish different levels of social stratification , 12. AltTo identify potential differences in association patterns between self-rated health and the selected health conditions, machine learning methods based on classification trees, namely random forests and the J48 algorithm , are applied to European individuals who participated in the sixth wave of the Survey of Health, Ageing and Retirement in Europe (SHARE) . The J48The data analyzed herein are taken from the sixth edition of the Survey of Health, Ageing and Retirement in Europe (SHARE), conducted in 2015. SHARE is a panel survey that is representative of the non-institutionalized population in Europe aged 50 and over. It gathers information about multiple aspects of this population, including demographics, work, family, health, housing, etc. [n = 27,230 from an original sample of 28,790, 94.6% with complete information). This age range was set for two main reasons in order to reduce possible sources of bias in our results: first, a minimum age of 65 years was used to account for the known effect of retirement on health perception and self-assessment of health. Individuals’ perception is substantially alleviated by retirement [The working sample comprised all persons aged between 65 and 79 years old residing in the 17 European countries  participating in the sixth edition of SHARE who answered all the questions included in our analysis . Here, the final variable was dichotomized as no chronic disease and chronic disease .Activities of daily living (ADL): Participants were asked whether, “because of physical, mental, emotional, or memory problems”, they had any difficulty doing these activities : dressing (including putting on shoes and socks); eating (such as cutting up your food); using the toilet (including getting up and down); bathing and showering; getting in and out of bed; and walking across a room. The final variable was dichotomized as no limitations and limited (having difficulties to perform one or more of the activities).Instrumental activities of daily living (IADL). Participants were asked whether they had any difficulty doing each of the following everyday activities: doing work around the house or garden; leaving the house independently/accessing transportation; shopping for groceries; doing personal laundry; managing money; preparing a hot meal; taking medications; and making telephone calls. Individuals were required to exclude any difficulties expected to last less than three months. The final variable was dichotomized as no limitations and limited (having difficulties to perform one or more of the activities).Depression: This variable was measured using the EURO-D scale, developed and validated by the EURODEP Concerted Action Project . EURO-D Self-rated health: The variable was based on responses to the question ‘How is your health in general?’ . Following common practice , the fivEducation: The original information was coded using the International Standard Classification of Education, that is, the ISCED 1997 scale, designed by UNESCO to facilitate cross-country comparisons. The original values were grouped as follows: low , medium , and high .The classification algorithm selected was the J48 , an updath fold of the cross-validation procedure, the ith subset is used to test the performance of a model trained on the remaining k − 1 subsets. In that way, all the different folds contribute to the training and validation process in different steps. In this case, the number of folds was set at 10. Complementarily, overfitting was controlled by pruning the decision trees to avoid branches that might be too complex and specific to the subsample analyzed in each case [The k-fold cross-validation procedure was used in order to avoid overfitting, i.e., when the noise in the training data has a relatively high influence on the learning process of the model and the final model is too specific for this training data . Under kach case .The predictive capacity of the J48 algorithm was validated by comparing the accuracies  of each of the models obtained using this algorithm with the values obtained from random forest (RF). RF fits an ensemble of decision trees and combines the results of them , what haAll the algorithms and their respective measures of accuracy were implemented using the Waikato Environment for Knowledge Analysis (WEKA)  softwareTable As for the results by educational level, we observe in all the cases a clear health gradient according to education, with lower educated individuals showing worse health results. However, the magnitude of these differences is much greater in the case of women, again with higher differences in the case of depression, especially between low and medium educated population.Figures In the case of women with a medium level of education Fig. , the treFinally, in the case of highly educated women Fig. , the decIn the case of the male respondents, there is almost no variation in the decision trees with level of education with the same pattern being observed for the prediction of self-rated health Figs. , and 6. The only exception to this general pattern is observed among low educated men Fig.  for whomThis study assesses the influence of various specific health conditions, both physical  and mental (depression), in predicting responses about self-rated health in European women and men aged between 65 and 79 according to their educational attainment . The predictive capacity was assessed by means of classification trees based on the J48 algorithm, which belongs to the family of machine learning methods, and by using data from the sixth wave of the SHARE survey. The approach contributes to a better understanding of the health conditions that associate with individuals’ responses to the question about their general health, and how this relates with the health inequalities we observe when self-rated health is used as the health outcome.The results presented here show the existence of differences in health conditions associated with the health perception of women and men. Indeed, in the case of women, these patterns are much more heterogeneous when the level of educational attainment is considered, whereas among men the pattern remains largely the same. The heterogeneous pattern described for female respondents does not, however, translate into different levels of accuracy as shown by the overlap between the confidence intervals of this indicator for the three educational groups. In fact, the simplest pattern, which is that of highly educated women, is the one that shows the highest levels of accuracy. However, we applied this same model to the cases of low and middle educated women as a sensitivity analysis but the results showed a significant reduction in the accuracy values (57% and 59% respectively for low and middle educated women) in the predictions of self-perceived health compared to the results obtained with the specific models. This result underscores the greater importance of education in identifying health inequalities among women compared to men. Among men, education does not lead to different associations among the four health conditions analyzed, though the higher the education, the higher the accuracy of the model. This seems to point, in the direction of the resource substitution theory, which states that the absence of one or more socio-economic resources may be offset by the greater influence of other resources . In thisThis study is not free of limitations. The fact of working with data from a survey implies that all responses are subject to the perception of the person interviewed. This implies that there is an effect of subjectivity in the response process itself to the questions for the four indicators used in this study to predict self-rated health. In addition, we have employed cross-sectional data; yet, there is a clear need in the future to analyze longitudinal data to test whether the effects of health conditions on self-rated health remain unchanged with age. A further limitation is the fact that the study analyzed aggregate data for Europe as a whole, without considering the specific characteristics of each country. It is hoped that this limitation can be addressed in future studies.Finally, it is important to note that the analysis has been performed for the age range prior to the separation between the trend in mortality and self-rated health, which is also indicative of a change in self-reported health. In the future, it would be interesting to see if the results obtained are also applicable for ages 80 years and older. Therefore, conclusions from this research only apply to the age range between retirement and the reduction of the association between self-rated health and mortality.These results serve to highlight the weight that the step in the process prior to giving a response has on the final outcome, as stressed earlier by Jylhä . It appeThe fact that the same factors that act as social determinants of health inequalities appear also to influence the decision-making process when reporting self-rated health has implications for the use and interpretation of this indicator. Future research needs to examine other possible social determinants of health – in addition to education – such as employment, because of their possible impact on the reference group used in defining self-rated health. Likely country differences must be also tested in line with the third factor proposed by Jylhä , cultura


Staphylococcus aureus (MRSA) infection is a worldwide concern given its presence even in non-hospitalized healthy individuals, such as university students.Methicillin-resistant To identify in the literature the prevalence of colonization by MRSA among healthcare students.Integrative review of the literature conducted in Universidade Federal do Piauí.A search for primary studies was performed in the following databases: Medical Literature Analysis and Retrieval System on-line; Cumulative Index to Nursing and Allied Health Literature; Web of Science; Scopus; and LILACS.This review included 27 studies that demonstrated MRSA infection prevalence ranging from 0.0 to 15.3% among students.The prevalence of colonization of MRSA among healthcare students is high, and the nasal cavity was cited as an important reservoir location for these microorganisms. Staphylococcus aureus is considered to be a persistent member of the human endogenous microbiota and has historically been associated with important and serious cases of infection. It has the ability to rapidly develop resistance to antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) is considered to be a paradigm for bacterial infections, since it is associated with high rates of morbidity and mortality.34 In the United States and Taiwan, the prevalence of strains acquired in the community is 52%, thus exceeding the proportion of strains acquired in hospital environments.5 There have also been reports of cases of MRSA acquired in the community.7In assisting carriers of bacterial infections or colonized or infected patients, or in handling contaminated objects, healthcare workers’ hands can become contaminated. These workers may subsequently transmit the microorganism to other patients. However, this situation is not exclusive to the hospital environment. Clinically manifested diseases in the community or in professionals and/or patients may lead to situations in which some individuals are asymptomatic carriers, also called colonized individuals or simply carriers, when the disease is present in the host organism without causing apparent manifestations.Staphylococcus aureus infection and can act as a source of dissemination both in the community and in hospital environments, and for carrying bacteria from one of these environments to another.1Healthcare students play an important role in the epidemiology and pathogenesis of 1 Hence, it has become relevant to summarize the knowledge of MRSA that has resulted from research on this subject.In Brazil, this topic has been little addressed, but it is known that the presence of MRSA among students has been gradually spreading.Staphylococcus aureus among healthcare students.The objective of this study was to identify in the literature the prevalence of colonization by methicillin-resistant 8 To preserve methodological rigor, the following steps were taken to conduct this review: formulation of the research question; idealization of sampling plan and data collection strategies; extraction of relevant data from studies included in the review; and, finally, analysis and interpretation of the data.8This study was an integrative review of the literature, incorporating a method of searching for secondary data.Staphylococcus; O – prevalence.9 Therefore, the following question was asked: “What evidence is available in the literature regarding the prevalence of methicillin-resistant Staphylococcus aureus colonization among healthcare students?”The research question was elaborated in accordance with the PVO strategy . Thus, in line with the objective of the study, the following structure was used: P - healthcare students; V – methicillin-resistant Searching for and selection of studies took place between the months of November 2019 and January 2020 and were carried out by two independent reviewers. Any divergences were resolved by a third reviewer.After the search stage, original articles were selected, based on reviewing their titles and abstracts, in accordance with the following inclusion criteria: original articles covering the population of undergraduate students in the field of healthcare who experienced clinical activities that brought them into direct contact with patients.The full text of each article was then read, with a view to choosing studies that answered the research question. Through this process, articles involving high school or technical students, those that did not comply with selection criteria mentioned above, those that did not answer the research question and those that were duplicates were excluded, as also were opinion articles, theoretical reflections, dissertations and book chapters.The following databases were selected: Medical Literature Analysis and Retrieval System online (MEDLINE) via National Library of Medicine National Institutes of Health (PubMed); Cumulative Index to Nursing and Allied Health Literature (CINAHL); Web of Science; Scopus; and Literatura Latino-americana e do Caribe em Ciências da Saúde (LILACS) via Biblioteca Virtual em Saúde (BVS).The descriptors and keywords used in the search were applied in accordance with particularities of each database. They were obtained by consulting the Descritores em Ciências da Saúde (DeCS), Medical Subject Headings (MeSH) and titles from CINAHL. During the search, descriptors were cross-referenced with each other using the Boolean operators “or” and “and”. Descriptors were inserted in the English language, since all journals indexed in these databases have descriptors in English in their articles; with the exception of BVS, in which descriptors were inserted in English and Portuguese. To expand the search, there was no limitation on the time of publication or language. 9 , in order to identify duplicates and gather together all publications. In addition, the reference lists of these articles were consulted in order to find any additional studies. The selection of studies followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)9 .10 Furthermore, the protocol for this review was previously assessed by experts in the method used. After fully evaluating the texts, a descriptive analysis on the results found was carried out, in which a synthesis of all the studies included in the review was presented, along with comparisons between them.For data analysis and extraction, a data collection instrument that had been validated by Ursi was chosen for this study and was adapted for use in it.37The final sample for this review comprised 30 primary articles, which were characterized taking into account the authors, year of publication, country, objective and main results . These s37Regarding the locations of the studies, they were carried out in Brazil, Malaysia, Colombia, China, Palestine, Spain, Brunei, India, Turkey, Czech Republic, Saudi Arabia, Madagascar, Pakistan, Nepal, Tanzania, South Korea, Iran, Ireland, Jordan, Italy, Nigeria, Poland and Ethiopia.37 Two studies involved students from more than one undergraduate course.28The populations addressed by the researchers of these 30 studies were nursing students, medical students, health science students and dental students.37To detect colonizing microorganisms, samples were collected using the technique of swab smears from nasal specimens, in all of these studies except for four studies, in which specimens were collected from more than one anatomical site.26 The percentages found are shown in Regarding the prevalence of MRSA, the student population in some studies was divided into groups before exposure to healthcare and after such exposure.38Worldwide, occurrence of healthcare-associated infections (HAI) is one of the main public health problems, with severe human and economic repercussions. According to the Centers for Disease Control and Prevention (CDC), MRSA infections have outperformed HIV as the leading cause of morbidity and mortality in the United States.39 However, the results systematized in the present study revealed that presence of MRSA has also been reported among non-hospitalized healthy individuals, such as undergraduate students, ranging from 0.0% to 15.3%.26Studies have revealed high prevalence of MRSA in patients and healthcare professionals with exposure to the healthcare system.40 This was observed in the present study, thus indicating that MRSA infection was present in students who were not exposed to hospital environments. This may indicate the presence of community-acquired MRSA strains.1 It needs to be borne in mind that in the studies discussed here, students who had been hospitalized within the last few months had been excluded, considering that hospitalization could be a confounding factor for occurrences of MRSA.Data in the literature have highlighted occurrences of MRSA infection in healthy populations that live in agglomerations or experience such conditions but which have little or no contact with healthcare services, as is the case of undergraduate students within the field of healthcare.5Identification of high frequencies of MRSA in students before they were exposed to experiences of clinical care is a matter for concern. It indicates that there is a need for effective infection prevention and control policies, in relation to hygiene and surveillance.5 In this regard, studies that have addressed the prevalence of MRSA among students after exposure to hospital environments can provide evidence that exposure to MRSA in hospitals can play a critical role in achieving nasal colonization by MRSA.Clinical practice among students in the field of healthcare is part of the teaching-learning process. In relation to this process, there is exposure to occupational risks, especially through recognition of the variability of care provided to patients.Staphylococcus aureus, whose prevalence reaches, on average, 40% in the adult population.6 Possibly for this reason, the nasal cavity was the site most chosen by researchers for sample collection in their studies, thus showing the importance of the upper airways in transmission and acquisition of pathogenic microorganisms. The throat and palms are also important reservoirs for MRSA.26According to the literature, the nostrils are the main colonization site for Staphylococcus aureus is considered to be a major concern, especially with regard to MRSA.1It is known that students in the field of healthcare, as they progress through the curriculum with increasing complexity of care practices, whether in hospitals or other healthcare delivery environments, become carriers of microbes. In this, acquisition of 5 This aspect of infection could not be analyzed in the present study, since the studies included in this review were cross-sectional, which did not allow the study sample to be monitored.Thus, MRSA rates in students may increase according to their clinical exposure, as well as from isolated occurrences. In another study, there was greater potential for virulence in samples from groups working in clinics.5 Likewise, the MRSA rate also varies in different locations.41The prevalences found need to be analyzed with caution, considering that occurrences of infections caused by MRSA may differ according to the scenarios within which they occur. This may be due to measures that are taken to control infection and may be dependent on effective implementation.Staphylococcus aureus among healthcare students.This study presented some limitations due to the choice of databases and keywords. Use of the CINAHL database may have restricted the search, as it is a specific database for the field of nursing. In addition, the choice of databases and keywords may have camouflaged studies on the same topic that were not indexed in the same database. Hence, it can be suggested that similar investigations should be conducted, with cross-referencing of other databases, in order to investigate Brazilian scientific production on colonization by Staphylococcus aureus among healthcare students is high, and the nasal cavity was cited in this study as an important reservoir for these microorganisms.The prevalence of colonization by methicillin-resistant Efforts need to be made to implement standards and routines that are designed to limit the spread of MRSA strains among students, given that once MRSA has become established within a community, its eradication and control is difficult. Furthermore, in view of the high morbidity and mortality and exponential growth of series of microbial resistance, implementation of control strategies is prudent.Therefore, education on infection control measures in undergraduate healthcare courses is of great importance, as also is implementation of adequate and effective infection control programs to reduce the prevalence of MRSA.